WO2013047567A1 - フラビンアデニンジヌクレオチドまたはその塩を有効成分として含有する角膜上皮細胞死の抑制剤 - Google Patents
フラビンアデニンジヌクレオチドまたはその塩を有効成分として含有する角膜上皮細胞死の抑制剤 Download PDFInfo
- Publication number
- WO2013047567A1 WO2013047567A1 PCT/JP2012/074662 JP2012074662W WO2013047567A1 WO 2013047567 A1 WO2013047567 A1 WO 2013047567A1 JP 2012074662 W JP2012074662 W JP 2012074662W WO 2013047567 A1 WO2013047567 A1 WO 2013047567A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- corneal epithelial
- cell death
- epithelial cell
- salt
- adenine dinucleotide
- Prior art date
Links
- JJJQETLJZPASEC-HGAZGAJRSA-N Cc(cc1N2CC([C@@H]([C@@H](COP(O)(OP(O)(OCC(O[C@H](C3O)[n]4c5ncnc(N)c5nc4)=C3O)=O)=O)O)O)O)c(C)cc1N=C(C(N1)=O)C2=NC1=O Chemical compound Cc(cc1N2CC([C@@H]([C@@H](COP(O)(OP(O)(OCC(O[C@H](C3O)[n]4c5ncnc(N)c5nc4)=C3O)=O)=O)O)O)O)c(C)cc1N=C(C(N1)=O)C2=NC1=O JJJQETLJZPASEC-HGAZGAJRSA-N 0.000 description 1
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
- A61K9/0012—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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7084—Compounds having two nucleosides or nucleotides, e.g. nicotinamide-adenine dinucleotide, flavine-adenine dinucleotide
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
- C07H19/20—Purine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
- C07H19/207—Purine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids the phosphoric or polyphosphoric acids being esterified by a further hydroxylic compound, e.g. flavine adenine dinucleotide or nicotinamide-adenine dinucleotide
Definitions
- the present invention is an inhibitor of corneal epithelial cell death containing a flavin adenine dinucleotide (FAD) or a salt thereof (hereinafter collectively referred to as “FAD etc.”) as an active ingredient,
- the present invention relates to an inhibitor, wherein the corneal epithelial cell death is induced by ultraviolet irradiation.
- the present invention also relates to a method for suppressing corneal epithelial cell death comprising administering to a patient a pharmaceutically effective amount of FAD or the like, wherein the corneal epithelial cell death is induced by ultraviolet irradiation.
- Non-patent Document 2 discloses that UV-B induces apoptosis (cell death) of corneal epithelial cells.
- Document 1 discloses that UV-B leads to corneal epithelial damage, corneal edema, turbidity, and the like.
- FAD is a coenzyme-type vitamin B 2 that is directly involved in cellular redox, and is known to promote corneal enzyme respiratory metabolism. Furthermore, the Furabitan ® ophthalmic solution 0.05% attachment (Non-Patent Document 3), the disodium salt of FAD is useful for keratitis which is implicated vitamin B 2 deficiency or metabolic disorders It is described that there is.
- the present inventors conducted extensive research to search for drugs that suppress corneal epithelial cell death induced by ultraviolet irradiation. As a result, flavin adenine dinucleotide disodium salt (hereinafter also referred to as “the present compound”) is prominent.
- the present invention has been completed by finding that it has an excellent cell death inhibitory effect.
- the present invention relates to an inhibitor of corneal epithelial cell death containing flavin adenine dinucleotide or a salt thereof (FAD or the like) as an active ingredient, wherein the corneal epithelial cell death is induced by ultraviolet irradiation ( Hereinafter also referred to as “this agent”.
- Another aspect of the present invention is an inhibitor of corneal epithelial cell death containing FAD or the like as an active ingredient, wherein the corneal epithelial cell death is induced by ultraviolet B wave irradiation.
- the present agent has a concentration of FAD and the like of 0.01 to 1% (w / v).
- another aspect of the present invention is the present agent having a concentration of FAD or the like of 0.05% (w / v).
- the other aspect of this invention is this agent whose dosage form is ophthalmic administration. Moreover, the other aspect of this invention is this agent whose dosage form is an eye drop.
- the present invention relates to a method for inhibiting corneal epithelial cell death comprising administering to a patient a pharmaceutically effective amount of FAD or the like, wherein the corneal epithelial cell death is induced by ultraviolet irradiation (hereinafter referred to as “ This method is also provided).
