KR20020084136A - 소마토트로핀의 지속적인 방출을 위한 비수성 주사제제들 - Google Patents
소마토트로핀의 지속적인 방출을 위한 비수성 주사제제들 Download PDFInfo
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- KR20020084136A KR20020084136A KR1020027010551A KR20027010551A KR20020084136A KR 20020084136 A KR20020084136 A KR 20020084136A KR 1020027010551 A KR1020027010551 A KR 1020027010551A KR 20027010551 A KR20027010551 A KR 20027010551A KR 20020084136 A KR20020084136 A KR 20020084136A
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- KR
- South Korea
- Prior art keywords
- somatotropin
- composition
- bioavailability enhancing
- enhancing component
- bioavailability
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- MJIBOYFUEIDNPI-HBNMXAOGSA-L zinc 5-[2,3-dihydroxy-5-[(2R,3R,4S,5R,6S)-4,5,6-tris[[3,4-dihydroxy-5-(3,4,5-trihydroxybenzoyl)oxybenzoyl]oxy]-2-[[3,4-dihydroxy-5-(3,4,5-trihydroxybenzoyl)oxybenzoyl]oxymethyl]oxan-3-yl]oxycarbonylphenoxy]carbonyl-3-hydroxybenzene-1,2-diolate Chemical compound [Zn++].Oc1cc(cc(O)c1O)C(=O)Oc1cc(cc(O)c1O)C(=O)OC[C@H]1O[C@@H](OC(=O)c2cc(O)c(O)c(OC(=O)c3cc(O)c(O)c(O)c3)c2)[C@H](OC(=O)c2cc(O)c(O)c(OC(=O)c3cc(O)c(O)c(O)c3)c2)[C@@H](OC(=O)c2cc(O)c(O)c(OC(=O)c3cc(O)c(O)c(O)c3)c2)[C@@H]1OC(=O)c1cc(O)c(O)c(OC(=O)c2cc(O)c([O-])c([O-])c2)c1 MJIBOYFUEIDNPI-HBNMXAOGSA-L 0.000 description 1
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Abstract
Description
생체이용도향상성분(BEC) | %BEC | %ZnbST1 | 소수성 캐리어 |
히스티딘-HCl | 3 | 42 | SO:AlMS 95:52 |
히스티딘-HCl | 5 | 38 | SO:AlMS 95:5 |
히스티딘-HCl | 4.5 | 43 | SO:AlMS 95:5 |
히스티딘-HCl | 1 | 38 | SO:AlMS 95:5 |
히스티딘-HCl | 2.5 | 38 | SO:AlMS 95:5 |
히스티딘-HCl | 10 | 38 | SO:AlMS 95:5 |
폴리히스티딘-HCl | 5 | 38 | SO:AlMS 95:5 |
아르기닌 | 5 | 38.5 | SO:AlMS 95:5 |
히스티딘없는 염기 | 5 | 38.4 | SO:AlMS 95:5 |
글루탐산 | 5 | 38 | SO:AlMS 95:5 |
글루탐산나트륨 | 5 | 38 | SO:AlMS 95:5 |
글리신 | 5 | 38 | SO:AlMS 95:5 |
메티오닌 | 5 | 38 | SO:AlMS 95:5 |
트립토판 | 5 | 38 | SO:AlMS 95:5 |
