JP2013537903A - カラノライド、その誘導体及び類似体についての医薬組成物並びにそれを製造するための方法 - Google Patents
カラノライド、その誘導体及び類似体についての医薬組成物並びにそれを製造するための方法 Download PDFInfo
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- JP2013537903A JP2013537903A JP2013530106A JP2013530106A JP2013537903A JP 2013537903 A JP2013537903 A JP 2013537903A JP 2013530106 A JP2013530106 A JP 2013530106A JP 2013530106 A JP2013530106 A JP 2013530106A JP 2013537903 A JP2013537903 A JP 2013537903A
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- calanolide
- pharmaceutical composition
- oil
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- NIDRYBLTWYFCFV-FMTVUPSXSA-N (+)-calanolide A Chemical group C1=CC(C)(C)OC2=C1C(O[C@H](C)[C@@H](C)[C@@H]1O)=C1C1=C2C(CCC)=CC(=O)O1 NIDRYBLTWYFCFV-FMTVUPSXSA-N 0.000 claims description 63
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- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- 235000019871 vegetable fat Nutrition 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 description 1
- 229960002555 zidovudine Drugs 0.000 description 1
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Abstract
Description
a.カラノライド又はカラノライド(複数)の混合物
b.1つ又は複数の溶解度向上剤、及び
c.1つ又は複数の界面活性剤
を含む医薬組成物を提供することである。
「医薬組成物」は、個々の成分又は構成要素がそれら自体薬学的に許容されるものであり、処方された投薬量のカラノライドが哺乳動物、特にヒトへ送達されるように適合されている組成物を規定するものと理解すべきである。
第1の態様では、本発明はその最も広い態様において
a.カラノライド又はカラノライド(複数)の混合物
b.1つ又は複数の溶解度向上剤、及び
c.1つ又は複数の界面活性剤
を含む医薬組成物を提供する。
a.重量で全組成物の約0.5%〜約80%の量のカラノライド又はカラノライド(複数)の混合物
b.重量で全組成物の約0.5%〜約90%の量の1つ又は複数の溶解度向上剤、及び
c.重量で全組成物の約0.1%〜約80%の量の1つ又は複数の界面活性剤
を含み、この医薬組成物は経口又は非経口投与のための高い溶解度及び生物学的利用能を有する。
a.重量で全組成物の約5%〜約50%の量のカラノライド又はカラノライド(複数)の混合物
b.重量で全組成物の約10%〜約60%の量の1つ又は複数の溶解度向上剤、及び
c.重量で全組成物の約5%〜約50%の量の1つ又は複数の界面活性剤
を含み、この医薬組成物は経口又は非経口投与のための高い溶解度及び生物学的利用能を有する。
a.重量で全組成物の約10%〜約35%の量のカラノライド又はカラノライド(複数)の混合物
b.重量で全組成物の約25%〜約50%の量の1つ又は複数の溶解度向上剤、及び
c.重量で全組成物の約20%〜約40%の量の1つ又は複数の界面活性剤
を含み、この医薬組成物は経口又は非経口投与のための高い溶解度及び生物学的利用能を有する。
本発明の医薬組成物の第1の必須成分は、活性構成要素としてカラノライド又はカラノライド(複数)の混合物を含む。
