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WO2009014510A1 - Formulation pharmaceutique d'administration, dans l'oeil, de composés inhibiteurs des récepteurs tyrosine kinases - Google Patents

Formulation pharmaceutique d'administration, dans l'oeil, de composés inhibiteurs des récepteurs tyrosine kinases Download PDF

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Publication number
WO2009014510A1
WO2009014510A1 PCT/US2006/062359 US2006062359W WO2009014510A1 WO 2009014510 A1 WO2009014510 A1 WO 2009014510A1 US 2006062359 W US2006062359 W US 2006062359W WO 2009014510 A1 WO2009014510 A1 WO 2009014510A1
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WO
WIPO (PCT)
Prior art keywords
peg
composition
ophthalmic
gel
solvent
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.)
Ceased
Application number
PCT/US2006/062359
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English (en)
Inventor
Wesley Wehsin Han
Rajni Jani
Huixiang Zhang
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
Priority to AU2007356856A priority Critical patent/AU2007356856A1/en
Priority to BRPI0721885-0A priority patent/BRPI0721885A2/pt
Priority to MX2009012879A priority patent/MX2009012879A/es
Priority to KR1020107003198A priority patent/KR20100051811A/ko
Priority to JP2010516954A priority patent/JP2010534201A/ja
Priority to PCT/US2006/062359 priority patent/WO2009014510A1/fr
Priority to CN200780053631A priority patent/CN101687042A/zh
Priority to CA2693888A priority patent/CA2693888A1/fr
Priority to EP06851209A priority patent/EP2178564A1/fr
Publication of WO2009014510A1 publication Critical patent/WO2009014510A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • A61K31/415—1,2-Diazoles
    • A61K31/416—1,2-Diazoles condensed with carbocyclic ring systems, e.g. indazole
    • 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
    • A61K9/0048—Eye, e.g. artificial tears
    • 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
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • A61K9/0048—Eye, e.g. artificial tears
    • A61K9/0051—Ocular inserts, ocular implants

