JP2004143156A - Ophthalmic solution - Google Patents
Ophthalmic solution Download PDFInfo
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- JP2004143156A JP2004143156A JP2003336258A JP2003336258A JP2004143156A JP 2004143156 A JP2004143156 A JP 2004143156A JP 2003336258 A JP2003336258 A JP 2003336258A JP 2003336258 A JP2003336258 A JP 2003336258A JP 2004143156 A JP2004143156 A JP 2004143156A
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- Prior art keywords
- ketotifen fumarate
- ophthalmic solution
- eye
- chlorobutanol
- itching
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- 239000002997 ophthalmic solution Substances 0.000 title abstract description 14
- 229940054534 ophthalmic solution Drugs 0.000 title abstract description 13
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 claims abstract description 26
- 229960003630 ketotifen fumarate Drugs 0.000 claims abstract description 23
- YNQQEYBLVYAWNX-WLHGVMLRSA-N ketotifen fumarate Chemical compound OC(=O)\C=C\C(O)=O.C1CN(C)CCC1=C1C2=CC=CC=C2CC(=O)C2=C1C=CS2 YNQQEYBLVYAWNX-WLHGVMLRSA-N 0.000 claims abstract description 23
- 229960004926 chlorobutanol Drugs 0.000 claims abstract description 13
- 239000005526 vasoconstrictor agent Substances 0.000 claims abstract description 11
- 239000003889 eye drop Substances 0.000 claims description 20
- 238000002360 preparation method Methods 0.000 claims description 7
- 229940021790 tetrahydrozoline hydrochloride Drugs 0.000 claims description 6
- BJORNXNYWNIWEY-UHFFFAOYSA-N tetrahydrozoline hydrochloride Chemical compound Cl.N1CCN=C1C1C2=CC=CC=C2CCC1 BJORNXNYWNIWEY-UHFFFAOYSA-N 0.000 claims description 6
- DJDFFEBSKJCGHC-UHFFFAOYSA-N Naphazoline Chemical compound Cl.C=1C=CC2=CC=CC=C2C=1CC1=NCCN1 DJDFFEBSKJCGHC-UHFFFAOYSA-N 0.000 claims description 2
- 229960004760 naphazoline hydrochloride Drugs 0.000 claims description 2
- 229960003733 phenylephrine hydrochloride Drugs 0.000 claims description 2
- OCYSGIYOVXAGKQ-FVGYRXGTSA-N phenylephrine hydrochloride Chemical compound [H+].[Cl-].CNC[C@H](O)C1=CC=CC(O)=C1 OCYSGIYOVXAGKQ-FVGYRXGTSA-N 0.000 claims description 2
- 206010015958 Eye pain Diseases 0.000 abstract description 17
- 208000003251 Pruritus Diseases 0.000 abstract description 15
- 230000007803 itching Effects 0.000 abstract description 12
- 239000000243 solution Substances 0.000 abstract description 5
- 229940012356 eye drops Drugs 0.000 description 12
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- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 5
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- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 5
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 5
- 229920000053 polysorbate 80 Polymers 0.000 description 5
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 5
- MKYBYDHXWVHEJW-UHFFFAOYSA-N N-[1-oxo-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propan-2-yl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(C(C)NC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 MKYBYDHXWVHEJW-UHFFFAOYSA-N 0.000 description 4
- 239000000739 antihistaminic agent Substances 0.000 description 4
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- 230000007794 irritation Effects 0.000 description 4
- 230000003204 osmotic effect Effects 0.000 description 4
- 229940068968 polysorbate 80 Drugs 0.000 description 4
- 229940065427 vitamin b6 100 mg Drugs 0.000 description 4
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 3
- DBAKFASWICGISY-BTJKTKAUSA-N Chlorpheniramine maleate Chemical compound OC(=O)\C=C/C(O)=O.C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Cl)C=C1 DBAKFASWICGISY-BTJKTKAUSA-N 0.000 description 3
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 3
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 3
- 230000001387 anti-histamine Effects 0.000 description 3
