CN1634070A - Eye drop of pazufloxacin mesilate, its preparing method and application - Google Patents
Eye drop of pazufloxacin mesilate, its preparing method and application Download PDFInfo
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- CN1634070A CN1634070A CN 200410064997 CN200410064997A CN1634070A CN 1634070 A CN1634070 A CN 1634070A CN 200410064997 CN200410064997 CN 200410064997 CN 200410064997 A CN200410064997 A CN 200410064997A CN 1634070 A CN1634070 A CN 1634070A
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- Prior art keywords
- eye drop
- pazufloxacin mesilate
- solution
- pazufloxacin
- dissolving
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- XAGMUUZPGZWTRP-ZETCQYMHSA-N LSM-5745 Chemical compound C([C@@H](N1C2=C(C(C(C(O)=O)=C1)=O)C=C1F)C)OC2=C1C1(N)CC1 XAGMUUZPGZWTRP-ZETCQYMHSA-N 0.000 title claims abstract description 70
- 229960002625 pazufloxacin Drugs 0.000 title claims abstract description 68
- 239000003889 eye drop Substances 0.000 title claims abstract description 51
- 238000000034 method Methods 0.000 title description 7
- 239000000243 solution Substances 0.000 claims abstract description 38
- 238000003756 stirring Methods 0.000 claims abstract description 25
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 24
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims abstract description 21
- 239000004327 boric acid Substances 0.000 claims abstract description 21
- 239000007788 liquid Substances 0.000 claims abstract description 19
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 16
- 239000002904 solvent Substances 0.000 claims abstract description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 14
- 239000003381 stabilizer Substances 0.000 claims abstract description 10
- 239000000872 buffer Substances 0.000 claims abstract description 4
- 241000191967 Staphylococcus aureus Species 0.000 claims description 26
- 239000003814 drug Substances 0.000 claims description 25
- 239000007853 buffer solution Substances 0.000 claims description 20
- 206010023332 keratitis Diseases 0.000 claims description 20
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 claims description 19
- 208000015181 infectious disease Diseases 0.000 claims description 17
- 238000002360 preparation method Methods 0.000 claims description 17
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- 229960001617 ethyl hydroxybenzoate Drugs 0.000 claims description 11
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 claims description 11
- GYCKQBWUSACYIF-UHFFFAOYSA-N o-hydroxybenzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1O GYCKQBWUSACYIF-UHFFFAOYSA-N 0.000 claims description 11
- 239000008363 phosphate buffer Substances 0.000 claims description 11
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 claims description 10
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 claims description 10
- BEGBSFPALGFMJI-UHFFFAOYSA-N ethene;sodium Chemical group [Na].C=C BEGBSFPALGFMJI-UHFFFAOYSA-N 0.000 claims description 9
- 230000002421 anti-septic effect Effects 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
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- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 5
- 206010064996 Ulcerative keratitis Diseases 0.000 claims description 5
- 239000011575 calcium Substances 0.000 claims description 5
- 229910052791 calcium Inorganic materials 0.000 claims description 5
- 210000000795 conjunctiva Anatomy 0.000 claims description 5
- 201000007717 corneal ulcer Diseases 0.000 claims description 5
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 claims description 5
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 claims description 5
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- 235000010265 sodium sulphite Nutrition 0.000 claims description 5
- DHMQDGOQFOQNFH-UHFFFAOYSA-M Aminoacetate Chemical compound NCC([O-])=O DHMQDGOQFOQNFH-UHFFFAOYSA-M 0.000 claims description 4
- WHGYBXFWUBPSRW-UHFFFAOYSA-N Cycloheptaamylose Natural products O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO WHGYBXFWUBPSRW-UHFFFAOYSA-N 0.000 claims description 4
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 4
- 229960002233 benzalkonium bromide Drugs 0.000 claims description 4
- KHSLHYAUZSPBIU-UHFFFAOYSA-M benzododecinium bromide Chemical compound [Br-].CCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 KHSLHYAUZSPBIU-UHFFFAOYSA-M 0.000 claims description 4
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 claims description 4
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- 239000001509 sodium citrate Substances 0.000 claims description 4
- 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 4
- 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 4
- 239000000463 material Substances 0.000 claims description 3
- QFOHBWFCKVYLES-UHFFFAOYSA-N Butylparaben Chemical compound CCCCOC(=O)C1=CC=C(O)C=C1 QFOHBWFCKVYLES-UHFFFAOYSA-N 0.000 claims description 2
- 229960000686 benzalkonium chloride Drugs 0.000 claims description 2
- XIWFQDBQMCDYJT-UHFFFAOYSA-M benzyl-dimethyl-tridecylazanium;chloride Chemical compound [Cl-].CCCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 XIWFQDBQMCDYJT-UHFFFAOYSA-M 0.000 claims description 2
- 239000000706 filtrate Substances 0.000 claims description 2
- 150000003242 quaternary ammonium salts Chemical class 0.000 claims description 2
- 235000011083 sodium citrates Nutrition 0.000 claims description 2
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 claims description 2
- 235000010262 sodium metabisulphite Nutrition 0.000 claims description 2
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 claims description 2
- 235000019345 sodium thiosulphate Nutrition 0.000 claims description 2
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- 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 group FC1=CC(C(C(C(O)=O)=C2)=O)=C3N2C(C)COC3=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-UHFFFAOYSA-N 0.000 description 10
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- WUWFMDMBOJLQIV-UHFFFAOYSA-N 7-(3-aminopyrrolidin-1-yl)-1-(2,4-difluorophenyl)-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid Chemical compound C1C(N)CCN1C(C(=C1)F)=NC2=C1C(=O)C(C(O)=O)=CN2C1=CC=C(F)C=C1F WUWFMDMBOJLQIV-UHFFFAOYSA-N 0.000 description 3
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Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The disclosed eye drop is prepared from Pazufloxacin mesilate, preservative agent, stabilizer, viscosity increaser and solvent through the steps of, (1) preparing boric acid and cushion liquid, (2) charging preservative into buffer agent, heating, stirring, dissolving and charging into stabilizing agent, charging Pazufloxacin mesilate, heating and stirring till dissolving, obtaining solution 1, (3) charging viscosity increaser into buffer agent or boric acid water, stirring till dissolving to obtain solution 2, (4) filtering the solution to obtained filtration liquid, (5) filtering the solution 2 to obtain filtration liquid, (6) merging the filtration liquid obtained in step (4) and (5), stirring, dissolving and charging into boric acid water or cushion agent, adjusting pH with hydrochloric acid or NaOH.
