JP6356548B2 - エクセナチドの経口投与用の方法及び組成物 - Google Patents
エクセナチドの経口投与用の方法及び組成物 Download PDFInfo
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- JP6356548B2 JP6356548B2 JP2014181740A JP2014181740A JP6356548B2 JP 6356548 B2 JP6356548 B2 JP 6356548B2 JP 2014181740 A JP2014181740 A JP 2014181740A JP 2014181740 A JP2014181740 A JP 2014181740A JP 6356548 B2 JP6356548 B2 JP 6356548B2
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Description
別の実施形態において、本発明のエクセナチド製剤は、肥満を防ぐのに有用である。別の実施形態において、本発明のエクセナチド製剤は、過剰な脂肪組織を防ぐのに有用である。別の実施形態において、本発明のエクセナチド製剤は、食物摂取量の増加に関連する健康上のリスクを防ぐのに有用である。別の実施形態において、本発明のエクセナチド製剤は、II型糖尿病、心リスクの増大、高血圧、アテローム性動脈硬化、変形性関節症、および、全身麻酔を含む手術の合併症の発生率の増加などの、肥満に関連する疾患を防ぐのに有用である。別の実施形態において、本発明のエクセナチド製剤は、II型糖尿病、心リスクの増大、高血圧、アテローム性動脈硬化、変形性関節症、および、全身麻酔を含む手術の合併症の発生率の増加などの、肥満に関連する疾患を処置するのに有用である。別の実施形態において、本発明のエクセナチド製剤は、II型糖尿病、心リスクの増大、高血圧、アテローム性動脈硬化、変形性関節症、および、全身麻酔を含む手術の合併症の発生率の増加などの、肥満に関連する疾患を進行させるリスクを減らすために有用である。
動物:
重量約9kgのオスのビーグル犬が、以下に記載のすべての実験で用いられた。
材料および実験方法
製剤:
(1)150ミリグラム(mg)のNa‐EDTA(Sigma‐Aldrich,St.Louis,MO)、125mgのダイズトリプシンインヒビター(SBTI;Sigma)、50μgのエクセナチド、および、0.8ミリリットル(ml)の魚油を含有する製剤を用意した。
エクセナチドがプロテアーゼから保護されるとともに十二指腸で吸収されることが可能かどうかを試験するために、製剤1(処置)または3(対照)を、約9kgのビーグル犬の十二指腸に直接投与するか、または、約16kgのブタに内視鏡によって投与した。
材料および実験方法
製剤:
以下の製剤を用意した。
(1)2.5μgの市販のバイエッタを含む注射用製剤
(2)2.5μgのGeneScript(Piscataway,NJ)のバイエッタを含む注射用製剤
(3)150ミリグラム(mg)のNa‐EDTA(Sigma‐Aldrich,St.Louis,MO)、125mgのダイズトリプシンインヒビター(SBTI;Sigma)、50μgのエクセナチド(GeneScript(Piscataway,NJ))、および、0.8ミリリットル(ml)の魚油を含有する経口製剤
(4)150ミリグラム(mg)のNa‐EDTA(Sigma‐Aldrich,St.Louis,MO)、125mgのダイズトリプシンインヒビター(SBTI;Sigma)、および、0.8ミリリットル(ml)の魚油を含有する経口製剤
(5)150ミリグラム(mg)のNa‐EDTA(Sigma‐Aldrich,St.Louis,MO)、125mgのダイズトリプシンインヒビター(SBTI;Sigma)、50μgのエクセナチド(GeneScript(Piscataway,NJ))、および、0.8ミリリットル(ml)の魚油を含有するハードゼラチンカプセル(直腸)
エクセナチドを含む経口または直腸剤形の効果を試験するために、経口または直腸製剤を市販の注射用製剤と比較した。
材料および実験方法
研究は平均重量約10kgの4匹のビーグル犬で行われた。すべてのイヌは空腸内にカニューレを挿入され、薬物は空腸を介して投与された。一晩絶食後、これらのイヌに、様々な量の経口GLP‐1アナログまたはこのアナログの皮下注射を与えた。経口グルコース負荷後のグルコース可動域への作用を測定するために、GLP‐1アナログの吸収を評価した。対照実験は、GLP‐1アナログの投与を含まない経口投与からなる。経口投与と経口グルコース負荷との間の間隔は、30分であった。主要有効性エンドポイントは、150分以上の間隔における事前の経口ブドウ糖負荷試験(pre‐OGTT)のグルコースレベル以上のグルコース可動域であった(曲線(AUC)0−150分下の増加領域)。
GLP‐1アナログの空腸への直接的な点滴注入は、グルコース負荷後のグルコース可動域を著しく(ss)抑制した(プラシーボとの比較、および、別のグループのなかでの比較の双方)。
核錠の調製:
エクセナチドおよびプロテアーゼインヒビターを含む核錠を、当該技術分野で周知の方法を用いて調製する。
コーティングは、当該技術分野で知られている任意の遅延放出コーティングであってもよい。例えば、コーティングは、以下の成分からなるポリマーであってもよい。
−4mgのEudragit L−100(アクリル酸エステルおよびメタクリル酸エステルのポリマー)
−4mgのタルクNF
−0.4mgのポリエチレングリコール6000NF
Cペプチドのレベルは、観察されるエクセナチドレベルの上昇への、内因性および外因性エクセナチドの相対的な寄与を決定するために、同様に測定される。