- 229940046978 chlorpheniramine maleate Drugs 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 229940041616 menthol Drugs 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- QFOHBWFCKVYLES-UHFFFAOYSA-N Butylparaben Chemical compound CCCCOC(=O)C1=CC=C(O)C=C1 QFOHBWFCKVYLES-UHFFFAOYSA-N 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000003042 antagnostic effect Effects 0.000 description 2
- 239000000043 antiallergic agent Substances 0.000 description 2
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- -1 terpenoid compound Chemical class 0.000 description 2
- DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 description 1
- CIVCELMLGDGMKZ-UHFFFAOYSA-N 2,4-dichloro-6-methylpyridine-3-carboxylic acid Chemical compound CC1=CC(Cl)=C(C(O)=O)C(Cl)=N1 CIVCELMLGDGMKZ-UHFFFAOYSA-N 0.000 description 1
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 229920001287 Chondroitin sulfate Polymers 0.000 description 1
- 241000723346 Cinnamomum camphora Species 0.000 description 1
- SNPLKNRPJHDVJA-ZETCQYMHSA-N D-panthenol Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCCO SNPLKNRPJHDVJA-ZETCQYMHSA-N 0.000 description 1
- VWWQXMAJTJZDQX-UHFFFAOYSA-N Flavine adenine dinucleotide Natural products C1=NC2=C(N)N=CN=C2N1C(C(O)C1O)OC1COP(O)(=O)OP(O)(=O)OCC(O)C(O)C(O)CN1C2=NC(=O)NC(=O)C2=NC2=C1C=C(C)C(C)=C2 VWWQXMAJTJZDQX-UHFFFAOYSA-N 0.000 description 1
- BIVBRWYINDPWKA-VLQRKCJKSA-L Glycyrrhizinate dipotassium Chemical compound [K+].[K+].O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@H]1CC[C@]2(C)[C@H]3C(=O)C=C4[C@@H]5C[C@](C)(CC[C@@]5(CC[C@@]4(C)[C@]3(C)CC[C@H]2C1(C)C)C)C(O)=O)C([O-])=O)[C@@H]1O[C@H](C([O-])=O)[C@@H](O)[C@H](O)[C@H]1O BIVBRWYINDPWKA-VLQRKCJKSA-L 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 208000030961 allergic reaction Diseases 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000001139 anti-pruritic effect Effects 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 229910021538 borax Inorganic materials 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 229930008380 camphor Natural products 0.000 description 1
- 239000010624 camphor oil Substances 0.000 description 1
- 229960000411 camphor oil Drugs 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 229940059329 chondroitin sulfate Drugs 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229960000525 diphenhydramine hydrochloride Drugs 0.000 description 1
- 229940101029 dipotassium glycyrrhizinate Drugs 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000002444 effect on eosinophils Effects 0.000 description 1
- 230000001210 effect on neutrophils Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 210000003979 eosinophil Anatomy 0.000 description 1
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000010642 eucalyptus oil Substances 0.000 description 1
- 229940044949 eucalyptus oil Drugs 0.000 description 1
- FVTCRASFADXXNN-SCRDCRAPSA-N flavin mononucleotide Chemical compound OP(=O)(O)OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O FVTCRASFADXXNN-SCRDCRAPSA-N 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
- 229960001340 histamine Drugs 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 150000002617 leukotrienes Chemical class 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 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
- 238000013508 migration Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- OSZNNLWOYWAHSS-UHFFFAOYSA-M neostigmine methyl sulfate Chemical compound COS([O-])(=O)=O.CN(C)C(=O)OC1=CC=CC([N+](C)(C)C)=C1 OSZNNLWOYWAHSS-UHFFFAOYSA-M 0.000 description 1
- 229960002253 neostigmine methylsulfate Drugs 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229940101267 panthenol Drugs 0.000 description 1
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- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- ZUFQODAHGAHPFQ-UHFFFAOYSA-N pyridoxine hydrochloride Chemical compound Cl.CC1=NC=C(CO)C(CO)=C1O ZUFQODAHGAHPFQ-UHFFFAOYSA-N 0.000 description 1
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Abstract
Description
本発明は、フマル酸ケトチフェンを配合する点眼剤に関する。 The present invention relates to eye drops containing ketotifen fumarate.
