CN103565740A - Loteprednol etabonate suspension eye drops - Google Patents
Loteprednol etabonate suspension eye drops Download PDFInfo
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Abstract
The invention discloses loteprednol etabonate suspension eye drops. The loteprednol etabonate suspension eye drops contain loteprednol etabonate as an active component, water and one or more accessory materials for suspension eye drops. The used loteprednol etabonate micro-powder meets the particle size distribution conditions comprising that D50 is in a range of 3.0-4.0 microns, the maximum particle size is less than 30 microns, a ratio of micro-powder particles having sizes of 1-8 microns is in a range of 79-85%, and a ratio of micro-powder particles having sizes of 1-4 microns is in a range of 49-56%.
Description
Technical field:
The present invention relates to a kind of glucocorticoid eye suspendible eye drop.
Background technology:
Loteprednol etabonate (CAS:82034-46-6, Loteprednol etabonate), it is a kind of novel glucocorticoid, owing to having it, to rise ocular hypertensive side effect less, therefore for the preparation of ophthalmic preparation, existing ophthalmic preparation has the Loteprednol etabonate suspendible eye drop (trade name: Lu Dashu) of Bausch & Lomb Incorporated production.US Patent No. 5540930 and US5747061A disclose a kind of Loteprednol etabonate suspensoid that eye is used, nose is used that is applicable to, and all disclosing the Loteprednol etabonate grain size of micropowder scope adopting is 0.1-30 μ m, but unexposed particle size distribution more specifically.(Yu Qingzhen, Shanghai medicine the 20th volume o. 11th in 1999 disclose particle size range and the distribution as the dexamethasone drug powder of active component in 36-37) to China's document " development of compound tobramycin suspendible eye drop ".Wherein approach the micropowder that 99% drug particles is 1-5 μ m, we find, the suspensoid of preparing according to this diameter of aspirin particle scope, no doubt can meet national standard, but due to adding of the adjuvants such as suspending agent, liquid viscosity is increased, make to obtain suspension after drug particles precipitates completely, need the jolting of long period can realize sufficient redispersion, in Chinese Pharmacopoeia, eye is not made stipulations by the redispersibility of suspensoid, China's document " the suspending agent screening of acyclovir ophthalmic suspension " (Liu Jie etc., food and pharmaceutical the 10th volume o. 11th in 2008, a kind of detection method of redispersibility is disclosed 21-23), by adopting the nessler colorimetric tube upset of 25ml to mix, detect the redispersibility that average upset number of times characterizes suspensoid, but in fact, after unpacking, place and pollute for a long time, the packing specification of eye drop is generally no more than 5ml, and different from the glass material of color comparison tube, eye-drop liquid bottle is generally the plastic materials such as PET/PE/PP, the tension force of its inner surface and imbibition characteristic and glass material also exist obvious difference, in fact through us, test discovery, adopt suspension and conventional 25ml or the glass material color comparison tube of 50ml of conventional plastic bottle fractional pack, when redispersibility is tested, show characteristic inconsistent.Performance bad when some suspension of doing well in conventional redispersibility test adopts fractional pack to test again.In addition, a lot of user are when being used suspendible eye drop, often adopt jolting form to carry out redispersion, and jolting or upset number of times are generally all less, also different with the upset in common test, and, a lot of user are when drug development, development person often ignores this point, therefore the suspension of preparing, it all cannot realize sufficient redispersion in a lot of actual situations about using, thereby cause and splash into dosage and nominal standard dose is not inconsistent, especially along with the use of medicine, to the later stage, drug level and labelled amount produce larger difference, thereby will directly affect therapeutic effect.
Summary of the invention:
By test, the discovery that we are surprised, when selecting the active component micropowder of specific particle size distribution, resulting Loteprednol etabonate suspendible eye drop, when meeting suspensoid quality standard, through jolting for several times, just can be realized sufficient redispersion.Solved existing suspendible eye drop causes the drug level that splashes in eye and nominal value not to be inconsistent problem because redispersibility is bad.
The percentage ratio that relates to grain size of micropowder scope in description of the present invention and embodiment is particulate percentages, and the micro powder granule number in certain particle size range accounts for the percentage ratio of total particle number.Generally take laser particle analyzer to detect.
The particle diameter of indication of the present invention is D50 particle diameter, corresponding particle diameter when the cumulative particle sizes distribution number of a sample reaches 50%.Its physical significance be particle diameter be less than it granule number account for 50% of total amount.
