WO2003026744A1 - Utilisation d'epothilones et analogues en chirurgie ophtalmique - Google Patents

Utilisation d'epothilones et analogues en chirurgie ophtalmique Download PDF

Info

Publication number
WO2003026744A1
WO2003026744A1 PCT/US2002/030315 US0230315W WO03026744A1 WO 2003026744 A1 WO2003026744 A1 WO 2003026744A1 US 0230315 W US0230315 W US 0230315W WO 03026744 A1 WO03026744 A1 WO 03026744A1
Authority
WO
WIPO (PCT)
Prior art keywords
composition
administered
eye
group
alkyl
Prior art date
Application number
PCT/US2002/030315
Other languages
English (en)
Inventor
Peter G. Klimko
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.
Priority to US10/275,463 priority Critical patent/US20040058899A1/en
Publication of WO2003026744A1 publication Critical patent/WO2003026744A1/fr

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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
    • 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
    • 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
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • 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
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels

Definitions

  • compositions containing epothilones and their analogs in conjunction with ophthalmic surgery. These compositions may be used to prevent or treat posterior capsular opacification following extracapsular extraction of a cataractous lens with or without artificial intraocular lens implantation. They may also be used to prevent or retard fistula closure resulted from glaucoma filtration surgery (GFS).
  • GFS glaucoma filtration surgery
  • Cataract extraction a common surgical procedure, is performed on a patient when the natural crystallin lens of the eye becomes, for a variety of reasons, clouded or cataractous.
  • the procedure involves i) making an incision in the anterior chamber of the eye in order to gain access to the lens capsular bag, ii) disintegration and removal of the defective lens, and iii) implantation of an artificial intraocular lens (IOL).
  • IOL intraocular lens
  • a portion of the anterior membrane of the lens capsular bag is removed in order to allow implantation of the IOL.
  • the capsular bag is normally cleaned by the ophthalmic surgeon in order to remove residual lens epithelial cells and other tissue debris.
  • PCO posterior capsular opacification
  • Glaucoma is a progressive disease which leads to optic nerve damage and, ultimately, total loss of vision.
  • the causes of this disease have been the subject of extensive studies for many years, but are still not fully understood.
  • the principal symptom of and/or risk factor for the disease is elevated intraocular pressure or ocular hypertension due to excess aqueous humor in the anterior chamber of the eye.
  • IOP elevated intraocular pressure
  • beta-blockers and carbonic anhydrase inhibitors can be at least partially controlled by administering drugs which either reduce the production of aqueous humor within the eye, such as beta-blockers and carbonic anhydrase inhibitors, or increase the outflow of aqueous humor from the eye, such as miotics and sympathomimetics.
  • GFS generally involves the creation of a fistula to promote the drainage of aqueous humor. Typically, this includes the creation of an elevation of the conjunctiva at the surgical site. This elevation is commonly referred to as a filtering bleb.
  • the filtering blebs which are most often associated with good IOP control are avascular and are either low profile and diffuse, or elevated with numerous cystic spaces. Studies have suggested that aqueous fluid in the filtering bleb usually filters through the conjunctiva and mixes with the tear film, or is adsorbed by vascular or perivascular co ⁇ junctival tissue.
  • GFS ulcerative colitis
  • a scar tissue forms in the filtration bleb. This reduces the drainage capacity of the filtration system created by the surgery, which then causes the patient's IOP to return to abnormally high levels
  • anti-inflammatory and antiproliferative agents can be applied to the surgical site. See, e.g. U.S. Patent No. 5,811,453, the contents of which are by this reference incorporated herein.
  • the use of these types of drugs has had only limited success. Many of these drugs cannot be used at the concentrations which would be most effective at suppressing scar formation since they are toxic to other ophthalmic tissue.
  • the surgical failure rate (from re-closure of the surgically created bleb) is high in certain groups, such as patients with previous failed filtering surgery, prior cataract extraction, aphakia, or neovascular glaucoma.
