CN102716074A - Bimatoprost eye drops and preparation method thereof - Google Patents
Bimatoprost eye drops and preparation method thereof Download PDFInfo
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- CN102716074A CN102716074A CN2012102154560A CN201210215456A CN102716074A CN 102716074 A CN102716074 A CN 102716074A CN 2012102154560 A CN2012102154560 A CN 2012102154560A CN 201210215456 A CN201210215456 A CN 201210215456A CN 102716074 A CN102716074 A CN 102716074A
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Abstract
The invention discloses a bimatoprost composition. The composition comprises an effective treatment dose of bimatoprost, non-ionic surfactant and a pharmaceutically acceptable carrier; the invention also provides a preparation method for the bimatoprost composition; and by the bimatoprost composition, the problem of low dissolubility of bimatoprost in the preparation process can be solved, the stability of bimatoprost at high temperature is improved, and the forming of relative substances is reduced.
Description
Technical field
The invention belongs to medical technical field, relate to new prostaglandins anti-glaucoma medicine preparation, specifically a kind of plain eye drop in Bei Mei prostatitis and preparation method thereof that contains.
Background technology
Glaucoma is the too high oculopathy that causes optic nerve lesion of one type of intraocular pressure (IOP), is world's second largest diseases causing blindness, the blind most important reason of irreversibility.
At present glaucoma treatment is intended to reduce IOP, and appearance efficient, the newtype drug derivatives of prostaglandins that has no side effect, for glaucoma patient has brought Gospel.The prostaglandins medicine more and more receives patient's welcome with good intraocular pressure lowering effect with remarkable safety, and the domestic prostaglandins medicine that has gone on the market comprises at present: latanoprost, travoprost and Bei Mei prostatitis are plain.
Bei Mei prostatitis plain (Bimatoprost) is a kind of synthetic prostaglandin analog, has the active activity of the intraocular pressure of reduction.Its chemical name is:
(Z)-7-[(1R, 2R, 3R, 5S)-3,5-dihydroxy-2 [(1E, 3S)-3-hydroxyl-5-phenyl-1-pentenyl] cyclopenta]-5-N-ethyl heptene amide.
Bei Mei prostatitis element is the plain type anti-glaucoma medicine in second filial generation prostatitis, has become a line anti-glaucoma agents abroad.Different with latanoprost and travoprost; It is a kind of synthetic prostatitis amide; Optionally simulated the effect of naturally occurring prostatitis amide, had dual blood pressure lowering mechanism, can reduce intraocular pressure through trabecular reticulum and two outflow approach of Fructus Vitis viniferae sclera through increasing aqueous humor.External clinical studies show is dripped once (evening) Bei Mei prostatitis element every day, can reduce intraocular pressure 7～8mmHg.Drip first with intraocular pressure after about 4 hours and begin to reduce, effect reaches maximum within 8～12 hours.The plain average intraocular pressure lowering effect in external existing bibliographical information Bei Mei prostatitis can reach more than 30%, compares with timolol, and reducing iop has significant difference.No matter compare with latanoprost, be glaucoma, normal-pressure glaucoma or ocular hypertension patient, and the plain intraocular pressure lowering amplitude in Bei Mei prostatitis is bigger; Up-to-date foreign study shows: for the glaucomatous control of intraocular pressure in the daytime of stripping off property, Bei Mei prostatitis element also has better effect than latanoprost.Compare with travoprost, Bei Mei prostatitis element also provides better intraocular pressure lowering effect, has more patient can reach lower target intraocular pressure through using Bei Mei prostatitis element.
The plain route of administration in Bei Mei prostatitis is the eye drip administration; The plain eye drop in Bei Mei prostatitis went on the market in the U.S. in 2006, and commodity are called the Lumigan eye drop, and its disclosed prescription is Bei Mei prostatitis plain 0.03%; Benzalkonium chloride (antiseptic) 0.005%, adjuvant are sodium chloride, sodium hydrogen phosphate, citric acid.Of its incidental description, the PH of this commercially available eye drop is 6.8-7.8, and osmotic pressure is 290mOsmol/kg.
