JP2017061552A - プロリポソーム型テストステロン調合物 - Google Patents
プロリポソーム型テストステロン調合物 Download PDFInfo
- Publication number
- JP2017061552A JP2017061552A JP2016234097A JP2016234097A JP2017061552A JP 2017061552 A JP2017061552 A JP 2017061552A JP 2016234097 A JP2016234097 A JP 2016234097A JP 2016234097 A JP2016234097 A JP 2016234097A JP 2017061552 A JP2017061552 A JP 2017061552A
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- Prior art keywords
- testosterone
- plf
- proliposome
- formulation
- oral preparation
- Prior art date
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Abstract
【解決手段】テストステロンがリン脂質/コレステロール系に取り込まれた、プロリポソーム型粉末分散物であって、該粉末分散物と、少なくとも1種の医薬的に許容し得る賦形剤とを含む医薬組成物。該医薬品組成物は錠剤又はカプセル剤である経口剤であって、遅延放出コーティングでコーティングされる。
【選択図】図24
Description
本願は、2012年5月9日に出願された米国特許出願第61/644,996号の優先権を主張し、その開示内容は参照することにより本明細書に組み込まれる。
医薬組成物
Pharmacoat,Methocel);ヒドロキシプロピルメチルセルロースフタレート(HPMCP);ヒドロキシプロピルメチルセルロースサクシネート(HPMCS);及びヒドロキシプロピルメチルセルロースアセテートサクシネート(例えば、AQQAT(Shin Etsu))がある。その性能は、置換の程度及びタイプに基づいて変わり得る。例えば、HP−50、HP−55、HP−55S、HP−55FグレードなどのHPMCPが適している。その性能は、置換の程度及びタイプに基づいて変わり得る。例えば、ヒドロキシプロピルメチルセルロースアセテートサクシネートの適切なグレードは、特に限定されないが、pH5で溶解するAS−LG(LF)、pH5.5で溶解するAS−MG(MF)、及び、より高いpHで溶解するAS−HG(HF)を含む。これらのポリマーは、顆粒、又は水性分散物(ポリ酢酸ビニルフタレート(PVAP))のための微粉末として提供される。PVAPはpH>5で溶解し、水蒸気及び胃液に対して、透過性がはるかに小さい。
投与量
投薬方法及び治療処方
併用療法
製造のキット/物品
比較プロリポソーム型調合物(「PLF−C」)、PLF−C1、PLF−C2、PLF−C3、及びPLF−C4は、テストステロンとジミリスチルホスファチジルグリセロールナトリウム(DMPG)を含有した。表1は、これら調合物のそれぞれを作るために使用された成分と量を示す。PLF−C1については、0.5gのテストステロンを3mlの9:1のエタノール対水混合物(v/v)に溶解し、この溶液に0.5gのDMPGを添加した。次に、溶媒の完全な蒸発が達成されるまで、典型的には一晩、溶液を室温で攪拌した。溶媒を蒸発させて得られた粉末調合物を、メッシュ#60のような適切な篩に通した。次に、篩にかけた粉末をガラスバイアルに移し、遮光して室温で保存した。
腸溶コーティングされたPLF−C1カプセルとコーティングされていないPLF−C1カプセルからのテストステロンのインビトロ溶解プロファイルが得られた。これらの試験のために、3つの異なる溶解媒体を腸溶コーティングカプセルのために使用した。腸溶コーティングカプセル(n=3)を、500mlの、1)0.1N HCl(pH1.20)に1時間;酢酸ナトリウム緩衝液(pH4.50)に1時間;リン酸カリウム緩衝液(pH6.80)に3時間、溶解した。コーティングされていないカプセル(n=3)については、0.1N HCl(pH1.20)のみを使用し、1、2、及び2.5時間後、試料を採取した。溶解は、USPタイプ1装置で、毎分50回転の速度(rpm)で37℃で、0.5時間、1時間、2時間、3時間、進行させた。各時点で、5mlの試料を採取した。各時点で放出されたテストステロンの量は、以下の高圧液体クロマトグラフィー(HPLC)アッセイ法を用いて、各時点の試料を分析して決定した。分析した各調合物について、25mgのテストステロンを含む調合物の量を25mlのエタノールに溶解した。テストステロン濃度が10μg/mlに達するまで、このストック溶液をさらにメタノール:水(1:1)溶液で適切に希釈した。次に20μlのアリコートをHPLCに注入した。HPLC分析で使用された移動相の組成は、アセトニトリル:水(0.2%ギ酸を有する)(75:25v/v)の溶液であった。相の分離は、C18(100×4.6mm)Kinetex、Phenomenex(登録商標)カラムを1.0ml/分の流速で使用して行った。各試料の総実行時間は5分であり、フォトダイオードアレイ(PDA)検出器を、波長243nmに設定した。コーティングされていない及びコーティングされたカプセル調合物の両方とも、PBS(pH6.80)中3時間で、3.46%未満の薬物放出を示した。腸溶コーティングされたカプセルは、酸性pHで2時間無傷のままであった。
