JPH10287552A - Sterilized eye lotion of acyclovir aqueous suspension and its production - Google Patents
Sterilized eye lotion of acyclovir aqueous suspension and its productionInfo
- Publication number
- JPH10287552A JPH10287552A JP9267497A JP9267497A JPH10287552A JP H10287552 A JPH10287552 A JP H10287552A JP 9267497 A JP9267497 A JP 9267497A JP 9267497 A JP9267497 A JP 9267497A JP H10287552 A JPH10287552 A JP H10287552A
- Authority
- JP
- Japan
- Prior art keywords
- acyclovir
- aqueous suspension
- sterilized
- dispersant
- suspension
- 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.)
- Withdrawn
Links
- 229960004150 aciclovir Drugs 0.000 title claims abstract description 74
- 239000007900 aqueous suspension Substances 0.000 title claims abstract description 39
- MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 title claims abstract 23
- 238000004519 manufacturing process Methods 0.000 title claims description 13
- 239000006210 lotion Substances 0.000 title abstract 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 27
- 239000002270 dispersing agent Substances 0.000 claims abstract description 21
- 238000010438 heat treatment Methods 0.000 claims abstract description 15
- 238000001914 filtration Methods 0.000 claims abstract description 14
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 claims abstract description 6
- 229920000642 polymer Polymers 0.000 claims abstract description 6
- 239000003349 gelling agent Substances 0.000 claims abstract description 5
- 239000000725 suspension Substances 0.000 claims description 15
- 239000002997 ophthalmic solution Substances 0.000 claims description 10
- 229940054534 ophthalmic solution Drugs 0.000 claims description 9
- 229920002683 Glycosaminoglycan Polymers 0.000 claims description 5
- 239000006185 dispersion Substances 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 5
- 125000000600 disaccharide group Chemical group 0.000 claims 2
- 238000002360 preparation method Methods 0.000 abstract description 12
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical group C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 abstract description 2
- 239000003443 antiviral agent Substances 0.000 abstract description 2
- -1 i.e. Chemical compound 0.000 abstract description 2
- RMLUKZWYIKEASN-UHFFFAOYSA-M sodium;2-amino-9-(2-hydroxyethoxymethyl)purin-6-olate Chemical compound [Na+].O=C1[N-]C(N)=NC2=C1N=CN2COCCO RMLUKZWYIKEASN-UHFFFAOYSA-M 0.000 description 52
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 18
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 15
- 239000003889 eye drop Substances 0.000 description 10
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 9
- 239000004327 boric acid Substances 0.000 description 9
- 239000011780 sodium chloride Substances 0.000 description 9
- 229910021538 borax Inorganic materials 0.000 description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
- 239000004328 sodium tetraborate Substances 0.000 description 8
- 235000010339 sodium tetraborate Nutrition 0.000 description 8
- 239000000243 solution Substances 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 6
- 239000000679 carrageenan Substances 0.000 description 5
- 235000010418 carrageenan Nutrition 0.000 description 5
- 229920001525 carrageenan Polymers 0.000 description 5
- 229940113118 carrageenan Drugs 0.000 description 5
- 229940012356 eye drops Drugs 0.000 description 5
- 239000011148 porous material Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 5
- 229910019142 PO4 Inorganic materials 0.000 description 4
- 239000007853 buffer solution Substances 0.000 description 4
- 239000007979 citrate buffer Substances 0.000 description 4
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 230000003204 osmotic effect Effects 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 4
- 239000008363 phosphate buffer Substances 0.000 description 4
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 4
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 4
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 229920002385 Sodium hyaluronate Polymers 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 150000002016 disaccharides Chemical class 0.000 description 3
- 239000003885 eye ointment Substances 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000002674 ointment Substances 0.000 description 3
- 229940010747 sodium hyaluronate Drugs 0.000 description 3
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 description 3
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
- CFKMVGJGLGKFKI-UHFFFAOYSA-N 4-chloro-m-cresol Chemical compound CC1=CC(O)=CC=C1Cl CFKMVGJGLGKFKI-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 229940015162 acyclovir ophthalmic solution Drugs 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- UDEWPOVQBGFNGE-UHFFFAOYSA-N benzoic acid n-propyl ester Natural products CCCOC(=O)C1=CC=CC=C1 UDEWPOVQBGFNGE-UHFFFAOYSA-N 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- OLXYLDUSSBULGU-UHFFFAOYSA-N methyl pyridine-4-carboxylate Chemical compound COC(=O)C1=CC=NC=C1 OLXYLDUSSBULGU-UHFFFAOYSA-N 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229940057838 polyethylene glycol 4000 Drugs 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 239000012929 tonicity agent Substances 0.000 description 2