(式中、
R1はC1〜C6アルキル又はアリールであり;R2は
であり、R3はC1〜C6アルキル又はアリールであり;R4とR5は同じであるか又は異なっており、それぞれ
である。アリール基は適切な任意のアリール置換基であってよいが、アリールは、好ましくはC6〜C14環構造、最も好ましくはフェニルである。
本発明の一実施形態では、カラノライド粒子は、適切な任意の形態、例えば結晶形態、半結晶形態、無定形、半無定形又はその組合せで存在していてよい。
本発明の医薬組成物の第2の成分は、油、ピロリドン誘導体、ポリグリコール、脂肪族アミド、ポリエーテル、アルコール、アルコールのエステル、ジメチルスルホキシド、シクロデキストリン及びその組合せからなる群から選択される1つ又は複数の溶解度向上剤を含む。
本発明による医薬組成物の第3の成分は1つ又は複数の界面活性剤を含む。
本発明は、
i.カラノライドを1つ又は複数の溶解度向上剤と20℃〜65℃の温度で混合するステップと
ii.1つ又は複数の界面活性剤を、ステップ(i)で得られた生成混合物と混合して均一混合物を形成させるステップと
を含む医薬組成物を製造するための方法であって、上記ステップ(i)の混合プロセスが分散ミルで粉末混合物を1〜40時間粉砕する追加のステップをさらに含むことができる方法も提供する。
i)重量で全組成物の約0.5%〜約80%の量のカラノライド又はカラノライド(複数)の混合物を、重量で全組成物の約0.5%〜約90%の量の1つ又は複数の溶解度向上剤と20℃〜65℃の温度で混合するステップと
ii)ステップ(i)で得られた生成混合物を、約0.1%〜約80%の量の1つ又は複数の界面活性剤と混合して均一混合物を形成させるステップと
を含む本発明の医薬組成物を製造するための方法であって、上記ステップ(i)の混合プロセスが分散ミルで粉末混合物を1〜40時間粉砕する追加のステップをさらに含むことができる方法を提供する。
i)重量で全組成物の約5%〜約50%の量のカラノライド又はカラノライド(複数)の混合物を、重量で全組成物の約10%〜約60%の量の1つ又は複数の溶解度向上剤と20℃〜65℃の温度で混合するステップと
ii)ステップ(i)で得られた生成混合物を約5%〜約50%の量の1つ又は複数の界面活性剤と混合して均一混合物を形成させるステップと
を含む医薬組成物を調製するための方法であって、上記ステップ(i)の混合プロセスが分散ミルで粉末混合物を1〜40時間粉砕する追加のステップをさらに含むことができる方法を提供する。
i)重量で全組成物の約10%〜約35%の量のカラノライド又はカラノライド(複数)の混合物を、重量で全組成物の約25%〜約50%の量の1つ又は複数の溶解度向上剤と20℃〜65℃の温度で混合するステップと
ii)ステップ(i)で得られた生成混合物を約20%〜約40%の量の1つ又は複数の界面活性剤と混合して均一混合物を形成させるステップと
を含む医薬組成物を調製するための方法であって、上記ステップ(i)の混合プロセスが分散ミルで粉末混合物を1〜40時間粉砕する追加のステップをさらに含むことができる方法を提供する。
本発明のさらに他の態様では、医薬組成物は単位剤形で存在することが好都合であり、当業界で周知の方法のいずれかによって調製することができる。
本発明の医薬組成物を軟質カプセル剤の形態で調製する場合、その組成物を、慣用的な任意の可塑剤を含むゼラチン、デンプン、カラギーナン又はセルロースソフトシェル中にカプセル化することができる。適切な可塑剤は、グリセリン、ソルビトール、プロピレングリコール、ポリエチレングリコール及びこれらの可塑剤の混合物である。さらに、カプセル材料は、保存剤、乳白剤、着色剤及び香味剤などの添加物を含むことができる。
液体又は半固体での本発明の医薬組成物は、硬質シェルカプセル剤の形態で調製することができる。組成物を、慣用的な任意の可塑剤を含むゼラチン、デンプン、カラギーナン又はセルロース硬質シェル中にカプセル化することができる。適切な可塑剤は、グリセリン、ソルビトール、プロピレングリコール、ポリエチレングリコール及びこれらの可塑剤の混合物である。さらに、カプセル材料は、保存剤、乳白剤、着色剤及び香味剤などの添加物を含むことができる。シェルは通常、連結された2つの部分中に供給される。その一方は本発明の組成物で充填され、他方は、充填シェル部分を覆って配置されてキャップとしての役目を果たす。次いで2つの部分を、ゼラチンバンディング又はCapsulgel(LICAPSという用語はCapsulgelの商標名である)から販売されているLICAPSシステムによるなどの好都合な任意の手段で密封することができる。