  • the epothilones are a family of macrolactones which potently inhibit the growth of cancer cells in vitro and the growth of tumors in vivo [Danishefsky et. al, J. Org. Che . vol. 64, p. 8434 (1999); Danishefsky et. al, Proc. Natl. Acad. Sci. USA, issue 95, p. 9643 (1998); Nicolau et. al, Angew. Chem. Intl. Ed. Engl.. issue 37, p. 2014 (1998)]. They are among the most potent antitumor agents discovered to date and they maintain their efficacy against a wide range of multidrug-resistant cancers.
  • the present invention provides improved methods to prevent and/or retard the formation of secondary cataracts and/or ophthalmic scar tissue.
  • the methods involve the administration of an ophthalmic composition containing one or more epothilones and/or analogs thereof to the surgical site at the time of or after surgery.
  • the compounds of the present invention useful for the prevention or retardation of secondary cataracts and ophthalmic scarring, especially scarring associated with fistula closure after GFS are those of formula I:
  • Y O, NH, or a functionally modified amino group
  • Z O, NOH, or NNH 2 , where the OH and NH 2 may be free or functionally modified
  • R 1 H or optionally substituted alkyl
  • X is a direct bond (olefin stereochemistry in this case can be E or Z), 0, CH 2 , OCH 2 , CH 2 O, S, NH, or a functionally modified amino group;
  • R 5 is H, alkyl, or halogen
  • Preferred compounds of formula I are those wherein:
  • Y is O orNH; R 2 and R 3 are H;
  • Z is O
  • R 1 is H or CH 3 ;
  • TM a single or double bond
  • X is a direct bond, CH 2 , O, or NH
  • R 5 is H, C M alkyl, or Cl; and R 6 is aryl or heteroaryl.
  • R 5 is H, C M alkyl, or Cl; and R 6 is aryl or heteroaryl.
  • R 6 is aryl or heteroaryl.
  • Source Reference Source Reference: Source Reference: Source Reference: Source Reference: Source Reference: Source Reference: Source Reference: Danishefsky etal., Johnson etal., Danishefsky etal., Danishefsky etal., J. Or ⁇ . Chem. vol. 65, Orq Lett., vol. 2, p.1633 Org -ett, vol. 2, p.1537 Orq. Lett , vol. 2, p 1637 p.6525 (2000) (2000) (2000) (2000) (2000) (2000) (2000) (2000) (2000) (2000)
  • Source Reference Source Reference: Source Reference:
  • enantiomerically pure compositions >98% enantiomeric excess of the desired enantiomer
  • references for the synthesis of enantiomerically enriched samples of epothilones and analogs can be found, in addition to the epothilone-related literature cited above, in the following publications, all of which are incorporated in their entirety by reference: Johnson, J.; et ⁇ l Org. Lett.. 2:1537 (2000); Danishefsky, S.J. et ⁇ l. Org.
  • the individual enantiomers can be procured by a number of methods, including but not limited to: enantioselective synthesis from the appropriate enantiomerically pure or enriched starting material; synthesis from racemic/non-racemic or achiral starting materials using a chiral reagent, catalyst, solvent, etc. (see for example: Asymmetric Synthesis, J. D. Morrison and J. W. Scott, Eds. Academic Press Publishers, (New York) 1985), volumes 1-5; Principles of Asymmetric Synthesis, R.E. Gawley and J. Aube, Eds.; Elsevier Publishers (Amsterdam 1996)); and isolation from racemic and non-racemic mixtures by a number of known methods, e.g.
  • Wavy line attachments indicate that the configuration at that site may be either alpha ( ⁇ ) or beta ( ⁇ ). Hatched lines indicate the ⁇ configuration. A solid triangular line indicates the ⁇ configuration.
  • free hydroxy group means an OH.
  • functionally modified hydroxy group means an OH which has been functionalized to form: an ether, in which an alkyl group is substituted for the hydrogen; an ester, in which an acyl group is substituted for the hydrogen; a carbamate, in which an aminocarbonyl group is substituted for the hydrogen; or a carbonate, in which an alkoxycarbonyl group is substituted for the hydrogen.
  • free amino group means an NH 2 .
  • the term "functionally modified amino group” means an NH 2 which has been functionalized to form: an alkoxyamino or hydroxyamino group, in which an alkoxy or hydroxy group is substituted for one of the hydrogens; an alkylamino group, in which an alkyl group is substituted for one or both of the hydrogens; an amide, in which an acyl group is substituted for one of the hydrogens; a carbamate, in which an alkoxycarbonyl group is substituted for one of the hydrogens; a urea, in which an aminocarbonyl group is substituted for one of the hydrogens; or a sulfonamide, in which an alkylsulfonyl, a cycloalkylsulfonyl, a heterocycloalkylsulfonyl, a cycloalkenylsulfonyl, an arylsulfonyl, or a heteroarylsulfonyl group is substituted for one of
  • sulfonyl represents an SO 2 .
  • the sulfonyl group is bonded from the sulfur atom to two other groups.
  • a dialkylsulfonyl group can be represented as alkyl 1 -SO 2 -alkyl 2 , where alkyl 1 and alkyl 2 are the same or different alkyl groups,
  • An arylsulfonylamide can be represented by aryl-SO 2 -NWW 1 , where aryl is an aryl group and NWW 1 is a free or functionally modifed amino group, with the aryl and NWW groups being bonded to the sulfur atom.
  • acyl represents a group that is linked by a carbon atom that has a double bond to an oxygen atom and a single bond to another carbon atom.
  • alkyl includes straight or branched chain aliphatic hydrocarbon groups that are saturated and have 1 to 15 carbon atoms.
  • the alkyl groups may be substituted with other groups, such as halogen, hydroxyl or alkoxy.
  • Preferred straight or branched alkyl groups include methyl, ethyl, propyl, isopropyl, butyl and t-butyl.
  • cycloalkyl includes straight or branched chain, saturated or unsaturated aliphatic hydrocarbon groups which connect to form one or more rings, which can be fused or isolated. The rings may be substituted with other groups, such as halogen, hydroxyl, alkoxy, or lower alkyl.
  • Preferred cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.
  • heterocycloalkyl refers to cycloalkyl groups which contain at least one heteroatom such as O, S, or N in the ring. Heterocycloalkenyl rings may be isolated, with 5 to 8 ring atoms, or fused, with 8 to 10 atoms.
  • the heterocycloalkyl ring(s) hydrogens or heteroatoms with open valency may be substituted with other groups, such as lower alkyl, acyl, or halogen.
  • Preferred heterocycloalkyl groups include piperidine, piperazine, pyrrolidine, tetrahydrofuranyl, tetrahydropyranyl, and tetrahydrothienyl.
  • alkenyl includes straight or branched chain hydrocarbon groups having 1 to 15 carbon atoms with at least one carbon-carbon double bond.
  • the chain hydrogens may be substituted with other groups, such as halogen.
  • Preferred straight or branched alkeny groups include, allyl, 1-butenyl, l-methyl-2-propenyl and 4-pentenyl.
  • cycloalkenyl includes straight or branched chain, saturated or unsaturated aliphatic hydrocarbon groups which connect to form one or more non- aromatic rings containing a carbon-carbon double bond, which can be fused or isolated.
  • the rings may be substituted with other groups, such as halogen, hydroxyl, alkoxy, or lower alkyl.
  • Preferred cycloalkenyl groups include cyclopentenyl and cyclohexenyl.
  • alkoxy represents an alkyl group attached through an oxygen linkage.
  • carbonyl group represents a carbon atom double bonded to an oxygen atom, wherein the carbon atom has two free valencies.
  • alkoxycarbonyl represents an alkoxy group bonded from its oxygen atom to the carbon of a carbonyl group, the carbonyl group itself being bonded to another atom through its carbon atom.
  • aminocarbonyl represents an amino group bonded from its nitrogen atom to the carbon atom of a carbonyl group, the carbonyl group itself being bonded to another atom through its carbon atom.
  • lower alkyl represents alkyl groups containing one to six carbons (C
  • halogen represents fluoro, chloro, bromo, or iodo.
  • aryl refers to carbon-based rings which are aromatic.
  • the rings may be isolated, such as phenyl, or fused, such as naphthyl.
  • the ring hydrogens may be substituted with other groups, such as lower alkyl, or halogen.
  • heteroaryl refers to aromatic hydrocarbon rings which contain at least one heteroatom such as O, S, or N in the ring. Heteroaryl rings may be isolated, with 5 to 6 ring atoms, or fused, with 8 to 10 atoms.
  • the heteroaryl ring(s) hydrogens or heteroatoms with open valency may be substituted with other groups, such as lower alkyl or halogen. Examples of heteroaryl groups include imidazole, pyridine, indole, quinoline, furan, thiophene, pyrrole, tetrahydroquinoline, dihydrobenzofuran, and dihydrobenzindole.
  • the compounds of this invention may be administered by any of several routes, including: a) topical ocular, intraocular injection, or irrigating solution delivery; b) application from a surgical sponge; or c) incorporation into an implantable film, viscoelastic, or other bioerodible device, which is left in the eye for sustained delivery to the affected area.
  • topical ophthalmic compositions are preferred for preventing or retarding fistula closure, and will be in the form of a solution, suspension, gel, or formulated as part of a device, such as a collagen shield or other bioerodible or non- bioerodible device.
  • Various excipients may be contained in the topical ophthalmic solutions, suspensions or gels of the present invention.
  • buffers e.g., borate, carbonate, phosphate
  • tonicity agents e.g., sodium chloride, potassium chloride, polyols
  • preservatives e.g., polyquaterniums, polybiguanides, BAC
  • chelating agents e.g., EDTA
  • viscosity enhancing agents e.g., polyethoxylated glycols
  • solubilizing agents e.g., polyethoxylated castor oils, including polyoxl-35 castor oil (Cremophor EL ® , BASF Corp., Parsippany, NJ); Polysorbate 20, 60 and 80; Pluronic ® F-68, F-84 and P-103 (BASF Corp.); or cyclodextrin
  • tonicity agents e.g., sodium chloride, potassium chloride, polyols
  • preservatives e.g., polyquaterniums, polybiguanides, BAC
  • viscoelastics and gels may be useful in topical ophthalmic gel compositions of the present invention, including, but not limited to, mucopolysaccharides (e.g. hyaluronates and chondroitin sulfates) carbomers, polyvinyl alcohol-borate complexes, or xanthan, gellan, or guar gums.
  • mucopolysaccharides e.g. hyaluronates and chondroitin sulfates
  • carbomers e.g. hyaluronates and chondroitin sulfates
  • Non-solid vehicles useful for delivery of the compounds of the present invention are preferably aqueous and are formulated so as to be chemically and physically compatible with ophthalmic tissues.
  • viscoelastic formulations currently utilized in connection with intraocular surgical procedures such as HEALON® (sodium hyaluronate) (Pharmacia Corp., Peapack, New Jersey, USA), PROVISO ® (sodium hyaluronate) (Alcon Laboratories, Inc., Fort Worth, Texas, USA), or NISCOAT® (sodium chondroitin sulfate-sodium hyaluronate) (Alcon Laboratories, Inc.), or CELLUGEL ® (hydroxy-propylmethyl-cellulose) are preferred as vehicles for the above- described compounds, especially for the prevention or retardation of secondary cataracts. Such viscous formulations tend to adhere to tissue.
  • viscous formulations for use in preventing or retarding secondary cataract formation are those containing hyaluronic acid or its ophthalmically acceptable salts, esters and amides, which are relatively more dispersive, i.e. less cohesive, than HEALO ⁇ ® , such as NISCOAT ® or the hyaluronic acid amide derivatives disclosed in WO 00/01733, the contents of which are by this reference incorporated herein.
  • Most preferred among the viscoelastic vehicles are "non-aspirating" viscoelastics that may be left in the eye at the close of surgery without significant risk of a deleterious, post-operative intraocular pressure spike.
  • non-aspirating viscoelastics including hydrophobically modified hyaluronate and especially hyaluronic acid (HA) amides
  • HA hyaluronic acid
  • a viscous solution or semi-solid composition may therefore be preferable in some cases.
  • the viscosity of the composition will not be a primary concern, since leakage of the composition from the capsular bag will be a less significant problem.
  • the use of a less viscous aqueous solution as the vehicle may therefore be preferred in such cases.
  • compositions can be applied to the lens capsule by means of various techniques.
  • the compositions can be applied to the interior of the capsular bag by means of a syringe following removal of the crystallin lens, or can be injected into the lens capsule prior to removal of the crystallin lens by means of phacoemulsification or other methods.
  • the less viscous aqueous solutions useful as a vehicle for the compounds of the present invention must similarly be compatible with intraocular tissues, and should preferably help to maintain the integrity and function of intraocular tissues during or after the surgical procedure.
  • the most basic irrigating solutions generally comprise saline, or phosphate-buffered saline. More advanced irrigating solutions, however, are preferred.
  • physiologically balanced irrigating solution refers to a solution which is adapted to maintain the physical structure and function of tissues during invasive or noninvasive medical procedures.
  • This type of solution will typically contain electrolytes, such as sodium, potassium, calcium, magnesium and/or chloride; an energy source, such as dextrose; and a bicarbonate-buffer to maintain the pH of the solution at or near physiological levels.
  • electrolytes such as sodium, potassium, calcium, magnesium and/or chloride
  • an energy source such as dextrose
  • a bicarbonate-buffer to maintain the pH of the solution at or near physiological levels.
  • Various solutions of this type are known (e.g., Lactated Ringers Solution), BSS ® Sterile Irrigating Solution, and BSS Plus ® Sterile Intraocular Irrigating Solution (Alcon Laboratories, Inc., Fort Worth, Texas, USA) are examples of physiologically balanced intraocular irrigating solutions. The latter type of solution is described in United States Patent No. 4,550,022 (Garabedian, et al.), the entire contents of which are incorporated herein by reference.
  • Preferred aqueous solutions include physiologically balanced irrigating solutions, such as BSS® (Balanced Salt Solution) and BSS Plus® (Balanced Salt Solution Enriched with Bicarbonate, Dextrose and Glutathione) available from Alcon Laboratories, Inc., Fort Worth, Texas. Also preferred is BION TEARS ® Lubricant Eye Drops, also available from Alcon Laboratories, Inc., Fort Worth, Texas.
  • BSS® Breast Salt Solution
  • BSS Plus® Balanced Salt Solution Enriched with Bicarbonate, Dextrose and Glutathione
  • compositions must be sterile and should not include any agents (e.g., antimicrobial preservatives) which will be toxic to sensitive ocular tissues.
  • Preservatives can be used to prevent microbial contamination during use. Suitable preservatives include: benzalkonium chloride, thimerosal, chlorobutanol, methyl paraben, propyl paraben, phenylethyl alcohol, edetate disodium, sorbic acid, polyquatemium-1, or other agents known to those skilled in the art.
  • Such preservatives are typically employed at a level of from 0.001 to 1.0% weight/volume ("% w/v").
  • the above-described compositions can be formulated in accordance with techniques known to those skilled in the art.
  • the epothilones of the invention can also be incorporated in an intraocular drug delivery system providing a slower release effect than would ordinarily be achieved with the ⁇ reviously discussed aqueous and viscoelastic vehicles.
  • Topical ophthalmic bioerodible and non-bioerodible devices e.g., conjunctival implant
  • formula (I) compounds See, for example, Weiner, A.L., Polymeric Drug Delivery Systems For The Eye, in Polymeric Site-specific Pharmacotherapy, Ed., A.J. Domb, John Wiley & Sons, pages 316-327 (1994).
  • topical ophthalmic compositions useful in the methods of the present invention will vary, particular topical ophthalmic compositions will be formulated to effect the administration of a compound of formula (I) topically to the eye.
  • the active substance in solid form could be coated with or encapsulated by an ophthalmologically acceptable carrier substance.
  • examples of systems, which are generally known for encapsulating drugs, are liposomes which are membrane-like vesicles, and microspheres based on polymers of lactic and glycolic acid.
  • a slow release system can alternatively be prepared by adding the epothilone of interest in dissolved form to a carrier matrix under conditions so that a desired amount of the substance is incorporated.
  • a carrier matrix is a gel, for instance a biodegradable gel of hyaluronic acid as disclosed in EP 408731.
  • a slow release composition comprising the epothilone of interest can be deposited directly on the tissue at the surgical site, under conditions so that the composition is bound to the tissue or forms an interpenetrating network with the tissue surface layer.
  • a preferred embodiment of the invention comprises intraocular administration of the epothilone compound in an amount of about 0.005 to 5 ⁇ g and especially 0.1 to 5 ⁇ g, in approximately 0.1 mL of a viscoelastic medium, especially PROVISO ® , Healon® or Viscoat® sterile ophthalmic viscoelastic solutions.
  • a viscoelastic medium especially PROVISO ® , Healon® or Viscoat® sterile ophthalmic viscoelastic solutions.
  • the dose would preferably be considerably higher, for instance up to about 25 ⁇ g, concentration being dictated by the volume of the vehicle or implant.
  • Another preferred embodiment comprises irrigating solution delivery of the epothilone compound at a concentration of about 0.05 to about 100 ⁇ g per mL.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Dermatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne une méthode pour prévenir ou retarder l'opacification capsulaire postérieure ou la formation de cicatrices consécutives à une intervention chirurgicale ophtalmique, consistant à utiliser des épothilones et leurs analogues pour traiter le champ opératoire.
PCT/US2002/030315 2001-09-25 2002-09-25 Utilisation d'epothilones et analogues en chirurgie ophtalmique WO2003026744A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US10/275,463 US20040058899A1 (en) 2002-09-25 2002-09-25 Use of epothilones and analogs in conjunction with ophthalmic surgery

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US32468901P 2001-09-25 2001-09-25
US32466301P 2001-09-25 2001-09-25
US60/324,689 2001-09-25
US60/324,663 2001-09-25

Publications (1)

Publication Number Publication Date
WO2003026744A1 true WO2003026744A1 (fr) 2003-04-03

Family

ID=26984565

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2002/030315 WO2003026744A1 (fr) 2001-09-25 2002-09-25 Utilisation d'epothilones et analogues en chirurgie ophtalmique

Country Status (1)

Country Link
WO (1) WO2003026744A1 (fr)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6867305B2 (en) 1996-12-03 2005-03-15 Sloan-Kettering Institute For Cancer Research Synthesis of epothilones, intermediates thereto and analogues thereof
WO2006064281A1 (fr) * 2004-12-17 2006-06-22 Jin Jun Zhang Solution de traitement et procede pour la prevention d'opacification capsulaire posterieure par l'induction selective de detachement et/ou de mort de cellules epitheliales de cristallin
US7169930B2 (en) * 2002-08-02 2007-01-30 The Scripps Research Institute Analogs of epothilone
USRE41990E1 (en) 1996-12-03 2010-12-07 Sloan-Kettering Institute For Cancer Research Synthesis of epothilones, intermediates thereto, analogues and uses thereof
US8114432B2 (en) 2002-09-17 2012-02-14 Jin Jun Zhang Treatment solution and method for preventing posterior capsular opacification by selectively inducing detachment and/or death of lens epithelial cells
US20210238187A1 (en) * 2017-04-11 2021-08-05 William Marsh Rice University Aziridine containing epothilone analogs, methods of synthesis, methods of treatment, and drug conjugates

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994025020A1 (fr) * 1993-04-28 1994-11-10 Pharmacia Ab Procede et moyen d'inhibition de l'opacification de la capsule posterieure
WO1999043653A1 (fr) * 1998-02-25 1999-09-02 Sloan-Kettering Institute For Cancer Research Synthese d'epothilones, de leurs intermediaires et de leurs analogues
WO1999054318A1 (fr) * 1998-04-21 1999-10-28 Bristol-Myers Squibb Company Derives d'epothilone 12,13-cyclopropane
US5994341A (en) * 1993-07-19 1999-11-30 Angiogenesis Technologies, Inc. Anti-angiogenic Compositions and methods for the treatment of arthritis
WO1999067252A2 (fr) * 1998-06-22 1999-12-29 Novartis Ag Derives de l'epothilone, leur synthese et leur utilisation
WO2000049021A2 (fr) * 1999-02-18 2000-08-24 Schering Aktiengesellschaft Derives de 16-halogeno-epothilon, leur procede de production et leur utilisation pharmaceutique

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994025020A1 (fr) * 1993-04-28 1994-11-10 Pharmacia Ab Procede et moyen d'inhibition de l'opacification de la capsule posterieure
US5994341A (en) * 1993-07-19 1999-11-30 Angiogenesis Technologies, Inc. Anti-angiogenic Compositions and methods for the treatment of arthritis
WO1999043653A1 (fr) * 1998-02-25 1999-09-02 Sloan-Kettering Institute For Cancer Research Synthese d'epothilones, de leurs intermediaires et de leurs analogues
WO1999054318A1 (fr) * 1998-04-21 1999-10-28 Bristol-Myers Squibb Company Derives d'epothilone 12,13-cyclopropane
WO1999067252A2 (fr) * 1998-06-22 1999-12-29 Novartis Ag Derives de l'epothilone, leur synthese et leur utilisation
WO2000049021A2 (fr) * 1999-02-18 2000-08-24 Schering Aktiengesellschaft Derives de 16-halogeno-epothilon, leur procede de production et leur utilisation pharmaceutique

Non-Patent Citations (14)

* Cited by examiner, † Cited by third party
Title
ALTMANN K-H ET AL: "Epothilones and related structures - a new class of microtubule inhibitors with potent in vivo antitumor activity", BBA - REVIEWS ON CANCER, ELSEVIER SCIENCE BV, AMSTERDAM, NL, vol. 1470, no. 3, 17 May 2000 (2000-05-17), pages M79 - M91, XP004281887, ISSN: 0304-419X *
APPLE D J ET AL: "POSTERIOR CAPSULE OPACIFICATION", SURVEY OF OPHTHALMOLOGY, SURVEY OF OPHTHALMOLOGY INC, XX, vol. 37, no. 2, September 1992 (1992-09-01), pages 73 - 116, XP001098853, ISSN: 0039-6257 *
BOLLAG ET AL: "Epothilones a new class of microtubule-stabilizing agents with a taxol-like mechanism of action", CANCER RESEARCH, AMERICAN ASSOCIATION FOR CANCER RESEARCH, BALTIMORE, MD, US, vol. 55, 1 June 1995 (1995-06-01), pages 2325 - 2333, XP002111282, ISSN: 0008-5472 *
CHOU T C ET AL: "DESOXYEPOTHILONE B: AN EFFICACIOUS MICROTUBULE-TARGETED ANTITUMOR AGENT WITH A PROMISING IN VIVO PROFILE RELATIVE TO EPOTHILONE B", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF USA, NATIONAL ACADEMY OF SCIENCE. WASHINGTON, US, vol. 95, no. 16, 1998, pages 9642 - 9647, XP000910107, ISSN: 0027-8424 *
COSTA V P ET AL: "WOUND HEALING MODULATION IN GLAUCOMA FILTRATION SURGERY", OPHTHALMIC SURGERY, SLACK, PITMAN, NJ, US, vol. 24, no. 3, March 1993 (1993-03-01), pages 152 - 170, XP002923717, ISSN: 0022-023X *
ISHIOKA MISAKI ET AL: "Trabeculectomy with mitomycin C for post-keratoplasty glaucoma.", BRITISH JOURNAL OF OPHTHALMOLOGY, vol. 84, no. 7, July 2000 (2000-07-01), pages 714 - 717, XP002229605, ISSN: 0007-1161 *
JACOBI PHILIPP C ET AL: "Adjunctive mitomycin C in primary trabeculectomy in young adults: A long-term study of case-matched young patients.", GRAEFE'S ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY, vol. 236, no. 9, 1998, pages 652 - 657, XP002229606, ISSN: 0721-832X *
JAMPEL HENRY D ET AL: "Glaucoma filtration surgery in nonhuman primates using taxol an etoposide in polyanhydride carriers.", INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, vol. 34, no. 11, 1993, pages 3076 - 3083, XP008013191, ISSN: 0146-0404 *
LEE D A ET AL: "THE USE OF BIOERODIBLE POLYMERS AND 5-FLUOROURACIL IN GLAUCOMA FILTRATION SURGERY", INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, ASSOCIATION FOR RESEARCH IN VISION AND, US, vol. 29, no. 11, 1 November 1988 (1988-11-01), pages 1692 - 1697, XP000565392, ISSN: 0146-0404 *
LEGLER U F C ET AL: "INHIBITION OF POSTERIOR CAPSULE OPACIFICATION: THE EFFECT OF COLCHICINE IN A SUSTAINED DRUG DELIVERY SYSTEM", JOURNAL CATARACT AND REFRACTIVE SURGERY, AMERICAN SOCIETY OF CATARACT AND REFRACTIVE, US, vol. 19, no. 4, 1 July 1993 (1993-07-01), pages 462 - 470, XP000565374, ISSN: 0886-3350 *
MEMBREY W L ET AL: "Glaucoma surgery with or without adjunctive antiproliferatives in normal tension glaucoma: 1 Intraocular pressure control and complications.", BRITISH JOURNAL OF OPHTHALMOLOGY, vol. 84, no. 6, June 2000 (2000-06-01), pages 586 - 590, XP002229604, ISSN: 0007-1161 *
TURACLI E ET AL: "A COMPARATIVE CLINICAL TRIAL OF MITOMYCIN C AND CYCLOSPORIN A IN TRABECULECTOMY", EUROPEAN JOURNAL OF OPHTHALMOLOGY, MILAN, IT, vol. 6, no. 4, 1996, pages 398 - 401, XP009003662, ISSN: 1120-6721 *
WANG M ET AL: "A UNIFIED AND QUANTITATIVE RECEPTOR MODEL FOR THE MICROTUBULE BINDING OF PACLITAXEL AND EPOTHILONE", ORGANIC LETTERS, AMERICAN CHEMICAL SOCIETY, US, vol. 1, no. 1, January 1999 (1999-01-01), pages 43 - 46, XP000983329, ISSN: 1523-7060 *
WELLER M ET AL: "EVALUATION OF DAUNOMYCIN TOXICITY ON LENS EPITHELIUM IN-VITRO", INTERNATIONAL OPHTHALMOLOGY, vol. 12, no. 2, 1988, pages 127 - 130, XP008013199, ISSN: 0165-5701 *

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6867305B2 (en) 1996-12-03 2005-03-15 Sloan-Kettering Institute For Cancer Research Synthesis of epothilones, intermediates thereto and analogues thereof
USRE41990E1 (en) 1996-12-03 2010-12-07 Sloan-Kettering Institute For Cancer Research Synthesis of epothilones, intermediates thereto, analogues and uses thereof
US7169930B2 (en) * 2002-08-02 2007-01-30 The Scripps Research Institute Analogs of epothilone
US7875270B2 (en) 2002-09-17 2011-01-25 Abbott Medical Optics Inc. Treatment solution and method for preventing posterior capsular opacification by selectively inducing detachment and/or death of lens epithelial cells
US8114432B2 (en) 2002-09-17 2012-02-14 Jin Jun Zhang Treatment solution and method for preventing posterior capsular opacification by selectively inducing detachment and/or death of lens epithelial cells
WO2006064281A1 (fr) * 2004-12-17 2006-06-22 Jin Jun Zhang Solution de traitement et procede pour la prevention d'opacification capsulaire posterieure par l'induction selective de detachement et/ou de mort de cellules epitheliales de cristallin
JP2008524194A (ja) * 2004-12-17 2008-07-10 ジン ジュン ザン， 水晶体上皮細胞の剥離および／または死滅を選択的に誘発することによって後嚢混濁を予防するための処置溶液および方法
JP4906737B2 (ja) * 2004-12-17 2012-03-28 ジン ジュン ザン， 水晶体上皮細胞の剥離および／または死滅を選択的に誘発することによって後嚢混濁を予防するための処置溶液および方法
US20210238187A1 (en) * 2017-04-11 2021-08-05 William Marsh Rice University Aziridine containing epothilone analogs, methods of synthesis, methods of treatment, and drug conjugates

Similar Documents

Publication Publication Date Title
US10555953B2 (en) Pharmaceutical composition for treatment of increased intraocular pressure
US6242480B1 (en) Ophthalmic viscoelastic compositions
AU704591B2 (en) Use of phosphonylmethoxyalkyl nucleosides for the treatment of raised intraocular pressure
JP5705773B2 (ja) プロスタミド含有生分解性眼内インプラント
US6107343A (en) Ophthalmic and aural compositions containing diclofenac potassium
Lee et al. Glaucoma filtration surgery in rabbits using bioerodible polymers and 5-fluorouracil
KR102322747B1 (ko) 프로스타마이드-함유 안구내 이식물
WO1995012401A1 (fr) Methode et moyens de prevention de la cataracte
ES2278049T3 (es) Uso de inhibidores de proteasoma para tratar trastornos de ojo seco.
KR100471586B1 (ko) 황반부종치료제
WO2003026744A1 (fr) Utilisation d'epothilones et analogues en chirurgie ophtalmique
US20040058899A1 (en) Use of epothilones and analogs in conjunction with ophthalmic surgery
US6232343B1 (en) Ophthalmic preparations
US6433007B1 (en) Methods for the prevention and treatment of post-surgical complications
ZA200303557B (en) Intraocular irrigating solution having improved flow characteristics
JP2004530452A (ja) 外科手術において使用するための非吸引性遷移粘弾性物質
WO2000035432A2 (fr) Compositions viscoelastiques ameliorees et leurs procedes d'utilisation
AU767411B2 (en) Method and composition for prevention of scar formation in glaucoma filtration bleb and drainage fistula
MXPA04007802A (es) Tratamiento de desordenes oftalmicos utilizando urea o derivados de urea.
RU2148404C1 (ru) Фармацевтическая композиция для медикаментозного расширения зрачка в офтальмологии
WO2024105703A1 (fr) Nouvelle formulation ophtalmique
RU2183114C1 (ru) Фармацевтическая композиция для пролонгированного обезболивания в офтальмологии "полианестетик"

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 10275463

Country of ref document: US

AK Designated states

Kind code of ref document: A1

Designated state(s): AU BR CA CN JP KP KR MX PL US

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FR GB GR IE IT LU MC NL PT SE SK TR

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: JP

WWW Wipo information: withdrawn in national office

Country of ref document: JP