JP2020536089A - アセトアミノフェン−プレガバリン組み合わせ及び疼痛を処置する方法 - Google Patents
アセトアミノフェン−プレガバリン組み合わせ及び疼痛を処置する方法 Download PDFInfo
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- JP2020536089A JP2020536089A JP2020518795A JP2020518795A JP2020536089A JP 2020536089 A JP2020536089 A JP 2020536089A JP 2020518795 A JP2020518795 A JP 2020518795A JP 2020518795 A JP2020518795 A JP 2020518795A JP 2020536089 A JP2020536089 A JP 2020536089A
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- FQCQGOZEWWPOKI-UHFFFAOYSA-K trisalicylate-choline Chemical compound [Mg+2].C[N+](C)(C)CCO.OC1=CC=CC=C1C([O-])=O.OC1=CC=CC=C1C([O-])=O.OC1=CC=CC=C1C([O-])=O FQCQGOZEWWPOKI-UHFFFAOYSA-K 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 238000000539 two dimensional gel electrophoresis Methods 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 1
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- 235000010447 xylitol Nutrition 0.000 description 1
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- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
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Abstract
Description
本願は、2017年10月3日に出願された米国仮出願第62/567,384号の利益を主張し、その内容全体が、参照により、本明細書に組み込まれる。
参照による組み込み
疼痛。
非オピオイド鎮痛薬。
ガバペンチノイド
薬学的に許容され得る塩
製剤。
投与量。
薬学的に許容され得る賦形剤
純度
薬物動態及び薬力学。
a)用量Dとして表すことができる、投与された薬物の量
b)τとして表すことができる、投与間隔
c)分布容積Vdとして表すことができ、
d)濃度C0又はCssであって、
e)薬物の半減期t1/2であって、
i)CL(クリアランス)として表すことができ、
j)fとして表すことができ、
k)投与後の薬物のピーク血漿濃度Cmax
l)薬物がCmaxに達するのに要する時間tmax
m)次の用量が投与される前に薬物が到達する最低濃度Cmin及び
n)
本明細書において使用される実験法
室温で、水中において、異なるpH値で、プレガバリン(PGB)及びアセトアミノフェン(APAP)の溶解度を決定した。50mg/mLの濃度で水中にアセトアミノフェンを、100mg/mLの濃度でプレガバリンを添加することによって、試料を調製した。次いで、必要とされる範囲にpHを調整した。HPLC−UVによって、活性成分の濃度を決定した。
[実施例6] 組み合わせ製剤の体性疼痛に対する効果の分析
[実施例7] 異なる緩衝液とpHを用いた、組み合わせ製剤中の不純物レベルの分析。
実施形態
Claims (83)
- 液体単位投薬形態中に、
a)ガバペンチノイドと、
b)アセトアミノフェンと、
c)pH調整剤と、
d)水と、
を含む医薬組成物。 - 前記ガバペンチノイドが、ガバペンチン又は薬学的に許容され得るその塩である、請求項1に記載の医薬組成物。
- 前記ガバペンチノイドが、プレガバリン又は薬学的に許容され得るその塩である、請求項1に記載の医薬組成物。
- 前記液体単位投薬形態が、酸、前記酸の共役塩基又は前記酸及び前記酸の前記共役塩基の両方をさらに含む、請求項1に記載の医薬組成物。
- 前記酸がクエン酸である、請求項4に記載の医薬組成物。
- 前記酸が酢酸である、請求項4に記載の医薬組成物。
- 前記酸がリン酸である、請求項4に記載の医薬組成物。
- 前記液体単位投薬形態が等張性誘導剤をさらに含む、請求項1に記載の医薬組成物。
- 前記等張性誘導剤が塩化ナトリウムである、請求項8に記載の医薬組成物。
- 前記等張性誘導剤がマンニトールである、請求項8に記載の医薬組成物。
- 前記pH調整剤が水酸化ナトリウムである、請求項1に記載の医薬組成物。
- 前記pH調整剤が塩酸である、請求項1に記載の医薬組成物。
- 前記ガバペンチノイドが、前記液体単位投薬形態中に、約0.1mg/mL〜約50mg/mLの量で存在する、請求項1に記載の医薬組成物。