調合物PLF−C1、PLF−C2、及びPLF−C3を、ラット(n=3)に経口投与後のインビボ性能について試験した。これらの試験は、それぞれ約250gの体重のオスのスプラーグドーレイ(Sprague-Dawley)ラット(Charles River−Wilmington, MA)を含む施設動物倫理委員会(IACUC)認可インビボプロトコールを使用し、頚静脈にカニューレを挿入し、試験のために使用した。自由流動性のプロリポソーム粉末形態のPLF−C1調合物と、HPMC懸濁液中のテストステロンのテストステロン対照溶液(0.5%(wt/vol)を、経口投与後の摂食ラットで試験した。
調合物PLF−C5については、テストステロンを、エタノール:水(9:1)の混合物に溶解した。この溶液に、ジミリスチルホスファチジルグリセロールナトリウム(DMPG)及び乳糖一水和物を加え、溶媒が室温で完全に蒸発するまで室温で一晩撹拌した。乳糖が分散を助け、動物試験のための投薬溶液を調製しながら、塊の形成を回避するように、乳糖を添加した。
異なる媒体中のテストステロンの溶解度を試験した。a)塩酸緩衝液(pH1.20)、b)酢酸緩衝液(pH4.50)、c)リン酸緩衝液(PBS)pH6.80、及びd)ナノ純水、のいずれかの10mlを含有する4個のガラスバイアルの各々に、テストステロン(100mg)を加えた。これらの試料を室温で72時間、水浴中で振とうさせた。試料を適当に希釈し、比較例2に記載されたHPLCアッセイ法により分析した。リン酸緩衝液pH6.80中のテストステロンの溶解度は高かった。図6を参照されたい。
エタノールと水の9:1混合物(v/v)にテストステロンを溶解し、次にジステアロイルホスファチジルコリン(DSPC)とコレステロールを、DSPC対コレステロール9:1の比(w/w)で加えることにより、プロリポソーム型調合物(PLF)−1、PLF−2、PLF−3、及びPLF−4を調製した。生じた分散物を、溶媒が完全に蒸発するまで、室温で一晩攪拌した。これらの調合物の組成は表5に詳述される。溶媒の除去により得られた粉末を適切な篩(メッシュ#60)に通過させ、ガラスビンに移し、室温で遮光して保存した。
10分間の超音波処理後の、0.5%、1%、又は2%のSLS中の、a)10mgの純粋なテストステロン、及びb)10mgのテストステロンと同等の調合物PLF−2、の溶解度を測定した。これらの試験について、純粋なテストステロン10mgを秤量し、メスフラスコ中にそれぞれ0.5%、1%、又は2%(w/w)SLSで溶解させた。10mgのテストステロンを含有する量の調合物PLF−2を秤量し、テストステロン対照について記載したものと同じ方法で試料溶液を調製した。これらの溶液を、超音波処理器中で10分間超音波処理した。次に、試料を濾過し、各濃度のSLSで適切に希釈した。各濃度のSLSについて可溶性テストステロンの量を、比較例2で記載したHPLCアッセイ法を使用して測定した。テストステロン対照とPLF−2の両方とも、1%w/w SLS中で高いテストステロン溶解性に関連していた。図8を参照されたい。
調合物PLF−1を、サイズ”00”の硬ゼラチンカプセルサイズに充填した。これらのカプセルのいくつかは、比較例2に記載されたように腸溶コーティングされた。腸溶コーティングカプセル(n=3)及び非コーティングカプセル(n=3)の両方の溶解を、900mlのリン酸カリウム緩衝液(pH6.80)中で行い、37℃±5℃で3時間のコースで溶解条件を維持した。溶解の0.5、1、2、3時間後に試料(5ml)を採取し、次に、比較例2で上記したようにHPLCアッセイ法に従って測定した。PLF−1の安定性データは表6に要約され、インビトロ放出プロフィールは図9に示される。
実施例2に記載された調製法に従って、調合物PLF−2とPLF−4を調製した。次にこれらの調合物を、一晩絶食後のオスのスプラーグドーレイ(SD)ラットに経口投与した。調合物PLF−2を、体重1kg当たり300mg、150mg、31mg、15.5mg、及び7.75mg用量の用量で試験した。調合物PLF−4は、300mg/kg体重の用量で経口投与した。
1.5mgのテストステロンを、エタノールと水の9:1混合物(v/v)20mlに溶解し、次に1.35mgのジステアロイルホスファチジルコリン(DSPC)と0.15mgのコレステロール(すなわち、DSPC対コレステロール(w/w)の比率9:1)を添加して、PLF−5と呼ぶ基剤調合物を調製した。生じた分散物を、溶媒が完全に蒸発するまで、室温で一晩攪拌した。溶媒の除去により得られた粉末を適切な篩(メッシュ#60)に通過させ、ガラスビンに移し、室温で遮光して保存した。次に、表7に示したように及び後述のように、PLF−5調合物をさらに調製して、PLF−5調合物(a〜d)とした。
3mgのテストステロンをエタノールと水の9:1(v/v)混合物40mlに溶解し、次に2.7mgのDSPCと0.30mgのコレステロール(すなわち、DSPC対コレステロールの比率9:1(W/W))を添加して、PLF−6と呼ぶ基剤調合物を調製した。生じた分散物を、溶媒が完全に蒸発するまで、室温で一晩攪拌した。溶媒の除去により得られた粉末を適切な篩(メッシュ#60)に通過させた。
カプセル形のPLF−2と錠剤形のPLF−6の溶解を、互いに、及び未調合のテストステロン(T1−175)と比較した。PLF−2とPLF−6は、それぞれ実施例5と7に記載のように調製され、表9に報告されるように、賦形剤の外部添加によりさらに調製した。カプセル、錠剤の形態の調合物の溶解を、1%(w/w)SLSを有するPBS(pH6.80)中の純粋な薬剤の溶解と比較した。1%(w/w)の添加は、0.5時間以内に薬剤の完全な放出を示した。このインビトロ放出プロフィールは、図14に示される。表9中の調合物a、b、cは、図14の線a、b、cと相関した。