Description
One. technical field
The present invention relates to a kind of eye drop, specifically relate to eye drop of pazufloxacin mesilate and preparation method and application thereof.
Two. technical background
Pazufloxacin belongs to third generation quinolones anti-infectives, and it is is at first researched and developed by Japan folic hill chemical company, abroad goes on the market on April 12nd, 2002.Quinolones is the newer synthetic antibacterial drug of a class, the application point of it and other antimicrobial drug is different, it serves as the effect target with the DNA of antibacterial, play a role and make DNA of bacteria can't form superhelix by hindering DNA topology isomerase II and IV, further cause chromosomal irreversible lesion, cause the bacterial cell can't schizogamy.It has the selective toxicity effect to antibacterial.Antibacterial can not conducted chemical sproof influence but quinolones is not subject to plasmid because of plasmid conduction wide-scale distribution to many antibiotic drug resistance, thereby and many antibacterials between do not have cross resistance.The antimicrobial spectrum of quinolones is constantly being widened, develop into anti-Gram-negative and positive bacteria, anaerobe, mycobacterium, legionella, mycoplasma and chlamydial super wide spectrum from the narrow spectrum of single anti-gram negative bacteria, established their leading positions in anti-infectives.
The chemical name of Pazufloxacin Mesilate: (S)-(-)-10-(1-amino-1-cyclopropyl)-9-fluoro-3-methyl-2,3-dihydro-7-oxo-7H-pyrido [1,2,3-de] [1,4] benzoxazinyl-6-carboxylic acid mesylate, its chemical structural formula:
Molecular formula: C
16H
15FN
2O
4CH
4SO
3
Molecular weight: 414.41
Pazufloxacin Mesilate is a kind of potent extensive pedigree antibiotic.The G+ bacterium is comprised that staphylococcus aureus, streptococcus and enterococcal MIC are 0.2-100 μ g/ml, the G-bacterium is comprised that the MIC of Enterobacter, haemophilus is 0.025-3.13 μ g/ml.MIC to Rhodopseudomonas, Xanthomonas, acinetobacter, alcaligenes and Moraxella etc. is 0.05-50 μ g/ml.MIC to Legionnella is 0.025 μ g/ml, is 6.25-25 μ g/ml to the MIC of anaerobe such as fragile bacterium, clostridium difficile and Peptostreptococcus.The in-vitro antibacterial test shows that the antibacterial activity of Pazufloxacin Mesilate is ofloxacin and norfloxacin 2-32 a times, than the low 2-16 of ciprofloxacin doubly, is 1-8 times of tosulfloxacin.Antibacterial tests shows that oral Pazufloxacin Mesilate comprises that to G+ and the G-bacterium of mice systemic infection, pulmonary and the urinary tract infection of anti-quinoline promise class serratia marcesens and bacillus pyocyaneus all has good curative effect in the body.To the bacterial infection model of most mices, the vivo bacteria corrosion action of Pazufloxacin Mesilate is equivalent to or is better than ofloxacin, ciprofloxacin, norfloxacin and tosulfloxacin.At systemic infection and the pulmonary infection model of mice G+ bacterium, the antibacterial activity of Pazufloxacin Mesilate is lower than tosulfloxacin, and invalid to methicillin resistant staphylococcus aureus.To the mice systemic infection model of the serratia marcesens and the bacillus pyocyaneus of anti-quinoline promise class, the comparison of the antibacterial activity of Pazufloxacin Mesilate according to the strong 2-14 of medicine doubly.
Since successfully in the molecular structure of Pazufloxacin Mesilate 7 introduced amino cyclopropyl.Its side effect (comprising central nervous system's toxicity and phototoxicity) is all than obviously reducing with veriety.With theophylline clothes together, do not influence the metabolism of theophylline.This product oral absorption is good, and blood drug level is very high, distributes well at lung tissue inflammation part and ophthalmic, can be distributed in other any tissue except that the central nervous system, shows that this medicine can be used for treating the tissue infection at many positions.Mainly from urine, drain, therefore multiple infection disease is all had very high efficient, especially infect better as biliary tract infection, urinary tract infection and intraocular infection curative effect to respiratory tract infection, surgical operation.
Clinical drug studies show that many infectious disease can both treat with Pazufloxacin, wherein better with the bacterial infection curative effect in respiratory bacillary infection, urinary tract bacterial infection and skin, soft tissue, bone, joint especially, some sexually transmitted disease (gonococcus, chlamydia, chancroid infect) and pelvic infection are also effective in cure.Severe chronic respiratory tract infection person in 278, intravenous injection 300-500mg Pazufloxacin continues 3-14 days, and clinical effective rate and total antibiotic effective percentage are respectively 75.1% and 69.2%.Medicine is respectively 82.9%, 67.3% and 42.9% to the sterilizing rate of gram positive bacteria, negative bacterium and accomplice.Blended urinary tract infection person, intravenous injection 300-500mg Pazufloxacin continues 5 days, and medicine is respectively 79.3% and 91.9% to the sterilizing rate of Gram-positive and negative bacterium, and total effective rate is 85.9%.83 post-operative infections (comprising peritonitis, pneumonia and pyemia) patient accepts Pazufloxacin treatment, medicine to low-grade infection person's effective percentage be 87.5% (34/40) and severe infection person's effective percentage be 75% (27/36).Effective percentage to pseudomonas aeruginosa the infected is 80% (12/15), and sterilizing rate is 68.8%.Another studies show that medicine is respectively 77.8% (21/27), 88.2% (15/17), 100% (3/3) and 71.4% (15/21) to the effective percentage of intra-abdominal infection, biliary tract infection, liver abscess and trauma infection contamination.Medicine is 95.5% to the effective percentage of female genital tract infection, and the effective percentage of skin, soft tissue infection is 86.4%, and visible Pazufloxacin is a kind of curative effect broad ectrum antibiotic preferably.But relevant so far application Pazufloxacin Mesilate is made as eye drop, and this does not see listing at home and abroad as yet.