이미다졸 | 5 | 38 | SO:AlMS 95:5 |
이미다졸-HCl | 5 | 38 | SO:AlMS 95:5 |
부펙사막산 | 5 | 38 | SO:AlMS 95:5 |
히스티딘 히드록사메이트 | 5 | 38 | SO:AlMS 95:5 |
살리실 히드록사민산 | 5 | 38 | SO:AlMS 95:5 |
카프릴로 히드록사민산 | 5 | 38 | SO:AlMS 95:5 |
수베로 히드록사민산 | 5 | 38 | SO:AlMS 95:5 |
트리할로즈 디하이드레이트 | 5 | 34 | SO:AlMS 95:5 |
트리할로즈 디하이드레이트 | 10 | 34 | SO:AlMS 95:5 |
트리할로즈 디하이드레이트 | 15 | 34 | SO:AlMS 95:5 |
트리할로즈 디하이드레이트 | 14 | 31 | SO:AlMS 95:5 |
트리할로즈 디하이드레이트 | 5 | 38.5 | SO:AlMS 95:5 |
트리할로즈 옥타아세테이트 | 5 | 38 | SO:AlMS 95:5 |
슈크로즈 | 15 | 33 | SO:AlMS 95:5 |
슈크로즈 옥타아세테이트 | 4 | 38 | SO:AlMS 95:5 |
슈크로즈 옥타설페이트 | 5 | 38 | SO:AlMS 95:5 |
일염기성과 이염기성인산나트륨; 6:4 몰비 | 5 | 38 | SO:AlMS 95:5 |
일염기성 인산나트륨 | 5 | 38.3 | SO:AlMS 95:5 |
이염기성 인산나트륨 | 5 | 38.3 | SO:AlMS 95:5 |
황산나트륨 | 5 | 38.3 | SO:AlMS 95:5 |
질산나트륨 | 5 | 38.3 | SO:AlMS 95:5 |
일염기성과 이염기성인산칼륨; 6:4 몰비 | 5 | 38.3 | SO:AlMS 95:5 |
일염기성과 이염기성인산칼슘; 6:4 몰비 | 5 | 38.3 | SO:AlMS 95:5 |
시트르산칼륨 | 5 | 38.3 | SO:AlMS 95:5 |
황산암모늄 | 5 | 38.3 | SO:AlMS 95:5 |
Claims (22)
- 소마토트로핀과, 조성물이 비경구투여되는 동물내에서의 소마토트로핀의 생체이용도를 향상시키는 성분을 포함하는 조성물:상기 생체이용도 향상성분은 다음 물질중 하나 또는 그 이상을 포함하고,a) 비환원성 탄수화물,b) 아미노산, 아미노산 유도체, 아미노산 중합체 또는 폴리히스티딘,c) 히드록사메이트 또는 히드록사메이트 유도체, 또는d) 옥소산염;상기 소마토트로핀과 생체이용도 향상성분은 실질적으로 비수성의 소수성 캐리어내에 현탁된다.
- 제 1항에 있어서, 상기 소마토트로핀은 인간, 말, 소 또는 돼지의 소마토트로핀인 것을 특징으로 하는 조성물.
- 제 1항에 있어서, 상기 소마토트로핀은 조성물의 약 10∼50중량%로 존재하는 것을 특징으로 하는 조성물.
- 제 1항에 있어서, 상기 생체이용도 향상성분은 최소한 하나의 폴리올, 최소한 하나의 탄수화물 에스테르, 및 그들의 혼합물로부터 선택된 비환원성 탄수화물인 것을 특징으로 하는 조성물.
- 제 1항에 있어서, 상기 생체이용도 향상성분은 비환원성 탄수화물을 포함하고;상기 비환원성 탄수화물은 조성물의 약 5∼20중량%로 존재하는 폴리올인 것을 특징으로 하는 조성물.
- 제 1항에 있어서, 상기 생체이용도 향상성분은 아미노산, 아미노산 유도체, 및 아미노산 중합체 중 하나 또는 그 이상을 포함하는 것을 특징으로 하는 조성물.
- 제 6항에 있어서, 상기 생체이용도 향상성분은 조성물의 약 1∼20중량%로 존재하는 것을 특징으로 하는 조성물.
- 제 1항에 있어서, 상기 생체이용도 향상성분은 하나 또는 그 이상의 히드록사메이트 유도체를 포함하는 것을 특징으로 하는 조성물.
- 제 8항에 있어서, 상기 생체이용도 향상성분은 조성물의 약 1∼20중량%로 존재하는 것을 특징으로 하는 조성물.
- 제 1항에 있어서, 상기 생체이용도 향상성분은 최소한 하나의 옥소산염을 포함하는 것을 특징으로 하는 조성물.