表10に報告されるように、Avicel(登録商標)PH102とExplotab(登録商標)崩壊剤の外部添加により、カプセル調合物PLF−9(a〜e)(Explotab(登録商標)崩壊剤を含むか又は含まない、最少量のAvicel(登録商標)で調製された2つの調合物を含む)を調製した。本例に記載されたすべての調合物の組成は、表10に記載される。これらの調合物の溶解は、カプセルシンカーを有するタイプII装置を使用して、SLSを含有しないPBS(pH6.80)中で行った。これらの試験の目的は、Avicel(登録商標)対テストステロンの比率の上昇が、プロリポソーム型調合物からのテストステロン溶解性を上昇させるかどうかを調べることであった。
実施例2に記載されるようにPLF−2を作成するために使用されたものと同じプロトコールに従って調製されたPLF−10に、表11に報告されるように、Avicel(登録商標)PH102とExplotab(登録商標)崩壊剤を外部添加することにより、HPMCサイズ「0」カプセル調合物PLF−11(aとb)及びPLF−12(cとd)を調製した。これらの調合物はすべて、Explotab(登録商標)崩壊剤を含むか又は含まない最小量のAvicel(登録商標)を含有した。表11の調合物を、Vcaps(登録商標)Plusヒプロメロース(HPMC)カプセル(Capsugel Gelgium NV)に充填した。インビトロ溶解試験は、タイプII装置を75rpmで使用して行った。使用された溶解媒体は、a)1%(w/v)SLSを有するPBS;b)2%(w/v)SLSを有するPBS;c)0.5%(w/v)SLSを有するPBS;d)1%(w/v)SLSを有するPBS。1%(w/v)SLSと2%(w/v)SLSを含有する媒体は、2時間以内に、完全な薬剤放出を示した。調合物(a〜d)のインビトロ溶解プロフィールは図16に示される。
Vcaps(HPMC)サイズ「0」とVcaps(登録商標)Plus(HPMC)サイズ「0」カプセル(Capsugel Belgium NV)に充填された調合物の崩壊回数を調べるために、表12に提供示される調合物PLF−14(a)とPLF−15(b)を調製した。Vcaps(登録商標)対Vcaps Plus(登録商標)カプセル化調合物を比較するために、調合物PLF−14も調製した。各カプセルタイプを評価するために、サイズ「0」カプセルが使用された。Vcaps(登録商標)とVcaps Plus(登録商標)の比較試験を行うために、カプセルにAvicel(登録商標)のみを充填した。
基剤調合物PLF−13をさらに調製して、崩壊剤とともに、種々の量の異なる希釈剤Avicel(登録商標)PH102、Prosolv(登録商標)SMCC90(Silicified Micro Crystalline Cellulose)、及び無水リン酸水素カルシウムの外部添加により、PLF−16(a)、PLF−17(b)、PLF−18(c)、PLF−19(d)、PLF−20(e)、PLF−21(f)、及びPLF(g)を作成した。これらの調合物は、表13に記載された成分を使用して調製された。PLF−13は、テストステロン、DSPC、及びコレステロールを1:0.9:1の比率で含有し、これは、1カプセル当たりそれぞれ60mg、54mg、及び6mgに相関した。
PLF−13は、PLF−2について実施例2で記載したように調製したが、PLF−13の調製は、10gのバッチサイズのスケールとした。表13の調合物を、Vcaps(登録商標)サイズ「0」HPMCカプセル(Capsugel Belgium NV)で充填した。インビトロ溶解は、タイプII装置を75rpmで使用して、0.5%SLSを有する1000mlのPBS(pH6.80)中で行った。これらの試験でシンカーは使用しなかった。より多量のAvicel(登録商標)PH102とDCPを含有する調合物は、より良好な放出プロフィールを示した(図17)。
実施例2のPLF−2の調製の記載に従って、プロリポソーム型調合物基剤を調製したが、バッチサイズは15gのスケールとした。表14に報告されているように賦形剤を外部添加し、Vcaps(登録商標)HPMCサイズ「0」HPMCカプセル(Capsulate Belgium NV)中に充填することにより、基剤PLF−2調合物をさらに調製して、PLF−25とした。表14にも記載されている調合物PLF−24は、テストステロンを含有しないプラセボ対照として機能した。PLF−24とPLF−25は、本発明のカプセルの遅延放出コーティング(例えば、腸溶コーティング)法を最適化するための試みの一部として調製された。
表17に報告されているように、PLF−23と2つの異なるグレードの微結晶セルロース(Prosolv(登録商標)HD90とProsolv(登録商標)SMCC90)との用手的混合を含む、賦形剤の外部添加により、基剤調合物PLF−23とPLF−28とをさらに調製して、それぞれPLF−26とPLF−27を作成した。PLF−23とPLF−28は、互いに、及びPLF−2(これは実施例2に記載されており、テストステロン、DSPC、及びコレステロールを1:0.9:1の比率で含む)と組成が同一である。PLF−23とPLF−28を調製するのに使用された方法もまた、PLF−2を調製するのに使用された方法と同じである。表17にも記載されているように、微結晶セルロースを除いて、賦形剤の外部添加により、PLF−28をさらに調製してPLF−29とした。
A.プロリポソーム型テストステロン調合物の調製と最適化