Three, summary of the invention
1. goal of the invention:
The object of the present invention is to provide a kind of eye drop of pazufloxacin mesilate and preparation method and application thereof.
2. technical scheme:
(1). a kind of eye drop of pazufloxacin mesilate is characterized in that by following materials of weight proportions medicine made:
Pazufloxacin Mesilate 6.0-60g
Antiseptic 0.5-4g
Stabilizing agent 5.0-25g
Viscosifier 0.05-50g
Solvent 500-5000mL
Make the 100-1000 bottle
Above-mentioned antiseptic has two big classes, and a class is a parabens, comprises methyl hydroxybenzoate, ethyl hydroxybenzoate, propylparaben, butoben; Another kind of is that quaternary ammonium salt comprises benzalkonium bromide, benzalkonium chloride.
Above-mentioned stabilizing agent comprises sodium sulfite, sodium pyrosulfite, sodium thiosulfate, sodium citrate, sodium ethylene diamine tetracetate, sodium ethylene diamine tetracetate calcium.
Above-mentioned viscosifier comprise methylcellulose, cycloheptaamylose, polyvinylpyrrolidone (PVP-30), hyaluronic acid sodium, PVAC polyvinylalcohol
124Deng.
Above-mentioned solvent comprises 1-3% boric acid water, phosphate buffer, borate buffer solution, glycinate acid buffer.
(2). the preparation technology of eye drop of pazufloxacin mesilate, its preparation process is:
(a) the boric acid water of preparation 1-3, pH is that phosphate buffer, borate buffer solution and the glycinate buffer 500-5000mL of 4.9-5.05 is stand-by.
(b) take by weighing the antiseptic of 0.5-4g and the stabilizing agent of 5.0-25g, earlier antiseptic is added solvent 300-3000mL, the heated and stirred dissolving, wait to dissolve the back and add stabilizing agent, after the stirring and dissolving, the Pazufloxacin Mesilate that adds 6.0-60g again is stirred to dissolving, gets solution one;
(c) take by weighing the viscosifier of 0.05-50g, add solvent 100-1000mL, stirring and dissolving, solution two;
(d) solution one usefulness 4# sand mold funnel filters, and complete the swinging with solvent 40-400mL of filter washed container and funnel, and washing liquid is filtered into filter flask;
(e) solution dual-purpose 3# sand mold funnel is filtered, filter flask is gone in filter again, and complete the swinging with solvent 40-400mL of filter washed container and funnel, and washing liquid is filtered into filter flask;
(f) filtrate of step (d), (e) is merged, the back solubilizer that stirs is to 500-5000mL, is 3.5-4.5 with hydrochloric acid or the NaOH adjusting pH value of 0.1N-3N, promptly obtains eye drop of pazufloxacin mesilate.
(3), we adopt the eye drop of pazufloxacin mesilate of development voluntarily to carry out the experiment of bacterial keratitis model body internal therapy, found that this medicine for all having significant therapeutic effect, and can stop the formation and development of corneal ulcer by experimental rabbit bacterial keratitis due to golden Portugal bacterium and the charrin's disease.By golden Portugal bacterium and charrin's disease eye and the keratitis and the corneal ulcer that cause, local eye drip finds no obvious irritation and toxicity to experimental rabbit, also finds no obvious anaphylaxis, and bibliographical information this product does not have photosensitive reaction yet.Bacterial infection, the eye keratitis that particularly golden Portugal bacterium and bacillus pyocyaneus cause is the most common and the most serious infection of present ophthalmology, and is anxious because of onset, development is fast, prognosis is often not good.Because antibiotic and sugar skin hormone class medicine are in the extensive use of clinical ophthalmology, new drug resistance strain constantly occurs, and brings difficulty to treatment.Therefore, filter out very necessity of how better antibacterials for clinical ophthalmology.Mechanism of action analysis from such medicine, Pazufloxacin Mesilate is the quinolones of new chemical constitution, therefore may be with not having cross resistance between many antibacterials, eye drop of pazufloxacin mesilate should require and the eye drop of the new antibacterials that produce just like this.
3. beneficial effect
(1) to bacterial infection, especially staphylococcus aureus and charrin's disease eye and the conjunctiva/keratitis and the corneal ulcer that cause all have significant therapeutic effect.
(2) preparation technology of eye drop of the present invention is simple, and production operation is convenient, thereby helps suitability for industrialized production.
Four, the specific embodiment
Execute example 1:
(1) prescription is formed
Pazufloxacin Mesilate 19.82g
Ethyl hydroxybenzoate 1.5g
Calcium disodium chelate 5.0g
Hyaluronic acid sodium 2.5g
Add to 5000mL with 1.9% boric acid water
Make 1000 bottles
(2) preparation technology
Take by weighing the boric acid of 95g, add injection water 5000mL, it is stand-by to be made into 1.9% boric acid solution.
Take by weighing the ethyl hydroxybenzoate of recipe quantity, calcium disodium chelate, earlier ethyl hydroxybenzoate is added 1.9% boric acid solution 3000mL, the heated and stirred dissolving, add calcium disodium chelate after waiting to dissolve, after the stirring and dissolving, the Pazufloxacin Mesilate that adds recipe quantity stirs and causes dissolving, gets solution one.
Take by weighing the recipe quantity hyaluronic acid sodium, add 1.9% boric acid solution 1000mL, stir swelling, get solution two.
Solution one usefulness 4# sand mold funnel is filtered into filter flask, and complete the swinging with 1.9% boric acid solution 400mL of filter washed container and funnel, and washing liquid is filtered into filter flask.Solution dual-purpose 3# sand mold funnel is filtered, filter flask is gone in filter again, and complete the swinging with 400mL 1.9% boric acid solution of filter washed container and funnel, and washing liquid is filtered into filter flask.Add 1.9% boric acid solution after waiting to stir to 5000mL, regulating pH value with hydrochloric acid (1N) or NaOH (1N) is 4.0, promptly.
