KR20120006991A - 급속 섭취를 위한 인슐린 제형 - Google Patents
급속 섭취를 위한 인슐린 제형 Download PDFInfo
- Publication number
- KR20120006991A KR20120006991A KR1020117023159A KR20117023159A KR20120006991A KR 20120006991 A KR20120006991 A KR 20120006991A KR 1020117023159 A KR1020117023159 A KR 1020117023159A KR 20117023159 A KR20117023159 A KR 20117023159A KR 20120006991 A KR20120006991 A KR 20120006991A
- Authority
- KR
- South Korea
- Prior art keywords
- insulin
- acid
- formulation
- formulations
- edta
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 title claims abstract description 533
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- 229940125396 insulin Drugs 0.000 title claims abstract description 259
- 239000000203 mixture Substances 0.000 title claims abstract description 104
- 238000009472 formulation Methods 0.000 title claims abstract description 87
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims abstract description 171
- PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 claims abstract description 58
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims abstract description 54
- 239000002738 chelating agent Substances 0.000 claims abstract description 50
- 101000976075 Homo sapiens Insulin Proteins 0.000 claims abstract description 35
- 239000002904 solvent Substances 0.000 claims abstract description 35
- 239000001509 sodium citrate Substances 0.000 claims abstract description 26
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000011701 zinc Substances 0.000 claims abstract description 13
- 229910052725 zinc Inorganic materials 0.000 claims abstract description 13
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 10
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 claims abstract description 10
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- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 claims description 17
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- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 12
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- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 9
- FCKYPQBAHLOOJQ-UHFFFAOYSA-N Cyclohexane-1,2-diaminetetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)C1CCCCC1N(CC(O)=O)CC(O)=O FCKYPQBAHLOOJQ-UHFFFAOYSA-N 0.000 claims description 9
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 9
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- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 8
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 claims description 8
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- 229910052751 metal Inorganic materials 0.000 claims description 8
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- ACTRVOBWPAIOHC-UHFFFAOYSA-N succimer Chemical compound OC(=O)C(S)C(S)C(O)=O ACTRVOBWPAIOHC-UHFFFAOYSA-N 0.000 claims description 8
- 235000003704 aspartic acid Nutrition 0.000 claims description 7
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims description 7
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims description 6
- AGBQKNBQESQNJD-UHFFFAOYSA-N lipoic acid Chemical compound OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 claims description 6
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- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 5
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- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 claims description 4
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- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 claims 1
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20140146209A (ko) * | 2012-04-16 | 2014-12-24 | 바이오델 아이엔씨 | 인슐린 및 인슐린 유사체의 약동학 및 약역학과 주사 통증을 조절하기 위한 마그네슘 조성물 |
| KR20160122145A (ko) * | 2014-01-13 | 2016-10-21 | 써멀린 다이어비티즈, 엘엘씨 | 초속효성 인슐린 제형 및 약제학적 전달 시스템 |