テストステロンとリン脂質(表19)とをエタノールに溶解し、窒素ガスを使用して溶媒を蒸発させた。乾燥粉末を#60メッシュスクリーンに通して、均一な粒径分布を作成した。この試験で使用されたリン脂質は、不活性成分ガイド(Inactive Ingredient Guide)(FDA)からのものである。
Caco−2細胞培養:Caco−2細胞の単層を、4μm孔径ポリカーボネートTranswell(登録商標)フィルター上で、以下の方法により調製した。Caco−2細胞をT−75フラスコ中で37℃で、5%CO2と95%空気の雰囲気中で、必要な補助物質を有するダルベッコー改変イーグル培地(DMEM、pH7.2)を使用して増殖させた。培地は、90%コンフルエンスに達する前に、少なくとも1回交換した。細胞をハンクス液(Ca+2,Mg+2を含まないHBSS)で洗浄し、1mM EDTA中の0.25%トリプシンで37℃で5分間トリプシン処理をした。細胞を10mlのDMEMに再懸濁し、4μm孔径Transwell(登録商標)インサートに7.5×10細胞/mlの密度で接種した。フラスコに5mlのDMEMを加えて、細胞懸濁液対DMEMの1:1希釈を作成し、細胞を再接種した。Transwell(登録商標)インサート中の細胞を約5日間増殖させ、細胞の耐性を、耐性が100Ωより大きくなるまで、1日置きに測定した。
いったん細胞の耐性が100Ωより高くなったら、DMEMを注意深く吸引し、マイクロピペットを使用して、ドナーコンパートメント中で1.5mlのCa+2,Mg+2含有HBSS(これは、37℃水浴で加温されている)とレシーバーコンパートメント中の2.5mlで置換し、室温で30分間平衡化させた。次に、Ca+2,Mg+2含有HBSSをドナーコンパートメントから注意深く吸引し、前日調製されたCa+2,Mg+2含有HBSS(これは、37℃水浴に30分間入れておいた)に再懸濁されていた0.5mlの調合物で置換した。各調合物は3重測定で試験した。各ウェル(細胞が無傷のままであることを確認するために)について耐性を測定し、300μlの試料をレシーバーコンパートメントから取り除き、300μlの新鮮なCa+2,Mg+2含有HBSSを補った。5、15、30、45、60、90、120、150、180、210、240、270、330分に、試料を取り出した。輸送されたテストステロン量を、HPLCによる100μlの試料の分析により測定した。実験は、3重測定で行った。対照:1.未調合のテストステロン対照:2.テストステロンプロリポソーム型調合物。
DSPCへのコレステロールの添加は、腸管膜を通過するテストステロンの改良された輸送を促進する。膜を通過するテストステロンの改良された輸送は、驚くべき有益な結果である。
性腺機能低下症のヒト対象を含む臨床試験を行った。試験のために患者を募集する前に、医学検査を行った。試験は、施設動物倫理委員会(IACUC)により認可された臨床試験プロトコールを使用して、摂食及び絶食条件下で行った。試験の開始前に、すべての患者からインフォームドコンセントを得た。2つの異なる用量(120及び240mg)の薬剤を経口投与後の、テストステロンの薬物動態値を集めた。異なる治療条件下でのテストステロンとその主要な代謝物であるジヒドロテストステロン(DHT)の平均血漿濃度を、図21、22に示す。食物の存在下では、テストステロンの吸収は遅れた。より高濃度のテストステロンの投与が、テストステロンの血漿濃度の直線的上昇を示すことはなかった。テストステロンのピーク血漿濃度(Cmax)は、両群について、薬剤投与の5時間後(Cmax)に見られた。
臨床試験のために、腸溶コーティングカプセルの形態の経口剤形をパイロットスケールで調製した。このカプセルは、カプセル1個当たり表20に示す成分を有する医薬組成物を含有した。
性腺機能低下症を有する34人のヒト対象で臨床試験を行い、表21に示された成分の1カプセル当たりの量を含有し、実施例17に記載する方法に従って調製されたテストステロンの経口剤形による、15日間の治療期間にわたるテストステロンの薬物動態を評価した。300ng/dL以下の血清テストステロンを有する対象を、性腺機能低下症と見なした。試験に参加するためのすべての男性についての選定基準は、肥満度指数ボディマスインデックス(BMI)が39Kg/m2未満で、年齢が19才以上で、体重要件が55Kg以上であった。すべての対象は、試験に参加する前に、試験の目的を理解し、インフォームドコンセント用紙に署名した。対象群を17名の2群に分け、それぞれ120mg又は240mg(すなわち、120mg用量を2回同時に与えた)の調合テストステロンを15日間、1日2回(すなわち、朝と晩)に投与した。丸1日経過後、及び投与処方の開始後15日目に、対象から1時間毎に血漿試料を採取した。
この試験の目的は、表21に示された成分の1カプセル当たりの量を含有し、実施例17に記載する方法に従って調製されたテストステロンの経口剤形の毒性と毒性動態を評価することであった。これらの試験について、プラセボと3つの異なる用量の調合テストステロンをビーグル犬に、少なくとも90日間連続で1日1回投与した。さらに詳しくは、この試験の毒性試験部分で、16匹のオスのビーグル犬を4つの処理群に割り当てた。動物には、目標用量レベルの0、15、75、又は150mg/kg/日の調合テストステロンを、91日間連続で経口投与した。これらの用量レベルは、0、120mg、600mg、及び1200mgの剤形と同等であった。92日目に、動物を安楽死させ、完全な剖検を行った。プロトコールで特定された組織(精巣を含む)を採取し、Experimental Pathlogy Laboratories (EPL), Inc.に送った。すべての群からの組織を処理し、パラフィン包埋し、切片を作成し、ヘマトキシリンとエオシン(H&E)で染色した。得られたスライドを、光学顕微鏡による評価のために、Bret Saladino, DVM, Diplomate ACVP of Calvert Laboratorisに送った。
