CN113712913A - 一种奥泽沙星混悬滴眼液组合物 - Google Patents
一种奥泽沙星混悬滴眼液组合物 Download PDFInfo
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- CN113712913A CN113712913A CN202010447776.3A CN202010447776A CN113712913A CN 113712913 A CN113712913 A CN 113712913A CN 202010447776 A CN202010447776 A CN 202010447776A CN 113712913 A CN113712913 A CN 113712913A
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- 239000000203 mixture Substances 0.000 title claims abstract description 18
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- 229950011011 ozenoxacin Drugs 0.000 claims abstract description 32
- 230000003204 osmotic effect Effects 0.000 claims abstract description 9
- 239000003755 preservative agent Substances 0.000 claims abstract description 5
- 230000002335 preservative effect Effects 0.000 claims abstract description 5
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 24
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- -1 polyoxyethylene Polymers 0.000 claims description 9
- 239000000243 solution Substances 0.000 claims description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 6
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 6
- 229960000686 benzalkonium chloride Drugs 0.000 claims description 6
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 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
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 4
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- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 claims description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 2
- GHXZTYHSJHQHIJ-UHFFFAOYSA-N Chlorhexidine Chemical compound C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 GHXZTYHSJHQHIJ-UHFFFAOYSA-N 0.000 claims description 2
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- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 2
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- 229960002233 benzalkonium bromide 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
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- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 4
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- DDHVILIIHBIMQU-YJGQQKNPSA-L mupirocin calcium hydrate Chemical compound O.O.[Ca+2].C[C@H](O)[C@H](C)[C@@H]1O[C@H]1C[C@@H]1[C@@H](O)[C@@H](O)[C@H](C\C(C)=C\C(=O)OCCCCCCCCC([O-])=O)OC1.C[C@H](O)[C@H](C)[C@@H]1O[C@H]1C[C@@H]1[C@@H](O)[C@@H](O)[C@H](C\C(C)=C\C(=O)OCCCCCCCCC([O-])=O)OC1 DDHVILIIHBIMQU-YJGQQKNPSA-L 0.000 description 1
