JP5986296B2 - シクロスポリン含有の無刺激性ナノエマルジョン目薬組成物 - Google Patents
シクロスポリン含有の無刺激性ナノエマルジョン目薬組成物 Download PDFInfo
- Publication number
- JP5986296B2 JP5986296B2 JP2015508845A JP2015508845A JP5986296B2 JP 5986296 B2 JP5986296 B2 JP 5986296B2 JP 2015508845 A JP2015508845 A JP 2015508845A JP 2015508845 A JP2015508845 A JP 2015508845A JP 5986296 B2 JP5986296 B2 JP 5986296B2
- Authority
- JP
- Japan
- Prior art keywords
- eye drop
- drop composition
- castor oil
- cyclosporine
- present
- 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.)
- Active
Links
Images
Classifications
-
- 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
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
- A61K38/13—Cyclosporins
-
- 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
- A61K47/32—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
- 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
- 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
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
-
- 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
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
- A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
-
- 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
- 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
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Immunology (AREA)
- Dispersion Chemistry (AREA)
- Ophthalmology & Optometry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- General Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biophysics (AREA)
- Inorganic Chemistry (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Biochemistry (AREA)
Description
上記の第1溶液を上記の第2溶液に混合して、高速攪拌式や高速せん断式機械を使用しなくて単純攪拌させる段階;
上記の可溶化剤としてポリオキシエチレンヒマシ油(Polyethoxylated castor oil)またはポリオキシエチレン硬化ヒマシ油(Polyethoxylated hydrogenated castor oil)が用いられることができるし、上記の可溶化剤にエタノールが追加に含まれることができる。また、上記の漸増剤としてグリセリン及び/またはヒアルロン酸ナトリウムが使用できる。
漸増剤をリン酸塩緩衝液に溶解させて第2溶液を生成させる段階;及び
上記の第1溶液を上記の第2溶液に混合して単純攪拌させる段階を含むことを特徴とする。
下記の表1の1−Aないし1−Jの各組成比率によりシクロスポリンをそれぞれの可溶化剤に混合した(第1液)。pHを7.2で合わせたリン酸塩緩衝液にグリセリン及びポロキサマー188を各組成により混合した後、この溶液に第1液を分散させてエマルジョンを製造した。等張化剤としてNaClを使用してモル浸透圧濃度(osmolarity)を300ミリオスモル(mOsmol)に調整した。
下記の表2のようにPolyethoxylated castor oil及びethanol量を調節して上記の実施例1で組成物1−Aを作る方法と同一に下記の組成物2−Aないし2−Iを製造した。
下記の表3のように漸増剤の種類及び量を調節して、上記の実施例1で組成物1−Aを作る方法と同一に下記の組成物3−Aないし3−Fを製造した。
下記の表4のようにシクロスポリンAの濃度を変化させて組成物4−Aないし4−Eを製造した。
上記の実施例1ないし4で製造したエマルジョンに対してレーザー回折粒度分析機を使用して粒径の平均粒子の大きさを測定してその結果を下記の表6に表わした。この際に、現在販売されているAllergan Inc.のレスタシス点眼液0.05%製剤(Lot番号:69297)をcontrol(対照組成物)1、大韓民国特許第1008189号の実施例6−G製剤をcontrol2で使用した。
これに比べて、組成物1−Cないし1−Fの場合、乳化剤の使用なしではエマルジョンの形成にならず、乳化剤を使用した1−Gないし1−Jの場合、平均粒径が数μmで非常に大きく現れた。
本発明の組成物1−A、1−B、3−A、3−C、及び3−Eに対して時間による粒子の大きさの変化及びpHの変化を常温で試験して、その結果を表7及び表8に表わした。
下記の表7及び表8に表わしたように、本発明の組成物は時間が経つことにより粒子の大きさ及びエマルジョンpHに有意的な変化を表わしていないことがわかった。
点眼液の透明度の評価によって点眼液を目に点滴した時の透明度と視界の曇り程度をin vitro(試験管内)であらかじめ観察するために本発明によって製造された目薬組成物4−Cないし4−E、及びcontrol1(レスタシス)の透明度のテストを行った。
しかし、本発明による4−Cないし4−Eの目薬組成物は初めから透明だけでなく、ずっと透明性が維持されるので、視界くもりのような望ましくない作用を起こさないということがわかる。
被験者を各群当たり4人ずつ3群にして下記の表10のように3×3交差実験を通じて刺激性テストを行った。総3期に掛けて実験を行って、各被験者に本発明による組成物2−C、control1、及びcontrol2をそれぞれ点眼の後、刺激性の程度を表11のように点数で表わした。
本発明による目薬組成物の薬効を評価するためにAlbino rabbitに対して、下記のような実験を実施した。
Claims (6)
- シクロスポリン0.01ないし1重量%;
ポリオキシエチレンヒマシ油(Polyethoxylated castor oil)またはポリオキシエチレン硬化ヒマシ油(Polyethoxylated hydrogenated castor oil)0.5ないし9.79重量%;
リン酸塩緩衝液90ないし99.29重量%;および
エタノール0.1ないし3重量%を含むナノエマルジョン目薬組成物であり、
