FI70671C - Foerfarande foer framstaellning av en mot denaturering bestaendig proteinloesning - Google Patents
Foerfarande foer framstaellning av en mot denaturering bestaendig proteinloesning Download PDFInfo
- Publication number
- FI70671C FI70671C FI801361A FI801361A FI70671C FI 70671 C FI70671 C FI 70671C FI 801361 A FI801361 A FI 801361A FI 801361 A FI801361 A FI 801361A FI 70671 C FI70671 C FI 70671C
- Authority
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- Finland
- Prior art keywords
- solution
- insulin
- proteins
- aqueous
- formula
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- 238000000034 method Methods 0.000 title claims description 17
- 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 claims description 83
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/62—Insulins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Zoology (AREA)
- Epidemiology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Toxicology (AREA)
- Pharmacology & Pharmacy (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Engineering & Computer Science (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2917535A DE2917535C2 (de) | 1979-04-30 | 1979-04-30 | Gegen Denaturierung beständige Insulinlösungen |
| DE2917535 | 1979-04-30 | ||
| DE19792952119 DE2952119A1 (de) | 1979-12-22 | 1979-12-22 | Gegen denaturierung bestaendige, waessrige protein-loesungen |
| DE2952119 | 1979-12-22 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI801361A7 FI801361A7 (fi) | 1980-10-31 |
| FI70671B FI70671B (fi) | 1986-06-26 |
| FI70671C true FI70671C (fi) | 1986-10-06 |
Family
ID=25778936
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI801361A FI70671C (fi) | 1979-04-30 | 1980-04-28 | Foerfarande foer framstaellning av en mot denaturering bestaendig proteinloesning |
Country Status (11)
Families Citing this family (52)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SU1011126A1 (ru) * | 1981-07-14 | 1983-04-15 | Всесоюзный научно-исследовательский и испытательный институт медицинской техники | Средство дл лечени сахарного диабета |
| 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. |
| US4609546A (en) * | 1982-06-24 | 1986-09-02 | Japan Chemical Research Co., Ltd. | Long-acting composition |
| US4457916A (en) * | 1982-08-31 | 1984-07-03 | Asahi Kasei Kogyo Kabushiki Kaisha | Method for stabilizing Tumor Necrosis Factor and a stable aqueous solution or powder containing the same |
| DE3325223A1 (de) * | 1983-07-13 | 1985-01-24 | Hoechst Ag, 6230 Frankfurt | Gegen denaturierung bestaendige, waessrige proteinloesungen, verfahren zu ihrer herstellung und ihre verwendung |
| CA1244347A (en) * | 1984-05-29 | 1988-11-08 | Eddie H. Massey | Stabilized insulin formulations |
| US4839341A (en) * | 1984-05-29 | 1989-06-13 | Eli Lilly And Company | Stabilized insulin formulations |
| DE3443877A1 (de) * | 1984-06-09 | 1985-12-12 | Hoechst Ag | Insulinzubereitungen, verfahren zu deren herstellung und deren verwendung |
| AU626840B2 (en) * | 1988-02-26 | 1992-08-13 | Genentech Inc. | Human relaxin formulation |
| US5981485A (en) * | 1997-07-14 | 1999-11-09 | Genentech, Inc. | Human growth hormone aqueous formulation |
| IL87055A (en) * | 1988-07-08 | 1994-06-24 | Illana Gozes | Conjugates of vasoactive intestinal peptide (vip) and of fragments thereof and pharmaceutical compositions comprising them |
| US5447912A (en) * | 1989-09-18 | 1995-09-05 | Senetek, Plc | Erection-inducing methods and compositions |
