WO2016208742A1 - Injection - Google Patents

Injection Download PDF

Info

Publication number
WO2016208742A1
WO2016208742A1 PCT/JP2016/068896 JP2016068896W WO2016208742A1 WO 2016208742 A1 WO2016208742 A1 WO 2016208742A1 JP 2016068896 W JP2016068896 W JP 2016068896W WO 2016208742 A1 WO2016208742 A1 WO 2016208742A1
Authority
WO
WIPO (PCT)
Prior art keywords
injection
dimethyl sulfoxide
water
solvent
gellan gum
Prior art date
Application number
PCT/JP2016/068896
Other languages
English (en)
Japanese (ja)
Inventor
達也 宮崎
高明 岡部
賢治 眞崎
和人 山田
Original Assignee
参天製薬株式会社
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 参天製薬株式会社 filed Critical 参天製薬株式会社
Publication of WO2016208742A1 publication Critical patent/WO2016208742A1/fr

Links

Images

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
    • A61K9/08—Solutions
    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
    • 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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
    • 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
    • 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
    • A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
    • 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

Definitions

  • the present invention relates to an injection, an injection preparation manufacturing method, a filtration sterilization method, and a depot formation method.
  • Patent Document 1 discloses a preparation for intraocular administration for sustained release of a sulfonylbenzimidazole derivative as a drug.
  • Injections need to be sterilized during the manufacturing process to remove bacteria and the like.
  • sterilization of injections has generally been performed by heating.
  • the heating step when the heating step is included, there is a problem that the production efficiency is remarkably lowered, and there is a problem that a component that undergoes modification, decomposition, or the like by heating cannot be used.
  • the liquid composition to be an injection can be sterilized by filtration using a filter or the like instead of heating.
  • a filter or the like instead of heating.
  • the present invention has been made in view of the above circumstances, and is a novel injection that is excellent in sustained release of a poorly water-soluble drug and suitable for filtration sterilization, a method for producing the injection, and sterilizing a liquid composition by filtration. It is an object to provide a method and a deposition method.
  • the present inventors have found that an injection can be obtained by containing gellan gum and a solvent that is a mixed solvent of dimethyl sulfoxide or dimethyl sulfoxide and water in addition to a poorly water-soluble drug, and completed the present invention. It came to do.
  • An injection containing a poorly water-soluble drug, gellan gum and a solvent is an injection which is a mixed solvent of dimethyl sulfoxide or a dimethyl sulfoxide, and water.
  • the poorly water-soluble drug is 2-[[[2-[(hydroxyacetyl) amino] -4-pyridinyl] methyl] thio] -N- [4- (trifluoromethoxy) phenyl] -3-pyridinecarboxamide.
  • the content of the poorly water-soluble drug is 0.01 to 50% (w / v) and the gellan gum content is 0.01 to 3% (w).
  • (4-1) The content of the poorly water-soluble drug is 0.01 to 50% (w / v) with respect to the total volume of the injection, any one of (1) to (3) Injections.
  • (4-2) The injection according to any one of (1) to (3), wherein the gellan gum content is 0.01 to 3% (w / v) with respect to the total volume of the injection.
  • Agent. (4-3) The injection according to any one of (1) to (3), wherein the content of the solvent is 47 to 99.98% (w / v) with respect to the total volume of the injection.
  • (8-1) The injection according to any one of (1) to (8), which is used for prevention and / or treatment of eye diseases.
  • (8-2) The injection according to any one of (1) to (8-1) for use as a prophylactic and / or therapeutic agent for eye diseases.
  • (8-3) The injection according to any one of (1) to (8-2), for topical administration in the eye.
  • (8-4) The injection according to any one of (1) to (8-3) for posterior ocular administration.
  • (8-5) The injection according to any one of (1) to (8-4), which is used for prevention and / or treatment of posterior eye diseases.
  • (8-6) The injection according to any one of (1) to (8-5), for sustained drug release.
  • a method of filter sterilizing a liquid composition containing a poorly water-soluble drug and gellan gum A method comprising adding dimethyl sulfoxide or a mixed solvent of dimethyl sulfoxide and water to the liquid composition.
  • a method for forming a depot comprising contacting a liquid composition containing a poorly water-soluble drug, gellan gum and a solvent with water, phosphate buffer, tears, anterior aqueous humor or vitreous humor, The deposition method, wherein the solvent is dimethyl sulfoxide or a mixed solvent of dimethyl sulfoxide and water.