Na−EDTA、SBTI、および、エクセナチド、および、魚油の混合物は、核錠または核カプセルで処方され、腸溶コーティングまたはゼラチンコーティングでコーティングされ、ヒト被験体に投与される。被験体の血糖値を先の例に記載の如く周期的に測定する。加えて、被験体の組み換えエクセナチドの血漿レベル、および、その活性を試験する。コーティングされた丸剤は、機能的なエクセナチドを被験体に送達することが示され、エクセナチドは被験体の血糖値を著しく低下させており、活性なエクセナチドが経口投与を介して血流に送達可能であることを示している。様々なタイプの商業的に利用可能な遅延放出コーティングは、どのコーティングがエクセナチドのもっとも優れた送達を提供するのかを決定するために試験され、このコーティングは次の例で使用される。
様々なオメガ3脂肪酸またはオメガ3脂肪酸源(例えば、明細書中に記載のもの)は、本発明の方法および組成物における経口投与後にエクセナチドを保存する能力を比較される。エクセナチド錠剤またはカプセルは、エクセナチドを魚油の代わりに代替的な源と混合するという点を除けば、上記例に記載の如く処方される。オメガ3脂肪酸の最も効果的な源が次の例で用いられる。
様々なプロテアーゼインヒビター(非毒性または許容可能な毒性プロフィールを有するかのいずれか。例えば、明細書に記載の上記のもの)は、本発明の方法および組成物における経口投与後にエクセナチドを保存する能力を比較される。エクセナチド錠剤またはカプセルは、代替的なプロテアーゼインヒビターをDBTIの代わりに用いるという点を除けば、上記例に記載の如く処方される。最適な量を決定するためにプロテアーゼインヒビターの量も変化する。最も効果的なプロテアーゼインヒビター/量が次の例で用いられる。
様々なエンハンサー(明細書に記載の上記のもの)は、本発明の方法および組成物における経口投与後にエクセナチドの吸収を促進する能力を比較される。エクセナチド錠剤またはカプセルは、代替的なエンハンサーをEDTAの代わりに用いるという点を除けば、上記例に記載の如く処方される。最適な量を決定するためにエンハンサーの量も変化する。最も効果的なエンハンサー/量が次の例で用いられる。
様々なタイプおよび量のエクセナチド(明細書に記載の上記のもの)は、本発明の方法および組成物における経口投与後に血糖を制御する能力を比較される。エクセナチド錠剤またはカプセルは、エクセナチドのタイプおよび量が変化するという点を除けば、上記例に記載の如く処方される。最も効果的なタイプ/量のエクセナチドが臨床試験で用いられる。
Claims (13)
- エクセナチドを含む注射用剤形に関連する副作用を低減するための、エクセナチドとプロテアーゼインヒビターとオメガ3脂肪酸とを含む経口又は直腸投与用医薬組成物。
- 前記オメガ3脂肪酸が魚油由来であることを特徴とする請求項1記載の組成物。
- 前記プロテアーゼインヒビターがダイズトリプシンインヒビター(SBTI)、セリンプロテアーゼインヒビター又はトリプシンインヒビターから選択されることを特徴とする請求項1記載の組成物。
- 前記副作用が吐き気又は胃不全麻痺から選択されることを特徴とする請求項1記載の組成物。
- EDTAまたはその塩、及び胆汁酸またはそのアルカリ金属塩からなる群から選択される、腸管粘膜バリアを通過する前記エクセナチドタンパク質の吸収を高める物質をさらに含むことを特徴とする請求項1記載の組成物。
- 前記物質がEDTAまたはその塩であることを特徴とする請求項5記載の組成物。
- 前記物質が胆汁酸またはそのアルカリ金属塩であることを特徴とする請求項5記載の組成物。
- 被験体の胃で前記エクセナチドの消化を抑制するコーティングをさらに含むことを特徴とする請求項1記載の組成物。
- 前記コーティングが腸溶コーティング又はゼラチンコーティングであることを特徴とする請求項8記載の組成物。
- 被験体における真性糖尿病を処置するための請求項1〜9のいずれか一項に記載の組成物。
- 被験体における食物摂取量を減少させるための請求項1〜9のいずれか一項に記載の組成物。
- 被験体における胃運動を減少させるための請求項1〜9のいずれか一項に記載の組成物。
- 被験体における血漿グルカゴンを減少させるための請求項1〜9のいずれか一項に記載の組成物。
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Families Citing this family (52)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2722054B1 (en) * | 2005-09-06 | 2018-03-21 | Oramed Pharmaceuticals Inc. | Methods and compositions for oral administration of proteins |
BRPI0907077A2 (pt) | 2008-03-26 | 2016-07-26 | Oramed Ltd | métodos e composições para administração oral de proteínas |
US20110046053A1 (en) * | 2008-05-05 | 2011-02-24 | Oramed Ltd. | Methods and compositions for oral administration of exenatide |
AU2010279575B2 (en) | 2009-08-03 | 2016-05-05 | Incube Labs, Llc | Swallowable capsule and method for stimulating incretin production within the intestinal tract |
JP2013503862A (ja) | 2009-09-08 | 2013-02-04 | シグネーチャー セラピューティクス,インク. | 酵素切断可能なケトン修飾オピオイドプロドラッグとその任意選択のインヒビターとを含んでなる組成物 |
US8721620B2 (en) | 2009-12-24 | 2014-05-13 | Rani Therapeutics, Llc | Swallowable drug delivery device and methods of drug delivery |
