CN102988280B

CN102988280B - Garenoxacin eye drops

Info

Publication number: CN102988280B
Application number: CN201210378498.6A
Authority: CN
Inventors: 武俊芳; 牛杰; 李晓鹏; 韩晓红; 高利洁; 范文艳; 崔柳苏; 李颖虹; 焦俊娜; 许娜
Original assignee: Xinxiang Medical University
Current assignee: Xinxiang Medical University
Priority date: 2012-10-08
Filing date: 2012-10-08
Publication date: 2014-03-19
Anticipated expiration: 2032-10-08
Also published as: CN102988280A

Abstract

The invention relates to Garenoxacin eye drops and a preparation method thereof, belonging to the technical field of Western medicine preparation. Garenoxacin is wrapped by carrageenan and is prepared into the eye drops by adopting conventional preparations. The Garenoxacin eye drops can obviously reduce produced impurity, is enhanced in stability, not only is beneficial to improving the product quality, but also can avoid bitterness of liquor entering the nasal cavity or the oral cavity, is long in standing time in the eyes, and can improve the curative effect.

Description

A kind of T-3811 eye drop

Technical field

The invention belongs to Western medicine preparation technical field, particularly a kind of T-3811 eye drop.

Background technology

T-3811 chemistry 1-cyclopropyl-8-(difluoromethoxy)-7-[(1R by name)-2,3-dihydro-1-methyl-1H-isoindol-5-yl]-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid monomethanesulfonate, CAS is 223652-82-2, this product has entered the III clinical trial phase stage in the U.S., in Japan, enters the II clinical trial phase stage.This compound has activity to gram-positive bacteria and gram-negative bacteria, and some fastbacteria is still kept to active.This medicine can be injected also can be oral, and as oral, only need take once every day.

T-3811 has activity to multiple gram-positive bacteria, and the scope of MIC50s is 0.025-1.56mcg/mL, stronger than ciprofloxacin and levofloxacin star activity.For methicillin and mediated quinolone resistance staphylococcus aureus, drug resistance of vancomycin enterococcus and penicillin resistance streptococcus pneumoniae, its active and trovafloxacin quite or stronger.To detected most of bacterial strains, the activity of garenoxacin is all strong than levofloxacin, and trovafloxacin quite or stronger (ICAAC, Abs F158, F159; In JIUYUE, 1997) .Garenoxacin is also effective to multiple gram-negative bacteria, zoopery shows that oral garenoxacin infects mice PRSP or the effect of mediated quinolone resistance staphylococcus aureus systemic infection is better than ciprofloxacin, levofloxacin and trovafloxacin, hypodermic effect is better than ciprofloxacin (ICAAC, Abs F 159).Garenoxacin is suitable at mice, rat and Canis familiaris L. pharmacokinetic properties and ciprofloxacin with it, and oral administration biaavailability is in the scope of 43-96%.There is no at present T-3811 eye drop development and report both at home and abroad, and eye drop belongs to medicine for external use, the position of its effect is completely different with the dosage form of taking in conduct.Study and develop a kind of T-3811 eye drop and seem particularly urgent.

Summary of the invention

Object of the present invention is exactly the defect for prior art, and a kind of T-3811 eye drop and preparation method thereof is provided, to reach safely, effectively to treat the object that ophthalmology catches.

In order to achieve the above object, the present invention adopts following technical scheme: T-3811 and additives are dissolved in and in water for injection, make water-soluble solution or T-3811 and additives are made to the packaged with powder, granule, block, tablet, dissolve and form clear and bright solution before use with water for injection.

In implementing the process of the test of the technical program, we find that T-3811 dissolubility in water is extremely low, need to add cosolvent to increase dissolubility by test.Simultaneously the aqueous solution of T-3811 is also unstable, particularly more unstable under to illumination and hot environment.The passing in time of the aqueous solution of T-3811 can produce certain degradation impurity, and the existence of degradation impurity can affect the toxicology characteristic of said preparation.