固体形態の本発明の医薬組成物は、錠剤、例えば非コーティング錠剤、コーティング錠剤又は即時放出錠剤の形態で調製することができる。一般に、医薬組成物は、本発明の医薬組成物を均一且つ密に1つ又は複数の固体薬学的に許容される添加剤と一緒にし、次いで必要なら、生成物を所望の剤形に成形することによって調製する。
本発明の医薬組成物は、筋肉内注射剤、髄腔内注射剤、皮内注射剤、腹腔内注射剤及び皮下注射剤を含む非経口投与用の単位剤形で調製することができる。
或いは、本発明の医薬組成物を、持続放出系を用いて送達し、カラノライドの制御放出をもたらして、より頻度の低い投与を可能にするか、又は活性構成要素の薬物動態又は毒性プロファイルを改善することができる。様々な種類の持続放出材料が確立されており、これらは当業者に周知である。例えば、本発明の組成物を、持続放出錠剤、又は前記組成物の即時放出の1つの層と持続放出の1つの層を備えた二重層錠剤として処方することができる。
他の実施形態では、本発明は、カラノライドの経口又は非経口での生物学的利用能を増大させる方法であって、そうした組成物を必要とする哺乳動物、特にヒトに、カラノライド、1つ又は複数の溶解性向上及び1つ又は複数の界面活性剤を含む治療有効量の医薬組成物を経口又は非経口で投与することを含む方法を提供する。前記方法は、カラノライドの溶解性を改善することによって、投与されたカラノライドの生物学的利用能を向上させる。
本発明の他の実施形態では、患者への医薬組成物の投与の投薬量及び回数は様々であり、患者の年齢及び体重、性別、患者の状態、投与方式などのいくつかの要素に依存し、それは担当医が判断すべきことである。
本発明の一実施形態では、経口単位剤形中に含まれるカラノライドの量は一般に、約10mg〜約1000mgのカラノライド、より好ましくは20〜200mgで変動してよく、例えば、25、50、100、125、150又は200mgのカラノライドである。最も好ましくは、経口単位剤形は約100mg〜約150mgのカラノライドを含む。
本発明のさらに他の実施形態によれば、それを必要とする対象への本発明の医薬組成物の投与方法であって、前記方法が経口又は非経口経路で治療有効量の本発明の医薬組成物を投与することを含み、前記組成物が高い溶解度及び生物学的利用能を有する方法が提供される。
一実施形態では、本発明の医薬組成物は少なくとも1つの追加の抗HIV剤をさらに含む。好ましい実施形態では、抗HIV剤は、プロテアーゼ阻害剤、非ヌクレオシド逆転写酵素阻害剤、ヌクレオシド逆転写酵素阻害剤、ヌクレオチド逆転写酵素阻害剤、インテグラーゼ阻害剤、侵入及び融合阻害剤、成熟阻害剤並びにその組合せから選択することができる。
比較のために、以下の処方(formula)による対照組成物を調製した。
カラノライドAの液剤のための処方物
以下の処方物は、ソフトゲル充填に適したカラノライドAの溶液を提供し、以下の例9及び10に示すような向上した水への溶解度及び生物学的利用能を有する。
カラノライドAの液剤のための処方物
以下の処方物は、ソフトゲル充填に適したカラノライドAの溶液を提供し、以下の例9及び10に示すような向上しれた水への溶解度及び生物学的利用能を有する。
カラノライドAの液剤のための処方物
以下の処方物は、非経口(筋肉内又は皮下)投与用に無菌的に充填するのに適したカラノライドAの溶液を提供し、以下の例9及び11に示すような向上した水への溶解度及び生物学的利用能を有する。
カラノライドAの液剤のための処方物
以下の処方物は、硬質カプセル中への液体充填に適したカラノライドAの溶液を提供し、以下の例9に示すような向上した水への溶解度を有する。
カラノライドAの液剤のための処方物
以下の処方物は、非経口(筋肉内又は皮下)投与用に無菌的に充填するのに適したカラノライドAの溶液を提供し、以下の例9に示すような向上した水への溶解度を有する。
カラノライドAの液剤のための処方物
以下の処方物は、ソフトゲル充填に適したカラノライドAの溶液を提供する。
カラノライドA錠剤のための処方物
以下の処方物は、錠剤中に圧入するのに適したカラノライドAの粉末混合物を提供する。
カラノライドA硬質カプセル剤のための処方物
以下の処方物は、硬質カプセル中に充填するのに適したカラノライドAの粉末を提供する。