Definitions

  • the present invention relates to compositions and methods useful for treating pathological states that arise or are exacerbated by ocular angiogenesis and vascular leakage such as AMD, DR, diabetic macular edema etc., and more specifically, to compositions containing at least one anti-angiogenic agent, anti-inflammatory agent, or anti -vascular permeability agent for use in treating angiogenic ocular disorders.
  • Abnormal neovascularization or angiogenesis and enhanced vascular permeability are major causes for many ocular disorders including age-related macular degeneration (AMD), retinopathy of prematurity (ROP), ischemic retinal vein occlusions and diabetic retinopathy (DR).
  • AMD and DR are among the most common cause of severe, irreversible vision loss.
  • central vision loss is secondary to angiogenesis, the development of new blood vessels from pre-existing vasculature, and alterations in vascular permeability properties.
  • the angiogenic process is known by the activation of quiescent endothelial cells in pre-existing blood vessels.
  • the normal retinal circulation is resistant to neovascular stimuli, and very little endothelial cell proliferation takes place in the retinal vessels.
  • neovascular stimuli including tissue hypoxia, inflammatory cell infiltration and penetration barrier breakdown, all increase the local concentration of cytokines (VEGF, PDGF, FGF, TNF, IGF etc.), integrins and proteinases resulting in the formation of new vessels, which then disrupt the organizational structure of the neural retina or break through the inner limiting membranes into the vitreous.
  • VEGF vascular leakage and retinal edema
  • VEGF vascular leakage
  • other growth factors such as PDGF, FGF, TNF, and IGF etc.
  • growth factor inhibitors can play a significant role in inhibiting retinal damage and the associated loss of vision upon local delivery in the eye or via oral dosing.
  • PDT photodynamic therapy
  • the effects of photocoagulation on ocular neovascularization and increased vascular permeability are achieved only through the thermal destruction of retinal cells.
  • PDT usually requires a slow infusion of the dye, followed by application of non-thermal laser-light.
  • Treatment usually causes the abnormal vessels to temporarily stop or decrease their leaking.
  • PDT treatment may have to be repeated every three months up to 3 to 4 times during the first year.
  • Potential problems associated with PDT treatment include headaches, blurring, and decreased sharpness and gaps in vision and, in 1-4% of patients, a substantial decrease in vision with partial recovery in many patients.
  • a poorly water soluble compound is a substance that is not soluble at a therapeutically effective concentration in an aqueous physiologically acceptable vehicle.
  • Aqueous solubility is an important parameter in formulation development of a poorly water soluble compound. What is needed is a formulation that provides increased solubility of the compound while also providing sufficient bioavailability of the compound so as to maintain its therapeutic potential.
  • the present invention provides safe and effective formulations for ocular administration of poorly soluble compounds for the treatment of ocular diseases caused by endothelial cell proliferation, vascular leakage, inflammation and angiogenesis.
  • compositions for treating ocular diseases due to angiogenesis and increased vascular permeability are provided.
  • the compositions of the invention include (a) an active agent, and (b) a suitable co-solvent, such as high molecular weight polyethylene glycol (i.e., PEG 1500 to PEG 8000) or blends of high and low molecular weight PEGs, in appropriate amount to obtain an erodible gel.
  • a suitable co-solvent such as high molecular weight polyethylene glycol (i.e., PEG 1500 to PEG 8000) or blends of high and low molecular weight PEGs, in appropriate amount to obtain an erodible gel.
  • the amount and molecular weight of co-solvent plays a very important role on the efficacy of the formulation upon local delivery.
  • a wide variety of molecules may be utilized within the scope of the present invention, especially those molecules having very low solubility.
  • the term “poor solubility” is used to refer to a compound having a solubility in water of less than 10 microgram/mL.
  • the active agent for use in the compositions of the invention may be an anti-angiogenic agent, an anti-inflammatory agent, or an anti-vascular permeability agent, or any other poorly water soluble active agent useful for treating ocular disorders.
  • the erodible gel compositions of the present invention are preferably administered to the eye of a patient suffering from a disorder characterized by neovascularization, inflammation, or vascular permeability via posterior juxtascleral administration or intravitreal injection.
  • compositions that contain an active agent for use in the treatment of ocular disorders caused by endothelial cell proliferation, enhanced vascular permeability, inflammation, or angiogenesis.
  • the compositions of the invention are useful in preventing or inhibiting neovascularization and vascular leakage associated with such ocular disorders. In some cases, the compositions of the invention cause regression of neovascularization.
  • active agents should be understood to be any molecule, either synthetic or naturally occurring, which acts to inhibit vascular growth, reduce vascular permeability, and/or decrease inflammation.