Embodiment 2:
(1) prescription is formed:
1. Pazufloxacin Mesilate 7810.0mg
2.. ethyl hydroxybenzoate 600.0mg
3.. sodium ethylene diamine tetracetate 2500.0mg
4.. methylcellulose 2500.0mg
Add to 1000..0ml with phosphate buffer
Make 200 bottles
(2) preparation technology:
Take by weighing the NaH of 10g
2PO
4, 9gNa
2HPO
4Add injection water 1000mL, it is stand-by near 5.0 phosphate buffer to be made into pH.
Take by weighing the ethyl hydroxybenzoate of recipe quantity, ethylenediamine tetrem disodium, elder generation adds ethyl hydroxybenzoate the phosphate buffer 600ml of above-mentioned configuration, the heated and stirred dissolving adds sodium ethylene diamine tetracetate after waiting to dissolve, after the stirring and dissolving, the Pazufloxacin Mesilate that adds recipe quantity is stirred to dissolving, gets solution one;
Take by weighing the recipe quantity methylcellulose, add the phosphate buffer 200mL of above-mentioned configuration, stirring and dissolving gets solution two;
Solution one usefulness 4# sand mold funnel filters, and the complete phosphate buffer 80mL with above-mentioned configuration of filter swings and washes container and funnel, and washing liquid is filtered into filter flask;
Solution dual-purpose 3# sand mold funnel is filtered, filter flask is gone in filter again, and the complete phosphate buffer 80mL with above-mentioned configuration of filter swings and washes container and funnel, and washing liquid is filtered into filter flask; After waiting to stir, the phosphate buffer that adds above-mentioned configuration is to 1000mL, and with the NaOH of 2N hydrochloric acid or 2N, regulating pH value is 4.2, promptly.
Embodiment 3:
(1) prescription is formed:
1. Pazufloxacin Mesilate 991.0mg
2. methyl hydroxybenzoate 115.0mg
3. propylparaben 55.0mg
4. sodium sulfite 500.0mg
5. polyvinylpyrrolidone (PVP-30) 5000.0mg
Add with borate buffer solution to 500.0ml
Make 100 bottles
(2) preparation technology:
Take by weighing 15g H
3BO
3With 7.5g Na
2B
4O
710H
2O adds injection water 500.0mL, and it is stand-by near 5.0 borate buffer solution to be made into pH.
Take by weighing recipe quantity. methyl hydroxybenzoate, propylparaben, sodium sulfite, with methyl hydroxybenzoate, propylparaben adds the borate buffer solution 300mL of above-mentioned configuration earlier, the heated and stirred dissolving, add sodium sulfite after waiting to dissolve, after the stirring and dissolving, the Pazufloxacin Mesilate that adds recipe quantity is stirred to dissolving, gets solution one;
Take by weighing recipe quantity polyvinylpyrrolidone (PVP-30), add the borate buffer solution 100.0mL of above-mentioned configuration, stirring and dissolving gets solution two;
Solution one usefulness 4# sand mold funnel filters, and complete the swinging with borate buffer solution 40mL of filter washed container and funnel, and washing liquid is filtered into filter flask;
Solution dual-purpose 3# sand mold funnel is filtered, filter flask is gone in filter again, and complete the swinging with borate buffer solution 40mL of filter washed container and funnel, and washing liquid is filtered into filter flask; After waiting to stir, add above-mentioned configuration borate buffer solution to 500.0mL, with the NaOH of 2.5N hydrochloric acid or 2.5N, regulating pH value is 4.10, promptly.
Embodiment 4:
(1) prescription is formed:
1. Pazufloxacin Mesilate 3905.0mg
2.5% benzalkonium bromide, 2000.0 μ l (200 μ l contain 0.01g)
3. sodium citrate 1000.0mg
4. cycloheptaamylose (the 2500.0mg of β-cyclodextron)
Add to 1000.0ml with 2.5% boric acid water
(2) preparation technology:
Take by weighing the boric acid of 25g, add injection water 1000.0mL, it is stand-by to be made into 2.5% borate solution.Get the benzalkonium bromide of recipe quantity, sodium citrate, add 2.5% boric acid solution 800.0mL with cycloheptaamylose, stirring and dissolving, wait that the Pazufloxacin Mesilate that dissolves back adding recipe quantity is stirred to abundant dissolving, yet be filtered into filter flask with the sand mold funnel, complete the swinging with 2.5% boric acid solution 100mL of filter washed container and funnel, and washing liquid is filtered into filter flask.Add 2.5% boric acid solution after waiting to stir to 1000.0mL, with the NaOH of hydrochloric acid (1.5N) or 1.5N, regulating pH value is 4.08, promptly.
Embodiment 5:
(1) prescription is formed:
1.. Pazufloxacin Mesilate 1952.0mg
2. ethyl hydroxybenzoate 150.0mg
3. sodium ethylene diamine tetracetate calcium 500.0mg
4. PVAC polyvinylalcohol
1247000.0mg
Add to 500.0ml with borate buffer solution
(2) preparation technology:
Take by weighing 15g H
3BO
3With 7.5g Na
2B
4O
710H
2O adds injection water 500.0mL, and it is stand-by near 5.0 borate buffer solution to be made into pH.
Take by weighing the ethyl hydroxybenzoate of recipe quantity, sodium ethylene diamine tetracetate calcium, the boric acid water that earlier ethyl hydroxybenzoate is added the borate buffer solution 300mL of above-mentioned configuration, the heated and stirred dissolving, add sodium ethylene diamine tetracetate calcium after waiting to dissolve, after the stirring and dissolving, the Pazufloxacin Mesilate that adds recipe quantity is stirred to dissolving, gets solution one;
Take by weighing the recipe quantity PVAC polyvinylalcohol
124, adding borate buffer solution 100.0mL, stirring and dissolving gets solution two;
Solution one usefulness 4# sand mold funnel filters, and complete the swinging with borate buffer solution 40mL of filter washed container and funnel, and washing liquid is filtered into filter flask;
Solution dual-purpose 3# sand mold funnel is filtered, filter flask is gone in filter again, and complete the swinging with borate buffer solution 40mL of filter washed container and funnel, and washing liquid is filtered into filter flask; Add borate buffer solution to 500.0mL after waiting to stir, with the NaOH of hydrochloric acid (1.5N) or 1.5N, regulating pH value is 4.05, promptly.