- ZUQUTHURQVDNKF-JAJWTYFOSA-N 1-[(2S,3R,4R,5S,6R)-3-amino-2,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]ethanone Chemical compound C(C)(=O)[C@]1(O)[C@@H]([C@@H](O)[C@H](O)[C@H](O1)CO)N ZUQUTHURQVDNKF-JAJWTYFOSA-N 0.000 description 1
- QTWJRLJHJPIABL-UHFFFAOYSA-N 2-methylphenol;3-methylphenol;4-methylphenol Chemical compound CC1=CC=C(O)C=C1.CC1=CC=CC(O)=C1.CC1=CC=CC=C1O QTWJRLJHJPIABL-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 239000004287 Dehydroacetic acid Substances 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- UYTPUPDQBNUYGX-UHFFFAOYSA-N Guanine Natural products O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229960000686 benzalkonium 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
- 229960001950 benzethonium chloride Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 229960004365 benzoic acid Drugs 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 229960002242 chlorocresol Drugs 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 229930003836 cresol Natural products 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 235000019258 dehydroacetic acid Nutrition 0.000 description 1
- JEQRBTDTEKWZBW-UHFFFAOYSA-N dehydroacetic acid Chemical compound CC(=O)C1=C(O)OC(C)=CC1=O JEQRBTDTEKWZBW-UHFFFAOYSA-N 0.000 description 1
- 229940061632 dehydroacetic acid Drugs 0.000 description 1
- PGRHXDWITVMQBC-UHFFFAOYSA-N dehydroacetic acid Natural products CC(=O)C1C(=O)OC(C)=CC1=O PGRHXDWITVMQBC-UHFFFAOYSA-N 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 206010023332 keratitis Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 238000010979 pH adjustment Methods 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 229940067107 phenylethyl alcohol Drugs 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 229960004063 propylene glycol Drugs 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 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
- 239000003871 white petrolatum Substances 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は、アシクロビルの点
眼剤を調製するにあたり、加温溶解しろ過することで滅
菌が可能となった、水性懸濁剤の形態を有する、アシク
ロビル点眼剤およびその製造方法に関するものである。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an acyclovir ophthalmic solution in the form of an aqueous suspension which can be sterilized by heating, dissolving and filtering to prepare an acyclovir ophthalmic solution and its production. It is about the method.
【０００２】[0002]
【従来の技術】アシクロビル（９−｛〔２−ｈｙｄｒｏ
ｘｙｅｔｈｏｘｙ〕ｍｅｔｈｙｌ｝ｇｕａｎｉｎｅ）
は、ヘルペス群ウイルス感染細胞に高い選択性を有し、
正常細胞への障害が低い抗ウイルス剤であり、従来より
注射剤、錠剤、軟膏剤等の形状で用いられている。2. Description of the Related Art Acyclovir (9-｛[2-hydro]
xyethoxy] methyl @ guanine)
Has high selectivity for herpes group virus infected cells,
It is an antiviral agent that causes less damage to normal cells and has been used in the form of injections, tablets, ointments and the like.
【０００３】アシクロビルは、水には溶けにくく、酸性
又はアルカリ性水溶液に溶けるが、水溶液中では不安定
である。従って注射剤では、ｐＨ調節剤として水酸化ナ
トリウム等を加え可溶化し、凍結乾燥し、用時溶解する
ことで使用されてきた。しかし、この注射剤のｐＨは１
０以上あり、点眼液として用いることは不可能であり、
水性の懸濁性点眼剤とするにも滅菌及び安定性に問題が
あった。従って眼科用製剤としては単純ヘルペスウイル
スに起因する角膜炎に対して眼軟膏剤が用いられてい
る。Acyclovir is poorly soluble in water and soluble in acidic or alkaline aqueous solutions, but is unstable in aqueous solutions. Therefore, injections have been used by solubilizing sodium hydroxide or the like as a pH adjuster, freeze-drying and dissolving at the time of use. However, the pH of this injection is 1
0 or more, it is impossible to use as eye drops,
Aqueous suspension eye drops also have problems in sterilization and stability. Therefore, as ophthalmic preparations, ophthalmic ointments are used for keratitis caused by herpes simplex virus.
【０００４】しかし、眼軟膏剤を用いる場合、いくつか
の問題点が指摘されている。すなわち、自分の眼に眼軟
膏を塗布することは、手間がかかり容易ではない。ま
た、眼軟膏を調製する際に基剤として用いられている白
色ワセリンが、眼に塗布した後、瞬きするたびに視界を
遮るなどの問題点が指摘されている。[0004] However, some problems have been pointed out when using eye ointments. That is, it is troublesome and difficult to apply the eye ointment to one's own eyes. In addition, it has been pointed out that white petrolatum used as a base when preparing an ointment ointment obstructs the field of vision every time it blinks after being applied to the eyes.
【０００５】[0005]
【発明が解決しようとする課題】本発明者らは、上記の
ような問題点が提起されている現状において、アシクロ
ビルの眼科用製剤について、一般的な水性点眼剤と同様
にいつでもどこでも点眼が容易にでき、点眼後の視界が
遮蔽されることもなく、また製造段階でろ過滅菌するこ
とが可能な点眼剤を提供するものである。SUMMARY OF THE INVENTION Under the present situation in which the above-mentioned problems have been raised, the present inventors have found that it is easy to apply ophthalmic ophthalmic preparations of acyclovir anytime and anywhere similarly to general aqueous eye drops. It is intended to provide an eye drop which does not obstruct the view after instillation and which can be sterilized by filtration at the production stage.
【０００６】[0006]
【課題を解決するための手段】本発明者らは、これら問
題点を解決すべく、アシクロビル点眼製剤について種々
検討してきた結果、ろ過滅菌が可能なアシクロビルの水
性懸濁点眼剤を調製することができ、これら問題点を解
決し本発明を完成させた。Means for Solving the Problems In order to solve these problems, the present inventors have conducted various studies on acyclovir ophthalmic preparations. As a result, it has been found that an aqueous suspension of acyclovir which can be sterilized by filtration can be prepared. These problems were solved and the present invention was completed.
