CN1562030A - Gatiflxacin eye gels based on HPMC medium and its preparing method - Google Patents
Gatiflxacin eye gels based on HPMC medium and its preparing method Download PDFInfo
- Publication number
- CN1562030A CN1562030A CN 200410020427 CN200410020427A CN1562030A CN 1562030 A CN1562030 A CN 1562030A CN 200410020427 CN200410020427 CN 200410020427 CN 200410020427 A CN200410020427 A CN 200410020427A CN 1562030 A CN1562030 A CN 1562030A
- Authority
- CN
- China
- Prior art keywords
- hpmc
- gatifloxacin
- gel
- preparation
- matrix
- 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.)
- Granted
Links
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 title claims abstract 10
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 title claims abstract 10
- 239000000499 gel Substances 0.000 title 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 22
- XUBOMFCQGDBHNK-JTQLQIEISA-N (S)-gatifloxacin Chemical compound FC1=CC(C(C(C(O)=O)=CN2C3CC3)=O)=C2C(OC)=C1N1CCN[C@@H](C)C1 XUBOMFCQGDBHNK-JTQLQIEISA-N 0.000 claims abstract description 20
- 229960003923 gatifloxacin Drugs 0.000 claims abstract description 20
- 238000002360 preparation method Methods 0.000 claims abstract description 16
- 238000003756 stirring Methods 0.000 claims abstract description 14
- 239000000758 substrate Substances 0.000 claims abstract description 9
- -1 isotonic regulator Substances 0.000 claims abstract description 7
- 239000011159 matrix material Substances 0.000 claims abstract description 7
- 239000003961 penetration enhancing agent Substances 0.000 claims abstract description 7
- 239000012982 microporous membrane Substances 0.000 claims abstract description 3
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims abstract 9
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims abstract 9
- 229940100655 ophthalmic gel Drugs 0.000 claims abstract 5
- 239000003755 preservative agent Substances 0.000 claims abstract 4
- 230000002335 preservative effect Effects 0.000 claims abstract 3
- 239000003002 pH adjusting agent Substances 0.000 claims abstract 2
- 239000007787 solid Substances 0.000 claims abstract 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical group [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 14
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical group [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
- 229960002233 benzalkonium bromide Drugs 0.000 claims description 7
- KHSLHYAUZSPBIU-UHFFFAOYSA-M benzododecinium bromide Chemical compound [Br-].CCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 KHSLHYAUZSPBIU-UHFFFAOYSA-M 0.000 claims description 7
- 239000011780 sodium chloride Substances 0.000 claims description 7
- 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
- 239000000203 mixture Substances 0.000 claims description 6
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 5
- 229920000609 methyl cellulose Polymers 0.000 claims description 5
- 239000001923 methylcellulose Substances 0.000 claims description 5
- 229960002900 methylcellulose Drugs 0.000 claims description 5
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 claims description 4
- GSDSWSVVBLHKDQ-JTQLQIEISA-N Levofloxacin Chemical compound C([C@@H](N1C2=C(C(C(C(O)=O)=C1)=O)C=C1F)C)OC2=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-JTQLQIEISA-N 0.000 claims 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 claims description 3
- AXTGDCSMTYGJND-UHFFFAOYSA-N 1-dodecylazepan-2-one Chemical compound CCCCCCCCCCCCN1CCCCCC1=O AXTGDCSMTYGJND-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
- 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 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
- 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 claims description 2
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 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
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 2
- QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 claims description 2
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 claims description 2
- 229960000583 acetic acid Drugs 0.000 claims description 2
- 229960000686 benzalkonium chloride 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
- 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 claims description 2
- 229960004926 chlorobutanol Drugs 0.000 claims description 2
- 229960003964 deoxycholic acid Drugs 0.000 claims description 2
- KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 claims description 2
- 229940089161 ginsenoside Drugs 0.000 claims description 2
- 229930182494 ginsenoside Natural products 0.000 claims description 2
- 239000012362 glacial acetic acid Substances 0.000 claims description 2
- 239000008103 glucose Substances 0.000 claims description 2
