CN1644200A - Ganciclovir as ophthalmic medicine and its preparation - Google Patents
Ganciclovir as ophthalmic medicine and its preparation Download PDFInfo
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Abstract
An antiviral ganciclovir in the form of eye drop or eye cream for treating ophthalmophany is prepared from the ganciclovir and pharmacologically acceptable assistant. Its advantages are low poison and high curative effect and selectivity. Its preparing process is also disclosed.
Description
Technical field
The present invention relates to new antiviral drug ganciclovir eye medication and preparation method thereof.
Background technology
Viral keratitis is caused by viral infection such as herpetoviridae herpes simplex virus type 1s, be the common multiple oculopathy of serious harm human body vision, untreated person's blind rate is high, and there is nearly 5,000,000 patients every year in China because of infective virus keratitis blinding or visual deterioration.Existing antiviral medicament for the eyes such as idoxuridine, vidarabine, cytosine arabinoside and ancitabine etc. easily produce drug resistance or tangible untoward reaction are arranged; 0.1% aciclovir eye drop and 3.0% eye ointment of Hubei Prov. Medicine Industry Inst development have curative effect preferably in clinical treatment list bleb keratitis, and since nineteen eighty-three was identified operation, annual clinical use amount was all more than 1.5 hundred million in nearly 5 years; But acyclovir also has weak point, and its water solublity is relatively poor, and dissolubility only 0.13% in 25 ℃ water, and 0.1% eye drop of being prepared is easily separated out crystallization in cold cool season, and influence is used; 3.0% eye ointment dosage is bigger than normal, increases adverse reaction rate.Secondly, the same with other ucleosides antiviral drugs, the acyclovir ophthalmic preparation long period uses repeatedly and viral drug resistance strain also can occur.Therefore, clinical ophthalmology is badly in need of a kind of efficient, low toxicity, new anti-virus ophthalmic preparation that selectivity is strong.
Ganciclovir (Ganciclovir), in June, 1988, in Britain's approval listing, intravenous injection was used for treatment and epidemic prevention defective patient, organ transplantation person's cytomegalovirus infection first.
Summary of the invention
The object of the present invention is to provide a kind of efficient, low toxicity, new antiviral drug ganciclovir eye medication that selectivity is strong and preparation method thereof.
Technical scheme provided by the invention is: the medication of ganciclovir eye is that it comprises pharmaceutically useful auxiliary agent and antiviral effective dose and be dispersed in ganciclovir in the described auxiliary agent.
In example of the present invention, the medication of ganciclovir eye comprises eye drop and Eye ointments.
The pH value of above-mentioned eye drop is 5.0～8.0, preferred pH value 6.0～8.0, and the content of ganciclovir is 0.01～0.20wt%, preferred 0.05～0.15wt%.Described auxiliary agent is cosolvent, isoosmotic adjusting agent, pH regulator agent, antiseptic, water for injection.PH regulator agent preferred boric acid-sodium borate wherein; The preferred tween 80 of cosolvent, its content are 0.05～0.35wt%; The preferred bromo geramine of antiseptic, its content are 0.008-0.012wt%; The preferred sodium chloride of isoosmotic adjusting agent, its content are 0.25～0.30wt%.Its preparation method is: ganciclovir and auxiliary agent are placed retort, add the injection water, heating makes it dissolving, boils 20～30 minutes, is cooled to room temperature, adds to the full amount of water for injection, and mocromembrane filters, and packing under aseptic condition is sealed.
Above-mentioned Eye ointments, the content of ganciclovir are 0.5～3.0wt%, preferred 0.5～2.0wt%.Described auxiliary agent comprises 80～85wt% Yellow Vaselin, 10～15wt% lanoline, 5～10wt% white oil.Its preparation method is: ganciclovir is ground, is screened to below the 75 μ m; With the auxiliary agent heating and melting, after the filtration, be heated to 130～150 ℃ of sterilizations 60～80 minutes in addition, be cooled to room temperature; The ganciclovir micropowder that ground is moistening with the sterilized liquid paraffin wax, add the sterilization auxiliary agent and stir evenly fill.
