WO1993018785A1 - Nouveau medicament - Google Patents

Nouveau medicament Download PDF

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Publication number
WO1993018785A1
WO1993018785A1 PCT/DK1993/000098 DK9300098W WO9318785A1 WO 1993018785 A1 WO1993018785 A1 WO 1993018785A1 DK 9300098 W DK9300098 W DK 9300098W WO 9318785 A1 WO9318785 A1 WO 9318785A1
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WO
WIPO (PCT)
Prior art keywords
formula
medicament
gly
ala
glp
Prior art date
Application number
PCT/DK1993/000098
Other languages
English (en)
Inventor
Ole Kirk
Lone Pridal
Original Assignee
Novo Nordisk A/S
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.)
Filing date
Publication date
Application filed by Novo Nordisk A/S filed Critical Novo Nordisk A/S
Priority to EP93907819A priority Critical patent/EP0631504A1/fr
Priority to JP5516181A priority patent/JPH07504669A/ja
Publication of WO1993018785A1 publication Critical patent/WO1993018785A1/fr
Priority to KR1019940703281A priority patent/KR950700754A/ko

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22—Hormones
    • A61K38/26—Glucagons
    • 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
    • A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
    • 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
    • A61K9/0043—Nose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics

Definitions

  • the present invention relates to novel medica ⁇ ments containing GLP-l(7-37) , GLP-1(7-36)amide or analogues or functional derivatives thereof and a phospholipid, and to a method for preparing such medicaments.
  • Glucagon-li e peptide-1 is a peptide sequence found in the C-terminal portion of mammalian proglucagon.
  • GLP-1(1-36)amide like gluca- gon, stimulates insulin release from isolated precultured rat pancreatic islets in the presence of glucose in a dose-dependent manner (Schmidt, .E. et al. Diabetolo ia 28 (1985) 704-7) .
  • This finding suggests that GLP-1(1-36) amide and related peptides might be useful in the treatment of type 2 diabetes.
  • GIP glucose dependent insulinotropic peptide
  • 87/06941 (to The General Hospital Corporation) relates to a peptide fragment which comprises GLP-l(7-37) and functional derivatives thereof and to its use as an insulinotropic agent.
  • 90/11296 (to The General Hospital Corporation) relates to a peptide fragment which comprises GLP-l(7-36) and functional derivatives thereof and has an insulinotropic activity which exceeds the insulinotropic activity of GLP-l(l-36) or GLP-
  • the present invention is based on the fact that when GLP-1 related peptides are administered in a formula ⁇ tion comprising certain phospholipids, a very favourable absorption profile is found. Also, the phospholipids exert a stabilizing effect on the peptides.
  • the present inven ⁇ tion relates to a medicament for intranasal administration of a peptide fragment of formula I:
  • X is NH 2 or Gly-OH, or analogues or functional derivatives thereof, which medicament further comprises at least one phospholipid of the general formula II: (0) (OH) -OR ' ' '
  • R 1 and 1 ' are the same or different each repre ⁇ senting hydrogen, alkyl, alkenyl, alkanoyl, alkenoyl, alka- dienoyl, alkatrienoyl or alkatetraenoyl containing not more than 14 carbon atoms in each group, with the proviso that R 1 and R 1 ' are not hydrogen at the same time, and R" 1 is 2-
  • the invention relates to a medicament comprising GLP-1(7-36)amide.
  • the invention relates to a medicament comprising GLP-l(7-37). In a further preferred embodiment, the invention relates to a medicament comprising fragments of GLP-l(7-37).
  • the invention relates to a medicament comprising functional derivatives of fragments of GLP-l(7-37). In a further preferred embodiment, the invention relates to a medicament comprising analogues of GLP-1(7-37) .
  • the invention relates to a medicament comprising functional derivatives of analogues of GLP-l(7-37).
  • the invention relates to a medicament comprising a phospholipid of formula II wherein R , n is 2-(trimethylammonio)ethyl.
  • the invention relates to a medicament comprising a phospholipid of formula II wherein R 1 is alkyl having from 4 to 12 carbon atoms. In a further preferred embodiment, the invention relates to a medicament comprising a phospholipid of formula II wherein R' is alkanoyl having from 4 to 12 carbon atoms.
  • the invention relates to a medicament comprising a phospholipid of formula II wherein R 1 is decanoyl.
