JP4898431B2 - 複数薬物の持続放出のための方法およびデバイス - Google Patents
複数薬物の持続放出のための方法およびデバイス Download PDFInfo
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- JP4898431B2 JP4898431B2 JP2006513416A JP2006513416A JP4898431B2 JP 4898431 B2 JP4898431 B2 JP 4898431B2 JP 2006513416 A JP2006513416 A JP 2006513416A JP 2006513416 A JP2006513416 A JP 2006513416A JP 4898431 B2 JP4898431 B2 JP 4898431B2
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Description
本出願は、2003年4月29日に受理された米国特許仮出願第60/466,318号、および2003年5月27日に受理された米国特許仮出願第60/473,579号の利益を享受する。上掲の出願の全体を参照として本明細書中に取り入れておく。
本発明は、長期間にわたって複数の薬物を実質的に一定の比率で制御放出させるための薬物送達デバイスに関する。さらに特定すると、本発明は、避妊法、ホルモン置換療法、ならびに良性卵巣分泌障害などのような生殖に関する状態および疾患の治療法に関する。
利便性を計るため、請求の範囲、本明細書および実施例において使用している特定の語句および言葉遣いの意味について以下に記載しておく。
p−Glu−His−Trp−Ser−Tyr−Gly−Leu−Arg−Pro−Gly−NH2(配列番号1)
本明細書において使用しているように、「LHRHアゴニスト」および「LHRHアンタゴニスト」という語は、それぞれ、生理学的に活性であって、LHRHの生物学的活性を増強する、または阻害するようなペプチド類または非ペプチドアナログ類をさす。例えば、本発明に従う方法おいて有用なLHRHアゴニストとしては、Cystorelin(ヘキスト(Hoechst)社)、Gonadorelin(アイエルスト(Ayerst)社)、Zoladex.TM(ICI社)、Buserelin(ヘキスト(Hoechst)社)、Leuprolide(アボット(Abbott)社/タケダ(Takeda)社)、Decapeptyl(デバイオファーム(Debiopharm)社、イプセン(Ipsen)社/ビューフォー(Beaufour)社)、Nafarelin(シンテックス(Syntex)社)、Lutrelin(ワイエス(Wyeth)社)およびHistrelin(オルト(Ortho)社)などが挙げられるが、これらに限定されるわけではない。LHRH、LHRHアナログ類、LHRHアゴニスト類およびLHRHアンタゴニスト類は当該分野においては既知であり、以下の特許を含む多数の特許に記載されている:米国特許第4,705,778号、第4,690,916号、第4,530,920号、第4,481,190号、第4,419,347号、第4,341,767号、第4,318,905号、第4,234,571号、第4,386,074号、第4,244,946号、第4,218,439号、第4,215,038号、第4,072,668号、第4,431,635号、第4,317,815号、第4,010,125号、第4,504,414号、第4,493,934号、第4,377,515号、第4,338,305号、第4,089,946号、第4,111,923号、第4,512,923号、4,008,209号および第4,010,149号。これらの全てを参照として本明細書中に取り入れておく、上掲の特許中に記載されているLHRH組成物は、本明細書に従う方法に使用することができる。
例示として、図1に本発明のひとつの実施態様を示す。この図に示されている薬物送達デバイスは、単に説明のために記載したものであり、本発明を制限するためのものではない。当業者であれば、治療を受ける特定の哺乳類に依存して、また、被治療者の状態および重篤度により、薬物送達デバイスは、多様な形状、大きさ、および容積に製造することができる。図1においては、薬物送達デバイス10は、ヒトの膣管内への挿入に適した形状、大きさの本体11を有する。薬物送達デバイス10は、拡散によって患者の膣管内に薬物を放出するポリマーから形成されている本体11を有する。図1に示す薬物送達デバイス10は、2つの円筒状単位区分12および13から構成されており、結合手段14によってそれぞれ接続されている。図1には円筒状単位区分を示しているが、当業者であれば、そのような区分は、多様な形状、大きさおよび容積に製造できることは自明である。2つの区分は、接合手段を用いずに直接融合させることもできる。そのような処方は、実施例9の多口鋳型に含まれる。図示したデバイスは2個の区分を有しているが、本発明に従う薬物送達デバイスは、3個、4個、5個、6個またはそれ以上の区分を有することができる。特定の用途のために必要な区分の数および大きさは、とりわけ、送達される投与薬物の種類、デバイス内の拡散および薬物相互作用防止用の偽区分の必要性に従って決まる。
別の側面から見ると、本発明は、哺乳類の雌に薬物を送達するための方法に関する。該方法は、上述に従って薬物送達デバイスを調製することを含む。次に、処置される哺乳類の雌の膣管内に該デバイスを挿入するが、哺乳類の雌に有効量の薬物を送達するのに十分な時間にわたってその場所に保持される。本発明は、膣内薬物送達デバイスについて記載しているが、本発明は、哺乳類の雄に薬物を投与するためのデバイスの製造および使用についても包含している。この場合には哺乳類の雄への使用(例えば、皮下への埋込み、または直腸坐剤など)に適した形状および大きさのデバイスを製造する。雄用の薬物送達デバイスは、広範な用途に使用するため、ならびに、以下に記載したような多様な疾患および医学的状態、特に前立腺癌などのような男性特異的疾患の治療を行うために、任意の適切な活性物質を含む。粘膜投与のその他の経路としては、鼻粘膜、および口腔内粘膜などが挙げられるが、これらに限定されるわけではなく、薬物、ならびに治療を要する疾患もしくは状態によって決まる。
ひとつの実施態様においては、本発明は、薬物送達デバイスを用い、有効量のLHRH組成物(すなわち、黄体形成ホルモン放出ホルモン(LHRH)、LHRHアナログ類、LHRHアゴニスト類および/もしくはLHRHアンタゴニスト類、ならびに/または、LHRH受容体に結合することができるそれらの非ペプチドアナログ類)、有効量のエストロゲン様ステロイドおよび/もしくはその受容体調節物質、ならびに有効量のプロゲステロン様ステロイドおよび/もしくはその受容体調節物質を送達することにより、哺乳類の雌(患者)の良性卵巣分泌障害を治療する方法に関する。好ましくは、月経周期のうちの誘導性卵胞期、可能であれば月経の開始時期にデバイスを投与する。患者の良性卵巣分泌障害が無月経を特徴とする場合には、本発明の方法は、妊娠していないことを確認した後に、随時開始することができる。良性卵巣分泌障害の治療に対し、LHRH組成物の連続送達を性ステロイドの送達と組み合わせることについては、米国特許第5,130,137号(クロウレイ(Crowley),Jr.)に詳細に記載されており、本明細書中に参照として該特許全体を取り入れておく。
別の実施態様においては、本発明は、哺乳類において妊娠を妨害する方法に関する。そのような方法は、月経周期の卵胞期中の正常月経開始時に、有効量のLHRH組成物(すなわち、黄体形成ホルモン放出ホルモン(LHRH)、LHRHアナログ類、LHRHアゴニスト類および/もしくはLHRHアンタゴニスト類、ならびに/またはLHRH受容体に結合することができる非ペプチド性のそれらのアナログ類)ならびに有効量のエストロゲン様ステロイドおよび/もしくはエストロゲン受容体選択的調節物質(SERM)を投与することを含む。次に、月経周期の黄体期中に、有効量のLHRH組成物、有効量のエストロゲン様ステロイドおよび/もしくはSERM、ならびに有効量のプロゲステロン様ステロイドおよび/もしくはプロゲスチン受容体選択的調節物質(SPRM)を投与することを含む。黄体期に続き、LHRH組成物ならびに有効量のエストロゲン様ステロイドおよび/もしくはSERMを投与すると、一般的には月経が始まるはずである。避妊用に、LHRH組成物の連続送達を性ステロイドの送達と組み合わせることについては、米国特許第4,762,717号(クロウレイ(Crowley),Jr.)に詳細に記載されており、本明細書中に参考としてその全体を取り入れておく。
別の側面から見ると、本発明は、閉経周辺期または閉経後の女性を治療する方法に関するが、未熟卵巣機能不全(premature ovarian failure)(例えば、外科的手術、放射線照射または化学療法などにより、卵巣の機能が失われてしまった若い女性など)を有する全ての年代の女性を治療の対象として含む。このような側面から見ると、本発明は、エストロゲンの分泌低下を治療するための方法、ならびに、閉経、閉経周辺期および閉経後の女性に現れる症状および徴候を緩和するための方法を提供する。ひとつの実施態様においては、そのような方法は、以下のVに記載しているような薬物送達デバイスを提供し、ここで、該デバイスは、薬物透過性ポリマー物質、ならびに、(i)アンドロゲンもしくはアンドロゲン受容体選択的調節物質(SARM)、(ii)エストロゲンもしくはエストロゲン受容体選択的調節物質(SERM)、および(iii)プロゲスチンもしくはプロゲスチン受容体選択的調節物質(SPRM)、あるいは、個々の患者の必要に応じた上記物質の任意の組み合わせを含む。薬物送達デバイスを女性の膣内に挿入し、有効量の性ステロイドまたは性ステロイド調節物質を女性の体内に放出させる。閉経周辺期または閉経後の女性の治療を目的として置換ホルモン類を連続的に送達することに関しては、2000年6月2日に受理された米国特許出願第09/585,935号(K.A.マーティン(Martin)ら)に詳細に記載されており、参照として全体を本明細書中に取り入れておく。
図1に示すような膣内薬物送達デバイスは、アルドリッヒ・ケミカル( Aldrich Chemical )社製のポリ(エチル−コ−酢酸ビニル)(EVA)(カタログ番号34,050-2;ロット番号07322DR)を用いて調製した。630mg のプロゲステロン(シグマ( Sigma )社);カタログ番号P-3972)または2.8mgのエストラジオール(シグマ( Sigma )社);カタログ番号E-1072)は、別異のシンチレーションバイアルに入れた約5mlのジクロロメタン(フルカケミカル(Flka Chem.)社;カタログ番号66740;ロット番号404915/1 62800)にそれぞれ別々に溶解した。次に、プロゲステロン溶液には1400mgのEVAを、エストラジオール溶液には1800mgのEVAを加え、回転振とう機を用いてEVA/薬物組成物を混合することにより、ポリマー混合物を調製した。次に、溶媒としてエタノール(ファルマコ(Pharmaco)社;カタログ番号111 USP 200 CSGL;ロット番号M8241)を用い、ドライアイス中で、得られた混合物を溶液流延した。一晩かけて溶媒を留去し、乾燥EVA/薬物混合物を粉砕した。EVA/薬物粉末を射出成形ユニット(DSM、オランダ国ゲレーン)に入れた。射出機を約80℃に加熱した。溶融EVA/薬物組成物をステンレススチールの鋳型に押出し(鋳型は10℃)、外径が50mmおよび横断面の直径が4mmの1800mgのリングを成形した。