Embodiment 6 0.3% eye drop of pazufloxacin mesilate are to the experimental therapy of rabbit Pseudomonas Aeruginosa Keratitis and staphylococcus aureus property keratitis
1 material.
1.1. animal: New Zealand's white rabbit, the male and female dual-purpose, body weight 2-3kg is by providing production licence number by kind warren, Nanjing: SCXK (Soviet Union) 2002-0025.Test and checked that eyes were no abnormal in preceding 24 hours.
1.2 strain: standard strain bacillus pyocyaneus (ATCC-27853), staphylococcus aureus (cultivation of clinical infection strains separation) is provided by the Nanjing first medical university first Affiliated Hospital antibiotics chamber.
1.3 medicine: 0.15%, 0.3% and 0.6% eye drop of pazufloxacin mesilate, produce by Zhejiang Sapuaisi Pharmacy Co., Ltd., lot number:, 040623,031215,0406220.3% ofloxacin eye drops (lot number: 04040302 Wuhan Wujing Medicine Co., Ltd, the accurate word H420227210.9%NaCL of traditional Chinese medicines injection, lot number: 2004020603.Nanjing Xiaoying Pharmaceutical Factory, the accurate word H32023210 of traditional Chinese medicines
2 methods.
2.1 antibacterial culturing and bacterial concentration:
Staphylococcus aureus and bacillus pyocyaneus strain 2d before experiment that staphylococcus aureus and bacillus pyocyaneus strain are preserved in room temperature (4 ℃) refrigerator cold-storage are inoculated on the blood agar culture-medium, cultivate 24h through 37 ℃, encircle microbionation in fluid medium with the oese peek, cultivate 48h, taking-up placement refrigerator (＜4 ℃) preservation standby ((2wk) through 37 ℃.With normal saline the bacillus pyocyaneus bacterial concentration is diluted to 10 during experimental infection
8/ ml.Staphylococcus aureus is diluted to 10
7/ ml.
2.2. (1) the angle mould damage splashes into antibacterial method (bacillus pyocyaneus):
Rabbit is pressed 1g/kg, and (20% anesthesia is oppressed center in superficial keratectomy with the 2mm trepan earlier, presses down gently about half-twist, to scratch corneal epithelium degree of being, the scar of formation 2mm diameter through ear vein injection urethane; The trepan of reuse 6mm causes the scar of 6mm diameter in the scar outer ring.Light pulling eye eyelid becomes little cup-shaped, splashes into 0.1ml bacillus pyocyaneus experiment bacterium liquid with the 1ml syringe of being furnished with No. 6 syringe needles to the cornea scar, restores catacleisis 10s.Sub-cage rearing then.
(2) bacterial injection method in the cornea: (staphylococcus aureus)
Family exempts from by after the anesthesia of last method, is fixed in the center of superficial keratectomy with the trepan of 6mm, makes by last method to form circular scar, injects 0.05ml along the edge of scar in the cornea of center then and tests usefulness staphylococcus aureus bacterium liquid.Sub-cage rearing then.
2.3 experimental therapy method:
Get 50 of rabbit behind the charrin's disease, be divided into the normal saline matched group at random, 10 groups of positive drug group and 0.15%, 0.3% and 0.6% tested medicine groups etc., 5 every group, every group of 10 experimental eyes, 6h begins to drip medicine behind the charrin's disease, and golden Portugal bacterium infects back 4h and begins to drip medicine, and see that inflammatory reaction has appearred in lagophthalmos this moment, shed tears, the eye conjunctiva, the iris congestion of blood vessel, secretions increases.Matched group drips the equivalent normal saline.The positive drug group is dripped 0.3% ofloxacin eye drops, its excess-three group drips 0.15% respectively, 0.3% and 0.6% eye drop of pazufloxacin mesilate. each is organized and drips medicine every day 6 times, put drops in one's eyes for each every 2, successive administration 6 days, every day, O﹠A was respectively organized after the medication the therapeutical effect of rabbit Pseudomonas Aeruginosa Keratitis keratitis and staphylococcus aureus keratitis, observed to the 2nd day after the drug withdrawal, yet judged
2.4 evaluation criterion scoring:
2.4. (1). the cornea inflammatory conditions::
0. divide eyes bright, no redness and secretions
0.5 divide cornea not have covering.Eyes have redness slightly
1. divide cornea white covering less than 6mrn
2. divide cornea white covering to be full of 6mrn
3. divide cornea white covering greater than 6mrn
2.4 (2) corneal opacity degree (being as the criterion) with the finest and close position
Cornea was Clear ﹠ Transparent in 0 minute, did not have muddy.
1 fen cornea be dispersed in or diffusivity slightly muddy, visible iris texture
Cornea was translucent in 2 minutes, and iris is smudgy, and the pupil size reluctantly as seen
Cornea was muddy fully in 3 minutes, and iris is beyond recognition
2.4. (3) antibacterial culturing: the experimental rabbit cornea place antibacterial calibrating time, for putting drops in one's eyes back the 1st, 5 day, gently please on rabbit cornea, smear once with disinfecting cotton swab, yet be inoculated in the plate of culture medium, put 37 ℃ of cultivation 18h and carry out antibacterial culturing respectively, judge the antibacterial culturing positive and negative.
3. experimental result
The normal saline matched group: exempt from cornea with bacillus pyocyaneus or infection of staphylococcus aureus after respectively at 6h and 4h, tangible inflammatory reaction promptly occurs, show as and shed tears, the eye conjunctiva, the iris congestion of blood vessel, edema, secretions increases.The 24h cornea begins muddiness, and antibacterial culturing is all positive; To have seen that injury region produces white covering, shown the scorching formation of rabbit cornea. the corneal injury total mark that this moment, bacillus pyocyaneus and staphylococcus aureus caused is respectively 30 and 17, and antibacterial culturing is all positive; It is 45 and 26 that 48h corneal injury total mark is respectively,
Covering to the 5th day most of lagophthalmos still occupies cornea, ulcer.Antibacterial culturing is still all positive.