- 前記アセトアミノフェンが、前記液体単位投薬形態中に、約2mg/mL〜約20mg/mLの量で存在する、請求項1に記載の医薬組成物。
- 前記液体単位投薬形態が約5%以下のレベルで前記ガバペンチノイドの分解生成物をさらに含む、請求項1に記載の医薬組成物。
- 前記ガバペンチノイドの前記分解生成物が、4−(2−メチルプロピル)ピロリジン−2−オンである、請求項15に記載の医薬組成物。
- 前記液体単位投薬形態が約0.5%以下のレベルで前記アセトアミノフェンの分解生成物をさらに含む、請求項1に記載の医薬組成物。
- 前記アセトアミノフェンの前記分解生成物が、4−アミノフェノールである、請求項17に記載の医薬組成物。
- 前記液体単位投薬形態が約4〜約7のpHを有する、請求項1に記載の医薬組成物。
- 前記液体単位投薬形態の前記pHが約5である、請求項19に記載の医薬組成物。
- 前記液体単位投薬形態の前記pHが約5.5である、請求項19に記載の医薬組成物。
- 前記液体単位投薬形態の前記pHが約6である、請求項19に記載の医薬組成物。
- 前記液体単位投薬形態が、
e)酸、前記酸の共役塩基又は前記酸及び前記酸の前記共役塩基の両方と、
f)塩化ナトリウムと、
g)前記ガバペンチノイドの分解生成物と、
h)前記アセトアミノフェンの分解生成物と、
をさらに含む、請求項1に記載の医薬組成物。 - 前記液体単位投薬形態が、
a)前記ガバペンチノイドであって、前記ガバペンチノイドがプレガバリン又は薬学的に許容され得るその塩であり、前記プレガバリンが、前記液体単位投薬形態中に、約0.1〜約20mg/mLの量で存在する、ガバペンチノイドと、
b)前記アセトアミノフェンであって、前記液体単位投薬形態中で、約10mg/mLの量で存在する、アセトアミノフェンと、
c)前記pH調整剤であって、水酸化ナトリウムである、pH調整剤と、
d)約1.87mg/mLのリン酸二水素ナトリウムと、
e)約5.5mg/mLの塩化ナトリウムと、
f)水と、
を含み、
前記液体単位投薬形態が約5〜約7のpHを有する、請求項1に記載の医薬組成物。 - 前記液体単位投薬形態の前記pHが約6である、請求項24に記載の医薬組成物。
- 前記液体単位投薬形態が、
a)前記ガバペンチノイドであって、前記ガバペンチノイドがプレガバリン又は薬学的に許容され得るその塩であり、前記プレガバリンが、前記液体単位投薬形態中に、約0.1〜約20mg/mLの量で存在する、ガバペンチノイドと、
b)前記アセトアミノフェンであって、前記液体単位投薬形態中で、約10mg/mLの量で存在する、アセトアミノフェンと、
c)前記pH調整剤であって、水酸化ナトリウムである、pH調整剤と、
d)約2.101mg/mLのクエン酸一水和物と、
e)約2.25mg/mLの塩化ナトリウムと、
f)水と、
を含み、
前記液体単位投薬形態が約5〜約7のpHを有する、請求項1に記載の医薬組成物。 - 前記液体単位投薬形態の前記pHが約6である、請求項26に記載の医薬組成物。
- 前記液体単位投薬形態が、
a)前記ガバペンチノイドであって、前記ガバペンチノイドがプレガバリン又は薬学的に許容され得るその塩であり、前記プレガバリンが、前記液体単位投薬形態中に、約0.1〜約20mg/mLの量で存在する、ガバペンチノイドと、
b)前記アセトアミノフェンであって、前記液体単位投薬形態中で、約10mg/mLの量で存在する、アセトアミノフェンと、
c)前記pH調整剤であって、水酸化ナトリウムである、pH調整剤と、
d)約1.55mg/mLのL−ヒスチジンと、
e)約2.25mg/mLの塩化ナトリウムと、
f)水と、
を含み、
前記液体単位投薬形態が約5〜約7のpHを有する、請求項1に記載の医薬組成物。 - 前記液体単位投薬形態の前記pHが約6である、請求項28に記載の医薬組成物。
- 前記液体単位投薬形態が、
a)前記ガバペンチノイドであって、前記ガバペンチノイドがプレガバリン又は薬学的に許容され得るその塩であり、前記プレガバリンが、前記液体単位投薬形態中に、約0.1〜約20mg/mLの量で存在する、ガバペンチノイドと、
b)前記アセトアミノフェンであって、前記液体単位投薬形態中で、約10mg/mLの量で存在する、アセトアミノフェンと、
c)前記pH調整剤であって、水酸化ナトリウムである、pH調整剤と、
d)約2.101mg/mLのクエン酸一水和物と、
e)約5mg/mLの塩化ナトリウムと、
f)水と、
を含み、
前記液体単位投薬形態が約5〜約7のpHを有する、請求項1に記載の医薬組成物。 - 前記液体単位投薬形態の前記pHが約5.5である、請求項30に記載の医薬組成物。
- 前記液体単位投薬形態が、
a)前記ガバペンチノイドであって、前記ガバペンチノイドがプレガバリン又は薬学的に許容され得るその塩であり、前記プレガバリンが、前記液体単位投薬形態中に、約0.1〜約20mg/mLの量で存在する、ガバペンチノイドと、
b)前記アセトアミノフェンであって、前記液体単位投薬形態中で、約10mg/mLの量で存在する、アセトアミノフェンと、
c)前記pH調整剤であって、水酸化ナトリウムである、pH調整剤と、
d)約0.6mg/mLの酢酸と、
e)約5mg/mLの塩化ナトリウムと、
f)水と、
を含み、
前記液体単位投薬形態が約5〜約7のpHを有する、請求項1に記載の医薬組成物。 - 前記液体単位投薬形態の前記pHが約5.5である、請求項32に記載の医薬組成物。
- 前記液体単位投薬形態が、
