CN104069118B - Eye drop and preparation method thereof - Google Patents
Eye drop and preparation method thereof Download PDFInfo
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- CN104069118B CN104069118B CN201410310812.6A CN201410310812A CN104069118B CN 104069118 B CN104069118 B CN 104069118B CN 201410310812 A CN201410310812 A CN 201410310812A CN 104069118 B CN104069118 B CN 104069118B
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- eye drop
- eye
- tobramycin
- taurine
- antibacterial
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Abstract
The invention provides a kind of eye drop, wherein tobramycin, moxifloxacin hydrochloride and taurine combine with special ratios, have synergism for antibacterial and treatment eye inflammation disease.
Description
Technical field
The present invention relates to a kind of eye drop and preparation method thereof, wherein with tobramycin, moxifloxacin hydrochloride and taurine
For active component.
Background technology
Tobramycin is a kind of aminoglycoside medicine, through active transport by bacterial cell membrane, sub-with bacterial ribosome 30S
The specific receptor protein binding of unit, the formation of initiation complex between interference messenger ribonucleic acid and 30S subunit, suppresses albumen
Synthesis；Make DNA mispronounce, cause the synthesis of non-functioning protein；Polysome division is made to lose the merit of synthetic proteins
Energy.It is clinically used for the local infection of the external eyes caused by sensitive bacterial and appendages.It is compared with other aminoglycoside antibioticss,
Antimicrobial spectrum is wider, and curative effect is higher, and toxic reaction is little.Staphylococcus aureus in gram positive bacteria, streptococcus etc. and leather are blue cloudy
Property bacterium in some serratia marcecens and shigella dysenteriae etc. all sensitive to tobramycin.It is clinically used for treating conjunctivitis, keratitis, lachrymal sac
Inflammation, blepharitis, meibomitis etc..
Moxifloxacin (Avelox, Avalox) is the super broad spectrum quinolone class medicine that Bayer A.G develops, trade name
For " visiing multiple pleasure ", in JIUYUE, 1999 lists in Germany, and the same year, December obtained FDA approval listing in the U.S..Moxifloxacin shows in vitro
Go out gram positive bacteria, gram-negative bacteria, anaerobe, acid fast bacteria and atypical microorganism such as mycoplasma, chlamydia and legionella
There is broad spectrum antibiotic activity.Antibacterial mechanisms is interference II, IV topoisomerase.Topoisomerase is to control DNA topological sum DNA again
System, repair and transcribe in key enzyme.Moxifloxacin activity in vivo is high.Can be quickly by the most complete after moxifloxacin oral
Absorb.Absolute bioavailability a total of about 91%.When reaching peak 0.5～4 hour.Moxifloxacin is administered not to be affected by feed.Partly decline
Phase reaches 12 hours.Without cytochrome P 450 enzymes metabolism.Decrease the probability of drug drug interaction.Renal metabolism 45%,
Liver metabolism 52%, the patient of renal function injury and slight hepatic insufficiency is without adjusting dosage.
Taurine (i.e. taurine) first finds from the bile of cattle, is a kind of free amino acid, but is not albumen
The constituent of matter, was considered as the essential nutrients of cat from 1977, was also that infant nutrition institute is required.Experiment finds to lack cattle
During sulfonic acid, then causing cat retinal degeneration, visual performance goes down；Monkey retinal ultrastructure has degeneration to change.Clinical ophthalmology
Inflammatory reaction when being mainly used as suppression eye allergy, maintain the controlling of the pellucidity retinal diseases relevant with photic damage of crystal
Treat and prevent or delay cataractous formation.
In prior art, not yet it is disclosed tobramycin, moxifloxacin hydrochloride and taurine three combination and is used as eye drop.
Summary of the invention
Present invention applicant is surprised to find that and tobramycin, moxifloxacin hydrochloride and taurine is made with special ratios combination
Use for eye drop, for antibacterial and treatment eye inflammation disease, there is synergism.