- 제 10항에 있어서, 상기 옥소산염은 다음 물질중 하나, 또는 둘 이상의 혼합물에서 선택되는 것을 특징으로 하는 조성물 :일염기성 인산나트륨, 이염기성 인산나트륨, 일염기성 인산칼륨, 이염기성 인산칼륨, 일염기성 인산칼슘, 이염기성 인산칼슘, 질산나트륨, 이염기성 황산나트륨, 인산염, 질산염, 황산염, 및 이들의 혼합물.
- 제 10항에 있어서, 상기 생체이용도 향상성분은 조성물의 약 1∼20중량%로 존재하는 것을 특징으로 하는 조성물.
- 제 1항에 있어서, 상기 소수성 캐리어는 오일 또는 지방을 포함하는 것을 특징으로 하는 조성물.
- 제 1항에 있어서, 상기 소마토트로핀은 약 32∼42중량%로 존재하는 소 소마토트로핀의 아연염이고 ;상기 생체이용도 향상성분은 일염기성 인산나트륨과 이염기성 인산나트륨염의 혼합물이고, 상기 일염기성 인산나트륨 대 이염기성 인산나트륨의 몰비는 6:4이고, 약 2∼10중량%로 존재하는 것을 특징으로 하는 조성물.
- 다음을 포함하는 조성물의 제조방법:소마토트로핀과, 생체이용도 향상성분으로서 다음 물질중 하나 또는 그 이상을 포함하고,a) 비환원성 탄수화물,b) 아미노산, 아미노산 유도체, 아미노산 중합체, 폴리히스티딘,c) 히드록사메이트 또는 히드록사메이트 유도체, 또는d) 옥소산염;상기 소마토트로핀과 생체이용도 향상성분은 실질적으로 비수성의 소수성 캐리어내에 현탁된다;상기 방법은 다음의 단계들을 포함한다:동결건조된 무수고체상태의 소마토트로핀, 무수고체상태의 생체이용도 향상성분, 및 소수성 캐리어를 제공하는 단계;생체이용도 향상성분과 소수성 캐리어를 혼합하여 첫번째 현탁액을 제조하는 단계; 그리고,소마토트로핀과 첫번째 현탁액을 혼합하여 두번째 현탁액을 제조하는 단계.
- 다음을 포함하는 조성물을 포유동물에 주사하는 것을 포함하는 방법:소마토트로핀과, 생체이용도 향상성분으로서, 다음 물질중 하나 또는 그 이상을 포함하고,a) 비환원성 탄수화물,b) 아미노산, 아미노산 유도체, 아미노산 중합체, 폴리히스티딘,c) 히드록사메이트 또는 히드록사메이트 유도체, 또는d) 옥소산염;상기 소마토트로핀과 생체이용도 향상성분은 실질적으로 비수성인 소수성 캐리어내에 현탁된다.
- 제 16항에 있어서, 상기 소마토트로핀은 조성물내에 10∼50중량%로 존재하고, 생체이용도 향상성분은 옥소산 또는 옥소산의 혼합물로 조성물내에 약 0.5∼30중량%로 존재하고, 소수성 캐리어는 조성물내에 약 40∼90중량%로 존재하는 것을 특징으로 하는 방법.
- 다음을 포함하는 조성물:소마토트로핀과, 생체이용도 향상성분으로서 하나 또는 그 이상의 비환원성 탄수화물을 포함하고; 그리고상기 소마토트로핀과 생체이용도 향상성분은 실질적으로 비수성인 소수성 캐리어내에 현탁된다.
- 다음을 포함하는 조성물:소마토트로핀과, 생체이용도 향상성분으로서 아미노산, 아미노산 유도체, 아미노산 중합체, 및 폴리히스티딘으로 이루어진 그룹에서 선택된 하나 또는 그 이상의 화합물을 포함하고; 그리고상기 소마토트로핀과 생체이용도 향상성분은 실질적으로 비수성인 소수성 캐리어내에 현탁된다.