The invention provides a kind of Loteprednol etabonate suspendible eye drop, contain the Loteprednol etabonate as active component, water is applicable to the adjuvant of suspendible eye drop with one or more, it is characterized in that, described Loteprednol etabonate micropowder, its particle size distribution meets the following conditions simultaneously:
D50 is 3.0-4.0 μ m, and maximum particle diameter is less than 30 μ m,
Particle diameter is at the micropowder of 1-8 μ m, and particulate percentages is 79%-85%, wherein
Particle diameter is at the micropowder of 1-4 μ m, and particulate percentages is 49%-56%.
Described suspendible eye drop, the bulking value percentage composition that it is characterized in that Loteprednol etabonate is 0.1%-2%.Preferred 0.2%-1%.
Described suspendible eye drop, it is characterized in that containing one or more eye medicinals, described eye medicinal is selected from one or more in hyaluronic acid or its salt, antibiotic, described antibiotic is selected from a kind of in quinolones, fluoroquinolones, aminoglycoside antibiotics, preferably a kind of in tobramycin, gentamycin, Gatifloxacin, ofloxacin, levofloxacin or its salt.
Described suspendible eye drop, the described adjuvant that is applicable to suspendible eye drop is selected from one or more in pH adjusting agent, osmotic pressure regulator, suspending agent, antioxidant, chelating agen, surfactant.
Described pH adjusting agent is selected from one or more in phosphoric acid and salt, boric acid and salt thereof, citric acid and salt thereof, acetic acid and salt thereof, tartaric acid and salt thereof, sulphuric acid, hydrochloric acid, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, tromethane.
Described osmotic pressure regulator is selected from glycerol, propylene glycol, sodium chloride, potassium chloride, Sorbitol, mannitol.One or more in preferred sodium chloride, glycerol, propylene glycol.
Described antibacterial is selected from one or more in benzalkonium chloride, benzethonium chloride, sorbic acid, potassium sorbate, benzyl alcohol, methyl parahydroxybenzoate (methyl hydroxybenzoate), propyl p-hydroxybenzoate (propylparaben), chlorobutanol.
Described suspending agent is selected from one or more in sodium carboxymethyl cellulose, hydroxypropyl emthylcellulose, hydroxypropyl cellulose, hydroxyethyl-cellulose, polyvinyl alcohol, carboxy vinyl polymer, polyvinyl pyrrolidone, carbomer.One or more in preferred carbomer, hydroxypropyl emthylcellulose, methylcellulose, hydroxyethyl-cellulose, polyvinyl pyrrolidone.
Described surfactant is selected from tween 80, polyoxyethylene castor oil 60, HCO60, polyglycol distearate, Polyethylene Glycol, lecithin, sucrose ester, polyoxyethylene aliphatic alcohol ether, one or more in poloxamer, tyloxapol (Tyloxapol), preferably one or more in tween 80, HCO60, polyoxyethylene castor oil 60, tyloxapol (Tyloxapol).
Described chelating agen is selected from disodium edetate or calcium disodium edetate.
Described antioxidant can be selected from one or more in sodium sulfite, sodium sulfite, sodium pyrosulfite.
Loteprednol etabonate suspendible eye drop preferably, is characterized in that the component that the described adjuvant that is applicable to suspendible eye drop contains following percent weight in volume:
Glycerol and/or propylene glycol, 1%-5%,
Tyloxapol, 0.1%-1%,
PVP K30,0.2%-1%.
Preferably also contain
Disodium edetate or calcium disodium edetate, 0.01%-0.1%,
Antibacterial, 0.01%-0.1%.
Described percent weight in volume is the percentage ratio of composition weight and suspendible eye drop volume.
The preparation method that a kind of Loteprednol etabonate micropowder is provided of the present invention, it is characterized in that, Loteprednol etabonate is dissolved in the organic solvent dissolving each other with water, separately getting water for injection stirs, stir on limit, limit slowly splashes into the organic solvent solution of Loteprednol etabonate, all splashes into rear lasting stirring 15-30min.Filtration obtains Loteprednol etabonate micropowder.
The preparation method of described Loteprednol etabonate micropowder, one or more in the preferred lower alcohol of organic solvent, acetone, oxolane, described lower alcohol is the monohydric alcohol of C1-C4, the envelope-bulk to weight ratio of described organic solvent and Loteprednol etabonate is preferably 1:10-20, preferably by the organic solvent that has dissolved Loteprednol etabonate filtering with microporous membrane degerming.The volume ratio of described water for injection and organic solvent is preferably 5-10:1.