Claims (22)
- (a)テストステロンと、
(b)コレステロールと、
(c)少なくとも1種のリン脂質と、
を含むプロリポソーム型粉末分散物であって、
(a)と(b)は、重量比(a:b)が(1:0.05)〜(1:0.30)の範囲で存在し、
(a)、(b)、及び(c)は、(a:(b+c))の重量比が(1:1.0)〜(1:2.5)の範囲で存在する、前記分散物。 - 前記リン脂質が、ジステアロイルホスファチジルコリン、ジパルミトイルホスファチジルコリン、ジミリストイルホスファチジルコリン、卵ホスファチジルコリン、大豆ホスファチジルコリン、ジミリシチルホスファチジルグリセロールナトリウム、1,2−ジミリストイルホスファチジン酸、ジパルミトイルホスファチジルグリセロール、ジパルミトイルホスフェート、1,2−ジステアロイル−sn−グリセロ−3−ホスホ−rac−グリセロール、1,2−ジステアロイル−sn−グリセロ−3−ホスファチジン酸、ホスファチジルセリン、及びスフィンゴミエリン、又はこれらの組合せから選択される、請求項1に記載のプロリポソーム型粉末分散物。
- 請求項1に記載のプロリポソーム型粉末分散物と、少なくとも1種の医薬的に許容し得る賦形剤と、を含む医薬組成物。
- 請求項3に記載の医薬組成物を含む経口剤であって、該経口剤が錠剤又はカプセル剤であり、かつ該錠剤又はカプセル剤が遅延放出コーティングでコーティングされている、前記経口剤。
- 請求項3に記載の医薬組成物を含む経口剤であって、該経口剤が錠剤又はカプセル剤であり、かつ該錠剤又はカプセル剤が、腸溶コーティングでコーティングされている、前記経口剤。
- 請求項1に記載のプロリポソーム型粉末分散物と、少なくとも1種の医薬的に許容し得る賦形剤と、を含む経口剤であって、
前記テストステロンが50mg〜260mgの範囲の量で存在し、摂取5時間後に、テストステロンが300〜950ng/dLの範囲となる平均血漿テストステロン濃度の絶食時薬物動態プロフィールを有する、前記経口剤。 - 前記経口剤がカプセル剤であり、該カプセル剤が遅延放出コーティングによりコーティングされている、請求項6に記載の経口剤。
- 請求項1に記載のプロリポソーム型粉末分散物の治療有効量を含む、テストステロン療法の必要な個体を治療するための医薬組成物。
- 請求項6に記載の経口剤の治療有効量を含む、テストステロン療法の必要な個体を治療するための医薬組成物。
- 前記リン脂質が、ジステアロイルホスファチジルコリン、ジパルミトイルホスファチジルコリン、ジミリストイルホスファチジルコリン、卵ホスファチジルコリン、大豆ホスファチジルコリン、ジミリシチルホスファチジルグリセロールナトリウム、1,2−ジミリストイル−ホスファチジン酸、ジパルミトイルホスファチジルグリセロール、ジパルミトイルホスフェート、1,2−ジステアロイル−sn−グリセロ−3−ホスホ−rac−グリセロール、1,2−ジステアロイル−sn−グリセロ−3−ホスファチジン酸、ホスファチジルセリン、及びスフィンゴミエリン、又はこれらの組合せから選択され、
(a)と(b)は、重量比(a:b)が(1.0:0.08)〜(1.0:0.012)の範囲で存在し、
(a)、(b)、及び(c)は、(a:(b+c))の重量比が(1.0:1.0)〜(1.0:1.2)の範囲で存在する、
請求項1に記載のプロリポソーム型粉末分散物。 - 前記リン脂質がジステアロイルホスファチジルコリンである、請求項2又は10に記載のプロリポソーム型粉末分散物。
- 請求項10に記載のプロリポソーム型粉末分散物と、少なくとも1種の医薬的に許容し得る賦形剤と、を含む医薬組成物。
- 請求項11に記載のプロリポソーム型粉末分散物と、少なくとも1種の医薬的に許容し得る賦形剤と、を含む医薬組成物。
- 請求項10に記載のプロリポソーム型粉末分散物の治療有効量を含む、テストステロン療法の必要な個体を治療するための医薬組成物。
- 前記分散物は、微結晶セルロースと混合されており、
該分散物と該微結晶セルロースは、(1:0.5)〜(1:2)の範囲の重量比で存在する、
請求項1に記載のプロリポソーム型粉末分散物。 - 前記分散物は、微結晶セルロースと混合されており、
該分散物と該微結晶セルロースは、(1:0.5)〜(1:2)の範囲の重量比で存在する、
請求項6に記載の経口剤。 - 前記分散物と前記微結晶セルロースは、(1:0.5)〜(1:1)の範囲の重量比で存在する、
請求項15に記載のプロリポソーム型粉末分散物。 - 前記分散物と前記微結晶セルロースは、(1:0.5)〜(1:1)の範囲の重量比で存在し、
天然のテストステロンが、50〜260mgの範囲の量で存在し、摂取5時間後に、テストステロンが300〜950ng/dLの範囲となる平均血漿テストステロン濃度の絶食時薬物動態プロフィールを有する、
請求項16に記載の経口剤。 - 前記分散物と前記微結晶セルロースは、(1:0.5)〜(1:1)の範囲の重量比で存在する、請求項16に記載の経口剤。
- 前記テストステロンは天然のテストステロンである、請求項1、2、10、11、15、および17のいずれか1項に記載のプロリポソーム型粉末分散物。
- 前記テストステロンは天然のテストステロンである、請求項4〜7、16、18、および19のいずれか1項に記載の経口剤。
