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US20070281914A1 - Use of a steroid prodrug for the treatment of disease of the posterior segment of the eye - Google Patents

Use of a steroid prodrug for the treatment of disease of the posterior segment of the eye Download PDF

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Publication number
US20070281914A1
US20070281914A1 US11/444,337 US44433706A US2007281914A1 US 20070281914 A1 US20070281914 A1 US 20070281914A1 US 44433706 A US44433706 A US 44433706A US 2007281914 A1 US2007281914 A1 US 2007281914A1
Authority
US
United States
Prior art keywords
prodrug
composition
steroid
dexamethasone
disease
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.)
Abandoned
Application number
US11/444,337
Other languages
English (en)
Inventor
Laura Rabinovich-Guilatt
Gregory Lambert
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.)
Novagali SA
Original Assignee
Novagali SA
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
Priority to US11/444,337 priority Critical patent/US20070281914A1/en
Priority to EP06290901.5A priority patent/EP1864667B1/en
Priority to DK06290902.3T priority patent/DK1864668T3/da
Priority to EP06290902A priority patent/EP1864668B1/en
Priority to EP10177382.8A priority patent/EP2319517B1/en
Priority to PL06290901T priority patent/PL1864667T3/pl
Priority to PL10177382T priority patent/PL2319517T3/pl
Priority to SI200631521T priority patent/SI1864668T1/sl
Priority to PL10177375T priority patent/PL2322183T3/pl
Priority to US11/444,349 priority patent/US20070280902A1/en
Application filed by Novagali SA filed Critical Novagali SA
Priority to PT62909023T priority patent/PT1864668E/pt
Priority to PT62909015T priority patent/PT1864667E/pt
Priority to EP10177375.2A priority patent/EP2322183B1/en
Priority to PL06290902T priority patent/PL1864668T3/pl
Priority to ES06290902T priority patent/ES2399976T3/es
Priority to DK10177382.8T priority patent/DK2319517T3/da
Assigned to NOVAGALI PHARMA SA reassignment NOVAGALI PHARMA SA ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: LAMBERT, GREGORY, RABINOVICH-GUILATT, LAURA
Priority to KR1020087031197A priority patent/KR101408317B1/ko
Priority to PCT/EP2007/055414 priority patent/WO2007138114A1/en
Priority to JP2009512616A priority patent/JP5455624B2/ja
Priority to CN2007800201723A priority patent/CN101553235B/zh
Priority to AU2007267079A priority patent/AU2007267079B2/en
Priority to PCT/EP2007/055413 priority patent/WO2007138113A1/en
Priority to CA2653902A priority patent/CA2653902C/en
Priority to US11/806,554 priority patent/US8227452B2/en
Priority to KR1020147002130A priority patent/KR101541416B1/ko
Priority to US11/806,556 priority patent/US9192567B2/en
Priority to JP2009512617A priority patent/JP5284953B2/ja
Publication of US20070281914A1 publication Critical patent/US20070281914A1/en
Priority to HK08104425.9A priority patent/HK1110219B/en
Priority to HK08104540.9A priority patent/HK1110221B/en
Priority to IL195626A priority patent/IL195626A/en
Abandoned legal-status Critical Current

Links

Classifications

    • 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
    • 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
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
    • 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
    • A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/543—Lipids, e.g. triglycerides; Polyamines, e.g. spermine or spermidine
    • 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
    • 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
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • 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
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy

Definitions

  • the present invention relates to the field of the treatment of the ophthalmic diseases, in particular of the intraocular diseases of a human being or an animal, by at least one steroid, and in particular by at least one corticosteroid.
  • the invention particularly focuses on ophthalmic compositions or devices, preferably ophthalmic emulsions, comprising at least one steroid, preferably a corticosteroid.
  • the invention also relates to the administration of such ophthalmic compositions, and in particular to their administration intraocularly.
  • the invention relates also to the controlled release of therapeutic active agents, in particular of corticosteroids intraocularly, in particular in the posterior segment of the eye.
  • a posterior ocular condition is a disease which primarily affects a posterior ocular site such as choroid or sclera, vitreous, vitreous chamber, retina, optic nerve, and blood vessels and nerves which vascularize or innervate a posterior ocular site
  • Steroids are already largely used to treat ophthalmic diseases affecting the posterior chamber of the eye, in particular central retinal vein occlusion (CRVO), branch retinal vein occlusion (BRVO), choroidal macular edema (CME), diabetic macular edema (DME), diabetic macular retinopathy, uveitis, and age related macular degeneration (ARMD).
  • CRVO central retinal vein occlusion
  • BRVO branch retinal vein occlusion
  • CME choroidal macular edema
  • DME diabetic macular edema
  • uveitis uveitis
  • age related macular degeneration ARMD
  • corticosteroids in the anterior segment of the eye was in particular related to the appearance of these side effects, and was thus undesirable.
  • the effectiveness of the treatment is in particular related to the presence of the active compound and hence to the half life of the drug.
  • a known corticosteroid, the dexamethasone has a half life of 3.5 hours when injected intraocularly (Kwak, Arch Ophthalmol, 1992). Thus, the injections must be repeated to maintain a therapeutic effect.
  • RETISERTTM fluocinolone acetonide intravitreal implant, Bausch & Lomb 0.59 mg is a sterile implant designed to release fluocinolone acetonide locally to the posterior segment of the eye.
  • RETISERTTM was recently approved by the FDA and is indicated for the treatment of chronic non-infectious uveitis affecting the posterior segment of the eye.
  • clinical trials of this implant systematically results in a raise of the intraocular pressure (IOP) and cataracts as main adverse effects.
  • IOP intraocular pressure
  • Posurdex is another intraocular device being developed by Allergan containing 700 micrograms of dexamethasone which are released during the first month post implantation. Its efficacy has been evaluated among others in cases of persistant macular edema (Williams, ISOPT communication, 2006) and for anti-inflammatory effects after cataract surgery (Tan, Ophthalmology, 2004). However, a safety and efficacy clinical study of 700 micrograms dexamethasone implant for the treatment of macular edema showed significant increases in IOP (to ⁇ 25 mm Hg) in 15% of patients (Williams, ISOPT communication, Berlin, 2006).
  • steroid-containing devices being developed in research are triamcinolone acetonide/polycaprolactone implants (Beeley, J Biomed Mater Res A, 2005), triamcinolone/polyvinyl alcohol implants (Ciulla, Br J Ophthalmol, 2003), betamethasone polymeric implants (Kato, IOVS, 2004 and Okabe, IOVS, 2003) and others.
  • this invention relates to the use of prodrugs of steroids, especially corticosteroids, for the preparation of a medicament or an ophthalmic composition intended for the treatment of an ocular condition or disease of a human being or an animal, said medicament or ophthalmic composition being administered by invasive means, preferably by intraocular injection, more preferably by intravitreal injection, for in-situ sustained release of therapeutic effective agents.
  • the inventors observed that intraocular, more especially intravitreal, injections of a corticosteroid prodrug, the dexamethasone palmitate, resulted in the in-situ release of dexamethasone.
  • the Inventors suppose that there might be a selective uptake of the steroid prodrug, preferably a lipophilic ester of a steroid, by the ocular inflammatory cells (macrophages).
  • the increased macrophage activity at the inflamed sites may result in a targeted cleavage of the active moiety only in the disease location, with no unspecific release. Therefore, fewer side effects occasioned by the therapeutic agent are expected to be observed.
  • the drug would be release at the very location of the disease, resulting in a decrease of unwanted adverse effects in other ocular structures where the prodrug is not hydrolyzed.
  • the invention also allows to maintain the desired effect in the ocular condition for an extended period of time during which an amount of the prodrug is present at the ocular site such that it allows the release of an effective amount of the active drug for an extended period of time, which is preferably at least one month
  • prodrug in the invention is meant a lipophilic long-chain prodrug ester of steroid, preferably of corticosteroid, said ester group comprising an alkyl group of more than 10 carbons preferentially of more than 14 carbons, even more preferentially of 16 carbons.
  • the prodrug does not have any direct therapeutic and/or physiologic effect, and is therefore called “inactive”, whereas the drug released by hydrolysis of the prodrug does have a physiological therapeutic effect.
  • the invention is directed to the use of a composition comprising at least one prodrug of a steroid, preferably of a corticosteroid, for the preparation of an ophthalmic composition intended for the treatment of an ocular condition or disease of a human being or an animal.
  • composition according to the invention comprises at least one prodrug of corticosteroid, which is preferably selected from: alclometasone dipropionate, amcinonide, amcinafel, amcinafide, beclamethasone, betamethasone, betamethasone dipropionate, betamethasone valerate, clobetasone propionate, chloroprednisone, clocortelone, Cortisol, cortisone, cortodoxone, difluorosone diacetate, descinolone, desonide, defluprednate, dihydroxycortisone, desoximetasone, dexamethasone, deflazacort, diflorasone, diflorasone diacetate, dichlorisone, esters of betamethasone, fluazacort, flucetonide, flucloronide, fludrotisone, fluorocortisone, flumethasone, flunisolide, fluocinonide, fluo
  • the corticosteroid is selected from: cortisone, dexamethasone, fluocinolone, hydrocortisone, methylprednisolone, prednisolone, prednisone, and triamcinolone.
  • the composition comprises a prodrug of dexamethasone, more preferably dexamethasone palmitate.