Replens(登録商標)(コロンビア・ラボラトリーズ(Columbia Laboratories)社、ニュージャージー州リビングストン)の名称で市販されているヒドロゲルを用い、GnRHを含む組成物を調製した。GnRHを含む組成物は、10mgのGnRHを2gのReplensと混合することによって調製した。次に、2gのGnRH/Replens混合物を5匹のアカゲザルの膣管内に挿入し、9時間放置した。9時間の間、1時間おきに採血を行った。血液サンプルは遠心分離によって血餅から血清を分離し、RIAアッセイを行ってGnRHを測定した。GnRH濃度は、従来から行われているGnRHに対する二重抗体RIA法に基づいて求めた(このプロトコールを変形し、抗体を変えることにより、GnRHアゴニスト類もしくはGnRHアンタゴニスト類も測定することができる)。
実施例1の記載の従い、エストラジオール、プロゲステロン、GnRHを含む膣内薬物送達デバイスを調製した。回転振とう機(100RPM)上、37℃の放出媒質(PBS:EtOH=70:30、pH=6)中にエストラジオール、プロゲステロン、GnRHリングを入れた。一定時間に媒質を採取し、Aglient 1100 Series HPLC(アジレント(Agilent)社、カリフォルニア州フォレストシティ)を用いてHPLCによって測定した。エストラジオールおよびプロゲステロンは230nmのUVで検出し、GnRHは215nmで測定した。結果は、5点で作成した検量線と比較し、曲線下面積法に基づいて計算した。結果は、実験期間中に放出された量(μg)の累積放出率として表した。
EVA/薬物混合物以外は上記の実施例1の記載に従い、エストラジオールおよびプロゲステロンを含むEVA混合物を調製したが、これらについては、射出成形または押出しによるリング形成を行わなかった。乾燥後、組成物(ディスク状)の放出速度について評価を行った。回転振とう機(100RPM)上、37℃において、100mlの放出媒質(PBS:EtOH=70:30)にエストラジオールおよびプロゲステロンを入れた。規定の時間に媒質を採取し、、Agilent 1100 Series HPLC(アジレント(Agilent)社、カリフォルニア州フォレストシティ)を用いてHPLCによって測定した。エストラジオールおよびプロゲステロンは230nmのUVで検出した。結果は、5点で作成した検量線と比較し、曲線下面積法に基づいて計算した。結果を図5に示す。
EVA/薬物混合物以外は上記の実施例1の記載に従い、エストラジオールおよびプロゲステロンを含むEVA混合物を調製したが、これらについては、射出成形または押出しによるリング形成を行わなかった。また、市販のセルロース誘導体Methocel(登録商標)(ダウ・ケミカルズ(Dow Chwmicals)社、ミシガン州ミッドランド)を混合物に添加し、セルロース誘導体が放出速度に与える影響を評価した。概説すると、エタノールを入れた2本の別異のバイアルに、エストラジオールおよびプロゲステロンをそれぞれ溶解し、低濃度(5重量%)および高濃度(25重量%)のMethocelを加えた。これらの溶液をEVAを含む塩化メチレン溶液にゆっくりと加えて乳化した。得られたエマルションは、鋳型に溶液流延し、ドライアイス上で冷却した。昇華後、溶媒を1cm×1cmのサンプルに切断して、シンチレーションバイアルに入れ、0.1Mのリン酸緩衝生理食塩水(pH=6.10)およびエタノールを70:30の割合で加えた。バイアルは、回転振とう機(100RPM)上の37℃のインキュベーターに入れた。緩衝液は、規定の時間に置換した。エストラジオールおよびプロゲステロンの放出量は、280nmまたは250nmにおいて、UV/VIS分光光度計を用いてそれぞれ測定した。次に、累積放出量を時間の関数としてプロットすることにより、放出速度を求めた。図6に示すように、Methocelを添加することにより、疑似ゼロ次放出が得られた。また、セルロース誘導体のプロゲステロンに対する比が高くなるほど、プロゲステロンの放出速度が速くなった。本実施例は、薬物送達デバイスからの薬物の放出速度は、セルロース誘導体などの賦形剤を使用することによって加速させることができることを示している。
EVA/薬物混合物以外は上記の実施例1の記載に従い、エストラジオールおよびプロゲステロンを含むEVA混合物を調製したが、これらについては、射出成形または押出しによるさらなる加工は行わなかった。また、EVA/薬物混合物を合わせ、片面にはエストラジオールを含み、もう一方の面にはプロゲステロンを含む二面ディスクを成形した。乾燥後、ディスクの放出速度を評価した。概説すると、回転振とう機(100RPM)上、37℃において、100mlの放出媒質(PBS:EtOH=70:30、pH=6)にエストラジオールおよびプロゲステロンを入れた。測定のため、規定の時間に媒質を100%回収し、新たに100mlの放出媒質を加えた。Agilent 1100 Series HPLC(アジレント(Agilent)社、カリフォルニア州フォレストシティ)を用いて媒質を測定した。エストラジオールおよびプロゲステロンは、230nmにおいてUV検出を行った。結果は、5点で作成した検量線と比較し、曲線下面積法に基づいて計算し、累積放出%として図7に示している。図7からわかるように、エストラジオールおよびプロゲステロンは、独立した二相性放出動態を示した。
GnRHおよびReplens(登録商標)(LDSコンシューマー・プロダクツ(LDS Consumer Products)社、アイオワ州セダーラピッズ)という名称で市販されているポリアクリル酸(ポリカルボフィル)系ヒドロゲルを含むポリマー混合物は、10mgのGnRHを2gのヒドロゲルと混合する(0.5%wt/wt;pH=7)ことによって調製した。5匹のアカゲザルの膣管内に、GnRH/ヒドロゲルの2gのアリコートを入れ、48時間放置した。規定の時間間隔で血液サンプルを採取し、GnRHおよびLHの濃度を測定した。
図9に示すような膣内投与用の多連結薬物送達デバイスは、アルドリッヒ・ケミカル( Aldrich Chemical )社製のポリ(エチル−コ−酢酸ビニル)(EVA)(カタログ番号34,050-2;ロット番号07322DR)を用いて調製することができる。630mg のプロゲステロン(シグマ( Sigma )社);カタログ番号P-3972)および3.0mgのエストラジオール(シグマ( Sigma )社);カタログ番号E-1072)は、別異のシンチレーションバイアルに入れた約5mlのジクロロメタン(フルカケミカル(Fluka Chem.)社;カタログ番号66740;ロット番号404915/1 62800)にそれぞれ別々に溶解した。次に、プロゲステロン溶液には1000mgのEVAを、エストラジオール溶液には300mgのEVAを加え、回転振とう機を用いてEVA/薬物組成物を混合することにより、ポリマー混合物を調製した。同様に、GnRHアゴニスト(2.5mg(D−Trp6−Pro9−Net−GnRH))、110mgのメチルセルロースおよび50mgのEVAを含む混合物は、5mlの塩化メチレンに該混合物を溶解することによって調製した。
膣内デバイスの水和速度は、ポリマー内への水の浸潤速度を含む多数の因子によって決まる。水の浸潤速度は、ポリマー内の浸透圧によって調節することができる。浸透圧は、薬物調製時に塩類(NaCl、KClなど)を加えることによって調節することができる。
Claims (22)
- 薬物送達デバイスであって、全体に亘り均一な横断面を有する埋め込み可能な本体を含み、該本体が2つまたはそれ以上の区分を有し、
各区分は、お互いに別の区分の末端に連結する第一および第二末端を有し、膜を有しておらず、エチレン−酢酸ビニルコポリマーを含む薬物透過性ポリマー物質を含み、
少なくとも1つの区分は、前記薬物透過性ポリマー物質と薬物との均一な混合物を含み、ゼロ次速度で該薬物の放出をもたらすことを特徴とする、薬物送達デバイス。 - 2つまたはそれ以上の区分が、それぞれ薬物を含むことを特徴とする請求項1記載の薬物送達デバイス。
- 2つ以上の区分から薬物を同時に放出するための薬物送達デバイスであって、お互いに末端で結合した2つまたはそれ以上の弧型の区分を有するリング型の埋め込み可能な本体を含み、各区分は膜を有しておらず、該区分の少なくとも2つの区分が、エチレン−酢酸ビニルコポリマーを含む薬物透過性ポリマー物質と薬物との均一な混合物から成り、ゼロ次速度で該薬物の放出をもたらすことを特徴とする、薬物送達デバイス。
- リングの形状であることを特徴とする請求項1または2記載の薬物送達デバイス。
- 前記デバイスが膣リングとして使用されることを特徴とする請求項3または4記載の薬物送達デバイス。
- 前記区分の末端が結合手段によって付着されていることを特徴とする請求項1から5いずれか1項記載の薬物送達デバイス。
- 前記結合手段が接着材料であることを特徴とする請求項6記載の薬物送達デバイス。
- 外径が40mm〜80mmである膣リングであることを特徴とする請求項5記載の薬物送達デバイス。
- 横断面の直径が0.5mm〜12mmであることを特徴とする請求項5記載の薬物送達デバイス。
- 薬物が性ホルモンステロイドを含むことを特徴とする請求項1から9いずれか1項記載の薬物送達デバイス。
- 薬物が避妊剤であることを特徴とする請求項1から9いずれか1項記載の薬物送達デバイス。
- 薬物は、インターフェロン、抗血管形成因子、成長因子、ホルモン、酵素、トランスフェラーゼ、加水分解酵素、リアーゼ、イソメラーゼ、プロテアーゼ、リガーゼおよび酸化還元酵素、酵素阻害剤、ステロイド、抗癌剤および抗生物質より成る群から選択されることを特徴とする請求項1から9いずれか1項記載の薬物送達デバイス。
- 薬物は、成長ホルモン、多糖、抗原および抗体より成る群から選択されることを特徴とする請求項1から9いずれか1項記載の薬物送達デバイス。
- 哺乳類の雌に薬物を送達するために使用され、哺乳類の雌の膣管に挿入され、哺乳類の雌に有効量の薬物を送達するのに十分な期間にわたって該哺乳類の雌の膣管内に保持されることを特徴とする、請求項1から13いずれか1項記載の薬物送達デバイス。
- リング型薬物送達デバイスを作成する方法であって、
(a)エチレン−酢酸ビニルコポリマーを含む第一の薬物透過性ポリマー物質を第一の薬物と混合して均一な第一のポリマー混合物を調製し;
(b)工程(a)の第一のポリマー混合物を鋳型に入れて第一のリングを形成し;