- 229960003639 laurocapram Drugs 0.000 claims description 2
- 239000000594 mannitol Substances 0.000 claims description 2
- 235000010355 mannitol Nutrition 0.000 claims description 2
- 229960001180 norfloxacin Drugs 0.000 claims description 2
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 claims description 2
- 229960000502 poloxamer Drugs 0.000 claims description 2
- 229920001983 poloxamer Polymers 0.000 claims description 2
- 239000001509 sodium citrate Substances 0.000 claims description 2
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 claims description 2
- 239000000600 sorbitol Substances 0.000 claims description 2
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 claims description 2
- 229940033663 thimerosal Drugs 0.000 claims description 2
- 238000005303 weighing Methods 0.000 claims description 2
- 235000010981 methylcellulose Nutrition 0.000 claims 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 claims 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 claims 1
- 229920002385 Sodium hyaluronate Polymers 0.000 claims 1
- 229960003260 chlorhexidine Drugs 0.000 claims 1
- 230000007423 decrease Effects 0.000 claims 1
- 230000006355 external stress Effects 0.000 claims 1
- 239000012530 fluid Substances 0.000 claims 1
- 239000000661 sodium alginate Substances 0.000 claims 1
- 235000010413 sodium alginate Nutrition 0.000 claims 1
- 229940005550 sodium alginate Drugs 0.000 claims 1
- 229940010747 sodium hyaluronate Drugs 0.000 claims 1
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 abstract description 9
- 208000001860 Eye Infections Diseases 0.000 abstract description 4
- 206010010741 Conjunctivitis Diseases 0.000 abstract description 3
- 206010023332 keratitis Diseases 0.000 abstract description 3
- 206010064996 Ulcerative keratitis Diseases 0.000 abstract description 2
- 208000010217 blepharitis Diseases 0.000 abstract description 2
- 201000007717 corneal ulcer Diseases 0.000 abstract description 2
- 208000011323 eye infectious disease Diseases 0.000 abstract description 2
- 208000008025 hordeolum Diseases 0.000 abstract description 2
- 239000000463 material Substances 0.000 abstract description 2
- 206010044325 trachoma Diseases 0.000 abstract description 2
- 230000001225 therapeutic effect Effects 0.000 abstract 2
- 206010011844 Dacryocystitis Diseases 0.000 abstract 1
- 239000013543 active substance Substances 0.000 abstract 1
- 239000003732 agents acting on the eye Substances 0.000 abstract 1
- 201000001371 inclusion conjunctivitis Diseases 0.000 abstract 1
- 230000007794 irritation Effects 0.000 abstract 1
- 231100000053 low toxicity Toxicity 0.000 abstract 1
- 229940023490 ophthalmic product Drugs 0.000 abstract 1
- 229940021506 stye Drugs 0.000 abstract 1
- 210000001508 eye Anatomy 0.000 description 21
- 239000000243 solution Substances 0.000 description 14
- 239000003814 drug Substances 0.000 description 7
- 238000012856 packing Methods 0.000 description 6
- 230000001105 regulatory effect Effects 0.000 description 6
- 238000005070 sampling Methods 0.000 description 6
- 239000012528 membrane Substances 0.000 description 5
- 230000002924 anti-infective effect Effects 0.000 description 4
- 230000002421 anti-septic effect Effects 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000002260 anti-inflammatory agent Substances 0.000 description 3
- 229960005475 antiinfective agent Drugs 0.000 description 3
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 3
- 239000004327 boric acid Substances 0.000 description 3
- 239000003885 eye ointment Substances 0.000 description 3
- 208000035143 Bacterial infection Diseases 0.000 description 2
- 208000022362 bacterial infectious disease Diseases 0.000 description 2
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000003889 eye drop Substances 0.000 description 2
- 229960003376 levofloxacin Drugs 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 150000007660 quinolones Chemical class 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- GSDSWSVVBLHKDQ-UHFFFAOYSA-N 9-fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid Chemical compound FC1=CC(C(C(C(O)=O)=C2)=O)=C3N2C(C)COC3=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-UHFFFAOYSA-N 0.000 description 1
- 206010017533 Fungal infection Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- OJMMVQQUTAEWLP-UHFFFAOYSA-N Lincomycin Natural products CN1CC(CCC)CC1C(=O)NC(C(C)O)C1C(O)C(O)C(O)C(SC)O1 OJMMVQQUTAEWLP-UHFFFAOYSA-N 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- 241000390203 Trachoma Species 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 210000005252 bulbus oculi Anatomy 0.000 description 1
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 1