US20110262355A1 (en) | 2010-04-21 | 2011-10-27 | Jenkins Thomas E | Compositions comprising enzyme-cleavable opioid prodrugs and inhibitors thereof |
US8764733B2 (en) | 2010-12-23 | 2014-07-01 | Rani Therapeutics, Llc | Therapeutic agent preparations for delivery into a lumen of the intestinal tract using a swallowable drug delivery device |
US8846040B2 (en) | 2010-12-23 | 2014-09-30 | Rani Therapeutics, Llc | Therapeutic agent preparations comprising etanercept for delivery into a lumen of the intestinal tract using a swallowable drug delivery device |
US9402806B2 (en) | 2010-12-23 | 2016-08-02 | Rani Therapeutics, Llc | Therapeutic agent preparations for delivery into a lumen of the intestinal tract using a swallowable drug delivery device |
US8969293B2 (en) | 2010-12-23 | 2015-03-03 | Rani Therapeutics, Llc | Therapeutic agent preparations comprising exenatide for delivery into a lumen of the intestinal tract using a swallowable drug delivery device |
US8980822B2 (en) | 2010-12-23 | 2015-03-17 | Rani Therapeutics, Llc | Therapeutic agent preparations comprising pramlintide for delivery into a lumen of the intestinal tract using a swallowable drug delivery device |
US9284367B2 (en) | 2010-12-23 | 2016-03-15 | Rani Therapeutics, Llc | Therapeutic agent preparations for delivery into a lumen of the intestinal tract using a swallowable drug delivery device |
US9402807B2 (en) | 2010-12-23 | 2016-08-02 | Rani Therapeutics, Llc | Therapeutic agent preparations for delivery into a lumen of the intestinal tract using a swallowable drug delivery device |
US8734429B2 (en) | 2010-12-23 | 2014-05-27 | Rani Therapeutics, Llc | Device, system and methods for the oral delivery of therapeutic compounds |
US9149617B2 (en) | 2010-12-23 | 2015-10-06 | Rani Therapeutics, Llc | Device, system and methods for the oral delivery of therapeutic compounds |
US8809271B2 (en) | 2010-12-23 | 2014-08-19 | Rani Therapeutics, Llc | Therapeutic agent preparations comprising liraglutide for delivery into a lumen of the intestinal tract using a swallowable drug delivery device |
US9415004B2 (en) | 2010-12-23 | 2016-08-16 | Rani Therapeutics, Llc | Therapeutic agent preparations for delivery into a lumen of the intestinal tract using a swallowable drug delivery device |
US9283179B2 (en) | 2010-12-23 | 2016-03-15 | Rani Therapeutics, Llc | GnRH preparations for delivery into a lumen of the intestinal tract using a swallowable drug delivery device |
US10639272B2 (en) | 2010-12-23 | 2020-05-05 | Rani Therapeutics, Llc | Methods for delivering etanercept preparations into a lumen of the intestinal tract using a swallowable drug delivery device |
