EP1420791A1 - Utilisation de composes permettant de traiter des affections consecutives a une lesion du nerf corneen apres un lasik ou d'autres traumatismes ou chirurgies de l'oeil - Google Patents

Utilisation de composes permettant de traiter des affections consecutives a une lesion du nerf corneen apres un lasik ou d'autres traumatismes ou chirurgies de l'oeil

Info

Publication number
EP1420791A1
EP1420791A1 EP02756710A EP02756710A EP1420791A1 EP 1420791 A1 EP1420791 A1 EP 1420791A1 EP 02756710 A EP02756710 A EP 02756710A EP 02756710 A EP02756710 A EP 02756710A EP 1420791 A1 EP1420791 A1 EP 1420791A1
Authority
EP
European Patent Office
Prior art keywords
compound
injury
surgery
compounds
lasik
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.)
Withdrawn
Application number
EP02756710A
Other languages
German (de)
English (en)
Other versions
EP1420791A4 (fr
Inventor
Mark R. Hellberg
Iok-Hou Pang
John M. Yanni
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Alcon Inc
Original Assignee
Alcon Inc
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 Alcon Inc filed Critical Alcon Inc
Publication of EP1420791A1 publication Critical patent/EP1420791A1/fr
Publication of EP1420791A4 publication Critical patent/EP1420791A4/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7012—Compounds having a free or esterified carboxyl group attached, directly or through a carbon chain, to a carbon atom of the saccharide radical, e.g. glucuronic acid, neuraminic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/075—Ethers or acetals
    • A61K31/08—Ethers or acetals acyclic, e.g. paraformaldehyde
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/12—Ketones
    • A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/52—Purines, e.g. adenine
    • A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • 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
    • 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
    • A61P27/04—Artificial tears; Irrigation solutions