Families Citing this family (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9060927B2 (en) | 2009-03-03 | 2015-06-23 | Biodel Inc. | Insulin formulations for rapid uptake |
| US9018190B2 (en) | 2009-03-27 | 2015-04-28 | Adocia | Functionalized oligosaccharides |
| FR2943538B1 (fr) * | 2009-03-27 | 2011-05-20 | Adocia | Formulation a action rapide d'insuline recombinante humaine |
| US20120241356A1 (en) * | 2009-07-06 | 2012-09-27 | Sanofi-Aventis Deutschland Gmbh | Heat- and vibration-stable insulin preparations |
| CA2805031A1 (en) * | 2010-07-07 | 2012-01-12 | Biodel, Inc. | Compositions and methods for modulating the pharmacokinetics and pharmacodynamics of insulin |
| DK2741765T3 (en) * | 2011-08-10 | 2016-06-13 | Adocia | Injectable solution of at least one type of basal insulin |
| US20130231281A1 (en) | 2011-11-02 | 2013-09-05 | Adocia | Rapid acting insulin formulation comprising an oligosaccharide |
| CN104902922B (zh) | 2012-11-13 | 2017-12-12 | 阿道恰公司 | 包含经取代阴离子化合物的速效胰岛素制剂 |
| WO2014169081A2 (en) | 2013-04-09 | 2014-10-16 | Biodel, Inc. | Methods and devices for point of use mixing of pharmaceutical formulations |
| FR3020947B1 (fr) | 2014-05-14 | 2018-08-31 | Adocia | Composition aqueuse comprenant au moins une proteine et un agent solubilisant, sa preparation et ses utilisations |
| US9795678B2 (en) | 2014-05-14 | 2017-10-24 | Adocia | Fast-acting insulin composition comprising a substituted anionic compound and a polyanionic compound |
| BR112017004544A2 (pt) * | 2014-10-06 | 2018-01-23 | Univ Case Western Reserve | insulina de cadeia simples, composição farmacêutica e método para tratar diabetes mellitus |
| TW201630622A (zh) * | 2014-12-16 | 2016-09-01 | 美國禮來大藥廠 | 速效胰島素組合物 |
| JO3749B1 (ar) | 2015-08-27 | 2021-01-31 | Lilly Co Eli | تركيبات إنسولين سريعة المفعول |
| FR3043557B1 (fr) | 2015-11-16 | 2019-05-31 | Adocia | Composition a action rapide d'insuline comprenant un citrate substitue |
| GB201607918D0 (en) | 2016-05-06 | 2016-06-22 | Arecor Ltd | Novel formulations |
| CN107436311B (zh) * | 2016-05-25 | 2021-11-19 | 正大天晴药业集团股份有限公司 | 一种鉴别胰岛素单体或胰岛素多聚体的方法 |
| JP2019529506A (ja) | 2016-09-29 | 2019-10-17 | アレコル リミテッド | 新規の製剤 |
| GB201707189D0 (en) | 2017-05-05 | 2017-06-21 | Arecor Ltd | Novel formulations |
| GB201707187D0 (en) | 2017-05-05 | 2017-06-21 | Arecor Ltd | Novel formulations |
| GB201707188D0 (en) | 2017-05-05 | 2017-06-21 | Arecor Ltd | Novel formulations |
| US20180318426A1 (en) * | 2017-05-05 | 2018-11-08 | Merck Sharp & Dohme Corp. | Pharmaceutical formulations comprising insulin or insulin analogs conjugated to fucose for providing a basal pharmacodynamic profile |
| CN110662551B (zh) | 2017-06-01 | 2023-07-18 | 伊莱利利公司 | 速效胰岛素组合物 |
| JP2020534939A (ja) * | 2017-09-27 | 2020-12-03 | ベクトン・ディキンソン・アンド・カンパニーＢｅｃｔｏｎ， Ｄｉｃｋｉｎｓｏｎ Ａｎｄ Ｃｏｍｐａｎｙ | 漏出検出機能付きの流体供給装置 |
| US20210113763A1 (en) | 2018-04-04 | 2021-04-22 | Arecor Limited | Medical infusion pump system for the delivery of an insulin compound |
| US12357562B2 (en) | 2018-04-04 | 2025-07-15 | Arecor Limited | Injection pen system for the delivery of an insulin compound |
| KR102833828B1 (ko) | 2018-04-04 | 2025-07-15 | 아레콜 리미티드 | 인슐린 화합물의 전달을 위한 의료용 주입 펌프 시스템 |
| FR3083984A1 (fr) | 2018-07-23 | 2020-01-24 | Adocia | Dispositif pour injecter une solution d'insuline(s) |
| FR3083985A1 (fr) | 2018-07-23 | 2020-01-24 | Adocia | Dispositif pour injecter une solution d'insuline(s) |
| WO2019243627A1 (fr) | 2018-06-23 | 2019-12-26 | Adocia | Dispositif pour injecter une solution d'insuline(s) |
| CN112805238A (zh) * | 2018-07-03 | 2021-05-14 | 芬内克制药股份有限公司 | 无水硫代硫酸钠和其调配物 |
| WO2021108421A1 (en) | 2019-11-25 | 2021-06-03 | Aita Bio Inc. | Micropump and method of fabricating the same |
| GB202004814D0 (en) | 2020-04-01 | 2020-05-13 | Arecor Ltd | Novel formulations |
Family Cites Families (182)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2143590A (en) | 1936-09-26 | 1939-01-10 | Univ Alberta | Insulin preparation and process of producing crystals of insulin |