US9629799B2 (en) | 2010-12-23 | 2017-04-25 | Rani Therapeutics, Llc | Therapeutic agent preparations for delivery into a lumen of the intestinal tract using a swallowable drug delivery device |
US9861683B2 (en) | 2010-12-23 | 2018-01-09 | Rani Therapeutics, Llc | Therapeutic agent preparations for delivery into a lumen of the intestinal tract using a swallowable drug delivery device |
US8809269B2 (en) | 2010-12-23 | 2014-08-19 | Rani Therapeutics, Llc | Therapeutic agent preparations comprising insulin for delivery into a lumen of the intestinal tract using a swallowable drug delivery device |
US9259386B2 (en) | 2010-12-23 | 2016-02-16 | Rani Therapeutics, Llc | Therapeutic preparation comprising somatostatin or somatostatin analogoue for delivery into a lumen of the intestinal tract using a swallowable drug delivery device |
EP2663187B1 (en) | 2011-01-11 | 2016-06-01 | Signature Therapeutics, Inc. | Compositions comprising enzyme-cleavable oxycodone prodrug |
US20120178813A1 (en) | 2011-01-12 | 2012-07-12 | Thetis Pharmaceuticals Llc | Lipid-lowering antidiabetic agent |
KR20200006177A (ko) | 2011-03-02 | 2020-01-17 | 제롬 쉔타그 | 단독으로 또는 c형 간염 바이러스 감염과 결합되는 간 지방증의 치료를 위한 조성물, 방법 및 진단 |
WO2013003824A1 (en) * | 2011-06-29 | 2013-01-03 | Rani Therapeutics, Llc | Therapeutic agent preparations for delivery into a lumen of the intestinal tract using a swallowable drug delivery device |
DK2800579T3 (da) * | 2012-01-03 | 2017-11-13 | Oramed Ltd | Kapsler indeholdende olie-baserede flydende sammensætninger af kombinerede terapeutiske stoffer til behandling af diabetes |
JP6567827B2 (ja) | 2012-02-01 | 2019-08-28 | オラムド エルティーディー. | プロテアーゼ阻害剤を含有する組成物、該組成物を含む組成物、および、該組成物を製造および使用する方法 |
US8765811B2 (en) | 2012-07-10 | 2014-07-01 | Thetis Pharmaceuticals Llc | Tri-salt form of metformin |
US9382187B2 (en) | 2012-07-10 | 2016-07-05 | Thetis Pharmaceuticals Llc | Tri-salt form of metformin |
ITFI20120259A1 (it) * | 2012-11-27 | 2014-05-28 | Stefano Bacci | Analoghi del glucagon-like peptide (glp-1) per uso topico. |
EP2941267B1 (en) * | 2013-01-03 | 2022-11-16 | Oramed Ltd. | Compositions for use in treating nafld |
US9693968B2 (en) | 2013-03-14 | 2017-07-04 | Jerome J. Schentag | Cholestosome vesicles for incorporation of molecules into chylomicrons |
EP2799062A1 (en) * | 2013-05-03 | 2014-11-05 | Gilberto Borges de Brito | Pharmaceutical product for inducing magnified release of endogenous gut hormones, pyy and glp-1, to a therapeutic effect on obesity and dm2 |
EP3140316A1 (en) | 2014-05-05 | 2017-03-15 | Thetis Pharmaceuticals LLC | Compositions and methods relating to ionic salts of peptides |
JP2017521479A (ja) | 2014-05-15 | 2017-08-03 | ラニ セラピューティクス, エルエルシー | ポリペプチドおよび/またはタンパク質を含む固体塊の薬学的組成物およびそれを製造するための方法 |
