JP2015157803A - External pharmaceutical composition which is foamy when used - Google Patents
External pharmaceutical composition which is foamy when used Download PDFInfo
- Publication number
- JP2015157803A JP2015157803A JP2015022654A JP2015022654A JP2015157803A JP 2015157803 A JP2015157803 A JP 2015157803A JP 2015022654 A JP2015022654 A JP 2015022654A JP 2015022654 A JP2015022654 A JP 2015022654A JP 2015157803 A JP2015157803 A JP 2015157803A
- Authority
- JP
- Japan
- Prior art keywords
- pharmaceutical composition
- external
- polyoxyethylene
- external pharmaceutical
- vitamin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
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- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 101
- 239000004480 active ingredient Substances 0.000 claims abstract description 40
- 239000006260 foam Substances 0.000 claims abstract description 37
- 229940088594 vitamin Drugs 0.000 claims abstract description 33
- 229930003231 vitamin Natural products 0.000 claims abstract description 33
- 235000013343 vitamin Nutrition 0.000 claims abstract description 33
- 239000011782 vitamin Substances 0.000 claims abstract description 33
- 150000003431 steroids Chemical class 0.000 claims abstract description 28
- 239000002736 nonionic surfactant Substances 0.000 claims abstract description 21
- 239000002798 polar solvent Substances 0.000 claims abstract description 15
- -1 carboxylic acid diester Chemical class 0.000 claims description 88
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 38
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 34
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- 239000003945 anionic surfactant Substances 0.000 claims description 11
- 125000000217 alkyl group Chemical group 0.000 claims description 9
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- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 6
- CBGUOGMQLZIXBE-XGQKBEPLSA-N clobetasol propionate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CCl)(OC(=O)CC)[C@@]1(C)C[C@@H]2O CBGUOGMQLZIXBE-XGQKBEPLSA-N 0.000 claims description 6
- LDVVTQMJQSCDMK-UHFFFAOYSA-N 1,3-dihydroxypropan-2-yl formate Chemical compound OCC(CO)OC=O LDVVTQMJQSCDMK-UHFFFAOYSA-N 0.000 claims description 5
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- UREBDLICKHMUKA-DVTGEIKXSA-N betamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-DVTGEIKXSA-N 0.000 claims description 5
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- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 claims description 4
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- SHUZOJHMOBOZST-UHFFFAOYSA-N phylloquinone Natural products CC(C)CCCCC(C)CCC(C)CCCC(=CCC1=C(C)C(=O)c2ccccc2C1=O)C SHUZOJHMOBOZST-UHFFFAOYSA-N 0.000 claims description 4
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- 229940045997 vitamin a Drugs 0.000 claims description 4
- 229940046008 vitamin d Drugs 0.000 claims description 4
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- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 claims description 3
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- 229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 claims description 3
- 235000019156 vitamin B Nutrition 0.000 claims description 3
- 239000011720 vitamin B Substances 0.000 claims description 3
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- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims 1
- 239000005977 Ethylene Substances 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 64
- 238000009472 formulation Methods 0.000 abstract description 36
- 239000004615 ingredient Substances 0.000 abstract description 10
- 230000000694 effects Effects 0.000 abstract description 5
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- 206010040880 Skin irritation Diseases 0.000 abstract description 3
- 239000007788 liquid Substances 0.000 abstract description 3
- 230000036556 skin irritation Effects 0.000 abstract description 3
- 231100000475 skin irritation Toxicity 0.000 abstract description 3
- 150000003722 vitamin derivatives Chemical class 0.000 abstract description 3
- 230000003993 interaction Effects 0.000 abstract description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 230000002411 adverse Effects 0.000 abstract 1
- 239000003814 drug Substances 0.000 description 26
- 230000000052 comparative effect Effects 0.000 description 20
- 238000005187 foaming Methods 0.000 description 14
- 238000002360 preparation method Methods 0.000 description 12
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
- 239000002904 solvent Substances 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 239000000443 aerosol Substances 0.000 description 6
- 229920001223 polyethylene glycol Polymers 0.000 description 6
- 229920001296 polysiloxane Polymers 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 239000006097 ultraviolet radiation absorber Substances 0.000 description 5
- 239000004166 Lanolin Substances 0.000 description 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
- 239000002202 Polyethylene glycol Substances 0.000 description 4
- 230000007794 irritation Effects 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
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- 239000000843 powder Substances 0.000 description 4
- 238000005063 solubilization Methods 0.000 description 4
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- 235000019437 butane-1,3-diol Nutrition 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
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- 235000011187 glycerol Nutrition 0.000 description 3
- 229960005150 glycerol Drugs 0.000 description 3
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
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- DSEKYWAQQVUQTP-XEWMWGOFSA-N (2r,4r,4as,6as,6as,6br,8ar,12ar,14as,14bs)-2-hydroxy-4,4a,6a,6b,8a,11,11,14a-octamethyl-2,4,5,6,6a,7,8,9,10,12,12a,13,14,14b-tetradecahydro-1h-picen-3-one Chemical compound C([C@H]1[C@]2(C)CC[C@@]34C)C(C)(C)CC[C@]1(C)CC[C@]2(C)[C@H]4CC[C@@]1(C)[C@H]3C[C@@H](O)C(=O)[C@@H]1C DSEKYWAQQVUQTP-XEWMWGOFSA-N 0.000 description 2
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- XDOFQFKRPWOURC-UHFFFAOYSA-N 16-methylheptadecanoic acid Chemical compound CC(C)CCCCCCCCCCCCCCC(O)=O XDOFQFKRPWOURC-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
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Landscapes
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
本発明は、外用医薬組成物に関し、さらに詳細には、使用時に泡状を呈する外用医薬組成物に関する。 The present invention relates to a pharmaceutical composition for external use, and more particularly to a pharmaceutical composition for external use that exhibits a foam shape when used.
外用医薬の製剤には大きく分類して、ローション製剤、軟膏製剤、クリーム製剤、噴霧エアゾル製剤、泡沫エアゾルの５種の製剤が存在する。この内、噴霧エアゾル製剤、泡沫エアゾル製剤は、ともに均一且つ広域に患部へ物理的刺激を低減した形で薬剤を投与できることから注目を浴びている（例えば、特許文献１を参照）。その一方で、エアゾルの噴出用のガス組成物自体が皮膚に刺激を与える可能性が高いこともすでに知られている（例えば、特許文献２を参照）。これを避ける手段としては、発泡用のガスを充填せずに、ポンプ式フォーマーで泡沫などを形成する手段が存在する。しかしながら、この様なポンプ式フォーマーにより泡沫を形成するポンプ式フォーマー用組成物においても、溶剤成分や多価アルコールによる泡沫形成性、泡の持続性、泡のきめ細かさ等の泡質、べたつき、つっぱり感などの使用感、目詰まりによる吐出不良、液ダレ（泡ダレ）の発生、有効成分と製剤成分との望ましくない相互作用、有効成分の溶状、製造安定性、皮膚刺激などの安全性に関する副作用等の課題が存在し、その処方的自由度は極めて小さいものと言わざるを得ない。このため、ポンプ式フォーマー用の組成物において、上記の様な課題を解決する方法が求められていた。 There are roughly five types of preparations for external medicines: lotion preparations, ointment preparations, cream preparations, spray aerosol preparations and foam aerosols. Among these, spray aerosol preparations and foam aerosol preparations are attracting attention because they can administer the drug uniformly and over a wide area with reduced physical irritation (for example, see Patent Document 1). On the other hand, it is already known that the gas composition itself for aerosol ejection is highly likely to irritate the skin (see, for example, Patent Document 2). As means for avoiding this, there is means for forming foam or the like with a pump-type former without filling the foaming gas. However, even in such a pump-former composition that forms foam with such a pump-former, the foam-forming property by the solvent component or polyhydric alcohol, the persistence of the foam, the foam quality such as the fineness of the foam, the stickiness, the tension Side effects related to safety such as feeling of use such as feeling, ejection failure due to clogging, occurrence of liquid sag (foam sag), undesirable interaction between active ingredient and formulation ingredient, dissolution of active ingredient, manufacturing stability, skin irritation There is a problem such as, and the prescription freedom is inevitably small. For this reason, in the composition for pump type | formulas, the method of solving the above subjects was calculated | required.
一方、炭酸プロピレンなどの極性溶剤を泡沫形成エアゾルで使用することは既になされていたが（例えば、特許文献３、特許文献４を参照）、ポンプ式フォーマー用の組成物で使用されたことは発明者の知る限り行われていない。これは、ポンプ式フォーマーによる発泡が、発泡ガスによる発泡よりも発泡性が悪く、加えて、発泡条件が極めて限られ使用に不適であると考えられているためである。 On the other hand, polar solvents such as propylene carbonate have already been used in foam-forming aerosols (see, for example, Patent Document 3 and Patent Document 4), but it has been used in compositions for pump-type formers. As far as the person knows. This is because foaming by a pump-type former is worse than foaming by a foaming gas, and in addition, foaming conditions are extremely limited and are considered unsuitable for use.
さらに、ビタミン類を含有する発泡性医薬組成物としては、噴射ガスを使用した乾癬の局所治療用加圧型発泡性組成物（例えば、特許文献５を参照）が、さらに、ポンプフォーマー用組成物としては、化粧料として、１）尿素と、２）ビタミンＡ、ビタミンＤ、ビタミンＥ，ビタミンＫ及びそれらの誘導体からなる群より選択される脂溶性ビタミンの１種又は２種以上と、３）乳酸、リン酸、クエン酸、エデト酸及びそれらの塩からなる群より選択される１種又は２種以上と、４）ＨＬＢ値が１０以上である非イオン性界面活性剤の２種以上を含有する透明化粧料（例えば、特許文献６を参照）などが知られている。また、ステロイドを含有する発泡性皮膚外用剤としては、エタノールとプロピレングリコールとを溶剤として、有効成分としてプロピオン酸クロベタゾールを含有し、プロパン、イソブタンなどの噴射剤を含有する医薬組成物が知られている（例えば、特許文献７を参照）。 Further, as effervescent pharmaceutical compositions containing vitamins, a pressurized effervescent composition for local treatment of psoriasis using a propellant gas (see, for example, Patent Document 5), and further a composition for a pump former. As cosmetics, 1) urea, 2) one or more fat-soluble vitamins selected from the group consisting of vitamin A, vitamin D, vitamin E, vitamin K and their derivatives, and 3) Contains one or more selected from the group consisting of lactic acid, phosphoric acid, citric acid, edetic acid and salts thereof, and 4) two or more nonionic surfactants having an HLB value of 10 or more Transparent cosmetics (see, for example, Patent Document 6) are known. In addition, as an effervescent skin external preparation containing a steroid, a pharmaceutical composition containing ethanol and propylene glycol as a solvent, clobetasol propionate as an active ingredient, and a propellant such as propane or isobutane is known. (For example, see Patent Document 7).