- 다음을 포함하는 조성물:소마토트로핀과, 생체이용도 향상성분으로서 히드록사메이트와 히드록사메이트 유도체로 이루어진 그룹에서 선택된 하나 또는 그 이상의 화합물을 포함하고; 그리고상기 소마토트로핀과 생체이용도 향상성분은 실질적으로 비수성인 소수성 캐리어내에 현탁된다.
- 다음을 포함하는 조성물:소마토트로핀과, 생체이용도 향상성분으로서 하나 또는 그 이상의 옥소산염을 포함하고; 그리고상기 소마토트로핀과 생체이용도 향상성분은 실질적으로 비수성인 소수성 캐리어내에 현탁된다.
- 다음을 포함하는 생체적합성 조성물을 포유동물에게 주사하는 것을 포함하는, 포유동물에서 상승된 우유생산반응을 유지하기 위한 방법:포유동물에서 활성인 소마토트로핀과, 생체이용도 향상성분;상기 생체이용도 향상성분은 다음 물질중 하나, 또는 둘 또는 그 이상의 혼합물을 포함하고:a) 비환원성 탄수화물,b) 아미노산, 아미노산 유도체, 아미노산 중합체, 폴리히스티딘,c) 히드록사메이트 또는 히드록사메이트 유도체, 또는d) 옥소산염; 그리고상기 소마토트로핀과 생체이용도 향상성분은 실질적으로 비수성인 소수성 캐리어내에 현탁된다.
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US18462500P | 2000-02-24 | 2000-02-24 | |
US60/184,625 | 2000-02-24 |
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KR1020077018825A Division KR100890679B1 (ko) | 2000-02-24 | 2001-02-20 | 소마토트로핀의 지속적인 방출을 위한 비수성 주사제제들 |
KR1020087000990A Division KR20080011353A (ko) | 2000-02-24 | 2001-02-20 | 소마토트로핀의 지속적인 방출을 위한 비수성 주사제제들 |
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KR1020087031846A KR20090007504A (ko) | 2000-02-24 | 2001-02-20 | 소마토트로핀의 지속적인 방출을 위한 비수성 주사제제들 |
KR1020077018825A KR100890679B1 (ko) | 2000-02-24 | 2001-02-20 | 소마토트로핀의 지속적인 방출을 위한 비수성 주사제제들 |
KR1020027010551A KR100890125B1 (ko) | 2000-02-24 | 2001-02-20 | 소마토트로핀의 지속적인 방출을 위한 비수성 주사제제들 |
KR1020087000990A KR20080011353A (ko) | 2000-02-24 | 2001-02-20 | 소마토트로핀의 지속적인 방출을 위한 비수성 주사제제들 |
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KR1020087031846A KR20090007504A (ko) | 2000-02-24 | 2001-02-20 | 소마토트로핀의 지속적인 방출을 위한 비수성 주사제제들 |
KR1020077018825A KR100890679B1 (ko) | 2000-02-24 | 2001-02-20 | 소마토트로핀의 지속적인 방출을 위한 비수성 주사제제들 |
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Country Status (5)
Country | Link |
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US (2) | US6719990B2 (ko) |
KR (4) | KR20090007504A (ko) |
AU (1) | AU2001238540A1 (ko) |
MX (1) | MXPA02008261A (ko) |
WO (1) | WO2001062296A2 (ko) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20030162711A1 (en) * | 1996-04-24 | 2003-08-28 | Soren Bjorn | Pharmaceutical formulation |
US20070179096A1 (en) * | 1996-04-24 | 2007-08-02 | Novo Nordisk A/S | Pharmaceutical Formulation |
JPWO2005073180A1 (ja) * | 2003-12-25 | 2008-01-10 | 株式会社クレハ | ヒドロキサム酸誘導体、及び該誘導体を含むage生成阻害剤 |
EA201692083A1 (ru) | 2014-04-16 | 2017-03-31 | Вейкс-Фарма Гмбх | Фармацевтическая композиция для ветеринарии и ее применение |
CN115501172A (zh) | 2014-11-21 | 2022-12-23 | 丹麦技术大学 | 用于局部药物释放的凝胶制剂 |
Family Cites Families (40)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5474980A (en) * | 1984-10-04 | 1995-12-12 | Monsanto Company | Prolonged release of biologically active somatotropins |
KR890002631B1 (ko) | 1984-10-04 | 1989-07-21 | 몬산토 캄파니 | 생물학적으로 활성인 소마토트로핀을 지속적으로 유리하는 조성물 |
US4861868A (en) | 1985-02-22 | 1989-08-29 | Monsanto Company | Production of proteins in procaryotes |
IL79681A (en) | 1985-08-12 | 1991-06-10 | Int Minerals & Chem Corp | Transition metal complexes of growth hormones and their prolonged release compositions |