前記ナノエマルジョンの平均粒径の大きさが50nm以下であり、
上記の組成物は前記シクロスポリンと前記シクロスポリンの可溶化剤である前記ポリオキシエチレンヒマシ油またはポリオキシエチレン硬化ヒマシ油との単純混合物であり、上記成分以外にオイルと乳化剤とを含まないことを特徴とする、ナノエマルジョン目薬組成物。 - 前記シクロスポリンはシクロスポリンAであることを特徴とする請求項1に記載の目薬組成物。
- 前記目薬組成物は漸増剤をさらに含むことを特徴とする請求項1または2に記載の目薬組成物。
- 前記漸増剤はヒアルロン酸またはその塩、キトサン、ヒドロキシプロピルメチルセルロース、ヒドロキシプロピルセルロース、ヒドロキシエチルセルロース、ポリビニルピロリドン、カルボキシメチルセルロース、カルボマー、グリセリン、及びポリエチレンオキシドよりなる群から選択される1種以上であることを特徴とする、請求項3に記載の目薬組成物。
- 前記漸増剤はヒアルロン酸またはその塩であることを特徴とする、請求項4に記載の目薬組成物。
- 前記漸増剤は目薬組成物全体の0.1ないし5重量%含有することを特徴とする、請求項3乃至5いずれか一項に記載の目薬組成物。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR10-2012-0045708 | 2012-04-30 | ||
KR20120045708A KR101211902B1 (ko) | 2012-04-30 | 2012-04-30 | 사이클로스포린 함유 무자극성 나노에멀젼 안약 조성물 |
PCT/KR2013/000509 WO2013165074A1 (ko) | 2012-04-30 | 2013-01-22 | 사이클로스포린 함유 무자극성 나노에멀젼 안약 조성물 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2015514800A JP2015514800A (ja) | 2015-05-21 |
JP5986296B2 true JP5986296B2 (ja) | 2016-09-06 |
Family
ID=47907577
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2015508845A Active JP5986296B2 (ja) | 2012-04-30 | 2013-01-22 | シクロスポリン含有の無刺激性ナノエマルジョン目薬組成物 |
Country Status (10)
Country | Link |
---|---|
US (1) | US9320801B2 (ja) |
EP (1) | EP2845602B1 (ja) |
JP (1) | JP5986296B2 (ja) |
KR (1) | KR101211902B1 (ja) |
CN (1) | CN104302308B (ja) |
AU (1) | AU2013255231B2 (ja) |
ES (1) | ES2651412T3 (ja) |
RU (1) | RU2578415C1 (ja) |
SG (1) | SG11201407089SA (ja) |
WO (1) | WO2013165074A1 (ja) |
Families Citing this family (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ES2948387T3 (es) | 2012-08-24 | 2023-09-11 | Sun Pharmaceutical Ind Ltd | Formulación oftálmica de ácidos grasos polioxílicos o lípidos polioxílicos y tratamiento de afecciones oculares |
KR101587412B1 (ko) * | 2014-10-17 | 2016-01-21 | 주식회사 휴온스 | 사이클로스포린 및 트레할로스를 포함하는 안과용 조성물 |
US10455242B2 (en) * | 2015-03-04 | 2019-10-22 | Qualcomm Incorporated | Signaling output indications in codec-hybrid multi-layer video coding |
KR101587385B1 (ko) | 2015-07-29 | 2016-01-21 | 국제약품공업주식회사 | 사이클로스포린 함유 무자극성의 안약조성물 및 편리한 제조방법 |
FR3041883B1 (fr) * | 2015-10-02 | 2019-03-15 | Chu Clermont-Ferrand | Procede de preparation d'un collyre de ciclosporine a |
AU2017227585C1 (en) | 2016-02-29 | 2022-05-26 | Sun Pharmaceutical Industries Limited | Topical cyclosporine-containing formulations and uses thereof |
RU2620568C1 (ru) * | 2016-04-12 | 2017-05-26 | Государственное бюджетное образовательное учреждение высшего профессионального образования "Санкт-Петербургский государственный педиатрический медицинский университет" Министерства здравоохранения Российской Федерации (ГБОУ ВПО СПбГПМУ Минздрава России) | Препарат для лечения синдрома "сухого глаза" |
US10702578B2 (en) | 2017-08-02 | 2020-07-07 | Shilpa Medicare Limited | Ophthalmic compositions of cyclosporine |
CN109010270B (zh) * | 2018-09-03 | 2021-07-30 | 辅必成(上海)医药科技有限公司 | 一种阳离子材料制备的眼用乳 |
WO2021049825A1 (ko) * | 2019-09-09 | 2021-03-18 | 주식회사태준제약 | 사이클로스포린 및 멘톨 함유 나노 에멀젼 점안 조성물 및 그의 제조 방법 |
CN112957450A (zh) * | 2019-12-20 | 2021-06-15 | 艾棣维欣(苏州)生物制药有限公司 | 一种难溶性药物的水溶液及其制备方法 |
TW202402319A (zh) * | 2022-03-28 | 2024-01-16 | 日商中外製藥股份有限公司 | 含有包含聚氧乙烯構造的油性成分之化合物製劑 |
Family Cites Families (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH0558906A (ja) | 1991-09-06 | 1993-03-09 | Sankyo Co Ltd | シクロスポリン点眼製剤 |
DK0642332T3 (da) | 1992-05-13 | 1997-06-16 | Sandoz Ltd | Ophthalmiske præparater indeholdende cyclosporin |