(c)工程(b)の第一のリングを切断して第一の区分を作成し;
(d)第二の薬物透過性ポリマー物質および第二の薬物について工程(a)〜(c)を繰り返して第二の区分を作成し;さらに、
(e)前記第一の区分を前記第二の区分と連結してリング型の薬物送達デバイスを形成する;工程を含み、
該薬物送達デバイスが、膜を有しておらず、前記第一の薬物および第二の薬物をゼロ次速度で放出するように構成されることを特徴とする方法。 - リング型薬物送達デバイスを作成する方法であって、
(a)エチレン−酢酸ビニルコポリマーを含む第一の薬物透過性ポリマー物質を第一の薬物と混合して均一な第一のポリマー混合物を調製し;
(b)工程(a)の第一のポリマー混合物を鋳型に入れて、前記第一の薬物透過性ポリマー物質と前記第一の薬物の均一な組成物を有する第一の区分を成形し;
(c)エチレン−酢酸ビニルコポリマーを含む第二の薬物透過性ポリマー物質と第二の薬物の均一な混合物を含む第二の区分を提供し;さらに、
(d)前記第一の区分と前記第二の区分とを連結させて薬物送達デバイスを形成する;工程を含み、
前記第一の区分および第二の区分のそれぞれが膜を有しておらず、該薬物送達デバイスが前記第一の薬物と第二の薬物の少なくとも1つをゼロ次速度で放出するように構成されることを特徴とする方法。 - リング型の薬物送達デバイスを作成する方法であって、
(a)エチレン−酢酸ビニルコポリマーを含む第一の薬物透過性ポリマー物質を第一の薬物と混合して均一な第一のポリマー混合物を調製し;
(b)工程(a)の第一のポリマー混合物を鋳型に注入して、前記第一の薬物透過性ポリマー物質と前記第一の薬物の均一な組成物を有する第一の区分を形成し、該第一の区分は膜を有しておらず、前記第一の薬物をゼロ次速度で放出するように構成され;さらに、
(c)エチレン−酢酸ビニルコポリマーを含む第二の薬物透過性ポリマー物質と第二の薬物を含む少なくとも第二の区分を提供して、前記第二の薬物透過性ポリマー物質と前記第二の薬物との均一な組成物を有する第二の区分を形成し、該第二の区分は、前記第二の薬物をゼロ次速度で放出するように構成され;そして
(d)前記第一の区分と前記第二の区分とを連結させて薬物送達デバイスを形成する; 工程を含むことを特徴とする方法。 - 哺乳類の雌の良性卵巣分泌障害を治療するためのリング型薬物送達デバイスであって、エチレン−酢酸ビニルコポリマーを含む薬物透過性ポリマー物質と黄体形成ホルモン放出ホルモン(LHRH)との均一な混合物を含みかつ膜を有していない第一の区分、および前記薬物透過性ポリマー物質とエストロゲンステロイドとの均一な混合物を含みかつ膜を有していない第二の区分を含み、該薬物送達デバイスが哺乳類の膣内に挿入されて、該哺乳類の雌の体内に治療有効量のLHRHおよび有効量のエストロゲンステロイドをそれぞれゼロ次速度で放出することを特徴とする薬物送達デバイス。
- 哺乳類の雌の避妊のためのリング型薬物送達デバイスであって、エチレン−酢酸ビニルコポリマーを含む薬物透過性ポリマー物質と黄体形成ホルモン放出ホルモン(LHRH)との均一な混合物を含む第一の区分、前記薬物透過性ポリマー物質とエストロゲンステロイドとの均一な混合物を含む第二の区分、および前記薬物透過性ポリマー物質とプロゲステロンステロイドとの均一な混合物を含む第三の区分を含み、該薬物送達デバイスが膜を有しておらず、哺乳類の膣内に挿入されて、該哺乳類の雌の体内に有効量のLHRH、有効量のエストロゲンステロイドおよび有効量のプロゲステロンステロイドをそれぞれゼロ次速度で放出することを特徴とする薬物送達デバイス。
- 周期的***の停止の症状を呈している女性においてエストロゲンの分泌低下を治療するためのリング型薬物送達デバイスであって、エチレン−酢酸ビニルコポリマーを含む薬物透過性ポリマー物質と性ホルモンステロイドとの均一な混合物を含む第一の区分、および前記薬物透過性ポリマー物質とプロゲステロンステロイドとの均一な混合物を含む第二の区分を含み、該薬物送達デバイスが膜を有しておらず、女性の膣内に挿入されて、該女性の体内に有効量の性ホルモンステロイドをゼロ次速度で放出することを特徴とする薬物送達デバイス。
- 閉経期、閉経周辺期および閉経後を迎え、エストロゲン治療を必要としている女性に対して、そのような期間に伴う症状の緩和を図るためのリング型薬物送達デバイスであって、第一および第二の区分を有し、該第一の区分は、エチレン−酢酸ビニルコポリマーを含む薬物透過性ポリマー物質とエストロゲンステロイドとの均一な混合物を含み、該薬物送達デバイスが膜を有しておらず、女性の膣内に挿入されて、該女性の体内に有効量のエストロゲンステロイドをゼロ次速度で放出することを特徴とする薬物送達デバイス。
- 閉経期、閉経周辺期および閉経後を迎え、エストロゲン治療を必要としている女性に対して、そのような期間に伴う症状の緩和を図るためのリング型薬物送達デバイスであって、第一および第二の区分を有し、該第一の区分はエチレン−酢酸ビニルコポリマーを含む薬物透過性ポリマー物質と性ホルモンステロイドとの均一な混合物を含み、該薬物送達デバイスが膜を有しておらず、女性の膣内に挿入されて、該女性の体内に有効量の性ホルモンステロイドをゼロ次速度で放出することを特徴とする薬物送達デバイス。
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
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US60/473,579 | 2003-05-27 | ||
PCT/US2004/013172 WO2004096151A2 (en) | 2003-04-29 | 2004-04-29 | Methods and devices for the sustained release of multiple drugs |
Publications (3)
Publication Number | Publication Date |
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Families Citing this family (93)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6764505B1 (en) | 2001-04-12 | 2004-07-20 | Advanced Cardiovascular Systems, Inc. | Variable surface area stent |
GB0222522D0 (en) | 2002-09-27 | 2002-11-06 | Controlled Therapeutics Sct | Water-swellable polymers |
US7169178B1 (en) | 2002-11-12 | 2007-01-30 | Advanced Cardiovascular Systems, Inc. | Stent with drug coating |
JP2007505927A (ja) | 2003-09-19 | 2007-03-15 | ドラッグテック コーポレイション | 薬物送達システム |
ES2360806T3 (es) | 2004-07-09 | 2011-06-09 | The Population Council, Inc. | Composiciones de liberación prolongada que contienen moduladores de receptores de progesterona. |
GB0417401D0 (en) | 2004-08-05 | 2004-09-08 | Controlled Therapeutics Sct | Stabilised prostaglandin composition |
EP1827328B1 (en) * | 2004-12-14 | 2011-08-17 | Poly-Med, Inc. | Intravaginal ringed mesh device |
US9693953B2 (en) | 2006-06-02 | 2017-07-04 | Janet A. Chollet | Method of treating atrophic vaginitis |
GB0613333D0 (en) | 2006-07-05 | 2006-08-16 | Controlled Therapeutics Sct | Hydrophilic polyurethane compositions |
GB0613638D0 (en) | 2006-07-08 | 2006-08-16 | Controlled Therapeutics Sct | Polyurethane elastomers |
CA2657533A1 (en) * | 2006-07-12 | 2008-01-17 | Controlled Therapeutics (Scotland) Ltd. | Drug delivery polymer with hydrochloride salt of clindamycin |
GB0620685D0 (en) | 2006-10-18 | 2006-11-29 | Controlled Therapeutics Sct | Bioresorbable polymers |
EP2121107B1 (en) * | 2006-12-18 | 2012-10-31 | Eatlittle Inc. | Device for delivery of a substance |
WO2009061569A1 (en) * | 2007-11-05 | 2009-05-14 | Repros Therapeutics Inc. | Compositions and methods for treating dysfunctional uterine bleeding |
EP2057972A1 (en) * | 2007-11-07 | 2009-05-13 | N.V. Organon | Intrauterine deposit |
ATE508734T1 (de) * | 2007-11-22 | 2011-05-15 | Bayer Oy | System zur vaginalen freisetzung |
EP2062568A1 (en) * | 2007-11-22 | 2009-05-27 | Bayer Schering Pharma Oy | Vaginal delivery system |
LT2249757T (lt) | 2008-02-04 | 2017-09-25 | Ferring B.V. | Vientisi intravaginaliniai žiedai, apimantys progesteroną, ir jų gamybos bei panaudojimo būdai |