US4977140A (en) | 1985-08-23 | 1990-12-11 | Eli Lilly And Company | Injectable sustained release formulation |
US5631227A (en) | 1985-09-18 | 1997-05-20 | The Upjohn Company | Somatotropin analogs |
US4917685A (en) * | 1986-05-16 | 1990-04-17 | International Minerals & Chem. Corp. | Delivery device for the administration of stabilized growth promoting hormones |
US4816568A (en) * | 1986-05-16 | 1989-03-28 | International Minerals & Chemical Corp. | Stabilization of growth hormones |
US4857506A (en) * | 1987-01-12 | 1989-08-15 | American Cyanamid Company | Sustained release growth hormone compositions for parenteral administration and their use |
DE3782737T3 (de) * | 1987-08-21 | 1999-05-20 | Imcera Group Inc | Stabilisierung von Wachstumshormonen. |
GB8725427D0 (en) * | 1987-10-30 | 1987-12-02 | Lilly Industries Ltd | Somatotropin formulations |
CA1331133C (en) * | 1988-03-01 | 1994-08-02 | Michael Jon Pikal | Pharmaceutical growth hormone formulations |
US5096885A (en) * | 1988-04-15 | 1992-03-17 | Genentech, Inc. | Human growth hormone formulation |
EP0374120A3 (en) * | 1988-12-13 | 1991-07-31 | Monsanto Company | Comosition for controlled release of polypeptides |
US5037420A (en) * | 1988-12-13 | 1991-08-06 | Alza Corporation | Delivery system comprising two sections for delivering somatotropin |
US5034229A (en) | 1988-12-13 | 1991-07-23 | Alza Corporation | Dispenser for increasing feed conversion of hog |
US5219572A (en) | 1989-03-17 | 1993-06-15 | Pitman-Moore, Inc. | Controlled release delivery device for macromolecular proteins |
JP3009911B2 (ja) * | 1989-06-28 | 2000-02-14 | エーザイ株式会社 | ペプチド又は蛋白の内服用新規製剤 |
AU653325B2 (en) | 1990-02-12 | 1994-09-29 | Lucky Limited | A composition durably releasing bioactive polypeptides |
US5182369A (en) | 1990-02-28 | 1993-01-26 | Monsanto Company | Method for purifying somatotropin monomers |
DE69209173T2 (de) | 1991-06-24 | 1996-11-28 | American Cyanamid Co | Implantationzusammensetzungen, die biologisch aktive Proteine, Peptide oder Polypeptide enthalten |
US5801141A (en) * | 1991-06-24 | 1998-09-01 | American Cyanamid Company | Implant compositions containing a biologically active protein, peptide or polypeptide |
ATE140620T1 (de) | 1991-12-05 | 1996-08-15 | Mallinckrodt Veterinary Inc | Glasartige kohlenhydratenmatrize zur verabreichung von heilmitteln mit verzögerter wirkstoffabgabe |
RO111990B1 (ro) * | 1991-12-20 | 1997-04-30 | Novo Nordisk As | Preparate farmaceutice, continand un hormon de crestere sau un derivat al acestuia, si procedeu de preparare |
US5849704A (en) | 1991-12-20 | 1998-12-15 | Novo Nordisk A/S | Pharmaceutical formulation |
WO1993013792A1 (en) * | 1992-01-13 | 1993-07-22 | Pitman-Moore, Inc. | Delayed release device for transition metal/protein complexes |
JPH08502021A (ja) | 1992-04-07 | 1996-03-05 | マリンクロッド・ヴェタラネリィ・インコーポレイテッド | 生体相容性ソマトトロピン溶液 |
US5607691A (en) | 1992-06-12 | 1997-03-04 | Affymax Technologies N.V. | Compositions and methods for enhanced drug delivery |