a)前記ガバペンチノイドであって、前記ガバペンチノイドがプレガバリン又は薬学的に許容され得るその塩であり、前記プレガバリンが、前記液体単位投薬形態中に、約0.1〜約20mg/mLの量で存在する、ガバペンチノイドと、
b)前記アセトアミノフェンであって、前記液体単位投薬形態中で、約10mg/mLの量で存在する、アセトアミノフェンと、
c)前記pH調整剤であって、水酸化ナトリウムである、pH調整剤と、
d)約1.2mg/mLのリン酸二水素ナトリウムと、
e)約5.5mg/mLの塩化ナトリウムと、
f)水と、
を含み、
前記液体単位投薬形態が約5〜約7のpHを有する、請求項1に記載の医薬組成物。 - 前記液体単位投薬形態の前記pHが約6である、請求項34に記載の医薬組成物。
- 前記液体単位投薬形態が不純物をさらに含み、前記不純物が、
(a)高速液体クロマトグラフィー装置中に前記液体単位投薬形態を注入することであって、前記装置は、
(i)固定相として吸着性粒子を含有するクロマトグラフィーカラムと、
(ii)前記クロマトグラフィーカラムを通過する第一の移動相であって、2%アセトニトリルを有するpH7の水性リン酸二水素カリウムである第一の移動相と、
(iii)前記クロマトグラフィーカラムを通過する第二の移動相であって、60%アセトニトリルを有するpH7の水性リン酸二水素カリウムである第二の移動相と、
を備える、注入すること
(b)前記クロマトグラフィーカラムを通して前記液体単位投薬形態を34分間流すこと、
(c)前記第一の移動相の勾配と前記第二の移動相の勾配を用いて、前記クロマトグラフィーカラムから前記不純物を溶出することであって、前記第一の移動相と第二の移動相の各々を、前記クロマトグラフィーカラムを通して、1.5mL/分の流速で流す、溶出すること、
(d)前記溶出された単位投薬形態及び前記不純物のUVスペクトルを生成するために、前記不純物をUV検出器に通過させること、
(e)標準と比較した前記不純物の保持時間に基づいて、前記不純物を同定すること、並びに
(f)前記UVスペクトルから前記不純物に対して取得されたピークの積分に基づいて、前記不純物の量を計算すること、
に基づいて決定される、請求項1に記載の医薬組成物。 - 前記医薬組成物が、袋、ガラスバイアル又はプレフィルドシリンジに包装するために製剤化されている、請求項1に記載の医薬組成物。
- 前記医薬組成物が袋に包装するために製剤化されており、前記袋がポリマー袋である、請求項37に記載の医薬組成物。
- 前記ポリマー袋がポリプロピレン袋であり、及び前記ポリプロピレン袋がアルミニウムオーバーパウチ中にさらに包装されている、請求項38に記載の医薬組成物。
- 前記アルミニウムオーバーパウチが酸素消去剤を含有する、請求項39に記載の医薬組成物。
- 疼痛の処置を必要としている対象における疼痛を処置する方法であって、治療的に有効な量の液体単位投薬形態を前記対象に投与することを含み、前記液体単位投薬形態が、
a)ガバペンチノイドと、
b)アセトアミノフェンと、
c)pH調整剤と、
d)水と、
を含む、方法。 - 前記ガバペンチノイドが、ガバペンチン又は薬学的に許容され得るその塩である、請求項41に記載の方法。
- 前記ガバペンチノイドが、プレガバリン又は薬学的に許容され得るその塩である、請求項41に記載の方法。
- 前記液体単位投薬形態が、酸、前記酸の共役塩基又は前記酸及び前記酸の前記共役塩基の両方をさらに含む、請求項41に記載の方法。
- 前記酸がクエン酸である、請求項44に記載の方法。
- 前記酸が酢酸である、請求項44に記載の方法。
- 前記酸がリン酸である、請求項44に記載の方法。
- 前記液体単位投薬形態が等張性誘導剤をさらに含む、請求項41に記載の方法。
- 前記等張性誘導剤が塩化ナトリウムである、請求項48に記載の方法。
- 前記等張性誘導剤がマンニトールである、請求項48に記載の方法。
- 前記pH調整剤が水酸化ナトリウムである、請求項41に記載の方法。
- 前記pH調整剤が塩酸である、請求項41に記載の方法。
- 前記ガバペンチノイドが、前記液体単位投薬形態中に、約0.1mg/mL〜約50mg/mLの量で存在する、請求項41に記載の方法。
- 前記アセトアミノフェンが、前記液体単位投薬形態中に、約2mg/mL〜約20mg/mLの量で存在する、請求項41に記載の方法。
- 前記液体単位投薬形態が約5%以下のレベルで前記ガバペンチノイドの分解生成物をさらに含む、請求項41に記載の方法。
- 前記ガバペンチノイドの前記分解生成物が、4−(2−メチルプロピル)ピロリジン−2−オンである、請求項55に記載の方法。
- 前記液体単位投薬形態が0.5%以下のレベルで前記アセトアミノフェンの分解生成物をさらに含む、請求項41に記載の方法。
- 前記アセトアミノフェンの前記分解生成物が、4−アミノフェノールである、請求項57に記載の方法。
- 前記液体単位投薬形態が約4〜約7のpHを有する、請求項41に記載の方法。
- 前記液体単位投薬形態の前記pHが約5である、請求項59に記載の方法。
- 前記液体単位投薬形態の前記pHが約5.5である、請求項59に記載の方法。
- 前記液体単位投薬形態の前記pHが約6である、請求項59に記載の方法。
- 前記疼痛が術後疼痛である、請求項41に記載の方法。
- 前記液体単位投薬形態が、前記対象が外科手術を受ける前24時間以内に前記対象に投与される、請求項41に記載の方法。