フマル酸ケトチフェンは、アレルギー反応の際、ヒスタミンなどの遊離抑制作用・直接拮抗作用を有し、ロイコトリエンの産生と遊離抑制・拮抗作用を有しており、また、好中球・好酸球などの炎症細胞の遊走・浸潤抑制作用、活性酸素産生抑制作用を示すことが知られ、アレルギー症状の予防のため、点眼液や点鼻液等として臨床的に広く用いられている。 Ketotifen fumarate has an inhibitory action and a direct antagonistic action on histamine and the like during an allergic reaction, has a leukotriene production and release inhibitory and antagonistic action, and also has an effect on neutrophils and eosinophils. It is known to exhibit an inhibitory effect on the migration and infiltration of inflammatory cells and an active oxygen production, and is widely used clinically as eye drops, nasal drops and the like for preventing allergic symptoms.
フマル酸ケトチフェンを含有する点眼剤とした場合は、点眼時に眼痛を生じることが知られている。点眼時の眼痛を除去し、速効的な鎮痒効果を有するいくつかの点眼剤が開示されている。 It is known that ophthalmic solutions containing ketotifen fumarate cause eye pain when instilled. Several eye drops have been disclosed which eliminate eye pain during eye drops and have a rapid antipruritic effect.
たとえば、フマル酸ケトチフェン等の抗アレルギー薬と抗ヒスタミン薬及びメントール等のテルペノイド類を配合した点眼剤がある（特許文献１）。 For example, there is an eye drop prepared by mixing an antiallergic drug such as ketotifen fumarate with an antihistamine and a terpenoid such as menthol (Patent Document 1).
また、フマル酸ケトチフェン等の抗アレルギー薬と抗ヒスタミン薬、血管収縮薬及びメントール等のテルペノイド化合物を配合する点眼剤がある（特許文献２）。 が あ る Further, there is an eye drop which comprises an antiallergic drug such as ketotifen fumarate and a terpenoid compound such as an antihistamine, a vasoconstrictor and menthol (Patent Document 2).
しかしながら、フマル酸ケトチフェン、血管収縮薬及びクロロブタノールと組み合わせた点眼剤は知られていない。 However, no eye drops in combination with ketotifen fumarate, vasoconstrictors and chlorobutanol are known.
本発明は、フマル酸ケトチフェンを配合する点眼剤において、点眼時に眼痛を生じず、しかも目のかゆみを長時間抑えることのできる点眼剤を提供することである。 The present invention provides an ophthalmic solution containing ketotifen fumarate, which does not cause eye pain at the time of instillation and can suppress itching for a long time.
本発明者らは、かかる課題を解決するために鋭意研究した結果、フマル酸ケトチフェン、血管収縮薬及びクロロブタノールを配合した点眼剤が、意外にも、点眼時の眼痛を生じず、目のかゆみを長時間抑えることのできる点眼剤となることを見出し、本発明を完成した。 The present inventors have conducted intensive studies in order to solve such problems, and as a result, an eye drop containing ketotifen fumarate, a vasoconstrictor and chlorobutanol, surprisingly, did not cause eye pain at the time of instillation, and The present inventors have found that it is an eye drop that can suppress itch for a long time, and have completed the present invention.
本発明の点眼剤は、フマル酸ケトチフェンの眼痛防止ができ、目のかゆみを長時間抑えることのできる点眼剤である。 The ophthalmic solution of the present invention is an ophthalmic solution capable of preventing ketotifen fumarate from causing eye pain and suppressing itching of the eyes for a long time.
本発明は、フマル酸ケトチフェン、血管収縮薬及びクロロブタノールを配合することを特徴とする点眼剤である。 The present invention is an eye drop characterized by containing ketotifen fumarate, a vasoconstrictor and chlorobutanol.
