WO2011018800A2 - Nouvelle solution formant un gel in situ pour l’administration de médicaments par voie oculaire - Google Patents

Nouvelle solution formant un gel in situ pour l’administration de médicaments par voie oculaire Download PDF

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Publication number
WO2011018800A2
WO2011018800A2 PCT/IN2010/000536 IN2010000536W WO2011018800A2 WO 2011018800 A2 WO2011018800 A2 WO 2011018800A2 IN 2010000536 W IN2010000536 W IN 2010000536W WO 2011018800 A2 WO2011018800 A2 WO 2011018800A2
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WO
WIPO (PCT)
Prior art keywords
gel forming
situ gel
forming system
range
situ
Prior art date
Application number
PCT/IN2010/000536
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English (en)
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WO2011018800A3 (fr
Inventor
Nandan Mohan Chandavarkar
Kour Chand Jindal
Rajkumar Malayandi
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Fdc Limited
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 Fdc Limited filed Critical Fdc Limited
Publication of WO2011018800A2 publication Critical patent/WO2011018800A2/fr
Publication of WO2011018800A3 publication Critical patent/WO2011018800A3/fr

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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
    • A61K9/0048—Eye, e.g. artificial tears
    • 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
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • 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
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • 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
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • 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
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
    • 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 a novel in-situ gel forming solution for ocular drug delivery, comprising of natural polysaccharide with thixotropic behavior and thermoreversible polymers, using one or more combination of mechanisms such as thermal gelation, corneal mucoadhesion, lysosomal interaction and ionic gelation.
  • the combination of natural polysaccharide with thixotropic behavior and thermoreversible polymers, using the said mechanisms provides in-situ gel formation and leads to prolonged corneal residence time, improved corneal absorption, patient compliance and clinical success.
  • Topical drug delivery is a preferred method for the therapeutic treatment of most of the ocular problems and well-accepted route of administration for the treatment of various eye diseases.
  • a major problem in conventional ophthalmic drug delivery systems is poor ocular bioavailability due to ocular anatomical and physiological constraints, which include the poor permeability of cornea, nasolacrimal drainage and short retention time in the precorneal area.
  • the bioavailability of topically administered drug in the anterior chamber of eye is extremely low due to the protective barrier function of the cornea, its rapid clearance by the tear-fluid drainage, its absorption into the conjunctiva and its washout by aqueous humor from the anterior chamber.
  • Topically applied drugs can reach the intraocular tissues by either the corneal and/or the non-corneal pathways. Under normal conditions, the eye can accommodate only a very small volume of administered drugs without overflowing.
  • Ocular disorders are mainly treated by using drug formulations in the form of eye drops.
  • Eye drops are inefficient means of delivering ophthalmic drugs because of limited bioavailability and these can cause significant side effects due to systemic uptake of the drug, when the drug gets into the gastrointestinal tract through nasolacrimal drainage.
  • the drug contained in the drops is lost due to absorption through the conjunctiva or through the tear drainage.
  • Attempts to improve ocular bioavailability have been focused on overcoming precorneal constraints through improving corneal penetration and prolonging the precorneal retention and reducing the nasolacrimal drainage.
  • EP Patent No. 424043 describes liquid ophthalmic composition comprising at least one active principle and a sulphated polysaccharide or sulphated polysaccharide derivative in aqueous solution which undergoes a liquid-gel phase transition on interaction of the said sulphated polysaccharide or one of its derivatives with the proteins of the lachrymal fluid.
  • US Patent No. 5422116 describes formulation of pH sensitive in-situ gel for ophthalmic application using chitosan as a polymer.
  • the formulated ophthalmic solution consists of chitosen having the pH range in between 3 to 6.2.
  • the acidic pH of these formulations may not be suitable for the drugs which are unstable at acidic aqueous environment.
  • WO 93/00887 demonstrates use of carbomer as an aqueous gel forming agent in ophthalmic preparations.
  • Carbomer are acid insoluble polymers and swell above their pKa value preferably at neutral pH.
  • Carbomer based liquid formulations should be formulated with pH range of 6-7. These formulations are not suitable to load the drugs having physicochemical properties and chemical properties favorable to acidic environment.
  • Xanthan gum is a polysaccharide, which is known to be useful in many ophthalmic compositions as a viscosity enhancing agent.
