WO2002009739A1 - Traitement de troubles oculaires au moyen d'analogues de la somatostatine - Google Patents

Traitement de troubles oculaires au moyen d'analogues de la somatostatine Download PDF

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Publication number
WO2002009739A1
WO2002009739A1 PCT/EP2001/008620 EP0108620W WO0209739A1 WO 2002009739 A1 WO2002009739 A1 WO 2002009739A1 EP 0108620 W EP0108620 W EP 0108620W WO 0209739 A1 WO0209739 A1 WO 0209739A1
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WO
WIPO (PCT)
Prior art keywords
cys
trp
phe
lys
hydrogen
Prior art date
Application number
PCT/EP2001/008620
Other languages
English (en)
Inventor
Mario Fsadni
Kathrin Wyss
Original Assignee
Novartis Ag
Novartis-Erfindungen Verwaltungsgesellschaft M.B.H
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 Novartis Ag, Novartis-Erfindungen Verwaltungsgesellschaft M.B.H filed Critical Novartis Ag
Priority to AU2001283957A priority Critical patent/AU2001283957A1/en
Publication of WO2002009739A1 publication Critical patent/WO2002009739A1/fr

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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
    • A61K38/31—Somatostatins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents

Definitions

  • the present invention relates to a method of treating ocular disorders, in particular to a method of treating ocular neurodegeneration, comprising the administration of a somatostatin analogue, in particular octreotide, to an individual in need thereof.
  • the somatostatin class is a known class of small peptides comprising the naturally occurring somatostatin-14 and analogues having somatostatin related activity, e.g. as disclosed by A.S. Dutta in Small Peptides, Vol.19, Elsevier (1993).
  • a somatostatin peptide or "a somatostatin analogue” as used herein is meant any straight-chain or cyclic polypeptide having a structure based on that of the naturally occurring somatostatin-14 wherein one or more amino acid units have been omitted and/or replaced by one or more other amino radical(s) and/or wherein one or more functional groups have been replaced by one or more other functional groups and/or one or more groups have been replaced by one or several other isosteric groups.
  • the terms a somatostatin and a somatostatin analogue are used within this disclosure as synonyms.
  • the above mentioned somatostatins preferably octreotide, appear to maximize and / or preserve the function of the residual visual functions. Accordingly, the addressed somatostatins are highly useful in the treatment of glaucoma alone or in addition to ocular hypotensive agents or procedures. The benefit of said treatment is not dependant upon an effect on intraocular pressure (IOP).
  • IOP intraocular pressure
  • an addressed somatostatin in particular octreotide, is highly useful in the treatment and / or prevention of ocular disorders, selected from the group consisting of: Vision loss due to progressive retinal and / or optic nerve diseases such as glaucoma, retinitis pigmentosa, diabetic macular edema and age related macular degeneration.
  • treatment and / or prevention means the treatment and the prevention of a disorder, preferably the treatment or the prevention of a disorder, more preferably the treatment and in particular the prevention of a disorder.
  • Cyclic, bridge cyclic and straight-chain somatostatin analogues or derivatives are known and have been described together with processes for their production e.g. in US Patent 4,310,518.
  • Preferred somatostatin analogues are e. g. compounds of formula (I),
  • A is d. ⁇ alkyl, C 7-10 phenylalkyl or a group of formula RCO-, whereby i) R is hydrogen, C h alky!, phenyl or C 7- ⁇ 0 phenylalkyl, or ii) RCO- is
  • A' is hydrogen or C 1-3 alkyl
  • Yi and Y 2 represent together a direct bond or each of Yi and Y 2 is hydrogen
  • B is -Phe- optionally ring-substituted by halogen, NO 2 , NH , OH, C ⁇ -3 alkyl and /or C ⁇ -3 alkoxy (including pentafluoroalanine), naphthylalanine or pyridylalanine
  • C is (L)-Trp- or (D)-Trp- optionally a-N-methylated and optionally benzene- ring-substituted by halogen, NO 2 , NH 2 , OH, C ⁇ -3 alkyl and/or C ⁇ -3 alkoxy,