- 229940097572 chloromycetin Drugs 0.000 description 1
- 229960003405 ciprofloxacin Drugs 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- OJMMVQQUTAEWLP-KIDUDLJLSA-N lincomycin Chemical compound CN1C[C@H](CCC)C[C@H]1C(=O)N[C@H]([C@@H](C)O)[C@@H]1[C@H](O)[C@H](O)[C@@H](O)[C@@H](SC)O1 OJMMVQQUTAEWLP-KIDUDLJLSA-N 0.000 description 1
- 229960005287 lincomycin Drugs 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
- 230000000813 microbial effect Effects 0.000 description 1
- 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 description 1
- 229960001699 ofloxacin Drugs 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- NLVFBUXFDBBNBW-PBSUHMDJSA-N tobramycin Chemical compound N[C@@H]1C[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N NLVFBUXFDBBNBW-PBSUHMDJSA-N 0.000 description 1
- 229960000707 tobramycin Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 229940099259 vaseline Drugs 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
本发明涉及一种以HPMC为基质的加替沙星眼用凝胶剂及其制备方法。该凝胶剂相溶性好，它以加替沙星为活性物质，以亲水性高分子材料羟丙基甲基纤维素(HPMC)为基质，同时加入防腐剂、等渗调节剂、渗透促进剂、pH调节剂及水而制得。将加替沙星溶解于水，再加入基质、防腐剂、等渗调节剂、渗透促进剂搅拌溶解，用pH调节剂调节pH为5－9，溶液通过微孔滤膜过滤再从滤器上加水至总量。该制剂适用于治疗眼睑炎、麦粒肿、结膜炎、泪囊炎、角膜炎、角膜溃疡、沙眼等眼部感染。该凝胶剂为流动的半固体，使用方便，在眼内停留时间长，不易流失，能维持有效治疗浓度，增强治疗效果，且毒性低、刺激性小，是一个有效的眼用新药，具有良好的临床应用前景。The invention relates to a gatifloxacin ophthalmic gel with HPMC as a matrix and a preparation method thereof. The gel has good compatibility. It uses gatifloxacin as the active substance and the hydrophilic macromolecular material hydroxypropyl methylcellulose (HPMC) as the matrix. agent, pH adjuster and water. Dissolve gatifloxacin in water, then add substrate, preservative, isotonic regulator, penetration enhancer and stir to dissolve, adjust pH to 5-9 with pH regulator, filter the solution through a microporous membrane and add water from the filter to the total. The preparation is suitable for treating eye infections such as blepharitis, stye, conjunctivitis, dacryocystitis, keratitis, corneal ulcer and trachoma. The gel is a flowing semi-solid, easy to use, stays in the eye for a long time, is not easy to lose, can maintain the effective therapeutic concentration, enhance the therapeutic effect, and has low toxicity and irritation. It is an effective new ophthalmic drug with Good prospects for clinical application.
Description
Technical field:
The invention belongs to medical technical field, relating to a kind of is the Gatifloxacin gel for eye and preparation method thereof of substrate with HPMC.
Background technology:
According to statistics, the patient more than 80% is that ophthalmology infects in the patient that ophthalmology is gone to a doctor.Ophthalmology infects and comprises conjunctivitis, keratitis and global inflammation etc.; Divide from pathogen, comprise bacterial infection and fungal infection.Bacterial infection can use anti-infectives, but owing to there is blood-ocular barrier, causes medicine can not all penetrate ophthalmic, and the drug level in the eye inner tissue is low.Therefore the anti-infective that is used for ophthalmology is the good anti-infectives of those permeabilitys, as tobramycin, lincomycin and chloromycetin etc.In recent years, quinolones increases rapidly in the application of ophthalmology, as ofloxacin, levofloxacin, norfloxacin, ciprofloxacin etc.Gatifloxacin be the 4th generation quinolones, has a broad antifungal spectrum, side effect is little, has vast market prospect.
Current clinical anti-infectives commonly used is conventional dosage forms such as eye drop and eye ointment mostly.Eye drop after the administration, by tear is diluted to 0.1% of original concentration in a few minutes as the most frequently used dosage form of ophthalmology, bioavailability is low, only is 1%-10%, therefore needs to increase the eye dripping frequency, the patient uses inconvenience, poor compliance, and may cause general toxic reaction.Though the eye ointment release is slow, owing to being substrate with vaseline, greasy feeling is strong easily to produce " paste is looked " phenomenon, thereby the not very willing use of patient.And gel for eye adopts hydrophilic matrix, excellent biological compatibility is arranged, zest is little, some advantages that not only have Eye ointments, as increasing the time of contact in medicine and affected part, the effect time limit of prolong drug, and can alleviate medicine to the friction of eyeball with overcome the problem of " paste is looked ".The development work that this just impels people to carry out eye-gel preparation, for example, the Chinese patent CN1374085A of Zhao new people's application is a kind of aseptic eye-gel preparation, its effective ingredient is a levofloxacin, is mainly used in non-treatment ocular infection.
Summary of the invention:
The purpose of this invention is to provide a kind of is the Gatifloxacin gel for eye and preparation method thereof of substrate with HPMC.Gatifloxacin gel of the present invention (eye with) be a kind of be used for the treatment of ocular infection, water white transparency or flaxen semifluid gelatinous ophthalmic preparation, this gel within the eye the holdup time longer, be difficult for running off, can keep active drug concentration, and zest is little, toxicity is low, and the compatibility is good.It is an active component with the anti-inflammation agent, is aided with isoosmotic adjusting agent, pH regulator agent, antiseptic, thickening agent, water etc. and makes eye-gel preparation.
Gel of the present invention (eye is used), form by following component:
Constituent content (weight %)
Anti-inflammation agent 0.1-1
Substrate 0.1-40
Antiseptic 0.001-3
Isoosmotic adjusting agent 0.1-10
Penetration enhancer 0.005-20
It is the amount of 5-9 that the preparation pH value is regulated in the pH regulator agent
Water surplus
Active component in the gel for eye of the present invention is: Gatifloxacin
Substrate be selected from following: the mixture of one or more in hydroxypropyl emthylcellulose (HPMC), polyvinyl alcohol (PVA), hyaluronic acid sodium, the methylcellulose (MC) etc.;
Antiseptic be selected from following: the mixture of one or more in benzyl alcohol, chlorobutanol, thimerosal, hibitane, benzalkonium chloride, benzalkonium bromide, Metagin, second, the propyl ester etc.;
Isoosmotic adjusting agent is to be selected from sodium chloride, glucose, mannitol, sorbitol or suchlike material;
Penetration enhancer be selected from following: the mixture of one or more in sodium deoxycholate, laurocapram, HP-, disodiumedetate, Brij, ginsenoside, the poloxamer etc.;
The pH regulator agent is to adopt sodium hydroxide and/or hydrochloric acid, citric acid, sodium citrate, glacial acetic acid, triethanolamine etc.
The preparation method of gel for eye of the present invention
Step is as follows: by the weighing of above-mentioned prescription with anti-inflammation agent stirring and dissolving in water, add substrate, antiseptic, isoosmotic adjusting agent, penetration enhancer again, stirring makes dissolving, with pH regulator agent regulator solution pH value is 5-9, and solution adds water to total amount again by filtering with microporous membrane on filter, Quality Identification is carried out in sampling, after qualified, be sub-packed in eye drip with in the bottle under gnotobasis, packing promptly.
The physicochemical character of gel for eye product of the present invention is: water white transparency or flaxen mobile semisolid.
Advantage of the present invention is that this gel for eye is applicable to by multiple eye infections such as the pathogenic microbial blepharitis of sensitivity, hordeolum, conjunctivitis, dacryocystisis, keratitis, corneal ulcer, trachomas.Every day 1～2 time, be applied to ophthalmic with 0.5 inch gel respectively at every turn.This gel within the eye the holdup time longer, be difficult for to run off, can keep active drug concentration, and zest is little, toxicity is low, the compatibility is good.
The specific embodiment:
Following example will be further elaborated gel for eye of the present invention, but not limit content of the present invention.
Embodiment 1
Remove ionized water 39kg, add Gatifloxacin 0.15kg, stir and make dissolving.Get hydroxypropyl emthylcellulose 1kg, be sprinkled in the above-mentioned solution.Standing over night adds benzalkonium bromide 0.005kg again, sodium chloride 0.4kg, HP-2kg, stirring and dissolving.Regulating pH with 10%NaOH solution is 7.4, and solution adds water to total amount 50kg by the 0.22um microporous filter membrane on filter.Quality Identification is carried out in sampling, and qualified back is sub-packed in eye drip with in the bottle under gnotobasis, and packing promptly.
Embodiment 2
Remove ionized water 39kg, add Gatifloxacin 0.15kg, stir and make dissolving.Get hydroxypropyl emthylcellulose 4kg, be sprinkled in the above-mentioned solution.Standing over night adds benzalkonium bromide 0.005kg again, sodium chloride 0.4kg, HP-2kg, stirring and dissolving.Regulating pH with boric acid is 7, and solution adds water to total amount 50kg by the 0.22um microporous filter membrane on filter.Quality Identification is carried out in sampling, and qualified back is sub-packed in eye drip with in the bottle under gnotobasis, and packing promptly.
Embodiment 3
Remove ionized water 39kg, add Gatifloxacin 0.15kg, stir and make dissolving.Get methylcellulose 1kg, be sprinkled in the above-mentioned solution.Standing over night adds benzalkonium bromide 0.005kg again, sodium chloride 0.4kg, HP-2kg, stirring and dissolving.Regulating pH with 10%NaOH solution is 7, and solution adds water to total amount 50kg by the 0.22um microporous filter membrane on filter.Quality Identification is carried out in sampling, and qualified back is sub-packed in eye drip with in the bottle under gnotobasis, and packing promptly.
Embodiment 4
Remove ionized water 39kg, add Gatifloxacin 0.15kg, stir and make dissolving.Get hyaluronic acid sodium 1kg, be sprinkled in the above-mentioned solution.Standing over night adds benzalkonium bromide 0.005kg again, sodium chloride 0.4kg, HP-2kg, stirring and dissolving.Regulating pH with boric acid is 7, and solution adds water to total amount 50kg by the 0.22um microporous filter membrane on filter.Quality Identification is carried out in sampling, and qualified back is sub-packed in eye drip with in the bottle under gnotobasis, and packing promptly.
Embodiment 5
Remove ionized water 39kg, add Gatifloxacin 0.15kg, stir and make dissolving.Get polyvinyl alcohol 1kg, be sprinkled in the above-mentioned solution.Standing over night adds benzalkonium bromide 0.005kg again, sodium chloride 0.4kg, HP-2kg, stirring and dissolving.Regulating pH with boric acid is 7, and solution adds water to total amount 50kg by the 0.22um microporous filter membrane on filter.Quality Identification is carried out in sampling, and qualified back is sub-packed in eye drip with in the bottle under gnotobasis, and packing promptly.
Claims (4)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100204274A CN100427091C (en) | 2004-04-20 | 2004-04-20 | Gatifloxacin ophthalmic gel with HPMC as matrix and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100204274A CN100427091C (en) | 2004-04-20 | 2004-04-20 | Gatifloxacin ophthalmic gel with HPMC as matrix and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1562030A true CN1562030A (en) | 2005-01-12 |
| CN100427091C CN100427091C (en) | 2008-10-22 |
Family
ID=34479688
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2004100204274A Expired - Fee Related CN100427091C (en) | 2004-04-20 | 2004-04-20 | Gatifloxacin ophthalmic gel with HPMC as matrix and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100427091C (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1307995C (en) * | 2005-10-12 | 2007-04-04 | 周卓和 | Gatifloxacin eye drop and its preparing method |
| WO2007070413A1 (en) * | 2005-12-12 | 2007-06-21 | Allergan, Inc. | Treatment of corneal ulcers with topical gatifloxacin |
| WO2008044733A1 (en) | 2006-10-12 | 2008-04-17 | Kyorin Pharmaceutical Co., Ltd. | Aqueous liquid preparation having improved intraocular gatifloxacin penetration |
| WO2008044734A1 (en) * | 2006-10-12 | 2008-04-17 | Kyorin Pharmaceutical Co., Ltd. | Aqueous liquid preparation comprising gatifloxacin |
| WO2011063606A1 (en) | 2009-11-27 | 2011-06-03 | 沈阳兴齐制药有限公司 | Ophthalmic gel of gatifloxacin and preparation method thereof |
| WO2012068998A3 (en) * | 2010-11-24 | 2012-07-19 | 金健亚洲集团有限公司 | Triamcinolone acetonide ophthalmic preparation and preparation method thereof |
| CN103142463A (en) * | 2013-03-05 | 2013-06-12 | 宁夏康亚药业有限公司 | Eye medicament composition as well as preparation method and application thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1314452C (en) * | 2002-04-22 | 2007-05-09 | 沈阳药科大学 | Ocular in-situ gel preparatino with proper phase conversion temperature |
| CN1448137A (en) * | 2003-04-30 | 2003-10-15 | 江苏扬子江药业集团有限公司 | Gatifloxacin external and ophthalmic gel preparation |
-
2004
- 2004-04-20 CN CNB2004100204274A patent/CN100427091C/en not_active Expired - Fee Related