Ganciclovir eye of the present invention medication has efficiently, low toxicity, advantage that selectivity is strong.
The result shows according to effect experiment, in vitro tests, effective inhibition concentration (ED50) that ganciclovir suppresses Vero cell infection 5 strain herpes simplex virus I types (HSV-1) and II type (HSV-II) virus is 0.05～0.35 μ g/ml, and the antiviral index is 204～1428.In vivo test is inoculated tame rabbit cornea with HSV-I and is caused tentative rabbit herpetic keratitis model, beginning in 72 hours, and eye is used the 0.1% and 0.2% Eye Drops of Ganciclovir eye dripping of being developed respectively, per 3 hours 1 time, treats for 5 times every day.The result shows: the treatment of 0.1% and 0.2% Eye Drops of Ganciclovir is after 1 day, and pathological changes is clearly better, the recovery from illness of 85～74% focuses, and all the other pathological changes alleviate day by day, administration focus 100% recovery from illness in the 6th day.Average curative day was respectively 4.0 and 4.4 days.Two kinds of concentration eye drop differences do not have the remarkable meaning of statistics, but with acyclovir matched group comparing difference highly significant (P＜0.01).On lagophthalmos HSV keratitis superficialis model, drip and use the ganciclovir of being developed 0.1%, 0.05%, 0.025% and 0.01% eye drop is put 6 every day, each 50 μ l, the result demonstrates obvious amount-result relation, and 0.1% and 0.05% Eye Drops of Ganciclovir is evident in efficacy; With the tentative herpes ophthalmicus viral infection of 1.0% and 3.0% ganciclovir eye ointment treatment rabbit, most of rabbit are through treating 6 days (every day 3 times); the pathological changes eye virus separation detection feminine gender that is completely recovered, and the still all separable herpesvirus that detects of eye pasting substrate contrast lagophthalmos.Show 0.1% eye drop and equal avirulence of 1% eye ointment and irritative response through local application's acute toxicity test and eye irritation test.So in eye drop of the present invention, the suitable content of its Main Ingredients and Appearance ganciclovir is 0.01～0.20% (percentage by weight, down together), preferable content is 0.05～0.15%.Best content is 0.10%; In Eye ointments, the suitable content of its Main Ingredients and Appearance ganciclovir in preparation is 0.5～3.0% (percentage by weight, down together), and preferable content is 1.0～2.0%.Optimum content is 1.0%.
Dissolubility and the pH value of ganciclovir in water has very big relation, and increases with the temperature rising.Ophthalmic preparation has strict requirement to pH value, must be controlled between 5.0～8.0, could reduce the zest of ophthalmic.Be made into the ganciclovir solution of different pH value through preferred various buffer agent, test shows, being made into pH value with boric acid-sodium borate buffer agent is 7.0～8.0 0.1% Eye Drops of Ganciclovir, does not separate out crystallization in one month 4 ℃ of preservations.Separate out crystallization in cold season for avoiding eye drop, select for use toxicity low, nonirritant, the tween 80 of good hydrophilic property are as solubilizing agent, and the tween 80 of preferred variable concentrations adds in the 1.0% ganciclovir buffer solution of pH6.0～8.0, through placing one month at 4～5 ℃, the concentration of tween 80 is that 0.1～0.3% buffer solution is not all separated out crystallization, and the consumption of tween 80 is excessive, and production operation is difficulty, and the interference analysis Determination on content, so solubilizing agent tween 80 optium concentration is 0.1%.Use 0.1% tween 80, pH is boric acid-sodium borate buffer solution of 7.0～8.0, antibacterial is the 0.008-0.012% bromo geramine, isoosmotic adjusting agent is a sodium chloride, 0.1% Eye Drops of Ganciclovir of making thus, through the storage 4 years down of light stability test, hot accelerated stability test and room temperature condition, with zero the time relatively, all no abnormal variation of pH value, clarity, assay, determination of foreign matter, health examination.This eye drop to the big ear rabbit of Japan with 0.1% and 0.2% Eye Drops of Ganciclovir single and continuous 10 days multiple dosings, eye drop nonirritants as a result.