  • D is Lys, 4-aminocyclohexylAla or 4-aminocyclohexylGly
  • E is Thr, Ser, Val, Tyr, He, Leu or an aminobutyric or aminoisobutyric acid residue
  • G is a group of formula: -COOR 7 , -CH 2 OR 10 , -CONRnR ⁇ 2 or
  • R 7 is hydrogen or C h alky!
  • R 10 is hydrogen or the residue of a physiologically acceptable, physiologically hydrolysable ester
  • R 11 is hydrogen, C ⁇ -3 alkyl, phenyl or C 7- ⁇ 0 phenyl-alkyl
  • R 12 is hydrogen, C 1-3 alkyl or a group of formula -CH(R ⁇ 3 )-X ⁇
  • R 13 is CH 2 OH, -(CH 2 ) 2 -OH, -(CH 2 ) 3 -OH, or -CH(CH 3 )OH or represents the substituent attached to the a-carbon atom of a natural or synthetic a-amino acid (including hydrogen) and
  • ⁇ is a group of formula -COOR 7 , -CH 2 OR 10 or -CO-NR 14 R 15
  • R 7 and R 10 have the meanings given above,
  • R is hydrogen or C ⁇ - 3 alkyl
  • R15 is hydrogen, C ⁇ -3 alkyl, phenyl or C 7-10 phenylalkyl
  • R 1 6 is hydrogen or hydroxy
  • More preferred compounds of formula (I) are compounds (a) - (k).
  • a highly preferred compound of formula (I) is octreotide.
  • Compounds of formula (I) may exist e.g. in free form, salt form or in the form of complexes thereof.
  • Acid addition salts may be formed with e.g. organic acids, polymeric acids and inorganic acids. Such acid addition salt forms include e.g. the hydrochlorides and acetates.
  • Complexes are e.g. formed from compounds of the invention on addition of inorganic substances, e.g. inorganic salts or hydroxides such as Ca- and Zn-salts, and/or an addition of polymeric organic substances.
  • somatostatin analogues suitable for use in accordance with the present invention are: cyclo [-Asn-Phe-Phe-DTrp-Lys-Thr-Phe-Gaba-j, cyclo(Asu-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Tyr-Thr-Ser), and (D)Nal-Glu-Tyr-(D)Trp-Lys-Val-Lys-Thr-NH 2
  • a somatostatin analogue is preferably administered in the form of a pharmaceutical composition, by any conventional route, in particular enterally, e.g. orally, e.g. in the form of tablets, capsules, drink solutions, emulsions or microemulsion preconcentrates, nasally, pulmonary (by inhalation), parenterally, e.g. in the form of injectable solutions or suspensions, in the form of an implant, such as for example a biodegradable polymer loaded with a somatostatin, or topically.
  • a somatostatin analogue is preferably administered parenterally, typically subcutaneously and intramuscularily, e.g by injection and/or infusion.
  • the somatostatin analogue may also be administered in a slow release form, e.g. as disclosed in UK Patent Specification 2,265,311 B.
  • a somatostatin analogue may be administered, e.g. subcutaneously, in a dosage range of about 100 ⁇ g to 10 mg per day as a single dose or in divided doses.
  • octreotide may be administered at a dose of from 0.2 mg to 10 mg twice or three times daily.
  • such formulation may comprise the somatostatin peptide in a concentration from 2.0 to 10% by weight. The release period of such a formulation may be from 1 week to about 2 months.
  • the invention contemplates that an active ingredient discussed herein may be utilized in combination with pharmaceutically acceptable diluents and carriers.
  • Vehicle Carboxymethylcellulose 0.5 % (by weight)

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Ophthalmology & Optometry (AREA)
  • Endocrinology (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Epidemiology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

La présente invention se rapporte à une méthode de traitement de troubles oculaires par administration d'un analogue de somatostatine à un sujet justiciable d'un tel traitement.
PCT/EP2001/008620 2000-07-27 2001-07-25 Traitement de troubles oculaires au moyen d'analogues de la somatostatine WO2002009739A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2001283957A AU2001283957A1 (en) 2000-07-27 2001-07-25 Treatment of ocular disorders with somatostatin analogues

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP00116068 2000-07-27
EP00116068.8 2000-07-27

Publications (1)

Publication Number Publication Date
WO2002009739A1 true WO2002009739A1 (fr) 2002-02-07