The positive drug group: behind 0.3% ofloxacin eye drops, 24h has seen obvious therapeutic effect, removes indivedual rabbit conjunctivals, iris blood vessel mild hyperaemia, and outside the edema, absent lacrimation and other inflammatory reaction.The corneal injury total mark that bacillus pyocyaneus and staphylococcus aureus cause is 2 and 2.5, bacillus pyocyaneus or staphylococcus aureus bacteria cultivation results: positive eye is respectively 5 example and 4 examples, and it is 0.5 and 1.5 that all the other negative .48h corneal injury total marks are respectively.
0.15%, 0.3% and 0.6% eye drop of pazufloxacin mesilate group is as follows respectively:
0.15% eye drop of pazufloxacin mesilate: 24h sees obvious therapeutic effect, remove indivedual rabbit conjunctivals, iris blood vessel mild hyperaemia, outside the edema, absent lacrimation and other inflammatory reaction. the corneal injury total mark that bacillus pyocyaneus or staphylococcus aureus cause is 4 and 3.5, bacillus pyocyaneus or staphylococcus aureus bacteria cultivation results: positive eye is respectively 8 example and 7 examples, and all the other negative .48h corneal injury total marks are 1.5.
0.3% eye drop of pazufloxacin mesilate 24h sees obvious therapeutic effect, remove indivedual rabbit conjunctivals, iris blood vessel mild hyperaemia, outside the edema, absent lacrimation and other inflammatory reaction. the corneal injury total mark that bacillus pyocyaneus or staphylococcus aureus cause is 2, bacillus pyocyaneus or staphylococcus aureus bacteria cultivation results: positive eye is 4 examples respectively, and all the other are negative.48h corneal injury total mark is 0.
0.6% eye drop of pazufloxacin mesilate 24h sees obvious therapeutic effect, removes indivedual rabbit conjunctivals, iris blood vessel mild hyperaemia, and outside the edema, absent lacrimation and other inflammatory reaction.Bacillus pyocyaneus or staphylococcus aureus corneal injury total mark are 1.5, bacillus pyocyaneus or staphylococcus aureus bacteria cultivation results: positive eye is 4 examples, and all the other are negative; 48h corneal injury total mark is 0.
More than each eye drop of pazufloxacin mesilate group compare with the normal saline matched group, corneal injury total mark difference is very obvious.(p＜0.01)
And compare between three groups of eye drop of pazufloxacin mesilate and three groups of each integration differences all very little (p＞0.01) of comparing with 0.3% ofloxacin eye drops group, all negative through the 5th day treatment group bacteria cultivation results, illustrate all to have reached the effect that heals entirely.Detailed results sees Table 1, table 2.
4 conclusions
Adopt the man lagophthalmos shallow-layer cornea of damage, the Pseudomonas Aeruginosa Keratitis and the staphylococcus aureus property keratitis animal model that cause with charrin's disease and staphylococcus aureus.The treatment of employing eye drop of pazufloxacin mesilate, and compare with 0.3% ofloxacin eye drops respectively.The result shows: 0.15%, 0.3% and 0.6% eye drop of pazufloxacin mesilate has notable therapeutic effect to Pseudomonas Aeruginosa Keratitis keratitis and staphylococcus aureus property conjunctiva/keratitis, its effect is close with 0.3% ofloxacin eye drops, and can effectively prevent the formation of corneal ulcer.Prompting: homemade novel eye drop of pazufloxacin mesilate can be used as the active drug of treatment bacterial keratitis.
Table 1 eye drop of pazufloxacin mesilate is to lagophthalmos Pseudomonas Aeruginosa Keratitis keratitis therapeutic outcome
| Group | Sequence number | Natural law | ??????1/4d | ??????1d | ????2d | ????3d | ????4d | ????5d | ????6d |
| Lagophthalmos | About | About | About | About | About | About | About | ||
| The normal saline group | ??1 | ????0.5???0.5 | ????2?????2 | ??5?????5 | ??5?????5 | ??4?????4 | ??4?????4 | ??4?????3 | |
| ??2 | ????0.5???0.5 | ????2?????5 | ??4?????4 | ??5?????5 | ??4?????5 | ??4?????4 | ??4?????4 | ||
| ??3 | ????0.5???0.5 | ????4?????5 | ??5?????6 | ??4?????4 | ??3?????4 | ??3?????5 | ??4?????4 | ||
| ??4 | ????0.5???0.5 | ????2?????3 | ??4?????3 | ??4?????4 | ??5?????4 | ??3?????2 | ??4?????4 | ||
| ??5 | ????0.5???0.5 | ????2?????3 | ??4?????5 | ??4?????5 | ??3?????4 | ??3?????3 | ??4?????4 | ||
| Add up to | ????????5 | ???????30 | ????45 | ????45 | ????40 | ????35 | ????39 | ||
| 0.15 % Pazufloxacin eye drop | ??1 | ????0.5???0.5 | ????0.5???0 | ??0?????0 | ??0?????0 | ??0?????0 | ??0?????0 | ??0?????0 | |
| ??2 | ????0.5???0.5 | ????0.5???0.5 | ??0.5???0 | ??0?????0 | ??0?????0 | ??0?????0 | ??0?????0 | ||