Ganciclovir Eye ointments Yellow Vaselin is a substrate, and adding an amount of lanoline can increase adhesive attraction to cornea, promotes drug absorption; For adapting to the variation of temperature, the an amount of viscosity that adds white oil scalable eye ointment, ratio through screening Yellow Vaselin, lanoline, white oil three, with Yellow Vaselin: lanoline: the eye pasting substrate of white oil=form at 8.5: 1.0: 0.5 is prepared 1.0% ganciclovir eye ointment, respectively under three kinds of temperature such as 14～202 ℃ of 37 ± 2 ℃, 5 ± 2 ℃ and room temperatures through preliminarily stabilised investigation in 15 days, its content, pH value and zero point are relatively, and be basicly stable, and the outward appearance no abnormality seen changes.Storage is 4 years under the room temperature natural conditions, its outward appearance, the no abnormal variation of abnormal smells from the patient, and the medicine fineness still remains on below the 75 μ m, and uniformity is qualified, and content and pH value are stable.
The ophthalmic preparation of the present invention's preparation carries out clinical trial in nine tame hospitals, and ganciclovir 0.1% eye drop is treated 452 routine single bleb keratitis; Wherein 271 example systems carry out the double blind random controlled trial with acyclovir 0.1% eye drop, and 138 examples are that ganciclovir 0.1% eye drop enlarges clinical trial.The single, double blind method of 1% Eye Drops of Ganciclovir is treated dendroid, map shape and plate-like three type list bleb keratitis 314 examples altogether, cures 268 examples, total cure rate 85.35%.After only observing 3 examples (0.96%) medication in the clinical trial slight blepharoedema is arranged, the conjunctival congestion irritation can tolerate behind the minimizing medication number of times and continue treatment, and all the other all do not have part and whole body toxic and side effects.Ganciclovir 1.0% eye ointment is treated 468 routine single bleb keratitis, and wherein 313 example systems carry out the double blind random controlled trial with acyclovir 3.0% eye ointment, and 155 examples are that ganciclovir 1% eye ointment enlarges clinical trial.Treat dendroid, map shape and plate-like three type list bleb keratitis 311 examples altogether with the single, double blind method of 1% ganciclovir eye ointment, cure 274 examples, total cure rate 88.10%.2 examples are arranged, and (0,64% map shape keratitis patient furiously swells, itches and drug withdrawal respectively at occurring after the medication 2 times and 6 times, and wherein an example previously once had the eye ointment allergies, and all the other all do not have part and whole body toxicity.Once to 6 examples with 0.1% eye drop and 7 examples with single bleb keratitis patient of 1.0% eye ointment treatment forward and backwardly carry out blood in treatment, urinate chemically examine regulating liver-QI, renal function then tries, and is all no abnormal; Use 0.1% eye drop and the forward and backward seminal fluid of 1.0% eye ointment to chemically examine to 6 routine healthy volunteers respectively, the result is all normal.
The specific embodiment
The present invention further specifies with following embodiment, but the purpose of these embodiment only is to illustrate the present invention, and they are not construed as limiting the invention.
Embodiment 1, ganciclovir 0.1% eye drop and preparation technology thereof:
Take by weighing ganciclovir 1kg, sodium chloride 3kg, tween 80 1kg, 5% bromo geramine 2000ml, boric acid 10.5kg, sodium borate 2.9kg, place the retort of 2000 liters, add the distilled water of partial sterilization, heating makes it dissolving, boils 20 minutes.Naturally cool but to room temperature, add distilled water to 1000 liter of sterilization, filter with 0.3 μ m mocromembrane of sterilization, under aseptic condition, divide to be filled in the plastics eyedrops bottle, every 8ml seals.