| US2626228A (en) | 1945-05-17 | 1953-01-20 | Novo Terapeutisk Labor As | Method of producing crystalline insulin |
| US2819999A (en) | 1953-11-13 | 1958-01-14 | Novo Terapeutisk Labor As | Process for crystallization of insulin using freeze dried insulin as seeding material |
| US3649456A (en) | 1969-09-08 | 1972-03-14 | Rohm & Haas | Separation of polypeptide substances with macroreticular resins |
| US3683635A (en) | 1970-12-07 | 1972-08-15 | Mario Campanelli | Freeze stabilized insulin |
| FR2224175B1 (https=) | 1973-04-04 | 1978-04-14 | Isf Spa | |
| GB1479283A (en) | 1973-07-23 | 1977-07-13 | Bespak Industries Ltd | Inhaler for powdered medicament |
| US4153689A (en) | 1975-06-13 | 1979-05-08 | Takeda Chemical Industries, Ltd. | Stable insulin preparation for nasal administration |
| DE2629568C3 (de) | 1976-07-01 | 1981-09-10 | Hoechst Ag, 6000 Frankfurt | Verfahren zur Reinigung von Insulin, seinen Analogen und Derivaten |
| US4211769A (en) | 1977-08-24 | 1980-07-08 | Takeda Chemical Industries, Ltd. | Preparations for vaginal administration |
| US4377482A (en) | 1978-04-28 | 1983-03-22 | Salk Institute For Biological Studies | Mobile phase for liquid chromatography |
| US4196196A (en) | 1978-06-19 | 1980-04-01 | Tiholiz Ivan C | Divalen/monovalent bipolar cation therapy for enhancement of tissue perfusion and reperfusion in disease states |
| US4272398A (en) | 1978-08-17 | 1981-06-09 | The United States Of America As Represented By The Secretary Of Agriculture | Microencapsulation process |
| JPS55138393A (en) | 1979-04-13 | 1980-10-29 | Shionogi & Co Ltd | Semisynthesis of insulin |
| JPS6034925B2 (ja) | 1979-07-31 | 1985-08-12 | 帝人株式会社 | 持続性鼻腔用製剤およびその製造法 |
| DK147437A (en) | 1980-02-11 | 1900-01-01 | Process for preparing human insulin or threonine B30 esters of human insulin, or a salt or complex thereof | |
| IE50892B1 (en) | 1980-02-11 | 1986-08-06 | Novo Industri As | Process for preparing insulin esters |
| US4364385A (en) | 1981-03-13 | 1982-12-21 | Lossef Steven V | Insulin delivery device |
| DE3274065D1 (de) | 1981-07-08 | 1986-12-11 | Draco Ab | Powder inhalator |
| EP0083619A1 (en) | 1981-07-17 | 1983-07-20 | Nordisk Insulinlaboratorium | A stable aqueous, therapeutic insulin preparation and a process for preparing it |
| US5260306A (en) | 1981-07-24 | 1993-11-09 | Fisons Plc | Inhalation pharmaceuticals |
| DK353781A (da) | 1981-08-10 | 1983-02-11 | Novo Industri As | Fremgangsmaade til fremstilling af insulinderivater |
| KR890000664B1 (ko) | 1981-10-19 | 1989-03-22 | 바리 안소니 뉴우샘 | 미분된 베클로메타손 디프로피오네이트 일수화물의 제조방법 |
| FI78616C (fi) | 1982-02-05 | 1989-09-11 | Novo Industri As | Foerfarande foer framstaellning av en foer infusionsaendamaol avsedd stabiliserad insulinloesning, som har en foerhoejd zinkhalt. |
| US4459226A (en) | 1982-02-26 | 1984-07-10 | Eli Lilly And Company | Process for recovering insulin |
| US4659696A (en) | 1982-04-30 | 1987-04-21 | Takeda Chemical Industries, Ltd. | Pharmaceutical composition and its nasal or vaginal use |
| JPS59163313A (ja) | 1983-03-09 | 1984-09-14 | Teijin Ltd | 経鼻投与用ペプチドホルモン類組成物 |
| US4946828A (en) | 1985-03-12 | 1990-08-07 | Novo Nordisk A/S | Novel insulin peptides |
| US5785989A (en) | 1985-05-01 | 1998-07-28 | University Utah Research Foundation | Compositions and methods of manufacturing of oral dissolvable medicaments |
| PT83613B (en) | 1985-10-28 | 1988-11-21 | Lilly Co Eli | Process for the selective chemical removal of a protein amino-terminal residue |
| SE453566B (sv) | 1986-03-07 | 1988-02-15 | Draco Ab | Anordning vid pulverinhalatorer |
| JPS6320301A (ja) | 1986-07-11 | 1988-01-28 | Dainichi Color & Chem Mfg Co Ltd | キトサン微小粒体 |
| US5042975A (en) | 1986-07-25 | 1991-08-27 | Rutgers, The State University Of New Jersey | Iontotherapeutic device and process and iontotherapeutic unit dose |