| ??3 | ????0.5???0.5 | ????0?????0.5 | ??0?????0 | ??0?????0 | ??0?????0 | ??0?????0 | ??0?????0 | ||
| ??4 | ????0.5???0.5 | ????0.5???0.5 | ??0.5???0 | ??0?????0 | ??0?????0 | ??0?????0 | ??0?????0 | ||
| ??5 | ????0.5???0.5 | ????0.5???0.5 | ??0.5???0 | ??0?????0 | ??0?????0 | ??0?????0 | ??0?????0 | ||
| Add up to | ????????5 | ????????4 | ????1.5 | ?????0 | ?????0 | ?????0 | ?????0 | ||
| 0.3% Pazufloxacin eye drop | ??1 | ????0.5???0.5 | ????0.5???0.5 | ??0?????0 | ??0?????0 | ??0?????0 | ??0?????0 | ??0?????0 | |
| ??2 | ????0.5???0.5 | ????0?????0 | ??0?????0 | ??0?????0 | ??0?????0 | ??0?????0 | ??0?????0 | ||
| ??3 | ????0.5???0.5 | ????0.5???0 | ??0?????0 | ??0?????0 | ??0?????0 | ??0?????0 | ??0?????0 | ||
| ??4 | ????0.5???0.5 | ????0?????0 | ??0?????0 | ??0?????0 | ??0?????0 | ??0?????0 | ??0?????0 | ||
| ??5 | ????0.5???0.5 | ????0?????0.5 | ??0?????0 | ??0?????0 | ??0?????0 | ??0?????0 | ??0?????0 | ||
| Add up to | ????????5 | ???????2 | ?????0 | ?????0 | ?????0 | ?????0 | ?????0 | ||
| 0.6% Pazufloxacin eye drop | ??1 | ????0.5???0.5 | ????0.5???0.5 | ??0?????0 | ??0?????0 | ??0?????0 | ??0?????0 | ??0?????0 | |
| ??2 | ????0.5???0.5 | ????0?????0 | ??0?????0 | ??0?????0 | ??0?????0 | ??0?????0 | ??0?????0 | ||
| ??3 | ????0.5???0.5 | ????0?????0 | ??0?????0 | ??0?????0 | ??0?????0 | ??0?????0 | ??0?????0 | ||
| ??4 | ????0.5???0.5 | ????0?????0.5 | ??0?????0 | ??0?????0 | ??0?????0 | ??0?????0 | ??0?????0 | ||
| ??5 | ????0.5???0.5 | ????0?????0 | ??0?????0 | ??0?????0 | ??0?????0 | ??0?????0 | ??0?????0 | ||
| Add up to | ????????5 | ??????1.5 | ????0 | ?????0 | ?????0 | ?????0 | ????0 | ||
| 0.3% ofloxacin eye drops | ??1 | ????0.5???0.5 | ????0?????0 | ??0?????0 | ??0?????0 | ??0?????0 | ??0?????0 | ??0?????0 | |
| ??2 | ????0.5???0.5 | ????0.5???0.5 | ??0.5???0 | ??0?????0 | ??0?????0 | ??0?????0 | ??0?????0 | ||
| ??3 | ????0.5???0.5 | ????0.5???0 | ??0?????0 | ??0?????0 | ??0?????0 | ??0?????0 | ??0?????0 | ||
| ??4 | ????0.5???0.5 | ????0?????0.5 | ??0?????0 | ??0?????0 | ??0?????0 | ??0?????0 | ??0?????0 | ||
| ??5 | ????0.5???0.5 | ????0?????0 | ??0?????0 | ??0?????0 | ??0?????0 | ??0?????0 | ??0?????0 | ||
| Add up to | ????????5 | ????????2 | ????0.5 | ?????0 | ?????0 | ?????0 | ????0 |
Table 2 eye drop of pazufloxacin mesilate is to lagophthalmos staphylococcus aureus property keratitis therapeutic outcome
| Group | Sequence number | Natural law | ????1/6d | ????1d | ????2d | ????3d | ???4d | ???5d | ??6d |
| Lagophthalmos | About | About | About | About | About | About | About | ||
| The normal saline group | ??1 | ??1?????0.5 | ??3?????1 | ??3?????2 | ??5???2 | ??4???2 | ??4???2 | ??4???2 | |
| ??2 | ??1?????0.5 | ??2?????1 | ??3?????3 | ??5???4 | ??4???3 | ??4???3 | ??4???3 | ||
| ??3 | ??0.5???0.5 | ??1?????2 | ??3?????2 | ??3???2 | ??3???2 | ??3???2 | ??3???2 | ||
| ??4 | ??0.5???0.5 | ??2?????2 | ??2?????3 | ??5???4 | ??4???4 | ??4???4 | ??4???4 | ||
| ??5 | ??0.5???0.5 | ??2?????1 | ??3?????2 | ??4???3 | ??4???3 | ??4???3 | ??4???3 | ||
| Add up to | ??????6 | ????17 | ?????26 | ????37 | ????33 | ????33 | ????33 | ||
| 0.15 % Pazufloxacin eye drop | ??1 | ??0.5???0.5 | ??0.5???0 | ??0?????0 | ??0???0 | ??0???0 | ??0???0 | ??0???0 | |
| ??2 | ??0.5???0.5 | ??0.5???0.5 | ??0?????0 | ??0???0 | ??0???0 | ??0???0 | ??0???0 | ||
| ??3 | ??0.5???0.5 | ??0?????0.5 | ??0?????0.5 | ??0???0 | ??0???0 | ??0???0 | ??0???0 | ||
| ??4 | ??0.5???0.5 | ??0.5???0.5 | ??0.5???0 | ??0???0 | ??0???0 | ??0???0 | ??0???0 | ||
| ??5 | ??0.5???0.5 | ??0?????0.5 | ??0?????0.5 | ??0???0 | ??0???0 | ??0???0 | ??0???0 | ||
| Add up to | ??????5 | ????3.5 | ????1.5 | ????0 | ????0 | ????0 | ????0 | ||
| 0.3% Pazufloxacin eye drop | ??1 | ??0.5???0.5 | ??0.5???0 | ??0?????0 | ??0???0 | ??0???0 | ??0???0 | ??0???0 | |
| ??2 | ??0.5???0.5 | ??0.5???0 | ??0?????0 | ??0???0 | ??0???0 | ??0???0 | ??0???0 | ||
| ??3 | ??0.5???0.5 | ??0?????0.5 | ??0?????0 | ??0???0 | ??0???0 | ??0???0 | ??0???0 | ||
| ??4 | ??0.5???0.5 | ??0?????0.5 | ??0?????0 | ??0???0 | ??0???0 | ??0???0 | ??0???0 | ||
| ??5 | ??1?????0.5 | ??0?????0 | ??0?????0 | ??0???0 | ??0???0 | ??0???0 | ??0???0 | ||
| Add up to | ?????5.5 | ?????2 | ?????0 | ????0 | ????0 | ????0 | ????0 | ||
| 0.6% Pazufloxacin eye drop | ??1 | ??0.5???0.5 | ??0?????0.5 | ??0?????0 | ??0???0 | ??0???0 | ??0???0 | ??0???0 | |
| ??2 | ??0.5???0.5 | ??0?????0.5 | ??0?????0 | ??0???0 | ??0???0 | ??0???0 | ??0???0 | ||
| ??3 | ??0.5???0.5 | ??0.5???0 | ??0?????0 | ??0???0 | ??0???0 | ??0???0 | ??0???0 | ||
| ??4 | ??0.5???0.5 | ??0?????0.0 | ??0?????0 | ??0???0 | ??0???0 | ??0???0 | ??0???0 | ||
| ??5 | ??0.5???0.5 | ??0?????0 | ??0?????0 | ??0???0 | ??0???0 | ??0???0 | ??0???0 | ||