The screening test and the preparation technology thereof of embodiment 2, ganciclovir 0.1% eye drop buffer agent pH value:
Take by weighing ganciclovir 1kg, sodium chloride 3kg, tween 80 1kg, 5% bromo geramine 2000ml, boric acid 10.0～10.8kg, sodium borate 2.9～3.0kg, preparation technology according to embodiment 1, boric acid-sodium borate buffer agent is made into 0.1% Eye Drops of Ganciclovir of different pH value, 4～5 ℃ of placements, observe the influence of ganciclovir being separated out in 4,8,20,38,48 and 60 hours, the results are shown in Table shown in 1.
Table 1: the different pH value of buffer agent are to the influence of 0.1% Eye Drops of Ganciclovir
| Time (hour) | The pH value of the slow liquid of boric acid-sodium borate | Condition | ||||
| ??6.2 | ??6.5 | ??7.0 | ??7.5 | ??8.0 | ||
| ??0 | Molten entirely | Molten entirely | Molten entirely | Molten entirely | Molten entirely | ??25～30℃ |
| ??4 | Molten entirely | Molten entirely | Molten entirely | Molten entirely | Molten entirely | ??4℃ |
| ??8 | A little is separated out | A little is separated out | Molten entirely | Molten entirely | Molten entirely | ??4℃ |
| ??20 | Part is separated out | Part is separated out | Molten entirely | Molten entirely | Molten entirely | ??5℃ |
| ??38 | Part is separated out | Part is separated out | A little is separated out | Molten entirely | Molten entirely | ??4～5℃ |
| ??48 | Part is separated out | Part is separated out | A little is separated out | Molten entirely | Molten entirely | ??4～5℃ |
| ??60 | Part is separated out | Part is separated out | Part is separated out | A little is separated out | A little is separated out | ??4～5℃ |
The screening test and the preparation technology thereof of embodiment 3, ganciclovir 0.1% eye drop solubilizing agent concentration:
Take by weighing ganciclovir 1kg, sodium chloride 3kg, the about 1.0～2.5kg of tween 80,5% bromo geramine 2000ml, boric acid 10.5kg, preparation technology according to embodiment 1, the tween 80 of preparation variable concentrations adds 0.1% Eye Drops of Ganciclovir of different pH value respectively, placed one month at 4～5 ℃, observe the solubilization of tween 80, the results are shown in Table shown in 2 ganciclovir.
Table 2: various concentration solubilizing agents are to the influence of different pH value 0.1% Eye Drops of Ganciclovir
| The pH value | Time (my god) | The concentration of tween 80 | Condition | ||||||
| 0.05％ | 0.10％ | 0.15％ | 2.0％ | 0.25％ | 0.30％ | 0.35％ | |||
| 6. 2 | ????0 | Molten entirely | Molten entirely | Molten entirely | Molten entirely | Molten entirely | Molten entirely | Molten entirely | 20～25℃ |
| ????3 | Molten entirely | Molten entirely | Molten entirely | Molten entirely | Molten entirely | Molten entirely | Molten entirely | 4～5℃ | |
| ????6 | Separate out | Molten entirely | Molten entirely | Molten entirely | Molten entirely | Molten entirely | Molten entirely | 4～5℃ | |
| ????10 | Separate out | Separate out | Separate out | Molten entirely | Molten entirely | Molten entirely | Molten entirely | 4～5℃ | |
| ????15 | Separate out | Separate out | Separate out | Separate out | Molten entirely | Molten entirely | Molten entirely | 4～5℃ | |
| ????20 | Separate out | Separate out | Separate out | Separate out | Separate out | Separate out | A little is separated out | 4～5℃ | |
| ????30 | Separate out | Separate out | Separate out | Separate out | Separate out | Separate out | Separate out | 4～5℃ | |
| 7. 0 | ????0 | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | 20～25℃ |
| ????3 | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | 4～5℃ | |
| ????6 | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | 4～5℃ | |
| ????10 | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | 4～5℃ | |
| ????15 | A little is separated out | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | 4～5℃ | |
| ????20 | Separate out | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | 4～5℃ | |
| ????25 | Separate out | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | 4～5℃ | |
| ????30 | Separate out | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | 4～5℃ | |
| ????35 | Separate out | Separate out | Separate out | A little is separated out | A little is separated out | Dissolving | Dissolving | 2～3℃ | |
