US20110319487A1 - Polymeric delivery system for a nonviscous prostaglandin-based solution without preservatives - Google Patents

Polymeric delivery system for a nonviscous prostaglandin-based solution without preservatives Download PDF

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US20110319487A1
US20110319487A1 US13/170,716 US201113170716A US2011319487A1 US 20110319487 A1 US20110319487 A1 US 20110319487A1 US 201113170716 A US201113170716 A US 201113170716A US 2011319487 A1 US2011319487 A1 US 2011319487A1
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solution
prostaglandin
agent
advantageously
xalatan
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Fabrice Mercier
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Laboratoires Thea SAS
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Priority to US13/595,165 priority patent/US8637054B2/en
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    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
    • 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
    • A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
    • A61K31/5575—Eicosanoids, e.g. leukotrienes or prostaglandins having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • 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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/06—Antiglaucoma agents or miotics

Definitions

  • the invention concerns eye drops or an ophthalmic solution whose active ingredient includes at least one prostaglandin, said solution containing no antimicrobial agents, notably of the quaternary ammonium type (such as benzalkonium chloride [BAK]).
  • a quaternary ammonium type such as benzalkonium chloride [BAK]
  • a polymeric delivery system has been developed to allow the prostaglandin solution to be as effective as a solution containing BAK, but without the disadvantages from a toxicological and allergenic point of view.
  • Prostaglandins are well-known active ingredients administered topically to humans or animals in the form of eye drops for the treatment of glaucoma.
  • the usual dosage of these formulas is 1 drop a day in each eye, it being understood that prostaglandins can also be used in combination with a second antiglaucoma agent such as, for example, beta blockers, carbonic anhydrase inhibitors or alpha-adrenergic agonists.
  • prostaglandins are not water-soluble, meaning that they require a solubilization step before including them in the eye drop solution.
  • LDPE low-density polyethylene
  • prostaglandin-based ophthalmic solutions on the market include a preservative which, beyond its antimicrobial properties, also ensures solubilization of the active ingredient and, partially, its stabilization.
  • An example of this is the product sold by Pfizer under the Xalatan® brand, which combines latanoprost and BAK at 0.02% by weight. It should be pointed out that, despite the presence of BAK, these eye drops are not stable at ambient temperature and must be stored cold, at a temperature of approximately 5° C. Furthermore, the Allergan company sells eye drops under the Lumigan® brand, combining bimatoprost and BAK at 0.005% by weight.
  • antimicrobial preservatives are toxic in long-term use, to such an extent that today there is a tendency to limit their use by reducing their concentration as much as possible in eye drops or, even better, to eliminate them completely from the formulas.
  • Polysorbate 80 has also been proposed in ophthalmic solutions to partially reduce the concentration of BAK, as is the case, for example, of the product sold by Novartis under the Rescula® brand, combining unoprostone with a mixture of BAK and polysorbate 80 at 0.015% by weight of the solution.
  • document US2004/0082660 describes an ophthalmic solution with no BAK and containing a mixture of latanoprost and polysorbate 80.
  • the problem that the invention proposes to solve is therefore that of developing a prostaglandin-based formula that meets at least the following conditions:
  • Another objective is to propose a formulation that is sufficiently fluid to be packaged using an aseptic packaging technique such as “Blow-Fill-Seal” (single-dose unit).
  • the Applicant has developed a new delivery system enabling prostaglandin to act with the same effectiveness as that reported with BAK.
  • BAK and more generally quaternary ammonium molecules, have a so-called “soap” effect providing greater penetration by the active ingredient molecules into the eye tissue, but on the other hand they have a toxic effect (irritation, ocular dryness, inflammation, etc.).
  • the delivery system developed in the invention therefore provides equivalent penetration and activity using a different mechanism of action. In any case, it does not have the disadvantages of the conventional preservatives of the BAK type.
  • this invention concerns an ophthalmic solution including:
  • such a solution advantageously contains no antimicrobial preservatives, advantageously of the quaternary ammonium type, and even more advantageously benzalkonium chloride (BAK).
  • antimicrobial preservative designates a preservative with antimicrobial properties, i.e. a compound capable of protecting the ophthalmic solution from possible microbial contamination.