Institute of the present invention defined particle size scope is for adopting laser particle analyzer to detect the data that obtain.
A kind of suspendible eye drop provided by the invention, compare with suspendible eye drop of the prior art, in standing storage a period of time, in situation at the bottom of drug powder has been deposited to bottle completely, all after 5-6 jolting or upset, can realize very soon redispersion, and suspendible eye drop prepared by the micropowder that adopts existing particle size range, although testing with suspendible eye drop provided by the invention, its settling ratio and the redispersion that adopts 25ml glass color comparison tube to carry out there is no significant difference, but when suspendible eye drop is distributed into after plastic bottle fractional pack, in the upset experiment 2 and jolting experiment that are more similar to actual service condition, eye drop provided by the invention, show better redispersion characteristic, the upset of number of times still less and and jolting under can realize sufficient redispersion, the eye drop that redispersion Temin is aobvious is better than adopting the drug powder of existing particle size range to be prepared, illustrate that the present invention is by the particle size range of preferred Loteprednol etabonate micropowder, obtain a kind of which kind of mode that no matter adopts and can realize very soon redispersion, and with the better suspendible eye drop of the eye-drop liquid bottle suitability of plastic bottle material, by the later stage uniformity, test simultaneously, more show, the eye drop Loteprednol etabonate eye drop provided by the invention of preparing with existing particle size range drug powder is because its redispersibility is better, between the whole operating period, can keep higher uniformity of dosage units, effective ingredient concentration is substantially with using the consumption of eye drop to change.
The specific embodiment
Adopt Hydro 2000MU type laser particle analyzer.
Following embodiment calculates inventory according to every 1000ml suspension, and the accessory formula of all suspendible eye drops is as follows,
The Loteprednol etabonate micropowder preparation method formula of embodiment 1 ~ embodiment 15 sees the following form, wherein
Solvent A is oxolane; Solvent B is ethanol; Solvent C is methanol; Solvent D is acetone
Ratio 1 represents the envelope-bulk to weight ratio of organic solvent and Loteprednol etabonate
Ratio 2 is the volume ratio of solvent and water
In embodiment 2, component 2 is tobramycin, and in embodiment 6, component 2 is levofloxacin hydrochloride, and in embodiment 10, component 2 is GATIFLOXACIN.
Described Loteprednol etabonate micropowder preparation method is: medicine material is dissolved into (heating if desired) in organic solvent, cross 0.45 μ m microporous filter membrane, getting water for injection stirs, maintaining under stirring condition, speed with 0.5-1ml/s slowly drips the organic solvent that has dissolved medicine in water, after finishing, stop stirring, within standing 1 hour, filtration drying obtains drug powder.Described drug powder particle size distribution meets following condition simultaneously:
D50 is 3.0-4.0 μ m, and maximum particle diameter is less than 30 μ m,
Particle diameter is at the micropowder of 1-8 μ m, and particulate percentages is 79%-85%, wherein
Particle diameter is at the micropowder of 1-4 μ m, and particulate percentages is 49%-56%.
Compound method:
The adjuvant of recipe quantity and water-soluble medicine (are only limited to embodiment 2, 6, 10) be dissolved in the water of recipe quantity 90%, after fully dissolving, obtain liquid <1>, take out 10% of liquid <1>, drug powder is added wherein and stirs and make dense thick suspension, again dense thick suspension is added in raffinate <1>, stir and supply water for injection to recipe quantity, obtain target suspension, specification described in table on suspension is distributed into 2ml or the bottled eye drop of 5ml.Standby.
Embodiment 1-3 eye-drop liquid bottle adopts PET(polyethylene terephthalate) material, embodiment 4-7 eye-drop liquid bottle adopts PP(polypropylene) material, and embodiment 7-10 eye-drop liquid bottle adopts PE(polyethylene) material
Embodiment 1
Accessory formula is hydroxypropyl emthylcellulose 10g
Tween 80 0.5g
HCO60 0.5g
Propylparaben 0.5g
Methyl hydroxybenzoate 0.5g
Calcium disodium edetate 1g
Sodium chloride 7g
Water for injection is to 1000ml
Embodiment 2
Accessory formula is hydroxyethylmethyl-cellulose 20g
Tween 80 0.5g
Glycerol 10g
Hyaluronate sodium 1g
HCO60 0.5g
Benzalkonium chloride
Calcium disodium edetate 1g
Water for injection is to 1000ml
When preparation to after adding tobramycin in liquid <1> with sulfur acid for adjusting pH to 5-6.