As everyone knows, the process for preparation of eye drop is generally dosing-filtration-fill, and wherein filtering is 0.22 micron aseptic filtration, and is must step.Bei Mei prostatitis element is an insoluble drug; Benzalkonium chloride in original prescription is except that as the antiseptic; Owing to itself also be a kind of surfactant; So can play the effect of part solubilising, but this solubilization is far from being enough to Bei Mei prostatitis element, because Bei Mei prostatitis element is almost insoluble in water.Therefore ten minutes is easily by membrane retention or absorption in the preparation process of the plain eye drop in this commercially available Bei Mei prostatitis, and content descends after causing filtering.The prior art that addresses the above problem is for increasing initial inventory according to the content after filtering, and feeds intake as 130%, obtains the medicinal liquid of 100% content after the filtration.
But the problem that thereupon occurs is to waste raw material.The plain raw material in Bei Mei prostatitis is because synthetic being difficult for is very expensive, and units up to ten thousand one gram increases inventory and can increase production cost greatly.The aqueous solution of Bei Mei prostatitis element is also unstable simultaneously, and is particularly unstable more under the environment to illumination and heat.The plain aqueous solution passing in time in Bei Mei prostatitis can produce certain degradation impurity, and the existence of degradation impurity can influence the toxicology characteristic of said preparation.
Therefore, be badly in need of the plain eye drop in a kind of stability-enhanced Bei Mei prostatitis in this area, and the method for the plain eye drop in the Bei Mei prostatitis that can reduce production costs.
Summary of the invention
The purpose of this invention is to provide a kind of stable eye drop that contains Bei Mei prostatitis element and preparation method thereof, to reach safely, effectively to treat glaucomatous purpose.
In order to achieve the above object, inventor of the present invention adds non-ionic surface active agent and can improve its dissolubility greatly through discovering in a large number in the plain ophthalmic preparation in Bei Mei prostatitis, can solve the problem of wastage of material in the preparation process.Simultaneously, we also find, compare with disclosed prescription, add non-ionic surface active agent, have improved the stability of the plain ophthalmic preparation in Bei Mei prostatitis.
Add its deliquescent beneficial effect of non-ionic surface active agent raising and see embodiment 6.
Add non-ionic surface active agent raising stable beneficial effect see embodiment 7.
One aspect of the present invention provides a kind of Bei Mei of containing prostatitis plain preparation composition for eyes, and said compositions comprises Bei Mei prostatitis element, non-ionic surface active agent and the pharmaceutically acceptable carrier of treating effective dose.
The plain consumption in Bei Mei according to the invention prostatitis is 0.001-0.5% (w/v), is preferably 0.03% (w/v).
Ionic surfactant pack according to the invention is drawn together polyoxyethylene-type non-ionic surface active agent and polyol-based non-ionic surfactant, is preferably polyoxyethylene hydrogenated Oleum Ricini 60, polyoxyethylene hydrogenated Oleum Ricini 40, polyoxyethylene castor oil 35, polyoxyethylene sorbitan monoleate, Polyethylene Glycol-stearate and combination thereof.
In a preferred embodiment of the present invention, the consumption of said non-ionic surface active agent is 0.001-10% (w/v), is preferably 0.01-6% (w/v).
In the present invention, said pharmaceutically acceptable carrier is conventional in the art, and said pharmaceutically acceptable carrier includes but not limited to the component of one or more isoosmotic adjusting agent, PH regulator, antibacterial and solvent.
Dosage form at ophthalmic preparation according to the invention is gel for eye use or eye drop, and preferably, the dosage form of said ophthalmic preparation is an eye drop.
