AU2017348597A1 - Ophthalmic Solution Comprising Epinastine - Google Patents
Ophthalmic Solution Comprising Epinastine Download PDFInfo
- Publication number
- AU2017348597A1 AU2017348597A1 AU2017348597A AU2017348597A AU2017348597A1 AU 2017348597 A1 AU2017348597 A1 AU 2017348597A1 AU 2017348597 A AU2017348597 A AU 2017348597A AU 2017348597 A AU2017348597 A AU 2017348597A AU 2017348597 A1 AU2017348597 A1 AU 2017348597A1
- Authority
- AU
- Australia
- Prior art keywords
- ophthalmic solution
- salt
- epinastine
- acid
- ophthalmic
- 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.)
- Abandoned
Links
- 239000002997 ophthalmic solution Substances 0.000 title claims description 77
- 229940054534 ophthalmic solution Drugs 0.000 title claims description 75
- WHWZLSFABNNENI-UHFFFAOYSA-N epinastine Chemical compound C1C2=CC=CC=C2C2CN=C(N)N2C2=CC=CC=C21 WHWZLSFABNNENI-UHFFFAOYSA-N 0.000 title claims description 54
- 229960003449 epinastine Drugs 0.000 title claims description 40
- 150000003839 salts Chemical class 0.000 claims abstract description 62
- 239000004615 ingredient Substances 0.000 claims abstract description 30
- 239000003755 preservative agent Substances 0.000 claims description 80
- 230000002335 preservative effect Effects 0.000 claims description 50
- 239000012929 tonicity agent Substances 0.000 claims description 15
- 229960002548 epinastine hydrochloride Drugs 0.000 claims description 14
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 12
- 239000000243 solution Substances 0.000 claims description 11
- 239000006172 buffering agent Substances 0.000 claims description 10
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 6
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims description 6
- 239000004327 boric acid Substances 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- 239000003002 pH adjusting agent Substances 0.000 claims description 5
- 239000004480 active ingredient Substances 0.000 claims description 4
- 239000000654 additive Substances 0.000 claims description 4
- 230000000996 additive effect Effects 0.000 claims description 3
- 229910021538 borax Inorganic materials 0.000 claims description 3
- 239000004328 sodium tetraborate Substances 0.000 claims description 3
- 235000010339 sodium tetraborate Nutrition 0.000 claims description 3
- 229960001716 benzalkonium Drugs 0.000 claims 1
- CYDRXTMLKJDRQH-UHFFFAOYSA-N benzododecinium Chemical compound CCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 CYDRXTMLKJDRQH-UHFFFAOYSA-N 0.000 claims 1
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- 239000000203 mixture Substances 0.000 description 25
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
- 244000005700 microbiome Species 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
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- 208000002205 allergic conjunctivitis Diseases 0.000 description 3
- 208000024998 atopic conjunctivitis Diseases 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 229960003260 chlorhexidine Drugs 0.000 description 3
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- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 229960001950 benzethonium chloride Drugs 0.000 description 1
- UREZNYTWGJKWBI-UHFFFAOYSA-M benzethonium chloride Chemical compound [Cl-].C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 UREZNYTWGJKWBI-UHFFFAOYSA-M 0.000 description 1
- KHSLHYAUZSPBIU-UHFFFAOYSA-M benzododecinium bromide Chemical compound [Br-].CCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 KHSLHYAUZSPBIU-UHFFFAOYSA-M 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 229940095731 candida albicans Drugs 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 229960001777 castor oil Drugs 0.000 description 1
- 229960002152 chlorhexidine acetate Drugs 0.000 description 1
- 229960003333 chlorhexidine gluconate Drugs 0.000 description 1
- YZIYKJHYYHPJIB-UUPCJSQJSA-N chlorhexidine gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O.C1=CC(Cl)=CC=C1NC(=N)NC(=N)NCCCCCCNC(=N)NC(=N)NC1=CC=C(Cl)C=C1 YZIYKJHYYHPJIB-UUPCJSQJSA-N 0.000 description 1
- 229960004504 chlorhexidine hydrochloride Drugs 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 208000021921 corneal disease Diseases 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002526 disodium citrate Substances 0.000 description 1
- 235000019262 disodium citrate Nutrition 0.000 description 1
- CEYULKASIQJZGP-UHFFFAOYSA-L disodium;2-(carboxymethyl)-2-hydroxybutanedioate Chemical compound [Na+].[Na+].[O-]C(=O)CC(O)(C(=O)O)CC([O-])=O CEYULKASIQJZGP-UHFFFAOYSA-L 0.000 description 1
- LVXHNCUCBXIIPE-UHFFFAOYSA-L disodium;hydrogen phosphate;hydrate Chemical compound O.[Na+].[Na+].OP([O-])([O-])=O LVXHNCUCBXIIPE-UHFFFAOYSA-L 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
- 229940043264 dodecyl sulfate Drugs 0.000 description 1
- AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 229940074391 gallic acid Drugs 0.000 description 1
- 235000004515 gallic acid Nutrition 0.000 description 1