溶解性試験
試験方法
これらの試験は、本発明の医薬組成物の代表的製剤のカラノライドAの溶解度と、比較例Aに示した対照組成物と比較するために実施した。
ラットにおける経口生物学的利用能試験
例1及び例2で調製した本発明による医薬組成物の代表的製剤についての経口生物学的利用能試験を、比較例Aで示した対照組成物と比較した。
ラットにおける非経口生物学的利用能試験
例3で調製した本発明による医薬組成物の代表的製剤についての非経口生物学的利用能試験を、比較例Aで調製した対照組成物と比較した。
Cmaxでの経口又は非経口生物学的利用能の増大も提供する。
(参考文献)
Claims (43)
- a)カラノライド又はカラノライド(複数)の混合物、
b)1つ又は複数の溶解度向上剤、及び
c)1つ又は複数の界面活性剤
を含む経口又は非経口投与用のカラノライドの医薬組成物。 - 前記組成物が高い溶解度及び生物学的利用能を有する、請求項1に記載の医薬組成物。
- 前記組成物が、AUC(0〜24)で測定して少なくとも20%のカラノライドの経口又は非経口での生物学的利用能の増大を提供する、請求項2に記載の医薬組成物。
- 前記組成物が、Cmaxで測定して少なくとも30%のカラノライドの経口又は非経口での生物学的利用能の増大を提供する、請求項2に記載の医薬組成物。
- 前記組成物が、少なくとも20%のカラノライドの溶解度の増大を提供する、請求項2に記載の医薬組成物。
- 前記組成物が液体、半固体又は固体の形態である、請求項1に記載の医薬組成物。
- a)前記カラノライド又はカラノライド(複数)の混合物が重量で全組成物の約0.5%〜約80%の量で存在し、
b)前記溶解度向上剤が重量で全組成物の約0.5%〜約90%の量で存在し、
c)前記界面活性剤が重量で最終組成物の約0.1%〜約80%の量で存在する、
請求項1に記載の医薬組成物。 - a)前記カラノライド又はカラノライド(複数)の混合物が重量で全組成物の約5%〜約50%の量で存在し、
b)前記溶解度向上剤が重量で全組成物の約10%〜約60%の量で存在し、
c)前記界面活性剤が重量で最終組成物の約5%〜約50%の量で存在する、
請求項1に記載の医薬組成物。 - a)前記カラノライド又はカラノライド(複数)の混合物が重量で全組成物の約10%〜約35%の量で存在し、
b)前記溶解度向上剤が重量で全組成物の約25%〜約50%の量で存在し、
c)前記界面活性剤が重量で最終組成物の約20%〜約40%の量で存在する、
請求項1に記載の医薬組成物。 - 前記カラノライドが、カラノライド、その誘導体、薬学的に許容される塩、エステル、アミド、プロドラッグ、活性代謝産物、異性体、類似体及びその混合物からなる群から選択される、請求項1に記載の医薬組成物。
- 前記カラノライドが(+)カラノライドAである、請求項1に記載の医薬組成物。
- 組成物中に存在するカラノライド粒子が、結晶、半結晶、無定形、半無定形、液体、分散した固体の形態又はその形態の組合せ(単数又は複数)である、請求項1に記載の医薬組成物。
- 分散した固体の形態で存在するカラノライドの粒径が、1000ミクロン未満、50ミクロン未満又は0.1ミクロン未満の粒径からなる群から選択される、請求項12に記載の医薬組成物。
- 前記溶解度向上剤が、油、ピロリドン誘導体、ポリグリコール、脂肪族アミド、ポリエーテル、アルコール、アルコールのエステル、ジメチルスルホキシド、シクロデキストリン及びその組合せからなる群から選択される、請求項1に記載の医薬組成物。
- 前記油が、モノグリセリド、ジグリセリド、トリグリセリド、植物油、動物油、脂肪酸及びその組合せからなる群から選択される、請求項14に記載の医薬組成物。
- 前記油が、グリセリルモノカプレート、グリセリルモノカプリレート、グリセリルモノステアレート、グリセリルモノオレエート;グリセリルジカプリレート、グリセリルジラウレート;グリセリルトリカプリレート、グリセリルトリカプレート、グリセリルトリミリステート、グリセリルトリパルミテート、グリセリルトリステアレート;アーモンドオイル、杏仁油、ババス油、ボリジオイル、ブラックカラント種子油、キャノーラ油、ヒマシ油、ココナツオイル、コーンオイル、綿実油、月見草油、グレープシードオイル、ラッカセイ油、からし油、オリーブ油、ヤシ油、パーム核油、ピーナッツ油、グレープシードオイル、菜種油、サフラワー種子油、ゴマ油、大豆油、ヒマワリ種子油;魚油、うなぎ油、魚肝油、サメ肝油、ミンクオイル;ミリスチン酸、パルミチン酸、エイコサペンタエン酸、ドコサヘキサエン酸及びその混合物からなる群から選択される、請求項15に記載の医薬組成物。