| ????40 | Separate out | Separate out | Separate out | Separate out | Separate out | A little is separated out | A little is separated out | 2～3℃ | |
| 7. 5 | ????0 | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | 20～25℃ |
| ????3 | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | 4～5℃ | |
| ????6 | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | 4～5℃ | |
| ????10 | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | 4～5℃ | |
| ????15 | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | 4～5℃ | |
| ????20 | A little is separated out | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | 4～5℃ | |
| ????25 | Separate out | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | 4～5℃ | |
| ????30 | Separate out | A little is separated out | A little is separated out | Dissolving | Dissolving | Dissolving | Dissolving | 4～5℃ | |
| ????40 | Separate out | Separate out | Separate out | A little is separated out | Dissolving | Dissolving | Dissolving | 2～3℃ | |
| 8. 0 | ????0 | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | 20～25℃ |
| ????3 | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | 4～5℃ | |
| ????6 | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | 4～5℃ | |
| ????10 | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | 4～5℃ | |
| ????15 | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | 4～5℃ | |
| ????20 | A little is separated out | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | 4～5℃ | |
| ????25 | Separate out | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | Dissolving | 4～5℃ | |
| ????30 | Separate out | A little is separated out | A little is separated out | A little is separated out | Dissolving | Dissolving | Dissolving | 4～5℃ | |
| ????40 | Separate out | Separate out | Separate out | Separate out | A little is separated out | Dissolving | Dissolving | 2～3℃ | |
Embodiment 4, ganciclovir 0.1% eye drop nature storage stability test
890301,890302,890,303 3 batches of eye drop producing by embodiment 1 are encapsulated in the plastics eyedrops bottle, put in the carton, put in the sample cabinet, room temperature, regularly (0,1,2,3,6,12,18,24,36,48 month) carries out outward appearance, content, clarity, pH value and the sterility test of sample, high performance liquid chromatography detects related substance, the results are shown in Table 3.
Table 3, natural bin stability are investigated
| Lot number | Time (moon) | Content % | PH value | Outward appearance | Clarity | Sterility test | Related substance % |
| ??890301 | ????0 ????1 ????3 ????12 ????24 ????36 ????48 | ????98.86 ????98.70 ????99.21 ????101.30 ????99.91 ????101.42 ????99.80 | ????7.55 ????7.55 ????7.55 ????7.55 ????7.54 ????7.55 ????7.54 | Colourless liquid colourless liquid colourless liquid colourless liquid colourless liquid colourless liquid colourless liquid | Clear and bright clear and bright clear and bright | Qualified qualified qualified | ??＜1.0 ??＜1.0 ??＜1.0 ??＜1.0 ??＜1.0 ??＜1.0 ??＜1.0 |
| ??890302 | ????0 ????1 ????3 ????12 ????24 ????36 ????48 | ????98.95 ????98.30 ????98.29 ????100.7 ????99.38 ????101.42 ????100.12 | ????7.55 ????7.55 ????7.55 ????7.52 ????7.55 ????7.50 ????7.50 | Colourless liquid colourless liquid colourless liquid colourless liquid colourless liquid colourless liquid colourless liquid | Clear and bright clear and bright clear and bright | Qualified qualified qualified | ??＜1.0 ??＜1.0 ??＜1.0 ??＜1.0 ??＜1.0 ??＜1.0 ??＜1.0 |
| ??890303 | ????0 ????1 ????3 ????12 ????24 ????36 ????48 | ????98.85 ????98.50 ????99.09 ????100.70 ????100.63 ????100.05 ????100.61 | ????7.55 ????7.55 ????7.55 ????7.54 ????7.48 ????7.50 ????7.50 | Colourless liquid colourless liquid colourless liquid colourless liquid colourless liquid colourless liquid colourless liquid | Clear and bright clear and bright clear and bright | Qualified qualified qualified | ??＜1.0 ??＜1.0 ??＜1.0 ??＜1.0 ??＜1.0 ??＜1.0 ??＜1.0 |
Eye Drops of Ganciclovir was preserved 48 months under the room temperature natural conditions. and appearance luster and distilled water be no change relatively, and clarity is qualified, content and pH data and 0 month comparison no change, health examination is qualified, high performance liquid chromatography check result and 0 month comparison no change.
