JP2022501407A - ゾルピデム又はその薬学的に許容される塩の口腔粘膜溶液剤 - Google Patents
ゾルピデム又はその薬学的に許容される塩の口腔粘膜溶液剤 Download PDFInfo
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- JP2022501407A JP2022501407A JP2021517825A JP2021517825A JP2022501407A JP 2022501407 A JP2022501407 A JP 2022501407A JP 2021517825 A JP2021517825 A JP 2021517825A JP 2021517825 A JP2021517825 A JP 2021517825A JP 2022501407 A JP2022501407 A JP 2022501407A
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- zolpidem
- aqueous solution
- stable non
- pharmaceutically acceptable
- acceptable salt
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- 229960001475 zolpidem Drugs 0.000 title claims abstract description 38
- ZAFYATHCZYHLPB-UHFFFAOYSA-N zolpidem Chemical compound N1=C2C=CC(C)=CN2C(CC(=O)N(C)C)=C1C1=CC=C(C)C=C1 ZAFYATHCZYHLPB-UHFFFAOYSA-N 0.000 title claims abstract description 38
- 150000003839 salts Chemical class 0.000 title claims abstract description 28
- 239000000203 mixture Substances 0.000 claims abstract description 60
- 239000000243 solution Substances 0.000 claims abstract description 41
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- 238000002360 preparation method Methods 0.000 claims abstract description 20
- 239000003961 penetration enhancing agent Substances 0.000 claims abstract description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 21
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- 239000000825 pharmaceutical preparation Substances 0.000 claims description 13
- 229940127557 pharmaceutical product Drugs 0.000 claims description 13
- 239000003795 chemical substances by application Substances 0.000 claims description 10
- 239000003125 aqueous solvent Substances 0.000 claims description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 6
- 229920000642 polymer Polymers 0.000 claims description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 4
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- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 claims description 4
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 claims description 4
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- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 3
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- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 claims description 2
- XUGNVMKQXJXZCD-UHFFFAOYSA-N isopropyl palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC(C)C XUGNVMKQXJXZCD-UHFFFAOYSA-N 0.000 claims description 2
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Abstract
Description
本発明は、ゾルピデム又はその薬学的に許容される塩の安定な非水溶液剤に関する。本発明の溶液剤は、口腔粘膜経路による投与に好適である。より詳細には、本発明は、頬粘膜経路、舌下経路又は口腔粘膜経路による口腔への投与時に迅速な作用の発現をもたらすゾルピデム又は薬学的に許容される塩の安定な非水溶液剤であって、製剤のpHが5〜9の範囲にある、安定な非水溶液剤に関する。
睡眠は、中枢神経系(CNS)、並びに代謝、異化、体温、学習及び記憶固定の調節を含む体内の生理機能の調節において重要な役割を有する。不眠は、以下の特色、すなわち入眠困難(たとえば、入眠潜時(SOL)が30分超)、睡眠不足(たとえば、総睡眠時間(TST)が5.5〜6時間未満)、頻回の中途覚醒、再入眠できない早朝覚醒、若しくは非回復性睡眠の1つ又は複数を特徴とする睡眠障害である。