- ピロリドン誘導体が、2−ピロリドン、N−メチル−2−ピロリドン、N−エチル−2−ピロリドン、N−プロピル−2−ピロリドン、N−イソプロピル−2−ピロリドン、N−ブチル−2−ピロリドン、ポリビニルピロリドンK−30、ポリビニルピロリドンK−90及びその混合物からなる群から選択される、請求項14に記載の医薬組成物。
- 前記シクロデキストリンが、α−シクロデキストリン、β−シクロデキストリン、γ−シクロデキストリン、ヒドロキシプロピルα−シクロデキストリン、メチル化α−シクロデキストリン、メチル化β−シクロデキストリン、ヒドロキシエチルβ−シクロデキストリン、ヒドロキシプロピルβ−シクロデキストリン、ヒドロキシプロピルγ−シクロデキストリン及びメチル化γ−シクロデキストリン並びにその混合物からなる群から選択される、請求項14に記載の医薬組成物。
- 前記界面活性剤が、非イオン性界面活性剤、アニオン性界面活性剤、カチオン性界面活性剤及び双性イオン性界面活性剤並びにその組合せからなる群から選択される、請求項1に記載の医薬組成物。
- 前記非イオン性界面活性剤が、ポリオキシエチル化植物油、ポリオキシエチル化水素化植物油、ポリオキシエチレン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、ソルビタン脂肪酸エステル、ポリオキシエチレン−ポリオキシプロピレンブロックコポリマー、スクロース脂肪酸エステル、天然植物油トリグリセリドとポリアルキレンポリオールのエステル交換生成物並びにその混合物からなる群から選択される、請求項19に記載の医薬組成物。
- 前記非イオン性界面活性剤が、PEG−35ヒマシ油、PEG−40水素化ヒマシ油、PEG−20ソルビタンモノラウレート、PEG−20ソルビタンモノパルミテート、PEG−20ソルビタンモノオレエート、ポリオキシエチレン40ステアレート、PEG−6杏仁油、PEG−6コーンオイル、ソルビタンオレエート、ソルビタントリステアレート、ポロキサマー188、スクロースジステアレート及びその混合物からなる群から選択される、請求項20に記載の医薬組成物。
- 前記アニオン性界面活性剤が、オレイン酸ナトリウム、パルミチン酸ナトリウム、ラウリル硫酸ナトリウム、ジオクチルスルホコハク酸ナトリウム、コール酸ナトリウム及びその混合物からなる群から選択される、請求項19に記載の医薬組成物。
- 前記カチオン性界面活性剤が、ラウロイルカルニチン、セチルトリメチルアンモニウムブロミド、ドデシルアンモニウムクロリド、ベタイン、塩化ベンザルコニウム及びその混合物からなる群から選択される、請求項19に記載の医薬組成物。
- 前記双性イオン性界面活性剤が、大豆レシチン、水酸化レシチン、リゾホスファチジルコリン、ホスファチジルコリン、水素化レシチン及びその混合物からなる群から選択される、請求項19に記載の医薬組成物。
- 少なくとも1つの薬学的に許容される添加剤をさらに含む、請求項1に記載の医薬組成物。
- 前記組成物が経口又は非経口投与のための単位剤形で存在する、請求項1又は25に記載の医薬組成物。
- 経口投与のための単位剤形が、軟質ゼラチンカプセル剤、軟質カラギーナンカプセル剤、軟質デンプンカプセル剤、軟質セルロースカプセル剤、硬質ゼラチンカプセル剤、硬質カラギーナンカプセル剤、硬質デンプンカプセル剤、硬質セルロースカプセル剤、錠剤、コーティング錠剤、即時放出錠剤、持続放出錠剤、持続放出の1つの層と即時放出の1つの層を備えた二重層錠剤、経口液体製剤、顆粒剤及びペレット剤からなる群から選択される、請求項26に記載の医薬組成物。
- 非経口投与のための単位剤形が、筋肉内注射剤、髄腔内注射剤、皮内注射剤、腹腔内注射剤及び皮下注射剤からなる群から選択される、請求項26に記載の医薬組成物。
- 抗HIV剤、抗マイコバクテリア剤又はその組合せである少なくとも1つの追加の薬剤をさらに含む、請求項1に記載の医薬組成物。
- 前記少なくとも1つの追加の抗HIV剤が、プロテアーゼ阻害剤、非ヌクレオシド逆転写酵素阻害剤、ヌクレオシド逆転写酵素阻害剤、ヌクレオチド逆転写酵素阻害剤、インテグラーゼ阻害剤、侵入及び融合阻害剤、成熟阻害剤並びにその組合せから選択される、請求項29に記載の医薬組成物。
- 前記抗マイコバクテリア剤が抗TB剤である、請求項29に記載の医薬組成物。