| NZ221411A (en) | 1986-08-11 | 1989-10-27 | Innovata Biomed Ltd | Pharmaceutical compositions containing microcapsules and a surfactant |
| USRE35862E (en) | 1986-08-18 | 1998-07-28 | Emisphere Technologies, Inc. | Delivery systems for pharmacological agents encapsulated with proteinoids |
| AU610083B2 (en) * | 1986-08-18 | 1991-05-16 | Clinical Technologies Associates, Inc. | Delivery systems for pharmacological agents |
| ATE76311T1 (de) | 1986-08-19 | 1992-06-15 | Genentech Inc | Einrichtung und dispersion zum intrapulmonalen eingeben von polypeptidwuchsstoffen und zytokinen. |
| NO162160C (no) | 1987-01-09 | 1989-11-15 | Medi Cult As | Serumfritt vekstmedium, samt anvendelse derav. |
| US4861627A (en) | 1987-05-01 | 1989-08-29 | Massachusetts Institute Of Technology | Preparation of multiwall polymeric microcapsules |
| GB8723846D0 (en) | 1987-10-10 | 1987-11-11 | Danbiosyst Ltd | Bioadhesive microsphere drug delivery system |
| EP0360340A1 (en) | 1988-09-19 | 1990-03-28 | Akzo N.V. | Composition for nasal administration containing a peptide |
| JPH02104531A (ja) | 1988-10-14 | 1990-04-17 | Toyo Jozo Co Ltd | 経鼻投与用生理活性ペプチド組成物 |
| US5006343A (en) | 1988-12-29 | 1991-04-09 | Benson Bradley J | Pulmonary administration of pharmaceutically active substances |
| US5514646A (en) | 1989-02-09 | 1996-05-07 | Chance; Ronald E. | Insulin analogs modified at position 29 of the B chain |
| ES2062530T3 (es) | 1989-05-01 | 1994-12-16 | Alkermes Inc | Procedimiento para producir particulas pequeñas de moleculas biologicamente activas. |
| GB8921222D0 (en) | 1989-09-20 | 1989-11-08 | Riker Laboratories Inc | Medicinal aerosol formulations |
| US5188837A (en) | 1989-11-13 | 1993-02-23 | Nova Pharmaceutical Corporation | Lipsopheres for controlled delivery of substances |
| DE3942145A1 (de) | 1989-12-20 | 1991-06-27 | Boehringer Mannheim Gmbh | T-pa-solubilisierung |
| GB9001635D0 (en) | 1990-01-24 | 1990-03-21 | Ganderton David | Aerosol carriers |
| CA2081474A1 (en) | 1990-05-08 | 1991-11-09 | Manzer Durrani | Direct spray-dried drug/lipid powder composition |
| US5693338A (en) | 1994-09-29 | 1997-12-02 | Emisphere Technologies, Inc. | Diketopiperazine-based delivery systems |
| US6331318B1 (en) | 1994-09-30 | 2001-12-18 | Emisphere Technologies Inc. | Carbon-substituted diketopiperazine delivery systems |
| SE9002895D0 (sv) | 1990-09-12 | 1990-09-12 | Astra Ab | Inhalation devices for dispensing powders i |
| IL99699A (en) | 1990-10-10 | 2002-04-21 | Autoimmune Inc | Drug with the option of oral, intra-intestinal, or inhaled dosing for suppression of autoimmune response associated with type I diabetes |
| GB9024760D0 (en) | 1990-11-14 | 1991-01-02 | Riker Laboratories Inc | Inhalation device and medicament carrier |
| US5145684A (en) | 1991-01-25 | 1992-09-08 | Sterling Drug Inc. | Surface modified drug nanoparticles |
| WO1992014449A1 (en) | 1991-02-20 | 1992-09-03 | Nova Pharmaceutical Corporation | Controlled release microparticulate delivery system for proteins |
| US5492112A (en) | 1991-05-20 | 1996-02-20 | Dura Pharmaceuticals, Inc. | Dry powder inhaler |
| AU653026B2 (en) | 1991-06-07 | 1994-09-15 | Teikoku Seiyaku Kabushiki Kaisha | Physiologically active polypeptide-containing pharmaceutical composition |
| DE69230613T2 (de) | 1991-07-02 | 2000-12-28 | Inhale Inc | Verfahren und vorrichtung zum abgeben von medikamenten in aerosolform |
| GB9116610D0 (en) | 1991-08-01 | 1991-09-18 | Danbiosyst Uk | Preparation of microparticles |
| US6063910A (en) | 1991-11-14 | 2000-05-16 | The Trustees Of Princeton University | Preparation of protein microparticles by supercritical fluid precipitation |
| US5329976A (en) | 1991-12-09 | 1994-07-19 | Habley Medical Technology Corporation | Syringe-filling and medication mixing dispenser |