本発明で、フマル酸ケトチフェンの配合量は0.0069−0.138%w/v%、好ましくは0.0138−0.104w/v%、さらに好ましくは0.0207-0.104w/v%である。 で In the present invention, the compounding amount of ketotifen fumarate is 0.0069-0.138% w / v%, preferably 0.0138-0.104w / v%, more preferably 0.0207-0.104w / v%.
血管収縮薬の配合量は、血管収縮薬の種類により異なり、塩酸テトラヒドロゾリンは0.005−0.10w/v%、塩酸ナファゾリンは0.0003−0.006w/v%、塩酸フェニレフリンは0.01−0.2w/v%である。 The amount of the vasoconstrictor differs depending on the type of the vasoconstrictor, and is 0.005-0.10 w / v% for tetrahydrozoline hydrochloride, 0.0003-0.006 w / v% for naphazoline hydrochloride, and 0.01-0.2 w / v% for phenylephrine hydrochloride. .
クロロブタノールの配合量は、好ましくは0.05-0.4w/v%、さらに好ましくは0.1−0.4w/v%である。 The amount of chlorobutanol is preferably 0.05-0.4 w / v%, more preferably 0.1-0.4 w / v%.
血管収縮薬の配合量が下限を下回るとフマル酸ケトチフェンの眼痛防止効果が弱い。また、0.2w/v%を上回ると刺激が生じてしまう。クロロブタノールの配合量が0.05w/v%を下回ると目のかゆみを長時間抑えることができない。 る と When the amount of the vasoconstrictor is less than the lower limit, the effect of ketotifen fumarate for preventing eye pain is weak. If it exceeds 0.2 w / v%, irritation will occur. If the amount of chlorobutanol is less than 0.05 w / v%, itching cannot be suppressed for a long time.
また、目のかゆみを即座に防止するためには、更に、抗ヒスタミン薬を加えることが好ましい。抗ヒスタミン薬としては、マレイン酸クロルフェニラミン、塩酸ジフェンヒドラミン等が挙げられる。 Further, in order to immediately prevent itching of the eyes, it is preferable to further add an antihistamine. Examples of antihistamines include chlorpheniramine maleate, diphenhydramine hydrochloride and the like.
本発明の点眼剤には、眼痛を起こさない範囲で、必要に応じて、医薬上許容される他の成分を配合することができ、例えば、イプシロンアミノカプロン酸、グリチルリチン酸二カリウム等の抗炎症薬、塩酸ピリドキシン、リン酸リボフラビン、シアノコバラミン、パンテノール、酢酸トコフェノール、フラビンアデニンジヌクレオチドナトリウム等のビタミン類、メチル硫酸ネオスチグミン等のピント調節薬、コンドロイチン硫酸ナトリウム、アミノエチルスルホン酸等のアミノ酸類、塩化ナトリウム、塩化カリウム等の無機塩、ポリオキシエチレン硬化ヒマシ油、ポリオキシエチレンソルビタンモノオレート等の界面活性剤、メントール、カンフル、ユーカリ油等の精油、その他基剤成分として、ホウ砂、ホウ酸、塩化ベンザルコニウム、パラオキシ安息香酸エステル（パラオキシ安息香酸メチル、パラオキシ安息香酸エチル、パラオキシ安息香酸プロピル、パラオキシ安息香酸ブチル等）等を挙げることができる。 The eye drops of the present invention can contain other pharmaceutically acceptable components, if necessary, as long as they do not cause eye pain, and include, for example, anti-inflammatory substances such as epsilon aminocaproic acid and dipotassium glycyrrhizinate. Drugs, pyridoxine hydrochloride, riboflavin phosphate, cyanocobalamin, panthenol, tocophenol acetate, vitamins such as sodium flavin adenine dinucleotide, focus regulators such as neostigmine methyl sulfate, amino acids such as chondroitin sulfate, aminoethylsulfonic acid, Inorganic salts such as sodium chloride and potassium chloride; surfactants such as polyoxyethylene hydrogenated castor oil; polyoxyethylene sorbitan monooleate; essential oils such as menthol, camphor and eucalyptus oil; borax and boric acid as other base components , Benzalkonium chloride Paraoxybenzoates (methyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, butyl parahydroxybenzoate and the like) and the like.