In the present invention; Said isoosmotic adjusting agent is the usual component in the preparation of this area, can be selected from the mixture of any one or multiple arbitrary proportion in sodium chloride, glucose, mannitol, glycerol, propylene glycol, borate buffer or phosphate buffer and mixing thereof, Borax or the Chile saltpeter.Preferred osmotic pressure regulator is sodium chloride, glucose or the two mixture, or the combination of borate buffer or phosphate buffer.More preferably osmotic pressure regulator is the combination of sodium chloride and borate buffer or phosphate buffer
In preferred embodiment of the present invention, said isoosmotic adjusting agent is a sodium chloride, and content is the combination of 0.3-0.6% (w/v) and buffer 0.5-1.5% (w/v); Most preferably, said isoosmotic adjusting agent be 0.5% (w/v) sodium chloride and 0.8% (w/v) phosphate buffer or with the combination of 1.2% (w/v) borate buffer.The borate buffer of the preferred 1.0-1.5% of said buffer (w/v) (in boric acid and Borax weight with account for composition total weight percent) or content be the phosphate buffer (in the weight of sodium hydrogen phosphate and citric acid and account for composition total weight percent) of 0.8-1.2% (w/v).Preferably, buffer is a boronic acid containing 1.15%, the borate buffer of Borax 0.05% (w/v); Or phosphoric acid disodium hydrogen 0.75%, the phosphate buffer of citric acid 0.05% (w/v) is in the weight of said compositions.
Described antibacterial is the usual component in the preparation of this area, can be selected from the mixture of any one or multiple arbitrary proportion in methyl parahydroxybenzoate, ethylparaben, propyl p-hydroxybenzoate, benzyl alcohol, phenethanol, sorbic acid, salicylic acid, chlorobutanol, benzalkonium chloride, benzalkonium bromide, thimerosal or the phenoxyethanol.Preferably antibacterial is ethylparaben and propyl p-hydroxybenzoate mixture, and content is 0.01-0.04% (w/v), benzalkonium chloride, and content is that 0.005-0.01% (w/v) or benzalkonium bromide content are 0.015-0.05% (w/v).More preferably, said antibacterial is selected from 0.03% (w/v) ethylparaben and propyl p-hydroxybenzoate mixture, 0.005% (w/v) benzalkonium chloride, or 0.01% (w/v) benzalkonium bromide.
Described eye drop pH value of aqueous solution is 5.0～9.0.Preferred pH value is 6.0～8.0.Said PH regulator is selected from the usual component in the preparation of this area, and the routine that it is selected and content all can be followed is in the industry considered.Said PH regulator can be selected sodium hydroxide and/or hydrochloric acid, citric acid, sulphuric acid, sodium citrate, triethanolamine and composition thereof.Preferably, said PH regulator is selected from hydrochloric acid or sodium hydroxide.
As known in the art, need often to use buffer that pH value is adjusted to a required scope that is suitable for a usefulness.Known many buffer that comprises inorganic acid salt are like hac buffer, borate buffer, Palitzsch, PBS, Sha Shi PBS, lucky Fei Shi buffer or citrate buffer.
Described solvent is selected from the usual component in the preparation of this area, and the routine that it is selected and content all can be followed is in the industry considered.Preferably, said solvent is selected from normal saline and/or water for injection.
In addition, preparation of the present invention can also comprise other usual component in the ophthalmic preparation, for example thickening agent or viscosity intensifier, extender, antioxidant, metal chelating agent etc.
A kind of excipient commonly used in ophthalmic composition is viscosity intensifier or thickening agent.Use the thickening agent can be for various reasons, comprise from the improved formulations form contacting with the raising bioavailability to increasing with eyeball to make things convenient for administration.Viscosity intensifier can comprise the polymer that contains hydrophilic group, hydrophilic group such as monosaccharide, polysaccharide, ethylene oxide group, oh group, carboxylic acid or other charged functional groups.Be not in order to limit scope of the present invention, some useful examples of viscosity enhancing agents are methylcellulose, sodium carboxymethyl cellulose, hydroxypropyl emthylcellulose, polyvidone, polyvinyl alcohol and Polyethylene Glycol.
Extender can be selected from the mixture of any one or multiple arbitrary proportion in mannitol, sorbitol or the xylitol.
Antioxidant can be selected from the mixture of any one or multiple arbitrary proportion in sodium sulfite, sodium sulfite, sodium pyrosulfite, sodium thiosulfate, citric acid, tartaric acid, phosphoric acid, vitamin C, vitamin E, lecithin or the aminoacid.