The invention provides a kind of eye drop, wherein comprise tobramycin.
The invention provides a kind of eye drop, wherein comprise tobramycin and moxifloxacin hydrochloride.
The invention provides a kind of eye drop, wherein comprise tobramycin, moxifloxacin hydrochloride and taurine.
The invention provides a kind of eye drop, wherein comprise tobramycin, moxifloxacin hydrochloride and taurine, the weight of three
Amount ratio is 8:3:6.
Unless specifically stated otherwise, dosage unit of the present invention is weight.
The present invention is verified by experiments, only the compositions of the tobramycin of special ratios, moxifloxacin hydrochloride and taurine
Just there is Synergistic antimicrobial and the effect for the treatment of eye inflammation disease.Active component is different or active component is identical but consumption different
All can reduce therapeutic effect.
Detailed description of the invention
Embodiment 1
Eye drop prescription:
Tobramycin 4g
Moxifloxacin hydrochloride 1.5g
Taurine 3g
Sodium chloride 3g
EDTA-2Na 1g
Water for injection adds to 1000ml.
Preparation method:
(1) sodium chloride, EDTA-2Na, tobramycin, moxifloxacin hydrochloride and taurine water for injection are dissolved.
(2) using sulphuric acid or sodium hydroxide regulation pH value is 6.5-6.8.
(3) use 0.20 μm membrane filtration degerming, obtain eye drop.
(4) measuring eye drop pH value, osmotic pressure, content, after passed examination, fill is in eye-drop liquid bottle.
Antibacterial effect is tested
1. experiment in vitro
With escherichia coli, staphylococcus aureus, bacillus pyocyaneus, micrococcus scarlatinae, Candida albicans, kerekou pneumonia
Primary bacterium and Pseudomonas aeruginosa are test organisms, use nephelometry, investigate the fungistatic effect of antibacterial.
The preparation of bacteria suspension: escherichia coli, staphylococcus aureus, bacillus pyocyaneus, micrococcus scarlatinae, kerekou pneumonia
Primary bacterium and Pseudomonas aeruginosa are the most aseptically seeded in 10ml nutrient broth medium, 35 DEG C, cultivate 24h.Bacterium
Suspension physiological saline solution dilutes, and makes bacterial concentration reach 106cfu/ml.Candida albicans is aseptically seeded to 10ml
In improvement Martin's fluid medium, 25 DEG C, cultivate 48h.Bacteria suspension physiological saline solution dilutes, and makes bacterial concentration reach
106cfu/ml。
The preparation of test liquid: weigh respectively p-Hydroxybenzoate 0.2g and claim (measuring) take p-Hydroxybenzoate 0.2g,
Phenethanol 5ml, is dissolved in 100ml nutrient broth medium, for escherichia coli, staphylococcus aureus, bacillus pyocyaneus, suppuration
Property streptococcus, Klebsiella Pneumoniae and Pseudomonas aeruginosa test use.Weigh p-Hydroxybenzoate 0.2g respectively and claim (measuring)
Take p-Hydroxybenzoate 0.2g, phenethanol 5ml, be dissolved in 100ml improvement Martin's fluid medium, try for Candida albicans
With.Take 10ml test liquid in test tube, autoclaving.Each test bacterium sets 8 pipe test liquids, and sets one group of control tube.Aseptic bar
Under part, every test tube adds bacteria suspension 0.2ml.Escherichia coli, staphylococcus aureus, bacillus pyocyaneus, micrococcus scarlatinae,
Klebsiella Pneumoniae and Pseudomonas aeruginosa 35 DEG C, cultivate 24h, Candida albicans 25 DEG C, cultivate 48h.Observe solution in test tube
Whether clarify.
Test liquid group: table 1
Illustrate: comparative example 1-3 contains only tobramycin, moxifloxacin hydrochloride and single group of taurine one of which
Point, comparative example 4-6 contains two kinds of components, and comparative example 7-8 contains tobramycin, moxifloxacin hydrochloride and taurine three
Kind of component but consumption are varied from.