WO2009129459A1 (en) * | 2008-04-18 | 2009-10-22 | Combinent Biomedical Systems, Inc. | Devices that include ethylene-vinyl acetate copolymers and methods of making and using same |
TWI477276B (zh) | 2008-04-28 | 2015-03-21 | Repros Therapeutics Inc | 抗黃體素給藥方案 |
US9034365B2 (en) | 2008-05-20 | 2015-05-19 | Poly-Med, Inc. | Biostable, multipurpose, microbicidal intravaginal devices |
EP2140860A1 (en) * | 2008-07-03 | 2010-01-06 | Bayer Schering Pharma Oy | An improved method of contraception |
US20100040671A1 (en) * | 2008-08-12 | 2010-02-18 | Ahmed Salah U | Intravaginal Devices With a Rigid Support, Methods of Making, and Uses Thereof |
AU2009313304B2 (en) * | 2008-11-07 | 2014-07-24 | Vimac Ventures, Llc | Devices and methods for treating and/or preventing diseases |
FI121000B (fi) * | 2008-11-19 | 2010-06-15 | Bayer Schering Pharma Oy | Intravaginaalinen antojärjestelmä ja menetelmä sen valmistamiseksi |
US8568374B2 (en) * | 2009-05-04 | 2013-10-29 | Merck Sharp & Dohme B.V. | Intrauterine system |
JP5695035B2 (ja) | 2009-06-03 | 2015-04-01 | フォーサイト・ビジョン5・インコーポレイテッドForsight Vision5,Inc. | 前眼部薬物供給 |
EP2456421B1 (en) | 2009-07-21 | 2017-04-05 | The Population Council, Inc. | Multi-layered gradient vaginal ring |
EP3689364A1 (en) * | 2010-02-08 | 2020-08-05 | Shenzhen Evergreen Therapeutics Co., Ltd. | Methods for the use of progestogen as a glucocorticoid sensitizer |
CN103025320A (zh) * | 2010-03-28 | 2013-04-03 | 伊万斯彻有限公司 | ***内药物递送装置 |
AU2011256259A1 (en) | 2010-05-17 | 2012-11-08 | Novaer Holdings, Inc. | Drug delivery devices for delivery of ocular therapeutic agents |
KR20130045332A (ko) * | 2010-06-22 | 2013-05-03 | 지아시앙 차오 | 항콜린제를 포함하는 질내 기구 및 그 제조방법 |
US8580294B2 (en) | 2010-10-19 | 2013-11-12 | International Partnership For Microbicides | Platinum-catalyzed intravaginal rings |
CN103298519B (zh) | 2010-11-12 | 2016-09-14 | 犹他大学研究基金会 | 用于受控式润滑剂传递的***内装置 |
KR101263916B1 (ko) | 2011-01-11 | 2013-05-13 | 이장희 | 성 호르몬 방출 장치 및 이를 이용한 동물 피임 및 발정 유도 방법 |
DE202012012713U1 (de) * | 2011-03-04 | 2014-01-23 | Arstat, Inc. | Intravaginale Arzneimittelabgabevorrichtung |
EP2731587A1 (en) | 2011-07-15 | 2014-05-21 | Universiteit Gent | Intravaginal delivery system |
KR102192603B1 (ko) | 2011-09-14 | 2020-12-17 | 포사이트 비젼5, 인크. | 안내 삽입물 장치 및 방법 |
WO2013039993A1 (en) * | 2011-09-14 | 2013-03-21 | Royer Biomedical, Inc. | Bioresorbable drug delivery matrices based on cross-linked polysaccharides, dosage forms designed for delayed/controlled release |
PT2782584T (pt) | 2011-11-23 | 2021-09-02 | Therapeuticsmd Inc | Preparações e terapias de substituição para hormonoterapias naturais combinadas |
US9301920B2 (en) | 2012-06-18 | 2016-04-05 | Therapeuticsmd, Inc. | Natural combination hormone replacement formulations and therapies |
US20130166931A1 (en) * | 2011-12-23 | 2013-06-27 | Lsi Corporation | Reducing power consumption of memory |
CN102754908B (zh) | 2012-01-20 | 2015-06-10 | 奥驰亚客户服务公司 | 口腔用烟草产品 |
CN103039688B (zh) | 2012-01-20 | 2016-01-06 | 奥驰亚客户服务公司 | 口腔用产品 |
US9854831B2 (en) | 2012-01-20 | 2018-01-02 | Altria Client Services Llc | Oral product |
CN102754907B (zh) | 2012-01-20 | 2015-06-24 | 奥驰亚客户服务公司 | 口腔用产品 |
CN103040090B (zh) * | 2012-01-20 | 2016-03-30 | 奥驰亚客户服务公司 | 脱除烟草的口腔用产品 |
DE102012009057A1 (de) | 2012-05-09 | 2013-11-14 | Dr. Arabin GmbH & Co. KG | Rotationspessar mit zusätzlicher Wirkstoffkomponente |
NZ702467A (en) | 2012-05-31 | 2016-07-29 | Repros Therapeutics Inc | Formulations and methods for vaginal delivery of antiprogestins |
US20130338122A1 (en) | 2012-06-18 | 2013-12-19 | Therapeuticsmd, Inc. | Transdermal hormone replacement therapies |
US20150196640A1 (en) | 2012-06-18 | 2015-07-16 | Therapeuticsmd, Inc. | Progesterone formulations having a desirable pk profile |
US10806740B2 (en) | 2012-06-18 | 2020-10-20 | Therapeuticsmd, Inc. | Natural combination hormone replacement formulations and therapies |
US10806697B2 (en) | 2012-12-21 | 2020-10-20 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
AU2013334169B2 (en) | 2012-10-26 | 2018-03-29 | Forsight Vision5, Inc. | Ophthalmic system for sustained release of drug to eye |
EP2914268B1 (en) | 2012-11-02 | 2018-07-04 | Repros Therapeutics Inc. | Methods and compositions for treating progesterone-dependent conditions |
US9180091B2 (en) | 2012-12-21 | 2015-11-10 | Therapeuticsmd, Inc. | Soluble estradiol capsule for vaginal insertion |
US10471072B2 (en) | 2012-12-21 | 2019-11-12 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
US10537581B2 (en) | 2012-12-21 | 2020-01-21 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
US11246875B2 (en) | 2012-12-21 | 2022-02-15 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
US11266661B2 (en) | 2012-12-21 | 2022-03-08 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
US10568891B2 (en) | 2012-12-21 | 2020-02-25 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
