JP5642691B2 - ジアセレインを含有する医薬組成物 - Google Patents
ジアセレインを含有する医薬組成物 Download PDFInfo
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- JP5642691B2 JP5642691B2 JP2011534697A JP2011534697A JP5642691B2 JP 5642691 B2 JP5642691 B2 JP 5642691B2 JP 2011534697 A JP2011534697 A JP 2011534697A JP 2011534697 A JP2011534697 A JP 2011534697A JP 5642691 B2 JP5642691 B2 JP 5642691B2
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- diacerein
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Description
ジアセレイン(4,5−ビス(アセチルオキシ)−9,10−ジオキソ−2−アントラセンカルボン酸)は、高度に純化されたアントラキノン誘導体である。それはインターロイキン−1活性を阻害することが知られており、いくつかの国で変形性関節症治療用遅効性薬剤(Symptomatic Slow−Acting Drug in Osteoarthritis (SYSADOA))として認可されている。
本発明の目的は、炎症性疾患、自己免疫疾患またはそれらの合併症、例えば骨関節炎、I型/II型糖尿病または糖尿病性腎症を治療するためのジアセレインの1日1回投与用の制御放出製剤であって、有害な副作用が減少した制御放出製剤を提供することである。より具体的には、本発明のジアセレインの1日1回投与用の制御放出製剤は、膜制御製剤、マトリックス製剤または浸透圧ポンプ製剤であってよい。好ましい実施態様では、本発明のジアセレインの制御放出製剤は、市販の即時放出(IR)製剤と比較した場合にバイオアベイラビリティの増加をさらに提供することができる。より具体的には、該方法はジアセレインに起因する下痢の有害な副作用を減少させる。
ジアセレインの主要な有害副作用は、下痢および軟便である。インビトロおよびインビボ研究は、非吸収性のジアセレインが結腸内でレインに代謝されることを示している。レインは、ヒスタミンまたはセロトニンの放出ではなく、粘膜下ニューロンの興奮ならびにアセチルコリンおよび内因性プロスタグランジンの放出による塩素イオン分泌の活性化を通して、結腸内で緩下剤効果を誘発する。
1つの実施態様では、本発明の製剤は、ジアセレインと結腸粘膜の直接接触を最小化するために薬物コアをGI環境から分離することができる制御放出フィルムによって囲まれていてよい。
別の実施態様では、本発明の製剤は、制御放出マトリックスを形成するために、制御放出物質、例えば親水性ポリマー、疎水性ポリマーまたはワックスを含有してよい。ジアセレインはマトリックス中に捕捉され、ジアセレインと結腸粘膜の接触を回避する。
別の実施態様では、ジアセレインの放出速度は浸透圧ポンプシステムによって制御することができる。薬物含有コアは、水のみを透過させる半透膜によって覆われている。外部の液体(aqueous fluids)が浸透圧勾配によってコア内に半透膜を通じて吸収される場合、薬物は膜内の通路から放出される。該通路は穴(hole)、開口部(aperture)、開口部(orifice)、穴(bore)、弱くなった部分、または腐食してジアセレインの放出のための通路を形成する腐食しうる成分(erodible element)であってよい。
別の実施態様では、本発明の制御放出製剤は、市販の即時放出製剤(例えば、アルトロダール(Arthrodar(登録商標))、TRB Pharma s.a.)と比較した場合に、ジアセレインのバイオアベイラビリティの増加をさらに提供することができる。バイオアベイラビリティの増加は、有害な副作用を減少させるのに有益でありうると考えられている。バイオアベイラビリティを増加させる方法は、(a)界面活性剤の添加;(b)固体分散体(solid dispersion)の形成;(c)微粒子化またはナノ化(nanonized)ジアセレインの利用、(d)酸性化剤または緩衝剤の添加、および(e)シクロデキストリンとの錯体形成を含み、これらに限定されない。
本発明のジアセレインの医薬組成物は、炎症性疾患または自己免疫疾患、例えば関節リウマチ、骨関節炎、骨粗鬆症、炎症性腸疾患、例えば潰瘍性大腸炎およびクローン病、潰瘍性大腸炎、多発性硬化症、歯周炎、歯肉炎、移植片対宿主反応、乾癬、強皮症、アトピー性皮膚炎、喘息、全身性エリテマトーデス(SLE)、腎障害ならびに慢性閉塞性肺疾患(COPD)を治療するために用いることができる。治療されうる皮膚状態は上記の状態、ならびに乾癬性関節炎、表皮水疱症、アトピー性皮膚炎および血管炎も含む。抗血管形成活性は、加齢性黄斑変性症および癌などの状態の治療を可能にしうる。好ましくは、本発明の医薬組成物は、骨関節炎、I型/II型糖尿病または糖尿病性腎症を治療するために用いられ、かつ、有害な副作用が少ない。
本発明の50mgのジアセレイン製剤は、定常状態に達したヒト患者に経口投与された場合に、ヒトの中で1mg/L以上の濃度のレインの血漿濃度を12時間以上維持し;