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1307995C (en) * | 2005-10-12 | 2007-04-04 | 周卓和 | Gatifloxacin eye drop and its preparing method |
| WO2007070413A1 (en) * | 2005-12-12 | 2007-06-21 | Allergan, Inc. | Treatment of corneal ulcers with topical gatifloxacin |
| WO2008044733A1 (en) | 2006-10-12 | 2008-04-17 | Kyorin Pharmaceutical Co., Ltd. | Aqueous liquid preparation having improved intraocular gatifloxacin penetration |
| WO2008044734A1 (en) * | 2006-10-12 | 2008-04-17 | Kyorin Pharmaceutical Co., Ltd. | Aqueous liquid preparation comprising gatifloxacin |
| CN101547695B (en) * | 2006-10-12 | 2011-04-27 | 杏林制药株式会社 | Aqueous liquid preparation having improved intraocular gatifloxacin penetration |
| EP2078526A4 (en) * | 2006-10-12 | 2011-08-10 | Kyorin Seiyaku Kk | AQUEOUS LIQUID PREPARATION WITH ENHANCED INTRAOCULAR GATIFLOXACIN PENETRATION |
| JP5245078B2 (en) * | 2006-10-12 | 2013-07-24 | 杏林製薬株式会社 | Aqueous solution with improved intraocular transfer of gatifloxacin |
| WO2011063606A1 (en) | 2009-11-27 | 2011-06-03 | 沈阳兴齐制药有限公司 | Ophthalmic gel of gatifloxacin and preparation method thereof |
| US8901131B2 (en) | 2009-11-27 | 2014-12-02 | Shenyang Xingqi Pharmaceutical Co., Ltd. | Gatifloxacin-containing ophthalmic gel and preparation method thereof |
| WO2012068998A3 (en) * | 2010-11-24 | 2012-07-19 | 金健亚洲集团有限公司 | Triamcinolone acetonide ophthalmic preparation and preparation method thereof |
| CN103142463A (en) * | 2013-03-05 | 2013-06-12 | 宁夏康亚药业有限公司 | Eye medicament composition as well as preparation method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN100427091C (en) | 2008-10-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102811610B (en) | Non-irritating ophthalmic povidone-iodine composition | |
| JP4694773B2 (en) | Mucosal liquid composition | |
| US11576973B2 (en) | Pharmaceutical formulations that form gel in situ | |
| RU2630581C2 (en) | Protective agent for cornea and conjunctiva or suppressive agent in case of keratoconjunctivitis | |
| CN1732008A (en) | The use of rimexolone in the treatment of dry eye disease | |
| CN1160999A (en) | Non-irritation, non-sensitizing non-ototoxic otic antibacterial compositions | |
| CN107405360B (en) | Novel iodophor compositions and methods of use thereof | |
| CN101757621B (en) | Cyclodextrin inclusion drug composition for ocular inflammation resistance | |
| JP2011021002A (en) | Ophthalmic composition | |
| CN1562030A (en) | Gatiflxacin eye gels based on HPMC medium and its preparing method | |
| CN112972683A (en) | Locally administered medicinal composition of gellinzomib and the like | |
| Andrés-Guerrero et al. | Comparison of the in vitro tolerance and in vivo efficacy of traditional timolol maleate eye drops versus new formulations with bioadhesive polymers | |
| JPWO2008056786A1 (en) | Skin or mucous membrane composition | |
| CN1302812C (en) | Transmission system of medicine containing trehalose and hyaluronic acid for eye part and its preparation method | |
| CN1194664C (en) | In-vivo gel preparatino able to be dropped in eyes and its preparing process | |
| KR20030001490A (en) | Ophthalmic solution | |
| KR20190071674A (en) | Ophthalmic preparations and ophthalmic preparations | |
| JP4904687B2 (en) | Ophthalmic composition | |
| CN109528628A (en) | A kind of Pharmaceutical composition and its preparation method and application comprising levocarnitine | |
| US20090142321A1 (en) | Opthalmic composition | |
| CN1562038A (en) | L-ofloxacin lactate slow release gels for eye and its preparing method | |
| RU2677665C2 (en) | Ophthalmic composition for anionic soft contact lenses | |
| CN100563657C (en) | Enoxacin sustain-released ophthalmic gels and preparation method thereof | |
| JP5083502B2 (en) | Ophthalmic composition | |
| CN1180776C (en) | Ofloxacin eye ointment |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20081022 Termination date: 20120420 |