Metal chelating agent can be selected from the mixture of any one or multiple arbitrary proportion in disodiumedetate, calcium disodium chelate, tartaric acid, phosphoric acid or the two mercapto ethyl glycines.The preferable alloy chelating agent is disodiumedetate, calcium disodium chelate, calcium disodium chelate and calcium disodium chelate mixture.
The plain preparation composition for eyes in Bei Mei of the present invention prostatitis also can be prepared into various pharmaceutically acceptable dosage forms.Preferably, the dosage form of said compositions is gel for eye use or eye drop.More preferably, the dosage form of said compositions is an eye drop.
Method for preparing of the present invention is that non-ionic surface active agent is dissolved in the water for injection, adds Bei Mei prostatitis element, and stirring, heating make dissolving; Other get osmotic pressure regulator, antibacterial, buffer and or other pharmaceutically acceptable carriers such as viscosifier be dissolved in the water for injection that boils, stir and make dissolving; After being cooled to room temperature two liquid are merged, filter, be diluted to the preparation full dose with water for injection, regulate pH value to 6.5～8.0, through 0.22 μ m filtering with microporous membrane, sterile filling promptly gets in the plastics eyedrops bottle.
The packing of product of the present invention can be taked multiple-unit container, props up like 2.5ml/, also can take unit dose package, props up like 0.4ml/, and every disposable, and wherein unit dose package can add or not add antiseptic as required.
According to the plain eye drop in a kind of Bei Mei prostatitis that method for preparing of the present invention prepares, preparation technology is reasonable, and easy operating can make the impurity of its generation obviously reduce simultaneously, and stability increases, and not only is of value to and improves the quality of products, and can also improve curative effect.
The specific embodiment
Further specify through the following specific embodiment, how these instances just for making and use thing of the present invention that direction and guidance are provided, and be not intended to and limit scope of the present invention by any way.
Embodiment 1
Prescription:
Preparation technology: polyoxyethylene hydrogenated Oleum Ricini 60 is dissolved in the water for injection, adds Bei Mei prostatitis element, stirring, heating make dissolving; Other gets sodium chloride, BZK, EDTA-2Na, boric acid, Borax and is dissolved in the water for injection that boils, and stirs to make dissolving; After being cooled to room temperature two liquid are merged, filter, be diluted to the preparation full dose with water for injection, regulate pH value to 6.5～8.0, through 0.22 μ m filtering with microporous membrane, sterile filling promptly gets in the plastics eyedrops bottle.
Embodiment 2
Prescription:
Preparation technology: polyoxyethylene hydrogenated Oleum Ricini 40 is dissolved in the water for injection, adds Bei Mei prostatitis element, stirring, heating make dissolving; Other gets sodium chloride, benzalkonium bromide, EDTA-2Na, methylcellulose, boric acid, Borax and is dissolved in the water for injection that boils, and stirs to make dissolving; After being cooled to room temperature two liquid are merged, filter, be diluted to the preparation full dose with water for injection, regulate pH value to 6.5～8.0, through 0.22 μ m filtering with microporous membrane, sterile filling promptly gets in the plastics eyedrops bottle.
Embodiment 3
Prescription:
Preparation technology: polyoxyethylene hydrogenated Oleum Ricini 35 is dissolved in the water for injection, adds Bei Mei prostatitis element, stirring, heating make dissolving; Other gets sodium chloride, BZK, sodium pyrosulfite, sodium hydrogen phosphate, citric acid and is dissolved in the water for injection that boils, and stirs to make dissolving; After being cooled to room temperature two liquid are merged, filter, be diluted to the preparation full dose with water for injection, regulate pH value to 6.5～8.0, through 0.22 μ m filtering with microporous membrane, sterile filling promptly gets in the plastics eyedrops bottle.