本発明は、このような状況下為されたものであり、ビタミン類、ステロイド類などの有効成分を含有するポンプ式フォーマー用の組成物において、該有効成分と製剤成分との関係において生じる課題を解決するものであり、中でも、ビタミン類、ステロイドの塗布の均一性を高める手段を提供することを課題とする。 The present invention has been made under such circumstances, and in a composition for a pump-type former containing active ingredients such as vitamins and steroids, the problem that arises in relation to the active ingredients and the formulation ingredients The problem to be solved is to provide means for enhancing the uniformity of the application of vitamins and steroids.
この様な状況に鑑みて、本発明者らは、ポンプ式フォーマー用の組成物において、ビタミン類、ステロイド類などの有効成分と製剤成分との関係において生じる課題、とりわけ塗布の均一性を解決する手段を求めて、鋭意研究努力を重ねた結果、１）有効成分と、２）極性溶媒と、３）非イオン性界面活性剤とを含有する外用医薬組成物であって、前記有効成分は可溶化されており、使用時に泡状である、ポンプ式フォーマー用の外用医薬組成物に、ビタミン類、ステロイドなどの有効成分の均一性を高めるような特性を見出し、発明を完成させるに至った。即ち、本発明は、以下に示すとおりである。
＜１＞ １）有効成分と、２）極性溶剤と、３）非イオン性界面活性剤とを含有する外用医薬組成物であって、前記有効成分は可溶化されており、使用時に泡状であることを特徴とする、外用医薬組成物。
＜２＞ 前記有効成分として、ビタミン類及び／又はステロイドを選択することを特徴とする、＜１＞に記載の外用医薬組成物。
＜３＞ 前記ビタミン類は、ビタミンＡ又はその誘導体、ビタミンＢ又はその誘導体、油溶性ビタミンＣ、ビタミンＤ又はその誘導体、ビタミンＥ又はその誘導体、ビタミンＫ又はその誘導体、から選択される１種又は２種以上であることを特徴とする、＜１＞又は＜２＞に記載の外用医薬組成物。
＜４＞ 前記ステロイドは、ベタメタゾンの短鎖カルボン酸ジエステル及びクロベタゾールの短鎖カルボン酸エステルから選択されるものであることを特徴とする、＜１＞〜＜３＞何れかに記載の外用医薬組成物。
＜５＞ 前記極性溶剤が、Ｎ−アルキル−２−ピロリドン、炭酸ジエステル、クロタミトン、多価アルコールのアシル化物及びエーテル化物より選択される１種又は２種以上であることを特徴とする、＜１＞〜＜４＞何れかに記載の外用医薬組成物。
＜６＞ 前記非イオン性界面活性剤は、ポリオキシエチレンが付加されていても良い脂肪酸モノグリセリド、ポリグリセリンの脂肪酸エステル、ポリオキシエチレンが付加されていても良いソルビタン脂肪酸エステル、ポリオキシエチレン脂肪酸エステル、ポリオキシエチレンのアルキル乃至はアルケニルエーテル、ポリオキシエチレンポリオキシプロピレンアルキルエーテル、脂肪酸ジエタノールアミド及び水素添加されていても良いポリオキシエチレンヒマシ油から選択されるものであることを特徴とする、＜１＞〜＜５＞何れかに記載の外用医薬組成物。
＜７＞ 更に、アニオン性界面活性剤を含有することを特徴とする、＜１＞〜＜６＞何れかに記載の外用医薬組成物。
＜８＞ 使用時に形成される泡は、ポンプ式フォーマーによるものであることを特徴とする、＜１＞〜＜７＞何れかに記載の外用医薬組成物。In view of such a situation, the present inventors solve the problem that arises in the relationship between the active ingredient such as vitamins and steroids and the preparation ingredient, particularly the uniformity of application, in the composition for the pump type former. As a result of diligent research efforts seeking means, an external pharmaceutical composition containing 1) an active ingredient, 2) a polar solvent, and 3) a nonionic surfactant, the active ingredient being acceptable The invention has been completed by finding characteristics that enhance the uniformity of active ingredients such as vitamins and steroids in an external pharmaceutical composition for a pump-type former, which is dissolved and foamed when used. That is, the present invention is as follows.
<1> A pharmaceutical composition for external use containing 1) an active ingredient, 2) a polar solvent, and 3) a nonionic surfactant, wherein the active ingredient is solubilized and foamed during use A pharmaceutical composition for external use, which is characterized in that it exists.
<2> The external pharmaceutical composition according to <1>, wherein vitamins and / or steroids are selected as the active ingredient.
<3> The vitamin is one or more selected from vitamin A or a derivative thereof, vitamin B or a derivative thereof, oil-soluble vitamin C, vitamin D or a derivative thereof, vitamin E or a derivative thereof, vitamin K or a derivative thereof The external pharmaceutical composition according to <1> or <2>, wherein there are two or more kinds.
<4> The external pharmaceutical composition according to any one of <1> to <3>, wherein the steroid is selected from a short-chain carboxylic acid diester of betamethasone and a short-chain carboxylic acid ester of clobetasol. object.
<5> The polar solvent is one or more selected from N-alkyl-2-pyrrolidone, carbonic acid diester, crotamiton, acylated product and etherified product of polyhydric alcohol, <1 >-<4> External pharmaceutical composition in any one.
<6> The nonionic surfactant is a fatty acid monoglyceride to which polyoxyethylene may be added, a fatty acid ester of polyglycerol, a sorbitan fatty acid ester to which polyoxyethylene may be added, or a polyoxyethylene fatty acid ester. , Characterized by being selected from polyoxyethylene alkyl or alkenyl ether, polyoxyethylene polyoxypropylene alkyl ether, fatty acid diethanolamide and optionally hydrogenated polyoxyethylene castor oil, <1>-<5> External pharmaceutical composition in any one.
<7> The pharmaceutical composition for external use according to any one of <1> to <6>, further comprising an anionic surfactant.
<8> The external pharmaceutical composition according to any one of <1> to <7>, wherein the foam formed during use is due to a pump-type former.
本発明によれば、ポンプ式フォーマー用の組成物において、ビタミン類、ステロイド類などの有効成分と製剤成分との関係において生じる課題を解決する手段を提供することが出来る。ビタミン類及び／又はステロイド類においては、特に、これらの均一性を高める手段を提供することができる。 ADVANTAGE OF THE INVENTION According to this invention, in the composition for pump type | formers, the means which solves the subject which arises in the relationship between active ingredients, such as vitamins and steroids, and a formulation component can be provided. In the case of vitamins and / or steroids, in particular, a means for increasing the uniformity of these can be provided.
＜１＞本発明の外用医薬組成物の必須成分である有効成分
本発明の外用医薬組成物は、必須成分としてビタミン類、ステロイド類などの有効成分を含有することを特徴とする。本発明の外用医薬組成物に含有させることができる有効成分の内、ビタミン類としては、ビタミン類に属する化合物であれば特段の限定なく適用することができ、脂溶性ビタミンが好適に例示できる。前記ビタミン類に属する化合物としては、ビタミンＡ又はその誘導体、ビタミンＢ又はその誘導体、油溶性ビタミンＣ又はその誘導体、ビタミンＤ又はその誘導体、ビタミンＥ又はその誘導体、ビタミンＫ又はその誘導体が好適に例示でき、前記ビタミン類に属する化合物から１種又は２種以上を選択し外用医薬組成物に含有することが出来る。さらに、本発明の外用医薬組成物におけるビタミン類の好ましい含有量は、０．００００１〜３質量％、より好ましくは、０．０００５〜１質量％、さらに好ましくは、０．０００１〜０．１質量％である。これは、ビタミン類の含有量が少なすぎると期待される薬効が発揮されず、多すぎると、ビタミン類が可溶化されず、ビタミン類の均一性が低くなり、保持量が低下し、ビタミン類と製剤成分の好ましくない関係が生じるためである。<1> The active ingredient which is an essential component of the external pharmaceutical composition of the present invention The external pharmaceutical composition of the present invention is characterized by containing an active ingredient such as vitamins and steroids as an essential component. Among the active ingredients that can be contained in the external pharmaceutical composition of the present invention, as vitamins, any compound belonging to vitamins can be applied without particular limitation, and fat-soluble vitamins can be preferably exemplified. Preferred examples of the compounds belonging to the vitamins include vitamin A or a derivative thereof, vitamin B or a derivative thereof, oil-soluble vitamin C or a derivative thereof, vitamin D or a derivative thereof, vitamin E or a derivative thereof, vitamin K or a derivative thereof. One or two or more compounds selected from the vitamins can be selected and contained in the external pharmaceutical composition. Furthermore, the preferable content of vitamins in the external pharmaceutical composition of the present invention is 0.00001 to 3% by mass, more preferably 0.0005 to 1% by mass, and still more preferably 0.0001 to 0.1% by mass. %. This is because if the vitamin content is too low, the expected medicinal effects will not be exerted, and if it is too high, the vitamins will not be solubilized, the uniformity of the vitamins will be low, the holding amount will decrease, This is because there is an unfavorable relationship between and the formulation components.