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- 239000002674 ointment Substances 0.000 description 1
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- 230000008261 resistance mechanism Effects 0.000 description 1
- 206010040872 skin infection Diseases 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 229960003165 vancomycin Drugs 0.000 description 1
- MYPYJXKWCTUITO-LYRMYLQWSA-N vancomycin Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@@H](CC(C)C)NC)[C@H]1C[C@](C)(N)[C@H](O)[C@H](C)O1 MYPYJXKWCTUITO-LYRMYLQWSA-N 0.000 description 1
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Classifications
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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
- A61K9/10—Dispersions; Emulsions
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
-
- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Dispersion Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Ophthalmology & Optometry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明提供一种奥泽沙星滴眼液组合物，该组合物由渗透压调节剂、高分子化合物、酸碱调节剂、防腐剂等组成，该滴眼液临床疗效好，安全可靠，产品性质稳定。
Description
技术领域
本发明涉及眼科用药技术领域，特别涉及一种奥泽沙星混悬滴眼液组合物及其制备方法。
背景技术
奥泽沙星(Ozenoxacin)是新的非氟化喹诺酮化合物，其已显示对抗革兰氏阳性有机体，包括普通喹诺酮-抗性细菌的高水平活性。由于其双重靶向作用机理，奥泽沙星对某些抗性的突变型菌株具有活性。因此，由于其针对抗性革兰氏阳性细菌的高活性，奥泽沙星是绕开对抗生素的现有抗性机理的良好抗菌剂候选者。
奥泽沙星是继奈诺沙星、加雷沙星后全球第3个获批的非氟喹诺酮类抗菌药物。对MRSA、甲氧西林敏感金葡菌(MSSA)、耐氧氟沙星金葡菌、甲氧西林敏感和耐药表葡菌、耐氧氟沙星表葡菌的DNA旋转酶和拓扑异构酶Ⅳ的抑制作用明显强于那氟沙星、氧氟沙星、左氧氟沙星、氯林可霉素、红霉素和庆大霉素。不良反应更低，抗菌谱更广，并对耐甲氧西林金黄色葡萄球菌（MRSA），耐万古霉素的金黄葡萄球菌（VRSA），耐喹诺酮类药物金黄葡萄球菌（QRSA），耐青霉素肺炎链球菌（PRSP），喹诺酮耐药肺炎链球菌（QRSP）等耐药菌有很强的活性。
临床试验将本品软膏剂用于治疗皮肤和软组织感染，疗效优于莫匹罗星，无明显不良反应。本品杀菌活性较强，可能成为缩短疗程，且具有良好临床应用前景的喹诺酮类新药。
目前没有发现将奥泽沙星用于滴眼液，本发明的奥泽沙星滴眼液更具有临床应用前景。
发明内容
本发明为了弥补现有技术的不足，提供了一种奥泽沙星混悬滴眼液组合物及其制备方法。
本发明是通过如下技术方案实现的：
一种奥泽沙星混悬滴眼液组合物其组份包括以下重量分数的组分：奥泽沙星0.2～5.0，渗透压调节剂2.0-3.0，助悬剂0.2-2.0，pH调节剂6-7，表面活性剂剂0.01-1.0；防腐剂0.01-1.0；上述组分pH是6.0至7.0，渗透压摩尔浓度为280mOsmol/kg至320mOsmol/kg。
所述渗透压调节剂为选自甘油、丙二醇、氯化钠、氯化钾、山梨糖醇、甘露醇。中的一种或几种。
其中奥泽沙星滴眼液组合物所述pH调节剂为盐酸、枸橼酸、氢氧化钠、磷酸二氢钠、磷酸氢二钠中的一种或几种。
其中奥泽沙星滴眼液组合物所述防腐剂为苯扎氯铵、苯扎溴铵、氯已定中的一种或几种。
其中奥泽沙星滴眼液组合物所述助悬剂选自羧甲基纤维素钠、羟丙基甲基纤维素、羟丙基纤维素、羟乙基纤维素、聚乙烯基醇、羧乙烯聚合物、右旋糖酐、聚乙烯基吡咯烷酮、卡波姆中的一种或几种。
其中奥泽沙星滴眼液组合物所述表面活性剂选自吐温－80、聚氧乙烯蓖麻油60、聚氧乙烯氢化蓖麻油60、聚乙二醇－硬脂酸酯、聚乙二醇、卵磷脂、蔗糖酯、聚氧乙烯烷基醚、聚氧硬脂酸盐、聚氧乙烯一聚氧丙烯二醇、泰洛沙泊中的一种或几种。
奥泽沙星滴眼液组合物的制备方法包括以下步骤：
（1）首先依次将pH调节剂、渗透压调节剂、奥泽沙星加入适量水中，持续搅拌至溶解；
（2）将增稠剂加入适量水中，持续搅拌至分散均匀后加入防腐剂；
（3）将上述两溶液混合后持续搅拌；滴加氢氧化钠调节上述溶液pH至6.5，再补加至足量注射用水；
（4）分装后加盖包装。
（四）具体实施方式
实施例1
包含以下组分：
奥泽沙星1.0w/v%，依地酸二钠0.1 w/v%，丙二醇2.5 w/v%，苯扎氯铵0.0001 w/v%，聚乙烯基吡咯烷酮1.0w/v%，氢氧化钠pH调至6.5，加入注射用水至体积100%；
按上述配比制备奥泽沙星滴眼液，包括以下具体步骤：
①首先加入依地酸二钠、聚乙烯基吡咯烷酮、依地酸二钠，搅拌溶解后再加入苯扎氯铵，持续搅拌；
②将丙二醇加入上述溶液中，搅拌至溶解；
③加入奥泽沙星，持续搅拌至溶解完全；
④滴加氢氧化钠调节上述溶液pH至6.5，再补加至足量注射用水。
⑤分装后加盖包装。
实施例2
包含以下组分：
奥泽沙星0.5w/v%，依地酸二钠0.1 w/v%，丙二醇2.5 w/v%，苯扎氯铵0.0001 w/v%，聚乙烯基吡咯烷酮1.0w/v%，氢氧化钠pH调至6.5，加入注射用水至体积100%；
制备方法与实施例1相同。
实施例3
包含以下组分：
奥泽沙星2.0w/v%，依地酸二钠0.1 w/v%，丙二醇2.5 w/v%，苯扎氯铵0.0001 w/v%，聚乙烯基吡咯烷酮1.0w/v%，氢氧化钠pH调至6.5，加入注射用水至体积100%；
制备方法与实施例1相同。
上面以举例方式对本发明进行了说明，但本发明不限于上述具体实施例，凡基于本发明所做的任何改动或变型均属于本发明要求保护的范围。
Claims (7)
1.一种奥泽沙星混悬滴眼液组合物，其特征在于：包括以下重量分数的组分：奥泽沙星0.2-5，渗透压调节剂50-55，增稠剂50-55，pH调节剂8-11，防腐剂0.01-1；上述组分pH是6.0至7.0，渗透压摩尔浓度为280mOsmol/kg至320mOsmol/kg。
2.根据权利要求1所述的奥泽沙星滴眼液组合物，其特征在于：所述渗透压调节剂为选自甘油、丙二醇、氯化钠、氯化钾、山梨糖醇、甘露醇中的一种或几种。
3.根据权利要求1所述的奥泽沙星滴眼液组合物，其特征在于：所述pH调节剂为盐酸、枸橼酸、氢氧化钠、磷酸二氢钠、磷酸氢二钠中的一种或几种。
4.根据权利要求1所述的奥泽沙星滴眼液组合物，其特征在于：所述防腐剂为苯扎氯铵、苯扎溴铵、氯已定中的一种或几种。
5.根据权利要求1所述的奥泽沙星滴眼液组合物，其特征在于：所述助悬剂选自羧甲基纤维素钠、羟丙基甲基纤维素、羟丙基纤维素、羟乙基纤维素、聚乙烯基醇、羧乙烯聚合物、右旋糖酐、聚乙烯基吡咯烷酮、卡波姆、玻璃酸钠、泊洛沙姆中的一种或几种。
6.根据权利要求1所述的奥泽沙星滴眼液组合物，其特征在于：所述表面活性剂选自吐温－80、聚氧乙烯蓖麻油60、聚氧乙烯氢化蓖麻油60、聚乙二醇－硬脂酸酯、聚乙二醇、卵磷脂、蔗糖酯、聚氧乙烯烷基醚、聚氧硬脂酸盐、聚氧乙烯一聚氧丙烯二醇、泰洛沙泊中的一种或几种。
7.根据权利要求1所述的奥泽沙星滴眼液组合物的制备方法，其特征在于：
（1）首先依次将pH调节剂、表面活性剂、渗透压调节剂、加入适量水中，持续搅拌至溶解；
（2）将助悬剂加入适量水中，持续搅拌至分散均匀后加入防腐剂；
（3）将上述两溶液混合后，加入奥泽沙星；持续搅拌滴加氢氧化钠调节上述溶液pH至6.5，再补加至足量注射用水；
（4）分装后加盖包装。
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003226643A (ja) * | 2001-11-30 | 2003-08-12 | Toyama Chem Co Ltd | デスフルオロピリドンカルボン酸系化合物を含有する水溶液剤およびその粉末化物並びにそれら製造方法 |
| JP2007119456A (ja) * | 2005-09-30 | 2007-05-17 | Toyama Chem Co Ltd | 難溶性薬物のナノ微粒子を含有する水性懸濁液剤 |
| CN102186460A (zh) * | 2008-10-17 | 2011-09-14 | 菲尔若国际公司 | 药物局部组合物 |
| TW202017587A (zh) * | 2018-06-21 | 2020-05-16 | 美商路布里斯公司 | 用於促進傷口癒合之潤滑素(lubricin) |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003226643A (ja) * | 2001-11-30 | 2003-08-12 | Toyama Chem Co Ltd | デスフルオロピリドンカルボン酸系化合物を含有する水溶液剤およびその粉末化物並びにそれら製造方法 |
| JP2007119456A (ja) * | 2005-09-30 | 2007-05-17 | Toyama Chem Co Ltd | 難溶性薬物のナノ微粒子を含有する水性懸濁液剤 |
| CN102186460A (zh) * | 2008-10-17 | 2011-09-14 | 菲尔若国际公司 | 药物局部组合物 |
| TW202017587A (zh) * | 2018-06-21 | 2020-05-16 | 美商路布里斯公司 | 用於促進傷口癒合之潤滑素(lubricin) |
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