| JP3121080B2 (ja) | 1991-12-19 | 2000-12-25 | アール・ピー・シーラー コーポレイション | カプセル封入用溶液 |
| ATE146359T1 (de) | 1992-01-21 | 1997-01-15 | Stanford Res Inst Int | Verbessertes verfahren zur herstellung von mikronisierter polypeptidarzneimitteln |
| EP0558879B1 (en) | 1992-03-04 | 1997-05-14 | Astra Aktiebolag | Disposable inhaler |
| US5352461A (en) | 1992-03-11 | 1994-10-04 | Pharmaceutical Discovery Corporation | Self assembling diketopiperazine drug delivery system |
| KR100208979B1 (ko) | 1992-06-12 | 1999-07-15 | 야스이 쇼사꾸 | 기도내 투여용 제제 |
| GB9213874D0 (en) | 1992-06-30 | 1992-08-12 | Fisons Plc | Process to novel medicament form |
| US5785049A (en) | 1994-09-21 | 1998-07-28 | Inhale Therapeutic Systems | Method and apparatus for dispersion of dry powder medicaments |
| US6582728B1 (en) | 1992-07-08 | 2003-06-24 | Inhale Therapeutic Systems, Inc. | Spray drying of macromolecules to produce inhaleable dry powders |
| SK51695A3 (en) | 1992-10-19 | 1995-11-08 | Dura Pharma Inc | Dry powder medicament inhaler |
| US5888477A (en) | 1993-01-29 | 1999-03-30 | Aradigm Corporation | Use of monomeric insulin as a means for improving the bioavailability of inhaled insulin |
| US5364838A (en) | 1993-01-29 | 1994-11-15 | Miris Medical Corporation | Method of administration of insulin |
| US5747445A (en) | 1993-06-24 | 1998-05-05 | Astra Aktiebolag | Therapeutic preparation for inhalation |
| IS1796B (is) | 1993-06-24 | 2001-12-31 | Ab Astra | Fjölpeptíð lyfjablanda til innöndunar sem einnig inniheldur eykjaefnasamband |
| TW402506B (en) | 1993-06-24 | 2000-08-21 | Astra Ab | Therapeutic preparation for inhalation |
| US5562909A (en) | 1993-07-12 | 1996-10-08 | Massachusetts Institute Of Technology | Phosphazene polyelectrolytes as immunoadjuvants |
| WO1996010996A1 (en) | 1993-07-21 | 1996-04-18 | The University Of Kentucky Research Foundation | A multicompartment hard capsule with control release properties |
| US5534488A (en) | 1993-08-13 | 1996-07-09 | Eli Lilly And Company | Insulin formulation |
| EP1132404A3 (en) | 1993-09-17 | 2002-03-27 | Novo Nordisk A/S | Acylated insulin |
| GB9322014D0 (en) | 1993-10-26 | 1993-12-15 | Co Ordinated Drug Dev | Improvements in and relating to carrier particles for use in dry powder inhalers |
| AU686277B2 (en) | 1993-11-16 | 1998-02-05 | Pacira Pharmaceuticals, Inc. | Vesicles with controlled release of actives |
| EP0655237A1 (de) | 1993-11-27 | 1995-05-31 | Hoechst Aktiengesellschaft | Medizinische Aerosolformulierung |
| US5484606A (en) | 1994-01-24 | 1996-01-16 | The Procter & Gamble Company | Process for reducing the precipitation of difficulty soluble pharmaceutical actives |
| US6051256A (en) | 1994-03-07 | 2000-04-18 | Inhale Therapeutic Systems | Dispersible macromolecule compositions and methods for their preparation and use |
| ATE416755T1 (de) | 1994-03-07 | 2008-12-15 | Nektar Therapeutics | Verfahren und zusammensetzung für die pulmonale darreichung von insulin |
| US6395744B1 (en) | 1994-04-22 | 2002-05-28 | Queen's University At Kingston | Method and compositions for the treatment or amelioration of female sexual dysfunction |
| WO1995031979A1 (en) | 1994-05-19 | 1995-11-30 | R.P. Scherer International Corporation | Solutions of aryl or heteroaryl substituted alkanoic acids in lipophilic solvents and soft gelatin capsules containing such solutions |
| IL110024A (en) | 1994-06-15 | 1998-04-05 | Yissum Res Dev Co | Controlled release oral drug delivery system containing hydrogel- forming polymer |
| US5461031A (en) | 1994-06-16 | 1995-10-24 | Eli Lilly And Company | Monomeric insulin analog formulations |
| US5474978A (en) | 1994-06-16 | 1995-12-12 | Eli Lilly And Company | Insulin analog formulations |
| US5547929A (en) | 1994-09-12 | 1996-08-20 | Eli Lilly And Company | Insulin analog formulations |
| US5877174A (en) | 1994-12-01 | 1999-03-02 | Toyama Chemical Co., Ltd. | 2,3-diketopiperazine derivatives or their salts |