【０００７】すなわち、次に示した１〜１０の手段によ
る。 １．アシクロビルに水を加え、加温溶解した後ろ過して
なる、滅菌されたアシクロビル水性懸濁点眼剤。 ２．アシクロビルに水を加え、加温溶解した後ろ過して
なる、滅菌されたアシクロビル水性懸濁点眼剤の製造方
法。 ３．アシクロビルに水を加え、懸濁及び分散の目的で分
散剤を含有させ、加温溶解した後ろ過してなる、滅菌さ
れたアシクロビル水性懸濁点眼剤。 ４．アシクロビルに水を加え、懸濁及び分散の目的で分
散剤を含有させ、加温溶解した後ろ過してなる、滅菌さ
れたアシクロビル水性懸濁点眼剤の製造方法。 ５．アシクロビルとして０．１〜８重量％を含有させた
請求項１又は３記載の滅菌されたアシクロビル水性懸濁
点眼剤。 ６．アシクロビルとして０．１〜８重量％を含有させた
請求項２又は４記載の滅菌されたアシクロビル水性懸濁
点眼剤の製造方法。 ７．分散剤としてゲル化剤を０．０１〜５重量％含有さ
せた請求項３又は５記載の滅菌されたアシクロビル水性
懸濁点眼剤。 ８．分散剤としてゲル化剤を０．０１〜５重量％含有さ
せた請求項４又は６記載の滅菌されたアシクロビル水性
懸濁点眼剤の製造方法。 ９．分散剤としてエチレンオキシドと水の付加重合体又
はο−β−Ｄ−グルクロノシル（１→３）−Ｎ−アセチ
ル−β−グルコサミン（１→４）単位の二糖繰り返し構
造を持つムコ多糖を含有させた請求項３又は５記載の滅
菌されたアシクロビル水性懸濁点眼剤。 １０．分散剤としてエチレンオキシドと水の付加重合体
又はο−β−Ｄ−グルクロノシル（１→３）−Ｎ−アセ
チル−β−グルコサミン（１→４）単位の二糖繰り返し
構造を持つムコ多糖を含有させた請求項４又は６記載の
滅菌されたアシクロビル水性懸濁点眼剤の製造方法。That is, the following means 1 to 10 are used. 1. A sterilized acyclovir aqueous suspension eye drop prepared by adding water to acyclovir, heating, dissolving and filtering. 2. A method for producing a sterilized aqueous suspension of acyclovir suspension, which comprises adding water to acyclovir, heating, dissolving and filtering. 3. A sterilized aqueous suspension of acyclovir suspension obtained by adding water to acyclovir, adding a dispersant for the purpose of suspension and dispersion, heating, dissolving and filtering. 4. A method for producing a sterilized aqueous suspension of acyclovir suspension, which comprises adding water to acyclovir, adding a dispersant for the purpose of suspension and dispersion, heating, dissolving and filtering. 5. The sterilized aqueous suspension of acyclovir according to claim 1 or 3, which contains 0.1 to 8% by weight of acyclovir. 6. The method for producing a sterilized aqueous suspension of acyclovir suspension according to claim 2 or 4, which contains 0.1 to 8% by weight of acyclovir. 7. The sterilized aqueous suspension of acyclovir according to claim 3 or 5, which contains 0.01 to 5% by weight of a gelling agent as a dispersing agent. 8. The method for producing a sterilized aqueous suspension of acyclovir suspension according to claim 4 or 6, wherein a gelling agent is contained as a dispersant in an amount of 0.01 to 5% by weight. 9. As a dispersant, an addition polymer of ethylene oxide and water or mucopolysaccharide having a disaccharide repeating structure of o-β-D-glucuronosyl (1 → 3) -N-acetyl-β-glucosamine (1 → 4) units was contained. The sterilized aqueous suspension of acyclovir according to claim 3 or 5. 10. As a dispersant, an addition polymer of ethylene oxide and water or mucopolysaccharide having a disaccharide repeating structure of o-β-D-glucuronosyl (1 → 3) -N-acetyl-β-glucosamine (1 → 4) units was contained. The method for producing a sterilized aqueous suspension of acyclovir according to claim 4 or 6.
【０００８】[0008]
【発明の実施の形態】アシクロビルは常温の水に対する
溶解度は低いが、７０℃以上に加温することにより溶解
度が増し、約８ｗ／ｖ％まで溶解することが可能とな
る。この液を孔径０．２２μｍ以下のフィルターで熱時
ろ過することにより滅菌を行い、このろ液をはげしく攪
拌しながら急速冷却することにより、アシクロビルの再
結晶化を行い、粒径１０μｍ以下の水性懸濁点眼剤が調
製できる。BEST MODE FOR CARRYING OUT THE INVENTION Acyclovir has low solubility in water at room temperature, but its solubility increases when heated to 70 ° C. or higher, and it can be dissolved up to about 8 w / v%. The solution is sterilized by hot filtration with a filter having a pore size of 0.22 μm or less, and the filtrate is rapidly cooled with vigorous stirring to recrystallize acyclovir, thereby obtaining an aqueous suspension having a particle size of 10 μm or less. A clouding eye drop can be prepared.