EA201692548A1 (ru) | 2014-06-18 | 2017-10-31 | ТЕТИС ФАРМАСЬЮТИКАЛЗ ЭлЭлСи | Минеральные аминокислотные комплексы активных веществ |
US9242008B2 (en) | 2014-06-18 | 2016-01-26 | Thetis Pharmaceuticals Llc | Mineral amino-acid complexes of fatty acids |
ES2975708T3 (es) | 2015-01-29 | 2024-07-12 | Novo Nordisk As | Comprimidos que comprenden agonista del GLP-1 y recubrimiento entérico |
CN104740647A (zh) * | 2015-04-08 | 2015-07-01 | 东莞市麦亘生物科技有限公司 | 一种艾塞那肽口服制剂及其制备方法 |
ES2887723T3 (es) | 2015-05-22 | 2021-12-27 | Univ Leland Stanford Junior | Tratamiento de hipoglucemia posbariátrica con exendina(9-39) |
RU2702690C2 (ru) * | 2015-08-13 | 2019-10-09 | БИОЛИНГУС АйПи ЛЛСи | Способ получения продуктов, содержащих стабилизированные активные вещества, и композиций, содержащих таковые |
WO2017152014A1 (en) | 2016-03-04 | 2017-09-08 | Eiger Biopharmaceuticals, Inc. | Treatment of hyperinsulinemic hypoglycemia with exendin-4 derivatives |
EP3454907B1 (en) | 2016-06-03 | 2020-07-22 | Thetis Pharmaceuticals LLC | Compositions and methods relating to salts of specialized pro-resolving mediators of inflammation |
CN110267648A (zh) | 2016-11-21 | 2019-09-20 | 艾格尔峰生物制药有限公司 | 毒蜥外泌肽(9-39)的缓冲制剂 |
WO2020225068A1 (en) | 2019-05-06 | 2020-11-12 | Evonik Operations Gmbh | Preparation for use in weight management comprising omega-3 fatty acid salts and basic amino acids |
CN112057619A (zh) * | 2019-06-10 | 2020-12-11 | 苏州兰鼎生物制药有限公司 | 一种具有降血糖作用的药物组合物 |
WO2021166899A1 (ja) * | 2020-02-17 | 2021-08-26 | 宇部興産株式会社 | インクレチン様物質と組み合わせて使用するための消化管プロテアーゼ阻害剤を含む薬剤 |
FR3120189A1 (fr) | 2021-03-01 | 2022-09-02 | Farid Bennis | Composition pharmaceutique pour une administration par voie orale d’un agoniste du récepteur du GLP-1 |
WO2023249087A1 (ja) * | 2022-06-24 | 2023-12-28 | 三生医薬株式会社 | 医薬組成物およびその製造方法 |
Family Cites Families (42)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IL68769A (en) * | 1983-05-23 | 1986-02-28 | Hadassah Med Org | Pharmaceutical compositions containing insulin for oral administration |
JPS6350793A (ja) | 1986-08-20 | 1988-03-03 | 株式会社東芝 | 高速増殖炉の崩壊熱除去システム |
US5034415A (en) | 1987-08-07 | 1991-07-23 | Century Laboratories, Inc. | Treatment of diabetes mellitus |
ATE94404T1 (de) | 1988-07-21 | 1993-10-15 | Hoffmann La Roche | Insulinzubereitung. |
JPH02250823A (ja) * | 1989-03-24 | 1990-10-08 | Tsumura & Co | マイクロカプセル剤およびその製造方法 |
GB9007052D0 (en) | 1990-03-29 | 1990-05-30 | Skua Investments Ltd | Pharmaceutical formulations |
US5206219A (en) * | 1991-11-25 | 1993-04-27 | Applied Analytical Industries, Inc. | Oral compositions of proteinaceous medicaments |