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2001/008620 WO2002009739A1 (fr) 2000-07-27 2001-07-25 Traitement de troubles oculaires au moyen d'analogues de la somatostatine

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AU (1) AU2001283957A1 (fr)
WO (1) WO2002009739A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7189856B2 (en) 2001-12-28 2007-03-13 Gideon Shapiro Non-peptide somatostatin receptor ligands
EP1787658A1 (fr) 2005-11-10 2007-05-23 South Shore Properties Inc. Formulations à libération prolongée contenant des inhibiteurs de l'hormone de croissance analogues de la somatostatine
WO2011076368A2 (fr) 2009-12-22 2011-06-30 Bcn Peptides, S.A. Formulation peptidique ophtalmique topique

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000006185A2 (fr) * 1998-07-30 2000-02-10 Societe De Conseils De Recherches Et D'applications Scientifiques, S.A.S. Procedes d'utilisation d'un analogue de somatostatine
CA2263042A1 (fr) * 1999-02-25 2000-08-25 Robert W.A. Kuijpers Traitement de l'oedeme

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000006185A2 (fr) * 1998-07-30 2000-02-10 Societe De Conseils De Recherches Et D'applications Scientifiques, S.A.S. Procedes d'utilisation d'un analogue de somatostatine
CA2263042A1 (fr) * 1999-02-25 2000-08-25 Robert W.A. Kuijpers Traitement de l'oedeme

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
A.C. LAMBOOIJ ET AL.: "Somatostatin receptor 2A expression in choroidal neovascularization secondary to age-related macular degeneration.", INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, vol. 41, no. 8, July 2000 (2000-07-01), St. Louis, US, pages 2329 - 2335, XP000990309 *
A.C. LAMBOOIJ ET AL.: "Somatostatin receptor 2A expression in choroidal neovascularization secondary to AMD.", INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, vol. 41, no. 4 Suppl., 15 March 2000 (2000-03-15), St. Louis, US, pages S 836, XP002163800 *
C.W. SPRAUL ET AL.: "Effect of thalidomide, octreotide, and decortine on the migration and proliferation of RPE cells in vitro", INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, vol. 40, no. 4 Suppl., 15 March 1999 (1999-03-15), St. Louis, US, pages S 224, XP000990318 *
JAFFRAIN-REA M -L ET AL: "VISUAL IMPROVEMENT DURING OCTREOTIDE THERAPY IN A CASE OF EPISELLAR MENINGIOMA", CLINICAL NEUROLOGY AND NEUROSURGERY,NL,ELSEVIER, AMSTERDAM, vol. 100, no. 1, March 1998 (1998-03-01), pages 40 - 43, XP000907228, ISSN: 0303-8467 *
P.M. VAN HAGEN ET AL.: "Somatostatin and somatostatin receptors in retinal diseases.", EUROPEAN JOURNAL OF ENDOCRINOLOGY, vol. 143, no. Suppl. 1, October 2000 (2000-10-01), pages S 43 - S 51, XP000990364 *
R. KUYPERS ET AL.: "Somatostatin receptors in the human retina. A new target in the treatment of cystoid macular edema.", INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, vol. 40, no. 4 Suppl., 15 March 1999 (1999-03-15), St. Louis, US, pages S 795, XP000990319 *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7189856B2 (en) 2001-12-28 2007-03-13 Gideon Shapiro Non-peptide somatostatin receptor ligands
EP1787658A1 (fr) 2005-11-10 2007-05-23 South Shore Properties Inc. Formulations à libération prolongée contenant des inhibiteurs de l'hormone de croissance analogues de la somatostatine
WO2011076368A2 (fr) 2009-12-22 2011-06-30 Bcn Peptides, S.A. Formulation peptidique ophtalmique topique
US20130210728A1 (en) * 2009-12-22 2013-08-15 Bcn Peptides, S.A. Topical ophthalmic peptide formulation
AU2010335595B2 (en) * 2009-12-22 2015-08-27 Bcn Peptides, S.A. Topical ophthalmic peptide formulation
US9216208B2 (en) 2009-12-22 2015-12-22 Bcn Peptides, S.A. Topical ophthalmic peptide formulation

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