- 前記テストステロンは天然のテストステロンである、請求項3、8、9、及び12〜14のいずれか1項に記載の医薬組成物。
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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Families Citing this family (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10213440B2 (en) | 2014-08-20 | 2019-02-26 | Professional Compounding Centers Of America (Pcca) | Oral transmucosal pharmaceutical compositions including testosterone and an aromatase inhibitor |
KR101682821B1 (ko) | 2015-07-21 | 2016-12-06 | 서울대학교산학협력단 | 프로리포솜 제조방법 |
CN113181118A (zh) * | 2016-01-07 | 2021-07-30 | 健康科学西部大学 | 用于治疗膀胱癌的制剂 |
US20190248830A1 (en) * | 2016-01-08 | 2019-08-15 | Western University Of Health Sciences | Proliposomal testosterone undecanoate formulations |
KR102574139B1 (ko) | 2016-07-07 | 2023-09-05 | 삼성전자주식회사 | 무선 충전 모드를 변경하는 장치 및 방법 |
NZ753214A (en) | 2016-11-11 | 2022-02-25 | Univ Western Health Sciences | Methods of treating upper tract urothelial carcinomas |
CN111936121A (zh) | 2017-11-17 | 2020-11-13 | 赢创运营有限公司 | 制备包衣硬壳胶囊的方法 |
US10716774B1 (en) | 2018-01-05 | 2020-07-21 | Yale Pharmaceuticals LLC | Pharmaceutical compositions containing isotretinoin with improved dissolution profile and enhanced stability |
US20200101085A1 (en) * | 2018-09-28 | 2020-04-02 | Joel Studin | Transpore delivery of drugs and uses thereof |
US20220241155A1 (en) * | 2019-05-15 | 2022-08-04 | Evonik Operations Gmbh | Process for preparing filled hard-shell capsules with cellulose or starch-based coatings with a capsule-filling machine |
US11523992B2 (en) * | 2019-05-15 | 2022-12-13 | Evonik Operations Gmbh | Process for preparing filled hard-shell capsules with (meth)acrylate copolymer based coatings with a capsule-filling machine |
US20220265679A1 (en) * | 2019-08-09 | 2022-08-25 | Tesorx Pharma, Llc | Proliposomal testosterone undecanoate formulations |
CN110747271B (zh) * | 2019-12-02 | 2023-07-18 | 延边大学 | 关于pci术后血管损伤-再狭窄程度的标记物 |
CN111840240A (zh) * | 2020-05-29 | 2020-10-30 | 仁和堂药业有限公司 | 一种非那雄胺制剂及其应用 |
CN112121003B (zh) * | 2020-09-29 | 2022-02-01 | 江苏集萃新型药物制剂技术研究所有限公司 | 缓释制剂载药材料及其组合物、缓释制剂及其制备方法 |
EP4340838A1 (en) * | 2021-05-19 | 2024-03-27 | Alberto Paz | Orally administered compositions for cancer treatment |
CN114668719B (zh) * | 2022-02-21 | 2023-06-16 | 广东食品药品职业学院 | 双氢睾酮混悬剂与双氢睾酮冻干粉及其制备方法 |
WO2024056062A1 (zh) * | 2022-09-16 | 2024-03-21 | 长春金赛药业有限责任公司 | 一种甾体类激素磷脂组合物及其制备方法 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2003534252A (ja) * | 2000-05-02 | 2003-11-18 | エンズレル インコーポレイテッド | リポソーム薬物分配 |