- 前記抗TB剤が、イソニアジド、リファンピン、リファブチン、リファペンチン、エタンブトール、環状ペプチド、エチオナミド、フルオロキノロン、ピラジンアミド、PAS(p−アミノサリチル酸)、アミノグリコシド、サイクロセリン、チオアミド、リネゾリド、レボフロキサシン、シプロフロキサシン、モキシ又はガチフロキサシン、アミカシン、カナマイシン、ストレプトマイシン、カプレオマイシン、バイオマイシン、エンビオマイシン、クラリスロマイシン、チオアセタゾン、チオリダジン、アルギニン、ビタミンD及びその組合せを含む、請求項31に記載の医薬組成物。
- i)カラノライド又はカラノライド(複数)の混合物を20℃〜65℃の温度で1つ又は複数の溶解度向上剤と混合するステップと
ii)ステップ(i)で得られた生成混合物を1つ又は複数の界面活性剤と混合して均一混合物を形成させるステップと
を含む請求項1に記載の医薬組成物の調製のための方法であって、
ステップ(i)の混合プロセスが分散ミルで粉末混合物を1〜40時間粉砕する追加のステップをさらに含むことができる上記方法。 - i)重量で全組成物の約0.5%〜約80%の量のカラノライド又はカラノライド(複数)の混合物を20℃〜65℃の温度で、重量で全組成物の約0.5%〜約90%の量の1つ又は複数の溶解度向上剤と混合するステップと
ii)ステップ(i)で得られた生成混合物を約0.1%〜約80%の量の1つ又は複数の界面活性剤と混合して均一混合物を形成させるステップと
を含む請求項1に記載の医薬組成物の調製のための方法であって、
ステップ(i)の混合プロセスが分散ミルで粉末混合物を1〜40時間粉砕する追加のステップをさらに含むことができる上記方法。 - i)重量で全組成物の約5%〜約50%の量のカラノライド又はカラノライド(複数)の混合物を20℃〜65℃の温度で、重量で全組成物の約10%〜約60%の量の1つ又は複数の溶解度向上剤と混合するステップと
ii)ステップ(i)で得られた生成混合物を約5%〜約50%の量の1つ又は複数の界面活性剤と混合して均一混合物を形成させるステップと
を含む請求項1に記載の医薬組成物の調製のための方法であって、
ステップ(i)の混合プロセスが分散ミルで粉末混合物を1〜40時間粉砕する追加のステップをさらに含むことができる上記方法。 - i)重量で全組成物の約10%〜約35%の量のカラノライド又はカラノライド(複数)の混合物を20℃〜65℃の温度で、重量で全組成物の約25%〜約50%の量の1つ又は複数の溶解度向上剤と混合するステップと
ii)ステップ(i)で得られた生成混合物を約20%〜約40%の量の1つ又は複数の界面活性剤と混合して均一混合物を形成させるステップと
を含む請求項1に記載の医薬組成物の調製のための方法であって、
ステップ(i)の混合プロセスが分散ミルで粉末混合物を1〜40時間粉砕する追加のステップをさらに含むことができる上記方法。 - 前記組成物を、経口経路又は非経口経路で投与する、請求項1に記載の医薬組成物の送達方法。
- 哺乳動物のレトロウイルス疾患、特にHIV−1の治療及び予防のための医薬品の調製における、請求項1に記載の医薬組成物の使用。
- 前記哺乳動物がヒトである、請求項38に記載の医薬組成物の使用。
- 哺乳動物のマイコバクテリア疾患、特に結核の治療及び予防のための医薬品の調製における、請求項1に記載の医薬組成物の使用。
- 前記哺乳動物がヒトである、請求項40に記載の医薬組成物の使用。
- 哺乳動物のレトロウイルス疾患及びマイコバクテリア疾患を治療する方法であって、請求項1に記載の医薬組成物をそうした治療を必要とする哺乳動物に投与することを含む上記方法。
- 前記哺乳動物がヒトである、請求項42に記載の方法。
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JP2013530106A Pending JP2013537903A (ja) | 2010-09-22 | 2011-08-24 | カラノライド、その誘導体及び類似体についての医薬組成物並びにそれを製造するための方法 |
JP2015215932A Expired - Fee Related JP6240646B2 (ja) | 2010-09-22 | 2015-11-02 | カラノライドの医薬組成物及びその調製方法 |