- LRBQNJMCXXYXIU-QWKBTXIPSA-N gallotannic acid Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@H]2[C@@H]([C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-QWKBTXIPSA-N 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 229940045996 isethionic acid Drugs 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 229940099563 lactobionic acid Drugs 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 229960002969 oleic acid Drugs 0.000 description 1
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000010318 polygalacturonic acid Substances 0.000 description 1
- AVTYONGGKAJVTE-OLXYHTOASA-L potassium L-tartrate Chemical compound [K+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O AVTYONGGKAJVTE-OLXYHTOASA-L 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 239000004302 potassium sorbate Substances 0.000 description 1
- 235000010241 potassium sorbate Nutrition 0.000 description 1
- 229940069338 potassium sorbate Drugs 0.000 description 1
- 229940111695 potassium tartrate Drugs 0.000 description 1
- WSHYKIAQCMIPTB-UHFFFAOYSA-M potassium;2-oxo-3-(3-oxo-1-phenylbutyl)chromen-4-olate Chemical compound [K+].[O-]C=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 WSHYKIAQCMIPTB-UHFFFAOYSA-M 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- MCSINKKTEDDPNK-UHFFFAOYSA-N propyl propionate Chemical compound CCCOC(=O)CC MCSINKKTEDDPNK-UHFFFAOYSA-N 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- HELHAJAZNSDZJO-OLXYHTOASA-L sodium L-tartrate Chemical compound [Na+].[Na+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O HELHAJAZNSDZJO-OLXYHTOASA-L 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 235000011083 sodium citrates Nutrition 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 235000011008 sodium phosphates Nutrition 0.000 description 1
- 239000001476 sodium potassium tartrate Substances 0.000 description 1
- 235000011006 sodium potassium tartrate Nutrition 0.000 description 1
- LROWVYNUWKVTCU-STWYSWDKSA-M sodium sorbate Chemical compound [Na+].C\C=C\C=C\C([O-])=O LROWVYNUWKVTCU-STWYSWDKSA-M 0.000 description 1
- 235000019250 sodium sorbate Nutrition 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 239000001433 sodium tartrate Substances 0.000 description 1
- 229960002167 sodium tartrate Drugs 0.000 description 1
- 235000011004 sodium tartrates Nutrition 0.000 description 1
- HLWRUJAIJJEZDL-UHFFFAOYSA-M sodium;2-[2-[bis(carboxymethyl)amino]ethyl-(carboxymethyl)amino]acetate Chemical compound [Na+].OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC([O-])=O HLWRUJAIJJEZDL-UHFFFAOYSA-M 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000015523 tannic acid Nutrition 0.000 description 1
- 229940033123 tannic acid Drugs 0.000 description 1
- 229920002258 tannic acid Polymers 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- IIEOSQHRZNUOOC-UHFFFAOYSA-J tetrasodium dihydrogen phosphate hydrogen phosphate chloride Chemical compound [Cl-].[Na+].P(=O)(O)(O)[O-].[Na+].P(=O)(O)([O-])[O-].[Na+].[Na+] IIEOSQHRZNUOOC-UHFFFAOYSA-J 0.000 description 1
- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
Classifications
-
- 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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- 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
- A61K47/02—Inorganic compounds
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/14—Decongestants or antiallergics
Abstract
The present invention provides eye drops which contain epinastin or a salt thereof in a concentration exceeding 0.075% (w/v), the eye drops containing substantially no antiseptic or substantially no ingredient having antiseptic activity.
Description
benzalkonium chloride is used as a typical preservative for ophthalmic solutions because it is water-soluble and chemically stable, and also has higher preservative efficacy as compared to other preservatives. On the other hand, benzalkonium chloride has cytotoxicity and can induce corneal epithelium disorder if the exposure is increased.
it and patients suffering from disorder.
[0003]
Alesion®
0.05 ophthalmic solution, which is in Japan, is an ophthalmic solution comprising epinastine hydrochloride as (boric acid and edetic acid (EDTA)) instead of a commonlyDocument 1) .
order to repeatedly use an ophthalmic solution comprising salt thereof, not necessarily comprise a preservative such as benzalkonium chloride, secure instead o
An ophthalmic solution comprising epinastine or a salt the ophthalmic of both preservatives and with preservative efficacy is not known at ait.
Among ophthalmic solutions which have been marketed, an ophthalmi c solution comprising solution ophthalmic solution filled in a preservative-free container (container with a special structure for producing preservative efficacy). An ophthalmic solution whose active ingredient itself can produce preservative efficacy has not been reported. That is, it is not known that epinastine or a salt thereof itself can produce preservative efficacy.
