NO323933B1 - Stabil ikke-vandig formulering av en peptidforbindelse, fremgangsmate for fremstilling av denne og anvendelse av formuleringen til fremstillig av medikament. - Google Patents

Stabil ikke-vandig formulering av en peptidforbindelse, fremgangsmate for fremstilling av denne og anvendelse av formuleringen til fremstillig av medikament. Download PDF

Info

Publication number: NO323933B1
Authority: NO; Norway
Prior art keywords: leuprolide; formulation; formulations; peptide compound; aqueous
Prior art date: 1996-07-03

Application number

NO19986209A

Other languages

English (en)

Norwegian (no)

Other versions

NO986209L (no

NO986209D0 (no

Inventor

Jeremy Corwin Wright

Cynthia L Stevenson

Steven J Prestrelski

Sally Tao

Joe Leonard

James B Eckenhoff

Original Assignee

Alza Corp

Priority date (The priority date 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 date listed.)

1996-07-03

Filing date

1998-12-30

Publication date

2007-07-23

1998-12-30 Application filed by Alza Corp filed Critical Alza Corp

1998-12-30 Publication of NO986209L publication Critical patent/NO986209L/no

1998-12-30 Publication of NO986209D0 publication Critical patent/NO986209D0/no

2007-07-23 Publication of NO323933B1 publication Critical patent/NO323933B1/no

Links

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239000011159 matrix material Substances 0.000 description 1
CWWARWOPSKGELM-SARDKLJWSA-N methyl (2s)-2-[[(2s)-2-[[2-[[(2s)-2-[[(2s)-2-[[(2s)-5-amino-2-[[(2s)-5-amino-2-[[(2s)-1-[(2s)-6-amino-2-[[(2s)-1-[(2s)-2-amino-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-5 Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)OC)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CCCN=C(N)N)C1=CC=CC=C1 CWWARWOPSKGELM-SARDKLJWSA-N 0.000 description 1
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BLCLNMBMMGCOAS-UHFFFAOYSA-N n-[1-[[1-[[1-[[1-[[1-[[1-[[1-[2-[(carbamoylamino)carbamoyl]pyrrolidin-1-yl]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amin Chemical compound C1CCC(C(=O)NNC(N)=O)N1C(=O)C(CCCN=C(N)N)NC(=O)C(CC(C)C)NC(=O)C(COC(C)(C)C)NC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 BLCLNMBMMGCOAS-UHFFFAOYSA-N 0.000 description 1
PCJGZPGTCUMMOT-ISULXFBGSA-N neurotensin Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 PCJGZPGTCUMMOT-ISULXFBGSA-N 0.000 description 1
229910052757 nitrogen Chemical group 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
XNOPRXBHLZRZKH-DSZYJQQASA-N oxytocin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@H](N)C(=O)N1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)NCC(N)=O)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 XNOPRXBHLZRZKH-DSZYJQQASA-N 0.000 description 1
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230000000704 physical effect Effects 0.000 description 1
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239000002798 polar solvent Substances 0.000 description 1
239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
208000006155 precocious puberty Diseases 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
229960003415 propylparaben Drugs 0.000 description 1
230000005855 radiation Effects 0.000 description 1
238000009790 rate-determining step (RDS) Methods 0.000 description 1
NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 1
229960000553 somatostatin Drugs 0.000 description 1
230000001954 sterilising effect Effects 0.000 description 1
238000003860 storage Methods 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
239000000725 suspension Substances 0.000 description 1
230000002459 sustained effect Effects 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
102000003390 tumor necrosis factor Human genes 0.000 description 1
VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
229960003726 vasopressin Drugs 0.000 description 1
238000003260 vortexing Methods 0.000 description 1
229940033942 zoladex Drugs 0.000 description 1
NXSIJWJXMWBCBX-NWKQFZAZSA-N α-endorphin Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)NC(=O)CNC(=O)CNC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=CC=C1 NXSIJWJXMWBCBX-NWKQFZAZSA-N 0.000 description 1

Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/08—Peptides having 5 to 11 amino acids
- A61K38/09—Luteinising hormone-releasing hormone [LHRH], i.e. Gonadotropin-releasing hormone [GnRH]; Related peptides
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/18—Feminine contraceptives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/06—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Organic Chemistry (AREA)
Endocrinology (AREA)
Epidemiology (AREA)
Reproductive Health (AREA)
Diabetes (AREA)
Gynecology & Obstetrics (AREA)
Oil, Petroleum & Natural Gas (AREA)
Urology & Nephrology (AREA)
Dermatology (AREA)
Gastroenterology & Hepatology (AREA)
Immunology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Medicinal Preparation (AREA)
Peptides Or Proteins (AREA)

NO19986209A 1996-07-03 1998-12-30 Stabil ikke-vandig formulering av en peptidforbindelse, fremgangsmate for fremstilling av denne og anvendelse av formuleringen til fremstillig av medikament. NO323933B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US2112996P	1996-07-03	1996-07-03
PCT/US1997/010815 WO1998000152A1 (en)	1996-07-03	1997-07-01	Non-aqueous protic peptide formulations

Publications (3)

Publication Number	Publication Date
NO986209L NO986209L (no)	1998-12-30
NO986209D0 NO986209D0 (no)	1998-12-30
NO323933B1 true NO323933B1 (no)	2007-07-23

Family

ID=21802501

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO19986209A NO323933B1 (no)	1996-07-03	1998-12-30	Stabil ikke-vandig formulering av en peptidforbindelse, fremgangsmate for fremstilling av denne og anvendelse av formuleringen til fremstillig av medikament.

Country Status (27)

Country	Link
EP (1)	EP0909175B1 (de)
JP (3)	JP2001504802A (de)
CN (1)	CN1231256C (de)
AR (1)	AR008060A1 (de)
AT (1)	ATE241997T1 (de)
AU (1)	AU737664B2 (de)
BR (1)	BR9710130A (de)
CA (1)	CA2259403A1 (de)
CO (1)	CO4890854A1 (de)
CZ (1)	CZ433898A3 (de)
DE (1)	DE69722620T2 (de)
DK (1)	DK0909175T3 (de)
ES (1)	ES2201306T3 (de)
HU (1)	HUP9903942A3 (de)
ID (1)	ID19165A (de)
IL (1)	IL127769A (de)
MY (1)	MY121684A (de)
NO (1)	NO323933B1 (de)
NZ (1)	NZ333580A (de)
PL (1)	PL189402B1 (de)
PT (1)	PT909175E (de)
RO (1)	RO119862B1 (de)
RU (1)	RU2203085C2 (de)
SK (1)	SK284490B6 (de)
TW (1)	TW491703B (de)
WO (1)	WO1998000152A1 (de)
ZA (1)	ZA975942B (de)