本発明の100mgのジアセレイン製剤は、定常状態に達したヒト患者に経口投与された場合に、ヒトの中で2mg/L以上の濃度のレインの血漿濃度を12時間以上維持し;
本発明の150mgのジアセレイン製剤は、定常状態に達したヒト患者に経口投与された場合に、ヒトの中で3mg/L以上の濃度のレインの血漿濃度を12時間以上維持し;
かつ、
本発明の200mgのジアセレイン製剤は、定常状態に達したヒト患者に経口投与された場合に、ヒトの中で4mg/L以上の濃度のレインの血漿濃度を12時間以上維持する。
本発明の制御放出製剤は、別の有効成分、例えばアンジオテンシンII受容体遮断薬(ARBs)、アンジオテンシン変換酵素阻害剤(ACEIs)、血糖降下薬またはNSAIDsをさらに含んでよい。より具体的には、本発明のジアセレインの製剤は、糖尿病性腎症を治療するためのアンジオテンシン変換酵素阻害剤もしくはアンジオテンシンII受容体遮断薬、I型/II型糖尿病を治療するための血糖降下薬、または骨関節炎を治療するための非ステロイド性抗炎症薬(NSAID)をさらに含有してよい。
実施例1
固体分散体の製造
代表的な固体分散体の成分の許容範囲を第3表に示す。
ジアセレインを適切な有機溶媒に溶かすことにより、薬物溶液を形成してよい。次いで、担体、例えば親水性ポリマー、疎水性ポリマー、界面活性剤、水溶性賦形剤、もしくはワックス、または上記担体の組み合わせを薬物溶液に溶解または分散する。固体分散体を得るために上記溶液の噴霧乾燥が用いられてよく、または溶液は流動床を用いて適切な賦形剤(第二担体として機能する水溶性物質)上にコーティングされてよい。
シクロデキストリンとの錯体形成
シクロデキストリンとの代表的な錯体の成分の許容範囲を第4表に示す。
シクロデキストリンの水溶液を様々なパーセンテージで製造してよい。ジアセレインを上記溶液に加え、飽和溶液を得る。溶液を少なくとも72時間攪拌し、次いで全ての不溶解物質が沈殿するまで静置する。上清溶液を濾過し、オーブン、噴霧乾燥もしくは凍結乾燥によって乾燥し、または流動床を用いて適切な賦形剤(希釈剤として機能する)上にコーティングする。
マトリックスシステム(錠剤)
代表的な錠剤マトリックスシステムの成分の許容範囲を第5表に示す。
API部分は上記実施例に記載されているように製造する。ジアセレインAPI部分を制御放出物質と物理的に混合または顆粒化し、次いで混合物を圧縮してマトリックス錠剤を得る。任意に、酸性化剤または緩衝剤が錠剤製剤に含まれていてよい。
マトリックスシステム(錠剤)
2つの代表的なマトリックス錠剤製剤を第6表に示す。
顆粒剤Iの固体分散体は実施例1に記載されているように製造した。顆粒剤IIは湿式造粒法によって製造した。顆粒剤IおよびIIを滑沢剤と混合し、次いで圧縮してマトリックス錠剤を得た。
マトリックスシステム(錠剤)
さらなる代表的なマトリックス錠剤製剤を第7表に示す。
ジアセレイン、HPMC、マンニトール、クレモフォールおよび酒石酸を湿式造粒法によって顆粒化した。顆粒剤を滑沢剤と混合し、次いで圧縮した。
マトリックスシステム(ビーズ)
代表的なビーズマトリックスシステムの成分の許容範囲を第8表に示す。
ジアセレインを適切な有機溶媒に溶かし、薬物溶液を形成する。次いで、担体、例えば親水性ポリマー、疎水性ポリマー、界面活性剤、水溶性賦形剤、ワックスまたは上記担体の組み合わせを薬物溶液に溶解または分散する。流動床によって溶液を種上に噴霧し、マトリックスビーズを得る。次いで、ビーズを適切な大きさのカプセル剤にカプセル化する。
マトリックスシステム(ビーズ)
代表的なビーズマトリックス製剤を第9表に示す。
膜制御システム(錠剤)
代表的な膜制御錠剤製剤の成分の許容範囲を第10表に示す。
膜制御システム(錠剤)
3つの代表的な膜制御錠剤製剤を第11表に示す。
コア錠剤は、上記実施例に記載された固体分散法、または湿式造粒法によって製造した。次いで、コア錠剤をシールコートおよび持続放出コートでコーティングした。
膜制御システム(ビーズ)
代表的なビーズ膜制御システムの成分の許容範囲を第12表に示す。
ジアセレインを適切な有機溶媒に溶かし、薬物溶液を形成する。次いで、担体、例えば親水性ポリマー、疎水性ポリマー、界面活性剤、水溶性賦形剤、ワックスまたは上記担体の組み合わせを薬物溶液に溶解または分散する。流動床によって溶液を種上に噴霧し、コアビーズを得る。制御放出物質を細孔形成剤および可塑剤と共に有機溶媒に溶解し、コアビーズ用のコーティング溶液を得る。次いで、ビーズを制御放出膜でコーティングする。次いで、持続放出ビーズを適切な大きさのカプセル剤にカプセル化する。
膜制御システム(ビーズ)
代表的なビーズ膜制御システム製剤を第13表に示す。
浸透圧ポンプ(プッシュプル)システム
代表的な浸透圧ポンプ(プッシュプル)製剤の成分の許容範囲を第14表に示す。
浸透圧ポンプ(プッシュプル)システム
代表的なプッシュプル浸透圧ポンプ製剤を第15表に示す。
浸透圧ポンプシステム(インサイチュホール(in-situ hole))
代表的な浸透圧ポンプ(インサイチュホール)製剤の成分の許容範囲を第16表に示す。