  • a novel injection excellent in sustained release of a poorly water-soluble drug and suitable for filter sterilization a method for producing the injection, a method for filter sterilizing a liquid composition, and a depot formation method. be able to.
  • the injection of the present invention contains a poorly water-soluble drug (hereinafter sometimes simply referred to as “drug”), gellan gum and a solvent.
  • the solvent is dimethyl sulfoxide or a mixed solvent of dimethyl sulfoxide and water.
  • gellan gum forms a depot well at the site of injection and this depot has the effect of slow release of the drug.
  • the solvent promotes dissolution of poorly water-soluble drugs and gellan gum to give a liquid composition.
  • Such a liquid composition can be sterilized by filtration. Instead of the conventional sterilization by heating, filtration sterilization becomes possible, and the production efficiency of the injection can be remarkably improved.
  • the poorly water-soluble drug may be appropriately selected according to the drug efficacy required for the injection.
  • a preferable poorly water-soluble drug for example, 2-[[[2-[(hydroxyacetyl) amino] -4-pyridinyl] methyl] thio ] -N- [4- (trifluoromethoxy) phenyl] -3-pyridinecarboxamide or a salt thereof, steroids such as triamcinolone and fluocinolone acetonide. Only one of these three drugs may be used, or at least two may be used in combination.
  • the salt of the drug is not particularly limited as long as it is a pharmaceutically acceptable salt.
  • the salt includes a salt with an inorganic acid, a salt with an organic acid, a quaternary ammonium salt, a salt with a halogen ion, a salt with an alkali metal. And salts with alkaline earth metals, metal salts, salts with organic amines, and the like.
  • the content of the drug relative to the total volume of the injection is preferably 0.0001% (w / v) or more, more preferably 0.05% (w / V) or more, 0.1% (w / v) or more, 0.3% (w / v) or more, 0.5% (w / v) or more, 1% (w / v) or more, 2% ( w / v) or more and usually 50% (w / v) or less, more preferably 40% (w / v) or less, 30% (w / v) or less, 25% ( w / v) or less, 15% (w / v) or less, more preferably 2 to 15% (w / v).
  • the content of the drug relative to the total volume of the injection is, for example, that the drug is 2-[[[2-[(hydroxyacetyl) amino] -4-pyridinyl] methyl] thio] -N- [4- (trifluoromethoxy ) Phenyl] -3-pyridinecarboxamide or a salt thereof, a steroid such as triamcinolone, fluocinolone acetonide, it is preferably 0.01% (w / v) or more, more preferably 0.05% ( w / v) or more, 0.1% (w / v) or more, 0.3% (w / v) or more, 0.5% (w / v) or more, 1% (w / v) or more, 2% (W / v) or more, preferably 50% (w / v) or less, more preferably 40% (w / v) or less, 30% (w / v) or less, 25% (w / V) or less,
  • the gellan gum in the present invention may be one or more of ion-responsive deacylated gellan gum and heat-responsive native gellan gum.
  • Deacylated gellan gum is preferred because it does not require temperature adjustment of the injection, for example, adjustment to a high temperature before administration and solification.
  • the content of gellan gum relative to the total volume of the injection is 0.01% (w / v) or more, 0.03% (w / v) or more, or 0.05% (from the viewpoint of sufficiently exhibiting the above-described action) w / v) or more, more preferably 0.1% (w / v) or more, 0.2% (w / v) or more, 0.3% (w / v) or more, 0.4 % (W / v) or more.
  • the gellan gum content is preferably 3% (w / v) or less, more preferably 3.00% (w / v) or less, 2% (w / v) from the viewpoint of adjusting the viscosity of the injection. v) or less, 1% (w / v) or less.
  • the solvent is dimethyl sulfoxide or a mixed solvent of dimethyl sulfoxide and water.
  • the water is preferably distilled water for injection.
  • a solvent preferably has a volume ratio of dimethyl sulfoxide represented by “dimethyl sulfoxide / water” of 100/0 to 80/20, more preferably 97/3 to 83/17, still more preferably. Is 95/5 to 85/15, more preferably 93/7 to 87/13. When the ratio is such, the solubility of the poorly water-soluble drug and gellan gum can be increased, and a clear liquid composition is easily obtained.
  • the content of the solvent with respect to the total volume of the injection is dependent on the content of the poorly water-soluble drug and gellan gum, but from the viewpoint of promoting dissolution of these components, 47% (w / v) or more and 50% (w / v ) Or more, preferably 60% (w / v) or more, 70% (w / v) or more, for example, 75% (w / v) or more, 80% (w / v) or more, 85% (w / v) v) or more, 90% (w / v) or more may be sufficient.
  • the content of the solvent may be a content that occupies the injection except for the poorly water-soluble drug, gellan gum, and the additives described later contained as necessary.
  • It is preferably 0.98% (w / v) or less, more preferably 99.9% (w / v) or less, 99.5% (w / v) or less, 98% (w / v) or less. For example, it may be 97% (w / v) or less.