- Another aspect of the present invention is a method for inhibiting corneal epithelial cell death comprising administering a pharmaceutically effective amount of FAD or the like to a patient, wherein the corneal epithelial cell death is induced by ultraviolet B-wave irradiation. Is the method.
- Another aspect of the present invention is the present method, wherein the concentration of FAD or the like is 0.01 to 1% (w / v).
- Another embodiment of the present invention is the present method, wherein the concentration of FAD or the like is 0.05% (w / v).
- the present invention relates to the use of FAD or the like for use in the suppression of corneal epithelial cell death, wherein the corneal epithelial cell death is induced by ultraviolet irradiation (hereinafter also referred to as “first use”). Also provide.
- Another aspect of the present invention is the use of FAD or the like for use in the suppression of corneal epithelial cell death, wherein the corneal epithelial cell death is induced by ultraviolet B-wave irradiation. .
- Another aspect of the present invention is the first use of the present invention in which the concentration of FAD or the like is 0.01 to 1% (w / v).
- Another aspect of the present invention is the first book use in which the concentration of FAD or the like is 0.05% (w / v).
- the other aspect of this invention is 1st this use whose dosage form is eye drop administration. Moreover, the other aspect of this invention is 1st this use whose dosage form is eyedrops.
- the present invention relates to the use of FAD or the like for producing an inhibitor of corneal epithelial cell death, wherein the corneal epithelial cell death is induced by ultraviolet irradiation (hereinafter referred to as “second use”). Also provided).
- Another aspect of the present invention also provides use of FAD or the like for producing an inhibitor of corneal epithelial cell death, wherein the corneal epithelial cell death is induced by ultraviolet B wave irradiation.
- Another aspect of the present invention is the second use of the present invention in which the concentration of FAD or the like is 0.01 to 1% (w / v).
- Another aspect of the present invention is the second book use in which the concentration of FAD or the like is 0.05% (w / v).
- the other aspect of this invention is 2nd this use whose dosage form is eye drop administration.
- Another aspect of the present invention is the second use, wherein the dosage form is an eye drop.
- the present invention also provides a method for suppressing corneal epithelial cell death comprising administering a pharmaceutically effective amount of FAD or the like to a patient, wherein the corneal epithelial cell death is induced by ultraviolet irradiation. .
- the present invention also provides use of FAD or the like for use in suppressing corneal epithelial cell death, wherein the corneal epithelial cell death is induced by ultraviolet irradiation.
- the present invention also provides use of FAD or the like for producing an inhibitor of corneal epithelial cell death, wherein the corneal epithelial cell death is induced by ultraviolet irradiation.
- FIG. 2 is a graph showing the survival rate when corneal epithelial cells are treated with the present compound before UV-B irradiation.
- Flavin adenine dinucleotide is a compound represented by the following formula (1).
- the salt of flavin adenine dinucleotide is not particularly limited as long as it is a pharmaceutically acceptable salt.
- Salt with inorganic acid such as hydrochloric acid, hydrobromic acid, hydroiodic acid, nitric acid, sulfuric acid, phosphoric acid, acetic acid , Fumaric acid, maleic acid, succinic acid, citric acid, tartaric acid, adipic acid, gluconic acid, glucoheptic acid, glucuronic acid, terephthalic acid, methanesulfonic acid, lactic acid, hippuric acid, 1,2-ethanedisulfonic acid, isethionic acid, Organics such as lactobionic acid, oleic acid, pamoic acid, polygalacturonic acid, stearic acid, tannic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, lauryl sulfate
- the salt of flavin adenine dinucleotide is preferably a sodium salt, particularly preferably a flavin adenine dinucleotide disodium salt represented by the following formula (2).
- flavin adenine dinucleotide or a salt thereof may take the form of a hydrate or a solvate.
- the crystalline polymorph Forms and crystal polymorph groups are also within the scope of the present invention.
- the crystal polymorphism group means that the crystal form changes depending on the conditions and state of production, crystallization and storage of these crystals (including the formulated state in this state). Means the individual crystal forms at each stage and the whole process.
- Flavin adenine dinucleotide or a salt thereof can be produced according to a usual method in the field of synthetic organic chemistry. Moreover, what is marketed by Sigma etc. can also be used.