The antibacterial effect inspection technique guideline specified according to " Chinese Pharmacopoeia 2010 version two " annex, to the present invention
Test liquid carries out inhibitory effect checking test.
Experimental result is as follows:
Table 2 embodiment 1 inhibitory effect test organisms number declines lg value
Table 3 comparative example 1 inhibitory effect test organisms number declines lg value
Table 4 comparative example 2 inhibitory effect test organisms number declines lg value
Table 5 comparative example 3 inhibitory effect test organisms number declines lg value
Table 6 comparative example 4 inhibitory effect test organisms number declines lg value
Table 7 comparative example 5 inhibitory effect test organisms number declines lg value
Table 8 embodiment 6 inhibitory effect test organisms number declines lg value
Table 9 comparative example 7 inhibitory effect test organisms number declines lg value
Table 10 embodiment 8 inhibitory effect test organisms number declines lg value
Knowable to the data of table 2-table 9, the embodiment of the present invention 1 comprises tobramycin, moxifloxacin hydrochloride and taurine
Eye drop fungistatic effect is the strongest, relative to the combination of three kinds of components of one-component, the combination of two kinds of components and different amounts
(comparative example 1-8) the most substantially has collaborative fungistatic effect.
2. in vivo test
By the escherichia coli being inoculated on plain agar culture medium flat plate, staphylococcus aureus, bacillus pyocyaneus and blood
The micrococcus scarlatinae inoculating loop of agar plate scrapes, and normal saline is made into 2 × 10 respectively12CFU/L (survey than turbid instrument by photoelectricity
Determine concentration).By method (Ma Ji offers for Xiao Yi, Li Chen, Mei Qi Ping, Zhang Feng, remaining water English. rabbit eyes damage type bacterial keratitis move
The foundation of object model. Shaanxi medical journal, 2003；32 (2): 187-188) rabbit cornea damage (eyes) is caused with corneal trephine,
Rabbit every eye infections antibacterial 0.1mL, 2d Sterile Saline cotton swab takes eye discharge, puts in 4mL physiological saline solution bottle, uses
Its liquid is done antibacterial culturing by agar plate method.Carry out inflammatory score simultaneously, 0 grade: eye is bright without secretions；0.5 grade: nothing
Secretions covers, and eye is the redst and the most swollen；1 grade: secretions covers less than 6mm；2 grades: secretions covers and is full of 6mm；3 grades: secretions
Cover more than 6mm.According to standards of grading random packet.Treatment group (bacterial infection+eye drop of the present invention), does not treats matched group
(bacterial infection+drip normal saline), 6 rabbit of each group.Normal group (not modeling, not bacterial infection, a normal saline) 2
Only.Treatment group drips eye drop 0.8mL/d (eyes) of the present invention, does not treats matched group and Normal group drips normal saline 0.8mL/
D (eyes), every 0.1mL, 4 times/d, continuity point medicine 7d.Once mark every 24h eyes, Continuous Observation 7d, scoring knot
Fruit takes statistics and learns t inspection process.And before being administered 1d, after administration, 1,3,5,7d Sterile Saline cotton swabs take discharge of eye and make antibacterial
Cultivate, it is judged that yin and yang attribute result.D8 puts to death rabbit, takes cornea and puts in 40g/L formaldehyde and fixing to make pathological section, and HE dyes inspection
Look into.