API部分は上記実施例に記載されているように製造する。ジアセレインAPI部分をPEO、結合剤、浸透圧剤および抗酸化剤と物理的に混合または顆粒化する。混合物を滑沢剤と混合し、次いで圧縮してコア錠剤を得る。任意に、酸性化剤または緩衝剤がコア錠剤製剤に含まれていてよい。シールコーティング溶液は親水性ポリマー、浸透圧剤および滑沢剤を水に溶解または分散することによって製造し、次いで、コーティング溶液をコーター内でコア錠剤上に噴霧する。半透性コーティングはセルロースアセテートを細孔形成剤および可塑剤と共に有機溶媒に溶解し、次いでコーティング溶液をコーター内でシールコートされた錠剤上に噴霧することによって製造する。剤形の溶解中に少なくとも1つの通路が形成される。
浸透圧ポンプシステム(インサイチュホール)
代表的な浸透圧ポンプ(インサイチュホール)製剤を第17表に示す。
持続放出製剤(マトリックスシステム)
代表的なマトリックス持続放出製剤の成分の許容範囲を第18表に示す。
本発明の持続放出製剤は直接圧縮、圧縮造粒、湿式造粒法または押出球形化(extrusion and spheronization)によって製造することができる。
代表的なマトリックス持続放出錠剤製剤を第17表に示す。
膜制御システム
代表的な持続放出膜制御システム製剤の成分の許容範囲を第20表に示す。
コア錠剤は直接圧縮によって製造し、圧縮造粒を用い、または湿式造粒法を用いる。コアビーズは流動床造粒によって製造する。
膜制御システム用ビーズ製剤
代表的な膜制御システム用ビーズ製剤を第21表に示す。
ヒドロゲルマトリックス製剤
代表的なヒドロゲルマトリックス製剤を第22表に示す。
ヒドロゲルマトリックス製剤についての溶解データ
実施例20のジアセレインヒドロゲルマトリックス製剤について溶解試験を行った。溶解試験は、いわゆる「バスケット」法および/または「パドル・アンド・シンカー」法に従って行った。
「バスケット法」は、USP装置1を用いる。それは通常100rpm(毎分回転数)で運転され、通常ビーズ製剤用に用いられる。FDAガイダンスは「バスケット」法の説明を含んでいる。
「パドル・アンド・シンカー」法は、USP装置2を用いる。それは通常50rpmで運転される。「シンカー」は、カプセル剤を溶解容器に入れる前にカプセル剤を包むいくつかのワイアーであってよい。FDAガイダンスは「パドル・アンド・シンカー」法の説明を含んでいる。
持続放出製剤
代表的な持続放出製剤を下記の第25〜29表に示す。第25表および第26表は、製剤DIAC−3002、DIAC−3004、DIAC−3006、DIAC−3007、DIAC−3008、DIAC−3010、DIAC−3011およびDIAC−3012の活性層の組成を示している;第27表および第28表はこれらの製剤の持続放出(SR)フィルム層の組成を示している;第29表は製剤DIAC−3007、DIAC−3008、DIAC−3011およびDIAC−3012の遅延放出(DR)フィルム層の組成を示している(他の製剤はDRフィルム層を含有しない)。
持続放出製剤用の溶解データ
実施例22のジアセレイン持続放出製剤について溶解試験を行った。溶解試験は実施例21に記載された「バスケット」法および/または「パドル・アンド・シンカー」法に従って行った。
Claims (20)
- 炎症性疾患、自己免疫疾患またはそれらの合併症を治療するためのジアセレインの1日1回投与用の制御放出製剤であって、有害な副作用が減少した制御放出製剤であり、活性層、持続放出フィルム層、および遅延放出フィルム層を含み、該持続放出フィルム層がエチルセルロースポリマー、ポビドン、クエン酸トリエチルおよびタルクを含み、該遅延放出フィルム層がオイドラギット(Eudragit(登録商標))ポリマー、クエン酸トリエチルおよびタルクを含む、制御放出製剤。
- 該製剤が膜制御製剤、マトリックス製剤または浸透圧ポンプ製剤である、請求項1記載の制御放出製剤。
- 該製剤が、即時放出製剤と比較した場合にバイオアベイラビリティの増加を提供する、請求項2記載の制御放出製剤。
- 該製剤が界面活性剤、酸性化剤または緩衝剤を含む、請求項3記載の制御放出製剤。
- ジアセレインの粒径が2000μm未満である、請求項3記載の制御放出製剤。
- ジアセレインが固体担体中に非晶質状態として存在している、請求項3記載の制御放出製剤。
- ジアセレインがシクロデキストリンと錯体を形成している、請求項3記載の制御放出製剤。
- ジアセレインが結晶性である、請求項3記載の制御放出製剤。
- 50mgのジアセレインを含有する製剤が、定常状態に達したヒト患者に経口投与された場合に、ヒトの中で1mg/L以上の濃度のレインの血漿濃度を12時間以上維持する、請求項1記載の制御放出製剤。
- 100mgのジアセレインを含有する製剤が、定常状態に達したヒト患者に経口投与された場合に、ヒトの中で2mg/L以上の濃度のレインの血漿濃度を12時間以上維持する、請求項1記載の制御放出製剤。
- 150mgのジアセレインを含有する製剤が、定常状態に達したヒト患者に経口投与された場合に、ヒトの中で3mg/L以上の濃度のレインの血漿濃度を12時間以上維持する、請求項1記載の制御放出製剤。
- 200mgのジアセレインを含有する製剤が、定常状態に達したヒト患者に経口投与された場合に、ヒトの中で4mg/L以上の濃度のレインの血漿濃度を12時間以上維持する、請求項1記載の制御放出製剤。
- 前述の有害な副作用が下痢である、請求項1記載の制御放出製剤。
- I型/II型糖尿病または骨関節炎を治療するための、請求項1記載の制御放出製剤。
- I型/II型糖尿病からの合併症を治療するための、請求項1記載の制御放出製剤。
