JP2014506900A - タペンタドールを含む半固形の水性医薬組成物 - Google Patents
タペンタドールを含む半固形の水性医薬組成物 Download PDFInfo
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- JP2014506900A JP2014506900A JP2013555798A JP2013555798A JP2014506900A JP 2014506900 A JP2014506900 A JP 2014506900A JP 2013555798 A JP2013555798 A JP 2013555798A JP 2013555798 A JP2013555798 A JP 2013555798A JP 2014506900 A JP2014506900 A JP 2014506900A
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- tapentadol
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
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Abstract
Description
酸塩基反応、酸もしくは塩基触媒作用、酸化および還元が、これらの製品では生じる場合がある。これらの反応は、原体−成分相互作用、成分−成分相互作用又は容器−製品相互作用から発生し得る。pH感受性化合物については、これらの相互作用のうちのいずれもがpHを変え得るものであり、析出を引き起こし得る。酸化に不安定な原体またはビタミン、精油およびほとんどすべての油脂は、自己酸化によって酸化し得る。そのような反応は熱、光、過酸化物または他の不安定な化合物または、重金属、例えば銅または鉄によって開始され得る。
副次的な態様として、活性成分および賦形剤に対する微生物の影響を避けること、すなわち、微生物分解を回避することも望ましいかもしれない。
−飽和C8〜C18脂肪酸、例えばミリスチン酸およびステアリン酸;
−不飽和C8〜C18脂肪酸およびそれらのエステル、例えばオレイン酸およびエチルオレエート;
−植物油、例えば大豆油および落花生油を含む飽和および不飽和C8〜C18脂肪酸の混合物;硬化油、例えば硬化ヒマシ油;および動物脂;および
−モノグリセリド、ジグリセリド、トリグリセリドおよびそれらの混合物を含む、脂肪酸のグリセリド;好ましくはC6〜C12脂肪酸、より好ましくはC6〜C10脂肪酸のグリセリド、例えばカプリル酸/カプリン酸トリグリセリド混合物、最も好ましくは、欧州薬局方または米国薬局方に従う中鎖トリグリセリド(例えば、商標「Captex(登録商標)およびMiglyol(登録商標)」で知られ、市販されている);
−プロピレングリコール脂肪酸エステル、例えばプロピレングリコールモノカプリレート(商標「Capryol(登録商標)」で知られ、市販されている);
−羊毛脂、カルナウバろう、蜜蝋を含むワックス、および飽和C18〜C32炭化水素の混合物、例えば固形パラフィンおよび軟パラフィン(例えば、白色ワセリンゼリー)。
−ポリオキシエチレン−ソルビタン−脂肪酸エステル、例えばモノ−およびトリ−ラウリル、パルミチル、ステアリルおよびオレイルエステル、例えば、「polysorbat」の名称で公知のタイプ、および、界面活性剤tween20[ポリオキシエチレン(20)ソルビタンモノラウレート]、tween40[ポリオキシエチレン(20)ソルビタンモノパルミテート]、60[ポリオキシエチレン(20)ソルビタンモノステアレート]、tween65[ポリオキシエチレン(20)ソルビタントリステアレート]、tween80[ポリオキシエチレン(20)ソルビタンモノオレアート]、tween85[ポリオキシエチレン(20)ソルビタントリオレアート]、tween21[ポリオキシエチレン(4)ソルビタンモノラウレート]およびtween81[ポリオキシエチレン(5)ソルビタンモノオレアート]を含む商標名「Tween(登録商標)」で市販されているタイプ;
−ポリオキシエチレン−グリセロール−脂肪酸エステル、例えばモノ−およびトリ−ラウリル、パルミチル、ステアリルおよびオレイルエステル、例えば商標「Tagat(登録商標」)で公知であり市販されているタイプ
−ポリオキシエチレン脂肪酸エステル、好ましくは約8〜約18個の炭素原子を有する脂肪酸、例えば、ジグリコールステアレート、グリコールステアレート、グリコールジステアレートおよび12−ヒドロキシステアリン酸のポリオキシエチレンエステルの混合物、例えば、商標名「Solutol」(登録商標)で公知であり市販されているタイプ;
−α−コハク酸トコフェリルのポリオキシエチレンエステル、例えば、D−アルファ−トコフェリル−PEG−1000−スクシナート(TPGS);
−ポリグリコライズドグリセリド(polyglycolyzed glycerides)、例えば、商標「Gelucire(登録商標)」および「Labrasol(登録商標)」で公知であり市販されているタイプ;
−天然もしくは硬化ヒマシ油およびエチレンオキシドの反応生成物、例えば商標「Cremophor(登録商標)」で公知であり市販されている様々な液体の界面活性剤;
−グリセロール脂肪酸エステル、例えばモノ−およびトリ−ラウリル、パルミチル、ステアリルおよびオレイルエステル(ジグリコールステアレート、グリセロールモノステアレート、グリセロールモノパルミテートおよびグリセロールトリオレエートを含む);