PRIOR ART DOCUMENTS
NON-PATENT DOCUMENTS [0005]
Non-Patent Document
1: Alesion® 0.05% ophthalmic solution, Package insert
SUMMARY OF INVENTION (PROBLEM TO BE SOLVED BY THE INVENTION) [0006] An object of the present invention is to provide an ophthalmic solution comprising epinastine or a salt thereof wherein the ophthalmic solution is substantially free of preservatives and ingredients with preservative efficacy.
| (MEANS | FOR SOLVING THE | PROBLEMS) | 1 | |
| [0007] | The present | inventors | have extensively studi | ed to |
| develop | an ophthalmic | solution | comprising epinastine | or a |
salt thereof wherein . the ophthalmic solution is free of preservatives and ingredients with preservative efficacy or comprises them in a less content than usual, and then have found that an ophthalmic solution comprising epinastine or a salt thereof in a concentration of over 0.075% (w/v) can produce good preservative efficacy even if the solution is substantially free of preservatives and ingredients with preservative efficacy. Based upon the new findings, the present invention has been completed.
Specifically, the present invention provides the following embodiments.
(1) An ophthalmic solution comprising epinastine or a salt thereof in a concentration of over 0.075% (w/v) wherein the ophthalmic solution is substantially free of preservatives and ingredients with preservative efficacy.
(2) The ophthalmic solution of (1), wherein the concentration of epinastine or a salt thereof is 0.1% to 5.0% (w/v) .
(3) The ophthalmic solution of (1) or (2), wherein epinastine or a salt thereof is epinastine hydrochloride.
(4) The ophthalmic solution of (1), wherein the preservatives and ingredients with preservative efficacy are at least one selected from the group consisting of benzalkonium chloride, chlorhexidine or a salt thereof, boric acid, borax, and edetic acid or a salt thereof.
(5) An ophthalmic solution comprising only epinastine or a salt thereof in a concentration of over 0.075% (w/v) as an active ingredient and only a buffering agent, a tonicity agent and a pH adjuster as an additive.
(6) The ophthalmic solution of (5), wherein the concentration of epinastine or a salt thereof is 0.1% to 5.0% (w/v).
(7) The ophthalmic solution of (5) or (6), wherein epinastine or a salt thereof is epinastine hydrochloride.
| (8) | The | ophthalmic solution | of any | one | of | ( 5 ) to | (7) , |
| wherein | the buffering agent | is phosphoric | aci | d or a | salt | ||
| thereof. | |||||||
| (9) | The | ophthalmic solution | of any | one | of | ( 5 ) to | (8) , |
| wherein | the tonicity agent is | an ionic | toni | city | agent. | ||
| (10) | The | ophthalmic solution | of any one of | (1) | to (9) | which |
is a multi-dose ophthalmic solution.
(11) A method of providing preservative efficacy to an ophthalmic solution comprising epinastine or a salt thereof wherein the ophthalmic solution is substantially free of preservatives and ingredients with preservative efficacy, by composing epinastine or the salt thereof in a concentration of over 0.075% (w/v).
(12) A method of maintaining preservative efficacy in an ophthalmic solution comprising epinastine or a salt thereof wherein the ophthalmic solution is substantially free of preservative and ingredient with preservative efficacy, by composing epinastine or the salt thereof in a concentration of over 0.075% (w/v).
Each feature of the above (1) to (12) can be optionally selected and combined two or more.
Furthermore, the present invention also provides the following embodiments.
(13) A method of treating and/or preventing allergic conjunctivitis, which comprises administering a therapeutically effective amount of the ophthalmic solution of any one of (1) to (10) to a patient in need thereof.
(14) The ophthalmic solution of any one of (1) to (10) for use in treating and/or preventing allergic conjunctivitis.
(EFFECTS OF THE INVENTION) [0008] According to the present invention, an ophthalmic solution comprising epinastine or a salt thereof with preservative efficacy can be provided even if neither preservatives nor ingredients with preservative efficacy are used.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS [0009] Hereinafter, the present invention is explained in detail.
[0010] Epinastine as used herein is a compound represented by chemical name: (+)-3-Amino-9,13b-dihydro-lH dibenz [c,flimidazo[1,5-ajazepine, and also the following formula :
| [0011] | Epinastine iri the | ophthalmic solution | of | t θ |
| present | invention may be in | a salt form, and it | 1 s | not |
| particul | arly limited as | long as the salt | is | a |
pharmaceutically acceptable salt. Examples thereof include salts with an inorganic acid, an organic acid, and others.