Embodiment 3.-8 accessory formula see the following form (in 1000ml suspension)
Embodiment 9
Accessory formula is methylcellulose 20g
Tween 80 3g
Propylparaben 0.5g
Methyl hydroxybenzoate 0.5g
Calcium disodium edetate 1g
Sodium chloride 7g
Water for injection is to 1000ml
Embodiment 10
Accessory formula is hydroxypropyl emthylcellulose 50g
Tween 80 0.5g
Glycerol 10g
Polyoxyethylene castor oil 60 0.5g
Benzalkonium chloride
Calcium disodium edetate 1g
Water for injection is to 1000ml
Reference examples 1-1-reference examples 10-1
According to the formula of embodiment 1-embodiment 10, adopt fluid energy mill to pulverize respectively and obtain Loteprednol etabonate micropowder, gained drug powder mean diameter is 10 μ m, and maximum particle diameter is less than 30 μ m, and the eye drop that packing obtains is routine 1-1 ~ reference examples 10-1 in contrast.
Reference examples 1-2-reference examples 10-2
According to the formula of embodiment 1-embodiment 10, adopt fluid energy mill to pulverize respectively and obtain Loteprednol etabonate micropowder, gained drug powder maximum particle diameter is less than 20 μ m, between 90% drug powder particle diameter 1-3 μ m, the eye drop that packing obtains is routine 1-1 ~ reference examples 10-2 in contrast.
EXPERIMENTAL EXAMPLE again distributes
Settling volume is than detecting
According to the detection method of disclosed suspendible eye drop in 2010 editions appendix 10 of Chinese Pharmacopoeia, detect embodiment 1-embodiment 10, reference examples 1-1 ~ reference examples 10-1, and reference examples 1-2 ~ reference examples 10-2 makes the settling ratio H of suspendible eye drop.Through detecting the settling ratio of all samples, be all greater than 0.90, meet the requirement in Chinese Pharmacopoeia 2010 editions.
Upset experiment 1 turns at vertical plane internal rotation around its center of gravity
To test drugs packaging in 25 mL nessler colorimetric tubes, after the static placement of room temperature 2d, spin upside down color comparison tube to bottom without precipitation, in suspension without grumeleuse.In experiment, every upset once refers to and will test medicine be housed, and original state is that mouth of pipe color comparison tube straight up planar carries out dextrorotation turnback to the opposite direction of the mouth of pipe towards original sensing at major axis, and reversal rate is upset per second 2 times.The average upset of record number of times.The results are shown in following table, n=5
| Embodiment numbering | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 |
| Average upset number of times | 2.6 | 2.4 | 2.4 | 2.6 | 2.4 | 2.6 | 2.6 | 2.4 | 2.6 | 2.4 |
| Reference examples numbering | 1-1 | 2-1 | 3-1 | 4-1 | 5-1 | 6-1 | 7-1 | 8-1 | 9-1 | 10-1 |
| Average upset number of times | 2.4 | 2.4 | 2.6 | 2.4 | 2.6 | 2.6 | 2.6 | 2.4 | 2.6 | 2.4 |
| Reference examples numbering | 1-2 | 2-2 | 3-2 | 4-2 | 5-2 | 6-2 | 7-2 | 8-2 | 9-2 | 10-2 |
| Average upset number of times | 2.4 | 2.6 | 2.6 | 2.4 | 2.4 | 2.4 | 2.4 | 2.6 | 2.4 | 2.4 |
When upset experiment 1 shows to adopt 25ml nessler colorimetric tube as experimental facilities, the sample redispersion characteristic of all embodiment and reference examples is basically identical without significant difference.
Upset experiment 2
Adopt and divided the embodiment 1-embodiment 10 installing, reference examples 1-1 ~ reference examples 10-1, and reference examples 1-2 ~ reference examples 10-2, after standing 2d, every group samples 10 bottles, overturn after 6 times, from bottleneck sampling, from upper strata sampling 0.1ml, survey the wherein concentration of Loteprednol etabonate and the ratio of nominal value immediately, and carry out experimental result and see the following form, the check of t in groups of Data Processing in Experiment employing SAS system (
)
Upset experiment 2 shows, Loteprednol etabonate suspendible eye drop provided by the invention, and after being distributed into the packing of the following specification of 5ml, after the experiment of overturning, its Loteprednol etabonate content and nominal value recording from bottleneck sampling is basically identical.And suspendible eye drop prepared by the drug powder that adopts other particle size range, the Loteprednol etabonate content and the nominal value that from bottleneck sampling, record exist obvious gap (P < 0.05).Illustrate in fact, the redispersion characteristic of the suspendible eye drop that adopts larger packing and fractional pack when overturning experiment is also inconsistent, and the present invention is by the particle size range of preferred Loteprednol etabonate, the better Loteprednol etabonate suspendible of redispersion characteristic eye drop when a kind of employing fractional pack is provided.
Jolting experiment 1
Loteprednol etabonate suspendible eye drop after the packing that the employing embodiment of the present invention and reference examples provide, method of testing is: forearm stretches out parallel with horizontal plane, hand-held medicine bottle, bottleneck vertically upward, be take ancon as axle, and in vertical guide, 90 °, fast rotational forearm is extremely vertical with horizontal plane, now bottleneck direction is parallel with horizontal plane, then fast forearm is being rotated to original position, completing this process and be jolting once, each jolting activity should complete in 1s.
Adopt and divided the embodiment 1-embodiment 10 installing, reference examples 1-1 ~ reference examples 10-1, and reference examples 1-2 ~ reference examples 10-2, after standing 2d, every group samples 10 bottles, after jolting 5 times, bottleneck sampling, from upper strata sampling 0.1ml, surveys the wherein concentration of Loteprednol etabonate and the ratio of nominal value, and carry out experimental result and see the following form, the check of t in groups of Data Processing in Experiment employing SAS system (
)
Jolting experiment shows, Loteprednol etabonate suspendible eye drop provided by the invention, and after being distributed into the packing of the following specification of 5ml, after carrying out jolting experiment, content and the nominal value of its Loteprednol etabonate medicine recording from bottleneck sampling are basically identical.And suspendible eye drop prepared by the drug powder that adopts other particle size range, content and the nominal value of the Loteprednol etabonate recording from bottleneck sampling exist obvious gap (P < 0.05), and with in upset experiment, record Loteprednol etabonate content and compare also on the low side, illustrate in fact, the redispersion characteristic of the suspendible eye drop that adopts larger packing and fractional pack when carrying out jolting experiment is also inconsistent, compare with the redispersion form of employing upset, the suspendible eye drop providing in prior art, more be not suitable for the redispersion mode that adopts jolting.
Later stage uniformity testing
Get embodiment 1 ~ embodiment 10, reference examples 1-1 ~ reference examples 10-1, and reference examples 1-2 ~ reference examples 10-2 makes each 10 bottles of suspendible eye drops.Every day, level was overturn 2 times according to method in upset experiment 2 after shaking 2 times immediately, ooze 10% of eye drop at once, all the other time eye drops are uprightly placed, within the 10th day, measure the concentration of Loteprednol etabonate and the ratio of nominal value of eye drop, described level concussion method of testing is once: forearm stretches out parallel with horizontal plane, hand-held eye drop medicine bottle, take ancon as axle, in horizontal plane, fast rotational forearm is 90 °, keep bottleneck vertically upward, and then fast forearm is rotated to original position, each jolting activity should complete in 1s.Experimental result sees the following form, the check of t in groups of Data Processing in Experiment employing SAS system (
)
Prove by experiment, adopt the suspendible eye drop of different-grain diameter drug powder, in continuing use procedure, using later stage Loteprednol etabonate content to have larger difference, the suspendible eye drop that the embodiment of the present invention provides, even adopt aforementioned number of times less, more inviolent concussion and flipped form are carried out redispersion, between the whole operating period, to the last also can also keep the homogeneity of content, embodied good redispersion characteristic, and suspension in reference examples is when adopting same upset or concussion form, redispersibility is just poor, using the concentration of later stage medicinal liquid that significant variation has occurred.
By above-mentioned experiment, can prove, the suspendible eye drop of conventional particle diameter can in use can cause initial eye drip medicament contg low, to using, later stage eye drip medicament contg is high, front and back gap is greatly about 10% left and right, the starting stage of especially using at eye drop needs most the stage of medicine often, and at this moment conventional suspendible eye drop often content is lower, cause the medicine deficiency that tells on, and the main cause that eye drop is used the higher untoward reaction often of the stage drug level in later stage to produce.In the present invention, by preferable particle size, the generation of the problems referred to above will better be avoided.