Families Citing this family (40)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CZ433898A3 (cs) *	1996-07-03	1999-04-14	Alza Corporation	Nevodné protické peptidové formulace
US7258869B1 (en)	1999-02-08	2007-08-21	Alza Corporation	Stable non-aqueous single phase viscous vehicles and formulations utilizing such vehicle
US7919109B2 (en)	1999-02-08	2011-04-05	Intarcia Therapeutics, Inc.	Stable non-aqueous single phase viscous vehicles and formulations utilizing such vehicles
US20030119734A1 (en)	2001-06-28	2003-06-26	Flink James M.	Stable formulation of modified GLP-1
US7731947B2 (en)	2003-11-17	2010-06-08	Intarcia Therapeutics, Inc.	Composition and dosage form comprising an interferon particle formulation and suspending vehicle
US7772188B2 (en)	2003-01-28	2010-08-10	Ironwood Pharmaceuticals, Inc.	Methods and compositions for the treatment of gastrointestinal disorders
AU2004233869B2 (en) *	2003-04-25	2010-08-12	Boston Scientific Scimed, Inc.	Solid drug formulation and device for storage and controlled delivery thereof
PT1687019T (pt) *	2003-11-20	2018-02-26	Novo Nordisk As	Formulações de péptidos que contêm polietileno glicol que são ótimas para produção e para utilização em dispositivos de injeção
US11246913B2 (en)	2005-02-03	2022-02-15	Intarcia Therapeutics, Inc.	Suspension formulation comprising an insulinotropic peptide
WO2006083761A2 (en)	2005-02-03	2006-08-10	Alza Corporation	Solvent/polymer solutions as suspension vehicles
KR101106510B1 (ko)	2006-05-30	2012-01-20	인타르시아 세라퓨틱스 인코포레이티드	투피스, 내부채널 삼투압 전달 시스템 유동 조절기
CA2670821C (en)	2006-08-09	2012-05-15	Intarcia Therapeutics, Inc.	Osmotic delivery systems and piston assemblies
AU2013203271B2 (en) *	2007-01-19	2016-05-12	Hananja Ehf	Methods and compositions for the delivery of a therapeutic agent
CN106389330A (zh) *	2007-01-19	2017-02-15	哈南亚有限公司	用于递送治疗剂的方法和组合物
US20080275030A1 (en)	2007-01-19	2008-11-06	Sveinbjorn Gizurarson	Methods and Compositions for the Delivery of a Therapeutic Agent
CA2683610C (en)	2007-04-23	2013-01-08	Intarcia Therapeutics, Inc.	Suspension formulations of insulinotropic peptides and uses thereof
CA2691531C (en)	2007-06-22	2016-11-01	Board Of Regents,The University Of Texas System	Formation of stable submicron peptide or protein particles by thin film freezing
WO2009102467A2 (en)	2008-02-13	2009-08-20	Intarcia Therapeutics, Inc.	Devices, formulations, and methods for delivery of multiple beneficial agents
CA2730760A1 (en) *	2008-07-16	2010-01-21	Surmodics Pharmaceuticals, Inc.	Process for preparing microparticles containing bioactive peptides
US20120213846A1 (en)	2008-08-15	2012-08-23	Forest Laboratories Holdings Limited	Stable Solid Formulation of a GC-C Receptor Agonist Polypeptide Suitable for Oral Administration
WO2010056657A2 (en)	2008-11-16	2010-05-20	Board Of Regents, The Univesity Of Texas System	Low viscosity highly concentrated suspensions
US8748573B2 (en)	2009-08-06	2014-06-10	Ironwood Pharmaceuticals, Inc.	Formulations comprising linaclotide
MX378797B (es)	2009-09-28	2025-03-10	Intarcia Therapeutics Inc	Establecimiento y/o terminacion rapidos de suministro de estado estable sustancial de farmaco.
WO2011103311A2 (en)	2010-02-17	2011-08-25	Ironwood Pharmaceuticals, Inc	Treatments for gastrointestinal disorders
HRP20192207T1 (hr)	2010-08-11	2020-02-21	Ironwood Pharmaceuticals, Inc.	Stabilne formulacije linaklotida
US20120208755A1 (en)	2011-02-16	2012-08-16	Intarcia Therapeutics, Inc.	Compositions, Devices and Methods of Use Thereof for the Treatment of Cancers
HUE032237T2 (en)	2011-08-17	2017-09-28	Ironwood Pharmaceuticals Inc	Treatments for gastrointestinal disorders
US20130288968A1 (en) *	2012-04-30	2013-10-31	Sun Pharmaceutical Industries Ltd.	Leuprolide injection
WO2014124096A1 (en) *	2013-02-06	2014-08-14	Perosphere Inc.	Stable glucagon formulations
EP2823808A1 (de) *	2013-07-09	2015-01-14	Ipsen Pharma S.A.S.	Pharmazeutische Zusammensetzung für eine verzögerte Freisetzung von Lanreotid
US9889085B1 (en)	2014-09-30	2018-02-13	Intarcia Therapeutics, Inc.	Therapeutic methods for the treatment of diabetes and related conditions for patients with high baseline HbA1c
CN113598842A (zh)	2015-06-03	2021-11-05	因塔西亚制药公司	植入物放置和移除系统
KR102574993B1 (ko)	2016-05-16	2023-09-06	인타르시아 세라퓨틱스 인코포레이티드	글루카곤-수용체 선택적 폴리펩티드 및 이들의 이용 방법
USD860451S1 (en)	2016-06-02	2019-09-17	Intarcia Therapeutics, Inc.	Implant removal tool
USD840030S1 (en)	2016-06-02	2019-02-05	Intarcia Therapeutics, Inc.	Implant placement guide
WO2018129058A1 (en)	2017-01-03	2018-07-12	Intarcia Therapeutics, Inc.	Methods comprising continuous administration of a glp-1 receptor agonist and co-adminstration of a drug
EP3372224A1 (de)	2017-03-07	2018-09-12	Alrise Biosystems GmbH	Neues system zur kontrollierten wirkstoffabgabe durch mit wasser mischbare lösungsmittel zur herstellung von mit arzneimitteln beladenen mikro- und nanopartikeln
HUE066356T2 (hu)	2017-08-24	2024-07-28	Novo Nordisk As	GLP-1 készítmények és alkalmazásaik
PE20221575A1 (es)	2020-02-18	2022-10-06	Novo Nordisk As	Formulaciones farmaceuticas
WO2022187234A1 (en)	2021-03-01	2022-09-09	Stryker Corporation	Real time bur chatter compensation in surgical cutting burs