Definitions

  • the present invention is directed to the use of compounds that promote neuron
  • corneal nerves are damaged.
  • methods for surgery-induced dry eye include symptomatic reliefs such as the frequent local
  • artificial tears such as Tears Naturale or Bion Tears®, or other artificial tears
  • Neurotrophic factors are peptide molecules which stimulate or otherwise maintain
  • the neurotrophin (NT) family of peptides include nerve growth factor (NGF), brain-
  • BDNF derived neurotrophic factor
  • NT-3 NT-4/5 and NT-6. They act by binding to the neurotrophin receptors (NT-receptors), such as TrkA, TrkB, TrkC and p75NTR.
  • TrkA neurotrophin receptors
  • TrkB TrkB
  • TrkC neurotrophin receptors
  • p75NTR neurotrophin receptors
  • TrkA is selective for NGF
  • TrkB is selective for both BDNF and
  • TrkC is selective for NT-3. After binding, the NT-receptor complex is
  • TrkA and TrkB have been observed in the ocular tissue.
  • RNC retinal ganglion cells
  • DRC dopaminergic amacrine cells
  • optic nerve the optic nerve
  • CNTF Ciliary neurotrophic factor
  • bFGF Basic Fibroblast Growth Factor
  • neurotrophic factors that support survival of neurons. They are structurally unrelated to neurotrophins. They have also been shown to prevent lesion-induced death of neurons and
  • neurotrophic factors such as NGF
  • TrkA receptor (Lambiase et al. 1998, Lambiase et al. 2000).
  • neurotrophic factors are important for the health and normal function of the
  • compositions comprise one or more compound that promotes neuron
  • neurotrophic factor refers to NGF, BDNF, NT-3, NT-4/5, NT-6, CNTF, bFGF or other trophic factors which prevent,
  • neurotrophic factor stimulators include: AIT-082 (neotrofin), idebenone, CB-
  • NS521 ((l-(l-butyl)-4-(2-oxo-l-benzimidazolone) piperidine), SS-701, and KT-711 (all
  • AIT-082 (neotrofin).
  • the preceding molecules may be obtained
  • the methods of the present invention comprise administering to a human patient one
  • neurotrophic factor stimulators for the treatment of conditions resulting from corneal nerve
  • the methods of the present invention are particularly directed to the use of neuron
  • corneal nerve damage other conditions resulting from corneal nerve damage, such as a decrease in corneal
  • the neuron In general, the neuron
  • regeneration or neurite outgrowth promoting compounds will be formulated in solutions or
  • suspensions for topical ophthalmic or intraocular administration or as tablets, capsules or
  • solutions for systemic administration e.g., oral or intravenous.
  • the compounds for systemic administration e.g., oral or intravenous.
  • the compounds for systemic administration e.g., oral or intravenous.
  • the compounds for systemic administration e.g., oral or intravenous.
  • the compounds for systemic administration e.g., oral or intravenous.
  • the compounds for systemic administration e.g., oral or intravenous.
  • the compounds for systemic administration e.g., oral or intravenous.
  • treatment can also attenuate the decrease in corneal sensitivity caused by LASIK or other
  • the present invention is directed at the use of compounds that promote the
  • AIT-082 (Graul & Castaner 1997), idebenone (Nabeshima et al. 1994), ONO- 2506 (Matsui et al. 1998), NS521 (Gronborg et al. 1998), CB-1093 (Aimone et al. 1998) and
  • neurotrophic factor stimulators to treat dry eye or other iatrogenic injury
  • Topical ocular formulations of the neuron regeneration or neurite outgrowth promoting compounds are preferred due to ease of administration.
  • Topical ocular formulations of the neuron regeneration or neurite outgrowth promoting compounds are preferred due to ease of administration.
  • formulations may be in solutions or suspensions. In general, topical formulations will contain
  • the active neurotrophin factor stimulator and inert excipients are the active neurotrophin factor stimulator and inert excipients.
  • compositions of the present invention may be administered intraocularly following
  • compositions useful for corneal nerve damage to the corneal nerve, such as by LASIK or other surgeries.
  • intraocular administration will generally be intraocular injection compositions or surgical
  • Intraocular injection compositions will generally be comprised of an
  • aqueous solution e.g., balanced salt irrigating solutions, discussed below.
  • Irrigating Solution (Alcon Laboratories, Inc., Fort Worth, Texas, USA) are examples of
  • Retrobulbar and periocular injections are known to those skilled in the
  • pharmaceutically effective amount refers to
  • stimulators will generally be contained in the topical formulations or pharmaceutically acceptable carrier contemplated herein in an amount of from about 0.001 to about 10.0%
  • Topical formulations will generally be delivered to the eye one to six times a day, at the
  • Systemic administration compositions will generally contain
  • pharmaceutically acceptable carrier refers to any formulation
  • neurotrophic factor stimulator for the desired route of administration.
  • compositions of the present invention may contain additional pharmaceutically
  • compositions of the present invention resulting from injury to corneal nerves during surgery, the compositions of the present invention
  • agents may contain additional agents or may be dosed concurrently or sequentially with other agents or
  • compositions examples include: artificial tear, artificial moisterizing solutions or
  • the following example demonstrates the protective efficacy of a neurotrophic factor stimulator (propentofylline) against ocular tissue cell insult.
  • the Compounds can be administered systemically or locally to the eye (e.g., topically,
  • Ophthalmic solution formulations may be prepared by dissolving a
  • solution may include an ophthalmologically acceptable surfactant to assist in dissolving the
  • the ophthalmic solution may contain an agent to increase viscosity
  • hydroxymethylcellulose such as, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose,
  • methyl-cellulose methyl-cellulose, polyvinylpyrrolidone, or the like, to improve the retention of the
  • Gelling agents can also be used, including, but not
  • the active ingredient is combined with a preservative in an appropriate vehicle,
  • hydrophilic base may be prepared by suspending the active ingredient in a hydrophilic base prepared from the
  • formulations for analogous ophthalmic preparations; preservatives and tonicity agents can be
  • the Compounds are preferably formulated as topical ophthalmic suspensions or
  • the Compounds will normally be contained in these formulations in an amount 0.001% to 5% by weight, but preferably in an amount of 0.05% to
  • compositions and/or methods and in the steps or in the sequence of steps of the method
  • Brain-derived neurotrophic factor/neurotrophin-4 receptor TrkB is localized on ganglion cells and dopaminergics amacrine cells in the vertebrate retina, J. COMP.
  • NGF antisense oligonucleotide blocks protective effects of clenbuterol against
  • INVEST subjects and during manifestation of inflammatory diseases, INVEST. OPHTHALMOL. VIS.
  • Nerve growth factor promotes corneal healing: structural, biochemical, and
  • Brain-derived neurotrophic factor is a survival factor for cultured rat
  • cerebellar granule neurons and protects them against glutamate-induced neurotoxicity
  • INVEST basic fibroblast growth factor
  • BDNF Brain-derived neurotrophic factor

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Ophthalmology & Optometry (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Hydrogenated Pyridines (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