US10137031B2 (en) | 2013-11-14 | 2018-11-27 | International Partnership For Microbicides, Inc. | Combination therapy intravaginal rings |
AR100562A1 (es) | 2014-05-22 | 2016-10-12 | Therapeuticsmd Inc | Composición farmacéutica de estradiol y progesterona para terapia de reemplazo hormonal |
CN105392454B (zh) | 2014-06-28 | 2018-05-08 | 安德罗玛克实验室股份有限公司 | 用于预防早产的含有延长、不变和持续释放的孕酮的环扎子宫托 |
CN105277633B (zh) * | 2014-07-26 | 2017-06-23 | 浙江仙琚制药股份有限公司 | 一种炔诺酮衍生物及其中间体的杂质检测分析方法 |
AU2015296609A1 (en) | 2014-07-29 | 2016-12-22 | Therapeuticsmd, Inc. | Transdermal cream |
TW201618783A (zh) | 2014-08-07 | 2016-06-01 | 艾森塔製藥公司 | 以布魯頓(Bruton)氏酪胺酸激酶(BTK)佔據和BTK再合成速率為基礎之治療癌症、免疫和自體免疫疾病及發炎性疾病之方法 |
EP3017809A1 (en) | 2014-11-07 | 2016-05-11 | Ferring B.V. | Drug-device unit containing quinagolide |
PL3247327T3 (pl) | 2015-01-21 | 2020-02-28 | Bayer Oy | System dostarczania leków zawierający niesteroidowy lek przeciwzapalny (nlpz) i związek progesteronowy oraz sposoby wytwarzania |
JP2018509389A (ja) * | 2015-01-30 | 2018-04-05 | リ・ガリ・ベスローテン・フエンノートシャップLi Galli B.V. | 膣用薬物送達デバイス |
US20160296532A1 (en) | 2015-04-13 | 2016-10-13 | Forsight Vision5, Inc. | Ocular Insert Composition of a Semi-Crystalline or Crystalline Pharmaceutically Active Agent |
US11096888B2 (en) * | 2015-05-13 | 2021-08-24 | Bayer Oy | Long acting drug delivery device and its use in contraception |
US10328087B2 (en) | 2015-07-23 | 2019-06-25 | Therapeuticsmd, Inc. | Formulations for solubilizing hormones |
GB201517523D0 (en) * | 2015-10-05 | 2015-11-18 | Ostara Biomedical Ltd | Methods and compositions for managing reproduction |
EP3402471A4 (en) * | 2016-01-12 | 2019-08-28 | Repros Therapeutics Inc. | TRANS-CLOMIPHENE-BASED POLY THERAPY AND PROGESTERONE RECEPTOR ANTAGONIST FOR THE TREATMENT OF HORMONE-DEPENDENT PATHOLOGICAL CONDITIONS |
BR112018070199A2 (pt) | 2016-04-01 | 2019-01-29 | Therapeuticsmd Inc | composição farmacêutica de hormônio esteroide |
WO2017173044A1 (en) | 2016-04-01 | 2017-10-05 | Therapeuticsmd Inc. | Steroid hormone compositions in medium chain oils |
GB201708224D0 (en) | 2017-05-23 | 2017-07-05 | Juniper Pharmaceuticals Uk Ltd | Device |
FR3070619A1 (fr) * | 2017-09-01 | 2019-03-08 | Ab7 Innovation | Piece moulee monolithique en matrice multiple pour la diffusion d’actifs et son procede d’obtention |
US20200337888A1 (en) | 2017-10-27 | 2020-10-29 | Renovia Inc. | Devices, systems, and methods for training pelvic floor muscles |
CN108186553B (zh) * | 2018-02-13 | 2020-10-02 | 广东药科大学 | 一种***长效栓剂及其制备方法 |
EP3773542A1 (en) * | 2018-04-10 | 2021-02-17 | Li Galli B.V. | Vaginal systemic drug delivery |
CA3098551A1 (en) * | 2018-04-27 | 2019-10-31 | Evestra, Inc. | Estrogen prodrugs and methods of administering estrogen prodrugs |
US11690807B2 (en) | 2018-05-24 | 2023-07-04 | Celanese Eva Performance Polymers Llc | Implantable device for sustained release of a macromolecular drug compound |
CA3087410A1 (en) | 2018-05-24 | 2019-11-28 | Celanese EVA Performance Polymers Corporation | Implantable device for sustained release of a macromolecular drug compound |
BR112021019493A2 (pt) * | 2019-03-29 | 2021-12-07 | Bridget Martell | Anéis intravaginais de eva segmentados |
CN113164383B (zh) * | 2019-10-12 | 2022-08-12 | 国家卫生健康委科学技术研究所 | 用于黄体支持的***缓释给药***及其制备方法与应用 |
FR3107203B1 (fr) * | 2020-02-14 | 2023-11-24 | Ab7 Innovation | Matrice solide composite pour la délivrance prolongée d’actifs |
USD935018S1 (en) * | 2020-04-07 | 2021-11-02 | The Population Council, Inc. | Contraceptive |
WO2023031218A1 (en) | 2021-08-31 | 2023-03-09 | Ferring B.V. | Diagnosis and treatment of ectopic endometriosis |
WO2024151545A1 (en) * | 2023-01-09 | 2024-07-18 | Daré Bioscience, Inc. | Methods and devices for hormone replacement therapy |
WO2024155777A2 (en) | 2023-01-19 | 2024-07-25 | Dare Bioscience, Inc. | Compositions and techniques for treatment of polycystic ovarian syndrome (pcos) and endometriosis |
WO2024155775A2 (en) | 2023-01-19 | 2024-07-25 | Dare Bioscience, Inc. | Compositions and techniques for treatment of polycystic ovarian syndrome (pcos) and endometriosis |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5164793A (ja) * | 1974-10-18 | 1976-06-04 | Schering Ag | |
JPS61106508A (ja) * | 1984-10-12 | 1986-05-24 | アクゾ・エヌ・ヴエー | 2種以上の活性物質の放出システム |
WO1997002015A1 (en) * | 1995-07-04 | 1997-01-23 | Akzo Nobel N.V. | Ring-shaped devices |
JPH119699A (ja) * | 1997-06-24 | 1999-01-19 | Hoechst Marion Roussel | 腟内薬物供給装置 |
JP2002513690A (ja) * | 1998-05-01 | 2002-05-14 | エフイ−アイ エンタープライジズ,リミティド | 制御放出デバイスの射出成形製造方法 |
JP2003507109A (ja) * | 1999-08-26 | 2003-02-25 | エンハンス ファーマシューティカルズ,インコーポレイティド | 女性の頸管部を麻酔するための器具及び方法 |
Family Cites Families (96)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE1945275U (de) * | 1965-04-30 | 1966-09-01 | Ortho Pharma Corp | Intrauterine vorrichtung zur empfaengnisverhuetung. |