- “suppression of corneal epithelial cell death induced by ultraviolet irradiation” not only means suppressing the decrease in the number of viable corneal epithelial cells induced by ultraviolet irradiation, but also It also means preventing or treating corneal epithelial damage, corneal edema, turbidity, etc. accompanied by a decrease in the number of cells (ie, corneal epithelial cell death).
- UV light means three kinds of ultraviolet A wave (wavelength: 320 nm to less than 400 nm), ultraviolet B wave (wavelength: 290 nm to less than 320 nm), and ultraviolet C wave (wavelength: 200 nm to less than 290 nm). To do. As explained in the background section, it is known that “ultraviolet B wave (UV-B)” is clinically problematic as an inducer of corneal epithelial cell death.
- this agent is administered locally to the eye.
- administration form of this agent include ophthalmic administration (including ophthalmic ointment), subconjunctival administration, intraconjunctival sac administration, subtenon sac administration and the like, and ophthalmic administration is particularly preferable.
- the dosage form of this agent is not particularly limited as long as it can be used for topical ophthalmic administration, and examples thereof include eye drops, eye ointments, injections, patches, gels, insertion agents, and the like. Is preferred. In addition, these can be prepared using the normal technique currently used widely in the said field
- DDS drug delivery system
- the injection is selected as necessary from an isotonic agent such as sodium chloride; a buffering agent such as sodium phosphate; a surfactant such as polyoxyethylene sorbitan monooleate; and a thickener such as methylcellulose.
- an isotonic agent such as sodium chloride
- a buffering agent such as sodium phosphate
- a surfactant such as polyoxyethylene sorbitan monooleate
- a thickener such as methylcellulose.
- the intercalating agent is prepared by pulverizing and mixing a biodegradable polymer such as hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxyvinyl polymer, polyacrylic acid and the like together with the compound, and compressing the powder. If necessary, excipients, binders, stabilizers, pH adjusters and the like can be used.
- a biodegradable polymer such as hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxyvinyl polymer, polyacrylic acid and the like.
- the preparation for intraocular implant can be prepared using a biodegradable polymer, for example, a biodegradable polymer such as polylactic acid, polyglycolic acid, lactic acid / glycolic acid copolymer, and hydroxypropylcellulose.
- a biodegradable polymer such as polylactic acid, polyglycolic acid, lactic acid / glycolic acid copolymer, and hydroxypropylcellulose.
- the dose of this drug can be appropriately changed according to the dosage form, the severity of the symptoms of the patient to be administered, age, weight, doctor's judgment, etc. For example, when an eye drop is selected, 0.005 To 5% (w / v), preferably 0.01 to 1% (w / v), more preferably 0.02 to 0.5% (w / v), still more preferably 0.05% (w / v) Instill 1 to 2 drops of this drug containing FAD at the concentration of v).
- the concentration of FAD or the like described above can be the concentration of flavin adenine dinucleotide (free form) or the concentration of a flavin adenine dinucleotide salt.
- this drug can be appropriately changed according to the dosage form, the severity of the symptoms of the patient to be administered, age, weight, doctor's judgment, etc.For example, when an eye drop is selected as the dosage form, It can be administered to the eye topically by dividing it 1 to 10 times a day, preferably 2 to 8 times a day, more preferably 3 to 6 times a day.
- a method for suppressing corneal epithelial cell death comprising administering a pharmaceutically effective amount of FAD or the like to a patient, wherein the corneal epithelial cell death is induced by ultraviolet irradiation ( This method), use of FAD or the like for use in the suppression of corneal epithelial cell death, wherein the corneal epithelial cell death is induced by ultraviolet irradiation (first use), and corneal epithelial cell death
- FAD or the like for producing an inhibitor, wherein the corneal epithelial cell death is induced by ultraviolet irradiation (second main use).
- the definitions of the terms in these inventions are also as described above, and the preferred embodiments are the same as described above.
- SV40 immortalized human corneal epithelial cells (HCE-T: RIKEN, BioResource Center, Cell No .: RCB2280) were seeded in a 96-well plate (1 ⁇ 10 4 cells / well), and 10% FBS-containing DMEM / F- Cultured for 12 days in 12 media. The next day, the DMEM / F-12 medium containing 10% FBS was added to 0.0125% (w / v) or 0.05% (w / v) flavin adenine dinucleotide disodium salt PBS, 0.5% (w / v). v) Chondroitin sulfate sodium-containing PBS or PBS, and then cultured at 37 ° C.