【０００９】またアシクロビルの液中での分散の安定化
を図る目的で分散剤を加えておくと、より安定な滅菌さ
れたアシクロビルの水性懸濁剤が調製可能となる。If a dispersant is added for the purpose of stabilizing the dispersion of acyclovir in a liquid, a more stable sterilized aqueous suspension of acyclovir can be prepared.
【００１０】本発明におけるアシクロビルは、０．１〜
８重量％を含有し、分散剤は０．００００５〜５重量％
を含有するものがよい。In the present invention, acyclovir is used in an amount of 0.1 to 0.1%.
8% by weight, and the dispersant is 0.00005 to 5% by weight.
Is preferable.
【００１１】本発明の製剤に使用する分散剤としては多
糖類を用いることができ、特にカラギーナン、アルギン
酸又はその塩（たとえば、ナトリウム塩）が好ましい。
また、エチレンオキシドと水の付加重合体を用いること
ができ、特にポリエチレングリコール４０００が好まし
い。更にο−β−Ｄ−グルクロノシル（１→３）−Ｎ−
アセチル−β−グルコサミン（１→４）単位の二糖繰り
返し構造を持つムコ多糖を用いることができ、特に、ヒ
アルロン酸ナトリウムが好ましい。これらの少なくとも
１種以上を組み合わせて用いることもできる。As the dispersant used in the preparation of the present invention, polysaccharides can be used, and carrageenan, alginic acid or a salt thereof (eg, sodium salt) is particularly preferable.
Further, an addition polymer of ethylene oxide and water can be used, and polyethylene glycol 4000 is particularly preferable. Furthermore, ο-β-D-glucuronosyl (1 → 3) -N-
A mucopolysaccharide having a disaccharide repeating structure of acetyl-β-glucosamine (1 → 4) units can be used, and sodium hyaluronate is particularly preferable. At least one of these may be used in combination.
【００１２】アシクロビルを水に溶解させるときの温度
は、アシクロビルの溶解度が増す７０℃から８０℃位が
よい。The temperature at which acyclovir is dissolved in water is preferably from 70 ° C. to 80 ° C., at which the solubility of acyclovir increases.
【００１３】また、再結晶したアシクロビルの結晶の微
細化及び粒度の均一化のため、無菌操作下で物理的破砕
を加えることで製剤として安定性を向上することも可能
である。[0013] Further, in order to refine the crystals of recrystallized acyclovir and make the particle size uniform, it is possible to improve the stability of the preparation by subjecting it to physical crushing under aseptic operation.
【００１４】本発明の滅菌されたアシクロビル水性懸濁
点眼剤は、点眼剤の使用基準を満足させるために、点眼
剤で通常用いられる保存剤、等張化剤、ｐＨを調節する
ための緩衝液等を適当量加えることができる。The sterilized aqueous acyclovir suspension ophthalmic solution of the present invention comprises a preservative, a tonicity agent, and a buffer for adjusting pH, which are commonly used in ophthalmic solutions, in order to satisfy the standard of use of the ophthalmic solution. Etc. can be added in appropriate amounts.
【００１５】保存剤としては、パラオキシ安息香酸エス
テル類、フェノール、クレゾール、クロロクレゾールな
どのようなフェノール類、クロロブタノール、フェニル
エチルアルコール、プロピレングリコールなどのような
アルコール類、塩化ベンザルコニウム、塩化ベンゼトニ
ウムなどのような四級アンモニウム塩、安息香酸、サリ
チル酸、ソルビン酸、デヒドロ酢酸、亜硫酸などのよう
な酸類及びそれらの塩類などをあげることができる。Examples of preservatives include paraoxybenzoates, phenols such as phenol, cresol and chlorocresol, alcohols such as chlorobutanol, phenylethyl alcohol and propylene glycol, benzalkonium chloride and benzethonium chloride. And the like, such as quaternary ammonium salts, such as benzoic acid, salicylic acid, sorbic acid, dehydroacetic acid, and sulfurous acid, and salts thereof.
【００１６】等張化剤としては、塩化ナトリウム及びリ
ン酸ナトリウムなどのような塩類、ブドウ糖などのよう
な糖類、グリセリン、ソルビトール、ポリエチレングリ
コールなどのようなアルコール類をあげることができ
る。Examples of the tonicity agent include salts such as sodium chloride and sodium phosphate, sugars such as glucose, and alcohols such as glycerin, sorbitol, and polyethylene glycol.
【００１７】ｐＨ調節のために加えられる緩衝液として
はリン酸、ホウ酸、酒石酸、クエン酸及びこれらの塩を
単独あるいは組み合わせて使用することができる。As a buffer added for pH adjustment, phosphoric acid, boric acid, tartaric acid, citric acid and salts thereof can be used alone or in combination.
【００１８】更にこの水性懸濁点眼剤の安定性は高く、
４０℃１箇月保存でも全くアシクロビルの含量低下はみ
られない。Further, the stability of this aqueous suspension ophthalmic solution is high,
Even after storage at 40 ° C. for one month, no reduction in the content of acyclovir is observed.