La présente invention concerne des méthodes permettant de traiter des affections consécutives à une lésion du nerf cornéen après un LASIK (kératomileusie in-situ au laser) ou d'autres traumatismes ou chirurgies de l'oeil.
EP02756710A 2001-08-29 2002-07-23 Utilisation de composes permettant de traiter des affections consecutives a une lesion du nerf corneen apres un lasik ou d'autres traumatismes ou chirurgies de l'oeil Withdrawn EP1420791A4 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US31565201P 2001-08-29 2001-08-29
US315652P 2001-08-29
PCT/US2002/023871 WO2003020281A1 (fr) 2001-08-29 2002-07-23 Utilisation de composes permettant de traiter des affections consecutives a une lesion du nerf corneen apres un lasik ou d'autres traumatismes ou chirurgies de l'oeil

Publications (2)

Publication Number Publication Date
EP1420791A1 true EP1420791A1 (fr) 2004-05-26
EP1420791A4 EP1420791A4 (fr) 2004-09-15

Family

ID=23225436

Family Applications (1)

Application Number Title Priority Date Filing Date
EP02756710A Withdrawn EP1420791A4 (fr) 2001-08-29 2002-07-23 Utilisation de composes permettant de traiter des affections consecutives a une lesion du nerf corneen apres un lasik ou d'autres traumatismes ou chirurgies de l'oeil

Country Status (10)

Country Link
EP (1) EP1420791A4 (fr)
JP (1) JP2005502678A (fr)
CN (1) CN1549718A (fr)
AR (1) AR036194A1 (fr)
BR (1) BR0212151A (fr)
CA (1) CA2455896A1 (fr)
MX (1) MXPA04001255A (fr)
PL (1) PL368565A1 (fr)
WO (1) WO2003020281A1 (fr)
ZA (1) ZA200400837B (fr)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004091662A1 (fr) * 2003-04-18 2004-10-28 Senju Pharmaceutical Co. Ltd. Agent pour la reparation de la perception corneenne
ES2234428B1 (es) * 2003-12-09 2006-11-01 Universidad Miguel Hernandez Compuestos para el tratamiento de la sequedad de la superficie ocular provocada por la cirugia fotorrefractiva.
CN1997381B (zh) * 2004-04-23 2011-06-08 千寿制药株式会社 含有pacap及其衍生物的角膜神经突形成促进剂
JP4932480B2 (ja) * 2004-06-03 2012-05-16 千寿製薬株式会社 アミド化合物を含有する角膜知覚回復剤
US20090082455A1 (en) 2005-03-15 2009-03-26 Ono Pharmaceutical Co. Lted Therapeutic agent for ophthalmic disease
CN113350326B (zh) * 2021-07-28 2023-03-17 爱尔眼科医院集团股份有限公司 化合物lm22b-10在制备角膜上皮及神经损伤治疗药物中的应用

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0498718A1 (fr) * 1991-02-05 1992-08-12 Elf Sanofi Utilisation de dérivés 4-(3-trifluorométhylphényl)-1,2,3,6-tétrahydropyridiniques comme capteurs de radicaux libres
US5604244A (en) * 1995-06-07 1997-02-18 Alcon Laboratories, Inc. Intraocular irrigating solution containing a polyamine antagonist

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5166317A (en) * 1988-10-31 1992-11-24 Houston Biotechnology Incorporated Neurotrophic factor
US5767079A (en) * 1992-07-08 1998-06-16 Celtrix Pharmaceuticals, Inc. Method of treating ophthalmic disorders using TGF -β
TWI246421B (en) * 1998-12-03 2006-01-01 Alcon Mfg Ltd Use of neurotrophic factor stimulators for the treatment of ophthalmic neurodegenerative diseases
WO2001085152A2 (fr) * 2000-05-10 2001-11-15 Alcon, Inc. R-eliprodil applique au traitement du glaucome

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0498718A1 (fr) * 1991-02-05 1992-08-12 Elf Sanofi Utilisation de dérivés 4-(3-trifluorométhylphényl)-1,2,3,6-tétrahydropyridiniques comme capteurs de radicaux libres
US5604244A (en) * 1995-06-07 1997-02-18 Alcon Laboratories, Inc. Intraocular irrigating solution containing a polyamine antagonist

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of WO03020281A1 *

Also Published As

Publication number Publication date
EP1420791A4 (fr) 2004-09-15
MXPA04001255A (es) 2004-05-27
ZA200400837B (en) 2005-02-02
AR036194A1 (es) 2004-08-18
JP2005502678A (ja) 2005-01-27
CN1549718A (zh) 2004-11-24
BR0212151A (pt) 2004-08-24
WO2003020281A1 (fr) 2003-03-13
CA2455896A1 (fr) 2003-03-13
PL368565A1 (en) 2005-04-04

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