| US5830452A (en) * | 1990-11-20 | 1998-11-03 | Chiron Corporation | Method for enhancing the anti-tumor therapeutic index of interleukin-2 |
| DE19722950A1 (de) * | 1997-05-31 | 1998-12-03 | Huels Chemische Werke Ag | Renaturierung von Eiweißstoffen |
| DE19726167B4 (de) | 1997-06-20 | 2008-01-24 | Sanofi-Aventis Deutschland Gmbh | Insulin, Verfahren zu seiner Herstellung und es enthaltende pharmazeutische Zubereitung |
| PT917879E (pt) | 1997-11-22 | 2002-12-31 | Roche Diagnostics Gmbh | Processo melhorado para estabilizacao de proteinas |
| US6852694B2 (en) | 2001-02-21 | 2005-02-08 | Medtronic Minimed, Inc. | Stabilized insulin formulations |
| DE10114178A1 (de) | 2001-03-23 | 2002-10-10 | Aventis Pharma Gmbh | Zinkfreie und zinkarme Insulinzubereitungen mit verbesserter Stabilität |
| US6737401B2 (en) * | 2001-06-28 | 2004-05-18 | Metronic Minimed, Inc. | Methods of evaluating protein formulation stability and surfactant-stabilized insulin formulations derived therefrom |
| DE10227232A1 (de) * | 2002-06-18 | 2004-01-15 | Aventis Pharma Deutschland Gmbh | Saure Insulinzubereitungen mit verbesserter Stabilität |
| EP2077132A1 (en) | 2008-01-02 | 2009-07-08 | Boehringer Ingelheim Pharma GmbH & Co. KG | Dispensing device, storage device and method for dispensing a formulation |
| ES2669591T3 (es) | 2008-06-20 | 2018-05-28 | Novartis Ag | Inmunoglobulinas con agregación reducida |
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| JP5670421B2 (ja) | 2009-03-31 | 2015-02-18 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | コンポーネント表面のコーティング方法 |
| US9265910B2 (en) | 2009-05-18 | 2016-02-23 | Boehringer Ingelheim International Gmbh | Adapter, inhalation device, and nebulizer |
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| SI2498802T1 (sl) | 2009-11-13 | 2015-05-29 | Sanofi-Aventis Deutschland Gmbh | Farmacevtski sestavek, ki vsebuje agonist GLP-1, inzulin in metionin |
| US10016568B2 (en) | 2009-11-25 | 2018-07-10 | Boehringer Ingelheim International Gmbh | Nebulizer |
| JP5715640B2 (ja) | 2009-11-25 | 2015-05-13 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | ネブライザ |
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| US9943654B2 (en) | 2010-06-24 | 2018-04-17 | Boehringer Ingelheim International Gmbh | Nebulizer |
| US20140148384A1 (en) | 2010-08-30 | 2014-05-29 | Sanofi-Aventis Deutschland Gmbh | Use of ave0010 for the manufacture of a medicament for the treatment of diabetes mellitus type 2 |
| WO2012130757A1 (de) | 2011-04-01 | 2012-10-04 | Boehringer Ingelheim International Gmbh | Medizinisches gerät mit behälter |
| US9821032B2 (en) | 2011-05-13 | 2017-11-21 | Sanofi-Aventis Deutschland Gmbh | Pharmaceutical combination for improving glycemic control as add-on therapy to basal insulin |
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| CN103917241A (zh) | 2011-08-29 | 2014-07-09 | 赛诺菲-安万特德国有限公司 | 用于2型糖尿病患者中的血糖控制的药物组合 |
| TWI559929B (en) | 2011-09-01 | 2016-12-01 | Sanofi Aventis Deutschland | Pharmaceutical composition for use in the treatment of a neurodegenerative disease |
| WO2013152894A1 (de) | 2012-04-13 | 2013-10-17 | Boehringer Ingelheim International Gmbh | Zerstäuber mit kodiermitteln |
| WO2014076423A1 (fr) | 2012-11-13 | 2014-05-22 | Adocia | Formulation à action rapide d'insuline comprenant un composé anionique substitué |