| Add up to | ??????5 | ????1.5 | ?????0 | ????0 | ????0 | ????0 | ????0 | ||
| 0.3% ofloxacin eye drops | ??1 | ??0.5???0.5 | ??0?????0 | ??0?????0 | ??0???0 | ??0???0 | ??0???0 | ??0???0 | |
| ??2 | ??0.5???0.5 | ??0?????0 | ??0.5????0 | ??0???0 | ??0???0 | ??0???0 | ??0???0 | ||
| ??3 | ??0.5???0.5 | ??0?????0.5 | ??0?????0 | ??0???0 | ??0???0 | ??0???0 | ??0???0 | ||
| ??4 | ??0.5???1.5 | ??0?????1.5 | ??0?????1 | ??0???0 | ??0???0 | ??0???0 | ??0???0 | ||
| ??5 | ??0.5???0.5 | ??0?????0.5 | ??0?????0 | ??0???0 | ??0???0 | ??0???0 | ??0???0 | ||
| Add up to | ??????6 | ????2.5 | ????1.5 | ????0 | ????0 | ????0 | ????0 |
Claims (8)
1. eye drop of pazufloxacin mesilate is characterized in that by following materials of weight proportions medicine made:
Pazufloxacin Mesilate 6.0-60g
Antiseptic 0.5-4g
Stabilizing agent 5.0-25g
Viscosifier 0.05-50g
Solvent 500-5000mL
2. eye drop of pazufloxacin mesilate according to claim 1 is characterized in that above-mentioned antiseptic has two big classes, and a class is a parabens, comprises methyl hydroxybenzoate, ethyl hydroxybenzoate, propylparaben, butoben; Another kind of is that quaternary ammonium salt comprises benzalkonium bromide, benzalkonium chloride.
3. eye drop of pazufloxacin mesilate according to claim 1 is characterized in that above-mentioned stabilizing agent comprises sodium sulfite, sodium pyrosulfite, sodium thiosulfate, sodium citrate, sodium ethylene diamine tetracetate, sodium ethylene diamine tetracetate calcium.
4. eye drop of pazufloxacin mesilate according to claim 1 is characterized in that above-mentioned viscosifier comprise methylcellulose, cycloheptaamylose, polyvinylpyrrolidone, hyaluronic acid sodium, polyvinyl alcohol.
5. eye drop of pazufloxacin mesilate according to claim 1 is characterized in that above-mentioned solvent comprises that 1-3% boric acid water, pH are phosphate buffer, borate buffer solution and the glycinate acid buffer of 4.9-5.05.
6. the preparation method of eye drop of pazufloxacin mesilate, its preparation process is:
(1) the boric acid water of preparation 1-3, pH is that phosphate buffer, borate buffer solution and the glycinate buffer 500-5000mL of 4.9-5.05 is stand-by.
(2) take by weighing the antiseptic of 0.5-4g and the stabilizing agent of 5.0-25g, earlier antiseptic is added solvent 300-3000mL, the heated and stirred dissolving, wait to dissolve the back and add stabilizing agent, after the stirring and dissolving, the Pazufloxacin Mesilate that adds 6.0-60g again is stirred to dissolving, gets solution one;
(3) take by weighing the viscosifier of 0.05-50g, add solvent 100-1000mL, stirring and dissolving, solution two;
(4) solution one usefulness 4# sand mold funnel filters, and complete the swinging with solvent 40-400mL of filter washed container and funnel, and washing liquid is filtered into filter flask;
(5) solution dual-purpose 3# sand mold funnel is filtered, filter flask is gone in filter again, and complete the swinging with solvent 40-400mL of filter washed container and funnel, and washing liquid is filtered into filter flask;
(6) filtrate of step (4), (5) is merged, the back solubilizer that stirs is to 500-5000mL, is 3.5-4.5 with hydrochloric acid or the NaOH adjusting pH value of 0.1N-3N, promptly obtains eye drop of pazufloxacin mesilate.
7. the application of eye drop of pazufloxacin mesilate in preparation treatment infectious eye disease medicine.
8. the application of eye drop of pazufloxacin mesilate according to claim 7 in the preparation medicine, it is characterized in that described infectious eye disease mainly is by bacterial infection, especially staphylococcus aureus and charrin's disease eye and the conjunctiva/keratitis, the corneal ulcer that cause.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410064997 CN1634070A (en) | 2004-10-18 | 2004-10-18 | Eye drop of pazufloxacin mesilate, its preparing method and application |
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| CN 200410064997 CN1634070A (en) | 2004-10-18 | 2004-10-18 | Eye drop of pazufloxacin mesilate, its preparing method and application |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115919761A (en) * | 2023-01-29 | 2023-04-07 | 浙江莎普爱思药业股份有限公司 | Pazufloxacin mesilate liquid preparation and preparation method thereof |
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2004
- 2004-10-18 CN CN 200410064997 patent/CN1634070A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115919761A (en) * | 2023-01-29 | 2023-04-07 | 浙江莎普爱思药业股份有限公司 | Pazufloxacin mesilate liquid preparation and preparation method thereof |
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