CN1626090A - Combination of medication for antivirus in use for eye region and preparation method - Google Patents
Combination of medication for antivirus in use for eye region and preparation method Download PDFInfo
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- CN1626090A CN1626090A CN 200410064366 CN200410064366A CN1626090A CN 1626090 A CN1626090 A CN 1626090A CN 200410064366 CN200410064366 CN 200410064366 CN 200410064366 A CN200410064366 A CN 200410064366A CN 1626090 A CN1626090 A CN 1626090A
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Abstract
The present invention provides a combination of medication and preparation method thereof, particularly, provides an antivirus in use for eye region and preparation method thereof. The combination of medication is antivirus in use for eye taking Ganciclovir, Carbomer, hydroxypropylmethyl cellulose, and common preparation accessories in sue for eye as material. The invention prepares eye drops with in-situ gelatinizing technology.
Description
Technical field
The present invention relates to a kind of anti-viral pharmaceutical compositions that is used for eye, specifically, is the eye slow releasing preparation and preparation method thereof that contains ganciclovir.
Background technology
Being used for the treatment of at present two kinds of dosage forms using always the most in the medicine of ocular infection clinically is: solution and Eye ointments.The solution-type eye drop, its action principle is: carries out the transmission of medicine with lacrimal secretion after splashing into eyes, is characterized in being evenly distributed, but because the secretion that do not stop of conjunctival sac tear and getting rid of rapidly from nasolacrimal duct, make its holdup time in conjunctival sac very short, so the ophthalmic bioavailability is very low.Need frequent drug administration to keep normal drug level, bring very big inconvenience to patient, and increasing of administration number of times increased the probability that causes cross infection greatly.The Eye ointments curative effect is more lasting, but owing to use the restriction of adjuvant and process to make it be difficult to realize even administration, and use inconvenient.Therefore, improve the ophthalmic remedy dosage form, developing out convenient and practical long-acting control slow release becomes at present the direction of research both at home and abroad.
Ganciclovir (ganciclovir) has another name called gancyclovir, and the beautiful section of trade name is big, is synthetic ucleosides antiviral agents, the alternative herpes virus replication that suppresses.Herpes simplex virus (HSV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella zoster virus (VZV), human herpes (VAC) and human papillomavirus (HPV) etc. all there is very strong antivirus action (Yang Sen, the woods letter of credence, Deng. the clinical evaluation of ganciclovir and acyclovir treatment herpes zoster. Chinese skin cypridology magazine, 2002,16 (3): 101); Ganciclovir (ganciclovir) is to have the wide spectrum herpesvirus resisting activity, is the effective antiviral thing that first treatment human body cytomegalovirus (CMV) infects.4 kinds of preparations such as existing so far intravenous injection, capsule, intraocular implant and 0.15% eye ointment were approved for treatment cmv infection and herpetic keratitis first in Britain's listing in 1988.
At present existing bibliographical information ganciclovir eye drop (Li Haisheng, Huang Zhidong, Deng. the HPLC assay method of ganciclovir and eye drop thereof. external analytical instrumentation techniques and application, 1993,000 (003): 47-49), this eye drop is the solution-type eye drop, medicine is the holdup time weak point within the eye, bioavailability is low, needs frequent drug administration, easily pollutes.Document " preparation of ganciclovir gel and quality control " (Lin Guangyong, Zhu Guanghui, Wang Zengshou. the preparation of ganciclovir gel and quality control. the Guangdong pharmacy, 2002,12 (4): 24) reported the preparation of ganciclovir gel, this gel preparation is adjuvant with the carbomer, principal agent ganciclovir content height, and containing ganciclovir in the 100g preparation is 3g.External is gel, the gel state instability, the quality standard controllability of preparation is poor, and using method is to be applied to down in the conjunctival sac on a small quantity at every turn, it is not disposable but multiple dose, repeatedly use, repeatedly smear the pollution that easily causes in the use, and owing to be applied in down in the conjunctival sac, be difficult to realize even administration, cause the medication non-quantitative and smear inhomogeneously, use inconveniently, easily cause waste.
Summary of the invention
In order to address the above problem, technical scheme to be solved by this invention provides a kind of anti-viral pharmaceutical compositions that is used for eye, and it is the novel formulation that contains ganciclovir, and the eye that contains ganciclovir slow releasing preparation promptly is provided.Another technical scheme of the present invention has provided this preparation of drug combination method.
The invention provides a kind of anti-viral pharmaceutical compositions that is used for eye, it is to be active component by ganciclovir, the eye slow releasing preparation that carbomer, hydroxypropyl methylcellulose and ophthalmic preparation adjuvant pharmaceutically commonly used are made.