  • US Patent No. 3700451 discloses the gelable or gelled composition, which comprise a liquid medium, agar and a combination of natural gum gel-forming agents including xanthan gum and locust bean gum.
  • the gelable dispersions are easily gelled by heating to the gel-critical temperature and subsequently cooling them below the setting temperature.
  • the time required for gelation is more than that of precorneal elimination time, and hence this formulation is not suitable for retaining the drug in precorneal area in reproducible manner.
  • US Patent No. 4131677 describes ophthalmic composition containing echothiopate iodide and xanthan gum. Xanthan gum is reported to enhance the treatment effect of echothiopate iodide. However, patent does not describe any xanthan gum-containing compositions as capable of being administered as a liquid and of gelling upon contact with the eyes.
  • composition having a pH sensitive solution of a pharmaceutically acceptable vehicle of xanthan gum, locust bean gum and a pharmaceutically active drug in said liquid vehicle. Moreover, solution containing combination of xanthan gum and locust bean gum does not show sufficient gelling in wide range of physiological pH, and these solutions demonstrate pH dependent liquid gel reversibility.
  • US Patent No. 6174524 discloses ophthalmic drug delivery systems using xanthan gum aqueous dispersion as vehicles, which are administrable as a liquid and which gels upon contact with the eyes.
  • Xanthan gum when used alone in the ophthalmic formulation has the disadvantage that it requires lysosomal interaction to form a gel, which is a slow mechanism and therefore takes longer time to form a gel. By this time the product solution may drain off. Moreover, being shear thinning polymer, the product may not attain sufficiently high viscosity due to shear generated through blinking.
  • ophthalmic solutions that are liquid in the container and can be instilled as eye drops, but form gel on contact with the tear fluid and provide increased contact time with the possibility of improved drug absorption and increased duration of therapeutic effect.
  • sustained and controlled delivery of drugs to the ocular tissues is a main objective in light of major hurdles of optimum drug bioavailability including rapid turnover, lacrimal drainage, reflex blinking and drug dilution by tears.
  • the primary objective of the present invention is to provide a novel in-situ gel forming solution for ocular drug delivery comprising of natural polysaccharide with thixotropic behavior and thermoreversible polymer, and process for preparation thereof.
  • Another objective of the invention is to provide in-situ gel formation by one or more combination of mechanisms such as thermal gelation, corneal mucoadhesion, lysosomal interaction and ionic gelation which provides prolonged corneal residential time, improved corneal absorption, patient compliance and clinical success.
  • Yet another objective of the invention is to provide a novel in-situ gel forming solution having longer duration of action, and hence improved patient compliance and therapeutic response.
  • the present invention provides a novel in-situ gel forming solution for ocular drug delivery, consisting of natural polysaccharide with thixotropic behavior and thermoreversible polymers using one or more combination of mechanisms such as thermal gelation, corneal mucoadhesion, lysosomal interaction and ionic gelation.
  • the combination of natural polysaccharide with thixotropic behavior and thermoreversible polymers utilizing the said mechanisms provides in-situ gel formation in eye and leads to prolonged corneal residence time and improved corneal absorption to achieve patient compliance and clinical success.
  • 'thixotropic behavior' refers to a property exhibited by certain compounds of becoming fluid when stirred or shaken, and returning to the semisolid state upon standing.
  • thermosible polymer' refers to a polymer whose properties or action can be reversed by heating.
  • the present invention relates to a novel in-situ gel forming solution for ocular drug delivery, comprising of natural polysaccharide with thixotropic behavior and thermoreversible polymers, utilizing one or more combinations of mechanisms such as thermal gelation, corneal mucoadhesion, lysosomal interaction and ionic gelation.
  • the combination of natural polysaccharide with thixotropic behavior and thermoreversible polymers, using the said mechanisms provides in-situ gel formation and leads to prolonged corneal residence time, improved corneal absorption, patient compliance and clinic success.
  • the invention provides a novel in-situ gel forming system for ocular drug delivery comprises a combination of natural polysaccharide having thixotropic behavior, thermoreversible polymer and a vehicle along with one or more optional components selected from active pharmaceutical ingredient(s), buffer, preservative with or without stabilizer, pH modifier(s) and tonicity modifiers
  • the present invention demonstrates the application of natural polysaccharide with thixotropic behavior as polymer of pseudoplasticity, which offers the shear thinning property to the system.
  • the natural polysaccharide is selected from the group consisting of but not limited to xanthan gum, locust bean gum, guar gum and tamarind seed polysaccharide