さらに、本発明の外用医薬組成物に含有することができるステロイドとしては、糖質コルチコイドが好ましく、例えば、コルチゾン、ハイドロコルチゾン、酢酸フルドロコルチゾン等のコルチゾン類、プレドニゾロン、メチルプレドニゾロン等のプレドニゾロン類、デキサメタゾン及びその誘導体、ベタメタゾン及びその誘導体、クロベタゾール及びその誘導体が好適に例示でき、その誘導体としては、リン酸エステル、吉草酸エステル、酪酸エステル、プロピオン酸エステルなどが好ましく例示できる。また、該エステルは１種の酸のエステルであっても、混合酸のエステルでもよい。本発明のステロイドとしては、特に、ベタメタゾンの短鎖カルボン酸ジエステル及びクロベタゾールの短鎖カルボン酸エステルが好ましい。本発明のステロイドは、これらの例示に限定されるものではない。本発明の外用医薬組成物におけるステロイドの好ましい含有量は、０．００１〜１質量％、より好ましくは、０．００５〜０．５質量％である。これは、ステロイドの含有量が少なすぎると期待される薬効が発揮されず、多すぎると、外用医薬組成物に均一に相溶させ、製剤化することが困難であるためである。 Furthermore, the steroid that can be contained in the external pharmaceutical composition of the present invention is preferably a glucocorticoid, for example, cortisone such as cortisone, hydrocortisone, fludrocortisone acetate, prednisolones such as prednisolone, methylprednisolone, Dexamethasone and derivatives thereof, betamethasone and derivatives thereof, clobetasol and derivatives thereof can be preferably exemplified, and preferred derivatives thereof include phosphate esters, valerate esters, butyrate esters, propionate esters and the like. The ester may be an ester of one acid or a mixed acid. As the steroid of the present invention, betamethasone short-chain carboxylic acid diester and clobetasol short-chain carboxylic acid ester are particularly preferable. The steroid of the present invention is not limited to these examples. The preferable content of the steroid in the external pharmaceutical composition of the present invention is 0.001-1% by mass, more preferably 0.005-0.5% by mass. This is because the expected efficacy is not exhibited when the steroid content is too low, and when the steroid content is too high, it is difficult to uniformly dissolve the pharmaceutical composition into a pharmaceutical preparation for external use.
また、本発明の外用医薬組成物における有効成分としては、前記ビタミン類、ステロイド類のほか、例えば、テルビナフィン、ブテナフィン等の抗真菌剤、スプロフェン、ケトチフェン、ケトプロフェン、インドメタシン等の抗炎症剤、アジスロマイシン等の抗生剤、タクロリムス、シクロホスファミド等の免疫抑制剤、ナルフラフィンなどの鎮痒剤等が好適に例示でき、これらの好ましい含有量は０．００００００１〜１０質量％である。 In addition to the vitamins and steroids, the active ingredients in the external pharmaceutical composition of the present invention include, for example, antifungal agents such as terbinafine and butenafine, anti-inflammatory agents such as suprofen, ketotifen, ketoprofen and indomethacin, azithromycin and the like The antibacterial agent, tacrolimus, cyclophosphamide, and other immunosuppressive agents, and antipruritic agents, such as nalfraphine, can be preferably exemplified, and the preferred content thereof is 0.0000001 to 10% by mass.
さらに、本発明の外用医薬組成物の好ましい形態のひとつとして、前記ビタミン類及びステロイドから２種以上を選択し、両有効成分を組み合わせて使用することが好適に例示できる。本発明のビタミン類、ステロイド類を含有する外用医薬組成物は、皮膚炎症、湿疹、乾癬等の皮膚疾患の処置、即ち、治療、それ以上悪化させない予防的治療及び発症することを防ぐ予防に好適に適用される。また、ビタミン類及びステロイド類の含有量が前記の範囲であれば、本発明の外用医薬組成物に均一に相溶させ、両有効成分が可溶化され、使用時に泡の形状で使用することができる。このような製剤では、刺激感を感じることなくスムーズに患部に延展することができ、薬剤を患部に均一に分布させることが出来る。本発明の外用医薬組成物において、ビタミン類及びステロイドを組み合わせる場合に用いるビタミン類としてはマキサカルシトール、トレチノイントコフェリル、アダパレン、カルシポトリオールなどが好適に例示でき、糖質ステロイドとしては、ベタメタゾンの短鎖カルボン酸ジエステル及びクロベタゾールの短鎖カルボン酸エステルなどが好適に例示でき、かかる成分を組み合わせることが特に好ましい。かかるビタミン類及びステロイドの組み合わせにより製造される外用医薬組成物は、可溶化が比較的容易であり、均一性に優れる。 Furthermore, as one of the preferable forms of the external pharmaceutical composition of the present invention, it can be suitably exemplified that two or more kinds are selected from the vitamins and steroids, and both active ingredients are used in combination. The pharmaceutical composition for external use containing the vitamins and steroids of the present invention is suitable for treatment of skin diseases such as skin inflammation, eczema and psoriasis, that is, treatment, prophylactic treatment that does not worsen further, and prevention of onset. Applies to Further, if the content of vitamins and steroids is within the above range, it can be uniformly dissolved in the pharmaceutical composition for external use of the present invention so that both active ingredients are solubilized and used in the form of foam at the time of use. it can. Such a preparation can be smoothly spread to the affected area without feeling irritation, and the drug can be uniformly distributed to the affected area. In the pharmaceutical composition for external use of the present invention, as vitamins used in combination with vitamins and steroids, maxacalcitol, tretinointocopheryl, adapalene, calcipotriol and the like can be suitably exemplified, and as the carbohydrate steroid, betamethasone The short-chain carboxylic acid diester and clobetasol short-chain carboxylic acid ester can be suitably exemplified, and it is particularly preferable to combine such components. A pharmaceutical composition for external use produced by a combination of such vitamins and steroids is relatively easy to solubilize and is excellent in uniformity.
＜２＞本発明の外用医薬組成物の必須成分である極性溶剤
本発明の外用医薬組成物は、極性溶剤を含有することを特徴とする。本発明の極性溶剤としては、Ｎ−アルキル−２−ピロリドン、炭酸ジエステル、クロタミトン、多価アルコールのアシル化物及びエーテル化物から選択される１種又は２種以上の溶剤を選択し含有させることが好ましい。これらの溶剤は、ポンプ式フォーマーによる起泡性を損なうことなく、ビタミン類、ステロイド等の有効成分を可溶化し均一性を高め、有効成分の保持量を高く維持する作用を有する。さらに、かかる溶剤を使用することにより有効成分の可溶化し保持量を高く維持しながら、皮膚への刺激等の副作用を低減することが出来る。本発明の極性溶剤が、前記作用を発現するためには、かかる成分は外用医薬組成物全量に対して、全量で０．１〜１２質量％含有されることが好ましく、０．５〜１０質量％含有されることがより好ましい。これは少なすぎるとビタミン類、ステロイドなどの有効成分を溶解することができず、多すぎると起泡性が損なわれる場合が存するためである。本発明のＮ−アルキル−２−ピロリドンとしては、炭素数１〜４のアルキル基を有するＮ−アルキル−２−ピロリドンが好適に例示でき、特に、Ｎ−メチル−２−ピロリドン、Ｎ−エチル−２−ピロリドンが好適に例示できる。Ｎ−メチル−２−ピロリドンは、優れた特性を有する極性溶媒であり、ほとんどの有機溶媒、水と混合することができ、医薬添加物として使用されている実績がある。本発明の炭酸ジエステルとしては、環状構造を有する炭酸アルキレン、直鎖又は分岐の炭化水素基が２つ結合した炭酸ジアルキル等が好適に例示でき、特に、炭酸プロピレンが好ましい。本発明のクロタミトンは、優れた溶解性を有する極性溶剤であり、ビタミン類、ステロイドなどの有効成分の分解を抑制し安定性を向上させることができる。本発明の多価アルコールのアシル化物としては、短鎖もしくは中鎖脂肪酸のトリグリセリド又は短鎖乃至は長鎖の脂肪酸と（ポリ）エチレングリコールのエステルが好適に例示でき、より好ましくは、トリアセチン、トリカプリリン、トリオクタン酸グリセリン及びトリ（カプリル・カプリン酸）グリセリン、（ポリ）エチレングリコールモノアセテート、ポリエチレングリコールモノラウレート及びポリエチレングリコールモノオレートが挙げられる。本発明の多価アルコールのエーテル化物としては、ポリエチレングリコールアルキルエーテル、ポリオキチエチレンアルキルエーテル及びポリオキシエチレン・ポリオキシプロピレンアルキルエーテルが好適に例示でき、さらに好ましいものとしては、ジエチレングリコールモノエチルエーテル、ジエチレングリコールモノベンジルエーテル、ジエチレングリコールジエチルエーテル、トリエチレングリコールジメチルエーテル、ポリオキシエチレンラウリルエーテル、ポリオキチエチレンセチルエーテルが挙げられる。<2> Polar solvent as an essential component of the external pharmaceutical composition of the present invention The external pharmaceutical composition of the present invention is characterized by containing a polar solvent. As the polar solvent of the present invention, it is preferable to select and contain one or more solvents selected from N-alkyl-2-pyrrolidone, carbonic acid diester, crotamiton, acylated products and etherified products of polyhydric alcohols. . These solvents have the action of solubilizing active ingredients such as vitamins and steroids, improving uniformity, and maintaining a high retention amount of the active ingredients without impairing the foaming properties of the pump-type former. Furthermore, by using such a solvent, it is possible to reduce side effects such as irritation to the skin while solubilizing the active ingredient and maintaining a high retention amount. In order for the polar solvent of the present invention to exhibit the above-described action, it is preferable that the component is contained in an amount of 0.1 to 12% by mass, based on the total amount of the external pharmaceutical composition, % Content is more preferable. This is because if the amount is too small, active ingredients such as vitamins and steroids cannot be dissolved, and if the amount is too large, the foamability may be impaired. As the N-alkyl-2-pyrrolidone of the present invention, N-alkyl-2-pyrrolidone having an alkyl group having 1 to 4 carbon atoms can be suitably exemplified, and in particular, N-methyl-2-pyrrolidone, N-ethyl- 2-pyrrolidone can be suitably exemplified. N-methyl-2-pyrrolidone is a polar solvent having excellent properties, can be mixed with most organic solvents and water, and has a track record of being used as a pharmaceutical additive. Preferred examples of the carbonic acid diester of the present invention include alkylene carbonate having a cyclic structure, dialkyl carbonate having two linear or branched hydrocarbon groups bonded thereto, and propylene carbonate is particularly preferred. The crotamiton of the present invention is a polar solvent having excellent solubility, and can suppress the decomposition of active ingredients such as vitamins and steroids and improve the stability. Preferred examples of the acylated product of the polyhydric alcohol of the present invention include triglycerides of short chain or medium chain fatty acids or esters of short or long chain fatty acids and (poly) ethylene glycol, more preferably triacetin, trica Examples include prelin, glycerin trioctanoate and tri (capryl-capric acid) glycerin, (poly) ethylene glycol monoacetate, polyethylene glycol monolaurate and polyethylene glycol monooleate. Examples of the etherified product of the polyhydric alcohol of the present invention include polyethylene glycol alkyl ether, polyoxyethylene alkyl ether and polyoxyethylene / polyoxypropylene alkyl ether, and more preferable examples include diethylene glycol monoethyl ether and diethylene glycol. Examples thereof include monobenzyl ether, diethylene glycol diethyl ether, triethylene glycol dimethyl ether, polyoxyethylene lauryl ether, and polyoxyethylene cetyl ether.
＜３＞本発明の外用医薬組成物の必須成分である非イオン性界面活性剤
本発明の外用医薬組成物は、非イオン性界面活性剤を必須成分として含有することを特徴とする。本発明の非イオン性界面活性剤としては、ポリオキシエチレンが付加されていても良い脂肪酸モノグリセリド、ポリグリセリンの脂肪酸エステル、ポリオキシエチレン脂肪酸エステル、ポリオキシエチレンが付加されていても良いソルビタン脂肪酸エステル、ポリオキシエチレンのアルキル乃至はアルケニルエーテル、ポリオキシエチレンポリオキシプロピレンアルキルエーテル、脂肪酸ジエタノールアミド及び水素添加されていても良いポリオキシエチレンヒマシ油等の非イオン界面活性から選択される１種又２種以上を選択し本発明の外用医薬組成物に含有させることが好ましい。ここで、ポリオキシエチレン又はポリオキシプロピレンの平均付加モル数は２〜９０が好ましい。また、脂肪酸エステルを構成する脂肪酸の炭素数は平均で６〜２４が好ましく、より好ましくは、６〜２２である。アルキル基、アルケニル基の平均炭素数は１０〜２２が好ましい。脂肪酸ジエタノールアミドを構成する脂肪酸としては炭素数１０〜１８のものが好ましく、１０〜１４のものが特に好ましい。さらに、本発明における非イオン性界面活性剤の特に好ましい態様は、ポリオキシエチレン（平均付加モル数６〜１０）脂肪酸（平均炭素数６〜１４）グリセリル又は脂肪酸ジエタノールアミドと、ポリオキシエチレン（平均付加モル数２〜５０）アルキル乃至はアルケニルエーテル及び／又は素添加されていても良いポリオキシエチレン（平均付加モル数３０〜９０）ヒマシ油を含有する形態、ポリオキシエチレン（平均付加モル数２〜５０）アルキル乃至はアルケニルエーテルに加え、ポリオキシエチレンが付加されていても良い脂肪酸モノグリセリド、ポリグリセリンの脂肪酸エステル、ポリオキシエチレン（平均付加モル数５〜７０）脂肪酸エステル、ポリオキシエチレン（平均付加モル数１０〜５０）が付加されていても良いソルビタン脂肪酸（炭素数１２〜２２）エステル、ポリオキシエチレン（平均付加モル数２〜５０）ポリオキシプロピレン（平均付加モル数２〜５０）アルキルエーテル、水素添加されていても良いポリオキシエチレン（平均付加モル数３０〜９０）ヒマシ油から選択される１種又２種以上を選択し含有させる形態が好ましい。前記の好ましい形態において、ポリオキシエチレン脂肪酸グリセリル又は脂肪酸ジエタノールアミドと、ポリオキシエチレンアルキル乃至はアルケニルエーテル及び／又は水素添加されていても良いポリオキシエチレンの質量比は、１：４〜４：１が可溶化系を安定化させる意味で特に好ましい。さらに、前記の好ましい形態において、ポリオキシエチレン（平均付加モル数２〜５０）アルキル乃至はアルケニルエーテルと、ポリオキシエチレンが付加されていても良い脂肪酸モノグリセリド、ポリグリセリンの脂肪酸エステル、ポリオキシエチレン（平均付加モル数５〜７０）脂肪酸エステル、ポリオキシエチレン（平均付加モル数１０〜５０）が付加されていても良いソルビタン脂肪酸（炭素数１２〜１８）エステル、ポリオキシエチレン（平均付加モル数２〜５０）ポリオキシプロピレン（平均付加モル数２〜５０）アルキルエーテル、水素添加されていても良いポリオキシエチレン（平均付加モル数３０〜９０）ヒマシ油より選択される１種又は２種以上の非イオン性界面活性剤の質量比は、１：４〜４：１が可溶化系を安定化させる意味で好ましい。また、本発明の非イオン性界面活性剤は、１種類の非イオン界面活性剤を単独で使用することも出来るが、良質な泡質となりにくいため２種類以上の非イオン性界面活性剤を組み合わせて用いることが好ましい。尚、本発明の外用医薬組成物は、損傷されている可能性のある皮膚に投与され、洗浄行為を伴わない態様で使用される可能性も存することから、非イオン性界面活性剤のみを含有させることが好ましい。本発明の外用医薬組成物における、非イオン性界面活性剤の好ましい含有量は、医薬組成物全量に対して、０．５〜１０質量％であり、より好ましくは１〜８質量％である。<3> Nonionic surfactant which is an essential component of the external pharmaceutical composition of the present invention The external pharmaceutical composition of the present invention is characterized by containing a nonionic surfactant as an essential component. As the nonionic surfactant of the present invention, fatty acid monoglyceride to which polyoxyethylene may be added, fatty acid ester of polyglycerol, polyoxyethylene fatty acid ester, sorbitan fatty acid ester to which polyoxyethylene may be added 1 or 2 selected from nonionic surfactants such as polyoxyethylene alkyl or alkenyl ether, polyoxyethylene polyoxypropylene alkyl ether, fatty acid diethanolamide and optionally hydrogenated polyoxyethylene castor oil It is preferable that at least one species is selected and contained in the external pharmaceutical composition of the present invention. Here, the average added mole number of polyoxyethylene or polyoxypropylene is preferably 2 to 90. Moreover, 6-24 are preferable on average for the carbon number of the fatty acid which comprises fatty acid ester, More preferably, it is 6-22. As for the average carbon number of an alkyl group and an alkenyl group, 10-22 are preferable. As the fatty acid constituting the fatty acid diethanolamide, those having 10 to 18 carbon atoms are preferred, and those having 10 to 14 are particularly preferred. Furthermore, a particularly preferred embodiment of the nonionic surfactant in the present invention is a polyoxyethylene (average added mole number 6 to 10) fatty acid (average carbon number 6 to 14) glyceryl or fatty acid diethanolamide and polyoxyethylene (average Addition mole number 2-50) Alkyl or alkenyl ether and / or polyoxyethylene (average addition mole number 30-90) which may be primed, a form containing castor oil, polyoxyethylene (average addition mole number 2) -50) Fatty acid monoglyceride to which polyoxyethylene may be added in addition to alkyl or alkenyl ether, fatty acid ester of polyglycerin, polyoxyethylene (average added mole number 5 to 70) fatty acid ester, polyoxyethylene (average) Sol having an additional mole number of 10 to 50) may be added. Tan fatty acid (carbon number 12-22) ester, polyoxyethylene (average addition mole number 2-50) polyoxypropylene (average addition mole number 2-50) alkyl ether, hydrogenated polyoxyethylene (average (Addition mole number 30-90) The form which selects and contains 1 type, or 2 or more types selected from castor oil is preferable. In the preferred form, the mass ratio of polyoxyethylene fatty acid glyceryl or fatty acid diethanolamide to polyoxyethylene alkyl or alkenyl ether and / or polyoxyethylene which may be hydrogenated is 1: 4 to 4: 1. Is particularly preferred in the sense of stabilizing the solubilization system. Further, in the preferred form, polyoxyethylene (average added mole number 2 to 50) alkyl or alkenyl ether, fatty acid monoglyceride to which polyoxyethylene may be added, fatty acid ester of polyglycerol, polyoxyethylene ( Average addition mole number 5 to 70) Fatty acid ester, polyoxyethylene (average addition mole number 10 to 50) sorbitan fatty acid (carbon number 12 to 18) ester, polyoxyethylene (average addition mole number 2) -50) One or more selected from polyoxypropylene (average added mole number 2-50) alkyl ether, optionally hydrogenated polyoxyethylene (average added mole number 30-90) castor oil The mass ratio of the nonionic surfactant is 1: 4 to 4: 1, which stabilizes the solubilization system. Preferred in the sense that. In addition, the nonionic surfactant of the present invention can use one kind of nonionic surfactant alone, but since it is difficult to obtain a high quality foam, two or more kinds of nonionic surfactants are combined. Are preferably used. The external pharmaceutical composition of the present invention contains only a nonionic surfactant because it may be administered to skin that may be damaged and may be used in a mode that does not involve cleaning. It is preferable to make it. The preferable content of the nonionic surfactant in the external pharmaceutical composition of the present invention is 0.5 to 10% by mass, more preferably 1 to 8% by mass, based on the total amount of the pharmaceutical composition.
さらに、本発明の外用医薬組成物においては、前記非イオン界面活性剤にアニオン性界面活性剤を加える形態も好ましい。アニオン性界面活性剤は、唯１種を選択し外用医薬組成物に含有することも出来るし、複数の界面活性剤を選択し含有させることも出来る。本発明の外用医薬組成物においては、非イオン性界面活性剤にアニオン性界面活性剤を加えることにより、有効成分と製剤成分との好ましい状態を作り出すことが出来る。一方、カチオン性界面活性剤及び両性界面活性剤は実質的に含有しないことが好ましい。 Furthermore, in the external pharmaceutical composition of this invention, the form which adds an anionic surfactant to the said nonionic surfactant is also preferable. Only one kind of anionic surfactant can be selected and contained in the external pharmaceutical composition, or a plurality of surfactants can be selected and contained. In the external pharmaceutical composition of the present invention, by adding an anionic surfactant to the nonionic surfactant, a preferable state of the active ingredient and the formulation ingredient can be created. On the other hand, it is preferable that the cationic surfactant and the amphoteric surfactant are not substantially contained.
＜４＞本発明の外用医薬組成物のアニオン性界面活性剤
本発明の外用医薬組成物は、前記必須成分に加えアニオン性界面活性剤を含有することが好ましい。かかるアニオン性界面活性剤としては、例えば、ラウリン酸ナトリウム、パルミチン酸カリウム、ステアリン酸アルギニン等の炭素数１２〜２４の脂肪酸塩；ラウリル硫酸ナトリウム、ラウリル硫酸カリウム、セチル硫酸ナトリウム等のアルキル硫酸エステル塩；ポリオキシエチレンラウリル硫酸トリエタノールアミン等のアルキルエーテル硫酸エステル塩；ラウロイルサルコシンナトリウム等のＮ−アシルサルコシン塩；Ｎ−ステアロイル−Ｎ−メチルタウリンナトリウム、Ｎ−ミリストイル−Ｎ−メチルタウリンナトリウム等の脂肪酸アミドスルホン酸塩；モノステアリルリン酸ナトリウム等のアルキルリン酸塩；ポリオキシエチレンオレイルエーテルリン酸ナトリウム、ポリオキシエチレンステアリルエーテルリン酸ナトリウム、ポリオキシエチレンセチルエーテルリン酸ナトリウム等のポリオキシエチレンアルキルエーテルリン酸塩；ジ−２−エチルヘキシルスルホコハク酸ナトリウム等の長鎖スルホコハク酸塩；Ｎ−ラウロイルグルタミン酸モノナトリウム、Ｎ−ステアロイル−Ｌ−グルタミン酸ナトリウム、Ｎ−ステアロイル−Ｌ−グルタミン酸アルギニン、Ｎ−ステアロイルグルタミン酸ナトリウム、Ｎ−ミリストイル−Ｌ−グルタミン酸ナトリウム等の長鎖Ｎ−アシルグルタミン酸塩などが挙げられる。かかるアニオン性界面活性剤は、非イオン性界面活性剤と共に本発明の外用医薬組成物に含有させることにより、有効成分と製剤成分との関係において生じる課題、中でも、有効成分の可溶化を促進し均一性を高め、有効成分の保持量を高めることが出来る。本発明の外用医薬組成物における、アニオン性界面活性剤の好ましい含有量は、医薬組成物全量に対して、０．００１〜５質量％であり、より好ましくは０．０１〜３質量％である。これは、アニオン界面活性剤の含有量が低すぎると可溶化が促進させず、高すぎると皮膚刺激性等の作用が生じるためである。<4> Anionic surfactant of the external pharmaceutical composition of the present invention The external pharmaceutical composition of the present invention preferably contains an anionic surfactant in addition to the essential components. Examples of the anionic surfactant include fatty acid salts having 12 to 24 carbon atoms such as sodium laurate, potassium palmitate and arginine stearate; alkyl sulfate esters such as sodium lauryl sulfate, potassium lauryl sulfate and sodium cetyl sulfate. Alkyl ether sulfates such as polyoxyethylene lauryl sulfate triethanolamine; N-acyl sarcosine salts such as sodium lauroyl sarcosine; fatty acids such as sodium N-stearoyl-N-methyltaurine and sodium N-myristoyl-N-methyltaurine Amidosulfonates; alkyl phosphates such as sodium monostearyl phosphate; polyoxyethylene oleyl ether sodium phosphate, polyoxyethylene stearyl ether sodium phosphate, poly Polyoxyethylene alkyl ether phosphates such as sodium xylethylene cetyl ether; long-chain sulfosuccinates such as sodium di-2-ethylhexyl sulfosuccinate; monosodium N-lauroyl glutamate, sodium N-stearoyl-L-glutamate, Long chain N-acyl glutamates such as arginine N-stearoyl-L-glutamate, sodium N-stearoyl glutamate, sodium N-myristoyl-L-glutamate and the like can be mentioned. Such an anionic surfactant, together with the nonionic surfactant, promotes the solubilization of the active ingredient, particularly the problem that arises in the relationship between the active ingredient and the pharmaceutical ingredient, by including it in the external pharmaceutical composition of the present invention. Uniformity can be improved and the amount of active ingredients retained can be increased. The preferable content of the anionic surfactant in the external pharmaceutical composition of the present invention is 0.001 to 5 mass%, more preferably 0.01 to 3 mass%, based on the total amount of the pharmaceutical composition. . This is because solubilization is not promoted if the content of the anionic surfactant is too low, and effects such as skin irritation occur if the content is too high.
＜５＞本発明の外用医薬組成物
本発明の外用医薬組成物は、前記の必須成分を含有し、可溶化剤形であって、外用の形態で使用されることを特徴とする。本発明の外用医薬組成物においては、前記必須成分以外に、通常医薬組成物に用いられる製剤化のための任意の成分を含有することができる。このような成分としては、例えば、マカデミアナッツ油、アボガド油、トウモロコシ油、オリーブ油、ナタネ油、ゴマ油、ヒマシ油、サフラワー油、綿実油、ホホバ油、ヤシ油、パーム油、液状ラノリン、硬化ヤシ油、硬化油、モクロウ、硬化ヒマシ油、ミツロウ、キャンデリラロウ、カルナウバロウ、イボタロウ、ラノリン、還元ラノリン、硬質ラノリン、ホホバロウ等のオイル、ワックス類；流動パラフィン、スクワラン、プリスタン、オゾケライト、パラフィン、セレシン、ワセリン、マイクロクリスタリンワックス等の炭化水素類；オレイン酸、イソステアリン酸、ラウリン酸、ミリスチン酸、パルミチン酸、ステアリン酸、ベヘン酸、ウンデシレン酸等の高級脂肪酸類；セチルアルコール、ステアリルアルコール、イソステアリルアルコール、ベヘニルアルコール、オクチルドデカノール、ミリスチルアルコール、セトステアリルアルコール等の高級アルコール等；イソオクタン酸セチル、ミリスチン酸イソプロピル、イソステアリン酸ヘキシルデシル、ジ−２−エチルヘキサン酸エチレングリコール、ジカプリン酸ネオペンチルグリコール、ジ−２−ヘプチルウンデカン酸グリセリン、トリ−２−エチルヘキサン酸グリセリン、トリ−２−エチルヘキサン酸トリメチロールプロパン、トリイソステアリン酸トリメチロールプロパン、テトラ−２−エチルヘキサン酸ペンタンエリトリット等の合成エステル油類；ジメチルポリシロキサン、メチルフェニルポリシロキサン、ジフェニルポリシロキサン等の鎖状ポリシロキサン；オクタメチルシクロテトラシロキサン、デカメチルシクロペンタシロキサン、ドデカメチルシクロヘキサンシロキサン等の環状ポリシロキサン；アミノ変性ポリシロキサン、アルキル変性ポリシロキサン、フッ素変性ポリシロキサン等の変性ポリシロキサン等のシリコーン油等の油剤類；ポリエチレングリコール、グリセリン、１，３−ブチレングリコール、エリスリトール、ソルビトール、キシリトール、マルチトール、プロピレングリコール、ジプロピレングリコール、ジグリセリン、イソプレングリコール、１，２−ペンタンジオール、２，４−ヘキサンジオール、１，２−ヘキサンジオール、１，２−オクタンジオール等の多価アルコール類；乳酸、乳酸ナトリウム等の保湿成分類；表面を処理されていても良い、マイカ、タルク、カオリン、合成雲母、炭酸カルシウム、炭酸マグネシウム、無水ケイ酸（シリカ）、酸化アルミニウム、硫酸バリウム等の粉体類、；表面を処理されていても良い、ベンガラ、黄酸化鉄、黒酸化鉄、酸化コバルト、群青、紺青、酸化チタン、酸化亜鉛の無機顔料類；表面を処理されていても良い、雲母チタン、魚燐箔、オキシ塩化ビスマス等のパール剤類；レーキ化されていても良い赤色２０２号、赤色２２８号、赤色２２６号、黄色４号、青色４０４号、黄色５号、赤色５０５号、赤色２３０号、赤色２２３号、橙色２０１号、赤色２１３号、黄色２０４号、黄色２０３号、青色１号、緑色２０１号、紫色２０１号、赤色２０４号等の有機色素類；ポリエチレン末、ポリメタクリル酸メチル、ナイロン粉末、オルガノポリシロキサンエラストマー等の有機粉体類；パラアミノ安息香酸系紫外線吸収剤；アントラニル酸系紫外線吸収剤；サリチル酸系紫外線吸収剤、；桂皮酸系紫外線吸収剤、；ベンゾフェノン系紫外線吸収剤；糖系紫外線吸収剤；２−（２’−ヒドロキシ−５’−ｔ−オクチルフェニル）ベンゾトリアゾール、４−メトキシ−４’−ｔ−ブチルジベンゾイルメタン等の紫外線吸収剤類；エタノール、イソプロパノール等の低級アルコール類；フェノキシエタノール等の抗菌剤などが好ましく例示できる。さらに、前記極性溶剤以外の溶剤としては多価アルコールが好ましく例示でき、多価アルコールは、単独で使用することも出来るし、複数の多価アルコールを組み合わせ医薬組成物に含有させることも出来る。前記多価アルコールとしては１，３−ブチレングリコール、プロピレングリコール、１，２−ペンタンジオールなどが好適に例示でき、特に、１，３−ブチレングリコールが好ましい。多価アルコールの含有量は５〜４０質量％、より好ましくは、８〜３５質量％が好ましい。これらを用いて、常法に従って、可溶化形態の医薬組成物に加工し、ポンプ式フォーマーに充填し外用医薬に加工することができる。また、本発明の使用時に泡状を呈する外用医薬組成物は、使用時に泡状を呈する医薬外用剤であれば特段の限定なく適用することができ、例えば、ガス充填タイプのフォーマ容器に充填する外用医薬組成物、ノンガスタイプのフォーマー容器に充填する外用医薬組成物が好適に例示でき、特に、ノンガスタイプのフォーマー容器に充填するタイプの外用医薬組成物が好ましい。これは、ノンガスタイプのポンプフォーマー容器に充填するタイプの外用剤が、使用時における泡質、均一性に優れるためである。<5> The external pharmaceutical composition of the present invention The external pharmaceutical composition of the present invention contains the above-mentioned essential components, is in a solubilizing agent form, and is used in an external form. In the pharmaceutical composition for external use of the present invention, in addition to the essential components, any component for formulation that is usually used in a pharmaceutical composition can be contained. Examples of such ingredients include macadamia nut oil, avocado oil, corn oil, olive oil, rapeseed oil, sesame oil, castor oil, safflower oil, cottonseed oil, jojoba oil, coconut oil, palm oil, liquid lanolin, hydrogenated coconut oil, Hardened oil, mole, hardened castor oil, beeswax, candelilla wax, carnauba wax, ibotarou, lanolin, reduced lanolin, hard lanolin, jojoba wax and other oils, waxes; liquid paraffin, squalane, pristane, ozokerite, paraffin, ceresin, petrolatum, Hydrocarbons such as microcrystalline wax; higher fatty acids such as oleic acid, isostearic acid, lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, undecylenic acid; cetyl alcohol, stearyl alcohol, isostearyl Higher alcohols such as alcohol, behenyl alcohol, octyldodecanol, myristyl alcohol, cetostearyl alcohol; cetyl isooctanoate, isopropyl myristate, hexyldecyl isostearate, ethylene glycol di-2-ethylhexanoate, neopentyl glycol dicaprate, di Synthetic ester oils such as glycerin-2-heptylundecanoate, glycerin tri-2-ethylhexanoate, trimethylolpropane tri-2-ethylhexanoate, trimethylolpropane triisostearate, pentane erythritol tetra-2-ethylhexanoate Chain polymers such as dimethylpolysiloxane, methylphenylpolysiloxane and diphenylpolysiloxane; octamethylcyclotetrasiloxane, deca Cyclic polysiloxanes such as tilcyclopentasiloxane and dodecamethylcyclohexanesiloxane; oils such as silicone oils such as amino-modified polysiloxanes, alkyl-modified polysiloxanes, and modified polysiloxanes such as fluorine-modified polysiloxanes; polyethylene glycol, glycerin, 1, 3-butylene glycol, erythritol, sorbitol, xylitol, maltitol, propylene glycol, dipropylene glycol, diglycerin, isoprene glycol, 1,2-pentanediol, 2,4-hexanediol, 1,2-hexanediol, 1, Polyhydric alcohols such as 2-octanediol; Moisturizing ingredients such as lactic acid and sodium lactate; Mica, talc, kaolin, synthetic mica, calcium carbonate, carbonate Powders such as gnesium, anhydrous silicic acid (silica), aluminum oxide, barium sulfate; surface may be treated, bengara, yellow iron oxide, black iron oxide, cobalt oxide, ultramarine, bitumen, titanium oxide, Zinc oxide inorganic pigments; surface treated pearl agents such as titanium mica, fish phosphorus foil, bismuth oxychloride; red 202, red 228, red 226 optionally raked Yellow 4, Blue 404, Yellow 5, Red 505, Red 230, Red 223, Orange 201, Red 213, Yellow 204, Yellow 203, Blue 1, Green 201, Purple Organic pigments such as 201 and red 204; organic powders such as polyethylene powder, polymethyl methacrylate, nylon powder, organopolysiloxane elastomer; paraaminobenzoic acid series An external radiation absorber; anthranilic acid ultraviolet absorber; salicylic acid ultraviolet absorber; cinnamic acid ultraviolet absorber; benzophenone ultraviolet absorber; sugar ultraviolet absorber; 2- (2′-hydroxy-5′-t Preferred examples include UV absorbers such as -octylphenyl) benzotriazole and 4-methoxy-4'-t-butyldibenzoylmethane; lower alcohols such as ethanol and isopropanol; and antibacterial agents such as phenoxyethanol. Furthermore, a polyhydric alcohol can be preferably exemplified as a solvent other than the polar solvent, and the polyhydric alcohol can be used alone or a combination of a plurality of polyhydric alcohols can be contained in the pharmaceutical composition. As the polyhydric alcohol, 1,3-butylene glycol, propylene glycol, 1,2-pentanediol and the like can be suitably exemplified, and 1,3-butylene glycol is particularly preferable. The content of the polyhydric alcohol is preferably 5 to 40% by mass, more preferably 8 to 35% by mass. Using these, it can be processed into a pharmaceutical composition in a solubilized form according to a conventional method, filled into a pump-type former and processed into an external medicine. Moreover, the external pharmaceutical composition that exhibits a foam during use of the present invention can be applied without particular limitation as long as it is a pharmaceutical external preparation that exhibits a foam during use. For example, it is filled in a gas-filled former container An external pharmaceutical composition and an external pharmaceutical composition filled in a non-gas type former container can be suitably exemplified, and an external pharmaceutical composition filled in a non-gas type former container is particularly preferable. This is because the external preparation of the type filled in the non-gas type pump former container is excellent in foam quality and uniformity during use.
かくして得られた外用医薬組成物は、可溶化剤形故に、有効成分を溶解しており、使用時に泡の形状で使用できるため、スムースに刺激を感じさせることなく患部に延展でき、患部に均一に有効成分を分布させることができる。このような態様により、有効成分の効果をいかんなく発揮させることができる。
以下、実施例を挙げて本発明についてさらに詳細に説明を加える。The pharmaceutical composition for external use thus obtained dissolves the active ingredient because of the solubilizing agent, and can be used in the form of foam when in use, so it can be smoothly spread to the affected area without causing irritation, and uniform in the affected area. The active ingredient can be distributed in By such an aspect, the effect of an active ingredient can be exhibited fully.
Hereinafter, the present invention will be described in more detail with reference to examples.
以下の表１に示す処方に従って、本発明の外用医薬組成物１を作成した。即ち、処方成分を８０℃で加熱攪拌し、可溶化し、攪拌下室温まで冷却し、本発明の外用医薬組成物１を得た。また、表１の極性溶媒を水に置換した場合には、ベタメゾン酪酸エステルプロピオン酸エステルは溶解しなかった。前記外用医薬組成物１をポンプ式フォーマーに充填し、本発明の外用医薬１を得た。尚、表中の製剤成分の含有量は、組成物全量に対する質量％にて表示した。 According to the formulation shown in Table 1 below, an external pharmaceutical composition 1 of the present invention was prepared. That is, the prescription ingredients were heated and stirred at 80 ° C., solubilized, and cooled to room temperature with stirring to obtain an external pharmaceutical composition 1 of the present invention. Moreover, when the polar solvent of Table 1 was substituted with water, the betamethasone butyrate propionate was not dissolved. The external pharmaceutical composition 1 was filled in a pump-type former to obtain the external pharmaceutical 1 of the present invention. In addition, content of the formulation component in a table | surface was displayed by the mass% with respect to the composition whole quantity.
＜比較例１＞
以下に示す処方に従って、比較例の外用医薬組成物を作成した。即ち、イの部分を８０℃で加熱可溶化し、予め８０℃に温度調節しておいた口の成分に攪拌下、混合し分散させた。しかる後に攪拌下室温まで冷却して比較例１の外用医薬組成物を得た。比較例１の外用医薬組成物をポンプ式フォーマーに充填し、比較例１の外用医薬を得た。尚、表中の製剤成分の含有量は、組成物全量に対する質量％にて表示した。<Comparative Example 1>
According to the formulation shown below, an external pharmaceutical composition of a comparative example was prepared. That is, the portion a was heat-solubilized at 80 ° C., and was mixed and dispersed with stirring into the mouth ingredients that had been previously adjusted to 80 ° C. Thereafter, the mixture was cooled to room temperature with stirring to obtain an external pharmaceutical composition of Comparative Example 1. The external pharmaceutical composition of Comparative Example 1 was filled in a pump-type former to obtain the external pharmaceutical of Comparative Example 1. In addition, content of the formulation component in a table | surface was displayed by the mass% with respect to the composition whole quantity.
＜比較試験１＞
実施例１の外用医薬１、比較例１の外用医薬を用いそれぞれ泡状に吐出させた外用医薬１、比較例１の外用医薬を、スパーテル１盛りを取り、血球計数用のスライドグラス上に載せて、その上にカバーグラスを重ね、押しつぶした状態で顕微鏡下１０視野を観察し、不溶の数（１ｍＬあたり）を計数した。結果を表３に示した。これにより、本発明の製剤は、有効成分を均一に存在させる性質に優れることが分かった。<Comparison test 1>
The external medicine 1 of Example 1 and the external medicine 1 discharged in the form of foam using the external medicine of Comparative Example 1 and the external medicine of Comparative Example 1, respectively, were placed on a slide glass for counting blood cells. Then, a cover glass was placed thereon, and 10 visual fields were observed under the microscope in a crushed state, and the insoluble number (per 1 mL) was counted. The results are shown in Table 3. Thereby, it turned out that the formulation of this invention is excellent in the property to which an active ingredient exists uniformly.
＜使用試験＞
実施例１の外用医薬１、比較例１の外用医薬の泡の質（起泡性、持続性）、使用感（べたつき感、しっとり感）を以下の方法に従い評価した。
（１）泡の質（起泡性、持続性）：１０名の被験者により２５℃に保たれた室内で各試料を吐出させ手にとり、泡の質（起泡性、持続性）の観察を行った。尚、評価基準は以下の通りである。
◎非常に良好（良いと回答した被験者が８名以上）
○良好（良いと回答した被験者が６名以上８名未満）
△やや悪い（良いと回答した被験者が４名以上６名未満）
×悪い（良いと回答した被験者が４名未満）
（２）使用感（べたつき感、しっとり感）：１０名の被験者により２５℃に保たれた室内で各試料を吐出させ手にとり、使用感（しっとり感）の評価を行った。尚、評価基準は以下の通りである。
◎非常に良好（良いと回答した被験者が８名以上）
○良好（良いと回答した被験者が６名以上８名未満）
△やや悪い（良いと回答した被験者が４名以上６名未満）
×悪い（良いと回答した被験者が４名未満）
実施例１及び比較例１の外用医薬について、泡の質（起泡性、持続性）、使用感（べたつき感、しっとり感）について確かめたところ、実施例１の外用医薬は、比較例１の外用医薬に比較し、泡の質、使用感に優れることが確認された。また、実施例１及び比較例１の外用医薬組成物について、のびの良さ、のびの軽さについて確かめたところ、実施例１の外用医薬１は、比較例１の外用医薬に比較しのびが良く、軽いことが確認された。<Use test>
The foam quality (foaming property, sustainability) and the feeling of use (stickiness, moist feeling) of the external medicine 1 of Example 1 and the external medicine of Comparative Example 1 were evaluated according to the following methods.
(1) Foam quality (foaming property, sustainability): 10 subjects discharge each sample in a room kept at 25 ° C and take it in their hands to observe the quality of the foam (foaming property, sustainability). went. The evaluation criteria are as follows.
◎ Very good (more than 8 subjects answered good)
○ Good (6 or more and less than 8 subjects replied)
△ Slightly bad (4 or more and less than 6 subjects replied as good)
× Poor (less than 4 subjects answered good)
(2) Feeling of use (stickiness, moist feeling): Each test sample was ejected in a room kept at 25 ° C. by 10 subjects, and the feeling of use (moist feeling) was evaluated. The evaluation criteria are as follows.
◎ Very good (more than 8 subjects answered good)
○ Good (6 or more and less than 8 subjects replied)
△ Slightly bad (4 or more and less than 6 subjects replied as good)
× Poor (less than 4 subjects answered good)
About the external medicine of Example 1 and Comparative Example 1, when the foam quality (foaming property, persistence) and the feeling of use (stickiness, moist feeling) were confirmed, the external medicine of Example 1 was that of Comparative Example 1. Compared to external medicine, it was confirmed that the quality of foam and the feeling of use were excellent. Further, as to the external pharmaceutical composition of Example 1 and Comparative Example 1, it was confirmed about the goodness of the spread and the lightness of the spread. As a result, the external pharmaceutical 1 of Example 1 is better than the external medicine of Comparative Example 1, It was confirmed to be light.
実施例１と同様に、以下の表５に示す処方に従って本発明の外用医薬組成物２を作成した。このものをポンプ式フォーマーに充填し、本発明の外用医薬２を得た。このものはきめの細かい泡を吐出し、不溶物は確認できなかった。尚、表中の製剤成分の含有量は、組成物全量に対する質量％にて表示した。 In the same manner as in Example 1, an external pharmaceutical composition 2 of the present invention was prepared according to the formulation shown in Table 5 below. This was filled into a pump-type former to obtain the external medicine 2 of the present invention. This product ejected fine bubbles, and insoluble matter could not be confirmed. In addition, content of the formulation component in a table | surface was displayed by the mass% with respect to the composition whole quantity.
実施例１と同様に、以下の表６に示す処方に従って本発明の外用医薬組成物３を作成した。このものをポンプ式フォーマーに充填し、本発明の外用医薬３を得た。このものは、きめの細かい泡を吐出し、不溶物は確認できなかった。尚、表中の製剤成分の含有量は、組成物全量に対する質量％にて表示した。 Similarly to Example 1, an external pharmaceutical composition 3 of the present invention was prepared according to the formulation shown in Table 6 below. This was filled in a pump-type former to obtain the external medicine 3 of the present invention. This product ejected fine bubbles, and insoluble matter could not be confirmed. In addition, content of the formulation component in a table | surface was displayed by the mass% with respect to the composition whole quantity.
実施例１と同様に、下記の処方に従って外用医薬組成物４を作成し、ポンプ式フォーマーに充填し、本発明の外用医薬４を得た。このものは、きめの細かい泡を吐出し、不溶物は確認できなかった。尚、表中の製剤成分の含有量は、組成物全量に対する質量％にて表示した。 In the same manner as in Example 1, an external pharmaceutical composition 4 was prepared according to the following formulation and filled in a pump-type former to obtain an external pharmaceutical 4 of the present invention. This product ejected fine bubbles, and insoluble matter could not be confirmed. In addition, content of the formulation component in a table | surface was displayed by the mass% with respect to the composition whole quantity.
実施例１と同様に下記の処方に従って外用医薬組成物５を作成し、ポンプ式フォーマーに充填し、本発明の外用医薬５を得た。このものは、きめの細かい泡を吐出し、不溶物は確認できなかった。尚、表中の製剤成分の含有量は、組成物全量に対する質量％にて表示した。 In the same manner as in Example 1, an external pharmaceutical composition 5 was prepared according to the following formulation and filled in a pump-type former to obtain an external pharmaceutical 5 of the present invention. This product ejected fine bubbles, and insoluble matter could not be confirmed. In addition, content of the formulation component in a table | surface was displayed by the mass% with respect to the composition whole quantity.
実施例１と同様に下記の処方に従って外用医薬組成物６を作成し、ポンプ式フォーマーに充填し、本発明の外用医薬６を得た。このものは、きめの細かい泡を吐出し、不溶物は確認できなかった。尚、表中の製剤成分の含有量は、組成物全量に対する質量％にて表示した。 In the same manner as in Example 1, an external pharmaceutical composition 6 was prepared according to the following formulation and filled in a pump-type former to obtain an external pharmaceutical 6 of the present invention. This product ejected fine bubbles, and insoluble matter could not be confirmed. In addition, content of the formulation component in a table | surface was displayed by the mass% with respect to the composition whole quantity.
実施例１と同様に下記の処方に従って外用医薬組成物７を作成し、ポンプ式フォーマーに充填し、本発明の外用医薬７を得た。このものは、きめの細かい泡を吐出し、不溶物は確認できなかった。尚、表中の製剤成分の含有量は、組成物全量に対する質量％にて表示した。 In the same manner as in Example 1, an external pharmaceutical composition 7 was prepared according to the following formulation and filled in a pump-type former to obtain an external pharmaceutical 7 of the present invention. This product ejected fine bubbles, and insoluble matter could not be confirmed. In addition, content of the formulation component in a table | surface was displayed by the mass% with respect to the composition whole quantity.
実施例１と同様に下記の処方に従って外用医薬組成物８を作成し、ポンプ式フォーマーに充填し、本発明の外用医薬８を得た。このものは、きめの細かい泡を吐出し、不溶物は確認できなかった。尚、表中の製剤成分の含有量は、組成物全量に対する質量％にて表示した。 Similarly to Example 1, an external pharmaceutical composition 8 was prepared according to the following formulation and filled in a pump-type former to obtain an external pharmaceutical 8 of the present invention. This product ejected fine bubbles, and insoluble matter could not be confirmed. In addition, content of the formulation component in a table | surface was displayed by the mass% with respect to the composition whole quantity.
実施例１と同様に、以下の表に示す処方に従って本発明の外用医薬組成物９〜２６を作成した。このものをポンプ式フォーマーに充填し、本発明の外用医薬９〜２６を得た。このものはきめの細かい泡を吐出し、不溶物は確認できなかった。尚、表中の製剤成分の含有量は、組成物全量に対する質量％にて表示した。また、実施例３に記載の試験方法に従い、起泡性、持続性、使用感（しっとり感）を評価した。本発明の外用医薬９〜２６は、泡質、使用感に優れる外用医薬であることが分かった。 Similarly to Example 1, external pharmaceutical compositions 9 to 26 of the present invention were prepared according to the formulations shown in the following table. This was filled in a pump-type former to obtain external medicines 9 to 26 of the present invention. This product ejected fine bubbles, and insoluble matter could not be confirmed. In addition, content of the formulation component in a table | surface was displayed by the mass% with respect to the composition whole quantity. Moreover, according to the test method as described in Example 3, foaming property, sustainability, and feeling of use (moist feeling) were evaluated. It turned out that the external medicine 9-26 of this invention is an external medicine excellent in foam quality and a usability | use_condition.
実施例１と同様に、以下の表に示す処方に従って本発明の外用医薬組成物２７〜２９を作成した。このものをポンプ式フォーマーに充填し、本発明の外用医薬２７〜２９を得た。尚、表中の製剤成分の含有量は、組成物全量に対する質量％にて表示した。このものは、きめの細かい泡を吐出し、不溶物は確認できなかった。また、実施例３に記載の試験方法に従い、起泡性、持続性、使用感を評価した。本発明の外用医薬２７〜２９は、起泡性、持続性、使用感に優れる外用医薬であることが分かった。 Similarly to Example 1, external pharmaceutical compositions 27 to 29 of the present invention were prepared according to the formulations shown in the following table. This was filled in a pump-type former to obtain external medicines 27 to 29 of the present invention. In addition, content of the formulation component in a table | surface was displayed by the mass% with respect to the composition whole quantity. This product ejected fine bubbles, and insoluble matter could not be confirmed. Moreover, according to the test method as described in Example 3, foaming property, sustainability, and usability were evaluated. It turned out that the external medicine 27-29 of this invention is an external medicine excellent in foamability, durability, and a usability | use_condition.
実施例１と同様に、以下の表に示す処方に従って本発明の外用医薬組成物３０を作成した。このものをポンプ式フォーマーに充填し、本発明の外用医薬３０を得た。尚、表中の製剤成分の含有量は、組成物全量に対する質量％にて表示した。このものは、きめの細かい泡を吐出し、不溶物は確認できなかった。 Similarly to Example 1, an external pharmaceutical composition 30 of the present invention was prepared according to the formulation shown in the following table. This was filled in a pump-type former to obtain the external medicine 30 of the present invention. In addition, content of the formulation component in a table | surface was displayed by the mass% with respect to the composition whole quantity. This product ejected fine bubbles, and insoluble matter could not be confirmed.
実施例１と同様に、以下の表に示す処方に従って本発明の外用医薬組成物３１を作成し、ポンプ式フォーマーに充填し、本発明の外用医薬３１を得た。尚、表中の製剤成分の含有量は、組成物全量に対する質量％にて表示した。このものは、きめの細かい泡を吐出し、不溶物は確認できなかった。 In the same manner as in Example 1, an external pharmaceutical composition 31 of the present invention was prepared according to the formulation shown in the following table and filled in a pump-type former to obtain an external pharmaceutical 31 of the present invention. In addition, content of the formulation component in a table | surface was displayed by the mass% with respect to the composition whole quantity. This product ejected fine bubbles, and insoluble matter could not be confirmed.
以下の表に示す処方に従って本発明の外用医薬組成物３２〜３７、比較例２〜４の外用医薬組成物を作成し、ポンプ式フォーマーに充填し、本発明の外用医薬３２〜３７、比較例２〜４の外用医薬を得る。尚、表中の製剤成分の含有量は、組成物全量に対する質量％にて表示する。また、前記外用医薬組成物３２〜３７、比較例２〜４ の外用医薬組成物１００（ｇ）をビーカーに入れ、３０００ｒｐｍで１分間撹拌した後、２分間静置し泡と溶液の境界線が明瞭になったところで生成した泡の高さを測定し、泡質を目視にて確認する。本発明の外用医薬組成物は、比較例２〜４の外用医薬組成物に比較し、組成物の安定性、泡立ち、持続性、泡の肌理細かさなどの泡質、使用感に優れる。 According to the prescription shown in the following table, external pharmaceutical compositions 32-37 of the present invention and external pharmaceutical compositions of Comparative Examples 2-4 are prepared and filled in a pump former, and external pharmaceutical 32-32 of the present invention, Comparative Examples 2 to 4 external medicines are obtained. In addition, content of the formulation component in a table | surface is displayed by the mass% with respect to the composition whole quantity. Moreover, after putting the said external pharmaceutical composition 32-37 and the external pharmaceutical composition 100 (g) of Comparative Examples 2-4 into a beaker and stirring at 3000 rpm for 1 minute, it left still for 2 minutes and the boundary line of foam and a solution is When it becomes clear, the height of the generated foam is measured, and the quality of the foam is visually confirmed. The external pharmaceutical composition of the present invention is superior to the external pharmaceutical compositions of Comparative Examples 2 to 4, in terms of foam stability such as composition stability, foaming, sustainability, and fineness of foam, and a feeling of use.
以下の表に示す処方に従って本発明の外用医薬組成物３８〜４３、比較例５〜７の外用医薬組成物を作成し、ポンプ式フォーマーに充填し、本発明の外用医薬３８〜４３、比較例５〜７の外用医薬を得る。尚、表中の製剤成分の含有量は、組成物全量に対する質量％にて表示する。実施例１５に記載の方法に従い、外用医薬組成物３８〜４３、比較例５〜７の外用医薬組成物の泡の高さを測定し、泡質を目視にて確認する。本発明の外用医薬組成物は、比較例５〜７の外用医薬組成物に比較し、組成物の安定性、泡立ち、持続性、泡の肌理細かさなどの泡質、使用感に優れる。 According to the prescription shown in the following table, external pharmaceutical compositions 38 to 43 of the present invention and external pharmaceutical compositions of Comparative Examples 5 to 7 are prepared and filled in a pump-former, and the external pharmaceutical compositions 38 to 43 of the present invention and Comparative Examples are prepared. Obtain 5-7 topical medicines. In addition, content of the formulation component in a table | surface is displayed by the mass% with respect to the composition whole quantity. According to the method of Example 15, the height of the foam of the external pharmaceutical composition 38-43 and the external pharmaceutical composition of Comparative Examples 5-7 is measured, and foam quality is confirmed visually. The external pharmaceutical composition of the present invention is superior in the stability of the composition, foaming, persistence, foam quality such as fineness of the foam, and feeling of use, as compared with the external pharmaceutical compositions of Comparative Examples 5-7.
本発明は医薬に応用できる。 The present invention can be applied to medicine.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017217337A1 (en) * | 2016-06-16 | 2017-12-21 | 株式会社ポーラファルマ | Foam, screen foamer composition, and evaluation method for same |
| JP2017223592A (en) * | 2016-06-16 | 2017-12-21 | 株式会社ポーラファルマ | Foam, composition for screen foamer and method for evaluating the same |
| JP2018199707A (en) * | 2014-01-27 | 2018-12-20 | 株式会社ポーラファルマ | Method for producing external pharmaceutical composition that becomes foamy when in use |
Citations (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61210023A (en) * | 1985-03-15 | 1986-09-18 | Shiseido Co Ltd | Hair dyeing agent in aerosol state |
| JPH0372433A (en) * | 1989-04-28 | 1991-03-27 | Hisamitsu Pharmaceut Co Inc | Foamy aerosol preparation |
| JPH08291050A (en) * | 1995-02-22 | 1996-11-05 | Hisamitsu Pharmaceut Co Inc | Aerosol composition and aerosol-type external preparation |
| JP2002161020A (en) * | 2000-11-28 | 2002-06-04 | Kanebo Ltd | Foamy cosmetic |
| JP2003055160A (en) * | 2001-08-10 | 2003-02-26 | Kao Corp | Hair cosmetic |
| JP2004035458A (en) * | 2002-07-03 | 2004-02-05 | Kanebo Ltd | Transparent liquid cosmetic |
| JP2006137722A (en) * | 2004-11-15 | 2006-06-01 | Pola Chem Ind Inc | Foamable cosmetic |
| JP2007137813A (en) * | 2005-11-17 | 2007-06-07 | Kowa Co | Composition for non-aerosol type foaming agent and foaming agent using the composition |
| JP2008502663A (en) * | 2004-06-17 | 2008-01-31 | ガルデルマ・ソシエテ・アノニム | Pressurized foamable composition for topical treatment of psoriasis |
| JP2012126668A (en) * | 2010-12-14 | 2012-07-05 | Nakano Seiyaku Kk | Dyeing removing agent composition and method for removing dyeing |
| JP2012214422A (en) * | 2011-04-01 | 2012-11-08 | Maruho Co Ltd | Non-aerosol composition for foaming agent |
| JP2015022655A (en) * | 2013-07-22 | 2015-02-02 | 株式会社東芝 | Electronic apparatus, method, and program |
| JP2015526394A (en) * | 2012-06-18 | 2015-09-10 | ダート・ニューロサイエンス・（ケイマン）・リミテッド | Substituted thiophene- and furan-fused azolopyrimidin-5- (6H) -one compounds |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2010222323A (en) * | 2009-03-25 | 2010-10-07 | Kumano Yushi Kk | Makeup remover cosmetic composition |
| JP5754644B2 (en) * | 2011-11-04 | 2015-07-29 | 日油株式会社 | Liquid detergent composition |
| JP2013155143A (en) * | 2012-01-31 | 2013-08-15 | Kawaken Fine Chem Co Ltd | Hair detergent composition for foam discharge container |
| JP6396229B2 (en) * | 2014-01-27 | 2018-09-26 | 株式会社ポーラファルマ | Pharmaceutical composition for external use which exhibits foam when used |
-
2015
- 2015-01-22 JP JP2015022654A patent/JP6396229B2/en active Active
-
2018
- 2018-08-29 JP JP2018160895A patent/JP6684325B2/en active Active
Patent Citations (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61210023A (en) * | 1985-03-15 | 1986-09-18 | Shiseido Co Ltd | Hair dyeing agent in aerosol state |
| JPH0372433A (en) * | 1989-04-28 | 1991-03-27 | Hisamitsu Pharmaceut Co Inc | Foamy aerosol preparation |
| JPH08291050A (en) * | 1995-02-22 | 1996-11-05 | Hisamitsu Pharmaceut Co Inc | Aerosol composition and aerosol-type external preparation |
| JP2002161020A (en) * | 2000-11-28 | 2002-06-04 | Kanebo Ltd | Foamy cosmetic |
| JP2003055160A (en) * | 2001-08-10 | 2003-02-26 | Kao Corp | Hair cosmetic |
| JP2004035458A (en) * | 2002-07-03 | 2004-02-05 | Kanebo Ltd | Transparent liquid cosmetic |
| JP2008502663A (en) * | 2004-06-17 | 2008-01-31 | ガルデルマ・ソシエテ・アノニム | Pressurized foamable composition for topical treatment of psoriasis |
| JP2006137722A (en) * | 2004-11-15 | 2006-06-01 | Pola Chem Ind Inc | Foamable cosmetic |
| JP2007137813A (en) * | 2005-11-17 | 2007-06-07 | Kowa Co | Composition for non-aerosol type foaming agent and foaming agent using the composition |
| JP2012126668A (en) * | 2010-12-14 | 2012-07-05 | Nakano Seiyaku Kk | Dyeing removing agent composition and method for removing dyeing |
| JP2012214422A (en) * | 2011-04-01 | 2012-11-08 | Maruho Co Ltd | Non-aerosol composition for foaming agent |
| JP2015526394A (en) * | 2012-06-18 | 2015-09-10 | ダート・ニューロサイエンス・（ケイマン）・リミテッド | Substituted thiophene- and furan-fused azolopyrimidin-5- (6H) -one compounds |
| JP2015022655A (en) * | 2013-07-22 | 2015-02-02 | 株式会社東芝 | Electronic apparatus, method, and program |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2018199707A (en) * | 2014-01-27 | 2018-12-20 | 株式会社ポーラファルマ | Method for producing external pharmaceutical composition that becomes foamy when in use |
| WO2017217337A1 (en) * | 2016-06-16 | 2017-12-21 | 株式会社ポーラファルマ | Foam, screen foamer composition, and evaluation method for same |
| JP2017223592A (en) * | 2016-06-16 | 2017-12-21 | 株式会社ポーラファルマ | Foam, composition for screen foamer and method for evaluating the same |
| JP2017226654A (en) * | 2016-06-16 | 2017-12-28 | 株式会社ポーラファルマ | Foam, composition for screen foamer, and evaluation method of the same |
| JP2017226653A (en) * | 2016-06-16 | 2017-12-28 | 株式会社ポーラファルマ | Composition for screen foamer |
| CN109310633A (en) * | 2016-06-16 | 2019-02-05 | 宝丽制药股份有限公司 | Foam, the composition and its evaluation method for sieving infusion |
| US11090234B2 (en) | 2016-06-16 | 2021-08-17 | Pola Pharma Inc. | Foam, screen foamer composition, and evaluation method for same |
| CN109310633B (en) * | 2016-06-16 | 2021-10-22 | 宝丽制药股份有限公司 | Composition for foam and foam screening agent and evaluation method thereof |
| JP7073050B2 (en) | 2016-06-16 | 2022-05-23 | サンファーマ株式会社 | Composition for screen former |
| AU2017285599B2 (en) * | 2016-06-16 | 2023-03-23 | Pola Pharma Inc. | Foam, screen foamer composition, and evaluation method for same |
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| JP6396229B2 (en) | 2018-09-26 |
| JP2018199707A (en) | 2018-12-20 |
| JP6684325B2 (en) | 2020-04-22 |
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