  • the injection according to the present invention is preferably a clear liquid composition. Such a clear injection may be in a state that is visually clear.
  • the injection according to the present invention is preferably a dissolution type injection. In such a soluble injection, it is considered that components of an injection containing a poorly water-soluble drug and gellan gum are sufficiently dissolved in the above solvent, and preferably completely dissolved.
  • the injection according to the present invention preferably has a viscosity of 250 mPa ⁇ s or less, more preferably 200 mPa ⁇ s or less.
  • the injection according to the present invention may contain additives such as an osmotic pressure adjusting agent and a buffering agent in addition to the above components.
  • the additive normally used for an injection can be used. Since the poorly water-soluble drug is sufficiently dissolved in the injection according to the present invention, for example, it is not necessary to contain a surfactant, and it is preferable not to contain a surfactant.
  • the injection according to the present invention can form a depot, and preferably exhibits a sustained release property by forming a depot.
  • the conditions under which the depot is formed in the present invention may be contact with water, phosphate buffer, body fluid (tear fluid, anterior aqueous humor, vitreous humor, etc.) or simulated body fluid.
  • Formulation and administration according to various conditions The method should be adopted.
  • an injection that forms a depot by contact with body fluid may be injected into the body or vitreous.
  • it can also administer to various test solutions, such as a simulated body fluid and a phosphate buffer solution. Thereby, a depot is formed at each administration site, and the drug is released gradually.
  • a method for forming a depot comprising contacting a liquid composition comprising a poorly water-soluble drug, gellan gum and a solvent with water, phosphate buffer, tears, anterior aqueous humor or vitreous humor, the solvent comprising dimethyl sulfoxide
  • a deposition method which is a mixed solvent of dimethyl sulfoxide and water is also one aspect of the present invention.
  • the injection according to the present invention can be used, for example, as an ophthalmic injection.
  • an ophthalmic injection for example, when it is administered into the vitreous, a depot is formed in the vicinity of the administration site, so that the drug can be effectively and continuously supplied to the affected area (for example, the retina choroid).
  • the injection of the present invention can be suitably used for treatment / prevention of posterior eye diseases.
  • Posterior eye diseases include inflammation caused by various causes, viral and bacterial infections, angiogenesis of the retina choroid, diseases caused by increased vascular permeability, neoplastic diseases of the retina, choroidal hereditary diseases, glaucoma
  • the injection of the present invention may be used
  • the injection of the present invention can be produced by a suitable method.
  • gellan gum is added to the above solvent to prepare a base.
  • a liquid composition is prepared by adding a drug to this base and dissolving it uniformly.
  • Such a liquid composition can be obtained as a liquid, and preferably has the above-mentioned viscosity, so that it can be sterilized by filtration.
  • the filtration sterilization method is not particularly limited as long as it is a method suitable for the preparation of an injection, and specifically, a sterilization method by a filtration method in the 16th revision Japanese Pharmacopoeia is preferable.
  • the filter for sterilization can be used,
  • the filter for sterilization used by the sterilization method by the filtration method in the 16th revision Japanese Pharmacopoeia is preferable.
  • Such a sterilizing filter is not particularly limited, but may be a filter having a pore size of 0.45 ⁇ m or less, and preferred pore sizes are 0.45 ⁇ m or less, 0.30 ⁇ m or less, or 0.22 ⁇ m or less.
  • the filter for sterilization include resins such as polyvinylidene fluoride (PVDF), ceramics (chamberbell type), diatomaceous earth (Berkefeld type), porous semi-melted glass, and membrane filters.
  • a method of sterilizing a liquid composition containing a poorly water-soluble drug and gellan gum comprising adding dimethyl sulfoxide or a mixed solvent of dimethyl sulfoxide and water to the liquid composition is also a method of the present invention.
  • the method for incorporating these solvents into the liquid composition is not particularly limited, but as described above, it is preferable to blend gellan gum and a poorly water-soluble drug in the solvent.
  • a method for producing an injection comprising sterilizing a liquid composition containing a poorly water-soluble drug, gellan gum and a solvent, wherein the solvent is dimethyl sulfoxide or a mixed solvent of dimethyl sulfoxide and water Is also one aspect of the present invention.

Landscapes

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

Abstract

L'invention vise à proposer une nouvelle injection qui présente d'excellentes propriétés de libération prolongée d'un médicament. L'injection comprend un médicament difficilement soluble dans l'eau, de la gomme gellane et un solvant, le solvant étant du sulfoxyde de diméthyle ou un mélange de solvants constitué de sulfoxyde de diméthyle et d'eau.
PCT/JP2016/068896 2015-06-25 2016-06-24 Injection WO2016208742A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2015-127600 2015-06-25
JP2015127600 2015-06-25

Publications (1)

Publication Number Publication Date
WO2016208742A1 true WO2016208742A1 (fr) 2016-12-29

Family

ID=57585212

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2016/068896 WO2016208742A1 (fr) 2015-06-25 2016-06-24 Injection

Country Status (3)

Country Link
JP (1) JP2017008047A (fr)
TW (1) TW201705989A (fr)
WO (1) WO2016208742A1 (fr)

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH054951A (ja) * 1990-07-18 1993-01-14 Eisai Co Ltd １，４−ジヒドロナフトキノン誘導体およびその製造方法
JP2004196787A (ja) * 2002-12-04 2004-07-15 Santen Pharmaceut Co Ltd 結膜下デポによるドラッグデリバリーシステム
JP2004267918A (ja) * 2003-03-07 2004-09-30 Hamamatsu Photonics Kk 微粒子、その製造方法及び製造装置、並びに注射剤及びその製造方法
JP2013512262A (ja) * 2009-12-03 2013-04-11 ジエンス ヘンルイ メデイシンカンパニー リミテッド イリノテカン又はその塩酸塩のリポソーム及びその製造方法
JP2013103899A (ja) * 2011-11-11 2013-05-30 Fuji Chem Ind Co Ltd 難溶性薬物の新規な固体分散体
JP2013521245A (ja) * 2010-03-01 2013-06-10 ラボラトリオス・サルバト・ソシエダッド・アノニマ 耳の炎症の治療を目的とするフルオシノロンアセトニドの透明な水性溶液
WO2014095576A1 (fr) * 2012-12-18 2014-06-26 Jens Frauenfeld Particules salipro
JP2015083565A (ja) * 2013-09-20 2015-04-30 参天製薬株式会社 ポリエチレングリコール含有組成物

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH054951A (ja) * 1990-07-18 1993-01-14 Eisai Co Ltd １，４−ジヒドロナフトキノン誘導体およびその製造方法
JP2004196787A (ja) * 2002-12-04 2004-07-15 Santen Pharmaceut Co Ltd 結膜下デポによるドラッグデリバリーシステム
JP2004267918A (ja) * 2003-03-07 2004-09-30 Hamamatsu Photonics Kk 微粒子、その製造方法及び製造装置、並びに注射剤及びその製造方法
JP2013512262A (ja) * 2009-12-03 2013-04-11 ジエンス ヘンルイ メデイシンカンパニー リミテッド イリノテカン又はその塩酸塩のリポソーム及びその製造方法
JP2013521245A (ja) * 2010-03-01 2013-06-10 ラボラトリオス・サルバト・ソシエダッド・アノニマ 耳の炎症の治療を目的とするフルオシノロンアセトニドの透明な水性溶液
JP2013103899A (ja) * 2011-11-11 2013-05-30 Fuji Chem Ind Co Ltd 難溶性薬物の新規な固体分散体
WO2014095576A1 (fr) * 2012-12-18 2014-06-26 Jens Frauenfeld Particules salipro
JP2015083565A (ja) * 2013-09-20 2015-04-30 参天製薬株式会社 ポリエチレングリコール含有組成物

Also Published As

Publication number Publication date
TW201705989A (zh) 2017-02-16
JP2017008047A (ja) 2017-01-12

Similar Documents

Publication Publication Date Title
JP5592321B2 (ja) 眼の後部の処置のための組成物および方法
CN110664757B (zh) 纳米晶滴眼剂、其制备方法及其应用
EP3685828B1 (fr) Composition pharmaceutique ophtalmique, trousse ophtalmique et application pharmaceutique associée
US20110117189A1 (en) Ophthalmic compositions for treating pathologies of the posterior segment of the eye
JP2007535552A5 (fr)
RU2747803C2 (ru) Водная суспензия, содержащая наночастицы глюкокортикостероида
JP7072517B2 (ja) 局所用シクロスポリン含有製剤およびその使用
JP6423263B2 (ja) 注射剤およびデポ形成方法
CN102085203B (zh) 左氧氟沙星和醋酸泼尼松龙的眼用制剂及其制备方法
KR102638866B1 (ko) 사이클로스포린 및 멘톨 함유 나노 에멀젼 점안 조성물 및 그의 제조 방법
JP6931257B2 (ja) レバミピドを含有する新規ドライアイ治療用点眼組成物及びその可溶化及び安定化方法
CN102946855A (zh) 含有妥布霉素和地塞米松的局部用眼科混悬剂
CN111249442B (zh) 一种脂质纳米囊滴眼剂及其制备方法
WO2016208742A1 (fr) Injection
US5811417A (en) Process for producing a sterile prednisolone gel
DK3229780T3 (en) Ophthalmic composition for use in the treatment of dry eye syndrome
JP2023503081A (ja) 眼疾患の予防または治療用点眼組成物
JP2006257080A (ja) ステロイド化合物の副作用軽減または回避方法
CN111358751B (zh) 眼用药物组合物、眼用药盒及其医药用途
CN111358750B (zh) 一种眼用药物组合物及其医药用途
JP2019534269A5 (fr)
WO2002078713A1 (fr) Medicaments contre les affections retiniennes et choroidiennes contenant des steroides comme principe actif
JP3504656B2 (ja) 水性医薬組成物
Sarmento et al. Can (Natural) deep eutectic systems increase the efficacy of ocular therapeutics?
JP2022545082A (ja) ジフルプレドナートを含むインサイチュゲル形成性眼科用製剤

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 16814511

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 16814511

Country of ref document: EP

Kind code of ref document: A1