  • concentration of natural polysaccharide with thixotropic behavior in the present formulation is ranging from 0.1% to 3% w/v preferably 0.1 % to 0.9 % w/v.
  • thermoreversible polymers in the present invention are selected from the group consisting of but not limited to gelatin, poly(vinyl chloride), poly(acrylonitrile), polystyrene (atactic), poly(vinyl alcohol), agarose, carrageenans, benzohydroxamic acid, cellulose derivatives, polaxomer and polysaccharides.
  • thermoreversible polymers as rheological modifiers.
  • the role of thermoreversible polymers/ Theological modifiers is to retain the high viscosity of the polymers in presence of shear stress at physiological conditions.
  • the commonly used rheological modifiers are natural and semi-synthetic cellulose derivatives such as methylcellulose, hydroxypropyl methylcellulose, hydroxyethyl cellulose, carboxymethyl cellulose and its salts and polaxomer; preferably rheological modifiers are methylcellulose and polaxomer. These polymers also act as a lubricant surviving the purpose of lubrication.
  • thermoreversible polymers The role of thermoreversible polymers is to maintain the rigidity of gel or to retain the gel strength against shear stress and dilution, which is achieved through thermo-gelation properties of thermoreversible polymers at physiological pH.
  • the optimal concentration of methylcellulose present in the formulation is 0.1 - 2.5%, or the concentration of polaxomer used is in the range of 2.0% to 20% w/v.
  • the natural polysaccharide and thermoreversible polymers used in the present invention may also act as a lubricant that could be useful for the treatment of Ophthamological disorder.
  • the active ingredient is useful for diagnosis or treatment of various eye disorders, whereas the formulation without active ingredient is used to treat the dry eyes.
  • the active ingredient used optionally in the present invention is alone or in the combination, and is selected from the group consisting of ophthalmically acceptable agents including pharmaceutical agents, diagnostic agents, vitamins, nutrients and lubricants.
  • the ophthalmically acceptable agents include without limitation thereto, from the categories of local anesthetics, antimicrobial agents, antifungals, anti-inflammatory, antiglucoma, steroids, ⁇ -blocker, anti-cataract, antihistamics, immunosuppressant, cycloplegics, mydriatics, vasodilators, vasoconstrictors and lubricants.
  • the active ingredient used in the formulation is ranging from 0.00001% to 10% w/v.
  • the compatible buffering system selected in the present invention is compatible with polymer as well as other excipients such as tonicity modifiers and preservatives.
  • the buffering systems used in the formulation include but not limited to phosphate, citrate, citrophosphate and TRJS preferably buffering systems is phosphate and TRIS buffer, ranging from 0.01 to 20% w/v.
  • the suitable preservatives used in the system include but not limited to benzalkonium chloride, sodium perborate, thiomersal, chlorbutanol, sorbic acid, methylparaben, propylparaben, phenylethyl alcohol, disodium edentate, stabilized oxychloro complex and polyquard.
  • the most commonly used preservatives are sodium perborate, stabilized oxychloro complex and benzalkonium chloride, ranging from 0.0001% to 1% w/v.
  • the preservative used in the present invention is with or without stabilizer.
  • the stabilizer such as phosphogenic acid and its derivatives is used in the range of 0.06% to 0.0006% w/v.
  • the osmolarity of the present invention is 200-500 Osm/s
  • the viscosity of the present invention is 2-500cps
  • pH of the present invention varies depending on the API used in the formulation.
  • the suitable tonicity modifiers used in the system include but not limited to sodium chloride, potassium chloride, mannitol, dextrose, sucrose, glycerin and polyethylene glycol.
  • the ophthalmic gel forming solution prepared by using any one of the systems consisting of natural polysaccharide with thixotropic behavior and thermoreversible polymers that provide in-situ gel formation, by one or more combinations of mechanism such as thermal gelation, corneal mucoadhesion, lysosomal interaction and ionic gelation, provides prolonged corneal residence time, improved corneal absorption, patient compliance and clinical success.
  • the invention provides in-situ gel compositions comprising of:
  • the inactive excipients are dissolved with or without active ingredient(s) in part quantity of aqueous vehicle.
  • Natural polysaccharide with thixotropic behavior and thermoreversible polymer is dispersed in aqueous vehicle such as water, buffer, polyols or combination thereof, and subjected to sterilization by suitable means such as thermal sterilization and ionization sterilization depending upon the stability of active and inactive ingredients.
  • aqueous vehicle such as water, buffer, polyols or combination thereof
  • suitable means such as thermal sterilization and ionization sterilization depending upon the stability of active and inactive ingredients.
  • the sterilized polymeric dispersion is mixed aseptically with the aqueous vehicle, and pH adjusted, if required. Both solutions and dispersions are mixed aseptically and filtered through sterile terylene cloth, and filled in suitable container.