【００１９】以下、本発明を実施例により詳細に説明す
る。なお、本発明の滅菌されたアシクロビル水性懸濁点
眼剤は実施例に記載された処方例に限定されるものでは
ない。Hereinafter, the present invention will be described in detail with reference to examples. The sterilized acyclovir aqueous suspension ophthalmic solution of the present invention is not limited to the formulation examples described in the examples.
【００２０】 （実施例１） （１）処方 成 分 配合量（重量％） アシクロビル ３．０ カラギーナン ０．１ ホウ酸 ０．０５７ ホウ砂 ０．２１ 塩化ナトリウム ０．６６ パラオキシ安息香酸エチル ０．０２６ パラオキシ安息香酸プロピル ０．０１４ 滅菌精製水 適 量(Example 1) (1) Formulation Ingredients Compounding amount (% by weight) Acyclovir 3.0 Carrageenan 0.1 Boric acid 0.057 Borax 0.21 Sodium chloride 0.66 Ethyl paraoxybenzoate 0.026 Propyl parahydroxybenzoate 0.014 Sterile purified water qs
【００２１】（２）調製法 上記成分及び分量を用いて滅菌されたアシクロビル水性
懸濁点眼剤を調製した。すなわち、ホウ酸０．０５７
ｇ、ホウ砂０．２１ｇ、塩化ナトリウム０．６６ｇを滅
菌精製水１００ｃｃ．に溶解した液（ホウ酸・ホウ砂緩
衝液）を７０℃以上に加温し、アシクロビル３．０ｇと
分散剤としてカラギーナン０．１ｇを加え加熱溶解した
後、パラオキシ安息香酸エチル０．０２６ｇ、パラオキ
シ安息香酸プロピル０．０１４ｇを加えて溶解し、ホウ
酸・ホウ砂緩衝液を加えて全量１００ｃｃ．とし、孔径
０．２２μｍのメンブランフィルターでろ過した。この
ろ液をはげしく攪拌しながら急速に冷却し、ｐＨ７．
４、浸透圧比：約１．０の滅菌されたアシクロビル水性
懸濁点眼剤を得た。(2) Preparation Method A sterilized aqueous suspension of acyclovir was prepared using the above components and amounts. That is, boric acid 0.057
g, borax 0.21 g, and sodium chloride 0.66 g. The solution (boric acid / borax buffer solution) dissolved in water was heated to 70 ° C. or higher, and 3.0 g of acyclovir and 0.1 g of carrageenan as a dispersant were added and dissolved by heating. Then, 0.026 g of ethyl paraoxybenzoate, Add 0.014 g of propyl benzoate to dissolve, add boric acid / borax buffer solution, and add 100 cc. And filtered through a membrane filter with a pore size of 0.22 μm. The filtrate was rapidly cooled with vigorous stirring to a pH of 7.
4. A sterilized acyclovir aqueous suspension eye drop having an osmotic pressure ratio of about 1.0 was obtained.
【００２２】 （実施例２） （１）処方 成 分 配合量（重量％） アシクロビル ３．０ カラギーナン ０．０５ ホウ酸 ０．０５７ ホウ砂 ０．２１ 塩化ナトリウム ０．６６ パラオキシ安息香酸エチル ０．０２６ パラオキシ安息香酸プロピル ０．０１４ 滅菌精製水 適 量Example 2 (1) Prescription Component Ingredient Content (% by Weight) Acyclovir 3.0 Carrageenan 0.05 Boric Acid 0.057 Borax 0.21 Sodium Chloride 0.66 Ethyl Paraoxybenzoate 0.026 Propyl parahydroxybenzoate 0.014 Sterile purified water qs
【００２３】（２）調製法 上記成分及び分量を用いて滅菌されたアシクロビル水性
懸濁点眼剤を調製した。すなわち、ホウ酸０．０５７
ｇ、ホウ砂０．２１ｇ、塩化ナトリウム０．６６ｇを滅
菌精製水１００ｃｃ．に溶解した液（ホウ酸・ホウ砂緩
衝液）を７０℃以上に加温し、アシクロビル３．０ｇと
分散剤としてカラギーナン０．０５ｇを加え加熱溶解し
た後、パラオキシ安息香酸エチル０．０２６ｇ、パラオ
キシ安息香酸プロピル０．０１４ｇを加えて溶解し、ホ
ウ酸・ホウ砂緩衝液を加えて全量１００ｃｃ．とし、孔
径０．２２μｍのメンブランフィルターでろ過した。こ
のろ液をはげしく攪拌しながら急速に冷却し、ｐＨ７．
５、浸透圧比：約１．０の滅菌されたアシクロビル水性
懸濁点眼剤を得た。(2) Preparation method A sterilized acyclovir aqueous suspension ophthalmic solution was prepared using the above components and amounts. That is, boric acid 0.057
g, borax 0.21 g, and sodium chloride 0.66 g. The solution (boric acid / borax buffer solution) dissolved in water was heated to 70 ° C. or higher, 3.0 g of acyclovir and 0.05 g of carrageenan as a dispersant were added and dissolved by heating, and then 0.026 g of ethyl paraoxybenzoate, Add 0.014 g of propyl benzoate to dissolve, add boric acid / borax buffer solution, and add 100 cc. And filtered through a membrane filter with a pore size of 0.22 μm. The filtrate was rapidly cooled with vigorous stirring to a pH of 7.