JP2008521823A (ja) * | 2004-11-30 | 2008-06-26 | ウエスタン ユニバーシティ オブ ヘルス サイエンシズ | 被覆薬物送達製剤 |
Family Cites Families (30)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4744989A (en) | 1984-02-08 | 1988-05-17 | E. R. Squibb & Sons, Inc. | Method of preparing liposomes and products produced thereby |
US5002936A (en) | 1985-04-12 | 1991-03-26 | Seymour Lieberman | Lipophilic complexes of pharmacologically active inorganic mineral acid esters of organic compounds |
US5049388A (en) * | 1986-11-06 | 1991-09-17 | Research Development Foundation | Small particle aerosol liposome and liposome-drug combinations for medical use |
EP0361928B1 (en) | 1988-09-29 | 1994-04-27 | Shiseido Company Limited | Emulsified composition |
IE904098A1 (en) | 1989-11-13 | 1991-05-22 | Nova Pharm Corp | Lipospheres for controlled delivery of substances |
US20040175417A1 (en) | 1990-10-19 | 2004-09-09 | Gilead Sciences, Inc. | Amphotericin B liposome preparation |
US5323907A (en) | 1992-06-23 | 1994-06-28 | Multi-Comp, Inc. | Child resistant package assembly for dispensing pharmaceutical medications |
JP3017906B2 (ja) | 1993-10-08 | 2000-03-13 | 信越化学工業株式会社 | 腸溶性コーティング剤分散液 |
US6214375B1 (en) | 1996-07-16 | 2001-04-10 | Generex Pharmaceuticals, Inc. | Phospholipid formulations |
US6506783B1 (en) | 1997-05-16 | 2003-01-14 | The Procter & Gamble Company | Cancer treatments and pharmaceutical compositions therefor |
US6294192B1 (en) | 1999-02-26 | 2001-09-25 | Lipocine, Inc. | Triglyceride-free compositions and methods for improved delivery of hydrophobic therapeutic agents |
US20030236236A1 (en) | 1999-06-30 | 2003-12-25 | Feng-Jing Chen | Pharmaceutical compositions and dosage forms for administration of hydrophobic drugs |
US6858596B2 (en) * | 2000-08-05 | 2005-02-22 | Smithkline Beecham Corporation | Formulation containing anti-inflammatory androstane derivative |
WO2002051426A2 (en) | 2000-12-22 | 2002-07-04 | A Glenn Braswell | COMPOSITIONS AND METHODS FOR TREATING SEXUAL DYSFUNCTIONS, IMPROVING SEXUAL ACTIVITY AND INCREASING TESTOSTERONE LEVELS, AND IMPROVING MUSCLE STRENGTH AND MASS |
US6534080B2 (en) | 2001-02-12 | 2003-03-18 | Super Gen, Inc. | Method for administering camptothecins via injection of pharmaceutical composition comprising coated particles of a camptothecin |
US6759058B1 (en) * | 2001-04-25 | 2004-07-06 | Western Center For Drug Development College Of Pharmacy Western University Of Health Sciences | Enteric-coated proliposomal formulations for poorly water soluble drugs |