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

Abstract

L’invention concerne un nouveau système formant un gel in situ pour l’administration de médicaments par voie oculaire, qui comprend une combinaison d’un polysaccharide naturel ayant un comportement thixotropique, d’un polymère thermoréversible et d’un véhicule avec un ou plusieurs composants optionnels choisis parmi un ou plusieurs ingrédients pharmaceutiques actifs, un tampon, un conservateur avec ou sans stabilisateur, un ou plusieurs modificateurs du pH et des modificateurs de la tonicité.
PCT/IN2010/000536 2009-08-13 2010-08-13 Nouvelle solution formant un gel in situ pour l’administration de médicaments par voie oculaire WO2011018800A2 (fr)

Applications Claiming Priority (2)

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IN1874MU2009 2009-08-13
IN1874/MUM/2009 2009-08-13

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WO2011018800A2 true WO2011018800A2 (fr) 2011-02-17
WO2011018800A3 WO2011018800A3 (fr) 2011-07-21

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Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013012692A1 (fr) * 2011-07-19 2013-01-24 Bausch & Lomb Incorporated Compositions pharmaceutiques comprenant des polysaccharides à base de plante et utilisations de celles-ci
WO2013153550A3 (fr) * 2012-04-08 2013-12-27 Theracoat Ltd Préparations d'hydrogel thermoréversible pour leur utilisation dans le traitement de troubles de l'urothélium
CN103550819A (zh) * 2013-10-31 2014-02-05 天津市中科健新材料技术有限公司 一种吸收性制品
CN103977008A (zh) * 2013-02-07 2014-08-13 沈阳兴齐眼药股份有限公司 含有多佐胺和噻吗洛尔的眼用凝胶剂及其制备方法
US9757330B2 (en) 2013-10-18 2017-09-12 Industrial Technology Research Institute Recipe for in-situ gel, and implant, drug delivery system formed thereby
US9795569B2 (en) 2013-03-15 2017-10-24 Allergan Pharmaceuticals International Limited Pharmaceutical soft gelatin capsule dosage form with modified guar gum
CN107847604A (zh) * 2015-10-25 2018-03-27 艾威医药有限公司 眼用原位凝胶处方
CN110200904A (zh) * 2019-05-27 2019-09-06 上海昊海生物科技股份有限公司 一种降眼压缓释滴眼组合物及其制备方法
JP2020512971A (ja) * 2017-09-02 2020-04-30 アイビュー セラピューティクス、インコーポレイテッド インサイチュゲル形成医薬組成物および副鼻腔疾患のためのその使用

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US3700451A (en) 1970-04-06 1972-10-24 Itek Corp Gelable and gelled compositions
US4131677A (en) 1975-05-02 1978-12-26 Merck & Co., Inc. Anti-inflammatory oxazolo [5,4-b]pyridines
US4136173A (en) 1977-01-31 1979-01-23 American Home Products Corp. Mixed xanthan gum and locust beam gum therapeutic compositions
EP0424043A1 (fr) 1989-10-17 1991-04-24 LABORATOIRES MERCK, SHARP & DOHME-CHIBRET Composition ophthalmique aqueuse liquide à transition de phase liquide-gel
WO1993000887A1 (fr) 1991-07-10 1993-01-21 Laboratoire Europhta S.A. Compositions ophtalmiques a base d'acide polyacrylique
US5422116A (en) 1994-02-18 1995-06-06 Ciba-Geigy Corporation Liquid ophthalmic sustained release delivery system
US6174524B1 (en) 1999-03-26 2001-01-16 Alcon Laboratories, Inc. Gelling ophthalmic compositions containing xanthan gum