  • the prodrug is comprised in the emulsion in an amount of about 0.01% to about 10% w/w of the composition.
  • the prodrug is comprised in the amount of about 0.5% to about 3% w/w of the composition.
  • the prodrug is comprised in a amount of about 2% w/w of the composition.
  • the prodrug is comprised in an amount of about 1% w/w of the composition.
  • the composition of the invention includes at least one steroid prodrug dissolved in a ophthalmologically acceptable oil.
  • the composition of the invention includes at least one steroid prodrug dissolved in a physiologically acceptable oil which is emulsified into a oil-in-water emulsion by different techniques such as high shear and high pressure homogenization with suitable emulsifiers; final preparation can be sterilized by filtration or by autoclave.
  • the composition comprises at least one prodrug as above-defined, in combination with any ophtalmologically acceptable excipient or carrier.
  • the carrier may be selected from an ophtalmologically acceptable oil, phospholipid vesicles or oil-in-water emulsion or water-in-oil emulsion or any other suitable carrier about 20, at least about 30 or at least about 40 weight percent of the composition/emulsion, preferably 10% of the emulsion.
  • Excipient characteristics that are considered include, but are not limited to, the biocompatibility and biodegradability at the site of implantation, compatibility with the prodrug of interest, and processing temperatures.
  • the oil phase comprises at least about 1, at least about 5, at least about 10, at least about 20, at least about 30 or at least about 40 weight percent of the composition.
  • the oil represents 10 weight percent of the composition.
  • the composition of the invention is administered through one intraocular injection, more preferably through one intravitreal injection.
  • the composition of the invention is administered through the placement of an intraocular implant containing or combined with the composition of the invention.
  • the composition further comprises an active agent selected from cyclosporine, anti-VEGF, and/or an antibiotic.
  • composition comprises dexamethasone palmitate and at least one active agent selected from the group consisting of cyclosporine, anti-VEGF, and an antibiotic.
  • the invention also relates to a method of treatment of a human or animal ophthalmic condition or disease comprising the intraocular administration of the composition of the invention.
  • the method of the invention includes the administration of a steroid prodrug into an ocular site of a patient suffering from an ocular condition or disease.
  • the prodrug can be administered alone or in an ophtalmologically carrier suitable for intraocular administration.
  • the carrier may be an oil, phospholipid vesicles or oil-in-water emulsion, or any other suitable carrier.
  • the administrated prodrug will gradually release through its hydrolysis by endogenous enzymes in situ, to generate therapeutic levels of the active drug. This results in the improvement of ocular conditions by the action of the active drug in the very site of inflammation due to the ocular condition or disease.
  • the frequency of administration of the composition of the invention trough injection is once a month, preferably once every two months, more preferably once every six months. It is an advantage of this invention to provide a less frequent need for repeated administration.
  • the amount of the composition of the invention administered is such that, after one month, the molar ratio drug/prodrug in the target tissue, preferably in choroid or in retina, is equal or less than 1, preferentially of 0.5, more preferentially of 0.1.
  • the improvement of the ocular condition obtained by a method within the scope of the present invention can be determined by observing: an improved visual acuity, an improved visual contrast sensitivity, a decreased retinal or choroidal blood vessel leakage, a decreased retinal or macular thickness, or a reduced number of cells in the aqueous or vitreous humor or by determining a reduced flare.
  • the administration of the composition of the invention is invasive. More preferably, the composition of the invention is administered through an implant or through intraocular, preferably intravitreal injection.
  • compositions of the invention are useful for the treatment of conditions or diseases affecting the interior of the eye, preferably of the back of the eye. These compositions are especially useful for the treatment of the following conditions or diseases: uveitis, macular edema, macular degeneration, retinal detachment, ocular tumors, bacterial, fungal but viral infections, multifocal choroiditis, diabetic retinopathy, proliferative vitreoretinopathy (PVR), sympathetic opthalmia, Vogt Koyanagi-Harada (VKH) syndrome, histoplasmosis, uveal diffusion, and vascular occlusion.
  • conditions or diseases uveitis, macular edema, macular degeneration, retinal detachment, ocular tumors, bacterial, fungal but viral infections, multifocal choroiditis, diabetic retinopathy, proliferative vitreoretinopathy (PVR), sympathetic opthalmia, Vogt Koyanagi
  • the composition of the invention is within an implantable device and then used for the treatment of uveitis, macular edema, vascular occlusive conditions, proliferative vitreoretinopathy (PVR), and various other retinopathies.
  • PVR proliferative vitreoretinopathy
  • a liquid chromatographic-mass spectrometric method for the simultaneous determination of dexamethasone and dexamethasone palmitate in ocular tissues was developed.
  • Analytes and internal standard (roxithromycine) were extracted from the tissues using acetonitrile and separated by reverse phase liquid chromatography with a C8 column and a gradient mobile phase.
  • the compounds were detected by mass spectrometric detection (atmospheric pressure ionization) with selected ion monitoring (SIM) (393.0 for dexamethasone and 631.5 for dexamethasone palmitate).
  • SIM selected ion monitoring
  • the method was selective for both compounds and the limits of quantification were 32.7 ng/g of retina and 71.6 ng/g choroid.
  • the unweighed linear model was applied.
  • dexamethasone of more than 800 ng/g were maintained for at least 2 months in the target tissues. Moreover, considerable amounts of the prodrug dexapalmitate remained in both retina and choroid, indicating an even more long-lasting release.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Ophthalmology & Optometry (AREA)
  • Dermatology (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Virology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
US11/444,337 2006-06-01 2006-06-01 Use of a steroid prodrug for the treatment of disease of the posterior segment of the eye Abandoned US20070281914A1 (en)