Examples of the inorganic acid include hydrochloric acid, hydrobromic acid, hydroiodic acid, nitric acid,
| sulfuric acid, | phospho | ric acid, and others. | |||
| Examples | of the | organic acid | include | acetic | acid |
| oxalic acid, | fumaric | acid, maleic | acid, s | uccinic | acid |
| malic acid, | citric | acid, tartaric | acid, | adipic | acid |
gluconic acid, glucoheptonic acid, glucuronic acid, terephthalic acid, methanesulfonic acid, alanine, lactic acid, hippuric acid, 1,2-ethanedisulfonic acid, isethionic acid, lactobionic acid, oleic acid, gallic acid, pamoic acid, polygalacturonic acid, stearic acid, tannic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, p~ toluenesulfonic acid, lauryl sulfate, methyl sulfate, naphthalenesulfonic acid, sulfosalicylic acid, and others.
Particularly preferably, the salt of epinastine is monohydrochloride (epinastine hydrochloride).
[0012] Epinastine or a salt thereof as used herein may be in the form of a hydrate or a solvate.
[00131 The adequate content of epinastine or a salt thereof as used herein is over 0.075% (w/v). Also, the concentration thereof may be 0.085% (w/v) or more or 0.1% (w/v) or more. The upper limit is not limited as long as it is the concentration that is acceptable as ophthalmic formulations. For example, the upper limit is 5% (w/v).
The adequate content of epinastine or a salt thereof is preferably 0.1 to 5.0% (w/v), more preferably 0.1 to 3.0% (w/v), furthermore preferably 0.1 to 1.0% (w/v), and particularly preferably 0.1 to 0.5% (w/v) or 0.1 to 0.3% (w/v). Also, the content thereof may be 0.1% (w/v), 0.2% (w/v), 0.3% (w/v), 0.4% (w/v), or 0.5% (w/v).
When the ophthalmic solution c-f the present invention comprises a salt of epinastine, the values mean the content of the salt. The term % (w/v) means the mass (g) of an object ingredient (herein, epinastine or a salt thereof) in 100 mL of the ophthalmic solution. Hereinafter, the same shall apply to the followings unless otherwise specified. [0014] Examples of the preservatives as used herein include benzalkonium chloride, benzalkonium bromide, benzethonium chloride, chlorhexidine or a salt thereof, sorbic acid, or a salt thereof, methyl para-hydroxybenzoate, propyl para-hydroxybenzoate, chlorobutanol, and others.
Examples of chlorhexidine or a salt thereof include chlorhexidine gluconate, chlorhexidine hydrochloride, chlorhexidine acetate, and others.
Examples of sorbic acid or a salt thereof include sodium sorbate, potassium sorbate, and others.
[0015] Examples of the ingredients with preservative efficacy as used herein include boric acid, borax, edetic acid or a salt thereof, and others.
Examples of edetic acid or a salt thereof include monosodium edetate, disodium edetate, tetrasodium edetate, and others.
[0016] The term free of preservatives and ingredients with preservative efficacy as used herein means that an ophthalmic solution comprises none of the preservatives and ingredients with preservative efficacy or comprises the preservatives and ingredients with preservative efficacy in an amount which does not meet the requirement defined in the preservatives-effectiveness tests described in the Japanese Pharmacopoeia 17th Edition. The above amount that does not meet the requirement defined in the preservatives-effectiveness tests described in the Japanese Pharmacopoeia 17th Edition means an amount for producing not preservative efficacy of the preservatives and ingredients with preservative efficacy but another effect thereof. For example, when the preservatives and ingredients with preservative efficacy are EDTA, the amount thereof may be approximately 0.01% (w/v) or 0.02% (w/v). In such case, EDTA is added into an ophthalmic solution to produce not preservative efficacy thereof but stabilizing effect thereof. Also, when the preservatives and ingredients with preservative efficacy are boric acid, the amount thereof may be approximately 0.01% (w/v) or 0.02% (w/v). In such case, boric acid is added into an ophthalmic solution to produce not preservative efficacy thereof but buffering effect thereof. The term substantially as used herein indicates that the feature is not changed. Hence, the term substantially free of preservatives and ingredients with preservative efficacy as used herein means that an ophthalmic solution comprises none of preservatives and ingredients with preservative efficacy or comprises the preservatives and ingredients with preservative efficacy in an amount that does not meet the requirement defined in the preservatives-effectiveness tests described in the Japanese Pharmacopoeia 17th Edition when it is not intended to produce preservative efficacy.
[0017] The term multi-dose ophthalmic solution as used herein means an ophthalmic solution filled in a multi-dose container. The multi-dose container is designed so that a cap can be freely opened and closed for multiple uses of an ophthalmic solution. The multi-dose container can be used for a given period of time after first opening, and also can be easily carried. The size and shape of the container body as used herein are not particularly limited. The ophthalmic solution of the present invention may be placed in a unit-dose (single-use) container. More preferably, the ophthalmic solution is placed in a multi-dose container because it provides preservative efficacy. A container with a special structure for producing preservative efficacy such as backflow prevention function, for example, a PFMD (Preservative Free Multi Dose) container is not encompassed in the multi-dose container. The material of such container is not particularly limited. A commonlyused container such as a container made of polyethylene (PE), polypropylene (PP), or polyethylene terephthalate (PET) may be used.