US3454004A (en) * | 1967-08-18 | 1969-07-08 | Holland Rantos Co Inc | Intrauterine contraceptive device |
US3545439A (en) * | 1968-01-04 | 1970-12-08 | Upjohn Co | Medicated devices and methods |
NL6903028A (ja) * | 1969-02-26 | 1970-08-28 | ||
US3903880A (en) * | 1972-08-17 | 1975-09-09 | Alza Corp | Intrauterine device for managing the reproductive process |
US4069307A (en) * | 1970-10-01 | 1978-01-17 | Alza Corporation | Drug-delivery device comprising certain polymeric materials for controlled release of drug |
US3920805A (en) * | 1971-12-09 | 1975-11-18 | Upjohn Co | Pharmaceutical devices and method |
US3938515A (en) * | 1971-12-20 | 1976-02-17 | Alza Corporation | Novel drug permeable wall |
US3708511A (en) * | 1972-01-18 | 1973-01-02 | Organon | Novel {66 -steroids of the oestrane series |
NL7204025A (ja) * | 1972-03-24 | 1973-09-26 | ||
US3780935A (en) * | 1972-07-10 | 1973-12-25 | Lukacs & Jacoby Ass | Serum separating method |
NL7210262A (ja) * | 1972-07-26 | 1974-01-29 | ||
US4016251A (en) * | 1972-08-17 | 1977-04-05 | Alza Corporation | Vaginal drug dispensing device |
US3963119A (en) * | 1973-10-13 | 1976-06-15 | Lucaks And Jacoby Associates | Serum separating apparatus |
US4043928A (en) * | 1973-10-31 | 1977-08-23 | Lukacs And Jacoby Associates | Serum separating composition of matter |
US4155991A (en) * | 1974-10-18 | 1979-05-22 | Schering Aktiengesellschaft | Vaginal ring |
US4093709A (en) * | 1975-01-28 | 1978-06-06 | Alza Corporation | Drug delivery devices manufactured from poly(orthoesters) and poly(orthocarbonates) |
US4144317A (en) * | 1975-05-30 | 1979-03-13 | Alza Corporation | Device consisting of copolymer having acetoxy groups for delivering drugs |
US4096860A (en) * | 1975-10-08 | 1978-06-27 | Mclaughlin William F | Dual flow encatheter |
US3995633A (en) * | 1975-12-02 | 1976-12-07 | The Procter & Gamble Company | Vaginal Medicament dispensing device |
US3995634A (en) * | 1975-12-02 | 1976-12-07 | The Procter & Gamble Company | Vaginal cavity dispensing means and method |
US4219426A (en) * | 1976-03-19 | 1980-08-26 | Organon Teknika B.V. | Dialysis device |
US4237885A (en) * | 1978-10-23 | 1980-12-09 | Alza Corporation | Delivery system with mated members for storing and releasing a plurality of beneficial agents |
US4292965A (en) * | 1978-12-29 | 1981-10-06 | The Population Council, Inc. | Intravaginal ring |
DE3040978A1 (de) * | 1980-10-28 | 1982-05-27 | Schering Ag, 1000 Berlin Und 4619 Bergkamen | Vaginalring |
US4484559A (en) * | 1982-03-01 | 1984-11-27 | Mcdermott Incorporated | Apparatus for removing material such as concrete from underwater pipelines |
DE3214667C2 (de) * | 1982-04-21 | 1985-07-18 | Akzo Gmbh, 5600 Wuppertal | Zusammengesetzter Körper für die Langzeitabgabe von Wirkstoffen |
CA1223831A (en) | 1982-06-23 | 1987-07-07 | Dean Engelhardt | Modified nucleotides, methods of preparing and utilizing and compositions containing the same |
US4629449A (en) * | 1982-07-29 | 1986-12-16 | Alza Corporation | Vaginal dispenser for dispensing beneficial hormone |
NL8301035A (nl) * | 1983-03-23 | 1984-10-16 | Organon Teknika Bv | Macromoleculair materiaal met carbonylgroepen geschikt als sorbent voor stikstofverbindingen. |
US4558996A (en) * | 1983-06-30 | 1985-12-17 | Organon Teknika Corporation | Easy load peristaltic pump |
US4484599A (en) | 1983-09-23 | 1984-11-27 | Organon Teknika Corporation | Pinch-type pressure- or flow-regulating valve |
EP0180264A1 (en) * | 1984-10-12 | 1986-05-07 | Akzo N.V. | Release system for two or more active substances |
US4645502A (en) * | 1985-05-03 | 1987-02-24 | Alza Corporation | Transdermal delivery of highly ionized fat insoluble drugs |
US4762717A (en) * | 1986-03-21 | 1988-08-09 | The General Hospital Corporation | Continuous delivery of luteinizing hormone releasing hormone compositions in combination with sex steroid delivery for use as a contraceptive |
SE8602666D0 (sv) * | 1986-06-16 | 1986-06-16 | Leo Ab | Intravaginal devices |
US4938759A (en) * | 1986-09-02 | 1990-07-03 | Alza Corporation | Transdermal delivery device having a rate controlling adhesive |
CA1331563C (en) | 1987-08-03 | 1994-08-23 | Gaylen M. Zentner | Device for the controlled release of drugs with donnan-like modulation by charged insoluble resins |
EP0303306B1 (en) * | 1987-08-08 | 1993-03-10 | Akzo N.V. | Contraceptive implant |
US5474783A (en) * | 1988-03-04 | 1995-12-12 | Noven Pharmaceuticals, Inc. | Solubility parameter based drug delivery system and method for altering drug saturation concentration |
NO179479C (no) * | 1988-03-11 | 1996-10-16 | Teikoku Seiyaku Kk | Fremgangsmåte for fremstilling av et intravaginalt farmasöytisk preparat |
US5034229A (en) * | 1988-12-13 | 1991-07-23 | Alza Corporation | Dispenser for increasing feed conversion of hog |