Priority Applications (30)

Application Number Priority Date Filing Date Title
DK10177382.8T DK2319517T3 (da) 2006-06-01 2006-06-01 Anvendelse af prodrugs til okulær, intravenøs administration
DK06290902.3T DK1864668T3 (da) 2006-06-01 2006-06-01 Anvendelse af prodrug til okulær, intravitreal administration
EP06290902A EP1864668B1 (en) 2006-06-01 2006-06-01 Use of prodrugs for ocular intravitreous administration
EP10177382.8A EP2319517B1 (en) 2006-06-01 2006-06-01 Use of prodrugs for ocular intravitreous administration
PL06290901T PL1864667T3 (pl) 2006-06-01 2006-06-01 Zastosowanie proleków do podania do ciała szklistego oka
PL10177382T PL2319517T3 (pl) 2006-06-01 2006-06-01 Wykorzystanie proleku do podawania doocznego, śródszklistkowego
SI200631521T SI1864668T1 (sl) 2006-06-01 2006-06-01 Uporaba predzdravil za okularno intravitrealno dajanje
PL10177375T PL2322183T3 (pl) 2006-06-01 2006-06-01 Wykorzystanie proleku do podawania doocznego, śródszklistkowego
EP06290901.5A EP1864667B1 (en) 2006-06-01 2006-06-01 Use of prodrugs for ocular intravitreous administration
US11/444,349 US20070280902A1 (en) 2006-06-01 2006-06-01 Method for treating eye disease or conditions affecting the posterior segment of the eye
PT62909023T PT1864668E (pt) 2006-06-01 2006-06-01 Utilização de pró-fármacos para administração ocular intravítrea
PT62909015T PT1864667E (pt) 2006-06-01 2006-06-01 Uso de pró-fármacos para administração intravítrea ocular
EP10177375.2A EP2322183B1 (en) 2006-06-01 2006-06-01 Use of prodrugs for ocular intravitreous administration
PL06290902T PL1864668T3 (pl) 2006-06-01 2006-06-01 Wykorzystanie proleku do okulistycznego podawania śródszklistkowego
ES06290902T ES2399976T3 (es) 2006-06-01 2006-06-01 Uso de profármacos para la administración intravítrea ocular
US11/444,337 US20070281914A1 (en) 2006-06-01 2006-06-01 Use of a steroid prodrug for the treatment of disease of the posterior segment of the eye
KR1020087031197A KR101408317B1 (ko) 2006-06-01 2007-06-01 후안부 질환 치료를 위한 스테로이드 전구약물의 용도
JP2009512617A JP5284953B2 (ja) 2006-06-01 2007-06-01 硝子体内注入用のプロドラッグ
US11/806,554 US8227452B2 (en) 2006-06-01 2007-06-01 Use of a steroid prodrug for the treatment of disease of the posterior segment of the eye
JP2009512616A JP5455624B2 (ja) 2006-06-01 2007-06-01 後眼部の疾患治療用のステロイドプロドラッグの使用
CN2007800201723A CN101553235B (zh) 2006-06-01 2007-06-01 甾族化合物前药在治疗眼后段疾病中的用途
AU2007267079A AU2007267079B2 (en) 2006-06-01 2007-06-01 Use of a steroid prodrug for the treatment of disease of the posterior segment of the eye
PCT/EP2007/055413 WO2007138113A1 (en) 2006-06-01 2007-06-01 Use of a steroid prodrug for the treatment of disease of the posterior segment of the eye
CA2653902A CA2653902C (en) 2006-06-01 2007-06-01 Use of a steroid prodrug for the treatment of disease of the posterior segment of the eye
PCT/EP2007/055414 WO2007138114A1 (en) 2006-06-01 2007-06-01 Use of prodrugs for ocular intravireous administration
KR1020147002130A KR101541416B1 (ko) 2006-06-01 2007-06-01 후안부 질환 치료를 위한 스테로이드 전구약물의 용도
US11/806,556 US9192567B2 (en) 2006-06-01 2007-06-01 Method for treating eye disease or conditions affecting the posterior segment of the eye
HK08104425.9A HK1110219B (en) 2008-04-21 Use of prodrugs for ocular intravitreous administration
HK08104540.9A HK1110221B (en) 2008-04-23 Use of prodrugs for ocular intravitreous administration
IL195626A IL195626A (en) 2006-06-01 2008-12-01 Use of an ophthalmic device containing at least one prescription drug in combination with any carrier suitable for the provision of an eye for the preparation of a drug or an ophthalmic drug for the treatment of the disease in the back of the eye in a person or animal