- % CS group or“ base group ”.
- the corneal epithelial cells were irradiated with UV-B (80 mJ / cm 2 ) for about 1 minute.
- the medium of each group was replaced with DMEM / F-12 medium containing 10% FBS again, and cultured at 37 ° C. for 24 hours.
- CellTiter96 registered trademark
- AQueous One Solution Cell Proliferation Assay manufactured by Promega, catalog number: The number of viable cells was measured using G3580
- the survival rate was calculated according to the following formula 1.
- the flavin adenine dinucleotide disodium salt and chondroitin sulfate sodium salt used in this test were purchased from Kyowa Hakko Bio Co., Ltd. and Maruha Nichiro Foods, Inc., respectively.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Ophthalmology & Optometry (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
また、本発明の他の態様は、剤形が点眼剤である、本剤である。
また、本発明の他の態様は、剤形が点眼剤である、本方法である。
また、本発明の他の態様は、剤形が点眼剤である、第1の本使用である。
また、本発明の他の態様は、剤形が点眼剤である、第2の本使用である。
紫外線(UV-B)照射前に角膜上皮細胞をFADで処置した場合に、紫外線照射による生細胞数の低下が抑制されるか否かを評価した。
SV40不死化ヒト角膜上皮細胞(HCE-T:理化学研究所、バイオリソースセンター、Cell No.:RCB2280)を96ウェルプレートに播種(1×104個/ウェル)し、10%FBS含有DMEM/F-12培地で1日培養した。翌日、前記10%FBS含有DMEM/F-12培地を0.0125%(w/v)もしくは0.05%(w/v)フラビンアデニンジヌクレオチド二ナトリウム塩含有PBS、0.5%(w/v)コンドロイチン硫酸エステルナトリウム含有PBS、またはPBSに交換した後、37℃で60分間培養した(以下、それぞれ、「0.0125% FAD群」、「0.05% FAD群」、「0.5% CS群」または「基剤群」ともいう)。その後、角膜上皮細胞にUV-B照射(80mJ/cm2)を約1分間行った。各群の培地を再度10%FBS含有DMEM/F-12培地に交換してから、37℃で24時間培養した後、CellTiter96(登録商標) AQueous One Solution Cell Proliferation Assay(Promega社製、カタログ番号:G3580)を用いて生細胞数を測定し、下記式1に従って、生存率を算出した。なお、本試験で用いたフラビンアデニンジヌクレオチド二ナトリウム塩およびコンドロイチン硫酸エステルナトリウムは、それぞれ協和発酵バイオ株式会社および株式会社マルハニチロ食品から購入した。
生存率(%)=(各群の生細胞数/UV-B非照射群の生細胞数)×100
(結果)
試験結果を図1に示す。なお、図1中、値は平均値±標準誤差を示す(N=3)。
図1から明らかなように、UV-B照射前に角膜上皮細胞を本化合物で前処置しておいた場合、濃度依存的な角膜上皮細胞死の抑制作用が確認された。一方で、紫外線を浴びた角膜表面を保護することが知られているコンドロイチン硫酸エステルナトリウム(バイシン(登録商標)UV添付文書参照)で処置した群では、同作用は確認されなかった。すなわち、FADは紫外線照射によって誘発される角膜上皮細胞死を抑制することが示された。
製剤例を挙げて本発明の薬剤をさらに具体的に説明するが、本発明はこれらの製剤例にのみ限定されるものではない。
点眼剤(FAD濃度:0.05%(w/v)) 100ml中
フラビンアデニンジヌクレオチド二ナトリウム塩 0.05g
塩化ナトリウム 0.9g
リン酸水素ナトリウム水和物 適量
滅菌精製水 適量
滅菌精製水にフラビンアデニンジヌクレオチド二ナトリウム塩およびそれ以外の上記成分を加え、これらを十分に混合して点眼剤を調製する。フラビンアデニンジヌクレオチド二ナトリウム塩の添加量を変えることにより、FAD濃度が0.005%(w/v)、0.01%(w/v)または0.1%(w/v)である点眼剤を調製できる。
眼軟膏(FAD濃度:0.05%(w/w)) 100g中
フラビンアデニンジヌクレオチド二ナトリウム塩 0.05g
流動パラフィン 10mg
白色ワセリン 適量
均一に溶融した白色ワセリンおよび流動パラフィンにフラビンアデニンジヌクレオチド二ナトリウム塩を加え、これらを十分に混合して後に徐々に冷却することで眼軟膏を調製する。フラビンアデニンジヌクレオチド二ナトリウム塩の添加量を変えることにより、FAD濃度が0.005%(w/w)、0.01%(w/w)または0.1%(w/w)である眼軟膏を調製できる。
Claims (24)
- フラビンアデニンジヌクレオチドまたはその塩を有効成分として含有する角膜上皮細胞死の抑制剤であって、該角膜上皮細胞死が紫外線照射によって誘発される、抑制剤。
- 紫外線が紫外線B波である、請求項1に記載の抑制剤。
- フラビンアデニンジヌクレオチドまたはその塩の濃度が0.01~1%(w/v)である、請求項1または2に記載の抑制剤。