  • the present invention provides erodible gel compositions comprising an active agent in a therapeutically effective amount, a suspending agent, and a suitable amount of a co-solvent, such as high molecular weight polyethylene glycol (i.e., PEG 1500 to PEG 8000), or blends of high and low molecular weight PEGs, in appropriate amount to obtain an erodible gel.
  • a co-solvent such as high molecular weight polyethylene glycol (i.e., PEG 1500 to PEG 8000), or blends of high and low molecular weight PEGs, in appropriate amount to obtain an erodible gel.
  • PEG polyethylene glycols
  • They have a general chemical formula HOCH 2 (CH2 ⁇ CH 2 ) « CH 2 OH. They are nonvolatile, water soluble or water-miscible compounds and chemically inert, varying in molecular weight from several hundred to several thousand. They are liquids or waxy solids identified by numbers which are an approximate indication of molecular weight
  • the preferred co-solvent for use in the formulations of the invention is polyethylene glycol PEG 1500 to PEG 8000.
  • the most preferred co-solvent for use in the formulations of the present invention is PEG 1500 to PEG 3350.
  • the gel formulations of the present invention will include blends of high and low molecular weights of polyethylene glycols to achieve better results. For example, PEG 3350 and PEG 400 in a weight ratio of 4:6 form a water-miscible erodible gel.
  • the co-solvent will typically be present in the formulation of the invention in an amount from 70% to 99.999%.
  • the compositions for the invention will contain from 90% to 99.9% co-solvent.
  • the composition for intravitreal injection will contain 99% co-solvent.
  • the composition for posterior juxtascleral, periocular and topical administration will most preferably contain 99% co-solvent.
  • Polyethylene glycol or blends of high and low molecular weight PEG is identified as a key excipient for efficacious intravitreal, periocular and posterior juxtascleral erodible gel formulations.
  • the PEG water-miscible erodible gel formulation can dissolve in water at a controlled rate, while the active agent in the formulation forms a colloidal dispersion at the site of action. This suggests that the PEG water-soluble carrier can be eliminated from the eye. At the end of use, the system does not need to be retrieved. This is a significant improvement over other existing forms of delivering active agents to the eye of a patient because it allows for fewer invasive procedures while providing superior treatment of the neovascularization, vascular permeability or other ocular disorder.
  • the erosion can be controlled by the ratio of low and high molecular weights of PEGs.
  • the desirable bioavailability can be achieved by controlling the rate of erosion and the rate of dissolution of the colloidal particles which is formed in-situ.
  • compositions of the present invention may be included in the compositions of the present invention.
  • active agent that is poorly water soluble may be included in the compositions of the present invention.
  • anti-angiogenic agents, anti-inflammatory agents, or anti-vascular permeability agents are useful in the compositions of the invention.
  • Preferred anti-angiogenic agents include, but are not limited to, receptor tyrosine kinase inhibitors (RTKi), in particular, those having a multi -targeted receptor profile such as that described in further detail herein; angiostatic cortisenes; MMP inhibitors; integrin inhibitors; PDGF antagonists; antiproliferatives; HIF-I inhibitors; fibroblast growth factor inhibitors; epidermal growth factor inhibitors; TIMP inhibitors; insulin-like growth factor inhibitors; TNF inhibitors; antisense oligonucleotides; etc. and prodrugs of any of the aforementioned agents.
  • the preferred anti-angiogenic agent for use in the present invention is a multi-targeted receptor tyrosine kinase inhibitor (RTKi). Most preferred are
  • RTKi's with multi-target binding profiles such as N-[4-(3-amino-lH-indazol-4-yl) phenyl]-N'-(2-fluoro-5-methylphenyl) urea, having the binding profile substantially similar to that listed in Table 1.
  • Additional multi-targeted receptor tyrosine kinase inhibitors contemplated for use in the compositions of the present invention are described in U.S. Application Serial No. 2004/0235892, incorporated herein by reference.
  • multi-targeted receptor tyrosine kinase inhibitor refers to a compound having a receptor binding profile exhibiting selectivity for multiple receptors shown to be important in angiogenesis, such as the profile shown in Table 1, and described in co- pending U.S. application serial number 2006/0189608, incorporated herein by reference.
  • the compounds for use in the formulations of the present invention will have a receptor binding profile of KDR (VEGFR2), Tie-2 and PDGFR.
  • anti-VEGF antibody i.e., bevacizumab or ranibizumab
  • VEGF trap siRNA molecules, or a mixture thereof, targeting at least two of the tyrosine kinase receptors having IC 50 values of less than 200 nM in Table 1
  • glucocorticoids i.e., dexamethasone, fluoromethalone, medrysone, betamethasone, triamcinolone, triamcinolone acetonide, prednisone, prednisolone, hydrocortisone, rimexolone, and pharmaceutically acceptable salts thereof, prednicarbate, deflazacort, halomethasone, tixocortol, prednylidene (21-diethylaminoacetate), prednival, paramethasone, methylprednisolone, meprednisone, mazipred