US5002540A (en) * | 1989-05-22 | 1991-03-26 | Warren Kirschbaum | Intravaginal device and method for delivering a medicament |
US5252334A (en) * | 1989-09-08 | 1993-10-12 | Cygnus Therapeutic Systems | Solid matrix system for transdermal drug delivery |
HU208495B (en) * | 1990-06-27 | 1993-11-29 | Alkaloida Vegyeszeti Gyar | Process for producing retarde pharmaceutical compositions |
IE67345B1 (en) | 1991-03-12 | 1996-03-20 | Akzo Nv | Low dose dry pharmaceutical preparations |
US5211952A (en) * | 1991-04-12 | 1993-05-18 | University Of Southern California | Contraceptive methods and formulations for use therein |
US5340585A (en) * | 1991-04-12 | 1994-08-23 | University Of Southern California | Method and formulations for use in treating benign gynecological disorders |
US5302397A (en) * | 1991-11-19 | 1994-04-12 | Amsden Brian G | Polymer-based drug delivery system |
US6013853A (en) * | 1992-02-14 | 2000-01-11 | The University Of Texas System | Continuous release polymeric implant carrier |
EP0566135A1 (en) * | 1992-04-17 | 1993-10-20 | Takeda Chemical Industries, Ltd. | Transmucosal composition comprising a peptide and a cytidine derivative |
CA2098889A1 (en) * | 1992-07-06 | 1994-01-07 | Takashi Chinuki | Slow-releasing medicated resin moldings and process for producing the same |
US5482702A (en) * | 1993-04-27 | 1996-01-09 | Church & Dwight Co., Inc. | Hydrophilic polymer-coated microcrystallites of bicarbonate salt |
WO1995001167A2 (en) * | 1993-06-25 | 1995-01-12 | Alza Corporation | Incorporating poly-n-vinyl amide in a transdermal system |
GB2282384B8 (en) * | 1993-08-18 | 1997-09-04 | Europ Economic Community | Drug delivery agents incorporating mitomycin |
US5543150A (en) * | 1993-09-15 | 1996-08-06 | Columbia Laboratories, Inc. | Method of progesterone delivery and affect thereof |
CN1135716A (zh) | 1993-12-27 | 1996-11-13 | 阿克佐诺贝尔公司 | 经皮吸收的药用制剂 |
FR2717688B1 (fr) * | 1994-03-28 | 1996-07-05 | Lhd Lab Hygiene Dietetique | Système matriciel transdermique d'administration d'un oestrogène et/ou un progestatif à base d'EVA. |
FI97944C (fi) | 1994-07-05 | 1997-03-25 | Leiras Oy | Vaikuttavaa ainetta luovuttava laite |
US5681568A (en) * | 1994-08-19 | 1997-10-28 | Cambridge Neuroscience, Inc. | Device for delivery of substances and methods of use thereof |
US5593965A (en) * | 1994-10-20 | 1997-01-14 | Creighton University | Anti-tumor effects of GnRH-III |
IL116433A (en) * | 1994-12-19 | 2002-02-10 | Galen Chemicals Ltd | INTRAVAGINAL DRUG DELIVERY DEVICES FOR THE ADMINISTRATION OF 17β-OESTRADIOL PRECURSORS |
CA2216934A1 (en) * | 1995-04-03 | 1996-10-10 | Abbott Laboratories | Homogeneous mixtures of low temperature-melting drugs and additives for controlled release |
US5601839A (en) | 1995-04-26 | 1997-02-11 | Theratech, Inc. | Triacetin as a penetration enhancer for transdermal delivery of a basic drug |
US6572879B1 (en) * | 1995-06-07 | 2003-06-03 | Alza Corporation | Formulations for transdermal delivery of pergolide |
FR2739032B1 (fr) * | 1995-09-27 | 1997-11-21 | Lhd Lab Hygiene Dietetique | Systeme matriciel transdermique d'administration d'un oestrogene et/ou d'un progestatif a base d'eva, procede de preparation et utilisation en therapeutique |
US5780435A (en) * | 1995-12-15 | 1998-07-14 | Praecis Pharmaceuticals Incorporated | Methods for treating prostate cancer with LHRH-R antagonists |
US6156331A (en) * | 1996-02-02 | 2000-12-05 | Alza Corporation | Sustained delivery of an active agent using an implantable system |
US5869081A (en) * | 1996-06-28 | 1999-02-09 | The Population Council | Progesterone vaginal ring for treatment of infertility |
US6139873A (en) * | 1996-07-10 | 2000-10-31 | Cedars-Sinai Medical Center | Combined pharmaceutical estrogen-androgen-progestin |
US5972372A (en) | 1996-07-31 | 1999-10-26 | The Population Council, Inc. | Intravaginal rings with insertable drug-containing core |
US5945128A (en) * | 1996-09-04 | 1999-08-31 | Romano Deghenghi | Process to manufacture implants containing bioactive peptides |
CA2219698C (en) * | 1996-10-31 | 2007-09-04 | Takeda Chemical Industries, Ltd. | Sustained-release preparation |
US5985861A (en) * | 1996-11-04 | 1999-11-16 | Columbia Laboratories, Inc. | Progesterone for treating or reducing ischemia |
JPH10138432A (ja) * | 1996-11-14 | 1998-05-26 | Teijin Ltd | 磁気テープ用二軸配向積層ポリエステルフィルム |
US5968895A (en) * | 1996-12-11 | 1999-10-19 | Praecis Pharmaceuticals, Inc. | Pharmaceutical formulations for sustained drug delivery |
JPH10279499A (ja) * | 1997-04-04 | 1998-10-20 | Takeda Chem Ind Ltd | 子宮粘膜適用製剤 |
IL123813A0 (en) | 1997-04-11 | 1998-10-30 | Akzo Nobel Nv | Drug delivery system for two or more active substances |
TW577759B (en) * | 1997-04-18 | 2004-03-01 | Ipsen Pharma Biotech | Sustained release compositions in the form of microcapsules or implants and the process for their preparation |