● 少なくとも約2年の所望の貯蔵期間を有する透明な溶液剤の形態で所望の薬物濃度(0.5%〜10%w/v)を提供できない。それ故、市場で入手可能な大部分の製剤は、固形剤形である。
● 薬物の安定性の低下を招く水を必須成分として必要としており、薬物が保存中に溶液剤から沈殿する。
● これらの製剤において、口腔内の不快感などの副作用の可能性を引き起こすアルコールなど非常に高比率の透過促進剤を使用する。
● 5〜9のpH範囲の間で薬物の迅速な経粘膜透過を提供することにより、より速やかな作用の発現(20分未満のTmax)を実現できない。それ故、市場で入手可能な液体製剤は、5未満のpHで維持される。
1. 透明な非水溶液剤中で0.5%〜10%w/vの薬物の濃度を提供する;
2. 5〜9の広いpH範囲にわたり少なくとも2年の全貯蔵期間安定である製剤を提供する;及び
3. 薬物の経粘膜透過を損なうことなく、最大30%v/v製剤に使用される透過促進剤の量を最小限に抑える。
4. 5〜9のpH範囲にわたり薬物の迅速な経粘膜透過を提供することで、より速やかな作用の発現をもたらす。
本発明の主な目的は、ゾルピデム又はその薬学的に許容される塩の安定な非水溶液剤であって、製剤が薬物の迅速な経粘膜透過を提供する、安定な非水溶液剤を提供することである。
本発明は、薬物の迅速な口腔粘膜吸収を有する、ゾルピデム又はその薬学的に許容される塩の安定な非水溶液剤を提供する。
上記に開示された例は、本発明に包含される製剤の代表例である。本発明の範囲は、これらの例のいずれかに限定されるものではない。これらの本発明の代表的な製剤により得られる有利な特徴は、本発明の範囲に包含されるすべての製剤によっても得られる。
Claims (10)
- 0.5〜10%w/vのゾルピデム又はその薬学的に許容される塩、透過促進剤及び非水溶媒系を含むゾルピデム又はその薬学的に許容される塩の安定な非水溶液剤であって、前記製剤のpHは5〜9である安定な非水溶液剤。
- 前記溶液剤は、2.5%〜10%w/vのゾルピデム又はその薬学的に許容される塩を含む、請求項1に記載の安定な非水溶液剤。
- 前記製剤のpHは、6〜9の範囲、好ましくは7〜9の範囲にある、請求項1又は2に記載の安定な非水溶液剤。
- 前記透過促進剤は、1〜5の炭素鎖長を有する短鎖アルコール、グリココール酸ナトリウム、デオキシコール酸ナトリウム、タウロコール酸ナトリウム、グリコデオキシコール酸ナトリウム、タウロデオキシコール酸ナトリウム、オレイン酸、カプリン酸、ラウリン酸、レシチン、ミリスチン酸、パルミチン酸、リゾホスファチジルコリン、ホスファチジルコリン、アゾン、シクロデキストリン、硫酸ラウリルナトリウム、ポリオキシエチレン−9−ラウリルエーテル、ポリオキシチレン−20−セチルエーテル、塩化ベンザルコニウム、塩化セチルピリジニウム、ビタミンE TPGS、カプリロカプロイルポリオキシルグリセリド、ステアロイルマクロゴールグリセリド、プロピレングリコールジカプリロカプレート又はそれらの混合物を含む群から選択される、請求項1〜3のいずれか一項に記載の安定な非水溶液剤。
- 前記短鎖アルコールは、エタノール、イソプロピルアルコール又はそれらの混合物である、請求項4に記載の安定な非水溶液剤。
- 前記透過促進剤は、前記製剤の最大30%v/vである、請求項1〜5のいずれか一項に記載の安定な非水溶液剤。
- 前記透過促進剤は、前記製剤の2〜30%v/vの範囲、好ましくは前記製剤の10〜30%v/vの範囲にある、請求項1〜6のいずれか一項に記載の安定な非水溶液剤。
- 前記透過促進剤は、前記製剤の2〜25%v/vの範囲にある、請求項1〜7のいずれか一項に記載の安定な非水溶液剤。
- 前記非水溶媒系は、グリセロール、プロピレングリコール、ポリエチレングリコール、プロピレンカーボネート、グリコフロール、ミリスチン酸イソプロピル、パルミチン酸イソプロピル、ジメチルスルホキシド、クエン酸トリエチル、ジメチルアセトアミド、ベンジルアルコール、N−メチル−ピロリドン、ジメチルイソソルビド、酢酸エチル又はそれらの混合物から選択される、請求項1〜8のいずれか一項に記載の安定な非水溶液剤。
- 前記溶液剤は、ポリビニピロリドン、ポリ(ビニルピロリドン−co−酢酸ビニル)、ポリビニルポリピロリドン、ポリメタクリレート、ヒドロキシプロピルメチルセルロース、ヒドロキシプロピルメチルセルロースアセテートスクシネート、ヒドロキシエチルセルロース、ヒドロキシプロピルセルロース、ヒドロキシプロピルベータデクス、ポリビニルアルコール、ポリアクリル酸から選択されるポリマー又はそれらの混合物を最大5%w/vさらに含む、請求項1〜9のいずれか一項に記載の安定な非水溶液剤。
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PCT/IN2019/050734 WO2020075183A1 (en) | 2018-10-08 | 2019-10-04 | Oromucosal solutions of zolpidem or pharmaceutically acceptable salts thereof |
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ECSP21024213A (es) | 2021-06-30 |
AR116721A1 (es) | 2021-06-09 |
ZA202102322B (en) | 2023-01-25 |
CN112996488A (zh) | 2021-06-18 |
KR20210074311A (ko) | 2021-06-21 |
US20220000845A1 (en) | 2022-01-06 |
BR112021006551A2 (pt) | 2021-07-06 |
WO2020075183A1 (en) | 2020-04-16 |
PH12021550748A1 (en) | 2022-02-14 |
CA3115195A1 (en) | 2020-04-16 |
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TN2021000051A1 (en) | 2022-10-03 |
CL2021000856A1 (es) | 2021-09-24 |
MX2021003975A (es) | 2021-05-27 |
GEP20237492B (en) | 2023-04-10 |
SG11202103255RA (en) | 2021-04-29 |
EA202190765A1 (ru) | 2021-07-01 |
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