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4897256A (en) *	1986-11-25	1990-01-30	Abbott Laboratories	LHRH analog formulations
DE3886880T2 (de) *	1987-10-15	1994-07-14	Syntex Inc	Pulverförmige Zubereitungen zur intranasalen Verabreichung von Polypeptiden.
US4980163A (en) *	1989-03-01	1990-12-25	Public Health Research Institute Of The City Of New York	Novel bacteriocin compositions for use as enhanced broad range bactericides and methods of preventing and treating microbial infection
US5158761A (en) *	1989-04-05	1992-10-27	Toko Yakuhin Kogyo Kabushiki Kaisha	Spray gel base and spray gel preparation using thereof
IT1237197B (it) *	1989-11-16	1993-05-26	Sclavo Spa	Formulazioni farmaceutiche anidre e forme di dosaggio per la somministrazione rettale di calcitonina.
RU2008354C1 (ru) *	1991-03-13	1994-02-28	Данилевич Василий Николаевич	Способ хранения препарата протеиназ
JP3756512B2 (ja) *	1992-09-21	2006-03-15	ファルマシア・アンド・アップジョン・カンパニー・エルエルシー	徐放性タンパク質製剤
JP3698721B2 (ja) *	1993-02-23	2005-09-21	ジェネンテク・インコーポレイテッド	有機溶媒を用いて処理したポリペプチドの賦形剤安定化
US5955430A (en) *	1993-09-24	1999-09-21	University Of Southern California	Use of angiotensin II fragments and analogs thereof in tissue repair
JP3597233B2 (ja) *	1993-10-21	2004-12-02	久光製薬株式会社	経鼻組成物及びそれを含有する経鼻製剤
CZ433898A3 (cs) *	1996-07-03	1999-04-14	Alza Corporation	Nevodné protické peptidové formulace