- I型/II型糖尿病からの合併症が腎障害、網膜症、神経障害または足部潰瘍である、請求項15記載の制御放出製剤。
- 第一有効成分のジアセレインおよび炎症性疾患、自己免疫疾患またはそれらの合併症を治療するための第二有効成分を含む、請求項1記載の1日1回投与用の制御放出製剤。
- 前述の第二有効成分がアンジオテンシン変換酵素阻害剤、アンジオテンシンII受容体遮断薬、血糖降下薬、または非ステロイド性抗炎症薬である、請求項17記載の制御放出製剤。
- 該活性層が40.0重量%〜50.0重量%の微結晶セルロース、20.0重量%〜30.0重量%のジアセレイン、2.0重量%〜5.0重量%のポビドンおよび20.0重量%〜30.0重量%のマンニトールを含む、請求項1記載の制御放出製剤。
- 該活性層が50.0重量%の微結晶セルロース、25.0重量%のジアセレイン、2.0重量%のポビドンおよび23.0重量%のマンニトールを含む、請求項1記載の制御放出製剤。
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US10893108P | 2008-10-28 | 2008-10-28 | |
US61/108,931 | 2008-10-28 | ||
PCT/US2009/062302 WO2010051296A1 (en) | 2008-10-28 | 2009-10-28 | Pharmaceutical compositions containing diacerein |
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JP2012506911A JP2012506911A (ja) | 2012-03-22 |
JP2012506911A5 JP2012506911A5 (ja) | 2012-12-06 |
JP5642691B2 true JP5642691B2 (ja) | 2014-12-17 |
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US (2) | US20100104651A1 (ja) |
EP (1) | EP2349289B1 (ja) |
JP (1) | JP5642691B2 (ja) |
KR (1) | KR101718347B1 (ja) |
CN (1) | CN102202673B (ja) |
AR (1) | AR073918A1 (ja) |
AU (1) | AU2009308958B2 (ja) |
BR (1) | BRPI0920255A2 (ja) |
CA (1) | CA2741846C (ja) |
ES (1) | ES2585904T3 (ja) |
IL (1) | IL212483A (ja) |
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NZ (1) | NZ592376A (ja) |
PA (1) | PA8846801A1 (ja) |
RU (1) | RU2542461C2 (ja) |
SA (1) | SA109300644B1 (ja) |
TW (1) | TWI473610B (ja) |
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BR112012024936A2 (pt) * | 2010-04-08 | 2015-09-15 | Twi Biotechnology Inc | uso de diacereína ou de um sal, um análogo, uma prodroga, ou um metabólito ativo farmaceuticamente aceitável do mesmo |
CN101822660B (zh) * | 2010-05-13 | 2013-07-10 | 中国人民解放军肾脏病研究所 | 大黄酸类化合物或其盐在制备预防和治疗胰岛β细胞功能衰退药物中的应用 |
RU2603050C2 (ru) * | 2011-03-11 | 2016-11-20 | ТиДаблЮАй БАЙОТЕКНОЛОДЖИ, ИНК. | Способы и композиции для лечения гиперурикемии и метаболических нарушений, связанных с гиперурикемией |
CN102743370B (zh) * | 2011-06-27 | 2013-05-15 | 王子厚 | 双醋瑞因的用途 |
US9757424B2 (en) | 2011-09-27 | 2017-09-12 | Biomed Valley Discoveries, Inc. | Compositions and methods of treating gliomas |
WO2013100881A2 (en) * | 2011-12-27 | 2013-07-04 | Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi | Combined pharmaceutical formulation containing diacerein |