  • a preservative as meant in the invention is to be distinguished from preservatives acting on the solution's chemical preservation, for example antioxidants such as EDTA.
  • the solution claimed contains at least one prostaglandin as its active ingredient.
  • there is at least one prostaglandin in the solution and these are chosen from the group including 17-phenyl-13,14 dihydro trinor prostaglandin F 2 ⁇ isopropyl ester (latanoprost), 20-ethyl prostaglandin F 2 ⁇ , (+)-fluprostenol isopropyl ester (travoprost), 17-phenyl trinor prostaglandin F 2 ⁇ amide, 17-phenyl-13,14 dihydro trinor prostaglandin F 2 ⁇ ethyl amide (bimatoprost), tafluprost prostaglandin F 2 ⁇ ethanolamide, bimatoprost (free acid)-d 4 , bimatoprost-d 4 , latanoprost ethyl amide, 13,14 dihydro-15-keto-20-ethyl prostaglandin F 2 ⁇ (unoprostone), 13,
  • the concentration of prostaglandin in the solution is between 0.002 and 0.15% (w/v).
  • the prostaglandin(s) can be combined with a second active ingredient, notably with other classes of antiglaucoma agents so they can thus work synergistically.
  • these may include beta blockers chosen from the group including timolol maleate and carteolol chloride, carbonic anhydrase inhibitors such as those, for example, chosen from the group including dorzolamide chloride, or alpha-adrenergic agonist such as, for example, brimonidine tartrate.
  • beta blockers chosen from the group including timolol maleate and carteolol chloride
  • carbonic anhydrase inhibitors such as those, for example, chosen from the group including dorzolamide chloride
  • alpha-adrenergic agonist such as, for example, brimonidine tartrate.
  • combinations of prostaglandins and beta blockers include, for example:
  • Xalacom®—Pfizer Latanoprost 0.005%+Timolol 0.5%
  • the antiglaucoma agent accounts for between 0.1 and 0.5% (w/v) of the solution.
  • solubilizing agent capable of solubilizing the prostaglandin(s).
  • This solubilizing agent preferably non-ionic, advantageously has surface-active properties.
  • Another potential candidate is polyoxyl 15 hydroxystearate or macrogol 15 hydroxystearate (CAS number 70142-34-6), or polysorbate 20 (CAS number 9005-64-5), or polysorbate 60 (CAS number 9005-67-8) or polysorbate 80 (CAS number 9005-65-6).
  • concentration of the solubilizing agent in the solution is typically between 0.1 and 20% (w/v), advantageously between 0.5 and 5% (w/v).
  • ophthalmic solution Another important characteristic of the ophthalmic solution is its viscosity. This is advantageously between 8 and 20 mPa ⁇ s (cP), even more advantageously between 10 and 14 mPa ⁇ s (cP), when measured with a Brookfield RVDV III rotational viscometer at 25° C.
  • This solution can indeed be distinguished from an aqueous gel, typically characterized by a viscosity between 400 and 800 mPa ⁇ s (cP) and which constitutes a long-acting form to obtain sustained release of the active ingredient.
  • This invention is based on the development of a suitable gelling system, based on the combination of two gelling agents to obtain a nonviscous polymeric delivery system:
  • a carbomer is defined according to the European Parmacopoeia, i.e. “a cross-linked polymer of acrylic acid of very high relative molecular mass, comprising a large proportion of carboxylic groups” and by its CAS number 9003-01-4.
  • European Parmacopoeia i.e. “a cross-linked polymer of acrylic acid of very high relative molecular mass, comprising a large proportion of carboxylic groups” and by its CAS number 9003-01-4.
  • carbomers 910/934/934P/940/941/971 and 974P, advantageously 974P.
  • PEG or macrogol is defined according to the European Parmacopoeia, i.e. “a mixture of polymers with the general formula H—(OCH 2 —CH 2 )n-OH where n represents the average number of oxyethylene groups”.
  • the type of macrogol is defined by a number that indicates the average relative molecular mass. More advantageously, PEG 4000 having CAS number 25322-68-3 is used.
  • composition of the invention may contain the usual additives excluding antimicrobial preservatives.
  • additives excluding antimicrobial preservatives.
  • These may include, for example, non-ionic ionizing agents such as polyols (sorbitol, for example). They may also be antioxidants or buffer systems (for example, sodium hydroxide as a neutralizing agent).
  • the claimed composition is made of the ingredients listed in the table below, advantageously in the mentioned amounts:
  • the formulation of the invention can be presented in single-use (single-dose unit) bottles or in multi-dose bottles, for example Abak® or Comod® or the equivalent, such bottles allowing the eye drops to be applied over several days without preservatives.
  • the subject of the invention is thus a single-use (single-dose unit) or multi-dose bottle containing the ophthalmic solution described above, made of EP-quality LDPE containing no additives.
  • the solution according to the invention is stable for at least 18 months, or even at least 24 months, at ambient temperature (25° C.-30° C.).
  • the invention also concerns the use of the ophthalmic solution as described above in the production of a medicine to treat glaucoma in humans or animals, notably its capacity to reduce intraocular pressure and/or provide neuroprotection to the retinal tissue.