- フラビンアデニンジヌクレオチドまたはその塩の濃度が0.05%(w/v)である、請求項1または2に記載の抑制剤。
- 投与形態が点眼投与である、請求項1または2に記載の抑制剤。
- 剤形が点眼剤である、請求項5に記載の抑制剤。
- 薬学的に有効な量のフラビンアデニンジヌクレオチドまたはその塩を患者に投与することを含む角膜上皮細胞死の抑制方法であって、該角膜上皮細胞死が紫外線照射によって誘発される、方法。
- 紫外線が紫外線B波である、請求項7に記載の方法。
- フラビンアデニンジヌクレオチドまたはその塩の濃度が0.01~1%(w/v)である、請求項7または8に記載の方法。
- フラビンアデニンジヌクレオチドまたはその塩の濃度が0.05%(w/v)である、請求項7または8に記載の方法。
- 投与形態が点眼投与である、請求項7または8に記載の方法。
- 剤形が点眼剤である、請求項11に記載の方法。
- 角膜上皮細胞死の抑制に用いるためのフラビンアデニンジヌクレオチドまたはその塩の使用であって、該角膜上皮細胞死が紫外線照射によって誘発される、使用。
- 紫外線が紫外線B波である、請求項13に記載の使用。
- フラビンアデニンジヌクレオチドまたはその塩の濃度が0.01~1%(w/v)である、請求項13または14に記載の使用。
- フラビンアデニンジヌクレオチドまたはその塩の濃度が0.05%(w/v)である、請求項13または14に記載の使用。
- 投与形態が点眼投与である、請求項13または14に記載の使用。
- 剤形が点眼剤である、請求項17に記載の使用。
- 角膜上皮細胞死の抑制剤を製造するためのフラビンアデニンジヌクレオチドまたはその塩の使用であって、該角膜上皮細胞死が紫外線照射によって誘発される、使用。
- 紫外線が紫外線B波である、請求項19に記載の使用。
- フラビンアデニンジヌクレオチドまたはその塩の濃度が0.01~1%(w/v)である、請求項19または20に記載の使用。
- フラビンアデニンジヌクレオチドまたはその塩の濃度が0.05%(w/v)である、請求項19または20に記載の使用。
- 投与形態が点眼投与である、請求項19または20に記載の使用。
- 剤形が点眼剤である、請求項23に記載の使用。
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201280046826.0A CN103826642B (zh) | 2011-09-27 | 2012-09-26 | 含有黄素腺嘌呤二核苷酸或其盐作为有效成分的角膜上皮细胞死亡的抑制剂 |
SG11201400947XA SG11201400947XA (en) | 2011-09-27 | 2012-09-26 | Corneal epithelial cell death inhibitor containing flavin adenine dinucleotide or salt thereof as active ingredient |
MYPI2014000895A MY185239A (en) | 2011-09-27 | 2012-09-26 | Corneal epithelial cell death inhibitor containing flavin adenine dinucleotide or salt thereof as active ingredient |
KR1020147009783A KR20140082699A (ko) | 2011-09-27 | 2012-09-26 | 플라빈 아데닌 디뉴클레오티드 또는 그의 염을 유효 성분으로서 함유하는 각막상피세포사의 억제제 |
IN3350DEN2014 IN2014DN03350A (ja) | 2011-09-27 | 2014-04-25 |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2011210875 | 2011-09-27 | ||
JP2011-210875 | 2011-09-27 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2013047567A1 true WO2013047567A1 (ja) | 2013-04-04 |
Family
ID=47995597
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2012/074662 WO2013047567A1 (ja) | 2011-09-27 | 2012-09-26 | フラビンアデニンジヌクレオチドまたはその塩を有効成分として含有する角膜上皮細胞死の抑制剤 |
Country Status (8)
Country | Link |
---|---|
JP (1) | JP5969872B2 (ja) |
KR (1) | KR20140082699A (ja) |
CN (1) | CN103826642B (ja) |
IN (1) | IN2014DN03350A (ja) |
MY (1) | MY185239A (ja) |
SG (2) | SG10201602401PA (ja) |
TW (1) | TWI561238B (ja) |
WO (1) | WO2013047567A1 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2016046734A3 (en) * | 2014-09-22 | 2016-06-30 | University Of The Western Cape | Compounds and compositions for treatment of tuberculosis |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2004002358A (ja) * | 2002-04-01 | 2004-01-08 | Rohto Pharmaceut Co Ltd | 眼科用組成物 |