  • the invention relates to a medicament comprising a phospholipid of formula II wherein R' is hydrogen, with the proviso that R ! ' is different from hydrogen.
  • the invention relates to a medicament comprising a phospholipid of formula II wherein R 1 ' is alkyl having from 4 to 12 carbon atoms.
  • the invention relates to a medicament comprising a phospholipid of formula II wherein R' ' is alkanoyl having from 4 to 12 carbon atoms.
  • the invention relates to a medicament comprising a phospholipid of formula II wherein R 1 * is decanoyl.
  • the invention relates to a medicament comprising a phospholipid of formula II wherein R 1 ' is hydrogen, with the proviso that R 1 is different from hydrogen.
  • the invention relates to a medicament comprising didecanoyl L- ⁇ -phos- phatidylcholine.
  • the invention relates to a medicament comprising a solid diluent.
  • the invention relates to a solid medicament comprising from 0.01 to 75 % (W/W), preferably from 0.1 to 50 % (W/W) , more preferred from 0.5 to 25 % (W/W) of a peptide of formula I or ana ⁇ logues or functional derivatives thereof.
  • the invention relates to a solid medicament comprising from 10 to 99 % (W/W) , preferably from 10 to 80 % (W/W) , more preferred from 25 to 60 % (W/W) of a phospholipid of formula II.
  • the invention relates to a medicament comprising a liquid diluent.
  • the invention relates to a liquid medicament comprising from 0.0005 to 10 % (W/W), preferably from 0.001 to 5 % (W/W), more preferred from 0.01 to 5 % (W/W) of a peptide of formula I or ana ⁇ logues or functional derivatives thereof.
  • the invention relates to a liquid medicament comprising from 0.01 to 20 % (W/W) , preferably from 0.05 to 10 % (W/W) , more preferred from 0.1 to 5 % (W/W) of a phospholipid of formula II.
  • the invention relates to a method of making a medicament for intranasal administration of a peptide fragment of formula I:
  • X is NH 2 or Gly-OH, and analogues and functional derivatives thereof and further comprising at least one phospholipid of the general formula II:
  • R 1 and R 1 * are the same or different each repre ⁇ senting hydrogen, alkyl, alkenyl, alkanoyl, alkenoyl, alka- dienoyl, alkatrienoyl or alkatetraenoyl containing not more than 14 carbon atoms in each group, with the proviso that R 1 and R' • are not hydrogen at the same time, and R ⁇ n is 2- (trimethylammonio)ethyl, 2-aminoethyl or 2,3-dihydroxy- propyl, which method comprises mixing the required amounts of the peptide fragment of formula I and at least one phos- phopholipid of formula II, optionally in a solid or in a liquid diluent, and optionally further adding pH buffering agents, osmotic pressure controlling agents, preservatives or other ancillary agents.
  • the invention relates to a medicament for intranasal administration of a peptide fragment of formula I:
  • X is NH 2 or Gly-OH, or analogues or functional derivatives thereof, characterized in that it further com ⁇ prises at least one phospholipid of the general formula II:
  • R 1 and R' ' are the same or different each repre- senting hydrogen, alkyl, alkenyl, alkanoyl, alkenoyl, alka- dienoyl, alkatrienoyl or alkatetraenoyl containing not more than 14 carbon atoms in each group, with the proviso that R 1 and R 1 • are not hydrogen at the same time, and R" 1 is 2- (trimethylammonio)ethyl, 2-aminoethyl or 2,3-dihydroxypropyl when used as an insuliontropic agent in the treatment of diabetes.
  • analogues of GLPrl(7-37) means peptides which differ from GLP-l(7-37) in that at least one of the amino acid residues of GLP-1(7-37) indepen- dently have been exchanged by another amino acid residue, preferably one which can be coded for by the genetic code.
  • the definition also comprises the case when amino acid resi ⁇ dues are added at or deleted from the N-terminal and/or the C-terminal end of the peptide.
  • the total number of such additions, deletions and exchanges does not exceed five, more preferred it does not exceed three.
  • One advantage is that the absorption is slightly protracted. This is expedient because administration of the medicament can then take place as required immediately before a meal. In this way the peptide becomes available with its influence on the insulin secretion at the same time as the food arrives in the stomach. The patients need not plan their meals long time ahead and they thus experience an improved quality of life.
  • formulations according to the present invention can provide a plasma concentration of the peptide which .is fairly con ⁇ stant for a period of time sufficient to cover the duration of a meal.
  • formulations with tauro-24,25-dihydrofusidate, with ⁇ - cyclodextrin or with a plain phosphate buffer having a pH value of 7.4 tend to give a course of the plasma concentra ⁇ tion of the peptide which is less favourable: a very high initial peak which rather soon drops below the level obtain- able with the formulations with phospholipids.
  • Examples of preferred compounds of formula II are: dioctanoyl-L- ⁇ -phosphatidylcholine, dioctyl-O-L- ⁇ -phosphatidylcholine, didecanoyl-L- ⁇ -phosphatidylcholine, didecyl-O-L- ⁇ -phosphatidylcholine, decyl-O-L- ⁇ -lysophatidylcholine, dilauroyl-L- ⁇ -phosphatidylcholine, lauroyl-L- ⁇ -lysophosphatidylcholine.
  • the formulation of this invention may be liquid, e.g. adapted for administration as a spray or solid, e.g. a powder acceptable for snuffing.
  • Liquid formulations such as those based on aqueous formulations, may include ancil- lary agents, for example a pH-buffering system, preferably a phosphate r citrate or acetate buffer, a preservative and an osmotic pressure controlling agent, e.g. glycerol or sodium chloride.
  • Powder formulations may contain the pharmaceuti ⁇ cally active agent and the phospholipid of formula II in admixture with nasally acceptable powdery diluents or mix ⁇ tures thereof, e.g.
  • cellulose or derivatives thereof for example cellulose ethers or sodium carboxymethylcellulose, starch, a long chain fatty acid or a salt thereof, e.g. alu ⁇ minum stearate, an organic polymer, e.g. of an acrylic acid derivative or inorganic vehicles, such as talc or diatoma- ceous earth.
  • an organic polymer e.g. of an acrylic acid derivative or inorganic vehicles, such as talc or diatoma- ceous earth.
  • Supplementary addition of water-absorbing poly- mers for example polyethylene glycol or polyvinyl pyrroli- done may be desirable to improve adhesion of the powder for ⁇ mulation to the nasal mucosa.
  • Preferred liquid formulations are those in which the diluent is water.
  • Such formulations may be prepared by dispersing the phospholipid in the aqueous medium containing the GLP-1 derived active agent and ancillary agents, the dispersion being conducted by any method usually employed for suspension or emulsification, e.g. ultrasonic treatment. Adjustment of the aqueous phase to neutrality (i.e. to pH in the range from about 6.5 to about 8) may be accomplished in any of the preparatory steps.
  • proteases and peptidases are associated with the nasal mucosa (see R.E. Stratford and V.H.L. Lee: Int.Journ.Pharmaceutics .0 (1986), 73 - 82) it may be desirable to incorporate biocompatible protease and peptidase inhibitors into polypeptide containing formula ⁇ tions.
  • the concentration to be used of the GLP-1 derived active agent in the formulations of this invention will of course depend on the particular agent chosen, on its efficacy, on a comparison of its bioavailability by nasal administration and by other routes of administration, for example injection or infusion, and on the desired frequency of administration. Such pharmacological data can routinely be obtained by j-n vivo studies designed by those skilled in the art.
  • the total daily dose of the GLP-1 derived active agent to be given which i.a. depends on the particular agent and on the condition of the patient is determined by a medically skilled person.
  • the total daily dose is conveni ⁇ ently administered in submultiples thereof.
  • the total daily dose of a GLP-1 derived active agent to be administered nasally in the treatment of diabetes will be in the interval from 0.05 to 20 ⁇ g per kilogram of body weight.
  • An exemplary mode of preparing a GLP-l(7-36) amide formulation of this invention wherein the diluent is water comprises dissolving GLP-1(7-36)amide in water optio ⁇ nally in the presence of an acid, for example hydrochloric acid.
  • An aqueous solution of a preservative for example phenol, an alkyl phenol, such as cresol, or methyl p- hydroxybenzoate, is prepared separately, optionally also containing an agent rendering the solution isotonic, such as sodium chloride or glycerol.
  • the preservative solution may contain a buffering agent, such as sodium phos ⁇ phate, sodium citrate, sodium acetate or TRIS (tris(hydroxy- methyl)aminomethane) and a protease inhibitor.
  • a buffering agent such as sodium phos ⁇ phate, sodium citrate, sodium acetate or TRIS (tris(hydroxy- methyl)aminomethane) and a protease inhibitor.
  • the resulting preservative solution is then admixed with the solution of GLP-1(7-36)amide, optionally followed by addition of a base, for example a sodium hydroxide solution, to adjust the pH value to neutrality.
  • a base for example a sodium hydroxide solution
  • the phospolipid of formula II may be added to the solution of GLP-1(7-36)amide as a solution or an emulsion which is prepared by dissolving or suspending the phospholipid of formula II in water and, if necessary, subjecting any suspension to an ultrasonic treatment before mixing with the GLP-1(7-36)amide solution.
  • the phospholipid solution or emulsion may, if desired, con ⁇ tain the buffering agent and preservative.
  • the pH value of the formulation may be readjusted to neutrality. Finally, the resulting solution is made up to the calculated volume by addition of water.
  • the formulations of this invention may be used in any dosage dispensing device adapted for intranasal ad ⁇ ministration.
  • the device should be constructed with a view to ascertaining optimum metering accuracy and compatibility of is constructive elements, such as container, valve and actuator with the nasal formulation and could be based on a mechanical pump system, e.g. that of a metered-dose nebuli ⁇ zer, or on a pressurized aerosol system.
  • the aerosol system requires the propellant to be inert towards the formulation. Suitable propellants may be selected among such gases as fluorocarbons, hydrocarbons, nitrogen and dinitrogen oxide or mixtures thereof.
  • GLP-1(7-36) amide and GLP-l(7-37) were obtained from Bachem Feinkemicalien AG (Switzerland) and Peninsula Laboratories (England), respectively.
  • the concentration of GLP-1(7- 20 36)amide and GLP-l(7-37) in solution was monitored by stan ⁇ dard reversed phase HPLC employing a gradient of aceto- nitrile and 0.1% trifluoracetic acid (10-100% over 30 minutes) with UV detection at 280 nm.
  • the ⁇ -cyclodextrin was dissolved in distilled water, the peptide in question was added and the solution was freeze dried.
  • a solution containing 0.5 mg/ml of GLP-1(7-36)amide in the above described phospholipid vehicle and a solution con ⁇ taining 0.5 mg/ml of GLP-1(7-36) amide in a 5 mM sodium phos ⁇ phate buffer having a pH value of 7.4 were prepared.
  • Formulation 1 GLP-1(7-36)amide (250 ⁇ g) was dissolved in 1 ml of the phospholipid vehicle. 100 ⁇ l of this liquid formulation was applied in each of the nostrils of the rabbits in which it was tested.
  • Formulation 2 GLP-l(7-37) (250 ⁇ g) was dissolved in 1 ml of the phospholipid vehicle. 100 ⁇ l of this liquid formulation was applied in each of the nostrils of the rabbits in which it was tested.
  • Formulation 3 GLP-1(7-36)amide (50 ⁇ g) was dissolved in 1 ml of the tauro-24,25-dihydrofusidate vehicle. 100 ⁇ l of this liquid formulation was applied in each of the nostrils of the rabbits in which it was tested.
  • Formulation 4 GLP-1(7-36)amide (50 ⁇ g) was mixed with 100 mg of ⁇ -cyclodextrin. 20 mg of this powder formulation was applied in one nostril of each of the rabbits in which it was tested.
  • Formulation 5 GLP-1(7-36)amide (50 ⁇ g) was dissolved in 1 ml of a 20 mM sodium phosphate buffer having a pH value of 7.4. 100 ⁇ l of this liquid formulation was applied in each of the nostrils of the rabbits in which it was tested.
  • the liquid formulations were administered using an Eppendorf multipipette while the powder formulation was administered by cautiously blowing 20 mg thereof from a small tube into one nostril. 1,5 ml blood samples were withdrawn at the times indicated in Table 2 and the plasma concentration of the GLP-1 (7-36)amide and GLP-l(7-37) respectively was assayed by RIA as indicated under General methods.
  • Table 2 shows the observed increments in the plasma concen ⁇ trations of GLP-l(7-36)amide and GLP-l(7-37) respectively as a function of time after administration of the formulations 1 to 5 at 0 minutes.
  • the plasma concentrations are corrected for the basal level of GLP-1(7-36)amide .or GLP-l(7-37) respectively found in the plasma at 0 min and are expressed as percentage of the maximal plasma concentrations observed.
  • the maximal plasma concentrations observed for formulations 1 to 5 were 248 pM, 377 pM, 124 pM, 143 pM and 36 pM, respectively.
  • Formulation 2 GLP-l(7-37) (600 ⁇ g) was dissolved in 1 ml of the phospholipid vehicle. 100 ⁇ l of this liquid formulation was applied in nostril in each of eight rabbits.
  • the formulations were administered using an Eppendorf multi- pipette.
  • Table 3 shows the observed plasma concentrations of GLP-1(7- 36)amide and GLP-l(7-37) respectively in picomoles (pM) as a function of time after administration of the formulations.