5. A sterilized acyclovir aqueous suspension eye drop having an osmotic pressure ratio of about 1.0 was obtained.
【００２４】 （実施例３） （１）処方 成 分 配合量（重量％） アシクロビル ３．０ ヒアルロン酸ナトリウム ０．００００５ リン酸水素二ナトリウム １．７１９ クエン酸 ０．０４２ 塩化ナトリウム ０．５８ パラオキシ安息香酸エチル ０．０２６ パラオキシ安息香酸プロピル ０．０１４ 滅菌精製水 適 量(Example 3) (1) Formulation Ingredients Incorporation amount (% by weight) Acyclovir 3.0 Sodium hyaluronate 0.00005 Disodium hydrogen phosphate 1.719 Citric acid 0.042 Sodium chloride 0.58 Paraoxybenzoate Ethyl acid 0.026 Propyl parahydroxybenzoate 0.014 Sterilized purified water qs
【００２５】（２）調製法 上記成分及び分量を用いて滅菌されたアシクロビル水性
懸濁点眼剤を調製した。すなわち、リン酸水素二ナトリ
ウム１．７１９ｇ、クエン酸０．０４２ｇを滅菌精製水
１００ｃｃ．に溶解した液（リン酸・クエン酸緩衝液）
を７０℃以上に加温し、アシクロビル３．０ｇと分散剤
としてヒアルロン酸ナトリウム０．００００５ｇを加え
加熱溶解した後、塩化ナトリウム０．５８ｇ、パラオキ
シ安息香酸エチル０．０２６ｇ、パラオキシ安息香酸プ
ロピル０．０１４ｇを加えて溶解し、リン酸・クエン酸
緩衝液を加えて全量１００ｃｃ．とし、孔径０．２２μ
ｍのメンブランフィルターでろ過した。このろ液をはげ
しく攪拌しながら急速に冷却し、ｐＨ７．７、浸透圧
比：約１．０の滅菌されたアシクロビル水性懸濁点眼剤
を得た。(2) Preparation Method A sterilized aqueous suspension of acyclovir was prepared using the above components and amounts. That is, 1.719 g of disodium hydrogen phosphate and 0.042 g of citric acid were added to 100 cc of sterile purified water. Solution (phosphate / citrate buffer)
Was heated to 70 ° C. or higher, and 3.0 g of acyclovir and 0.00005 g of sodium hyaluronate as a dispersant were added and dissolved by heating. Then, sodium chloride 0.58 g, ethyl paraoxybenzoate 0.026 g, and propyl paraoxybenzoate 0. 014 g was added and dissolved, and a phosphate / citrate buffer solution was added to make a total amount of 100 cc. And a pore size of 0.22μ
m. The filtrate was rapidly cooled with vigorous stirring to obtain a sterilized aqueous suspension of acyclovir suspension having a pH of 7.7 and an osmotic pressure ratio of about 1.0.
【００２６】 （実施例４） （１）処方 成 分 配合量（重量％） アシクロビル ３．０ ポリエチレングリコール４０００ １．０ リン酸水素二ナトリウム １．７１９ クエン酸 ０．０４２ 塩化ナトリウム ０．４０ パラオキシ安息香酸エチル ０．０２６ パラオキシ安息香酸プロピル ０．０１４ 滅菌精製水 適 量Example 4 (1) Prescription Component Ingredient Content (% by weight) Acyclovir 3.0 Polyethylene glycol 4000 1.0 Disodium hydrogen phosphate 1.719 Citric acid 0.042 Sodium chloride 0.40 Paraoxybenzoate Ethyl acid 0.026 Propyl parahydroxybenzoate 0.014 Sterilized purified water qs
【００２７】（２）調製法 上記成分及び分量を用いて滅菌されたアシクロビル水性
懸濁点眼剤を調製した。すなわち、リン酸水素二ナトリ
ウム１．７１９ｇ、クエン酸０．０４２ｇを滅菌精製水
１００ｃｃ．に溶解した液（リン酸・クエン酸緩衝液）
を７０℃以上に加温し、アシクロビル３．０ｇと分散剤
としてポリエチレングリコール４０００１．０ｇを加え
加熱溶解した後、塩化ナトリウム０．４０ｇ、パラオキ
シ安息香酸エチル０．０２６ｇ、パラオキシ安息香酸プ
ロピル０．０１４ｇを加えて溶解し、リン酸・クエン酸
緩衝液を加えて全量１００ｃｃ．とし、孔径０．２２μ
ｍのメンブランフィルターでろ過した。このろ液をはげ
しく攪拌しながら急速に冷却し、ｐＨ７．７、浸透圧
比：約１．０の滅菌されたアシクロビル水性懸濁点眼剤
を得た。(2) Preparation Method A sterilized acyclovir aqueous suspension ophthalmic solution was prepared using the above components and amounts. That is, 1.719 g of disodium hydrogen phosphate and 0.042 g of citric acid were added to 100 cc of sterile purified water. Solution (phosphate / citrate buffer)
Was heated to 70 ° C. or higher, and 3.0 g of acyclovir and 40001.0 g of polyethylene glycol as a dispersant were added and dissolved by heating. Then, sodium chloride 0.40 g, ethyl paraoxybenzoate 0.026 g, and propyl paraoxybenzoate 0.014 g To dissolve and add a phosphate / citrate buffer solution to make a total amount of 100 cc. And a pore size of 0.22μ
m. The filtrate was rapidly cooled with vigorous stirring to obtain a sterilized aqueous suspension of acyclovir suspension having a pH of 7.7 and an osmotic pressure ratio of about 1.0.