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US5300295A (en) * 1990-05-01 1994-04-05 Mediventures, Inc. Ophthalmic drug delivery with thermoreversible polyoxyalkylene gels adjustable for pH
CA2839928C (fr) * 2003-06-13 2016-10-04 Alcon, Inc. Compositions ophtalmologiques contenant une association synergique de deux polymeres
JP4966854B2 (ja) * 2005-07-11 2012-07-04 千寿製薬株式会社 キサンタンガムおよびテルペノイドを含有する点眼剤
WO2009001899A1 (fr) * 2007-06-26 2008-12-31 Wakamoto Pharmaceutical Co., Ltd. Composition aqueuse

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Publication number Priority date Publication date Assignee Title
US3700451A (en) 1970-04-06 1972-10-24 Itek Corp Gelable and gelled compositions
US4131677A (en) 1975-05-02 1978-12-26 Merck & Co., Inc. Anti-inflammatory oxazolo [5,4-b]pyridines
US4136173A (en) 1977-01-31 1979-01-23 American Home Products Corp. Mixed xanthan gum and locust beam gum therapeutic compositions
EP0424043A1 (fr) 1989-10-17 1991-04-24 LABORATOIRES MERCK, SHARP & DOHME-CHIBRET Composition ophthalmique aqueuse liquide à transition de phase liquide-gel
WO1993000887A1 (fr) 1991-07-10 1993-01-21 Laboratoire Europhta S.A. Compositions ophtalmiques a base d'acide polyacrylique
US5422116A (en) 1994-02-18 1995-06-06 Ciba-Geigy Corporation Liquid ophthalmic sustained release delivery system
US6174524B1 (en) 1999-03-26 2001-01-16 Alcon Laboratories, Inc. Gelling ophthalmic compositions containing xanthan gum

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Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013012692A1 (fr) * 2011-07-19 2013-01-24 Bausch & Lomb Incorporated Compositions pharmaceutiques comprenant des polysaccharides à base de plante et utilisations de celles-ci
US8859525B2 (en) 2011-07-19 2014-10-14 Bausch & Lomb Incorporated Pharmaceutical compositions comprising mushroom-based polysaccharides and uses thereof
TWI475999B (zh) * 2011-07-19 2015-03-11 Bausch & Lomb 包括多醣之醫藥組合物及其用途
AU2012284291B2 (en) * 2011-07-19 2015-04-09 Bausch & Lomb Incorporated Pharmaceutical compositions comprising plant-based polysaccharides and uses thereof
WO2013153550A3 (fr) * 2012-04-08 2013-12-27 Theracoat Ltd Préparations d'hydrogel thermoréversible pour leur utilisation dans le traitement de troubles de l'urothélium
RU2635466C2 (ru) * 2012-04-08 2017-11-13 Теракоат Лтд Препараты термообратимого гидрогеля для применения при лечении нарушений уротелия
CN103977008A (zh) * 2013-02-07 2014-08-13 沈阳兴齐眼药股份有限公司 含有多佐胺和噻吗洛尔的眼用凝胶剂及其制备方法
US9795569B2 (en) 2013-03-15 2017-10-24 Allergan Pharmaceuticals International Limited Pharmaceutical soft gelatin capsule dosage form with modified guar gum
US9757330B2 (en) 2013-10-18 2017-09-12 Industrial Technology Research Institute Recipe for in-situ gel, and implant, drug delivery system formed thereby
CN103550819A (zh) * 2013-10-31 2014-02-05 天津市中科健新材料技术有限公司 一种吸收性制品
CN107847604A (zh) * 2015-10-25 2018-03-27 艾威医药有限公司 眼用原位凝胶处方
EP3365022A4 (fr) * 2015-10-25 2019-07-24 IVIEW Therapeutics, Inc. Formulations pharmaceutiques qui forment un gel in situ
CN107847604B (zh) * 2015-10-25 2020-11-10 艾威药业(珠海)有限公司 眼用原位凝胶处方
AU2016344349B2 (en) * 2015-10-25 2022-05-19 Iview Therapeutics, Inc. Pharmaceutical formulations that form gel in situ
JP2020512971A (ja) * 2017-09-02 2020-04-30 アイビュー セラピューティクス、インコーポレイテッド インサイチュゲル形成医薬組成物および副鼻腔疾患のためのその使用
CN110200904A (zh) * 2019-05-27 2019-09-06 上海昊海生物科技股份有限公司 一种降眼压缓释滴眼组合物及其制备方法
CN110200904B (zh) * 2019-05-27 2021-07-23 上海昊海生物科技股份有限公司 一种降眼压缓释滴眼组合物及其制备方法

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