US5359030A (en) | 1993-05-10 | 1994-10-25 | Protein Delivery, Inc. | Conjugation-stabilized polypeptide compositions, therapeutic delivery and diagnostic formulations comprising same, and method of making and using the same |
US5681811A (en) | 1993-05-10 | 1997-10-28 | Protein Delivery, Inc. | Conjugation-stabilized therapeutic agent compositions, delivery and diagnostic formulations comprising same, and method of making and using the same |
WO1995032222A1 (en) | 1994-05-19 | 1995-11-30 | Monsanto Company | Method for purifying somatotropin monomers |
US5904935A (en) | 1995-06-07 | 1999-05-18 | Alza Corporation | Peptide/protein suspending formulations |
ZA965368B (en) | 1995-07-14 | 1997-01-14 | Novo Nordisk As | A pharmaceutical formulation |
KR100210509B1 (ko) | 1996-01-10 | 1999-07-15 | 성재갑 | 지속성 동물 성장 호르몬 제형 및 이의 제조 방법 |
AUPN801296A0 (en) | 1996-02-12 | 1996-03-07 | Csl Limited | Stabilised growth hormone formulation and method of preparation thereof |
US5912014A (en) | 1996-03-15 | 1999-06-15 | Unigene Laboratories, Inc. | Oral salmon calcitonin pharmaceutical products |
ZA9711731B (en) | 1996-12-31 | 1998-07-01 | Monsanto Co | Aqueous glycerol formulations of somatotropin |
EP0913177A1 (de) | 1997-11-03 | 1999-05-06 | Roche Diagnostics GmbH | Verfahren zur Herstellung trockener, amorpher Produkte enthaltend biologisch aktive Materialien mittels Konvektionstrocknung, insbesondere Sprühtrocknung |
US6551613B1 (en) | 1998-09-08 | 2003-04-22 | Alza Corporation | Dosage form comprising therapeutic formulation |
US6162258A (en) | 1999-08-25 | 2000-12-19 | Osteotech, Inc. | Lyophilized monolithic bone implant and method for treating bone |
-
2001
- 2001-02-20 KR KR1020087031846A patent/KR20090007504A/ko not_active Application Discontinuation
- 2001-02-20 KR KR1020077018825A patent/KR100890679B1/ko active IP Right Grant
- 2001-02-20 KR KR1020027010551A patent/KR100890125B1/ko active IP Right Grant
- 2001-02-20 AU AU2001238540A patent/AU2001238540A1/en not_active Abandoned
- 2001-02-20 WO PCT/US2001/005408 patent/WO2001062296A2/en active Application Filing
- 2001-02-20 MX MXPA02008261A patent/MXPA02008261A/es active IP Right Grant
- 2001-02-20 KR KR1020087000990A patent/KR20080011353A/ko active IP Right Grant
- 2001-02-21 US US09/789,392 patent/US6719990B2/en not_active Expired - Lifetime
-
2004
- 2004-03-04 US US10/793,232 patent/US7048938B2/en not_active Expired - Lifetime
Also Published As
Publication number | Publication date |
---|---|
WO2001062296A3 (en) | 2002-05-30 |
KR100890679B1 (ko) | 2009-03-26 |
US7048938B2 (en) | 2006-05-23 |
US20010046954A1 (en) | 2001-11-29 |
MXPA02008261A (es) | 2002-11-29 |
KR20070091373A (ko) | 2007-09-10 |
KR20080011353A (ko) | 2008-02-01 |
WO2001062296A2 (en) | 2001-08-30 |
KR20090007504A (ko) | 2009-01-16 |
AU2001238540A1 (en) | 2001-09-03 |
US6719990B2 (en) | 2004-04-13 |
US20040171531A1 (en) | 2004-09-02 |
KR100890125B1 (ko) | 2009-03-24 |
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