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KR (1) | KR101710435B1 (ja) |
CN (1) | CN103249403B (ja) |
AU (1) | AU2011306573C1 (ja) |
CA (1) | CA2812372C (ja) |
ES (1) | ES2657813T3 (ja) |
HK (1) | HK1187838A1 (ja) |
MY (1) | MY158809A (ja) |
SG (1) | SG188263A1 (ja) |
WO (1) | WO2012039596A2 (ja) |
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WO2013032934A1 (en) * | 2011-08-26 | 2013-03-07 | Aegis Therapeutics, Llc | Compositions and methods thereof for oral administration of drugs |
WO2014165607A2 (en) * | 2013-04-02 | 2014-10-09 | Stealth Peptides International, Inc. | Aromatic-cationic peptide formulations, compositions and methods of use |
KR102178448B1 (ko) | 2014-04-11 | 2020-11-18 | 주식회사 만도 | 브레이크 시스템용 솔레노이드밸브 |
DK3185872T3 (da) | 2014-08-28 | 2021-06-21 | Univ Texas | Formulering af testosteron og metoder til behandling hermed |
US11135154B2 (en) | 2016-03-02 | 2021-10-05 | Teva Pharmaceutical Industries Ltd. | Medroxyprogesterone acetate injectable compositions and methods of use |
KR102351762B1 (ko) * | 2016-03-02 | 2022-01-18 | 더 보드 오브 리젠츠 오브 더 유니버시티 오브 텍사스 시스템 | 테스토스테론 제형 및 이를 이용한 치료 방법 |
CN105832752A (zh) * | 2016-04-08 | 2016-08-10 | 王金霞 | 一种临床护理上呼吸道感染的药物组合物 |
WO2019191734A1 (en) * | 2018-03-30 | 2019-10-03 | The Board Of Trustees Of The Leland Stanford Junior University | Sublingual and buccal administrations of fluorescent agents for optical imaging |
US11752095B2 (en) | 2018-09-07 | 2023-09-12 | Family Health International | Medroxyprogesterone acetate injectable compositions and methods of use |
CA3121920A1 (en) * | 2018-12-07 | 2020-06-11 | Neurocrine Biosciences, Inc. | Crf1 receptor antagonist, pharmaceutical formulations and solid forms thereof for the treatment of congenital adrenal hyperplasia |
CN113015519A (zh) * | 2019-09-12 | 2021-06-22 | 生物验证系统股份公司 | 利福布汀治疗方法、用途和组合物 |
US11344537B2 (en) | 2019-09-18 | 2022-05-31 | BioVersys AG | Rifabutin treatment methods, uses, and compositions |