NZ247516A (en) | 1993-04-28 | 1995-02-24 | Bernard Charles Sherman | Water dispersible pharmaceutical compositions comprising drug dissolved in solvent system comprising at least one alcohol and at least one surfactant |
KR100966245B1 (ko) * | 1997-03-12 | 2010-06-28 | 아보트 러보러터리즈 | 사이클로스포린 투여용 친수성 2원 시스템 |
US6057289A (en) | 1999-04-30 | 2000-05-02 | Pharmasolutions, Inc. | Pharmaceutical composition comprising cyclosporin in association with a carrier in a self-emulsifying drug delivery system |
WO2001028519A1 (de) * | 1999-10-20 | 2001-04-26 | Vesifact Ag | Mikroemulsion-prekonzentrate und mikroemulsionen |
US20040115287A1 (en) * | 2002-12-17 | 2004-06-17 | Lipocine, Inc. | Hydrophobic active agent compositions and methods |
US20050196370A1 (en) * | 2003-03-18 | 2005-09-08 | Zhi-Jian Yu | Stable ophthalmic oil-in-water emulsions with sodium hyaluronate for alleviating dry eye |
CN100478025C (zh) * | 2005-03-25 | 2009-04-15 | 中国科学院上海药物研究所 | 一种环孢菌素a眼用微乳制剂及其制备方法 |
KR100669510B1 (ko) | 2005-08-17 | 2007-01-16 | 보람제약주식회사 | 사이크로스포린을 함유한 나노 에멀젼 농축액 조성물 및 그제조방법 |
US10137083B2 (en) * | 2006-03-07 | 2018-11-27 | SGN Nanopharma Inc | Ophthalmic preparations |
CN101484138A (zh) * | 2006-03-07 | 2009-07-15 | 诺瓦瓦克斯有限公司 | 难溶性药用活性成分的纳米乳液和制备该乳液的方法 |
JP5026824B2 (ja) * | 2006-03-10 | 2012-09-19 | マルホ株式会社 | シクロスポリンを含有する液晶乳化型医薬組成物 |
PL2071917T3 (pl) * | 2006-09-29 | 2013-04-30 | Infa Sa | System opakowaniowy dla kompozycji farmaceutycznych oraz zestaw do podawania dożylnego |
CN101244256A (zh) * | 2007-02-16 | 2008-08-20 | 中国科学院上海药物研究所 | 一种环孢菌素a眼用微/亚微乳原位凝胶制剂及其制备方法 |
MX340897B (es) * | 2007-10-02 | 2016-07-29 | Theranos Inc | Dispositivos modulares de punto de cuidado y usos de los mismos. |
EA019867B1 (ru) * | 2007-10-08 | 2014-06-30 | Фовея Фармасьютикалс | Водные офтальмологические препараты |
US20090130198A1 (en) * | 2007-11-21 | 2009-05-21 | Innopharmax Inc. | Pharmaceutical composition with enhanced bioavailability |
US20110206739A1 (en) | 2008-03-28 | 2011-08-25 | University Of Massachusetts | Compositions and methods for the preparation of nanoemulsions |
KR101008189B1 (ko) | 2010-07-29 | 2011-01-17 | 에스씨바이오팜 주식회사 | 안구건조증 치료용 사이클로스포린 함유 안과용 나노에멀젼 조성물 |
-
2012
- 2012-04-30 KR KR20120045708A patent/KR101211902B1/ko active IP Right Grant
-
2013
- 2013-01-22 ES ES13784924.6T patent/ES2651412T3/es active Active
- 2013-01-22 AU AU2013255231A patent/AU2013255231B2/en active Active
- 2013-01-22 WO PCT/KR2013/000509 patent/WO2013165074A1/ko active Application Filing
- 2013-01-22 US US14/398,012 patent/US9320801B2/en active Active
- 2013-01-22 SG SG11201407089SA patent/SG11201407089SA/en unknown
- 2013-01-22 RU RU2014148138/15A patent/RU2578415C1/ru active
- 2013-01-22 CN CN201380016584.5A patent/CN104302308B/zh active Active
- 2013-01-22 JP JP2015508845A patent/JP5986296B2/ja active Active
- 2013-01-22 EP EP13784924.6A patent/EP2845602B1/en active Active
Also Published As
Publication number | Publication date |
---|---|
EP2845602A4 (en) | 2015-12-30 |
US20150125494A1 (en) | 2015-05-07 |
CN104302308B (zh) | 2018-05-29 |
JP2015514800A (ja) | 2015-05-21 |
CN104302308A (zh) | 2015-01-21 |
AU2013255231B2 (en) | 2015-08-13 |
ES2651412T3 (es) | 2018-01-26 |
EP2845602A1 (en) | 2015-03-11 |
WO2013165074A1 (ko) | 2013-11-07 |
AU2013255231A1 (en) | 2014-10-02 |
EP2845602B1 (en) | 2017-10-11 |
US9320801B2 (en) | 2016-04-26 |
SG11201407089SA (en) | 2014-12-30 |
RU2578415C1 (ru) | 2016-03-27 |
KR101211902B1 (ko) | 2012-12-13 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5986296B2 (ja) | シクロスポリン含有の無刺激性ナノエマルジョン目薬組成物 | |
Tamilvanan et al. | The potential of lipid emulsion for ocular delivery of lipophilic drugs | |
Singh et al. | Therapeutic nanoemulsions in ophthalmic drug administration: Concept in formulations and characterization techniques for ocular drug delivery | |
Hegde et al. | Microemulsion: new insights into the ocular drug delivery | |
EP2978409B1 (en) | Ophthalmic composition, method for preparing the same, and use of the same | |
Haβe et al. | Development and characterization of microemulsions for ocular application | |
CA2578176C (en) | Ophthalmic emulsions containing an immunosuppressive agent | |
AU670443B2 (en) | Oil-in-water emulsions of positively charged particles | |
DE69531179T2 (de) | Nanoemulsion von dem Öl-in-Wasser Typ, gebrauchbar als ein ophthalmischen Vehikel und Verfahren zur seiner Herstellung | |
PT1809238E (pt) | Emulsões oftálmicas contendo um agente imunossupressor | |
CA3032695C (en) | Methods of diagnosing and treating dry eye syndrome and compositions for treating a human eye | |
JPH05186333A (ja) | 眼用組成物 | |
Kassem et al. | Formulation and optimization of cationic nanoemulsions for enhanced ocular delivery of dorzolamide hydrochloride using Box-Behnken design: In vitro and in vivo assessments | |
Kesavan et al. | Positively charged microemulsions of dexamethasone: comparative effects of two cosurfactants on ocular drug delivery and bioavailability | |
Gohil et al. | Optimization of brinzolamide loaded microemulsion using formulation by design approach: characterization and in-vitro evaluation | |
KR101587385B1 (ko) | 사이클로스포린 함유 무자극성의 안약조성물 및 편리한 제조방법 | |
Mehetre et al. | Rationalized approach for formulation and optimization of ebastine microemulsion using design expert for solubility enhancement | |
Vikash et al. | Formulation and evaluation of ocular self-nanoemulsifying drug delivery system of brimonidine tartrate | |
Chaudhary et al. | Role of nanoemulsion as drugs delivery systems in opthalmology: A Comprehensive review | |
Abd-Elaty et al. | Engineering a novel water-in-oil biocompatible microemulsion system for the ocular delivery of dexamethasone sodium phosphate in the treatment of acute uveitis | |
Omran et al. | Carrageenan tethered ion sensitive smart nanogel containing oleophytocubosomes for improved ocular luteolin delivery | |
Srivastava et al. | QbD-driven thymoquinone laden nanoemulsion for glaucoma management: In vitro, ex vivo, and pre-clinical evaluation | |
AU2012200251A1 (en) | Ophthalmic emulsions containing an immunosuppressive agent |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20141028 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150312 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20150915 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20151215 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20160308 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20160707 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20160715 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20160802 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20160804 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5986296 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |