CN105534886A - 一种诺氟沙星滴眼剂及其制备方法 - Google Patents
一种诺氟沙星滴眼剂及其制备方法 Download PDFInfo
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- OGJPXUAPXNRGGI-UHFFFAOYSA-N norfloxacin Chemical compound C1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNCC1 OGJPXUAPXNRGGI-UHFFFAOYSA-N 0.000 title claims abstract description 54
- 229960001180 norfloxacin Drugs 0.000 title claims abstract description 54
- 239000003889 eye drop Substances 0.000 title claims abstract description 35
- 229940012356 eye drops Drugs 0.000 title claims abstract description 24
- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- 239000000243 solution Substances 0.000 claims abstract description 48
- 230000001105 regulatory effect Effects 0.000 claims abstract description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 24
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 18
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 claims description 18
- 239000003795 chemical substances by application Substances 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- 239000008215 water for injection Substances 0.000 claims description 12
- 230000000536 complexating effect Effects 0.000 claims description 10
- 229910021645 metal ion Inorganic materials 0.000 claims description 10
- 239000003002 pH adjusting agent Substances 0.000 claims description 10
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical group [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 claims description 9
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 9
- 229960004926 chlorobutanol Drugs 0.000 claims description 9
- 239000001632 sodium acetate Substances 0.000 claims description 9
- 235000017281 sodium acetate Nutrition 0.000 claims description 9
- 239000011780 sodium chloride Substances 0.000 claims description 9
- 230000002421 anti-septic effect Effects 0.000 claims description 8
- 238000001914 filtration Methods 0.000 claims description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 6
- 230000003204 osmotic effect Effects 0.000 claims description 6
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 4
- 229910021538 borax Inorganic materials 0.000 claims description 4
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims description 4
- 239000004327 boric acid Substances 0.000 claims description 4
- 235000010338 boric acid Nutrition 0.000 claims description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 4
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 claims description 4
- VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Chemical compound [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 claims description 4
- 239000004328 sodium tetraborate Substances 0.000 claims description 4
- 235000010339 sodium tetraborate Nutrition 0.000 claims description 4
- 238000012859 sterile filling Methods 0.000 claims description 4
- 238000003756 stirring Methods 0.000 claims description 4
- 239000005711 Benzoic acid Substances 0.000 claims description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 2
- 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 claims description 2
- 229930195725 Mannitol Natural products 0.000 claims description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 2
- 229960002233 benzalkonium bromide Drugs 0.000 claims description 2
- 229960000686 benzalkonium chloride Drugs 0.000 claims description 2
- KHSLHYAUZSPBIU-UHFFFAOYSA-M benzododecinium bromide Chemical compound [Br-].CCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 KHSLHYAUZSPBIU-UHFFFAOYSA-M 0.000 claims description 2
- 235000010233 benzoic acid Nutrition 0.000 claims description 2
- 229960004365 benzoic acid Drugs 0.000 claims description 2
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 claims description 2
- 235000015165 citric acid Nutrition 0.000 claims description 2
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims description 2
- 235000019800 disodium phosphate Nutrition 0.000 claims description 2
- 229910000397 disodium phosphate Inorganic materials 0.000 claims description 2
- 229960001617 ethyl hydroxybenzoate Drugs 0.000 claims description 2
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 claims description 2
- 239000008103 glucose Substances 0.000 claims description 2
- 235000001727 glucose Nutrition 0.000 claims description 2
- 235000011187 glycerol Nutrition 0.000 claims description 2
- 239000004310 lactic acid Substances 0.000 claims description 2
- 235000014655 lactic acid Nutrition 0.000 claims description 2
- 239000000594 mannitol Substances 0.000 claims description 2
- 235000010355 mannitol Nutrition 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 235000019799 monosodium phosphate Nutrition 0.000 claims description 2
- 229910000403 monosodium phosphate Inorganic materials 0.000 claims description 2
- GYCKQBWUSACYIF-UHFFFAOYSA-N o-hydroxybenzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1O GYCKQBWUSACYIF-UHFFFAOYSA-N 0.000 claims description 2
- 239000001103 potassium chloride Substances 0.000 claims description 2
- 235000011164 potassium chloride Nutrition 0.000 claims description 2
- 235000011118 potassium hydroxide Nutrition 0.000 claims description 2
- 235000010333 potassium nitrate Nutrition 0.000 claims description 2
- 239000004323 potassium nitrate Substances 0.000 claims description 2
- OTYBMLCTZGSZBG-UHFFFAOYSA-L potassium sulfate Chemical compound [K+].[K+].[O-]S([O-])(=O)=O OTYBMLCTZGSZBG-UHFFFAOYSA-L 0.000 claims description 2
- 229910052939 potassium sulfate Inorganic materials 0.000 claims description 2
- 235000011151 potassium sulphates Nutrition 0.000 claims description 2
- 239000003755 preservative agent Substances 0.000 claims description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 claims description 2
- 229960003415 propylparaben Drugs 0.000 claims description 2
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 claims description 2
- 239000004299 sodium benzoate Substances 0.000 claims description 2
- 235000010234 sodium benzoate Nutrition 0.000 claims description 2
- 229960003885 sodium benzoate Drugs 0.000 claims description 2
- 235000002639 sodium chloride Nutrition 0.000 claims description 2
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 claims description 2
- 235000011121 sodium hydroxide Nutrition 0.000 claims description 2
- 239000004317 sodium nitrate Substances 0.000 claims description 2
- 235000010344 sodium nitrate Nutrition 0.000 claims description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 claims description 2
- 235000011152 sodium sulphate Nutrition 0.000 claims description 2
- 230000001954 sterilising effect Effects 0.000 claims description 2
- 238000004659 sterilization and disinfection Methods 0.000 claims description 2
- 239000011975 tartaric acid Substances 0.000 claims description 2
- 235000002906 tartaric acid Nutrition 0.000 claims description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 3
- 235000011054 acetic acid Nutrition 0.000 claims 1
- 208000022873 Ocular disease Diseases 0.000 abstract description 5
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 4
- 206010059866 Drug resistance Diseases 0.000 abstract description 3
- 230000000694 effects Effects 0.000 abstract description 2
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- 206010010741 Conjunctivitis Diseases 0.000 description 2
- 241000588652 Neisseria gonorrhoeae Species 0.000 description 2
- 206010064996 Ulcerative keratitis Diseases 0.000 description 2
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- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 241000606701 Rickettsia Species 0.000 description 1
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- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
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- 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
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- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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- 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
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- 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
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Abstract
本发明公开了一种诺氟沙星滴眼剂及其制备方法,每1L滴眼剂中含有诺氟沙星2.4~3.5g,并且用pH调节剂调节pH值至5.0~5.6。本发明制备工艺流程简单易行,提高了诺氟沙星的溶解度和使用的稳定性,保证了药液的活性成分含量和抗菌效果,所得诺氟沙星滴眼剂对细菌感染性眼部疾病,特别是由耐药菌引起的感染性眼部疾病具有较好的治疗效果。
Description
技术领域
本发明专利属于药物制剂技术领域,具体涉及一种诺氟沙星滴眼剂及其制备方法。
背景技术
随着社会工业化的发展,空气污染日益严重,由细菌、支原体、立克次体、螺旋体等病原体引起的感染性眼部疾病日益增多,呈显著上升趋势。诺氟沙星作为第三代氟喹诺酮类广谱抗菌药,能够快速杀灭需氧革兰氏阴性杆菌,治愈感染引起的结膜炎、角膜炎和角膜溃疡等疾病,特别是对青霉素耐药的淋病奈瑟球菌、流感嗜血杆菌和卡他莫拉菌等致病菌引起的感染亦具有良好的治疗效果,不易产生细菌耐药性。
发明内容
本发明提供了一种诺氟沙星滴眼剂及其制备方法,所得到的产品可治愈由淋病奈瑟球菌、流感嗜血杆菌、卡他莫拉菌等致病菌引起的结膜炎、角膜炎和角膜溃疡等疾病;制备方法工艺简单易行,产品质量符合相关规定要求。
为实现本发明的目的,提供了如下具体技术方案:
根据本发明的一个方面,提供了一种诺氟沙星滴眼剂,其特征在于,每1L所述滴眼剂中含有诺氟沙星2.4~3.5g,并且用pH调节剂调节pH值至5.0~5.6。
优选地,所述pH调节剂选自醋酸钠、氢氧化钠、氢氧化钾、磷酸二氢钠、磷酸氢二钠、硼酸、硼砂、乳酸、枸橼酸中的至少一种。进一步优选地,所述pH调节剂为醋酸钠。
优选地,每1L所述滴眼剂中还含有渗透压调节剂;所述渗透压调节剂选自氯化钠、氯化钾、硫酸钠、硫酸钾、硝酸钠、硝酸钾、甘油、甘露醇、硼酸、硼砂、葡萄糖中的至少一种。进一步优选地,所述渗透压调节剂为氯化钠。
优选地,每1L所述滴眼剂中还含有防腐剂,所述防腐剂选自苯扎氯铵、苯扎溴铵、羟苯甲脂、羟苯乙酯、羟苯丙酯、三氯叔丁醇、苯甲酸、苯甲酸钠中的至少一种。进一步优选地,所述防腐剂为三氯叔丁醇。
优选地,每1L所述滴眼剂中还含有金属离子络合剂,所述金属离子络合剂选自依地酸二钠或酒石酸。进一步优选地,所述金属离子络合剂为依地酸二钠。
作为一个优选的实施方式,每1L所述滴眼剂含有如下组分:
诺氟沙星2.4~3.5g、氯化钠6.8~8.5g、依地酸二钠0.1~0.3g、三氯叔丁醇2.0~3.0g,并用pH调节剂醋酸钠调节pH值至5.0~5.6。
根据本申请的又一个方面,提供了上述任一种诺氟沙星滴眼剂的制备方法。该方法采用主药和辅料分别配制的工艺,避免了诺氟沙星在制备过程中析出而对产品工艺稳定性产生的负面影响。所述方法,先将诺氟沙星溶解于盐酸溶液中,得到的诺氟沙星盐酸溶液再与注射用水和选自等渗调节剂、金属离子络合剂、防腐剂中的至少一种混合,得到所述诺氟沙星滴眼剂。
优选地,所述方法包括以下步骤:
(1)将诺氟沙星溶解于1.0~1.5mol/L的盐酸溶液中,得到的溶液A;将等渗调节剂、金属离子络合剂、防腐剂的至少一种溶解于注射用水中,得到的溶液B;
(2)将步骤(1)中得到的溶液A与溶液B混合,得到溶液C;
(3)用pH调节剂调节步骤(2)中得到的溶液C的pH值至5.0~5.6,得到溶液D;
(4)过滤除菌,灌装后即得成品。
优选地,配制所述溶液A的诺氟沙星与盐酸溶液的重量/体积比为0.83kg/L~1.2kg/L;所述溶液D中的诺氟沙星的含量为2.4g/L~3.5g/L。
作为一个具体的实施方式,所述方法由以下步骤组成:
(1)称取3.0g诺氟沙星后,加入1.0mol/L盐酸3.5mL使其完全溶解,得到的溶液A;7.42g氯化钠,2.72g醋酸钠,0.1g依地酸二钠和3.0g三氯叔丁醇与注射用水加热搅拌至全溶,得到的溶液B;
(2)将步骤(1)中得到的溶液A与溶液B混合,得到溶液C;
(3)向步骤(2)中得到的溶液C加入注射用水至1L,搅拌均匀,得到溶液D;
(4)将步骤(3)中得到的溶液D依次经5μm钛棒过滤器、0.45μm微孔过滤膜和0.22μm微孔过滤膜,无菌灌装后即得成品。
本发明的一种具体实施方式中,诺氟沙星滴眼剂的制备方法采用主、辅料单独配置方法,首先依次准确称量等渗调节剂氯化钠,pH调节剂醋酸钠,金属离子络合剂依地酸二钠,防腐剂三氯叔丁醇,投入配料罐中,加入注射用水加热搅拌至均匀。
由于诺氟沙星在水中溶解度小,故而另外单独准确称取一定量的诺氟沙星,完全溶解于盐酸溶液中,增大了诺氟沙星的溶解度,避免制备过程中的诺氟沙星析出问题。具体地,主、辅料溶液混合后,加入注射用水至全量,搅拌均匀,使得药液浓度为3.0g/L,pH范围为5.0~5.6,解决了诺氟沙星在生产和使用过程中易受溶液pH的影响而析出的问题,保证了药液的治疗含量和抗菌效果。中间产品检验合格后,经无菌灌装、包装后即得成品。
本发明制备工艺流程简单易行,提高了诺氟沙星的溶解度和使用的稳定性,保证了药液的活性成分含量和抗菌效果,所得诺氟沙星滴眼剂对细菌感染性眼部疾病,特别是由耐药菌引起的感染性眼部疾病具有较好的治疗效果。
附图说明
图1为本发明提出的诺氟沙星滴眼剂制备工艺流程图
具体实施方式
以下结合具体实例对本发明的技术方案做进一步说明,有助于理解本发明,但并不限制本发明的内容。在本发明中所使用的术语,除非另有说明,一般具有本领域普通技术人员通常理解的含义。
实施例1
按照图1所示的操作步骤,制备浓度为3.0g/L,pH在5.0~5.6内的诺氟沙星滴眼剂,步骤如下:
(1)按照表1所示的配比,准确称取诺氟沙星原料药后,加入1.0mol/L盐酸3.5mL使其完全溶解,得到诺氟沙星溶液;
(2)依次准确称取表1中处方量的氯化钠,醋酸钠,依地酸二钠和三氯叔丁醇投入配料罐中,加入适量注射用水加热搅拌至全溶;
(3)将步骤(1)得到的诺氟沙星溶液加入至配料罐中,加入注射用水至1L,搅拌均匀;
(4)依次经5μm钛棒过滤器,0.45μm微孔过滤膜,0.22μm微孔过滤膜,无菌灌装后即得成品。
实施例2~8
实施例2~实施例8的操作与实施例1一致,区别是原料种类和配比。实施例1~8的原料种类和配比见表1所示。
表1
对比例1
原料种类和配比与实施例1一致,区别是没有主药、辅料分别配制过程,直接将原料一步配制成滴眼剂。在配制过程中有诺氟沙星析出现象。
实施例9
实施例1~8制备得到的诺氟沙星滴眼剂符合中华人民共和国药典(2010版)二部标准质量要求。实施例1~8和对比例1制备得到的诺氟沙星滴眼剂的具体分析检测见表2和表3所示,可见实施例1~8能够有效避免配制过程中有诺氟沙星析出现象,进而使得pH、渗透压、及药物含量均比对比例1更加符合要求,提高了生产制备过程中的质量控制能力。
表2
表3
以上所述,仅是本申请的几个实施例,并非对本申请做任何形式的限制,虽然本申请以较佳实施例揭示如上,然而并非用以限制本申请,任何熟悉本专业的技术人员,在不脱离本申请技术方案的范围内,利用上述揭示的技术内容做出些许的变动或修饰均等同于等效实施案例,均属于技术方案范围内。
Claims (10)
1.一种诺氟沙星滴眼剂,其特征在于,每1L所述滴眼剂中含有诺氟沙星2.4~3.5g,并且用pH调节剂调节pH值至5.0~5.6。
2.根据权利要求1所述的诺氟沙星滴眼剂,其特征在于,所述pH调节剂选自醋酸、醋酸钠、氢氧化钠、氢氧化钾、磷酸二氢钠、磷酸氢二钠、硼酸、硼砂、乳酸、枸橼酸中的至少一种。
3.根据权利要求1所述的诺氟沙星滴眼剂,其特征在于,每1L所述滴眼剂中还含有渗透压调节剂;所述渗透压调节剂选自氯化钠、氯化钾、硫酸钠、硫酸钾、硝酸钠、硝酸钾、甘油、甘露醇、硼酸、硼砂、葡萄糖中的至少一种。
4.根据权利要求1所述的诺氟沙星滴眼剂,其特征在于,每1L所述滴眼剂中还含有防腐剂;所述防腐剂选自苯扎氯铵、苯扎溴铵、羟苯甲脂、羟苯乙酯、羟苯丙酯、三氯叔丁醇、苯甲酸、苯甲酸钠中的至少一种。
5.根据权利要求1所述的诺氟沙星滴眼剂,其特征在于,每1L所述滴眼剂中还含有金属离子络合剂,所述金属离子络合剂选自依地酸二钠或酒石酸。
6.根据权利要求1所述的诺氟沙星滴眼剂,其特征在于,每1L所述滴眼剂含有如下组分:
诺氟沙星2.4~3.5g、氯化钠6.8~8.5g、依地酸二钠0.1~0.3g、三氯叔丁醇2.0~3.0g,并用pH调节剂醋酸钠调节pH值至5.0~5.6。
7.一种权利要求1至6任一项所述诺氟沙星滴眼剂的制备方法,其特征在于,先将诺氟沙星溶解于盐酸溶液中,得到的诺氟沙星盐酸溶液再与注射用水和选自等渗调节剂、金属离子络合剂、防腐剂中的至少一种混合,得到所述诺氟沙星滴眼剂。
8.根据权利要求7所述的方法,其特征在于,包括以下步骤:
(1)将诺氟沙星溶解于1.0~1.5mol/L的盐酸溶液中,得到的溶液A;将等渗调节剂、金属离子络合剂、防腐剂的至少一种溶解于注射用水中,得到的溶液B;
(2)将步骤(1)中得到的溶液A与溶液B混合,得到溶液C;
(3)用pH调节剂调节步骤(2)中得到的溶液C的pH值至5.0~5.6,得到溶液D;
(4)过滤除菌,灌装后即得成品。
9.根据权利要求7所述的方法,其特征在于,配制所述溶液A中的诺氟沙星与盐酸溶液的重量/体积比为0.83kg/L~1.2kg/L;所述溶液D中的诺氟沙星的含量为2.4g/L~3.5g/L。
10.根据权利要求7所述的方法,其特征在于,由以下步骤组成:
(1)称取3.0g诺氟沙星后,加入1.0mol/L盐酸3.5mL使其完全溶解,得到的溶液A;称取7.42g氯化钠,2.72g醋酸钠,0.1g依地酸二钠和3.0g三氯叔丁醇与注射用水加热搅拌至全溶,得到的溶液B;
(2)将步骤(1)中得到的溶液A与溶液B混合,得到溶液C;
(3)向步骤(2)中得到的溶液C加入注射用水至1L,搅拌均匀,得到溶液D;
(4)将步骤(3)中得到的溶液D依次经5μm钛棒过滤器、0.45μm微孔过滤膜和0.22μm微孔过滤膜,无菌灌装后即得成品。
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