| JP6643231B2 (ja) | 2013-08-09 | 2020-02-12 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | ネブライザ |
| EP2835146B1 (en) | 2013-08-09 | 2020-09-30 | Boehringer Ingelheim International GmbH | Nebulizer |
| PT3139982T (pt) | 2014-05-07 | 2022-04-05 | Boehringer Ingelheim Int | Nebulizador |
| DK3139984T3 (da) | 2014-05-07 | 2021-07-19 | Boehringer Ingelheim Int | Forstøver |
| CN106255554B (zh) | 2014-05-07 | 2021-05-04 | 勃林格殷格翰国际有限公司 | 容器、喷雾器及用途 |
| LT3229828T (lt) | 2014-12-12 | 2023-06-12 | Sanofi-Aventis Deutschland Gmbh | Insulino glargino/liksisenatido fiksuoto santykio kompozicija |
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| TWI748945B (zh) | 2015-03-13 | 2021-12-11 | 德商賽諾菲阿凡提斯德意志有限公司 | 第２型糖尿病病患治療 |
| TW201705975A (zh) | 2015-03-18 | 2017-02-16 | 賽諾菲阿凡提斯德意志有限公司 | 第２型糖尿病病患之治療 |
| JO3749B1 (ar) | 2015-08-27 | 2021-01-31 | Lilly Co Eli | تركيبات إنسولين سريعة المفعول |
| EA201992351A1 (ru) | 2017-06-01 | 2020-03-26 | Эли Лилли Энд Компани | Быстродействующие композиции инсулина |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2212695A1 (de) * | 1972-03-16 | 1973-09-20 | Hoechst Ag | Verfahren zur reinigung von insulin und insulinderivaten |
| US4179337A (en) * | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| GB1554157A (en) * | 1975-06-13 | 1979-10-17 | Takeda Chemical Industries Ltd | Stable insulin preparation for intra nasal administration |
| US4153689A (en) * | 1975-06-13 | 1979-05-08 | Takeda Chemical Industries, Ltd. | Stable insulin preparation for nasal administration |
| GB1563311A (en) * | 1975-09-26 | 1980-03-26 | Yamanouchi Pharma Co Ltd | Pharmaceutical composition of insulin for rectal use |
| DE3325223A1 (de) * | 1983-07-13 | 1985-01-24 | Hoechst Ag, 6230 Frankfurt | Gegen denaturierung bestaendige, waessrige proteinloesungen, verfahren zu ihrer herstellung und ihre verwendung |
| CA1244347A (en) * | 1984-05-29 | 1988-11-08 | Eddie H. Massey | Stabilized insulin formulations |
-
1980
- 1980-04-25 DE DE8080102252T patent/DE3064888D1/de not_active Expired
- 1980-04-25 EP EP80102252A patent/EP0018609B1/de not_active Expired
- 1980-04-28 IL IL59933A patent/IL59933A/xx unknown
- 1980-04-28 FI FI801361A patent/FI70671C/fi not_active IP Right Cessation
- 1980-04-28 GR GR61804A patent/GR67209B/el unknown
- 1980-04-28 EG EG256/80A patent/EG15017A/xx active
- 1980-04-29 CA CA000350871A patent/CA1146069A/en not_active Expired
- 1980-04-29 DK DK185180A patent/DK160459C/da not_active IP Right Cessation
- 1980-04-29 AU AU57877/80A patent/AU535040B2/en not_active Expired
- 1980-08-19 ES ES494356A patent/ES8106407A1/es not_active Expired
-
1987
- 1987-12-22 US US07/136,673 patent/US4885164A/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| DK160459B (da) | 1991-03-18 |
| ES494356A0 (es) | 1981-07-16 |
| DK185180A (da) | 1980-10-31 |
| EP0018609A1 (de) | 1980-11-12 |
| EP0018609B1 (de) | 1983-09-21 |
| CA1146069A (en) | 1983-05-10 |
| IL59933A (en) | 1984-06-29 |
| ES8106407A1 (es) | 1981-07-16 |
| FI801361A7 (fi) | 1980-10-31 |
| AU5787780A (en) | 1980-11-06 |
| FI70671B (fi) | 1986-06-26 |
| GR67209B (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1981-06-24 |
| DE3064888D1 (en) | 1983-10-27 |
| IL59933A0 (en) | 1980-06-30 |
| AU535040B2 (en) | 1984-03-01 |
| US4885164A (en) | 1989-12-05 |
| EG15017A (en) | 1985-12-31 |
| DK160459C (da) | 1991-08-26 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MA | Patent expired |
Owner name: AVENTIS PHARMA DEUTSCHLAND GMBH |