本発明の点眼剤は、従来の方法で製造することができ、点眼剤は、１日数回、１回１滴から数滴投与することができる。 眼 The eye drops of the present invention can be produced by a conventional method, and the eye drops can be administered several times a day, one to several drops at a time.
以下に、実施例及び試験例を示し、本発明を詳細に説明する。 実 施 Examples and test examples are shown below to explain the present invention in detail.
実施例１
処方 100mL中
フマル酸ケトチフェン 13.8mg
塩酸テトラヒドロゾリン 50mg
ε‐アミノカプロン酸 1000mg
アミノエチルスルホン酸 1000mg
ビタミンＢ６ 100mg
シアノコバラミン 10mg
クロロブタノール 100mg
グリセリン 1020mg
ポリソルベート80 100mg
塩化ベンザルコニウム 10mg
希塩酸 適量
滅菌精製水 全100mL
製造方法
滅菌精製水（約80ｍL)に各成分を溶解後、希塩酸を適量添加しｐHを5.3に調整後、全量を正確に100mLとした。その後ろ過滅菌を行い、無菌の点眼液とした。調製後浸透圧を測定したところ290mOsmであった。
Example 1
Formulation Ketotifen fumarate 13.8mg in 100mL
Tetrahydrozoline hydrochloride 50mg
ε-aminocaproic acid 1000mg
Aminoethylsulfonic acid 1000mg
Vitamin B6 100mg
Cyanocobalamin 10mg
Chlorobutanol 100mg
Glycerin 1020mg
Polysorbate 80 100mg
Benzalkonium chloride 10mg
Dilute hydrochloric acid qs.Sterile purified water total 100mL
Production Method After dissolving each component in sterile purified water (about 80 mL), an appropriate amount of dilute hydrochloric acid was added to adjust the pH to 5.3, and the total amount was made exactly 100 mL. Thereafter, the solution was sterilized by filtration to obtain a sterile ophthalmic solution. When the osmotic pressure was measured after preparation, it was 290 mOsm.
実施例２
処方 100mL中
フマル酸ケトチフェン 69mg
塩酸テトラヒドロゾリン 50mg
ε‐アミノカプロン酸 1000mg
マレイン酸クロルフェニラミン 30mg
アミノエチルスルホン酸 1000mg
ビタミンＢ６ 100mg
シアノコバラミン 10mg
クロロブタノール 100mg
グリセリン 1005mg
ポリソルベート80 100mg
塩化ベンザルコニウム 10mg
希塩酸 適量
滅菌精製水 全100mL
製造方法
滅菌精製水（約80ｍL)に各成分を溶解後、希塩酸を適量添加しｐHを5.3に調整後、全量を正確に100mLとした。その後ろ過滅菌を行い、無菌の点眼液とした。調製後浸透圧を測定したところ291mOsmであった。
Example 2
Prescription 100ml ketotifen fumarate 69mg
Tetrahydrozoline hydrochloride 50mg
ε-aminocaproic acid 1000mg
Chlorpheniramine maleate 30mg
Aminoethylsulfonic acid 1000mg
Vitamin B6 100mg
Cyanocobalamin 10mg
Chlorobutanol 100mg
Glycerin 1005mg
Polysorbate 80 100mg
Benzalkonium chloride 10mg
Dilute hydrochloric acid qs.Sterile purified water total 100mL
Production Method After dissolving each component in sterile purified water (about 80 mL), an appropriate amount of dilute hydrochloric acid was added to adjust the pH to 5.3, and the total amount was made exactly 100 mL. Thereafter, the solution was sterilized by filtration to obtain a sterile ophthalmic solution. The osmotic pressure measured after preparation was 291 mOsm.