  • this delivery system is less aggressive to eye tissue than the solubilization systems in the prior art, insofar as the reduction in intraocular pressure is more regular and linear after administration of the solution.
  • the eye drops are administered at a dose of one drop a day in each eye.
  • the invention also concerns a therapeutic treatment method for glaucoma in humans or animals consisting in instilling the previously described ophthalmic solution at a dose of one drop a day in each eye.
  • composition according to the present invention leads to a regular and progressive decrease of the intra-ocular pressure (TOP), without an intermediary initial IOP increase. Thanks the present composition, the IOP decrease starts earlier, with an end-effect at least equal possibly better. Without being bound to a theory, this effect on TOP could be due to the presence of the delivery system able to counteract or at least to attenuate the agressivity of the solubilizing agent. Moreover, a composition according to the invention is safe and well-tolerated.
  • FIG. 1 illustrates the effects of 2 eye drop formulations containing 0.005% latanoprost (EXAMPLE 1 composition indicated by full triangles and Xalatan® indicated by full circles) on intraocular pressure (TOP) in rats.
  • EXAMPLE 1 composition indicated by full triangles and Xalatan® indicated by full circles
  • TOP intraocular pressure
  • FIG. 2 reports clinical data concerning the tolerability of EXAMPLE 1 composition versus Xalatan®: A/ ocular subjective symptoms score upon instillation; B/ ocular subjective symptoms not upon instillation; C/ overall conjunctival hyperaemia.
  • the solution obtained is opalescent, free of visible particles, with pH between 6.6 and 7.2 (pH-neutral formulation) and osmolality between 270 and 340 mosmol/kg (isotonic formulation).
  • the solution's viscosity measured with a Brookfield rotational viscometer (Mobile no. 00/UL measurement chamber), is between 8.0 and 14.0 mPa ⁇ s at 25° C.
  • Xalatan® contains the antimicrobial agent benzalkonium chloride (BAK), whereas the EXAMPLE 1 formulation does not.
  • TOP Intraocular pressure
  • FIG. 1 The results of this study are shown in FIG. 1 .
  • Ocular tolerance to the EXAMPLE 1 product compared with Xalatan® was tested at 28 days with two instillations a day (50 ⁇ l) in pigmented rabbits.
  • the objective of this study was to compare the latanoprost single dose unit ophthalmic preparation (without preservative) and Xalatan® eye drops (benzalkonium chloride-preserved) after a 6 weeks treatment with one medication and 6 weeks with the other medication in newly diagnosed glaucomatous patients and in newly diagnosed patients with ocular hypertension.
  • the subjects were exchanged and took the other study medicine (with no washout period), in other words, those who received the first formulation with the preservative received the formation without preservatives during the second period and vice-versa.
  • the second period also lasted 6 weeks.
  • the EXAMPLE 1 formulation is effective on IOP starting at 8 AM and remains just as effective throughout the day, even though it does not contain any preservatives.
  • EXAMPLE 1 Latanoprost 0.005% single dose non-preserved eye drops
  • Xalatan Latanoprost 0.005% preserved eye drops
  • the Safety Set was composed of 213 patients in the EXAMPLE 1 group and 189 patients in the Xalatan group.
  • the modified Intent-to-treat (mITT) Set was composed of 353 patients: 189 in the EXAMPLE 1 group and 164 in the Xalatan group.
  • the Per protocol (PP) Set was composed of 177 patients in the EXAMPLE 1 group and 153 in the Xalatan group.
  • corneal thickness at D-42 ranged between 500 and 610 ⁇ m with a mean ⁇ SD value of 542 ⁇ 22 ⁇ m in the EXAMPLE 1 group and of 543 ⁇ 22 ⁇ m in the Xalatan group.
  • the mean treatment duration (on average 83 days) was similar in both treatment groups. Treatment compliance based upon instillation was >98% in each treatment group.
  • Ocular adverse events were reported in 18 (8.5%) patients in the EXAMPLE 1 group versus 22 (11.6%) in the Xalatan group.
  • the most frequent ocular AE regardless of treatment groups was drug intolerance which was reported in 1 (0.5%) patient in the EXAMPLE 1 group versus 4 (2.1%) patients in the Xalatan group.
  • Ocular AEs with a relationship with the study drug were reported in 8 (3.8%) patients in the EXAMPLE 1 group (including 1 patient with 1 moderate photophobia, and 1 patient with 1 mild optic disc haemorrhage, for which the relationship could not be assessed) versus 10 (5.3%) patients in the Xalatan group.
  • the study drug was withdrawn due to an ocular AE in 2 patients from the EXAMPLE 1 group (1 moderate drug intolerance on D7 and 1 moderate eye pruritus on D28) and in 1 patient in the Xalatan group (1 moderate allergic conjunctivitis on D9). All ocular AEs causing drug withdrawal were related to the study drug according to the investigator. All patients recovered when drug was withdrawn. No serious ocular AE was reported in this study.
  • SAEs systemic serious AEs
  • FIG. 2A The corresponding results are shown on FIG. 2A .
  • the tolerance was very satisfactory or satisfactory for more than 97% of patients in both treatment groups.
  • the rate of very satisfactory tolerance was higher in the EXAMPLE 1 group than in the Xalatan group on D15 (65.1% vs. 59.7%), on D42 (74.0% vs. 65.1%) and on D84 (71.4% vs. 62.9%).