1997
- 1997-07-01 CZ CZ984338A patent/CZ433898A3/cs unknown
- 1997-07-01 DK DK97930181T patent/DK0909175T3/da active
- 1997-07-01 AU AU34073/97A patent/AU737664B2/en not_active Ceased
- 1997-07-01 CN CNB971960534A patent/CN1231256C/zh not_active Expired - Fee Related
- 1997-07-01 PT PT97930181T patent/PT909175E/pt unknown
- 1997-07-01 SK SK1799-98A patent/SK284490B6/sk not_active IP Right Cessation
- 1997-07-01 IL IL127769A patent/IL127769A/en not_active IP Right Cessation
- 1997-07-01 PL PL97330869A patent/PL189402B1/pl not_active IP Right Cessation
- 1997-07-01 JP JP50421898A patent/JP2001504802A/ja not_active Withdrawn
- 1997-07-01 BR BR9710130A patent/BR9710130A/pt not_active Application Discontinuation
- 1997-07-01 ES ES97930181T patent/ES2201306T3/es not_active Expired - Lifetime
- 1997-07-01 WO PCT/US1997/010815 patent/WO1998000152A1/en not_active Ceased
- 1997-07-01 NZ NZ333580A patent/NZ333580A/en not_active IP Right Cessation
- 1997-07-01 CA CA002259403A patent/CA2259403A1/en not_active Abandoned
- 1997-07-01 RO RO98-01769A patent/RO119862B1/ro unknown
- 1997-07-01 HU HU9903942A patent/HUP9903942A3/hu unknown
- 1997-07-01 AT AT97930181T patent/ATE241997T1/de active
- 1997-07-01 DE DE69722620T patent/DE69722620T2/de not_active Expired - Lifetime
- 1997-07-01 EP EP97930181A patent/EP0909175B1/de not_active Expired - Lifetime
- 1997-07-01 RU RU99102540/14A patent/RU2203085C2/ru not_active IP Right Cessation
- 1997-07-02 AR ARP970102967A patent/AR008060A1/es unknown
- 1997-07-03 ID IDP972315A patent/ID19165A/id unknown
- 1997-07-03 CO CO97037097A patent/CO4890854A1/es unknown
- 1997-07-03 ZA ZA9705942A patent/ZA975942B/xx unknown
- 1997-07-03 MY MYPI97003024A patent/MY121684A/en unknown
- 1997-08-22 TW TW086109392A patent/TW491703B/zh not_active IP Right Cessation
1998
- 1998-12-30 NO NO19986209A patent/NO323933B1/no not_active IP Right Cessation
2008
- 2008-04-23 JP JP2008112307A patent/JP2008195739A/ja active Pending
2009
- 2009-10-05 JP JP2009231256A patent/JP2010043105A/ja active Pending

Also Published As

Publication number	Publication date
CO4890854A1 (es)	2000-02-28
BR9710130A (pt)	1999-08-10
JP2010043105A (ja)	2010-02-25
CN1224356A (zh)	1999-07-28
AU3407397A (en)	1998-01-21
SK179998A3 (en)	1999-05-07
IL127769A (en)	2006-10-31
EP0909175B1 (de)	2003-06-04
CA2259403A1 (en)	1998-01-08
MY121684A (en)	2006-02-28
HUP9903942A2 (hu)	2000-04-28
EP0909175A1 (de)	1999-04-21
HUP9903942A3 (en)	2000-07-28
AU737664B2 (en)	2001-08-30
ATE241997T1 (de)	2003-06-15
PL330869A1 (en)	1999-06-07
RO119862B1 (ro)	2005-05-30
DK0909175T3 (da)	2003-09-29
PL189402B1 (pl)	2005-08-31
CZ433898A3 (cs)	1999-04-14
PT909175E (pt)	2003-10-31
RU2203085C2 (ru)	2003-04-27
ES2201306T3 (es)	2004-03-16
SK284490B6 (sk)	2005-05-05
NO986209L (no)	1998-12-30
ZA975942B (en)	1998-04-16
DE69722620D1 (de)	2003-07-10
WO1998000152A1 (en)	1998-01-08
IL127769A0 (en)	1999-10-28
TW491703B (en)	2002-06-21
ID19165A (id)	1998-06-28
JP2008195739A (ja)	2008-08-28
DE69722620T2 (de)	2004-04-29
CN1231256C (zh)	2005-12-14
NO986209D0 (no)	1998-12-30
AR008060A1 (es)	1999-12-09
JP2001504802A (ja)	2001-04-10
NZ333580A (en)	2000-06-23

Legal Events

Date	Code	Title	Description
2013-03-11	MM1K	Lapsed by not paying the annual fees

Publication	Publication Date	Title
EP0909175B1 (de)	2003-06-04	Nicht-waessrige protische peptidzubereitungen
EP0909177B1 (de)	2004-02-11	Wässrige peptidzubereitung
EP1208846B1 (de)	2004-04-07	Nichtwässrige polar-aprotische Peptidformulierungen enthaltend LHRH-verwandte Verbindungen
US5981489A (en)	1999-11-09	Non-aqueous protic peptide formulations
AU2004242540B2 (en)	2007-12-13	Aqueous formulations of peptides
KR100594519B1 (ko)	2007-03-02	비수성양성자성펩티드제제
AU775395B2 (en)	2004-07-29	Non-aqueous polar aprotic peptide formulations
HK1124244A (en)	2009-07-10	Non-aqueous polar aprotic peptide formulations