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US11/444,349 US20070280902A1 (en) 2006-06-01 2006-06-01 Method for treating eye disease or conditions affecting the posterior segment of the eye
EP06290901.5A EP1864667B1 (en) 2006-06-01 2006-06-01 Use of prodrugs for ocular intravitreous administration
US11/444,337 US20070281914A1 (en) 2006-06-01 2006-06-01 Use of a steroid prodrug for the treatment of disease of the posterior segment of the eye
EP06290902A EP1864668B1 (en) 2006-06-01 2006-06-01 Use of prodrugs for ocular intravitreous administration

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US11/806,554 Division US8227452B2 (en) 2006-06-01 2007-06-01 Use of a steroid prodrug for the treatment of disease of the posterior segment of the eye

Publications (1)

Publication Number Publication Date
US20070281914A1 true US20070281914A1 (en) 2007-12-06

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Application Number Title Priority Date Filing Date
US11/444,349 Abandoned US20070280902A1 (en) 2006-06-01 2006-06-01 Method for treating eye disease or conditions affecting the posterior segment of the eye
US11/444,337 Abandoned US20070281914A1 (en) 2006-06-01 2006-06-01 Use of a steroid prodrug for the treatment of disease of the posterior segment of the eye
US11/806,556 Expired - Fee Related US9192567B2 (en) 2006-06-01 2007-06-01 Method for treating eye disease or conditions affecting the posterior segment of the eye
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US8663194B2 (en) 2008-05-12 2014-03-04 University Of Utah Research Foundation Intraocular drug delivery device and associated methods
US9095404B2 (en) 2008-05-12 2015-08-04 University Of Utah Research Foundation Intraocular drug delivery device and associated methods
US9877973B2 (en) 2008-05-12 2018-01-30 University Of Utah Research Foundation Intraocular drug delivery device and associated methods
US10064819B2 (en) 2008-05-12 2018-09-04 University Of Utah Research Foundation Intraocular drug delivery device and associated methods
WO2024167694A3 (en) * 2023-02-06 2024-10-10 Celularity Inc. Placental extracellular matrices for ocular delivery of ophthalmic therapeutic agents

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EP2322183A1 (en) 2011-05-18
US8227452B2 (en) 2012-07-24
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EP1864667A1 (en) 2007-12-12
CN101553235B (zh) 2012-12-05
AU2007267079A1 (en) 2007-12-06
PL2322183T3 (pl) 2015-01-30
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EP2322183B1 (en) 2014-10-22
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US20070281913A1 (en) 2007-12-06
EP1864667B1 (en) 2013-09-04
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