US6692766B1 (en) * | 1994-06-15 | 2004-02-17 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Controlled release oral drug delivery system |
US5824638A (en) * | 1995-05-22 | 1998-10-20 | Shire Laboratories, Inc. | Oral insulin delivery |
IL114673A (en) | 1995-07-19 | 2000-12-06 | Hadasit Med Res Service | Pharmaceutical compositions containing protein for oral administration |
JPH09208485A (ja) * | 1996-01-31 | 1997-08-12 | Teijin Ltd | ペプチド・蛋白質性薬物の水難溶性組成物 |
PT966297E (pt) * | 1996-08-08 | 2009-03-18 | Amylin Pharmaceuticals Inc | Regulação da motilidade gastrintestinal |
JPH10330287A (ja) * | 1997-03-31 | 1998-12-15 | Nippon Suisan Kaisha Ltd | 多価不飽和脂肪酸からなる消化管吸収促進剤およびそれを含有する薬剤 |
US5975893A (en) | 1997-06-20 | 1999-11-02 | Align Technology, Inc. | Method and system for incrementally moving teeth |
JP2000050793A (ja) * | 1998-08-07 | 2000-02-22 | Meiji Milk Prod Co Ltd | 人工乳組成物 |
JP2000128805A (ja) | 1998-10-27 | 2000-05-09 | Nippon Suisan Kaisha Ltd | 多価不飽和脂肪酸および高分子ゲルからなる経粘膜吸収促進剤及びそれを含有する薬剤 |
US6761903B2 (en) | 1999-06-30 | 2004-07-13 | Lipocine, Inc. | Clear oil-containing pharmaceutical compositions containing a therapeutic agent |
JP2001240558A (ja) | 2000-02-29 | 2001-09-04 | Nippon Suisan Kaisha Ltd | 多価不飽和脂肪酸を経粘膜吸収促進剤として含有する固形製剤。 |
US6673574B2 (en) | 2000-11-30 | 2004-01-06 | Unigene Laboratories Inc. | Oral delivery of peptides using enzyme-cleavable membrane translocators |
KR20010069322A (ko) | 2001-03-08 | 2001-07-25 | 서종수 | 휴대형정보단말기 또는 화상이동통신장치를 이용한전자경매방법 |
CN1160122C (zh) | 2001-04-20 | 2004-08-04 | 清华大学 | 一种制备口服胰岛素油相制剂的方法 |
KR100669588B1 (ko) | 2001-07-18 | 2007-01-15 | 솔레 엘엘씨 | 고단백질 바우만-벌크 저해물질 농축물 및 이의 제조 공정 |
US20030198666A1 (en) | 2002-01-07 | 2003-10-23 | Richat Abbas | Oral insulin therapy |
US7767828B2 (en) | 2003-11-12 | 2010-08-03 | Phenomix Corporation | Methyl and ethyl substituted pyrrolidine compounds and methods for selective inhibition of dipeptidyl peptidase-IV |
US20060286129A1 (en) * | 2003-12-19 | 2006-12-21 | Emisphere Technologies, Inc. | Oral GLP-1 formulations |
US20050143303A1 (en) | 2003-12-26 | 2005-06-30 | Nastech Pharmaceutical Company Inc. | Intranasal administration of glucose-regulating peptides |
US8076288B2 (en) * | 2004-02-11 | 2011-12-13 | Amylin Pharmaceuticals, Inc. | Hybrid polypeptides having glucose lowering activity |
CN101084016A (zh) | 2004-04-15 | 2007-12-05 | 克艾思马有限公司 | 能够容易穿透生物学障碍的组合物 |
EP1773878B1 (en) | 2004-07-19 | 2015-03-04 | Biocon Limited | Insulin-oligomer conjugates, formulations and uses thereof |
EP1789075A4 (en) * | 2004-08-25 | 2009-07-01 | Uab Research Foundation | ABSORPTION ENHANCER FOR DRUG ADMINISTRATION |
US20060046962A1 (en) * | 2004-08-25 | 2006-03-02 | Aegis Therapeutics Llc | Absorption enhancers for drug administration |