JP2004203836A (ja) * | 2002-12-26 | 2004-07-22 | Rohto Pharmaceut Co Ltd | 眼科用局所適用製剤 |
JP2005239622A (ja) * | 2004-02-26 | 2005-09-08 | Rohto Pharmaceut Co Ltd | 角膜障害治療剤 |
JP2006117656A (ja) * | 2004-09-27 | 2006-05-11 | Rohto Pharmaceut Co Ltd | ヒアルロン酸又はその塩を含有する粘膜適用組成物 |
JP2006282586A (ja) * | 2005-03-31 | 2006-10-19 | Kobayashi Pharmaceut Co Ltd | 眼科用組成物 |
JP2011137845A (ja) * | 2009-12-02 | 2011-07-14 | Rohto Pharmaceutical Co Ltd | シリコーンハイドロゲルコンタクトレンズ用眼科組成物 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2773076B1 (fr) * | 1997-12-29 | 2000-05-19 | Chauvin Lab Sa | Utilisation de la flavine-adenine-dinucleotide pour la preparation de compositions ophtalmiques utiles pour le traitement de l'oeil sec |
CN101301305A (zh) * | 2008-05-14 | 2008-11-12 | 北京润德康医药技术有限公司 | 一种黄素腺嘌呤二核苷酸二钠冻干粉针制剂及其制备方法 |
EP2735303A1 (en) * | 2012-11-23 | 2014-05-28 | Pilosciences | Hair growth compositions and methods |
-
2012
- 2012-09-26 MY MYPI2014000895A patent/MY185239A/en unknown
- 2012-09-26 TW TW101135280A patent/TWI561238B/zh not_active IP Right Cessation
- 2012-09-26 KR KR1020147009783A patent/KR20140082699A/ko not_active Application Discontinuation
- 2012-09-26 WO PCT/JP2012/074662 patent/WO2013047567A1/ja active Application Filing
- 2012-09-26 SG SG10201602401PA patent/SG10201602401PA/en unknown
- 2012-09-26 JP JP2012212575A patent/JP5969872B2/ja active Active
- 2012-09-26 CN CN201280046826.0A patent/CN103826642B/zh not_active Expired - Fee Related
- 2012-09-26 SG SG11201400947XA patent/SG11201400947XA/en unknown
-
2014
- 2014-04-25 IN IN3350DEN2014 patent/IN2014DN03350A/en unknown
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2004002358A (ja) * | 2002-04-01 | 2004-01-08 | Rohto Pharmaceut Co Ltd | 眼科用組成物 |
JP2004203836A (ja) * | 2002-12-26 | 2004-07-22 | Rohto Pharmaceut Co Ltd | 眼科用局所適用製剤 |
JP2005239622A (ja) * | 2004-02-26 | 2005-09-08 | Rohto Pharmaceut Co Ltd | 角膜障害治療剤 |
JP2006117656A (ja) * | 2004-09-27 | 2006-05-11 | Rohto Pharmaceut Co Ltd | ヒアルロン酸又はその塩を含有する粘膜適用組成物 |
JP2006282586A (ja) * | 2005-03-31 | 2006-10-19 | Kobayashi Pharmaceut Co Ltd | 眼科用組成物 |
JP2011137845A (ja) * | 2009-12-02 | 2011-07-14 | Rohto Pharmaceutical Co Ltd | シリコーンハイドロゲルコンタクトレンズ用眼科組成物 |
Non-Patent Citations (2)
Title |
---|
ASUKA SAKAMOTO ET AL.: "Effect of Flavin Adenine Dinucleotide on Ultraviolet B Induced Damage in Cultured Human Corneal Epithelial Cells", ABSTRACTS OF 132ND ANNUAL MEETING OF PHARMACEUTICAL SOCIETY OF JAPAN, vol. 3, 5 March 2012 (2012-03-05), pages 180 * |
M. NAKAMURA ET AL., FOLIA OPHTHALMOGICA JAPONICA, vol. 47, no. 9, 1996, pages 1082 - 1085 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2016046734A3 (en) * | 2014-09-22 | 2016-06-30 | University Of The Western Cape | Compounds and compositions for treatment of tuberculosis |