Claims (10)
1. a Loteprednol etabonate suspendible eye drop, contains as active component, and water and one or more are applicable to the adjuvant of suspendible eye drop, it is characterized in that, and described Loteprednol etabonate micropowder, its particle size distribution meets the following conditions simultaneously:
D50 is 3.0-4.0 μ m, and maximum particle diameter is less than 30 μ m,
Particle diameter is at the micropowder of 1-8 μ m, and particulate percentages is 79%-85%, wherein
Particle diameter is at the micropowder of 1-4 μ m, and particulate percentages is 49%-56%.
2. suspendible eye drop as claimed in claim 1, the bulking value percentage composition of its feature Loteprednol etabonate is 0.1%-2%.
3. suspendible eye drop as claimed in claim 1, is characterized in that containing one or more eye medicinals.
4. suspendible eye drop as claimed in claim 3, is characterized in that described eye medicinal is selected from one or more in hyaluronic acid or its salt, antibiotic.
5. the suspendible eye drop as described in as arbitrary in claim 1-4, is characterized in that the adjuvant of described suspendible eye drop is selected from one or more in pH adjusting agent, osmotic pressure regulator, suspending agent, antibacterial, antioxidant, chelating agen, surfactant.
6. suspendible eye drop as claimed in claim 10, is characterized in that described pH adjusting agent is selected from one or more in phosphoric acid and salt, boric acid and salt thereof, citric acid and salt thereof, acetic acid and salt thereof, tartaric acid and salt thereof, sulphuric acid, hydrochloric acid, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, tromethane.
7. suspendible eye drop as claimed in claim 10, is characterized in that described osmotic pressure regulator is selected from one or more in glycerol, propylene glycol, sodium chloride, potassium chloride, Sorbitol, mannitol.
8. suspendible eye drop as claimed in claim 10, is characterized in that described suspending agent is selected from one or more in sodium carboxymethyl cellulose, hydroxypropyl emthylcellulose, hydroxypropyl cellulose, hydroxyethyl-cellulose, polyvinyl alcohol, carboxy vinyl polymer, polyvinyl pyrrolidone, carbomer.
9. suspendible eye drop as claimed in claim 10, it is characterized in that described surfactant is selected from tween 80, polyoxyethylene castor oil 60, HCO60, Polyethylene Glycol-stearate, Polyethylene Glycol, lecithin, sucrose ester, polyoxyethylene alkyl ether, polyoxy stearate, polyoxyethylene one polyoxypropylene diols, tyloxapol (Tyloxapol).
10. suspendible eye drop as claimed in claim 1., it is characterized in that the component that the described adjuvant that is applicable to suspendible eye drop contains following percent weight in volume: glycerol and/or propylene glycol, 1%-5%, tyloxapol, 0.1%-1%, PVP K30,0.2%-1%.
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| CN106265502A (en) * | 2015-05-27 | 2017-01-04 | 天津金耀集团有限公司 | A kind of stable Loteprednol etabonate suspension eye drop composition |
| CN106902079A (en) * | 2015-12-21 | 2017-06-30 | 天津金耀集团有限公司 | A kind of Loteprednol etabonate suspension eye drop composition |
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| CN106265502A (en) * | 2015-05-27 | 2017-01-04 | 天津金耀集团有限公司 | A kind of stable Loteprednol etabonate suspension eye drop composition |
| CN106902079A (en) * | 2015-12-21 | 2017-06-30 | 天津金耀集团有限公司 | A kind of Loteprednol etabonate suspension eye drop composition |
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Application publication date: 20140212 Assignee: Tianjin Pharmaceutical Industry Group Corp., Ltd. Assignor: Tianjin Jinyao Group Co., Ltd. Contract record no.: 2015120000054 Denomination of invention: Loteprednol etabonate suspension eye drops License type: Common License Record date: 20150916 Application publication date: 20140212 Assignee: Pharmaceutical Co., Ltd. Tianjin Jin Yao Assignor: Tianjin Pharmaceutical Industry Group Corp., Ltd. Contract record no.: 2015120000076 Denomination of invention: Loteprednol etabonate suspension eye drops License type: Fen Xuke Record date: 20150929 |
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