US20040115226A1 (en) | 2002-12-12 | 2004-06-17 | Wenji Li | Free-flowing solid formulations with improved bio-availability of poorly water soluble drugs and process for making the same |
JO2505B1 (en) * | 2003-03-14 | 2009-10-05 | باير شيرنغ فارما اكتنجيسيلشافت | Pharmacy methods and formulations for obtaining acceptable serum testosterone levels |
EP1624857A2 (de) | 2003-05-12 | 2006-02-15 | Novosom AG | Injizierbare depots aus liposomalen aggregaten zur wirkstoffverabreichung |
US7879360B2 (en) | 2003-11-05 | 2011-02-01 | Elan Pharma International, Ltd. | Nanoparticulate compositions having a peptide as a surface stabilizer |
US20060051406A1 (en) | 2004-07-23 | 2006-03-09 | Manjeet Parmar | Formulation of insoluble small molecule therapeutics in lipid-based carriers |
WO2006062506A1 (en) | 2004-12-03 | 2006-06-15 | Enzrel, Inc. | Chitosan-coated liposome drug delivery of antioxidant or anti-inflammatory compounds |
JP2009518443A (ja) | 2005-12-06 | 2009-05-07 | リゲル ファーマシューティカルズ インコーポレーティッド | 脂質を主材料とする担体に内封された、不溶性小分子治療剤の製剤 |
US20070154403A1 (en) | 2006-01-05 | 2007-07-05 | Thomas Skold | Oral, Pulmonary and Transmucosal Delivery Composition |
AU2007235463B2 (en) | 2006-03-30 | 2012-11-22 | The Research Foundation Of State University Of New York | Compositions of less immunogenic and long-circulating protein-lipid complexes |
WO2008114274A1 (en) * | 2007-03-19 | 2008-09-25 | Fresenius Kabi Onclology Ltd. | Proliposomal and liposomal compositions |
US11304960B2 (en) * | 2009-01-08 | 2022-04-19 | Chandrashekar Giliyar | Steroidal compositions |
CA2816119C (en) * | 2010-10-29 | 2019-03-05 | Western University Of Health Sciences | Ternary mixture formulations |
US20120148675A1 (en) | 2010-12-10 | 2012-06-14 | Basawaraj Chickmath | Testosterone undecanoate compositions |
EP2744482A4 (en) | 2011-08-18 | 2015-03-11 | Monosol Rx Llc | STEROID HORMONE DELIVERY SYSTEMS AND METHODS OF PREPARATION THEREOF |
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Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2003534252A (ja) * | 2000-05-02 | 2003-11-18 | エンズレル インコーポレイテッド | リポソーム薬物分配 |
JP2008521823A (ja) * | 2004-11-30 | 2008-06-26 | ウエスタン ユニバーシティ オブ ヘルス サイエンシズ | 被覆薬物送達製剤 |
Non-Patent Citations (2)
Title |
---|
DRUG DELIV., 2010, VOL.17, NO.2, P.92-101, JPN6015052592 * |
EUR. J. ENDOCRINOL., 2004, VOL.150, NO.1, P.57-63, JPN6015052589 * |
Cited By (1)
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