[0018] The ophthalmic solution of the present invention may completely dissolve or partially suspend ingredients therein. More preferably, the ophthalmic solution is in the solution state that all ingredients are completely dissolved.
[0019] The ophthalmic solution of the present invention may comprise a buffering agent available as pharmaceutical additives. Examples thereof include phosphoric acid or a salt thereof, citric acid or a salt thereof, acetic acid or a salt thereof, carbonic acid or a salt thereof, tartaric acid or a salt thereof, ε-aminocaproic acid, trometamol, and others. They may be in the form of a hydrate or a solvate.
Examples of phosphoric acid or a salt thereof include sodium phosphate, sodium dihydrogen phosphate, disodium hydrogen phosphate, potassium phosphate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, and others. They may be in form of a hydrate.
| Examples | of citric | acid or | a | salt thereof | include | |
| sodium citrate | , disodium citrate, | and | others . | They | may be | |
| in the form of | a hydrate. | |||||
| Examples | of acetic | acid or | a | salt ther | e o f | include |
| sodium acetate | , potassium | acetate, | and | 1 others. | They | may be |
| in the form of | a hydrate. | |||||
| Examples | of carbonic | acid or | a | salt thereof | include | |
| sodium carbonate, sodium | hydrogen | carbonate, | and | others . | ||
| They may be in | the form of | a hydrate. | ||||
| Exampics | of tartaric | acid or | a | salt thereof | include |
sodium tartrate, potassium tartrate, and others. They may be in the form of a hydrate.
The buffering agent in the ophthalmic solution of the present invention is more preferably phosphoric acid or a salt thereof, particularly preferably sodium dihydrogen phosphate, disodium hydrogen phosphate c-r a hydrate thereof. Two or more of the buffering agents may be used in combination .
The content of the buffering agent in the ophthalmic solution of the present invention can be varied depending on the type of the buffering agent. The content thereof is preferably 0.001 to 10% (w/v), more preferably 0.01 to 5% (w/v), furthermore preferably 0.1 to 3% (w/v), most preferably 0.2 to 1.5% (w/v).
[00201 The ophthalmic solution of the present invention may comprise a tonicity agent available as pharmaceutical additives. Examples thereof include an ionic tonicity agent, a non-ionic tonicity agent, and others.
Examples of the ionic tonicity agent include sodium chloride, potassium chloride, calcium chloride, magnesium chloride, and others.
Examples of the non-ionic tonicity agent include glycerin, propylene glycol, polyethylene glycol, sorbitol, mannitol, trehalose, maltose, sucrose, and others.
The tonicity agent in the ophthalmic solution of the present invention is more preferably an ionic tonicity agent, particularly preferably sodium chloride. Two or more of the tonicity agents may be used in combination.
The content of the tonicity agent in the ophthalmic 25 solution of the present invention can be varied depending on the type of the tonicity agent. The content thereof is preferably 0.001 to 10% (w/v), more preferably 0.01 to 5% (w/v), furthermore preferably 0.1 to 1% (w/v), most preferably 0.2 to 0.5% (w/v).
The osmotic pressure ratio of the ophthalmic solution of the present invention is not limited as long as it is within a range acceptable for ophthalmic formulations. The osmotic pressure thereof is, for example, 0.5 to 2.0, preferably 0.7 to 1.6, more preferably 0.8 to 1.4, and furthermore preferably 0.9 to 1.2.
[00211 The ophthalmic solution of the present invention may comprise a pH adjuster available as pharmaceutical additives. The pH adjuster is, for example, an acid or a base. Examples of the acid include hydrochloric acid, phosphoric acid, citric acid, acetic acid, and others. Examples of the base include sodium hydroxide, potassium hydroxide, sodium carbonate, sodium hydrogen carbonate, and others .
invention is not limited as long as it is within a range acceptable for ophthalmic pH thereof is more preferably or 7.3.
[0022] The ophthalmic solution of the present invention may comprise one or more additives acceptable for ophthalmic formulations (except for preservatives and ingredients with preservative efficacy) besides the abovedescribed buffering agent, tc-nicity agent, and pH adjuster. Examples thereof include a solubilizing agent, a stabilizing agent, an antioxidant, a thickening agent, and others. In addition, unless otherwise specified, the ophthalmic solution may comprise any active ingredient used for ophthalmic formulations other than epinastine or salt thereof .