Abstract

Cette invention concerne de nouveaux médicaments contenant du GLP-1(7-37), de l'amide de GLP-1(7-36) ou des analogues ou des dérivés fonctionnels de ce dernier et un phospholipide. Ces médicaments sont adaptés à l'administration par voie nasale et possèdent une caractéristique d'absorption très favorable.
PCT/DK1993/000098 1992-03-19 1993-03-18 Nouveau medicament WO1993018785A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
EP93907819A EP0631504A1 (fr) 1992-03-19 1993-03-18 Nouveau medicament
JP5516181A JPH07504669A (ja) 1992-03-19 1993-03-18 新規薬剤
KR1019940703281A KR950700754A (ko) 1992-03-19 1994-09-17 신규의 약물(novel medicament)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DK364/92 1992-03-19
DK92364A DK36492D0 (da) 1992-03-19 1992-03-19 Praeparat

Publications (1)

Publication Number Publication Date
WO1993018785A1 true WO1993018785A1 (fr) 1993-09-30

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Application Number Title Priority Date Filing Date
PCT/DK1993/000098 WO1993018785A1 (fr) 1992-03-19 1993-03-18 Nouveau medicament

Country Status (6)

Country Link
EP (1) EP0631504A1 (fr)
JP (1) JPH07504669A (fr)
KR (1) KR950700754A (fr)
AU (1) AU3888793A (fr)
DK (1) DK36492D0 (fr)
WO (1) WO1993018785A1 (fr)

Cited By (36)

* Cited by examiner, † Cited by third party
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EP0619322A2 (fr) * 1993-04-07 1994-10-12 Pfizer Inc. Libération prolonguée des peptides
WO1997007814A1 (fr) * 1995-08-22 1997-03-06 Bionebraska, Inc. Composition destinee a une alimentation parenterale amelioree et procede correspondant
WO1999029336A1 (fr) * 1997-12-05 1999-06-17 Eli Lilly And Company Formulations de glp-1
WO1999043706A1 (fr) 1998-02-27 1999-09-02 Novo Nordisk A/S Derives d'analogues de glp-1
WO1999043708A1 (fr) 1998-02-27 1999-09-02 Novo Nordisk A/S Derives de gpl-1 et de l'extendine au profil d'action etendu
WO1999043707A1 (fr) 1998-02-27 1999-09-02 Novo Nordisk A/S Derives de glp-1 modifies a l'extremite n-terminale
EP0997151A2 (fr) * 1998-08-28 2000-05-03 Eli Lilly And Company Méthode d'administration de peptides à activité insulinotropique
US6162907A (en) * 1986-05-05 2000-12-19 The General Hospital Corporation DNA encoding insulinotropic hormone
US6284727B1 (en) 1993-04-07 2001-09-04 Scios, Inc. Prolonged delivery of peptides
EP1250126A2 (fr) * 2000-01-11 2002-10-23 Novo Nordisk A/S Distribution transepitheliale de derives de glp-1
US6720407B1 (en) 1998-08-28 2004-04-13 Eli Lilly And Company Method for administering insulinotropic peptides
US6852690B1 (en) 1995-08-22 2005-02-08 Amylin Pharmaceuticals, Inc. Method and composition for enhanced parenteral nutrition
WO2005065714A1 (fr) * 2003-12-26 2005-07-21 Nastech Pharmaceutical Company Inc. Administration intranasale de peptides regulant le glucose
EP1634605A2 (fr) 2000-03-08 2006-03-15 Novo Nordisk A/S Traitement de la dyslipidémie chez un patient souffrant de diabète de type 2
EP1666054A1 (fr) * 1998-08-28 2006-06-07 Eli Lilly & Company Méthode d' administration de peptides à activité insulinotropique
WO2007061434A2 (fr) * 2005-11-10 2007-05-31 Nastech Pharmaceutical Company Inc. Formulation pharmaceutique de glp-1 et son utilisation pour traiter un syndrome metabolique
WO2007065156A3 (fr) * 2005-12-02 2007-07-19 Nastech Pharm Co Formulation pharmaceutique pour la permeabilite epitheliale accrue de peptide de regulation du glucose
EP1826216A1 (fr) 1996-08-30 2007-08-29 Novo Nordisk A/S Dérivés de Glp-1
EP1840134A2 (fr) 1998-02-27 2007-10-03 Novo Nordisk A/S Dérivés du GLP-1
EP1932535A2 (fr) 1998-07-31 2008-06-18 Novo Nordisk A/S Stimulation de la prolifération de cellules beta
WO2009121804A1 (fr) 2008-03-31 2009-10-08 Glaxo Group Limited Fusions et conjugués médicamenteux
WO2010108937A2 (fr) 2009-03-27 2010-09-30 Glaxo Group Limited Fusions de médicament et conjugués afférents
US7847079B2 (en) 2001-12-21 2010-12-07 Human Genome Sciences, Inc. Albumin fusion proteins
WO2011039096A1 (fr) 2009-09-30 2011-04-07 Glaxo Group Limited Fusions de médicaments et conjugués présentant une demi-vie prolongée
US8114959B2 (en) 2003-06-03 2012-02-14 Novo Nordisk A/S Stabilized pharmaceutical peptide compositions
US8114833B2 (en) 2003-11-20 2012-02-14 Novo Nordisk A/S Propylene glycol-containing peptide formulations which are optimal for production and for use in injection devices
WO2012136792A2 (fr) 2011-04-07 2012-10-11 Glaxo Group Limited Compositions de cck
WO2012136790A1 (fr) 2011-04-07 2012-10-11 Glaxo Group Limited Compositions comprenant des protéines de fusion ou des conjugués ayant une demi-vie améliorée
WO2013083826A2 (fr) 2011-12-09 2013-06-13 Novo Nordisk A/S Agonistes du glp-1
US8748376B2 (en) 2004-11-12 2014-06-10 Novo Nordisk A/S Stable formulations of peptides
EP2769990A2 (fr) 2004-12-02 2014-08-27 Domantis Limited Anticorps bispecifiques de domaine visant l'albumine serique et GPL-1 ou PYY
US8846618B2 (en) 2001-06-28 2014-09-30 Novo Nordisk A/S Stable formulation of modified GLP-1
WO2014184726A3 (fr) * 2013-05-15 2015-02-19 Stichting Het Nederlands Kanker Instituut - Antoni Van Leeuwenhoek Ziekenhuis Composés et utilisation thérapeutique de ceux-ci
EP2932981A2 (fr) 2003-09-19 2015-10-21 Novo Nordisk A/S Nouveaux dérivés GLP-1 se liant à l'albumine
US11318191B2 (en) 2020-02-18 2022-05-03 Novo Nordisk A/S GLP-1 compositions and uses thereof
US11752198B2 (en) 2017-08-24 2023-09-12 Novo Nordisk A/S GLP-1 compositions and uses thereof

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CZ315594A3 (en) * 1992-06-15 1995-07-12 Pfizer Peptide of glucagon type, insulinotropic derivatives, process of their preparation, pharmaceutical composition containing such compounds and use
CA2358107C (fr) * 1998-12-22 2011-08-23 Eli Lilly And Company Formulation de longue conservation de peptide-1 de type glucagon

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WO1990009385A1 (fr) * 1989-02-17 1990-08-23 The Liposome Company, Inc. Excipient lipidique pour administration par voie nasale et autres applications locales
WO1991002545A1 (fr) * 1989-08-18 1991-03-07 Danbiosyst Uk Limited Compositions pharmaceutiques
WO1991011457A1 (fr) * 1990-01-24 1991-08-08 Buckley Douglas I Analogues de glp-1 utiles dans le traitement du diabete

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Publication number Priority date Publication date Assignee Title
WO1988004556A1 (fr) * 1986-12-16 1988-06-30 Novo Industri A/S Formulations nasales et leur procede de preparation
WO1990009385A1 (fr) * 1989-02-17 1990-08-23 The Liposome Company, Inc. Excipient lipidique pour administration par voie nasale et autres applications locales
WO1991002545A1 (fr) * 1989-08-18 1991-03-07 Danbiosyst Uk Limited Compositions pharmaceutiques
WO1991011457A1 (fr) * 1990-01-24 1991-08-08 Buckley Douglas I Analogues de glp-1 utiles dans le traitement du diabete

Cited By (51)

* Cited by examiner, † Cited by third party
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DK36492D0 (da) 1992-03-19
JPH07504669A (ja) 1995-05-25
AU3888793A (en) 1993-10-21
EP0631504A1 (fr) 1995-01-04
KR950700754A (ko) 1995-02-20

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