EA201491039A1 (ru) * | 2011-12-27 | 2015-02-27 | Сановел Илач Санайи Ве Тиджарет Аноним Ширкети | Комбинации диацереина и нестероидных противовоспалительных лекарственных средств |
CN102871982B (zh) * | 2012-10-16 | 2014-09-10 | 中国科学院上海药物研究所 | 一种药物渗透泵制剂 |
WO2014153241A1 (en) | 2013-03-14 | 2014-09-25 | The Regents Of The University Of Michigan | Treatment of staphylococcal disorders |
MX2017013489A (es) * | 2015-04-20 | 2018-05-22 | Twi Biotechnology Inc | Formulaciones que contienen diacereina y metodos para la reduccion de los niveles en sangre de acido urico usando los mismos. |
US10512625B2 (en) * | 2015-07-01 | 2019-12-24 | Twi Biotechnology, Inc. | Diacerein or rhein topical formulations and uses thereof |
US10154984B2 (en) * | 2015-07-01 | 2018-12-18 | Twi Biotechnology, Inc. | Diacerein or Rhein topical formulations and uses thereof |
US9744131B2 (en) * | 2015-07-01 | 2017-08-29 | Twi Biotechnology, Inc. | Diacerein or rhein topical formulations and uses thereof |
TWI743047B (zh) * | 2015-08-17 | 2021-10-21 | 安成生物科技股份有限公司 | 使用雙醋瑞因或其類似物抑制asc表現、nlrp3表現、以及/或nlrp3發炎體複合物的形成之方法 |
JP7084930B2 (ja) * | 2017-01-18 | 2022-06-15 | タイレックス, インコーポレーテッド | 炎症性腸疾患及び腸管大腸炎を処置するのに使用するための組成物 |
WO2018136706A1 (en) | 2017-01-19 | 2018-07-26 | Twi Biotechnology, Inc. | Methods and pharmaceutical compositions for preventing or treating immunoinflammatory dermal disorders |
CN107929264B (zh) * | 2017-12-04 | 2020-04-24 | 广东药科大学 | 双醋瑞因缓释微球及其制备方法 |
KR102075724B1 (ko) * | 2018-09-14 | 2020-02-10 | 한국원자력의학원 | 디아세레인을 유효성분으로 포함하는 항체의 종양 침투력 증진용 조성물 및 이의 용도 |
CN117017959A (zh) | 2018-11-14 | 2023-11-10 | 珠海岐微生物科技有限公司 | 用于眼内疾病或病症的动物模型、筛选方法和治疗方法 |
CN110787157A (zh) * | 2019-11-27 | 2020-02-14 | 中南民族大学 | 双醋瑞因在用于舒张预收缩的气管平滑肌及治疗哮喘中的应用 |
CN113440503B (zh) * | 2021-07-02 | 2022-03-18 | 温州医科大学附属口腔医院 | 超长效可控缓释介孔-透明质酸杂化靶向抗菌纳米材料及其制备方法、用途 |
CN115227664A (zh) * | 2022-06-27 | 2022-10-25 | 苏州中化药品工业有限公司 | 一种双醋瑞因胶囊及其制备方法与应用 |
WO2024200722A1 (en) * | 2023-03-28 | 2024-10-03 | Tillotts Pharma Ag | Solid oral dosage form comprising antibodies for sustained release in the lower gastrointestinal tract |
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US5225192A (en) * | 1988-10-17 | 1993-07-06 | Vectorpharma International S.P.A. | Poorly soluble medicaments supported on polymer substances in a form suitable for increasing their dissolving rate |