In order to solve this technical barrier, by repetition test, study, we filter out following technical scheme through research for many years: it is mixed by following supplementary material component: a kind of T-3811 eye drop, it is characterized in that it is mixed by following supplementary material component: every milliliter of every finished product contains T-3811 1-5mg, carrageenan, antioxidant, metal chelating agent, cosolvent, osmotic pressure regulator, antibacterial, surfactant, viscosifier, extender, described antioxidant is the mixture of vitamin C 0.1-0.4mg and lecithin 0.2-0.7mg, described metal chelating agent is the mixture of disodiumedetate 0.05-0.3mg and calcium disodium chelate 0.05-0.3mg, cosolvent is the mixture of sodium salicylate 1-6mg and lysine 1-5mg, described osmotic pressure regulator is sodium chloride 3-8mg and glucose 1-15mg mixture, described antibacterial is the mixture of methyl parahydroxybenzoate 0.5-lmg and propyl p-hydroxybenzoate 0.13-0.2mg, described surfactant is Polysorbate 0.1-0.4mg, described viscosifier are methylcellulose 0.2-0.5mg, described extender is the mixture of mannitol 20-80mg and sorbitol 30-120mg.

The preparation method of above-mentioned a kind of T-3811 eye drop, step is as follows: the carrageenan solutions that preparation concentration is 1%-15%, ratio in carrageenan and T-3811 powder 0.1-1:1 takes T-3811, then in T-3811, add carrageenan solutions, make T-3811 carrageenan clathrate, all the other steps are prepared into eye drop by eye drop conventional method.

Compared with prior art, a kind of T-3811 eye drop preparing according to preparation method of the present invention, take and go on the market levofloxacin eye drops as contrast, the irritant reaction situation to conjunctiva, cornea and iris after observation animal eyes contact test sample.Embodiment prescription and commercially available levofloxacin eye drops are after single-dose, after multiple dosing, the embodiment of the present invention and commercially available levofloxacin eye drops zest all meet the requirements, and the holdup time is obviously longer than commercially available eye drop within the eye in experimentation, to can be observed the present embodiment prescription.

A kind of T-3811 eye drop preparing according to preparation method of the present invention, can make the impurity of its generation obviously reduce, stability increases, and is not only of value to and improves the quality of products, and can also make medicinal liquid enter in nasal cavity or oral cavity to feel not pained, can improve curative effect.

The specific embodiment

Form is described in further detail foregoing of the present invention again by the following examples, but this should be interpreted as to the scope of the above-mentioned theme of the present invention only limits to following example, all technology realizing based on foregoing of the present invention all belong to scope of the present invention.

Embodiment 1

Take the supplementary material of preparation 100ml T-3811 eye drop, be T-3811 100mg, carrageenan 10mg, vitamin C 0.1mg, lecithin 0.2mg, disodiumedetate 0.05mg, calcium disodium chelate 0.05mg, sodium salicylate 1mg, lysine 1mg, sodium chloride 3mg, glucose 1mg, methyl parahydroxybenzoate 0.5mg, propyl p-hydroxybenzoate 0.13mg, Polysorbate 0.1mg, methylcellulose 0.2mg, mannitol 20mg, sorbitol 30mg.

The carrageenan solutions that preparation concentration is 10% then adds carrageenan solutions in T-3811, makes T-3811 carrageenan clathrate; Take recipe quantity vitamin C, disodiumedetate, calcium disodium chelate, sodium salicylate are dissolved in appropriate water for injection, add T-3811 carrageenan clathrate, and stirring, heating make to dissolve; Separately get lecithin, methyl hydroxybenzoate, propyl p-hydroxybenzoate, lysine, sodium chloride, glucose, Polysorbate, methylcellulose, mannitol, sorbitol are dissolved in the water for injection boiling in right amount, be stirred to dissolve; Two liquid are merged, filter, water for injection is diluted to amount of preparation, with Sharpe phosphate-buffered salt, regulate pH value to boil 30 minutes to 5.0-5.5, cooling room temperature, surveys intermediate, after qualified, by 0.22 micron of filtering with microporous membrane, sterile filling, in plastics eyedrops bottle, obtains.