- 前記液体単位投薬形態が、前記対象が外科手術を受けると同時に前記対象に投与される、請求項41に記載の方法。
- 前記液体単位投薬形態が、前記対象が外科手術を受けた後24時間以内に前記対象投与に投与される、請求項41に記載の方法。
- 前記投与が静脈内投与である、請求項41に記載の方法。
- 前記投与が筋肉内投与である、請求項41に記載の方法。
- 前記投与が皮下投与である、請求項41に記載の方法。
- 医薬製剤を製造する方法であって、
a)製造タンクに水を添加すること、
b)約1ppm未満の溶存酸素レベルを達成するために、窒素を注入することによって、前記製造タンク中の前記水から酸素を除去すること、
c)混合物を用意するために、前記製造タンク中の前記水にバッファを添加すること、
d)前記製造タンク中の前記混合物にpH調整剤を添加することであって、前記製造タンク中の前記混合物に前記pH調整剤を添加することが、前記混合物のpHを約pH4〜約pH7に調整することである、添加すること、
e)前記製造タンク中の前記混合物中にガバペンチノイドを配置すること、及び
f)前記製造タンク中の前記混合物中にアセトアミノフェンを配置すること、
を含む、方法。 - 前記製造タンクから前記混合物の一部を取り出すこと、及び前記製造タンクから取り出された前記混合物の前記一部を容器に包装することをさらに含む、請求項70に記載の方法。
- 前記容器がポリマー袋である、請求項71に記載の方法。
- 前記容器がガラスバイアル又はプレフィルドシリンジである、請求項71に記載の方法。
- 前記ポリマー袋がポリプロピレン袋であり、及び前記ポリプロピレン袋がアルミニウムオーバーパウチ中にさらに包装されている、請求項72に記載の方法。
- 前記アルミニウムオーバーパウチが酸素消去剤を含有する、請求項74に記載の医薬組成物。
- 前記ガバペンチノイドが、ガバペンチン又は薬学的に許容され得るその塩である、請求項70に記載の方法。
- 前記ガバペンチノイドが、プレガバリン又は薬学的に許容され得るその塩である、請求項70に記載の方法。
- 前記pH調整剤が水酸化ナトリウムである、請求項70に記載の方法。
- 前記pH調整剤が塩酸である、請求項70に記載の方法。
- 前記ガバペンチノイドが、前記ポリマー袋中に、約0.1mg/mL〜約50mg/mLの量で存在する、請求項72に記載の方法。
- 前記ガバペンチノイドが、前記ガラスバイアル中に、約0.1mg/mL〜約50mg/mLの量で存在する、請求項73に記載の方法。
- 前記アセトアミノフェンが、前記ポリマー袋中に、約2mg/mL〜約20mg/mLの量で存在する、請求項72に記載の方法。
- 前記アセトアミノフェンが、前記ガラスバイアル中に、約2mg/mL〜約20mg/mLの量で存在する、請求項73に記載の方法。
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Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5658919A (en) * | 1993-04-16 | 1997-08-19 | Mcneil-Ppc, Inc. | Aqueous pharmaceutical suspension and process for preparation thereof |
JP2010540668A (ja) * | 2007-10-09 | 2010-12-24 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | ベンフォチアミンと1または2種以上の医薬活性剤とを含む神経因性の疼痛状態の処置のための医薬組成物 |
US20120245230A1 (en) * | 2009-12-10 | 2012-09-27 | Tecnimede-Sociedade Tecnico- Medicinal, S.A. | Method and composition for preparing stable liquid formulations of paracetamol |
WO2017134540A1 (en) * | 2016-02-05 | 2017-08-10 | Innopharma, Inc. | Process of manufacturing a stable, ready to use infusion bag for an oxidation sensitive formulation |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU8668598A (en) | 1997-08-20 | 1999-03-08 | University Of Oklahoma, The | Gaba analogs to prevent and treat gastrointestinal damage |
EP1161263A1 (en) | 1999-03-10 | 2001-12-12 | Warner-Lambert Company Llc | Analgesic compositions comprising anti-epileptic compounds and methods of using same |
US20050004219A1 (en) | 2003-07-01 | 2005-01-06 | Medtronic, Inc. | Pump systems including injectable gabapentin compositions |