Wherein said carbomer is: Acritamer 940, Carbopol 941, carbomer 934.Further, described carbomer is: Acritamer 940.
Wherein the percent weight in volume of ganciclovir is 0.01%～0.15%w/v.Said percent weight in volume is meant in volume is the present composition of 100ml and contains ganciclovir 0.01～0.15g.
Described carbomer and hydroxypropyl methylcellulose, its weight proportion are 0.1～0.5: 1.0～4.0, and carbomer mixes the percent weight in volume that accounts for pharmaceutical composition with hydroxypropyl methylcellulose be 1.1%～4.5%w/v.Further, described carbomer and hydroxypropyl methylcellulose, its weight proportion is: 0.40: 1.30, carbomer mixes the percent weight in volume that accounts for pharmaceutical composition with hydroxypropyl methylcellulose be 1.7%w/v.
Carbomer (Carboxgpolmethylene) is the crosslinked high molecular polymer of acrylic acid and allyl sucrose.Carbomer is a white, loose shape; Tool acidity, hygroscopicity and little off-odor arranged can be water-soluble, ethanol, glycerol.Typical concentrations (percent weight in volume) is 0.1%～3.0%w/v.Carbomer becomes pH after the swelling in water be about 3 colloid solution, increases rapidly with in the alkali and back viscosity.Carbomer is to people's safety, and nonirritant, anaphylaxis or allergy are when pH value and concentration are suitable, to equal nonirritant such as eye, nasal mucosa.Carbomer has the product of various models according to the difference of its degree of polymerization, and raw material of the present invention is selected Acritamer 940, Carbopol 941, carbomer 934 for use, because of its viscosity height, good stability, purity height.Preferred Acritamer 940, its viscosity height, tackify are effective.
Described eye is an eye drop with slow releasing preparation, and the pH value of described eye drop is 5～6.5.
The present invention also provides this to be used for the preparation method of the anti-viral pharmaceutical compositions of eye, it is characterized in that:
A, carbomer is added the water for injection swelling, mix, form clear solution with pharmaceutically acceptable ophthalmic preparation adjuvant;
B, get ganciclovir and add the 0.1mol/L sodium hydroxide solution, heating makes dissolving, with the swelling thing mix homogeneously of a step gained, adds water for injection, regulates pH value with sodium hydroxide, the packing of sterilizing through after the assay was approved, promptly.
The adjuvant that described ophthalmic preparation is commonly used is: isoosmotic adjusting agent is sodium chloride, Borax; Antiseptic is ethyl hydroxybenzoate, phenethanol, domiphen bromide, boric acid, chlorhexidine or Benzalkonii Chloridum; The pH regulator agent is carbonate buffer solution, phosphate buffer, borate buffer solution, sodium hydroxide; Water for injection.Particularly, the raw material of medicine of the present invention is made up of following compositions, its percent weight in volume is: 0.01%-0.15%w/v ganciclovir, 0.1%～0.5%w/v carbomer, 1.0%～4.0%w/v hydroxypropyl methylcellulose, 0.20%～0.30%w/v sodium hydrogen phosphate, 0.4%～0.6%w/v sodium dihydrogen phosphate, 0.4%～0.6%w/v sodium chloride, 0.02%～0.04%w/v ethyl hydroxybenzoate, an amount of sodium hydroxide, surplus is a water for injection.
Because ganciclovir poorly water-soluble, dissolubility is 1.5mg/ml, 0.15% (w/v) just, its sodium salt is soluble in water, 5% aqueous solution pH=11, pH value descends can separate out precipitation (Lin Guangyong, Zhu Guanghui, Wang Zengshou, the preparation of ganciclovir gel and quality control, the Guangdong pharmacy, 2002 the 12nd the 4th phases of volume), the eye drop of pharmaceutical composition of the present invention is a ganciclovir original position gel eye drop, and the concentration of ganciclovir is 0.1～1.5mg/ml in this eye drop, therefore the concentration that also do not reach capacity or just reach capacity adopt preparation of drug combination method of the present invention that ganciclovir is fully dissolved.
Usually the pH value of eye drop is identical with the pH value of people's tear usually, and meta-alkalescence, pH value if pH value is improper, can cause the stimulation to eye between 7.3～7.5, increase the secretion of tear, cause medicine to be rinsed loss, even the damage cornea.PH value of the present invention is 5～6.5, slant acidity, be because the present invention adopts original position gel technology to prepare eye drop, make this pharmaceutical dosage form under acid condition, be clear and bright solution, adopt dosing pump water dropper packing, guarantee the content of principal agent ganciclovir, it is convenient when the patient uses, under the distinctive physiological environment effect of eye, influenced by the pH of tear behind the uniform distribution during medicine liquid droplet is pleasing to the eye, form gel, be covered in eyeball surface, do not influence the normal vision of eyes, drug slow discharges, and reaches the effect of long-acting slow-release and can reduce in the use pollution to preparation itself.
This eye drop is under 60 ℃, and 10 days heat stabilization test shows more stable constantly; At 40 ℃, under the condition of relative humidity 75%, accelerated test 6 months, every index has no significant change; Place to investigate at ambient temperature 18 months more stable; In illuminance is to place 10 days under 4500lux (illuminance, promptly lux degree lux represents the luminous flux that is subjected on the shot subject surface unit area) condition, and every index has no significant change.
Show by the pharmacokinetics test: the medicine of the present invention that uses this prepared increases stability of formulation for the result of use, the inherent quality that improve medicine, reduces the stimulation of medicine to eyes, and effect is remarkable.
Medicine of the present invention, principal agent ganciclovir content is little, steady quality, the drug level of can remaining valid in a long time, the bioavailability height is little to the zest of eye, reduce administration frequency, its preparation technology's science, the quality standard controllability height of preparation, quantitatively use, easy to use, aborning because final preparation is a solution, the processes of circulation such as the batching that relates to, fill can cut the waste relatively, easily form commercial production, reduce production costs, provide a kind of new medication to select for clinical.
Obviously, according to foregoing of the present invention,,, can also make modification, replacement or the change of other various ways not breaking away under the above-mentioned basic fundamental thought of the present invention prerequisite according to the ordinary skill knowledge and the customary means of this area.
The specific embodiment of form is described in further detail foregoing of the present invention again by the following examples.But this should be interpreted as that the scope of the above-mentioned theme of the present invention only limits to following example.All technology that realizes based on foregoing of the present invention all belong to scope of the present invention.
The specific embodiment
The preparation of embodiment 1 medicine of the present invention
Prescription: ganciclovir: 0.1g; Acritamer 940: 0.40g; Hydroxypropyl methylcellulose: 1.20g; Sodium hydrogen phosphate: 0.25g; Sodium dihydrogen phosphate: 0.50g; Sodium chloride: 0.5g, ethyl hydroxybenzoate: 0.03g; It is 6.5 that sodium hydroxide is regulated pH value in right amount.
Above-mentioned prescription is pressed following preparation technology:
A, get sodium hydrogen phosphate and sodium dihydrogen phosphate and methylcellulose, be dissolved in an amount of water for injection, form clear solution.
B, get carbomer and join swelling in an amount of water for injection, treat that swelling fully after, join in the clear solution of above-mentioned steps a, do not stop to stir, form clear solution.
C, taking ethylparaben, sodium chloride join in an amount of water for injection, to dissolving fully, and stir, and join in the above-mentioned steps b clear solution, form clear solution.
D, get ganciclovir and add 3ml 0.1mol/L sodium hydroxide, heating makes dissolving, joins in the clear solution of above-mentioned steps c mix homogeneously under not stopping to stir.
E, with behind the solution mix homogeneously, add the injection water to 100ml, regulating pH with sodium hydroxide is 5～6.5.Fill after the assay was approved, pressure sterilizing is standby.
The preparation of embodiment 2 medicines of the present invention
Prescription: ganciclovir: 0.05g; Acritamer 940: 0.30g; Hydroxypropyl methylcellulose: 2.20g; Sodium hydrogen phosphate: 0.25g; Sodium dihydrogen phosphate: 0.50g; Sodium chloride: 0.5g;
Above-mentioned prescription is pressed the prepared of embodiment 1.
Embodiment 3 preparation of drug combination of the present invention
Prescription: ganciclovir: 0.05g; Acritamer 940: 0.50g; Hydroxypropyl methylcellulose 1.30g; Sodium hydrogen phosphate: 0.20g; Sodium dihydrogen phosphate: 0.60g; Sodium chloride: 0.5g; Domiphen bromide: 0.03g; It is 6.0 that sodium hydroxide is regulated pH value in right amount.
Preparation technology by embodiment 1 prepares with above-mentioned prescription, fill after the assay was approved, and pressure sterilizing is standby.
Embodiment 4 preparation of drug combination of the present invention
Prescription: ganciclovir: 0.15g; Acritamer 940: 0.50g; Hydroxypropyl methylcellulose: 2.0g; Sodium hydrogen phosphate: 0.30g; Sodium dihydrogen phosphate: 0.60g; