JPWO2017145441A1 - 外用液剤 - Google Patents
外用液剤 Download PDFInfo
- Publication number
- JPWO2017145441A1 JPWO2017145441A1 JP2018500982A JP2018500982A JPWO2017145441A1 JP WO2017145441 A1 JPWO2017145441 A1 JP WO2017145441A1 JP 2018500982 A JP2018500982 A JP 2018500982A JP 2018500982 A JP2018500982 A JP 2018500982A JP WO2017145441 A1 JPWO2017145441 A1 JP WO2017145441A1
- Authority
- JP
- Japan
- Prior art keywords
- mass
- external
- anticholinergic agent
- acid ester
- dicarboxylic acid
- 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
Links
- 239000007788 liquid Substances 0.000 title claims description 27
- 239000000812 cholinergic antagonist Substances 0.000 claims abstract description 42
- -1 dicarboxylic acid ester Chemical class 0.000 claims abstract description 38
- 229940121948 Muscarinic receptor antagonist Drugs 0.000 claims abstract description 37
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000006210 lotion Substances 0.000 claims description 44
- 238000002360 preparation method Methods 0.000 claims description 44
- XIQVNETUBQGFHX-UHFFFAOYSA-N Ditropan Chemical group C=1C=CC=CC=1C(O)(C(=O)OCC#CCN(CC)CC)C1CCCCC1 XIQVNETUBQGFHX-UHFFFAOYSA-N 0.000 claims description 31
- 229960005434 oxybutynin Drugs 0.000 claims description 31
- 150000003839 salts Chemical class 0.000 claims description 20
- DOIRQSBPFJWKBE-UHFFFAOYSA-N dibutyl phthalate Chemical compound CCCCOC(=O)C1=CC=CC=C1C(=O)OCCCC DOIRQSBPFJWKBE-UHFFFAOYSA-N 0.000 claims description 8
- HBTAOSGHCXUEKI-UHFFFAOYSA-N 4-chloro-n,n-dimethyl-3-nitrobenzenesulfonamide Chemical compound CN(C)S(=O)(=O)C1=CC=C(Cl)C([N+]([O-])=O)=C1 HBTAOSGHCXUEKI-UHFFFAOYSA-N 0.000 claims description 7
- 229940031578 diisopropyl adipate Drugs 0.000 claims description 7
- 208000008454 Hyperhidrosis Diseases 0.000 claims description 6
- 229940031569 diisopropyl sebacate Drugs 0.000 claims description 6
- XFKBBSZEQRFVSL-UHFFFAOYSA-N dipropan-2-yl decanedioate Chemical compound CC(C)OC(=O)CCCCCCCCC(=O)OC(C)C XFKBBSZEQRFVSL-UHFFFAOYSA-N 0.000 claims description 6
- KSCKTBJJRVPGKM-UHFFFAOYSA-N octan-1-olate;titanium(4+) Chemical compound [Ti+4].CCCCCCCC[O-].CCCCCCCC[O-].CCCCCCCC[O-].CCCCCCCC[O-] KSCKTBJJRVPGKM-UHFFFAOYSA-N 0.000 claims description 6
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 5
- 230000037315 hyperhidrosis Effects 0.000 claims description 5
- 229940001447 lactate Drugs 0.000 claims description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 4
- RDOFJDLLWVCMRU-UHFFFAOYSA-N Diisobutyl adipate Chemical compound CC(C)COC(=O)CCCCC(=O)OCC(C)C RDOFJDLLWVCMRU-UHFFFAOYSA-N 0.000 claims description 4
- MUXOBHXGJLMRAB-UHFFFAOYSA-N Dimethyl succinate Chemical compound COC(=O)CCC(=O)OC MUXOBHXGJLMRAB-UHFFFAOYSA-N 0.000 claims description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 claims description 4
- 229910019142 PO4 Inorganic materials 0.000 claims description 4
- 229940022663 acetate Drugs 0.000 claims description 4
- 229940031769 diisobutyl adipate Drugs 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 4
- 239000010452 phosphate Substances 0.000 claims description 4
- 229940095064 tartrate Drugs 0.000 claims description 4
- CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical group C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 claims description 3
- 239000001540 sodium lactate Substances 0.000 claims description 3
- 229940005581 sodium lactate Drugs 0.000 claims description 3
- 235000011088 sodium lactate Nutrition 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 claims description 2
- 239000002552 dosage form Substances 0.000 claims description 2
- 238000012360 testing method Methods 0.000 description 23
- 210000003491 skin Anatomy 0.000 description 15
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- 239000000243 solution Substances 0.000 description 13
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- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 238000000034 method Methods 0.000 description 8
- 210000003780 hair follicle Anatomy 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- QCHFTSOMWOSFHM-WPRPVWTQSA-N (+)-Pilocarpine Chemical compound C1OC(=O)[C@@H](CC)[C@H]1CC1=CN=CN1C QCHFTSOMWOSFHM-WPRPVWTQSA-N 0.000 description 5
- QCHFTSOMWOSFHM-UHFFFAOYSA-N SJ000285536 Natural products C1OC(=O)C(CC)C1CC1=CN=CN1C QCHFTSOMWOSFHM-UHFFFAOYSA-N 0.000 description 5
- 238000009825 accumulation Methods 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 229960001416 pilocarpine Drugs 0.000 description 5
- 230000001166 anti-perspirative effect Effects 0.000 description 4
- 239000003213 antiperspirant Substances 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 239000004094 surface-active agent Substances 0.000 description 4
- 210000004243 sweat Anatomy 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000004359 castor oil Substances 0.000 description 3
- 235000019438 castor oil Nutrition 0.000 description 3
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 230000001078 anti-cholinergic effect Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- FLKPEMZONWLCSK-UHFFFAOYSA-N diethyl phthalate Chemical compound CCOC(=O)C1=CC=CC=C1C(=O)OCC FLKPEMZONWLCSK-UHFFFAOYSA-N 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 239000003925 fat Substances 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- LOUPRKONTZGTKE-LHHVKLHASA-N quinidine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@H]2[C@@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-LHHVKLHASA-N 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 description 2
- 231100000245 skin permeability Toxicity 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- AXOIZCJOOAYSMI-UHFFFAOYSA-N succinylcholine Chemical compound C[N+](C)(C)CCOC(=O)CCC(=O)OCC[N+](C)(C)C AXOIZCJOOAYSMI-UHFFFAOYSA-N 0.000 description 2
- 239000012085 test solution Substances 0.000 description 2
- MGSRCZKZVOBKFT-UHFFFAOYSA-N thymol Chemical compound CC(C)C1=CC=C(C)C=C1O MGSRCZKZVOBKFT-UHFFFAOYSA-N 0.000 description 2
- WYDUSKDSKCASEF-LJQANCHMSA-N (1s)-1-cyclohexyl-1-phenyl-3-pyrrolidin-1-ylpropan-1-ol Chemical compound C([C@](O)(C1CCCCC1)C=1C=CC=CC=1)CN1CCCC1 WYDUSKDSKCASEF-LJQANCHMSA-N 0.000 description 1
- ALSTYHKOOCGGFT-KTKRTIGZSA-N (9Z)-octadecen-1-ol Chemical compound CCCCCCCC\C=C/CCCCCCCCO ALSTYHKOOCGGFT-KTKRTIGZSA-N 0.000 description 1
- GFRUPHOKLBPHTQ-UHFFFAOYSA-N 2-(2-cyclohexyl-2-hydroxy-1-oxo-2-phenylethoxy)ethyl-diethyl-methylammonium Chemical compound C=1C=CC=CC=1C(O)(C(=O)OCC[N+](C)(CC)CC)C1CCCCC1 GFRUPHOKLBPHTQ-UHFFFAOYSA-N 0.000 description 1
- QCDWFXQBSFUVSP-UHFFFAOYSA-N 2-phenoxyethanol Chemical compound OCCOC1=CC=CC=C1 QCDWFXQBSFUVSP-UHFFFAOYSA-N 0.000 description 1
- BKLAJZNVMHLXAP-VKGMXUHCSA-N 3-[(1r,5s)-8,8-dimethyl-8-azoniabicyclo[3.2.1]octan-3-yl]-2,2-diphenylpropanenitrile Chemical compound C([C@H]1CC[C@@H](C2)[N+]1(C)C)C2CC(C#N)(C=1C=CC=CC=1)C1=CC=CC=C1 BKLAJZNVMHLXAP-VKGMXUHCSA-N 0.000 description 1
- IJALWSVNUBBQRA-UHFFFAOYSA-N 4-Isopropyl-3-methylphenol Chemical compound CC(C)C1=CC=C(O)C=C1C IJALWSVNUBBQRA-UHFFFAOYSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- NVOYVOBDTVTBDX-AGUVMIOSSA-N 8g15t83e6i Chemical compound C1([C@@H](CO)C(=O)OC2C[C@@H]3[N+]([C@H](C2)[C@@H]2[C@H]3O2)(C)CC)=CC=CC=C1 NVOYVOBDTVTBDX-AGUVMIOSSA-N 0.000 description 1
- 229930000680 A04AD01 - Scopolamine Natural products 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- YXSLJKQTIDHPOT-UHFFFAOYSA-N Atracurium Dibesylate Chemical compound C1=C(OC)C(OC)=CC=C1CC1[N+](CCC(=O)OCCCCCOC(=O)CC[N+]2(C)C(C3=CC(OC)=C(OC)C=C3CC2)CC=2C=C(OC)C(OC)=CC=2)(C)CCC2=CC(OC)=C(OC)C=C21 YXSLJKQTIDHPOT-UHFFFAOYSA-N 0.000 description 1
- 229930003347 Atropine Natural products 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- XTJFFFGAUHQWII-UHFFFAOYSA-N Dibutyl adipate Chemical compound CCCCOC(=O)CCCCC(=O)OCCCC XTJFFFGAUHQWII-UHFFFAOYSA-N 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- VPNYRYCIDCJBOM-UHFFFAOYSA-M Glycopyrronium bromide Chemical compound [Br-].C1[N+](C)(C)CCC1OC(=O)C(O)(C=1C=CC=CC=1)C1CCCC1 VPNYRYCIDCJBOM-UHFFFAOYSA-M 0.000 description 1
- ZTVIKZXZYLEVOL-MCOXGKPRSA-N Homatropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(O)C1=CC=CC=C1 ZTVIKZXZYLEVOL-MCOXGKPRSA-N 0.000 description 1
- RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 1
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- WMSYWJSZGVOIJW-ONUALHDOSA-L Mivacurium chloride Chemical compound [Cl-].[Cl-].C([C@@H]1C2=CC(OC)=C(OC)C=C2CC[N+]1(C)CCCOC(=O)CC/C=C/CCC(=O)OCCC[N+]1(CCC=2C=C(C(=CC=2[C@H]1CC=1C=C(OC)C(OC)=C(OC)C=1)OC)OC)C)C1=CC(OC)=C(OC)C(OC)=C1 WMSYWJSZGVOIJW-ONUALHDOSA-L 0.000 description 1
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Abstract
Description
本発明の一実施形態は、水、抗コリン作用薬及びジカルボン酸エステルを含む外用液剤であって、抗コリン作用薬の含有量が、上記外用液剤の全質量を基準として10質量%〜20質量%である、外用液剤である。上記外用液剤は、多汗症治療に用いることができる。
表1の組成に従ってローション剤を調製し、被験者(4名)の手のひらに500μLを塗布した。両手をすり合わせてローション剤を両手のひらに均一に広げ、3分後の「べたつき」の程度について以下の3段階を基準としてスコアを付与した。
0:べたつきを感じない
1:べたつきを感じる
2:強いべたつきを感じる
上記スコアの平均値に基づき、以下の3段階を基準としてべたつき度合いを評価した。
○:平均値が0.5未満
△:平均値が0.5以上1.0未満
×:平均値が1.0以上
表3の組成に従ってローション剤を調製し、以下の方法により、各ローション剤の力積値を測定した。力積値が小さい程粘性が低いことを示す。
1)ローション剤50μLを96穴プレートに入れ、32℃で一晩静置して乾燥させた。
2)乾燥させたローション剤に、テクスチャーアナライザのSUS製プローブ(直径5mm)を当接させた。
3)プローブを2mm/秒の速度で上昇させてローション剤から離れる際にかかる力を測定し、その曲線下面積を力積値(g・秒)として算出した。
表5の組成に従ってローション剤を調製し、被験者(3名)の手のひらに300μLを塗布した。比較例1、4、5及び9並びに実施例1〜3においては、試験例2と同じローション剤を用いた。両手をすり合わせてローション剤を両手のひらに均一に広げ、3分後の「べたつき」の程度について以下の4段階を基準としてスコアを付与した。
0:べたつきを感じない
1:わずかにべたつきを感じる
2:べたつきを感じる
3:強いべたつきを感じる
上記スコアの平均値に基づき、以下の5段階を基準としてべたつき度合いを評価した。
◎:平均値が0.1未満
○:平均値が0.1以上1.0未満
△:平均値が1.0以上2.0未満
×:平均値が2.0以上3.0未満
××:平均値が3.0以上
試験例2及び3の実施例1〜9及び比較例1のローション剤を用いて、以下の方法により、オキシブチニンの保存安定性を評価した。
1)ローション剤100μLを測り取り、重量を測定した。
2)移動相を50mL加えて混合し、各ローション剤のオキシブチニン濃度を高速液体クロマトグラフィー(HPLC)で測定した。HPLCの条件は以下の通りである。
移動相:0.1w/w%リン酸水溶液(ドデシル硫酸ナトリウムを0.5w/v%含む):アセトニトリル=45:55(v/v)
流速:1.5mL/分
カラム:TSKgel ODS−80Ts(東ソー株式会社)
保持時間:10分
3)ローション剤を60℃で2週間静置した後の液重量あたりのオキシブチニン含量の対理論値(%)を初期の対理論値(%)と比較した。対初期値が97.5%以上の場合には、オキシブチニンの保存安定性が良好であると評価した。
試験例3の比較例1及び実施例4のローション剤を用いて、以下の方法により、オキシブチニンの皮膚透過性を測定した。
1)ダーマトームしたヒト皮膚表面に5μLのローション剤を3cm2の面積に塗布した。
2)数秒間乾燥させた後、皮膚の真皮側がレセプター層側になるようにして、皮膚をフランツセルにセットした。レセプター層として生理食塩水を用いた。皮膚をセットしてから4、8、12、16、20及び24時間経過した時点でレセプター溶液をサンプリングした。サンプリングした溶液0.5mLにアセトニトリル0.5mLを加え撹拌し、さらに遠心分離して除タンパクを行い、試験溶液とした。
3)試験溶液のオキシブチニン濃度を、試験例4と同じ条件下でHPLCにより測定した。
4)得られた測定値から1時間あたりのオキシブチニンの皮膚透過速度を算出し、その最大値をJmax(μg/cm2/h)とした。また、24時間の累積透過量(μg/cm2)を求めた。
表9の組成に従ってローション剤を調製し、溶解状態を目視で確認した。さらに、ローション剤をブタの皮膚に塗布し、オキシブチニンの毛嚢への集積量を以下の方法で測定した。
1)軽く毛刈りしたブタの皮膚5cm2にローション剤20μLを塗布した。個体数n=3。
2)6時間後、消毒用エタノールで皮膚表面を清拭し、リン酸緩衝液で流水洗浄し、皮膚表面に付着するオキシブチニンを除去した。
3)皮膚から毛20本分の毛嚢部分を採取した。
4)抽出液1mLを用いて毛嚢からオキシブチニンを抽出した。抽出液として、試験例4の移動相を用いた。
5)HPLCによりオキシブチニンの濃度を測定した。HPLCの条件は試験例4と同じである。
表11の組成に従ってローション剤を調製した。ピロカルピン誘発発汗試験により、ローション剤の発汗抑制作用を測定した。また、試験例6と同様の方法により、ローション剤をブタの皮膚に塗布し、オキシブチニンの濃度を測定した。
1)ローション剤を40質量%エタノール水溶液で12倍に希釈した。
2)マウスの足蹠の約0.5cm2にローション剤10μL又は15μLを塗布した。個体数n=5〜6。
3)4時間後に麻酔下でヨウ素及びデンプン溶液を足蹠に塗布した。
4)ピロカルピン5μg/足を皮内投与した。5)5分後にヨウ素デンプン反応により生じる黒点の個数を計数した。
Claims (10)
- 水、抗コリン作用薬及びジカルボン酸エステルを含む外用液剤であって、抗コリン作用薬の含有量が、前記外用液剤の全質量を基準として10質量%〜20質量%である、外用液剤。
- 前記抗コリン作用薬が、オキシブチニン又はその薬学的に許容される塩である、請求項1に記載の外用液剤。
- 前記抗コリン作用薬の含有量が、前記外用液剤の全質量を基準として15質量%〜20質量%である、請求項1又は2に記載の外用液剤。
- 前記ジカルボン酸エステルが、アジピン酸ジイソプロピル、セバシン酸ジエチル、セバシン酸ジイソプロピル、アジピン酸ジイソブチル、コハク酸ジメチル及びフタル酸ジブチルからなる群から選択される1以上の化合物である、請求項1〜3のいずれか一項に記載の外用液剤。
- 前記抗コリン作用薬と前記ジカルボン酸エステルとの質量比が1:0.25〜1:0.75である、請求項1〜4のいずれか一項に記載の外用液剤。
- 前記ジカルボン酸エステルの含有量が、前記外用液剤の全質量を基準として2.5質量%〜15質量%である、請求項1〜5のいずれか一項に記載の外用液剤。
- 乳酸塩、酒石酸塩、酢酸塩及びリン酸塩からなる群から選択される1以上の塩をさらに含む、請求項1〜6のいずれか一項に記載の外用液剤。
- 前記塩が、乳酸ナトリウムである、請求項7に記載の外用液剤。
- ローションの剤形である、請求項1〜8のいずれか一項に記載の外用液剤。
- 多汗症治療用である、請求項1〜9のいずれか一項に記載の外用液剤。
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PCT/JP2016/081771 WO2017145441A1 (ja) | 2016-02-25 | 2016-10-26 | 外用液剤 |
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CN113520996B (zh) * | 2021-06-18 | 2022-11-18 | 北京斯利安药业有限公司 | 一种盐酸苯海索溶液剂及其制备方法与应用 |
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US7029694B2 (en) * | 2000-04-26 | 2006-04-18 | Watson Laboratories, Inc. | Compositions and methods for transdermal oxybutynin therapy |
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US20140037713A1 (en) | 2012-08-03 | 2014-02-06 | Antares Pharma Ipl, Ag | Transdermal compositions for anti-cholinergic agents |
WO2014105446A1 (en) * | 2012-12-27 | 2014-07-03 | Microdose Therapeutx, Inc. | Methods and compositions for administration of oxybutynin |
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