EP4117684A4 (en) * | 2020-04-20 | 2023-10-04 | Poviva Corp. | COMPOSITIONS AND METHODS FOR IMPROVED DELIVERY OF ANTIVIRAL AGENTS |
CN117462551B (zh) * | 2023-12-27 | 2024-05-17 | 深圳国家感染性疾病临床医学研究中心 | 茚地那韦和/或其衍生物在制备抗结核药物中的应用 |
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2011
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- 2011-08-24 AU AU2011306573A patent/AU2011306573C1/en not_active Ceased
- 2011-08-24 CA CA2812372A patent/CA2812372C/en not_active Expired - Fee Related
- 2011-08-24 KR KR1020137010033A patent/KR101710435B1/ko active IP Right Grant
- 2011-08-24 EP EP11770892.5A patent/EP2618815B1/en not_active Not-in-force
- 2011-08-24 JP JP2013530106A patent/JP2013537903A/ja active Pending
- 2011-08-24 ES ES11770892.5T patent/ES2657813T3/es active Active
- 2011-08-24 US US13/825,448 patent/US20130183383A1/en not_active Abandoned
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- 2011-08-24 CN CN201180045624.XA patent/CN103249403B/zh not_active Expired - Fee Related
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JP2009132712A (ja) * | 2007-11-21 | 2009-06-18 | Innopharmax Inc | 生物学的利用能を向上した医薬組成物 |
Also Published As
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MY158809A (en) | 2016-11-15 |
CA2812372C (en) | 2018-08-21 |
AU2011306573B2 (en) | 2014-10-23 |
WO2012039596A2 (en) | 2012-03-29 |
US20130183383A1 (en) | 2013-07-18 |
KR20140043297A (ko) | 2014-04-09 |
AU2011306573C1 (en) | 2015-02-19 |
SG188263A1 (en) | 2013-04-30 |
WO2012039596A3 (en) | 2012-08-16 |
CN103249403A (zh) | 2013-08-14 |
EP2618815A2 (en) | 2013-07-31 |
CA2812372A1 (en) | 2012-03-29 |
AU2011306573A1 (en) | 2013-04-11 |
CN103249403B (zh) | 2016-01-27 |
KR101710435B1 (ko) | 2017-03-08 |
ZA201301463B (en) | 2019-07-31 |
JP2016053059A (ja) | 2016-04-14 |
JP6240646B2 (ja) | 2017-11-29 |
EP2618815B1 (en) | 2017-11-15 |
ES2657813T3 (es) | 2018-03-07 |
HK1187838A1 (zh) | 2014-04-17 |
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