実施例３
処方 100mL中
フマル酸ケトチフェン 69mg
塩酸テトラヒドロゾリン 50mg
ε‐アミノカプロン酸 1000mg
マレイン酸クロルフェニラミン 30mg
アミノエチルスルホン酸 1000mg
ビタミンＢ６ 100mg
シアノコバラミン 10mg
クロロブタノール 300mg
グリセリン 910mg
ポリソルベート80 100mg
塩化ベンザルコニウム 10mg
希塩酸 適量
滅菌精製水 全100mL
製造方法
滅菌精製水（約80ｍL)に各成分を溶解後、希塩酸を適量添加しｐHを5.3に調整後、全量を正確に100mLとした。その後ろ過滅菌を行い、無菌の点眼液とした。調製後浸透圧を測定したところ292mOsmであった。
Example 3
Prescription 100ml ketotifen fumarate 69mg
Tetrahydrozoline hydrochloride 50mg
ε-aminocaproic acid 1000mg
Chlorpheniramine maleate 30mg
Aminoethylsulfonic acid 1000mg
Vitamin B6 100mg
Cyanocobalamin 10mg
Chlorobutanol 300mg
Glycerin 910mg
Polysorbate 80 100mg
Benzalkonium chloride 10mg
Dilute hydrochloric acid qs.Sterile purified water total 100mL
Production Method After dissolving each component in sterile purified water (about 80 mL), an appropriate amount of dilute hydrochloric acid was added to adjust the pH to 5.3, and the total amount was made exactly 100 mL. Thereafter, the solution was sterilized by filtration to obtain a sterile ophthalmic solution. After preparation, the osmotic pressure was measured to be 292 mOsm.
実施例４
処方 100mL中
フマル酸ケトチフェン 103.5mg
塩酸テトラヒドロゾリン 50mg
ε‐アミノカプロン酸 1000mg
アミノエチルスルホン酸 1000mg
ビタミンＢ６ 100mg
シアノコバラミン 10mg
クロロブタノール 300mg
グリセリン 913mg
ポリソルベート80 100mg
塩化ベンザルコニウム 10mg
希塩酸 適量
滅菌精製水 全100mL
製造方法
滅菌精製水（約80ｍL)に各成分を溶解後、希塩酸を適量添加しｐHを5.3に調整後、全量を正確に100mLとした。その後ろ過滅菌を行い、無菌の点眼液とした。調製後浸透圧を測定したところ290mOsmであった。
Example 4
Formulation Ketotifen fumarate 103.5mg in 100mL
Tetrahydrozoline hydrochloride 50mg
ε-aminocaproic acid 1000mg
Aminoethylsulfonic acid 1000mg
Vitamin B6 100mg
Cyanocobalamin 10mg
Chlorobutanol 300mg
Glycerin 913mg
Polysorbate 80 100mg
Benzalkonium chloride 10mg
Dilute hydrochloric acid qs.Sterile purified water total 100mL
Production Method After dissolving each component in sterile purified water (about 80 mL), an appropriate amount of dilute hydrochloric acid was added to adjust the pH to 5.3, and the total amount was made exactly 100 mL. Thereafter, the solution was sterilized by filtration to obtain a sterile ophthalmic solution. When the osmotic pressure was measured after preparation, it was 290 mOsm.
実施例５〜１２
実施例１と同様の製造方法により、表１に示した実施例５〜１２の点眼剤を調製した。
Examples 5 to 12
By the same manufacturing method as in Example 1, the eye drops of Examples 5 to 12 shown in Table 1 were prepared.
比較例１〜４
実施例１と同様の製造方法により、表２に示した比較例1〜４の点眼剤を調製した。
Comparative Examples 1-4
The eye drops of Comparative Examples 1 to 4 shown in Table 2 were prepared by the same production method as in Example 1.