| US5901703A (en) | 1995-02-06 | 1999-05-11 | Unisia Jecs Corporation | Medicine administering device for nasal cavities |
| US5653961A (en) | 1995-03-31 | 1997-08-05 | Minnesota Mining And Manufacturing Company | Butixocort aerosol formulations in hydrofluorocarbon propellant |
| US6258341B1 (en) | 1995-04-14 | 2001-07-10 | Inhale Therapeutic Systems, Inc. | Stable glassy state powder formulations |
| US6428771B1 (en) | 1995-05-15 | 2002-08-06 | Pharmaceutical Discovery Corporation | Method for drug delivery to the pulmonary system |
| US5653987A (en) | 1995-05-16 | 1997-08-05 | Modi; Pankaj | Liquid formulations for proteinic pharmaceuticals |
| US5766620A (en) | 1995-10-23 | 1998-06-16 | Theratech, Inc. | Buccal delivery of glucagon-like insulinotropic peptides |
| US5849322A (en) | 1995-10-23 | 1998-12-15 | Theratech, Inc. | Compositions and methods for buccal delivery of pharmaceutical agents |
| AU7678196A (en) * | 1995-11-13 | 1997-06-05 | Minimed, Inc. | Methods and compositions for the delivery of monomeric proteins |
| DE19545257A1 (de) | 1995-11-24 | 1997-06-19 | Schering Ag | Verfahren zur Herstellung von morphologisch einheitlichen Mikrokapseln sowie nach diesem Verfahren hergestellte Mikrokapseln |
| FR2746035B1 (fr) | 1996-03-15 | 1998-06-12 | Microparticules de gel composite susceptibles d'etre utilisees comme vecteur(s) de principe(s) actif(s), l'un de leurs procedes de preparation et leurs applications | |
| US5912014A (en) | 1996-03-15 | 1999-06-15 | Unigene Laboratories, Inc. | Oral salmon calcitonin pharmaceutical products |
| USRE37053E1 (en) | 1996-05-24 | 2001-02-13 | Massachusetts Institute Of Technology | Particles incorporating surfactants for pulmonary drug delivery |
| US5985309A (en) | 1996-05-24 | 1999-11-16 | Massachusetts Institute Of Technology | Preparation of particles for inhalation |
| US6503480B1 (en) | 1997-05-23 | 2003-01-07 | Massachusetts Institute Of Technology | Aerodynamically light particles for pulmonary drug delivery |
| US5874064A (en) | 1996-05-24 | 1999-02-23 | Massachusetts Institute Of Technology | Aerodynamically light particles for pulmonary drug delivery |
| US6254854B1 (en) | 1996-05-24 | 2001-07-03 | The Penn Research Foundation | Porous particles for deep lung delivery |
| AUPO066096A0 (en) | 1996-06-26 | 1996-07-18 | Peptide Delivery Systems Pty Ltd | Oral delivery of peptides |
| US5783556A (en) * | 1996-08-13 | 1998-07-21 | Genentech, Inc. | Formulated insulin-containing composition |
| US7312196B2 (en) | 1997-01-08 | 2007-12-25 | Amylin Pharmaceuticals, Inc. | Formulations for amylin agonist peptides |
| US6410511B2 (en) | 1997-01-08 | 2002-06-25 | Amylin Pharmaceuticals, Inc. | Formulations for amylin agonist peptides |
| EP1005490B1 (en) | 1997-03-20 | 2006-03-29 | Novo Nordisk A/S | Zinc free insulin crystals for use in pulmonary compositions |
| JP2001518916A (ja) | 1997-03-20 | 2001-10-16 | ノボ ノルディスク アクティーゼルスカブ | 結晶インスリンを含有する肺投与のための治療用粉末調合物 |
| US6310038B1 (en) | 1997-03-20 | 2001-10-30 | Novo Nordisk A/S | Pulmonary insulin crystals |
| US5898028A (en) | 1997-03-20 | 1999-04-27 | Novo Nordisk A/S | Method for producing powder formulation comprising an insulin |
| JP2001518915A (ja) | 1997-03-20 | 2001-10-16 | ノボ ノルディスク アクティーゼルスカブ | インシュリンと吸収増強剤の共沈殿による治療用粉末の調整法 |
| WO1999009997A1 (en) | 1997-08-26 | 1999-03-04 | Board Of Regents, The University Of Texas System | Edta and other chelators with or without antifungal antimicrobial agents for the prevention and treatment of fungal infections |
| EP1952802A3 (en) | 1997-10-01 | 2009-06-17 | Novadel Pharma Inc. | Buccal, polar and non-polar spray or capsule |
| WO1999034821A1 (en) | 1998-01-09 | 1999-07-15 | Novo Nordisk A/S | Stabilised insulin compositions |
| CN1423553A (zh) | 1998-04-09 | 2003-06-11 | 阿克西瓦有限公司 | 用于肺部给药的颗粒赋形剂 |