Examples of the solubilizing agent include polyoxyethylene hydrogenated castor oil, povidone, polysorbate 80, and others. Examples of the stabilizing agent include povidone, polysorbate 80, and others. Examples of the antioxidant include dibutylhydroxytoluene, sodium sulfite, and others. Examples of the thickening agent include carboxyvinyl polymer, hydroxyethyl cellulose, and others. They can be added in the range acceptable for ophthalmic formulations. Each additive may be added in an amount of 2% or less, 0.2% or less, 0.02% or less, or 0.002% or less.
[0023] The ophthalmic solution of the present invention is useful as an agent for treating allergic conjunctivitis. [0024] When the ophthalmic solution of the present invention is administered, its dose and administration is not particularly limited as long as it is sufficient to exhibit a desired efficacy. The ophthalmic solution can be administered at a dose of 1 drop a time, 1 to 10 times daily, preferably 2 to 6 times daily, more preferably 2 to 4 times, furthermore 2 times or 4 times daily. Also, the ophthalmic solution can be used with wearing contact lenses.
EXAMPLES [0025] Hereinafter, the present invention is illustrated in more detail in Formulation Examples and the results of Preservative Efficacy Test. The present invention, however, is not intended to be limited to them by any means.
[0026] [Formulation Examples]
Typical formulation examples of the present invention are shown below. The amount of each ingredient formulated in the following formulation examples is the content in 1 mL of the formulation.
[0027]
Formulation Example 1
In multi-dose container (1 mL)
| Epinastine hydrochloride | 1 | mg |
| Sodium dihydrogen phosphate | 3 | mg |
| Sodium chloride | 5 | mg |
Dilute hydrochloric acid
Sodium hydroxide
Purified water
Appropriate quantity
Appropriate quantity
Appropriate quantity [0028]
Formulation Example 2
In multi-dose container (1 mL)
| Epinastine hydrochloride | 3 mg |
| Sodium dihydrogen phosphate | 3 mg |
| Disodium hydrogen phosphate | 12 mg |
| Sodium chloride | 4 mg |
| Dilute hydrochloric acid | Appropriate quantity |
| Sodium hydroxide | Appropriate quantity |
| Purified water | Appropriate quantity |
| Γ O 0 9 Q 1 I vUi >J | |
| Preservative Efficacy Test (1) | |
| This test was performed | according to the |
preservatives-effectiveness tests described in the Japanese
Pharmacopoeia Seventeenth Edition.
mg)
Preparation of test disodium hydrogen formulations sodium di
| hydrogen | phosphate | (25 |
| hydrate | (122 mg), | and |
| ilved in | water and | the |
| .tion, and then a | pH |
amount was 10 mL to prepare the formulation of Example 1.
[00301
Example 1
In 1 mL of the formulation
Epinastine hydrochloride
Sodium dihydrogen phosphate Disodium hydrogen phosphate Sodium chloride
Dilute hydrochloric acid
Sodium hydroxide
Purified water pH mg
2.5 mg hydrate 12.2 mg mg
Appropriate quantity
Appropriate quantity
Appropriate quantity
6.7
According to a similar process to that of Example
1, the formulations of Examples [0032]
In 1 mL of the formulation
Epinastine Hydrochloride mg
2-5 mg
Disodium hydrogen phosphate hydrate 12.2 mg
Appropriate quantity
Purified Water pH quantity
6.7 [0033]
Example 3
In 1 mL of the formulation
Epinastine Hydrochloride
Sodium dihydrogen phosphate
Disodium hydrogen phosphate
Sodium chloride
Dilute hydrochloric acid
Sodium hydroxide
Purified water pH [0034]
Example 4
In 1 mL of the formulation
Epinastine Hydrochloride
Sodium dihydrogen phosphate
Disodium hydrogen phosphate
Sodium chloride
Dilute hydrochloric acid
Sodium hydroxide
Purified water pH [0035]
Comparative Example 1 mg
2.5 mg hydrate 12.2 mg
4.7 mg
Appropriate
Appropriate
Appropriate
6.7 quantity quantity quantity mg
2.5 mg hydrate 12.2 mg
4.5 mg
Appropriate
Appropriate
Appropriate
6.7 quantity quantity quantity
In 1 mL of the formulation
Epinastine hydrochloride
Sodium dihydrogen phosphate
Disodium hydrogen phosphate
Sodium chloride
Dilute hydrochloric acid
Sodium hydroxide
Purified water pH [0036]
Comparative Example 2
In 1 mL of the formulation
0.5 mg
2.5 mg hydrate 12.2 mg mg
Appropriate quantity
Appropriate quantity
Appropriate quantity
6.7
Epinastine hydrochloride
Sodium dihydrogen phosphate
Disodium hydrogen phosphate
Sodium chloride
Dilute hydrochloric acid
Sodium hydroxide
Purified water pH
0.75 mg
2.5 mg hydrate 12.2 mg
4.7 mg
Appropriate quantity
Appropriate quantity
Appropriate quantity
6.7 [0037]
2. Test Method