EP2722054B1 (en) * | 2005-09-06 | 2018-03-21 | Oramed Pharmaceuticals Inc. | Methods and compositions for oral administration of proteins |
US20070086972A1 (en) | 2005-09-12 | 2007-04-19 | Jacob Birnbaum | Hair growth compositions and methods for treating hair loss or related conditions |
US20070077283A1 (en) * | 2005-09-30 | 2007-04-05 | Nastech Pharmaceutical Company Inc. | Method of enhancing transmucosal delivery of therapeutic compounds |
CN101095942B (zh) * | 2006-06-30 | 2011-11-16 | 北京民海生物科技有限公司 | 一种包含稳定剂的Exendin-4注射剂药物配方 |
BRPI0907077A2 (pt) * | 2008-03-26 | 2016-07-26 | Oramed Ltd | métodos e composições para administração oral de proteínas |
US20110046053A1 (en) | 2008-05-05 | 2011-02-24 | Oramed Ltd. | Methods and compositions for oral administration of exenatide |
WO2010011439A2 (en) | 2008-06-17 | 2010-01-28 | Indiana University Research And Technology Corporation | Gip-based mixed agonists for treatment of metabolic disorders and obesity |
EP3741359A1 (en) | 2008-08-18 | 2020-11-25 | Entera Bio Ltd. | Methods and compositions for oral administration of proteins |
DK2800579T3 (da) | 2012-01-03 | 2017-11-13 | Oramed Ltd | Kapsler indeholdende olie-baserede flydende sammensætninger af kombinerede terapeutiske stoffer til behandling af diabetes |
JP6567827B2 (ja) | 2012-02-01 | 2019-08-28 | オラムド エルティーディー. | プロテアーゼ阻害剤を含有する組成物、該組成物を含む組成物、および、該組成物を製造および使用する方法 |
EP2941267B1 (en) | 2013-01-03 | 2022-11-16 | Oramed Ltd. | Compositions for use in treating nafld |
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AU2009245294B2 (en) | 2014-02-20 |
CA2723434C (en) | 2018-01-23 |
JP2018115204A (ja) | 2018-07-26 |
BRPI0908292A2 (pt) | 2015-08-04 |
US20210322305A1 (en) | 2021-10-21 |
NZ589390A (en) | 2011-11-25 |
BRPI0908292B1 (pt) | 2022-09-20 |
WO2009136392A3 (en) | 2010-03-11 |
US20130195939A1 (en) | 2013-08-01 |
JP2011519915A (ja) | 2011-07-14 |
JP2017008080A (ja) | 2017-01-12 |
RU2010146372A (ru) | 2012-06-20 |
US20110046053A1 (en) | 2011-02-24 |
ZA201008090B (en) | 2012-08-29 |
US10350162B2 (en) | 2019-07-16 |
DK2300031T3 (en) | 2017-10-30 |
CN102026646A (zh) | 2011-04-20 |
EP2300031A2 (en) | 2011-03-30 |
JP6379143B2 (ja) | 2018-08-22 |
CN105903005A (zh) | 2016-08-31 |
HK1223558A1 (zh) | 2017-08-04 |
WO2009136392A2 (en) | 2009-11-12 |
JP2015038082A (ja) | 2015-02-26 |
EP2300031B1 (en) | 2017-09-20 |
EP2300031A4 (en) | 2012-10-24 |
ES2645588T3 (es) | 2017-12-05 |
US20190314275A1 (en) | 2019-10-17 |
CA2723434A1 (en) | 2009-11-12 |
EP3275460A1 (en) | 2018-01-31 |
NO2300031T3 (ja) | 2018-02-17 |
RU2566063C2 (ru) | 2015-10-20 |
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