Embodiment 2

Take the supplementary material of preparation 100ml T-3811 eye drop, be T-3811 200mg, carrageenan 50mg, vitamin C 0.4mg, lecithin 0.7mg, disodiumedetate 0.3mg, calcium disodium chelate 0.3mg, sodium salicylate 6mg, lysine 5mg, sodium chloride 8mg, glucose 15mg, methyl parahydroxybenzoate 1mg, propyl p-hydroxybenzoate 0.2mg, Polysorbate 0.4mg, methylcellulose 0.5mg, mannitol 80mg, sorbitol 120mg.

The carrageenan solutions that preparation concentration is 5% then adds carrageenan solutions in T-3811, makes T-3811 carrageenan clathrate; Take recipe quantity vitamin C, disodiumedetate, calcium disodium chelate, sodium salicylate are dissolved in appropriate water for injection, add T-3811 carrageenan clathrate, and stirring, heating make to dissolve; Separately get lecithin, methyl hydroxybenzoate, propyl p-hydroxybenzoate, lysine, sodium chloride, glucose, Polysorbate, methylcellulose, mannitol, sorbitol are dissolved in the water for injection boiling in right amount, be stirred to dissolve; Two liquid are merged, filter, water for injection is diluted to amount of preparation, with Sharpe phosphate-buffered salt, regulate pH value to boil 30 minutes to 5.0-5.5, cooling room temperature, surveys intermediate, after qualified, by 0.22 micron of filtering with microporous membrane, sterile filling, in plastics eyedrops bottle, obtains.

Embodiment 3: to eye drop bitterness and the clinical research of the time of staying within the eye

Select 20 people to carry out clinical experiment, only have a people to feel to flow into the eye drop in oral cavity pained, all the other 19 people all think and can accept, and illustrate that T-3811 can effectively avoid the bitterness of medicine after carrageenan enclose, produce beyond thought effect.Other 20 people all represent eye drop of the present invention again the ophthalmic time of staying long, be longer than common Chloramphenicol Eye Drop.

Claims

1. a T-3811 eye drop, it is characterized in that it is mixed by following supplementary material component: every milliliter of every finished product contains T-3811 1-5mg, carrageenan, antioxidant, metal chelating agent, cosolvent, osmotic pressure regulator, antibacterial, surfactant, viscosifier, extender, described antioxidant is the mixture of vitamin C 0.1-0.4mg and lecithin 0.2-0.7mg, described metal chelating agent is the mixture of disodiumedetate 0.05-0.3mg and calcium disodium chelate 0.05-0.3mg, cosolvent is the mixture of sodium salicylate 1-6mg and lysine 1-5mg, described osmotic pressure regulator is sodium chloride 3-8mg and glucose 1-15mg mixture, described antibacterial is the mixture of methyl parahydroxybenzoate 0.5-lmg and propyl p-hydroxybenzoate 0.13-0.2mg, described surfactant is Polysorbate 0.1-0.4mg, described viscosifier are methylcellulose 0.2-0.5mg, described extender is the mixture of mannitol 20-80mg and sorbitol 30-120mg, described carrageenan solutions concentration is 1%-15%, the ratio of carrageenan and T-3811 powder is 0.1-1:1.

2. a kind of preparation method of T-3811 eye drop described in the claims 1, it is characterized in that step is as follows: the carrageenan solutions that preparation concentration is 1%-15%, ratio in carrageenan and T-3811 powder 0.1-1:1 takes T-3811, then in T-3811, add carrageenan solutions, make T-3811 carrageenan clathrate, all the other steps are prepared into eye drop by eye drop conventional method.