The following microorganisms were used as inoculum
Bacteria :
Escherichia Coli, Escherichia Coli ATCC 8739 (also referred to as E. coli)
Pseudomonas aeruginosa, Pseudomonas aeruginosa ATCC 9027 (also referred to as P. aeruginosa')
Staphylococcus aureus, Staphylococcus aureus ATCC 6538 (also referred to as S. aureus)
Yeast and Fungi:
Candida, Candida albicans ATCC 10231 (also referred to as C. albicans')
Aspergillus niger, Aspergillus brasiliensis ATCC16404 (also referred to as A. brasiliensis) [0038] A solution of each inoculum was inoculated to each test sample comprising each formulation so that the concentration of the solution in the test sample ranged from 105 to cfu/mL (in all of the microorganisms the of each cfu/ml. The prepared solution was inoculated to each test sample comprising each formulation of Examples 1-4 and Comparative Examples 1-2 so that the concentration of the solution in the test sample ranged from 10s to 10° cfu/mL, and then the resulting solution was homogeneously mixed to prepare a sample. The prepared samples were stored at 20 to 25°C in a place away from light, and 1 mL of each sample was collected with a micropipette at each sampling point (7 days later, 14 days later, or 28 days later) to measure the number of viable microorganisms. At each sampling point, the cap of the container filled in the sample solution was opened, sampling was performed, and then the cap was closed. [0039]
3. Test Results and Discussion
The test results are shown in Tables 1 and 2. The results of Tables 1 and 2 are the common logarithmic value of the ratio (B/A) of the number (B) of microorganisms at the time of inoculation to the number (A) of microorganisms when the viable microorganisms is measured. For example, when the value is 1, it shows that the measured number of viable microorganisms decreased to 10% of the number of inoculated microorganisms.
For determination of conformity or non-conformity in the test, when the value for bacterial species (E. colir P. aeruginosa, S. aureus) is 1.0 or more 7 days after inoculation and 3.0 or more 14 days or 28 days after inoculation as well as the value 7 days after inoculation for fungal species (C. albicans, A. brasiliensis) is not reduced as compared to the value 14 days or 28 days after inoculation, it was determined as being conformity.
[0040] [Table 1]
| 1 Microorganisms | Sampling Time | Comparative Example 1 | Example 1 | Example 2 |
| E . C o 1 i | 7 days later | 4.5 | 4.5 | 4.5 |
| 14 days later | 4.5 | 4.5 | 4.5 | |
| P. aeruginosa | 7 days later | 2.0 | 4 . 8 | 4.8 |
| 14 days later | 2.0 | 4 . 8 | 4 . 8 | |
| S. aureus | 7 days later | 1.7 | 4.7 | 4 . 7 |
| 14 days later | 4.7 | 4 . 7 | 4.7 | |
| C. albicans | 7 days later | 3.3 | 4 . 6 | 4.6 |
| 14 days later | 4.6 | 4.6 | 4.6 | |
| A» brasiliensis | 7 days later | 0.5 | 2.0 | 2.0 |
| 14 days later | 0.7 | 2 . 6 | 3.0 | |
| Determination | Nonconformity | Conformity | Conformity |
[0041] [Table 2]
| Microorganisms | Sampling Time | Comparative Example 2 | Example 3 | Example 4 |
| E. Coli | 7 days later | >4 . 4 | >4 . 4 | >4 . 4 |
| 28 days later | >4 . 4 | >4 . 4 | >4 . 4 | |
| P. aeruginosa | 7 days later | 3.9 | >5.0 | >5.0 |
| 28 days later | 2.9 | >5.0 | >5.0 | |
| S. aureus | 7 days later | >4 . 7 | >4.7 | >4.7 |
| 28 days later | >4.7 | >4.7 | 4 . 7 | |
| C. albicans | 7 days later | 3.3 | 3.2 | 3.7 |
| 28 days later | >4. 6 | >4.6 | >4.6 | |
| A. brasiliensis | 7 days later | 0.2 | 0.5 | 0.4 |
| 28 days later | 2.0 | 1.8 | 2.7 | |
| Determination | Nonconformity | Conformity | Conformity |
[0042] As shown in Tables 1 and 2, the formulations of
Examples 1-4 comprising epinastine or a salt thereof produced good preservative efficacy for all of the microorganisms without any preservatives and ingredients with preservative efficacy. On the other hand, it was shown that the formulations c-f Comparative Examples 1 and 2 did not produce good preservative efficacy. As a result, it was suggested that the ophthalmic solution comprising epinastine or a salt thereof in a concentration of over
0.075% (w/v) of the present invention could be used with repeatedly opening and closing a container as a multi-dose ophthalmic solution even if neither preservatives nor ingredients with preservative efficacy are used·
INDUSTRIAL APPLICABILITY an ophthalmic solution comprising epinastine or thereof in a concentration of over 0.075% ingredients with preservative free wherein the ophthalmic of preservatives and efficacy.