Embodiment 4
Prescription:
Preparation technology: polyoxyethylene sorbitan monoleate is dissolved in the water for injection, adds Bei Mei prostatitis element, stirring, heating make dissolving; Other gets sodium chloride, ethylparaben, propyl p-hydroxybenzoate, sodium hydrogen phosphate, citric acid and is dissolved in the water for injection that boils, and stirs to make dissolving; After being cooled to room temperature two liquid are merged, filter, be diluted to the preparation full dose with water for injection, regulate pH value to 6.5～8.0, through 0.22 μ m filtering with microporous membrane, sterile filling promptly gets in the plastics eyedrops bottle.
Embodiment 5
Prescription:
Preparation technology: polyoxyethylene sorbitan monoleate is dissolved in the water for injection, adds Bei Mei prostatitis element, stirring, heating make dissolving; Other gets sodium chloride, benzalkonium chloride, sodium carboxymethyl cellulose, sodium pyrosulfite, EDTA-2Na, sodium hydrogen phosphate, citric acid and is dissolved in the water for injection that boils, and stirs to make dissolving; After being cooled to room temperature two liquid are merged, filter, be diluted to the preparation full dose with water for injection, regulate pH value to 6.5～8.0, through 0.22 μ m filtering with microporous membrane, sterile filling promptly gets in the plastics eyedrops bottle.
The plain eye drop prescription in embodiment 6 Bei Mei prostatitis is to the comparison of the plain dissolubility in Bei Mei prostatitis
To carrying out the comparison of the plain dissolubility in Bei Mei prostatitis, compare two prescriptions changes in solubility in preparation technology by the prescription B that has added non-ionic surfactant polyoxyethylene castor oil hydrogenated 60 in open prescription A that has gone on the market and the prescription.
Prescription A
Preparation technology: the Bei Mei prostatitis element that takes by weighing recipe quantity is in water for injection, and stirring, heating make dissolving; Other gets sodium chloride, BZK, sodium hydrogen phosphate, citric acid in water for injection, stirs to make dissolving; After being cooled to room temperature two liquid are merged, filter, be diluted to the preparation full dose with water for injection, regulate pH value to 6.5～8.0, through 0.22 μ m filtering with microporous membrane, sterile filling promptly gets sample A in the plastics eyedrops bottle.
Prescription B
Preparation technology: polyoxyethylene hydrogenated Oleum Ricini 60 is dissolved in the water for injection, adds Bei Mei prostatitis element, stirring, heating make dissolving; Other gets sodium chloride, BZK, EDTA-2Na, boric acid, Borax and is dissolved in the water for injection that boils, and stirs to make dissolving; After being cooled to room temperature two liquid are merged, filter, be diluted to the preparation full dose with water for injection, regulate pH value to 6.5～8.0, through 0.22 μ m filtering with microporous membrane, sterile filling promptly gets sample B in the plastics eyedrops bottle.
Test sample A, the forward and backward content of sample B filtering with microporous membrane is seen table 1
Conclusion: the prescription filtering with microporous membrane front and back content that adds non-ionic surface active agent does not have to change basically, and the preceding content of filtering with microporous membrane is lower among the sample A, filters back content decline, possibly be not dissolving fully of principal agent, and tunicle has been held back.
Detection method of content: measure according to HPLC (two appendix VD of Chinese Pharmacopoeia version in 2000).
Chromatographic condition and system suitability test: use octadecylsilane chemically bonded silica to be filler; Mixed solution with water-acetonitrile-methanol (72: 18: 10) of containing 0.03% trifluoroacetic acid is a mobile phase; Flow velocity is 1ml/min; The detection wavelength is 210nm, and number of theoretical plate calculates by plain peak, Bei Mei prostatitis should be not less than 6000.
Algoscopy: precision takes by weighing the about 60mg of the plain reference substance in Bei Mei prostatitis; Dissolve and be diluted to the solution that concentration is 0.06mg/ml with retarder thinner [mixed solution of water-acetonitrile-methanol (78: 22: 10)]; As contrast solution: precision is measured these article 5ml, puts in the 25ml measuring bottle, adds retarder thinner to scale; Shake up, as need testing solution; Precision is measured reference substance solution and each 100ul of need testing solution, injects chromatograph of liquid, and the record chromatogram, promptly gets with calculated by peak area by external standard method.