Also Published As
Publication number | Publication date |
---|---|
SG10201602401PA (en) | 2016-04-28 |
JP2013082696A (ja) | 2013-05-09 |
SG11201400947XA (en) | 2014-07-30 |
TW201318628A (zh) | 2013-05-16 |
MY185239A (en) | 2021-04-30 |
CN103826642B (zh) | 2016-02-17 |
TWI561238B (en) | 2016-12-11 |
JP5969872B2 (ja) | 2016-08-17 |
CN103826642A (zh) | 2014-05-28 |
IN2014DN03350A (ja) | 2015-06-05 |
KR20140082699A (ko) | 2014-07-02 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
TW201216971A (en) | Therapeutic agent for dry eye characterized by the combination of P2Y2 receptor agonist and hyaluronic acid or salts thereof | |
WO2010141834A1 (en) | Ophthalmic formulations of fluticasone and methods of use | |
CA2755679A1 (en) | Ophthalmic formulations of cetirizine and methods of use | |
NZ519425A (en) | Solutions containing epinastin | |
US9713597B2 (en) | Stable aqueous formulation of (E)-4-carboxystyryl-4-chlorobenzyl sulfone | |
WO2016072440A1 (ja) | 眼科用水性組成物 | |
JP5981783B2 (ja) | ヒアルロン酸またはその塩およびプロピレングリコールを含有する点眼液 | |
JP5969872B2 (ja) | フラビンアデニンジヌクレオチドまたはその塩を有効成分として含有する角膜上皮細胞死の抑制剤 | |
JP2022520410A (ja) | 4-(7-ヒドロキシ-2-イソプロピル-4-オキソ-4h-キナゾリン-3-イル)-ベンゾニトリルの結晶形態及びその製剤 | |
JP4779382B2 (ja) | 点眼剤用組成物 | |
JP6063191B2 (ja) | ヒアルロン酸およびフラビンアデニンジヌクレオチドを組み合わせたことを特徴とする角膜上皮細胞死の抑制剤 | |
WO2010137681A1 (ja) | トラニラストを含有する網膜疾患の予防または治療剤、網膜疾患の予防または治療方法、トラニラストまたはその医薬的に許容される塩、ならびにその使用 | |
JP2011225605A (ja) | 点眼剤 | |
KR20150090045A (ko) | 피나플록사신 현탁 조성물 | |
ES2377342T3 (es) | Remedio para enfermedades corneales | |
WO2010010939A1 (ja) | 加齢黄斑変性の予防又は治療剤 | |
TW201605451A (zh) | 老年性黃斑部病變之預防或治療劑 | |
JP2017218384A (ja) | 網膜疾患の予防または治療のための医薬組成物 | |
JP2023536938A (ja) | 4-(7-ヒドロキシ-2-イソプロピル-4-オキソ-4h-キナゾリン-3-イル)-ベンゾニトリルの結晶形態及びその製剤 | |
TW201625255A (zh) | 後眼部疾病之預防或治療劑 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
WWE | Wipo information: entry into national phase |
Ref document number: 201280046826.0 Country of ref document: CN |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 12836892 Country of ref document: EP Kind code of ref document: A1 |
|
WWE | Wipo information: entry into national phase |
Ref document number: 12014500660 Country of ref document: PH |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
ENP | Entry into the national phase |
Ref document number: 20147009783 Country of ref document: KR Kind code of ref document: A |
|
122 | Ep: pct application non-entry in european phase |
Ref document number: 12836892 Country of ref document: EP Kind code of ref document: A1 |