  • compositions described herein may be delivered topically, via intravitreal injection, and via posterior juxtascleral and periocular routes.
  • Preferred co-solvents for use in the compositions of the present invention include ethylene glycol, propylene glycol, N-methyl pyrrolidinone, 2-pyrrolidinone, 3-pyrrolidinol, 1 ,4-butanediol, dimethylglycol monomethylether, diethyleneglycol monomethyl ether, solketal, glycerol, polyethylene glycol, polypropylene glycol etc.
  • the present inventors have discovered that certain active agents have a higher solubility in the presence of PEG than in water.
  • the compound N-[4-(3- amino-lH-indazol-4-yl) phenyl]-N'-(2-fluoro-5-methylphenyl) urea can dissolve completely and disperse in PEG 3350 and PEG 8000 when PEG melts at temperatures of about 6O 0 C to 95°C, and forms a wax-like pellet when cooled to room temperature. This pellet forms a colloidal like suspension when the pellet dissolves in water.
  • using blends of high and low molecular weight PEGs can make erodible gel with the compound uniformly dispersed in it (see examples).
  • the compound forms a solid solution in the matrix of the PEG.
  • the formulation of the invention will further comprise a polymer that acts as a suspending agent to enhance the physical stability of the formulation.
  • a polymer that acts as a suspending agent to enhance the physical stability of the formulation.
  • HPMC hydroxypropyl methyl cellulose
  • HEC hydroxyethyl cellulose
  • CMC Carboxymethylcellulose
  • carbopol polyvinyl alcohol, polyvinyl pyrrolidone (PVP), xanthan, gum tragacanth, gum acacia, sodium alginate and its esters etc.
  • PVP polyvinyl pyrrolidone
  • xanthan xanthan
  • gum tragacanth gum acacia
  • the specific dose level for any particular human or animal depends upon a variety of factors, including the activity of the active compound used, the age, body weight, general health, time and frequency of administration, route of administration and the severity of the pathologic condition undergoing therapy.
  • the preferred gel formulations of the invention for administration via intravitreal injection, periocular administration, posterior juxtascleral administration, topical ocular administration, may contain:
  • An active agent in a therapeutically effective amount is an active agent in a therapeutically effective amount
  • PEG 400, PEG 3350 or PEG 8000 as a co-solvent in an effective amount to obtain an erodible gel formulation.
  • Certain other preferred gel formulations of the invention may contain:
  • An anti-angiogenic agent in a therapeutically effective amount is an anti-angiogenic agent in a therapeutically effective amount
  • a ratio of polyethylene glycol co-solvent in an amount effective to form a gel solution Preferred ratios of high molecular weight PEG to low molecular weight PEG for the polyethylene glycol co-solvents for use in the gel formulations of the present invention are from 7:3 to 1 :8. Most preferred ratios of polyethylene glycol compounds for use in the gel formulations of the present invention are from 7 parts PEG 3350 to 3 parts PEG 400 (7:3) to 1 part PEG 3350 to 8 parts PEG 400 (1 :8). The most preferred ratio for the polyethylene glycol co-solvents for use in the gel formulations of the present invention is approximately 4 parts PEG 3350 to approximately 6 parts PEG 400, as illustrated in Table 2.
  • IVT or PJ Due to the intended route of administration (IVT or PJ), it is very important that the particle size of the formulations must be small to accomplish good syringibility, as well as comfort.
  • the prepared formulations (for IVT or PJ) exhibit excellent syringibility even when only 2 ⁇ L - lO ⁇ L of the formulation is injected in the eyes of the animals.
  • a suitable vessel weight and add PEG 3350 powder. Put the vessel to a 75-80 0 C water bath, mix and allow PEG 3350 to melt. Add RTKi (N-[4-(3-amino-lH-indazol-4-yl) phenyl]-N'-(2-fluoro-5-methylphenyl) urea) to the PEG melt. Mix and allow RTKi to dissolve to the melt completely. Put the vessel containing RTKi-PEG melt mixture to room temperature. A hard wax pellet is formed. It is not hygroscopic.
  • a suitable vessel weigh and add two different grades of PEG. For example, add PEG 3350 powder and PEG 400 liquid in adequate ratio. Add RTKi (N-[4-(3 -amino- IH- indazol-4-yl) phenyl]-N'-(2-fluoro-5-methylphenyl) urea) raw material powder to the vessel. Then put the vessel to a 70-90 0 C water bath, mix and allow PEG 3350 to melt and RTKi to dissolve completely. Allow the vessel containing RTKi-PEG melt mixture cool to room temperature. An RTKi-PEG water miscible erodible gel is formed.
  • RTKi N-[4-(3 -amino- IH- indazol-4-yl) phenyl]-N'-(2-fluoro-5-methylphenyl) urea
  • compositions and/or methods disclosed and claimed herein can be made and executed without undue experimentation in light of the present disclosure. While the compositions and methods of this invention have been described in terms of preferred embodiments, it will be apparent to those of skill in the art that variations may be applied to the compositions and/or methods and in the steps or in the sequence of steps of the method described herein without departing from the concept, spirit and scope of the invention. More specifically, it will be apparent that certain agents which are both chemically and structurally related may be substituted for the agents described herein to achieve similar results. All such substitutions and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and concept of the invention as defined by the appended claims.

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  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne le développement de compositions pharmaceutiques efficaces comportant un composé actif peu hydrosoluble en une quantité thérapeutiquement efficace et un cosolvant en une quantité appropriée pour traiter ou prévenir des maladies dues à la néovascularisation oculaire et la perméabilité vasculaire activée. Dans des aspects préférés, la composition est sous la forme d'un gel.
PCT/US2006/062359 2007-07-20 2007-07-20 Formulation pharmaceutique d'administration, dans l'oeil, de composés inhibiteurs des récepteurs tyrosine kinases Ceased WO2009014510A1 (fr)

Priority Applications (9)

Application Number Priority Date Filing Date Title
AU2007356856A AU2007356856A1 (en) 2007-07-20 2007-07-20 Pharmaceutical formulation for delivery of receptor tyrosine kinase inhibiting (RTKI) compounds to the eye
BRPI0721885-0A BRPI0721885A2 (pt) 2007-07-20 2007-07-20 Formulação farmacêutica para distribuição de compostos inibidores de receptores de tirosina quinase (rtki) para os olhos
MX2009012879A MX2009012879A (es) 2007-07-20 2007-07-20 Formulacion farmaceutica para suministrar a los ojos compuestos que inhiben el receptor tirosina cinasa (rtki).
KR1020107003198A KR20100051811A (ko) 2007-07-20 2007-07-20 눈에 수용체 티로신 키나제 저해(ｒｔｋｉ) 화합물을 전달하기 위한 약제학적 제제
JP2010516954A JP2010534201A (ja) 2007-07-20 2007-07-20 受容体チロシンキナーゼ阻害（ＲＴＫｉ）化合物の目への送達のための医薬製剤
PCT/US2006/062359 WO2009014510A1 (fr) 2007-07-20 2007-07-20 Formulation pharmaceutique d'administration, dans l'oeil, de composés inhibiteurs des récepteurs tyrosine kinases
CN200780053631A CN101687042A (zh) 2007-07-20 2007-07-20 用于递送作为受体酪氨酸激酶抑制剂(RTKi)的化合物至眼部的药物制剂
CA2693888A CA2693888A1 (fr) 2007-07-20 2007-07-20 Formulation pharmaceutique d'administration a l'oeil de composes inhibiteurs de tyrosine kinase receptrice
EP06851209A EP2178564A1 (fr) 2007-07-20 2007-07-20 Formulation pharmaceutique d'administration à l'oeil de composés inhibiteurs de tyrosine kinase réceptrice

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/US2006/062359 WO2009014510A1 (fr) 2007-07-20 2007-07-20 Formulation pharmaceutique d'administration, dans l'oeil, de composés inhibiteurs des récepteurs tyrosine kinases

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WO2009014510A1 true WO2009014510A1 (fr) 2009-01-29

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PCT/US2006/062359 Ceased WO2009014510A1 (fr) 2007-07-20 2007-07-20 Formulation pharmaceutique d'administration, dans l'oeil, de composés inhibiteurs des récepteurs tyrosine kinases

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EP (1) EP2178564A1 (fr)
JP (1) JP2010534201A (fr)
KR (1) KR20100051811A (fr)
CN (1) CN101687042A (fr)
AU (1) AU2007356856A1 (fr)
BR (1) BRPI0721885A2 (fr)
CA (1) CA2693888A1 (fr)
MX (1) MX2009012879A (fr)
WO (1) WO2009014510A1 (fr)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010101992A1 (fr) * 2009-03-03 2010-09-10 Alcon Research, Ltd. Composition pharmaceutique pour l'administration à l'oeil de composés inhibant les récepteurs tyrosine kinase (rtki)
CN102340993A (zh) * 2009-03-03 2012-02-01 爱尔康研究有限公司 向眼部递送受体酪氨酸激酶抑制性(RTKi)化合物的药物组合物
JP2013535451A (ja) * 2010-07-21 2013-09-12 アルコン リサーチ， リミテッド 増強された溶解度特徴を有する薬学的組成物
US8912236B2 (en) 2009-03-03 2014-12-16 Alcon Research, Ltd. Pharmaceutical composition for delivery of receptor tyrosine kinase inhibiting (RTKi) compounds to the eye
WO2015041294A1 (fr) 2013-09-20 2015-03-26 参天製薬株式会社 Composition contenant du polyéthylène glycol
US9707173B2 (en) 2008-12-05 2017-07-18 Alcon Research, Ltd. Pharmaceutical suspension

Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2703777A (en) * 1950-05-02 1955-03-08 Iso Sol Company Inc Ophthalmological preparations and vehicles and method of making the same
US4425344A (en) * 1980-08-01 1984-01-10 Smith And Nephew Associated Companies Limited Compositions for the treatment of glaucoma containing triamterene
US5605684A (en) * 1994-03-14 1997-02-25 Piacquadio; Daniel J. Topical thalidomide compositions for surface of mucosal wounds, ulcerations, and lesions
WO1999060948A2 (fr) * 1998-05-27 1999-12-02 Emiliya Mikhailovna Mironova Principe permettant de traiter des maladies oculaires
EP1437143A1 (fr) * 2001-09-28 2004-07-14 Santen Pharmaceutical Co., Ltd. Injections pour tissu oculaire contenant un medicament lie a du polyethylene glycol
US20040167109A1 (en) * 2003-02-20 2004-08-26 Bingaman David P Formulations of glucocorticoids to treat pathologic ocular angiogenesis
US20060189608A1 (en) * 2005-02-23 2006-08-24 Alcon, Inc. Methods for treating ocular angiogenesis, retinal edema, retinal ischemia, and diabetic retinopathy using selective RTK inhibitors
WO2006094064A2 (fr) * 2005-02-28 2006-09-08 Avocet Polymer Technologies, Inc. Methode de diminution de cicatrices a l'aide de vitamine d
US20060258698A1 (en) * 2005-02-09 2006-11-16 Sreenivasu Mudumba Liquid formulations for treatment of diseases or conditions
WO2007076358A1 (fr) * 2005-12-23 2007-07-05 Alcon, Inc. Preparation pharmaceutique pour l'administration, dans l'oeil, de composes inhibiteurs des récepteurs tyrosine kinases (rtki)

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2703777A (en) * 1950-05-02 1955-03-08 Iso Sol Company Inc Ophthalmological preparations and vehicles and method of making the same
US4425344A (en) * 1980-08-01 1984-01-10 Smith And Nephew Associated Companies Limited Compositions for the treatment of glaucoma containing triamterene
US5605684A (en) * 1994-03-14 1997-02-25 Piacquadio; Daniel J. Topical thalidomide compositions for surface of mucosal wounds, ulcerations, and lesions
WO1999060948A2 (fr) * 1998-05-27 1999-12-02 Emiliya Mikhailovna Mironova Principe permettant de traiter des maladies oculaires
EP1437143A1 (fr) * 2001-09-28 2004-07-14 Santen Pharmaceutical Co., Ltd. Injections pour tissu oculaire contenant un medicament lie a du polyethylene glycol
US20040167109A1 (en) * 2003-02-20 2004-08-26 Bingaman David P Formulations of glucocorticoids to treat pathologic ocular angiogenesis
US20060258698A1 (en) * 2005-02-09 2006-11-16 Sreenivasu Mudumba Liquid formulations for treatment of diseases or conditions
US20060189608A1 (en) * 2005-02-23 2006-08-24 Alcon, Inc. Methods for treating ocular angiogenesis, retinal edema, retinal ischemia, and diabetic retinopathy using selective RTK inhibitors
WO2006094064A2 (fr) * 2005-02-28 2006-09-08 Avocet Polymer Technologies, Inc. Methode de diminution de cicatrices a l'aide de vitamine d
WO2007076358A1 (fr) * 2005-12-23 2007-07-05 Alcon, Inc. Preparation pharmaceutique pour l'administration, dans l'oeil, de composes inhibiteurs des récepteurs tyrosine kinases (rtki)

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
SCHMIDT-ERFURTH ET AL: "Management of neovascular age-related macular degeneration", PROGRESS IN RETINAL AND EYE RESEARCH, OXFORD, GB, vol. 26, no. 4, 19 May 2007 (2007-05-19), pages 437 - 451, XP022085851, ISSN: 1350-9462 *

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9707173B2 (en) 2008-12-05 2017-07-18 Alcon Research, Ltd. Pharmaceutical suspension
WO2010101992A1 (fr) * 2009-03-03 2010-09-10 Alcon Research, Ltd. Composition pharmaceutique pour l'administration à l'oeil de composés inhibant les récepteurs tyrosine kinase (rtki)
CN102340993A (zh) * 2009-03-03 2012-02-01 爱尔康研究有限公司 向眼部递送受体酪氨酸激酶抑制性(RTKi)化合物的药物组合物
CN102340991A (zh) * 2009-03-03 2012-02-01 爱尔康研究有限公司 向眼部递送受体酪氨酸激酶抑制性(RTKi)化合物的药物组合物
AU2010221369B2 (en) * 2009-03-03 2014-03-13 Alcon Research, Ltd. Pharmaceutical composition for delivery of receptor tyrosine kinase inhibiting (RTKi) compounds to the eye
US8912236B2 (en) 2009-03-03 2014-12-16 Alcon Research, Ltd. Pharmaceutical composition for delivery of receptor tyrosine kinase inhibiting (RTKi) compounds to the eye
CN105362221A (zh) * 2009-03-03 2016-03-02 爱尔康研究有限公司 向眼部递送受体酪氨酸激酶抑制性(RTKi)化合物的药物组合物
JP2013535451A (ja) * 2010-07-21 2013-09-12 アルコン リサーチ， リミテッド 増強された溶解度特徴を有する薬学的組成物
WO2015041294A1 (fr) 2013-09-20 2015-03-26 参天製薬株式会社 Composition contenant du polyéthylène glycol

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JP2010534201A (ja) 2010-11-04
KR20100051811A (ko) 2010-05-18
BRPI0721885A2 (pt) 2014-02-25
CN101687042A (zh) 2010-03-31
AU2007356856A1 (en) 2009-01-29

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