Embodiment 7 stability experiments
Adopt the prescription among the embodiment 4 to prepare the plain eye drop in Bei Mei prostatitis, press commercially available back, place listing sample " Lu Meigen " (not containing surfactant) simultaneously, carry out influence factor's experiment and stability experiment.Result such as table 2:
Through the study on the stability experiment, this eye drop visible foreign matters, pH value, character, content, related substance etc. are all up to specification, and compare with commercially available sample, and embodiment 1,4 prescription stability of formulation are higher than commercially available sample.
Plain eye drop in embodiment 8 Bei Mei prostatitis and commercially available Lu Meigen eye drop toxicology test are relatively
One, test specimen
The plain eye drop specification in the embodiment of the invention 1 Bei Mei prostatitis: 2.5ml trial-production
The plain eye drop specification in the embodiment of the invention 4 Bei Mei prostatitis: 2.5ml trial-production
Commercially available Lu Meigen eye drop specification: 2.5ml lot number: 71412 manufacturing enterprises: U.S. Ai Ligen drugmaker
(test specimen of embodiment of the invention prescription preparation is according to " 2005 editions two appendix eye drop items of Chinese pharmacopoeia require to carry out drug content, its related substances, pH value, visible foreign matters, visual examination down.Be the test specimen after up-to-standard.)
Two, test objective
With listing Lu Meigen eye drop is contrast, observes behind the animal eyes contact test sample IR situation to conjunctiva, cornea and iris.
Three, test method and process
(1) single-dose test: get 8 of healthy white rabbit, be divided into 2 groups, left eye is with the prescription of the embodiment of the invention 1, example 4, and right eye all adopts the listing product as contrast.Respectively at before the eye drip with eye drip after 2h, 6h, 24h, 48h, 72h and used fluorescent staining in 7 days, slit lamp observation is to the irritative response of conjunctiva, cornea and iris.
(2) multiple dosing test: get 8 of healthy white rabbit, be divided into 2 groups, left eye is with the prescription of the embodiment of the invention 1, example 4, and right eye all adopts the listing product as contrast.Every day, eye drip was 5 times, and continuous 14 days, respectively at using fluorescent staining in 2,4,6,8,10,12,14 days before the eye drip with behind the eye drip, slit lamp observation was to the irritative response of conjunctiva, cornea and iris.Testing standard:
The score value result:
1. single-dose result of the test
2. multiple dosing result of the test
Four, conclusion
With the score value statistical calculations, the embodiment of the invention 1,4 and commercially available eye drop are behind single-dose, and be all non-stimulated to testing result, explains that this prescription does not increase zest.
Behind multiple dosing, the zest of finding the embodiment of the invention 1,4 prescriptions does not increase zest with commercially available eye drop, and can be observed present embodiment in the experimentation and write out a prescription that the holdup time obviously is longer than commercially available eye drop within the eye.
Claims (9)
1. the plain eye drop in a Bei Mei prostatitis, this eye drop contain that the Bei Mei prostatitis is plain to be active component, it is characterized in that it also contains non-ionic surface active agent and pharmaceutically acceptable carrier.
2. the plain eye drop in Bei Mei as claimed in claim 1 prostatitis is characterized in that: the plain consumption in said Bei Mei prostatitis is 0.001-0.5% (w/v).
3. the plain eye drop in Bei Mei as claimed in claim 1 prostatitis, it is characterized in that: said non-ionic surface active agent is polyoxyethylene-type non-ionic surface active agent and polyol-based non-ionic surfactant.
4. the plain eye drop in Bei Mei as claimed in claim 3 prostatitis is characterized in that: said non-ionic surface active agent is that polyoxyethylene hydrogenated Oleum Ricini 60, polyoxyethylene please be changed Oleum Ricini 40, polyoxyethylene castor oil 35, polyoxyethylene sorbitan monoleate, Polyethylene Glycol, stearate, Polyethylene Glycol-stearate combination.
5. the plain eye drop in Bei Mei as claimed in claim 4 prostatitis is characterized in that the consumption of said non-ionic surface active agent is 0.001-10% (w/v).
6. the plain eye drop in Bei Mei as claimed in claim 1 prostatitis, it is characterized in that: said pharmaceutically acceptable carrier comprises the component of one or more isoosmotic adjusting agent, PH buffer agent, antiseptic and solvent.
7. the plain eye drop in Bei Mei as claimed in claim 1 prostatitis, it is characterized in that: the dosage form of said eye drop is gel for eye use or eye drop.
8. method for preparing the plain eye drop in Bei Mei as claimed in claim 7 prostatitis is characterized in that this method may further comprise the steps:
(1) take by weighing non-ionic surface active agent and be dissolved in the water for injection, add Bei Mei prostatitis element, stirring, heating make dissolving;
(2) get other pharmaceutically acceptable carriers such as osmotic pressure regulator, antibacterial, PH buffer agent, viscosifier in addition and be dissolved in the water for injection that boils, stir and make dissolving;
(3) be cooled to after the room temperature two liquid are merged, filter, be diluted to the preparation full dose with water for injection;
(4) regulate pH value to 6.5～8.0, through 0.22 μ m filtering with microporous membrane, sterile filling promptly gets in the plastics eyedrops bottle.
9. method for preparing the plain eye drop in Bei Mei as claimed in claim 8 prostatitis is characterized in that this method is:
Prescription:
Preparation technology: take by weighing polyoxyethylene hydrogenated Oleum Ricini 60 and be dissolved in the water for injection, add Bei Mei prostatitis element, stirring, heating make dissolving; Get and ooze sodium chloride, EDTA-2Na, boric acid, Borax and be dissolved in the water for injection that boils, stir and make dissolving; After being cooled to room temperature two liquid are merged, filter, be diluted to the preparation full dose with water for injection, regulate pH value to 6.5～8.0, through 0.22 μ m filtering with microporous membrane, sterile filling promptly gets in the plastics eyedrops bottle.
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| CN 201210215456 CN102716074B (en) | 2012-06-28 | 2012-06-28 | Bimatoprost eye drops and preparation method thereof |
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| CN 201210215456 CN102716074B (en) | 2012-06-28 | 2012-06-28 | Bimatoprost eye drops and preparation method thereof |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104208015A (en) * | 2013-05-29 | 2014-12-17 | 天津金耀集团有限公司 | Eye preparation containing travoprost and antiseptic |
| CN111632025A (en) * | 2020-03-04 | 2020-09-08 | 吉林大学第一医院 | Temperature-sensitive in-situ gel for bimatoprost eyes and preparation method and application thereof |
| WO2021084522A1 (en) * | 2019-10-31 | 2021-05-06 | Rafarm Uk Limited | Bimatoprost 0.01% solution compositions for the treatment of ocular hypertension |
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| CN1688317A (en) * | 2002-09-09 | 2005-10-26 | 参天制药株式会社 | Transparent eye drops containing latanoprost |
| CN102083413A (en) * | 2008-05-30 | 2011-06-01 | 参天制药株式会社 | Method and composition for treating ocular hypertension and glaucoma |
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| CN1688317A (en) * | 2002-09-09 | 2005-10-26 | 参天制药株式会社 | Transparent eye drops containing latanoprost |
| CN102083413A (en) * | 2008-05-30 | 2011-06-01 | 参天制药株式会社 | Method and composition for treating ocular hypertension and glaucoma |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104208015A (en) * | 2013-05-29 | 2014-12-17 | 天津金耀集团有限公司 | Eye preparation containing travoprost and antiseptic |
| WO2021084522A1 (en) * | 2019-10-31 | 2021-05-06 | Rafarm Uk Limited | Bimatoprost 0.01% solution compositions for the treatment of ocular hypertension |
| CN111632025A (en) * | 2020-03-04 | 2020-09-08 | 吉林大学第一医院 | Temperature-sensitive in-situ gel for bimatoprost eyes and preparation method and application thereof |
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| CN102716074B (en) | 2013-10-16 |
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