GB2416122A (en) * | 2004-07-12 | 2006-01-18 | Ipsen Ltd | Botulinum neurotoxin composition |
US7488846B2 (en) * | 2005-04-11 | 2009-02-10 | Teva Pharmaceuical Industries Ltd. | Pregabalin free of lactam and a process for preparation thereof |
MX2007006091A (es) | 2007-05-21 | 2009-02-25 | World Trade Imp Export Wtie Ag | Composicion farmaceutica que comprende la combinacion de un agente antiinflamatorio no esteroideo y un agente anticonvulsionante. |
WO2015144825A1 (en) * | 2014-03-27 | 2015-10-01 | Sanovel Ilac Sanayi Ve Ticaret A.S. | Oral liquid pharmaceutical solution of gabapentin |
ES2607489T3 (es) * | 2014-05-23 | 2017-03-31 | Ares Trading S.A. | Composición farmacéutica líquida |
US10874626B2 (en) | 2016-04-07 | 2020-12-29 | Nevakar Inc. | Formulation for use in a method of treatment of pain |
-
2018
- 2018-10-02 WO PCT/US2018/053864 patent/WO2019070641A1/en unknown
- 2018-10-02 EP EP18864043.7A patent/EP3691748A4/en active Pending
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2022
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Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5658919A (en) * | 1993-04-16 | 1997-08-19 | Mcneil-Ppc, Inc. | Aqueous pharmaceutical suspension and process for preparation thereof |
JP2010540668A (ja) * | 2007-10-09 | 2010-12-24 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | ベンフォチアミンと1または2種以上の医薬活性剤とを含む神経因性の疼痛状態の処置のための医薬組成物 |
US20120245230A1 (en) * | 2009-12-10 | 2012-09-27 | Tecnimede-Sociedade Tecnico- Medicinal, S.A. | Method and composition for preparing stable liquid formulations of paracetamol |
WO2017134540A1 (en) * | 2016-02-05 | 2017-08-10 | Innopharma, Inc. | Process of manufacturing a stable, ready to use infusion bag for an oxidation sensitive formulation |
Non-Patent Citations (4)
Title |
---|
ACTA ANAESTHESIOL SCAND, vol. 51, JPN6022038016, 2007, pages 299 - 304, ISSN: 0004869285 * |
ACTA ANAESTHESIOL SCAND, vol. 53, JPN6022038014, 2009, pages 227 - 235, ISSN: 0004869284 * |
NEUROPHARMACOLOGY, vol. 58(4-5), JPN6022038015, 2010, pages 758 - 766, ISSN: 0004869283 * |
PHARMACOLOGY, vol. 93, JPN6022038012, 2014, pages 253 - 259, ISSN: 0004869282 * |
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US11547686B2 (en) | 2023-01-10 |
CA3075414A1 (en) | 2019-04-11 |
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