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US13/170,716 US20110319487A1 (en) 2010-06-29 2011-06-28 Polymeric delivery system for a nonviscous prostaglandin-based solution without preservatives
US13/595,165 US8637054B2 (en) 2010-06-29 2012-08-27 Polymeric delivery system for a nonviscous prostaglandin-based solution without preservatives

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US35969910P 2010-06-29 2010-06-29
FR1055236 2010-06-29
FR1055236A FR2961694B1 (fr) 2010-06-29 2010-06-29 Systeme de delivrance polymerique d'une solution non visqueuse a base de prostaglandine sans conservateur
US13/170,716 US20110319487A1 (en) 2010-06-29 2011-06-28 Polymeric delivery system for a nonviscous prostaglandin-based solution without preservatives

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* Cited by examiner, † Cited by third party
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WO2013122801A1 (en) * 2012-02-13 2013-08-22 Bausch & Lomb Incorporated Ophthalmic pharmaceutical compositions and methods of making and using same
US8637054B2 (en) 2010-06-29 2014-01-28 Laboratoires Thea Polymeric delivery system for a nonviscous prostaglandin-based solution without preservatives
WO2014134689A1 (en) 2013-03-08 2014-09-12 Polyactiva Pty Ltd Polymer conjugate for delivery of a bioactive agent
GR1008330B (el) * 2013-10-17 2014-10-20 "Φαρματεν Α.Β.Ε.Ε.", Φαρμακευτικο σκευασμα ελευθερο συντηρητικου για οφθαλμικη χορηγηση εχoν βελτιωμενες φυσικες ιδιοτητες και ογκο σταγονας
WO2015055301A1 (en) 2013-10-15 2015-04-23 Pharmathen S.A. Preservative free pharmaceutical compositions for ophthalmic administration
EP2886130A1 (en) * 2013-12-23 2015-06-24 Rafarm S.A. Ophthalmic pharmaceutical composition and process for the preparation thereof
EP3103439A1 (en) * 2015-06-09 2016-12-14 MEDproject Pharma-Enwicklungs- und Vertriebsgesellschaft mbH Drippable ophthalmic bimatoprost gel
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WO2018033854A1 (en) * 2016-08-15 2018-02-22 Santen Pharmaceutical Co., Ltd. Ophthalmic composition and a method for treating ocular hypertension and glaucoma
US10113033B2 (en) 2013-03-08 2018-10-30 Polyactiva Pty Ltd Polymer conjugate for delivery of a bioactive agent
US20190307768A1 (en) * 2016-11-09 2019-10-10 Taejoon Pharmaceutical Co., Ltd. Ophthalmic composition for lowering intraocular pressure
US11207417B2 (en) 2017-03-14 2021-12-28 Polyactiva Pty Ltd Drug-polymer conjugate
RU2772230C2 (ru) * 2016-11-09 2022-05-18 Таедзоон Фармасьютикал Ко., Лтд. Композиция в форме глазных капель для снижения внутриглазного давления
US11696955B2 (en) 2017-03-14 2023-07-11 Polyactiva Pty Ltd Drug-polymer conjugate
US11787906B2 (en) 2017-03-14 2023-10-17 Polyactiva Pty Ltd Biodegradable drug-polymer conjugate