US5569469A (en) * | 1984-10-16 | 1996-10-29 | Vectorpharma International, S.P.A. | Poorly soluble medicaments supported on polymer substances in a form suitable for increasing their dissolving rate |
IT1197316B (it) * | 1986-10-01 | 1988-11-30 | Proter Spa | Formulazione galenica ad uso orale di derivati della reina a lento rilascio per impiego terapeutico |
IT1230566B (it) * | 1988-10-17 | 1991-10-28 | Vectorpharma Int | Farmaci poco solubili supportati su sostanze polimeriche in forma atta all'aumento della velocita' di dissoluzione |
IT1241417B (it) * | 1990-03-06 | 1994-01-14 | Vectorpharma Int | Composizioni terapeutiche a rilascio controllato di farmaci supportatisu polimeri reticolati e rivestiti con film polimerici,e loro processodi preparazione |
IT1255522B (it) * | 1992-09-24 | 1995-11-09 | Ubaldo Conte | Compressa per impiego terapeutico atta a cedere una o piu' sostanze attive con differenti velocita' |
US5840881A (en) * | 1992-11-27 | 1998-11-24 | Takeda Chemical Industries, Ltd. | Composition containing a water-insoluble or slightly water-soluble compound with enhanced water-solubility |
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NZ530956A (en) * | 2001-08-25 | 2005-08-26 | Arakis Ltd | Diacerin, in combination with other therapies, for the treatment of renal impairment and systemic lupus erythematosus (SLE) |
FR2842738B1 (fr) * | 2002-07-23 | 2006-02-10 | Negma Lerads | Utilisation d'une rheine pour la preparation d'un medicament pour le traitement de l'inflammation chronique, la prevention et le traitement du rejet des transplantations d'organes et de tissus |
US20040186105A1 (en) * | 2002-08-30 | 2004-09-23 | Allenspach Carl T. | Pharmaceutical composition exhibiting consistent drug release profile |
AU2003230189A1 (en) * | 2003-01-29 | 2004-08-23 | Nitin Bhalachandra Dharmadhikari | Oral controlled release pharmaceutical composition containing metaxalone as active agent |
MXPA04009698A (es) * | 2004-10-04 | 2006-04-05 | Maria Elena Garcia Armenta | Formulaciones farmaceuticas solidas conteniendo diacereina y meloxicam. |
CN1748675A (zh) * | 2005-07-11 | 2006-03-22 | 丛晓东 | 大黄酸类化合物的复合物及制备方法与治疗糖尿病的应用 |
US8158152B2 (en) * | 2005-11-18 | 2012-04-17 | Scidose Llc | Lyophilization process and products obtained thereby |
CN100475201C (zh) * | 2007-03-19 | 2009-04-08 | 上海慈瑞医药科技有限公司 | 二乙酰大黄酸缓释片的制备方法 |
CA2926563A1 (en) * | 2007-09-27 | 2009-04-02 | Wockhardt Research Centre | Pharmaceutical compositions of rhein or diacerein |