【００２８】これらの実施例により得られた製剤は、ア
シクロビルが均一に分散した水性の懸濁点眼剤であり、
容易に点眼することができた。また、点眼後の視界も遮
蔽されることなく、一般的な水性点眼剤と比べても、十
分利便性の高い製剤であった。The preparations obtained according to these examples are aqueous suspension eye drops in which acyclovir is uniformly dispersed,
It could be easily instilled. In addition, the field of view after instillation was not obstructed, and the preparation was sufficiently convenient compared to general aqueous eye drops.
【００２９】[0029]
【発明の効果】以上説明したように、アシクロビルに水
を加え、必要であれば分散剤を加え、加温溶解し、ろ過
滅菌し、ろ液を急冷することでアシクロビルを再結晶さ
せることにより、点眼が容易にでき、点眼後の視界が遮
蔽されることもなく、一般的な水性点眼剤と同じよう
に、いつでもどこでも容易に用いることのできる、安定
な滅菌されたアシクロビル水性懸濁点眼剤が得られた。As described above, water is added to acyclovir, if necessary, a dispersant is added, the mixture is dissolved by heating, sterilized by filtration, and the filtrate is rapidly cooled to recrystallize acyclovir. A stable and sterilized aqueous suspension of acyclovir, which can be easily applied, without obstruction of the field of view after instillation, and can be easily used anytime and anywhere, like a general aqueous ophthalmic solution. Obtained.
───────────────────────────────────────────────────── フロントページの続き (72)発明者 高橋 勇 神奈川県厚木市森の里三丁目３番11号 (72)発明者 山我 洋 東京都武蔵村山市本町二丁目11番９号 有 限会社ナックコーポレーション内 ──────────────────────────────────────────────────続 き Continued on the front page (72) Inventor Isamu Takahashi 3-3-1-11 Morinosato, Atsugi-shi, Kanagawa (72) Inventor Hiroshi Yamaga 2-9-19-1 Honcho, Musashimurayama-shi, Tokyo NAC Corporation Limited Company Inside
Claims (10)
した後ろ過してなる、滅菌されたアシクロビル水性懸濁
点眼剤。1. A sterilized aqueous suspension of acyclovir, which is obtained by adding water to acyclovir, heating and dissolving and then filtering.
した後ろ過してなる、滅菌されたアシクロビル水性懸濁
点眼剤の製造方法。2. A method for producing a sterilized aqueous suspension of acyclovir suspension, which comprises adding water to acyclovir, heating and dissolving the mixture, followed by filtration.
分散の目的で分散剤を含有させ、加温溶解した後ろ過し
てなる、滅菌されたアシクロビル水性懸濁点眼剤。3. A sterilized aqueous suspension of acyclovir which is obtained by adding water to acyclovir, adding a dispersant for the purpose of suspension and dispersion, heating, dissolving and filtering.
分散の目的で分散剤を含有させ、加温溶解した後ろ過し
てなる、滅菌されたアシクロビル水性懸濁点眼剤の製造
方法。4. A method for producing a sterilized aqueous suspension of acyclovir suspension comprising adding water to acyclovir, adding a dispersant for the purpose of suspension and dispersion, heating, dissolving and filtering.
％を含有させた請求項１又は３記載の滅菌されたアシク
ロビル水性懸濁点眼剤。5. A sterilized aqueous suspension of acyclovir according to claim 1, which contains 0.1 to 8% by weight of acyclovir.
％を含有させた請求項２又は４記載の滅菌されたアシク
ロビル水性懸濁点眼剤の製造方法。6. The method for producing a sterilized aqueous suspension of acyclovir according to claim 2, wherein 0.1 to 8% by weight of acyclovir is contained.
５重量％含有させた請求項３又は５記載の滅菌されたア
シクロビル水性懸濁点眼剤。7. A dispersant comprising a gelling agent in an amount of 0.01 to
The sterilized aqueous suspension of acyclovir according to claim 3 or 5 which is contained in an amount of 5% by weight.
５重量％含有させた請求項４又は６記載の滅菌されたア
シクロビル水性懸濁点眼剤の製造方法。8. A gelling agent as a dispersant in an amount of from 0.01 to
The method for producing a sterilized acyclovir aqueous suspension ophthalmic solution according to claim 4 or 6, which contains 5% by weight.
の付加重合体又はο−β−Ｄ−グルクロノシル（１→
３）−Ｎ−アセチル−β−グルコサミン（１→４）単位
の二糖繰り返し構造を持つムコ多糖を含有させた請求項
３又は５記載の滅菌されたアシクロビル水性懸濁点眼
剤。9. An addition polymer of ethylene oxide and water or o-β-D-glucuronosyl (1 →
3) The sterilized acyclovir aqueous suspension ophthalmic solution according to claim 3 or 5, which contains a mucopolysaccharide having a repeating disaccharide structure of -N-acetyl-β-glucosamine (1 → 4) units.