There is inflammatory symptoms, the lighter's conjunctiva redness bloodshot eyes after infecting lagophthalmos 24h in four kinds of bacterium.Severe one general body state is not good enough companion
Conjunctiva redness is congested, and corneal edema thickens, and a large amount of secretions are yellow-white, is clung by upper palpebra inferior, and eyes close.Bacillus pyocyaneus
The micro-aobvious yellow green of lagophthalmos secretions infected.S. pyogenes infection inflammatory reaction is heavier, continues more than 7d.Standards of grading exist
1.5～3 grades.Bacteria cultivation results: be administered 4 kinds of antibacterial culturing of cornea secretions and be the positive, the embodiment of the present invention 1 eye drop
The treatment cornea secretions antibacterial culturing negative conversion rate escherichia coli of 5d, staphylococcus aureus, bacillus pyocyaneus are 100%,
Micrococcus scarlatinae 95%.Rabbit eyes appraisal result, compares with not treating matched group, and the embodiment of the present invention 1 eye drop is to large intestine
Angstrom uncommon bacterium, staphylococcus aureus, bacillus pyocyaneus, S. pyogenes infection group be administered after 4,5d have notable difference (P <
0.01, table 11).Pathological section, each Rotating fields of cornea that the front 3 kinds of bacterium of the embodiment of the present invention 1 eye drops in treatment infect is substantially complete,
Wound surface is covered by stratified squamous epithelium, and there is proliferation of fibrous tissue wound, the scarring healing of wound, has no that inflammatory cell soaks
Profit；Corneal edema seen from micrococcus scarlatinae treatment group part slice, thin piece, wound is the most associated with a small amount of cell infiltration；Do not treat
After matched group infects 4 kinds of bacterium, lagophthalmos all shows corneal edema, and vasodilation is congested, and wound is the most associated with ulcer, has a large amount of inflammation
Cellular infiltration and slough.Normal group cornea stands intact.
Table 11 is administered after 5d four kinds of antibacterial infected rabbits eye comparitive study (score value x ± s, n=12)
From table 11 data, the embodiment of the present invention 1 comprises the eye drop of tobramycin, moxifloxacin hydrochloride and taurine
The eye inflammation effect that treatment antibacterial infects is the strongest, relative to one-component, the combination of two kinds of components and the three of different amounts
The combination (comparative example 1-8) planting component the most substantially has synergistic therapeutic effect.
Claims (1)
1. an eye drop, wherein active component is made up of tobramycin, moxifloxacin hydrochloride and taurine, the weight ratio of three
Example is 8:3:6.
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|---|---|---|---|
| CN201410310812.6A CN104069118B (en) | 2014-07-01 | 2014-07-01 | Eye drop and preparation method thereof |
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| CN201410310812.6A CN104069118B (en) | 2014-07-01 | 2014-07-01 | Eye drop and preparation method thereof |
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| CN104069118B true CN104069118B (en) | 2016-08-24 |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080050335A1 (en) * | 2006-07-25 | 2008-02-28 | Osmotica Corp. | Ophthalmic Solutions |
| CN101461781A (en) * | 2009-01-06 | 2009-06-24 | 河北科技大学 | Gernebcin eye drops without bacteriostatic agent and preparation method thereof |
| CN101564374A (en) * | 2008-04-25 | 2009-10-28 | 北京和润创新医药科技发展有限公司 | Medicinal in situ forming eye gel |
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2014
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080050335A1 (en) * | 2006-07-25 | 2008-02-28 | Osmotica Corp. | Ophthalmic Solutions |
| CN101564374A (en) * | 2008-04-25 | 2009-10-28 | 北京和润创新医药科技发展有限公司 | Medicinal in situ forming eye gel |
| CN101461781A (en) * | 2009-01-06 | 2009-06-24 | 河北科技大学 | Gernebcin eye drops without bacteriostatic agent and preparation method thereof |
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| CN104069118A (en) | 2014-10-01 |
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Inventor after: Li Jian Inventor before: Huang Xiangbin Inventor before: Li Zhizheng Inventor before: Zhou Dai Inventor before: Xie Panjin |
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Effective date of registration: 20160718 Address after: 430040, Hubei, Wuhan Lake East and West Silver Lake office, gold and silver, 2 Hunan Street Applicant after: Wujing Pharmacy Co., Ltd. Wuhan Address before: The new Chengdu high tech Zone of Sichuan province 611731 City Road No. 22 Applicant before: Sichuan Xingkerong Pharmaceutical Co., Ltd. |
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