−セチルアルコール、ステアリルアルコール、セチルステアリルアルコールおよびコレステロールを含む脂肪アルコールまたはステロール。
−マクロゴールヒドロキシステアレート、マクロゴールグリセリルヒドロキシステアレートおよびマクロゴールグリセリルラウレートからなる群(ここで、マクロゴール部分は、好ましくは、15〜45個のエチレンオキサイド単位を含む);および/または
−セチルアルコール、ステアリルアルコールおよびセチルステアリルアルコールから成る群。
このタイプの例としては、高含有量の固体材料を有するパスタ剤が挙げられる。
しかしながら、一旦剪断応力が除去されると、流体は通常、その塑性流動特性を、ほとんどの場合にタイムラグ(チクソトロピー流体)とともに回復する。
−タペンタドール、水および好ましくは界面活性剤を含む水性相;および
−脂質を含む脂質相、および場合により他の成分、例えば界面活性剤、ワックスおよび/または滑剤;
を別々に調製し、その後、当該2つの相を、好ましくは両方の相が液体である上昇させた温度で混合することにより、作られる。
−タペンタドールの含有量は0.01〜50重量%の範囲内にある;および/または
−含水率は少なくとも0.5重量%である;および/または
−少なくとも10のHLB値を有する界面活性剤を含む;および/または
−脂質、好ましくはトリグリセリドを含む;および/または
−羊毛脂、カルナウバろう、蜜蝋、固形パラフィン、軟パラフィンおよび白色ワセリンゼリーから選択されるワックスを含む;
−いずれの保存剤も含まない;および/または
−少なくとも1つの水性および少なくとも1つの脂質相を含む二相または多相系であり、前記水性相は好ましくはコヒーレント相である;および/または
−非ニュートン流体である;および/または
−偽塑性流体の流体特性を示す;および/または
−局部的および/または局所的投与に適合されている;および/または
−どれがあるかは、小児、高齢および/または妊娠患者への投与に適合されている。
−その調製物は半固形および/または固体成分の溶融を含む。
クリーム剤は以下の組成によって製剤化された。
クリーム剤における異なる濃度のタペンタドールを用いる実験により、タペンタドールの保存効果が開始する濃度が、100mLの水性相における12〜25mgのタペンタドールHClであることが示される。従って、適当な濃度においてタペンタドールはクリーム剤用の保存剤として使用することができる。
本発明の例I−1およびI−2の粘度曲線を、以下のように決定した:
実験は、25.0の±0.1℃でHaake RotoVisco RV1装置(温度コントローラーDC30と一緒にセンサーC60/1°、Haake)によって行なわれた。物質(1.0mL)をステーターとローターの間に置き、そしてその間隙距離を0.052mmに調節した。実験を開始する前に、該物質を25.0℃に調節した。粘度曲線はソフトウェアRheoWin3で決定し、本発明のサンプルの特徴付けを行うために、種々の剪断応力(Δ=40s−1)の粘度値(n=4)を採取した。
pH3およびpH8でのタペンタドールの抗菌効果
15mg/mLのタペンタドール(遊離塩基)濃度を有するタペンタドール液剤を調製した。pH値を、クエン酸および1N NaOH溶液を使用して、3または8の標的値にそれぞれ調節した。追加の緩衝系は添加しなかった。プラセボ溶液が抗菌効果自体を示さないことを保証するために、pH調節用に異なる量の1N NaOH溶液を使用する場合であっても、同一のpH値に焦点を当ててプラセボ溶液pH8を調製した。
Claims (15)
- タペンタドールまたはその生理学的に許容可能な塩を含む半固形の水性医薬組成物。
- 局部および/または局所投与に適合されている、請求項1に記載の医薬組成物。
- 組成物の水性相のpH値が少なくとも5.5である、請求項1または2に記載の医薬組成物。
- 慢性または急性疼痛の治療において使用するための、請求項1〜3のいずれか1つに記載の医薬組成物。
- 疼痛が、リウマチ障害、関節疾患、有痛関節、術後の病訴、歯科外科、皮膚炎症(皮膚炎)、皮膚損傷、皮膚癌、口傷および/またはスポーツ外傷に関連する、請求項4に記載の医薬組成物。
- 軟膏剤、クリーム剤、マグマ剤、ゲル剤、乳剤、懸濁剤、ローション剤、リニメント剤、パスタ剤、湿布剤、懸濁ゲル剤およびエマルションゲル剤から成る群から選択される、請求項1〜5のいずれか1つに記載の医薬組成物。
- 二相性製剤または多相性製剤である、請求項1〜6のいずれか1つに記載の医薬組成物。
- タペンタドールの含有量が組成物の全重量を基準として少なくとも0.55重量%である、請求項1〜7のいずれか1つに記載の医薬組成物。
- (i)いずれの保存剤も含まないか;または
(ii)タペンタドールの非存在下で欧州薬局方に従って医薬組成物を十分に保存しないであろう量で保存剤を追加的に含む、請求項1〜8のいずれか1つに記載の医薬組成物。 - 保存剤の含有量が組成物の全重量を基準として最大で5.0重量%である、請求項9に記載の医薬組成物。
- 脂質および/または界面活性剤をさらに含む、請求項1〜10のいずれか1つに記載の医薬組成物。
- 脂質がモノグリセリド、ジグリセリドおよびトリグリセリドならびにこれらの混合物から成る群から選択される、請求項11に記載の医薬組成物。
- 界面活性剤が少なくとも12のHLB値を有する、請求項11または12に記載の医薬組成物。
- 偽塑性流体の流動特性を示す、請求項1〜13のいずれか1つに記載の医薬組成物。
- 加速保存条件下で少なくとも3か月の有効期間を示す、請求項1〜14のいずれか1つに記載の医薬組成物。
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