試験例1
方法：
成人健常者男女計10名に、検体として実施例5-12及び比較例１-4の点眼剤を点眼し、点眼時の眼痛刺激の程度を評価した。評価基準は、
×：眼痛を顕著に感じる。
△：眼痛を感じる。
○：眼痛をほとんど感じない。
◎：眼痛を全く感じない。
として、判定を行った。各検体ごとに眼痛刺激の程度の割合が多い評価を評点とした。その結果を表３に示す。本発明の点眼剤の実施例5-12は、比較例１-4に比べて、眼痛刺激を抑制し、有用であることが示された。
Test example 1
Method:
The eye drops of Examples 5-12 and Comparative Example 1-4 were instilled as samples into a total of 10 healthy adult men and women, and the degree of eye pain irritation at the time of instillation was evaluated. Evaluation criteria are
×: Eye pain is remarkably felt.
Δ: Eye pain is felt.
：: Almost no eye pain is felt.
A: No eye pain is felt.
The judgment was made as follows. The evaluation in which the ratio of the degree of eye pain irritation was large for each sample was evaluated. Table 3 shows the results. Example 5-12 of the ophthalmic solution of the present invention was shown to be more effective in suppressing eye pain irritation than Comparative Example 1-4.
試験例2
方法：
成人健常者10名に対し、1月から4月の間で、自覚症状として目のかゆみを感じた時に、検体として実施例5-12及び比較例１-4の点眼剤を点眼し、かゆみを抑制する時間を評価した。評価基準は、
×：点眼してかゆみが抑制されたのが５分以内であった。
△：点眼してかゆみが５〜15分抑制された。
○：点眼してかゆみが15〜30分抑制された。
◎：点眼してかゆみが30分以上抑制された。
として、判定を行った。各検体ごとにかゆみを抑制されたと感じる時間の割合が多い評価を評点とした。その結果を表４に示す。本願発明の点眼剤の実施例5-12は、比較例１-4に比べて、かゆみを抑制し、有用であることが示された。
Test example 2
Method:
For 10 healthy adults, between January and April, when they felt itchy as a subjective symptom, they applied the eye drops of Example 5-12 and Comparative Example 1-4 as specimens, The time to suppress was evaluated. Evaluation criteria are
C: Itching was suppressed within 5 minutes after instillation.
Δ: Itching was suppressed for 5 to 15 minutes upon instillation.
A: Itching was suppressed for 15 to 30 minutes after instillation.
：: Itching was suppressed for 30 minutes or more.
The judgment was made as follows. The evaluation in which the proportion of the time when the person felt that itching was suppressed for each sample was large was scored. Table 4 shows the results. Example 5-12 of the ophthalmic solution of the present invention suppressed itch and was shown to be useful as compared with Comparative Example 1-4.
本発明の点眼剤は、フマル酸ケトチフェン、血管収縮薬及びクロロブタノールを配合することを特徴とするフマル酸ケトチフェンの眼痛防止ができ、目のかゆみを長時間抑えることのできる極めて有用な点眼剤として用いることができる。
The eye drop of the present invention is an extremely useful eye drop of ketotifen fumarate, characterized by containing ketotifen fumarate, a vasoconstrictor and chlorobutanol, which can prevent eye pain and can suppress itching of eyes for a long time. Can be used as
Claims (4)
The ophthalmic preparation according to claim 1, wherein the vasoconstrictor is at least one selected from tetrahydrozoline hydrochloride, naphazoline hydrochloride and phenylephrine hydrochloride.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2010502564A (en) * | 2006-08-28 | 2010-01-28 | 千寿製薬株式会社 | Ophthalmic transdermal preparation |
| JP2020147557A (en) * | 2019-03-08 | 2020-09-17 | ロート製薬株式会社 | Ophthalmic composition having inhibited irritating sensation |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2010502564A (en) * | 2006-08-28 | 2010-01-28 | 千寿製薬株式会社 | Ophthalmic transdermal preparation |
| JP2020147557A (en) * | 2019-03-08 | 2020-09-17 | ロート製薬株式会社 | Ophthalmic composition having inhibited irritating sensation |
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