Claims (6)
1.
An ophthalmic solution comprising epinastine or a salt thereof ophthalmic solution is substantially free of and ingredients with preservative efficacy
The ophthalmic solution of claim
1, wherein the is
0.1 % to
The ophthalmic of wherein epinastine or a salt thereof is epinastine hydrochloride .
solution of claim
1, wherein the preservatives are at least one selected from the group consisting of benzalkonium boric acid, borax, and a salt thereof.
5. An ophthalmic solution comprising only epinastine or a salt thereof in a concentration of over 0.075% (w/v) as an active ingredient and only a buffering agent, a tonicity agent and a pH adjuster as an additive.
6.
The ophthalmic solution of claim 5, wherein the concentration of epinastine or a salt thereof is
0.1% to
5.0% (w/v) .
7. The ophthalmic
6, wherein epinastine or a salt thereof is epinastine hydrochloride.
11. A method of providing preservative efficacy to an ophthalmic solution comprising epinastine or a salt thereof wherein the ophthalmic solution is substantially free of preservatives and ingredients with preservative efficacy, by composing epinastine or the salt thereof in a concentration of over 0.075% (w/v).
12. A method of maintaining preservative efficacy in an ophthalmic solution comprising epinastine or a salt thereof wherein the ophthalmic solution is substantially free of preservatives and ingredients with preservative efficacy, by composing epinastine or the salt thereof in a 5 concentration of over 0.075% (w/v).
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2016-211535 | 2016-10-28 | ||
| JP2016211535A JP6134853B1 (en) | 2016-10-28 | 2016-10-28 | Epinastine-containing ophthalmic solution |
| PCT/JP2017/038948 WO2018079721A1 (en) | 2016-10-28 | 2017-10-27 | Epinastin-containing eye drops |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2017348597A1 true AU2017348597A1 (en) | 2019-05-16 |
Family
ID=58745757
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2017348597A Abandoned AU2017348597A1 (en) | 2016-10-28 | 2017-10-27 | Ophthalmic Solution Comprising Epinastine |
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| Country | Link |
|---|---|
| JP (1) | JP6134853B1 (en) |
| KR (3) | KR102659499B1 (en) |
| AU (1) | AU2017348597A1 (en) |
| MY (1) | MY192577A (en) |
| PH (1) | PH12019500934A1 (en) |
| TW (1) | TWI750248B (en) |
| WO (1) | WO2018079721A1 (en) |
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| TW201841620A (en) * | 2017-05-01 | 2018-12-01 | 日商參天製藥股份有限公司 | Ophthalmic solution |
| JP7355539B2 (en) * | 2018-07-20 | 2023-10-03 | ロート製薬株式会社 | Ophthalmic composition |
| JP7458159B2 (en) | 2018-09-28 | 2024-03-29 | ロート製薬株式会社 | Ophthalmic Composition |
| JP2019108320A (en) * | 2018-10-31 | 2019-07-04 | 参天製薬株式会社 | Ophthalmologic composition which suppresses deterioration of soft contact lens |
| JP6736752B2 (en) * | 2019-12-17 | 2020-08-05 | 参天製薬株式会社 | Eye drops containing epinastine |
| JP2020169213A (en) * | 2020-07-15 | 2020-10-15 | 参天製薬株式会社 | Epinastine-containing eye drops |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| DE19954516A1 (en) * | 1999-11-12 | 2001-05-17 | Boehringer Ingelheim Int | Solutions containing epinastine |
| EP2664329A1 (en) * | 2012-05-15 | 2013-11-20 | F. Holzer GmbH | Ophthalmological vehicle system |
| JPWO2015125921A1 (en) * | 2014-02-20 | 2017-03-30 | わかもと製薬株式会社 | Pharmaceutical aqueous composition having storage efficacy |
-
2016
- 2016-10-28 JP JP2016211535A patent/JP6134853B1/en active Active
-
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- 2017-10-27 TW TW106137043A patent/TWI750248B/en active
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| JP6134853B1 (en) | 2017-05-24 |
| WO2018079721A1 (en) | 2018-05-03 |
| JP2018070500A (en) | 2018-05-10 |
| KR102491425B1 (en) | 2023-01-20 |
| MY192577A (en) | 2022-08-29 |
| PH12019500934A1 (en) | 2019-12-02 |
| KR20190075956A (en) | 2019-07-01 |
| TWI750248B (en) | 2021-12-21 |
| KR20230014870A (en) | 2023-01-30 |
| TW201821060A (en) | 2018-06-16 |
| KR102659499B1 (en) | 2024-04-19 |
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Free format text: THE NATURE OF THE AMENDMENT IS: AMEND THE INVENTION TITLE TO READ OPHTHALMIC SOLUTION COMPRISING EPINASTINE |
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