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CN104288092A (zh) * 2013-07-16 2015-01-21 广东东阳光药业有限公司 拉坦前列素滴眼剂
US9115109B2 (en) * 2013-08-15 2015-08-25 Chirogate International Inc. Processes and intermediates for the preparations of isomer free prostaglandins
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MX2019002396A (es) 2016-08-31 2019-07-08 Aerie Pharmaceuticals Inc Composiciones oftalmicas.
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MX2019011784A (es) 2017-03-31 2019-11-18 Aerie Pharmaceuticals Inc Compuestos de aril ciclopropil-amino-isoquinolinil amida.
JP6931493B2 (ja) * 2017-06-22 2021-09-08 ヨンスン ファイン ケミカル カンパニー，リミテッド 緑内障治療用点眼組成物
JP6672512B2 (ja) * 2018-07-12 2020-03-25 ニコックス エス．エー． 一酸化窒素放出プロスタミドを含有する眼科用組成物
CA3145888A1 (en) * 2018-07-31 2020-02-06 Isilay KAVADARLI Ophthalmic formulations and uses thereof
CA3112391A1 (en) 2018-09-14 2020-03-19 Aerie Pharmaceuticals, Inc. Aryl cyclopropyl-amino-isoquinolinyl amide compounds
CN110711175A (zh) * 2019-11-12 2020-01-21 南京华盖制药有限公司 一种他氟前列素滴眼剂及其制备方法
US20230263727A1 (en) * 2022-01-14 2023-08-24 Somerset Therapeutics, Llc Ophthalmologically suitable low pka buffer-containing pilocarpine compositions and related methods
US20230248699A1 (en) 2022-02-09 2023-08-10 Somerset Therapeutics, Llc Formulations of pilocarpine and brimonidine compounds and related methods

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030018079A1 (en) * 2000-11-13 2003-01-23 Richardson Helene Treatment
US20090092665A1 (en) * 2007-10-08 2009-04-09 Lux Biosciences, Inc. OPHTHALMIC COMPOSITIONS COMPRISING CALCINEURIN INHIBITORS OR mTOR INHIBITORS
US8637054B2 (en) * 2010-06-29 2014-01-28 Laboratoires Thea Polymeric delivery system for a nonviscous prostaglandin-based solution without preservatives

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10021A (en) * 1853-09-13 Screw-eastemtito- for boots and shoes
IL80298A (en) 1986-10-14 1993-01-31 Res & Dev Co Ltd Eye drops
US5631287A (en) 1994-12-22 1997-05-20 Alcon Laboratories, Inc. Storage-stable prostaglandin compositions
US6646001B2 (en) * 1997-12-19 2003-11-11 Alcon Manufacturing, Ltd. Use of non-steroidal anti-inflammatory agents in combination with prostaglandin FP receptor agonists to treat glaucoma and ocular hypertension
HU226588B1 (en) * 1998-04-02 2009-04-28 Novartis Ag Method for stabilizing pharmaceutical compositions by special use an antioxidant
US7074827B2 (en) * 2002-10-24 2006-07-11 Sucampo Ag (Usa) Inc. Method for treating ocular hypertension and glaucoma
FR2918891B1 (fr) 2007-07-20 2009-09-25 Thea Sa Lab Solution ophtalmique a base de prostaglandines sans conservateur
CA2702478C (en) * 2007-10-16 2014-12-09 Sun Pharma Advanced Research Company Limited Ophthalmic composition
EP2127638A1 (en) * 2008-05-30 2009-12-02 Santen Pharmaceutical Co., Ltd Method and composition for treating ocular hypertension and glaucoma