US6416779B1 (en) * | 1997-06-11 | 2002-07-09 | Umd, Inc. | Device and method for intravaginal or transvaginal treatment of fungal, bacterial, viral or parasitic infections |
US6905701B2 (en) * | 1997-06-11 | 2005-06-14 | Umd, Inc. | Formulations for transmucosal vaginal delivery of bisphosphonates |
US6197327B1 (en) * | 1997-06-11 | 2001-03-06 | Umd, Inc. | Device and method for treatment of dysmenorrhea |
US6572874B1 (en) * | 1998-05-15 | 2003-06-03 | Umd, Inc. | Vaginal delivery of bisphosphonates |
US5941844A (en) * | 1997-11-17 | 1999-08-24 | Alza Corporation | Method and device for controlling mammalian reproductive cycle |
KR100568917B1 (ko) * | 1997-12-30 | 2006-04-07 | 알자 코포레이션 | 멤브레인 플러그를 갖는 익제 전달장치 |
USD442688S1 (en) * | 1998-01-28 | 2001-05-22 | N.V. Organon | Vaginal ring applicator |
EP0940678A1 (en) | 1998-03-02 | 1999-09-08 | Akzo Nobel N.V. | Analytical test device |
US5945123A (en) * | 1998-04-02 | 1999-08-31 | K-V Pharmaceutical Company | Maximizing effectiveness of substances used to improve health and well being |
US6218367B1 (en) * | 1998-09-15 | 2001-04-17 | Organomed Corporation | Paclitaxel-carbohydrate conjugates: design, synthesis and biological evaluations |
US6143314A (en) * | 1998-10-28 | 2000-11-07 | Atrix Laboratories, Inc. | Controlled release liquid delivery compositions with low initial drug burst |
US6159491A (en) * | 1999-02-12 | 2000-12-12 | Biovector Technologies, Inc. | Prolonged release bioadhesive vaginal gel dosage form |
EP1142959A4 (en) | 1999-08-25 | 2002-11-06 | Dai Ichi Kogyo Seiyaku Co Ltd | MOLDED RESIN COMPOSITION IN GEL FORM, CHEMICAL PRODUCT IN PACKAGED VOLATILE GEL, AND PROCESS FOR PRODUCING THE SAME. |
WO2001026648A1 (fr) | 1999-10-13 | 2001-04-19 | Senju Pharmaceutical Co., Ltd. | Preparation d'adhesif a usage ophtalmique pour l'absorption par voie percutanee |
US6264981B1 (en) * | 1999-10-27 | 2001-07-24 | Anesta Corporation | Oral transmucosal drug dosage using solid solution |
GB0102342D0 (en) * | 2001-01-30 | 2001-03-14 | Smithkline Beecham Plc | Pharmaceutical formulation |
US6687178B1 (en) * | 2001-02-23 | 2004-02-03 | Western Digital (Fremont), Inc. | Temperature dependent write current source for magnetic tunnel junction MRAM |
-
2004
- 2004-04-29 DE DE602004026173T patent/DE602004026173D1/de not_active Expired - Lifetime
- 2004-04-29 AT AT04760436T patent/ATE461681T1/de not_active IP Right Cessation
- 2004-04-29 EP EP04760436A patent/EP1620060B1/en not_active Expired - Lifetime
- 2004-04-29 JP JP2006513416A patent/JP4898431B2/ja not_active Expired - Lifetime
- 2004-04-29 AU AU2004233997A patent/AU2004233997C1/en not_active Expired
- 2004-04-29 CA CA2523859A patent/CA2523859C/en not_active Expired - Lifetime
- 2004-04-29 WO PCT/US2004/013172 patent/WO2004096151A2/en active Application Filing
- 2004-04-29 US US10/835,414 patent/US7833545B2/en active Active
-
2008
- 2008-05-22 US US12/125,629 patent/US20090060982A1/en not_active Abandoned
- 2008-05-22 US US12/125,581 patent/US7883718B2/en active Active
- 2008-05-22 US US12/125,606 patent/US20080286339A1/en not_active Abandoned
- 2008-05-22 US US12/125,593 patent/US7829112B2/en active Active
- 2008-05-22 US US12/125,571 patent/US7838024B2/en not_active Expired - Lifetime
-
2011
- 2011-01-14 US US13/007,222 patent/US20120202742A1/en not_active Abandoned
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5164793A (ja) * | 1974-10-18 | 1976-06-04 | Schering Ag | |
JPS61106508A (ja) * | 1984-10-12 | 1986-05-24 | アクゾ・エヌ・ヴエー | 2種以上の活性物質の放出システム |
WO1997002015A1 (en) * | 1995-07-04 | 1997-01-23 | Akzo Nobel N.V. | Ring-shaped devices |
JPH119699A (ja) * | 1997-06-24 | 1999-01-19 | Hoechst Marion Roussel | 腟内薬物供給装置 |
JP2002513690A (ja) * | 1998-05-01 | 2002-05-14 | エフイ−アイ エンタープライジズ,リミティド | 制御放出デバイスの射出成形製造方法 |
JP2003507109A (ja) * | 1999-08-26 | 2003-02-25 | エンハンス ファーマシューティカルズ,インコーポレイティド | 女性の頸管部を麻酔するための器具及び方法 |
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CA2523859A1 (en) | 2004-11-11 |
AU2004233997B2 (en) | 2009-12-17 |
AU2004233997A1 (en) | 2004-11-11 |
EP1620060B1 (en) | 2010-03-24 |
AU2004233997B8 (en) | 2010-01-14 |
ATE461681T1 (de) | 2010-04-15 |
CA2523859C (en) | 2011-08-02 |
US20070196433A1 (en) | 2007-08-23 |
US20080286339A1 (en) | 2008-11-20 |
US20080286322A1 (en) | 2008-11-20 |
US7838024B2 (en) | 2010-11-23 |
AU2004233997C1 (en) | 2014-01-30 |
WO2004096151A2 (en) | 2004-11-11 |
US20080248017A1 (en) | 2008-10-09 |
EP1620060A4 (en) | 2007-11-28 |
US20120202742A1 (en) | 2012-08-09 |
AU2004233997B9 (en) | 2013-01-10 |
DE602004026173D1 (de) | 2010-05-06 |
US7883718B2 (en) | 2011-02-08 |
US20090060982A1 (en) | 2009-03-05 |
US7833545B2 (en) | 2010-11-16 |
EP1620060A2 (en) | 2006-02-01 |
US20090274654A1 (en) | 2009-11-05 |
WO2004096151A3 (en) | 2006-05-11 |
US7829112B2 (en) | 2010-11-09 |
JP2007525461A (ja) | 2007-09-06 |
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