| US6552024B1 (en) | 1999-01-21 | 2003-04-22 | Lavipharm Laboratories Inc. | Compositions and methods for mucosal delivery |
| US6248363B1 (en) | 1999-11-23 | 2001-06-19 | Lipocine, Inc. | Solid carriers for improved delivery of active ingredients in pharmaceutical compositions |
| DE60026982T2 (de) | 1999-04-05 | 2006-11-16 | Mannkind Corp., Danbury | Verfahren zur bildung von feinem pulver |
| US7169889B1 (en) | 1999-06-19 | 2007-01-30 | Biocon Limited | Insulin prodrugs hydrolyzable in vivo to yield peglylated insulin |
| DK1808438T3 (da) | 1999-06-29 | 2014-10-27 | Mannkind Corp | Rensning og stabilisering af peptid og proteiner i lægemidler |
| US7464706B2 (en) | 1999-07-23 | 2008-12-16 | Mannkind Corporation | Unit dose cartridge and dry powder inhaler |
| DE60038511T2 (de) | 1999-07-23 | 2009-04-30 | Mannkind Corp., Valencia | Einzelportionskapseln für einen Trockenpulverinhalator |
| US6264981B1 (en) | 1999-10-27 | 2001-07-24 | Anesta Corporation | Oral transmucosal drug dosage using solid solution |
| NZ518401A (en) | 1999-10-29 | 2004-01-30 | Nektar Therapeutics | Dry powder compositions having improved dispersivity |
| US6465425B1 (en) | 2000-02-10 | 2002-10-15 | Alkermes Controlled Therapeutics, Inc. | Microencapsulation and sustained release of biologically active acid-stable or free sulfhydryl-containing proteins |
| NZ521034A (en) | 2000-02-28 | 2004-08-27 | Vectura Ltd | Improvements in or relating to the delivery of oral drugs |
| US6432383B1 (en) | 2000-03-30 | 2002-08-13 | Generex Pharmaceuticals Incorporated | Method for administering insulin |
| US7316999B2 (en) | 2000-06-02 | 2008-01-08 | Novo Nordisk A/S | Glucose dependent release of insulin from glucose sensing insulin derivatives |
| CN1141974C (zh) | 2000-06-07 | 2004-03-17 | 张昊 | 结肠定位释放的口服生物制剂 |
| CN100553636C (zh) | 2000-08-04 | 2009-10-28 | Dmi生物科学公司 | 二酮基哌嗪和包含它们的组合物的使用方法 |
| JP4147234B2 (ja) | 2004-09-27 | 2008-09-10 | キヤノン株式会社 | 吐出用液体、吐出方法、カートリッジ及び吐出装置 |
| DE10114178A1 (de) * | 2001-03-23 | 2002-10-10 | Aventis Pharma Gmbh | Zinkfreie und zinkarme Insulinzubereitungen mit verbesserter Stabilität |
| WO2003035030A1 (en) | 2001-10-24 | 2003-05-01 | Pari Gmbh | Kit for the preparation of a pharmaceutical composition |
| US20030198666A1 (en) | 2002-01-07 | 2003-10-23 | Richat Abbas | Oral insulin therapy |
| US20030143195A1 (en) | 2002-01-30 | 2003-07-31 | Pinsker Judy Senior | Use of histamine as a drug delivery enhancing compound for use in transmucosal or transdermal delivery |
| US7255102B2 (en) | 2002-02-01 | 2007-08-14 | Generex Pharmaceuticals Inc. | Metered dose spray device for use with macromolecular pharmaceutical agents such as insulin |
| WO2003074029A1 (en) | 2002-03-07 | 2003-09-12 | Vectura Limited | Fast melt multiparticulate formulations for oral delivery |
| US20030194420A1 (en) | 2002-04-11 | 2003-10-16 | Richard Holl | Process for loading a drug delivery device |
| WO2003094951A1 (en) | 2002-05-07 | 2003-11-20 | Novo Nordisk A/S | Soluble formulations comprising insulin aspart and insulin detemir |
| DE10227232A1 (de) | 2002-06-18 | 2004-01-15 | Aventis Pharma Deutschland Gmbh | Saure Insulinzubereitungen mit verbesserter Stabilität |
| DE10235168A1 (de) | 2002-08-01 | 2004-02-12 | Aventis Pharma Deutschland Gmbh | Verfahren zur Reinigung von Preproinsulin |
| BR0315194A (pt) | 2002-10-31 | 2005-08-23 | Umd Inc | Composições terapêuticas para liberação de droga para a, e através da, cobertura epitelial |
| BR0316685A (pt) | 2002-12-17 | 2005-11-01 | Nastech Pharm Co | Composições e métodos para a administração aperfeiçoada por via mucosal de peptìdeos fixadores ao receptor de y2 e métodos para tratar e prevenir a obesidade |
| EP1605916A4 (en) | 2003-02-12 | 2012-02-22 | R & P Korea Co Ltd | SOLVENT SYSTEM OF A SMOOTH MEDICAMENT WITH IMPROVED ELUTION RATE |
| US20040171518A1 (en) | 2003-02-27 | 2004-09-02 | Medtronic Minimed, Inc. | Compounds for protein stabilization and methods for their use |
| EP1605895A4 (en) | 2003-03-06 | 2011-08-24 | Emisphere Tech Inc | ORAL INSULIN THERAPIES AND PROTOCOL |
| US20050203001A1 (en) | 2004-03-05 | 2005-09-15 | Emisphere Technologies, Inc. | Oral insulin therapies and protocol |
| BR122019021416A2 (https=) * | 2003-09-19 | 2019-12-21 | ||
| US7192919B2 (en) | 2004-01-07 | 2007-03-20 | Stelios Tzannis | Sustained release compositions for delivery of pharmaceutical proteins |
| NZ548980A (en) | 2004-01-12 | 2009-10-30 | Mannkind Corp | Reducing serum proinsulin levels in type 2 diabetics |
| WO2005086814A2 (en) | 2004-03-09 | 2005-09-22 | The Uab Research Foundation | Methods and compositions related to regulation of cytokine production by glycogen synthase kinase 3 (gsk-3) |
| US20080085298A1 (en) | 2004-03-12 | 2008-04-10 | Biodel, Inc. | Rapid Mucosal Gel or Film Insulin Compositions |
| US7279457B2 (en) * | 2004-03-12 | 2007-10-09 | Biodel, Inc. | Rapid acting drug delivery compositions |
| US20080096800A1 (en) | 2004-03-12 | 2008-04-24 | Biodel, Inc. | Rapid mucosal gel or film insulin compositions |
| US20080090753A1 (en) | 2004-03-12 | 2008-04-17 | Biodel, Inc. | Rapid Acting Injectable Insulin Compositions |
| WO2006088473A2 (en) | 2004-04-23 | 2006-08-24 | Panduranga Rao Koritala | Microcapsules and nanocapsules for the transmucosal delivery of therapeutic and diagnostic agents |
| US7964012B2 (en) * | 2005-08-03 | 2011-06-21 | Hollingsworth & Vose Company | Filter media with improved conductivity |
| US7713929B2 (en) * | 2006-04-12 | 2010-05-11 | Biodel Inc. | Rapid acting and long acting insulin combination formulations |
| US8084420B2 (en) | 2005-09-29 | 2011-12-27 | Biodel Inc. | Rapid acting and long acting insulin combination formulations |
| WO2007041481A1 (en) | 2005-09-29 | 2007-04-12 | Biodel, Inc. | Rapid acting and prolonged acting insulin preparations |
| JP2009512709A (ja) | 2005-10-20 | 2009-03-26 | エムディーアールエヌエー，インコーポレイテッド | 速効型インスリンの経鼻投与 |
| US20090215669A1 (en) * | 2005-11-22 | 2009-08-27 | Dia-B Tech Limited | Compositions and methods for treatment of diabetes |
| US8093207B2 (en) | 2005-12-09 | 2012-01-10 | Unigene Laboratories, Inc. | Fast-acting oral peptide pharmaceutical products |
| FR2896164B1 (fr) * | 2006-01-18 | 2008-07-04 | Flamel Technologies Sa | Formulation colloidale d'insuline longue action et sa preparation |
| EP2012817A2 (en) | 2006-04-12 | 2009-01-14 | Biodel, Inc. | Rapid acting and long acting insulin combination formulations |
| US8084022B2 (en) | 2006-06-23 | 2011-12-27 | Aegis Therapeutics, Llc | Stabilizing alkylglycoside compositions and methods thereof |
| WO2008013955A2 (en) | 2006-07-27 | 2008-01-31 | Nektar Therapeutics | Sustained release formulations for pulmonary delivery |
| WO2008016729A1 (en) | 2006-08-04 | 2008-02-07 | Nastech Pharmaceutical Company Inc. | Compositions for intranasal delivery of human insulin and uses thereof |
| GB0700523D0 (en) | 2007-01-11 | 2007-02-21 | Insense Ltd | The Stabilisation Of Proteins |
| JP5552046B2 (ja) | 2007-06-13 | 2014-07-16 | ノボ・ノルデイスク・エー／エス | インスリン誘導体を含有する薬学的製剤 |
| EP2234644B1 (en) | 2008-01-04 | 2013-07-31 | Biodel, Inc. | Insulin formulations for insulin release as a function of tissue glucose levels |
| TWI394580B (zh) | 2008-04-28 | 2013-05-01 | Halozyme Inc | 超快起作用胰島素組成物 |
| US9060927B2 (en) | 2009-03-03 | 2015-06-23 | Biodel Inc. | Insulin formulations for rapid uptake |
| KR101775000B1 (ko) | 2009-06-26 | 2017-09-04 | 노보 노르디스크 에이/에스 | 인슐린, 니코틴아미드 및 아미노산을 포함하는 제제 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20140146209A (ko) * | 2012-04-16 | 2014-12-24 | 바이오델 아이엔씨 | 인슐린 및 인슐린 유사체의 약동학 및 약역학과 주사 통증을 조절하기 위한 마그네슘 조성물 |
| KR20160122145A (ko) * | 2014-01-13 | 2016-10-21 | 써멀린 다이어비티즈, 엘엘씨 | 초속효성 인슐린 제형 및 약제학적 전달 시스템 |
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