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030018079A1 (en) * 2000-11-13 2003-01-23 Richardson Helene Treatment
US20090092665A1 (en) * 2007-10-08 2009-04-09 Lux Biosciences, Inc. OPHTHALMIC COMPOSITIONS COMPRISING CALCINEURIN INHIBITORS OR mTOR INHIBITORS
US8637054B2 (en) * 2010-06-29 2014-01-28 Laboratoires Thea Polymeric delivery system for a nonviscous prostaglandin-based solution without preservatives

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
Ballal et al., In vitro antimicrobial activity of maleic acid and ethylenediaminetetraacetic acid on endodontic pathogens, Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011 Nov;112(5), printed from http://www.ncbi.nlm.nih.gov/pubmed/21872510, Abstract only,2 pages *
Kalachandra et al.,Lubrication and surface chemical properties of ophthalmic solutions, Ann Ophthalmol. 1985 Nov;17(11), printed from http://www.ncbi.nlm.nih.gov/pubmed/4083661, Abstract only, 1 page *
Reidmiller et al., Antimicrobial properties of the chelating agent EDTA on STrptococcal bovine mastitis isolates, J Food Prot, June 2006, 69(6), printed from http://www.ncbi.nlm.nih.gov/pubmed/16786875, Abstract only, 1 page *
URSAPHARM, The COMOD® system from URSAPHARM, 8/13/2009, printed from http://www.ursapharm.in/en/systems-production/the-comod-system/ with Google date sheet, 3 pages *
Winfield, Pharmaceutical Practice - Ophthalmic Products: Containers for eye drops, Churchhill Livingstone, 2004, 264, 269-270 *

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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US10702471B2 (en) * 2013-10-15 2020-07-07 Pharmathen S.A. Preservative free pharmaceutical compositions for ophthalmic administration
EP3973954A1 (en) * 2013-10-15 2022-03-30 Pharmathen S.A. Preservative free pharmaceutical compositions for ophthalmic administration
US10772830B1 (en) * 2013-10-15 2020-09-15 Pharmathen S.A. Preservative free pharmaceutical compositions for ophthalmic administration
US10350161B2 (en) 2013-10-15 2019-07-16 Pharmathen S.A. Preservative free pharmaceutical compositions for ophthalmic administration
WO2015055301A1 (en) 2013-10-15 2015-04-23 Pharmathen S.A. Preservative free pharmaceutical compositions for ophthalmic administration
GR1008330B (el) * 2013-10-17 2014-10-20 "Φαρματεν Α.Β.Ε.Ε.", Φαρμακευτικο σκευασμα ελευθερο συντηρητικου για οφθαλμικη χορηγηση εχoν βελτιωμενες φυσικες ιδιοτητες και ογκο σταγονας
EP2886130A1 (en) * 2013-12-23 2015-06-24 Rafarm S.A. Ophthalmic pharmaceutical composition and process for the preparation thereof
RU2698456C2 (ru) * 2015-06-09 2019-08-27 Медпроект Фарма-Энтвиклунгс- Унд Фертрибсгезельшафт Мбх Офтальмологический гель биматопроста, который наносится в виде капель
KR101889878B1 (ko) * 2015-06-09 2018-08-20 메드프로젝트 파마엔트비클룽스 운트 페르트리브스게젤샤프트 엠베하 적하 가능한 안과용 비마토프로스트 겔
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AU2016277336B2 (en) * 2015-06-09 2018-12-06 Medproject Pharma-Entwicklungs- Und Vertriebsgesellschaft Mbh Drippable ophthalmic bimatoprost gel
US10314780B2 (en) 2015-06-09 2019-06-11 Medproject Pharma-Entwicklungs-Und Vertriebsgesellschaft Mbh Drippable opthalmic bimatoprost gel
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WO2018033854A1 (en) * 2016-08-15 2018-02-22 Santen Pharmaceutical Co., Ltd. Ophthalmic composition and a method for treating ocular hypertension and glaucoma
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US11787906B2 (en) 2017-03-14 2023-10-17 Polyactiva Pty Ltd Biodegradable drug-polymer conjugate

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