WO2009048940A2 (en) * | 2007-10-08 | 2009-04-16 | Dr. Reddy's Laboratories Ltd. | Diacerein pharmaceutical formulations |
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2009
- 2009-10-07 TW TW98134006A patent/TWI473610B/zh not_active IP Right Cessation
- 2009-10-22 AR ARP090104059A patent/AR073918A1/es not_active Application Discontinuation
- 2009-10-27 SA SA109300644A patent/SA109300644B1/ar unknown
- 2009-10-28 WO PCT/US2009/062302 patent/WO2010051296A1/en active Application Filing
- 2009-10-28 RU RU2011121609/15A patent/RU2542461C2/ru not_active IP Right Cessation
- 2009-10-28 US US12/607,251 patent/US20100104651A1/en not_active Abandoned
- 2009-10-28 EP EP09824084.9A patent/EP2349289B1/en not_active Not-in-force
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- 2009-10-28 JP JP2011534697A patent/JP5642691B2/ja not_active Expired - Fee Related
- 2009-10-28 KR KR1020117012172A patent/KR101718347B1/ko active IP Right Grant
- 2009-10-28 CN CN2009801431098A patent/CN102202673B/zh not_active Expired - Fee Related
- 2009-10-28 PA PA20098846801A patent/PA8846801A1/es unknown
- 2009-10-28 ES ES09824084.9T patent/ES2585904T3/es active Active
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Also Published As
Publication number | Publication date |
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EP2349289A1 (en) | 2011-08-03 |
JP2012506911A (ja) | 2012-03-22 |
UY32204A (es) | 2010-05-31 |
US20130156857A1 (en) | 2013-06-20 |
US20100104651A1 (en) | 2010-04-29 |
AU2009308958B2 (en) | 2016-05-19 |
PA8846801A1 (es) | 2010-05-26 |
EP2349289B1 (en) | 2016-07-13 |
CN102202673A (zh) | 2011-09-28 |
AU2009308958A1 (en) | 2010-05-06 |
CA2741846A1 (en) | 2010-05-06 |
TWI473610B (zh) | 2015-02-21 |
AR073918A1 (es) | 2010-12-09 |
NZ592376A (en) | 2012-12-21 |
KR20110081316A (ko) | 2011-07-13 |
ES2585904T3 (es) | 2016-10-10 |
RU2542461C2 (ru) | 2015-02-20 |
CA2741846C (en) | 2018-03-27 |
IL212483A0 (en) | 2011-06-30 |
CN102202673B (zh) | 2013-07-31 |
EP2349289A4 (en) | 2013-12-04 |
RU2011121609A (ru) | 2012-12-10 |
MX2011004395A (es) | 2011-08-03 |
IL212483A (en) | 2017-10-31 |
KR101718347B1 (ko) | 2017-03-21 |
WO2010051296A1 (en) | 2010-05-06 |
BRPI0920255A2 (pt) | 2016-01-05 |
TW201018461A (en) | 2010-05-16 |
SA109300644B1 (ar) | 2014-10-28 |
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