Embodiment 5, ganciclovir 1.0% Eye ointments and preparation technology thereof:
Take by weighing ganciclovir 1kg, grind, sieve, examine under a microscope, microgranule is below 75 μ m, and is standby; Other takes by weighing Yellow Vaselin 50kg, lanoline 10kg, white oil 5kg, heating and melting.After filtering with No. seven sieves, substrate was heated to about 150 ℃ sterilization one hour, puts cold.Standby; The ganciclovir micropowder that ground is moistening with an amount of sterilized liquid paraffin wax, add sterilization matrix and stir evenly, adding Yellow Vaselin to full dose again is 100kg, and fill is that 2g/ props up, and presses tail, and whole process of production should be operated under aseptic condition.
Embodiment 6, ganciclovir 1.0% eye pasting substrate proportioning screening test and preparation technology thereof and heat stability are investigated test
Take by weighing ganciclovir 1kg, grind, sieve, examine under a microscope, microgranule is below 75 μ m, and is standby; Other takes by weighing Yellow Vaselin 50kg, lanoline 10kg, white oil 5kg (first group), or Yellow Vaselin 50kg, lanoline 10kg, white oil 10kg (second group) heating and melting.Preparation technology according to embodiment 5, ganciclovir 1.0% eye ointment of the preparing different eye pasting substrates eye ointment pipe (tin-tube) of packing into, at 5 ± 2 ℃, 37 ± 2 ℃, 20～30 ℃ of room temperatures were placed one month, investigate the outward appearance of substrate, the variation of denseness, first group of Yellow Vaselin: lanoline: white oil is 8.0: 1.0: 1.0, second group of Yellow Vaselin: lanoline: white oil is 8.5: 1.0: 0.5, and its result is as shown in table 4.
Table 4: ganciclovir 1.0% eye ointment base different substrates heat stability is investigated test
| Group | Time (my god) | ???????5±2℃ | ???????20～30℃ | ????37±2℃ | |||
| Outward appearance | Denseness | Outward appearance | Denseness | Outward appearance | Denseness | ||
| One group | ????0 ????5 ????10 ????20 ????30 | Yellow, fine and smooth | Extrude among the Yi Congguan | Yellow, fine and smooth | Extrude among the Yi Congguan | Yellow, fine and smooth | Substrate is thinning after 15 days |
| Two groups | ????0 ????5 ????10 ????20 ????30 | Yellow, fine and smooth | Extrude among the Yi Congguan | Yellow, fine and smooth | Extrude among the Yi Congguan | Yellow, fine and smooth | Consistency change is not obvious |
Embodiment 7, ganciclovir 0.1% eye ointment nature storage stability test
Press embodiment 4 and produce 890311,890312,890,313 3 batch samples, put into eye ointment pipe (tin-tube), pack in the carton, place in the sample cabinet, investigate appearance luster by sampling in 1,3,6,12,18,24,36,48 month, uniformity, fineness of the particles, content, high performance liquid chromatogram are checked related substance, the results are shown in Table 5.
Table 5: ganciclovir 1.0% eye ointment room temperature stability is investigated
| Lot number | Time (moon) | The mensuration project | |||||||
| Content | Abnormal smells from the patient | Fineness | PH value | Outward appearance | Uniformity | Sterility test | Related substance (%) | ||
| ??890311 | ??0 | ??97.30 | Do not have and smell flavor | Below the 75 μ m | ??6.7 | Yellow | Evenly | Qualified | ??＜1.0 |
| ??1 | ??95.83 | Do not have and smell flavor | Below the 75 μ m | ??6.7 | Yellow | Evenly | Qualified | ??＜1.0 | |
| ??3 | ??96.37 | Do not have and smell flavor | Below the 75 μ m | ??6.8 | Yellow | Evenly | Qualified | ??＜1.0 | |
| ??12 | ??93.55 | Do not have and smell flavor | Below the 75 μ m | ??6.7 | Yellow | Evenly | Qualified | ??＜1.0 | |
| ??24 | ??96.00 | Do not have and smell flavor | Below the 75 μ m | ??6.6 | Yellow | Evenly | Qualified | ??＜1.0 | |
| ??36 | ??97.76 | Do not have and smell flavor | Below the 75 μ m | ??6.5 | Yellow | Evenly | Qualified | ??＜1.0 | |
| ??48 | ??96.91 | Do not have and smell flavor | Below the 75 μ m | ??6.6 | Yellow | Evenly | Qualified | ??＜1.0 | |
| ??890312 | ??0 | ??93.22 | Do not have and smell flavor | Below the 75 μ m | ??6.7 | Yellow | Evenly | Qualified | ??＜1.0 |
| ??1 | ??97.46 | Do not have and smell flavor | Below the 75 μ m | ??6.6 | Yellow | Evenly | Qualified | ??＜1.0 | |
| ??3 | ??95.23 | Do not have and smell flavor | Below the 75 μ m | ??6.8 | Yellow | Evenly | Qualified | ??＜1.0 | |
| ??12 | ??94.42 | Do not have and smell flavor | Below the 75 μ m | ??6.6 | Yellow | Evenly | Qualified | ??＜1.0 | |
| ??24 | ??97.50 | Do not have and smell flavor | Below the 75 μ m | ??6.7 | Yellow | Evenly | Qualified | ??＜1.0 | |
| ??36 | ??96.86 | Do not have and smell flavor | Below the 75 μ m | ??6.7 | Yellow | Evenly | Qualified | ??＜1.0 | |
| ??48 | ??93.04 | Do not have and smell flavor | Below the 75 μ m | ??6.6 | Yellow | Evenly | Qualified | ??＜1.0 | |
| ??890313 | ??0 | ??97.42 | Do not have and smell flavor | Below the 75 μ m | ??6.8 | Yellow | Evenly | Qualified | ??＜1.0 |
| ??1 | ??96.20 | Do not have and smell flavor | Below the 75 μ m | ??6.6 | Yellow | Evenly | Qualified | ??＜1.0 | |
| ??3 | ??97.35 | Do not have and smell flavor | Below the 75 μ m | ??6.7 | Yellow | Evenly | Qualified | ??＜1.0 | |
| ??12 | ??94.42 | Do not have and smell flavor | Below the 75 μ m | ??6.8 | Yellow | Evenly | Qualified | ??＜1.0 | |
| ??24 | ??97.74 | Do not have and smell flavor | Below the 75 μ m | ??6.6 | Yellow | Evenly | Qualified | ??＜1.0 | |
| ??36 | ??96.61 | Do not have and smell flavor | Below the 75 μ m | ??6.6 | Yellow | Evenly | Qualified | ??＜1.0 | |
| ??48 | ??98.20 | Do not have and smell flavor | Below the 75 μ m | ??6.7 | Yellow | Evenly | Qualified | ??＜1.0 | |
The storage 48 months under the white right condition of room temperature of ganciclovir eye ointment, appearance luster and 5 ℃ of samples be no change relatively, and uniformity is qualified, fineness of the particles below 75 μ m, content and high-efficient liquid phase chromatogram and 0 month comparison no change.
Claims (10)
1. ganciclovir eye medication is that it comprises pharmaceutically useful auxiliary agent and antiviral effective dose and be dispersed in ganciclovir in the described auxiliary agent.
2. eye according to claim 1 medication is characterized in that: the medication of described eye is an eye drop, and its pH value is 5.0～8.0, and the content of ganciclovir is 0.01～0.20wt%.
3. eye according to claim 2 medication, it is characterized in that: described auxiliary agent is cosolvent, isoosmotic adjusting agent, pH regulator agent, antiseptic, water for injection.
4. eye according to claim 3 medication, it is characterized in that: the pH regulator agent is boric acid-sodium borate; Cosolvent is a tween 80, and its content is 0.05～0.35wt%; Antiseptic is a bromo geramine, and its content is 0.008-0.012wt%; Isoosmotic adjusting agent is a sodium chloride, and its content is 0.25～0.30wt%; All the other are water for injection.
5. according to claim 2 or 3 or 4 described medications, it is characterized in that: pH value is 6.0～8.0, and the content of ganciclovir is 0.05～0.15wt%.
6. eye according to claim 1 medication is characterized in that: the medication of described eye is an Eye ointments, and the content of ganciclovir is 0.5～3.0wt%.
7. eye according to claim 6 medication, it is characterized in that: described auxiliary agent comprises 80～85wt% Yellow Vaselin, 10～15wt% lanoline, 5～10wt% white oil.
8. according to claim 6 or 7 described medications, it is characterized in that: the content of ganciclovir is 0.5～2.0wt%.
9. claim 2 or 3 or the preparation method of 4 described medications, it is characterized in that: ganciclovir and auxiliary agent are placed retort, add the injection water, heating makes it dissolving, boiled 20～30 minutes, and be cooled to room temperature, add to the full amount of water for injection, mocromembrane filters, and packing under aseptic condition is sealed.
10. the preparation method of claim 6 or 7 described medications is characterized in that: ganciclovir is ground, is screened to below the 75 μ m; With the auxiliary agent heating and melting, after the filtration, be heated to 130～150 ℃ of sterilizations 60～80 minutes in addition, be cooled to room temperature; The ganciclovir micropowder that ground is moistening with the sterilized liquid paraffin wax, add the sterilization auxiliary agent and stir evenly fill.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410060851 CN1277542C (en) | 2004-09-14 | 2004-09-14 | Ganciclovir as ophthalmic medicine and its preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410060851 CN1277542C (en) | 2004-09-14 | 2004-09-14 | Ganciclovir as ophthalmic medicine and its preparation |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200610008488 Division CN1839844A (en) | 2004-09-14 | 2004-09-14 | Gancilorvir eye ointment and its preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1644200A true CN1644200A (en) | 2005-07-27 |
| CN1277542C CN1277542C (en) | 2006-10-04 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200410060851 Expired - Fee Related CN1277542C (en) | 2004-09-14 | 2004-09-14 | Ganciclovir as ophthalmic medicine and its preparation |
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| Country | Link |
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| CN (1) | CN1277542C (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102342911A (en) * | 2011-10-09 | 2012-02-08 | 南京恒道医药科技有限公司 | Ganciclovir eye drops and preparation method thereof |
| CN105342990A (en) * | 2015-10-30 | 2016-02-24 | 上海昊海生物科技股份有限公司 | Eye drops containing moxifloxacin hydrochloride and hexadecadrol and preparation method of eye drops |
-
2004
- 2004-09-14 CN CN 200410060851 patent/CN1277542C/en not_active Expired - Fee Related
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102342911A (en) * | 2011-10-09 | 2012-02-08 | 南京恒道医药科技有限公司 | Ganciclovir eye drops and preparation method thereof |
| CN105342990A (en) * | 2015-10-30 | 2016-02-24 | 上海昊海生物科技股份有限公司 | Eye drops containing moxifloxacin hydrochloride and hexadecadrol and preparation method of eye drops |
| CN105342990B (en) * | 2015-10-30 | 2020-05-19 | 上海昊海生物科技股份有限公司 | Eye drops containing moxifloxacin hydrochloride and dexamethasone and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1277542C (en) | 2006-10-04 |
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Granted publication date: 20061004 Termination date: 20160914 |