の付加重合体又はο−β−Ｄ−グルクロノシル（１→
３）−Ｎ−アセチル−β−グルコサミン（１→４）単位
の二糖繰り返し構造を持つムコ多糖を含有させた請求項
４又は６記載の滅菌されたアシクロビル水性懸濁点眼剤
の製造方法。10. An addition polymer of ethylene oxide and water or o-β-D-glucuronosyl (1 →
3) The method for producing a sterilized aqueous suspension of acyclovir suspension according to claim 4 or 6, which contains a mucopolysaccharide having a repeating disaccharide structure of -N-acetyl-β-glucosamine (1 → 4) units.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP9267497A JPH10287552A (en) | 1997-04-11 | 1997-04-11 | Sterilized eye lotion of acyclovir aqueous suspension and its production |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP9267497A JPH10287552A (en) | 1997-04-11 | 1997-04-11 | Sterilized eye lotion of acyclovir aqueous suspension and its production |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH10287552A true JPH10287552A (en) | 1998-10-27 |
Family
ID=14061042
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP9267497A Withdrawn JPH10287552A (en) | 1997-04-11 | 1997-04-11 | Sterilized eye lotion of acyclovir aqueous suspension and its production |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH10287552A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002026234A1 (en) * | 2000-09-29 | 2002-04-04 | Wakamoto Pharmaceutical Co., Ltd. | Eye drops comprising acyclovir suspension |
| JP2008179623A (en) * | 2006-12-27 | 2008-08-07 | Teijin Pharma Ltd | Sterile aqueous suspension pharmaceutical formulation |
| JP2012511009A (en) * | 2008-12-05 | 2012-05-17 | アルコン リサーチ， リミテッド | Pharmaceutical suspension |
| US8912236B2 (en) | 2009-03-03 | 2014-12-16 | Alcon Research, Ltd. | Pharmaceutical composition for delivery of receptor tyrosine kinase inhibiting (RTKi) compounds to the eye |
| JPWO2024071349A1 (en) * | 2022-09-29 | 2024-04-04 |
-
1997
- 1997-04-11 JP JP9267497A patent/JPH10287552A/en not_active Withdrawn
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002026234A1 (en) * | 2000-09-29 | 2002-04-04 | Wakamoto Pharmaceutical Co., Ltd. | Eye drops comprising acyclovir suspension |
| JP2008179623A (en) * | 2006-12-27 | 2008-08-07 | Teijin Pharma Ltd | Sterile aqueous suspension pharmaceutical formulation |
| JP2010514671A (en) * | 2006-12-27 | 2010-05-06 | ニコメッド ゲゼルシャフト ミット ベシュレンクテル ハフツング | Sterile aqueous suspension containing ciclesonide |
| JP2012511009A (en) * | 2008-12-05 | 2012-05-17 | アルコン リサーチ， リミテッド | Pharmaceutical suspension |
| US9707173B2 (en) | 2008-12-05 | 2017-07-18 | Alcon Research, Ltd. | Pharmaceutical suspension |
| US8912236B2 (en) | 2009-03-03 | 2014-12-16 | Alcon Research, Ltd. | Pharmaceutical composition for delivery of receptor tyrosine kinase inhibiting (RTKi) compounds to the eye |
| JPWO2024071349A1 (en) * | 2022-09-29 | 2024-04-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US9533052B2 (en) | Aqueous ophthalmic suspension of crystalline rebamipide | |
| JPS62123116A (en) | Aqueous solution agent | |
| EP0799615A1 (en) | Liposome eye drops | |
| EP2018154B1 (en) | Hydrogel suspension and manufacturing process thereof | |
| KR100878198B1 (en) | Gel Composition Containing Minoxidil | |
| DE69424033T2 (en) | PHARMACEUTICAL SUPPORT FOR TOPICAL OPHTHALMIC USE | |
| JPH10287552A (en) | Sterilized eye lotion of acyclovir aqueous suspension and its production | |
| US8536325B2 (en) | Process for purifying guar | |
| DE69808938T2 (en) | METHOD FOR PRODUCING PHARMACEUTICAL COMPOSITIONS | |
| KR101718733B1 (en) | Method for solubilizing Rebamipide and a solution for treating dry eye syndrome prepared thereby | |
| EP0233615B1 (en) | Aqueous preparation and method of preparation thereof | |
| AU650889B2 (en) | Process for preparing aqueous suspension | |
| JP4442118B2 (en) | Stable eye drops | |
| CN104721136A (en) | Brinzolamide nanosuspension used for eyes and preparation method thereof | |
| WO2005101982A2 (en) | A stable ophthalmic composition | |
| JP4541504B2 (en) | A stable aqueous solution formulation containing tranilast or a pharmacologically acceptable salt thereof as an active ingredient | |
| CN116407456A (en) | cosmetic composition | |
| JP2005247795A (en) | Stable eye drops | |
| JP2005247804A (en) | Eye drops | |
| TWI778069B (en) | Poorly water-soluble component solubilized micelle and liquid agent containing same | |
| CN116139249A (en) | A kind of cyclosporin suspension eye drop and preparation method thereof | |
| WO2025044131A1 (en) | Methods for producing ophthalmic composition of poorly water-soluble drugs | |
| JP2005272462A (en) | Composition for eye drops | |
| HK1149496B (en) | A pharmaceutical composition |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A300 | Withdrawal of application because of no request for examination |
Free format text: JAPANESE INTERMEDIATE CODE: A300 Effective date: 20040706 |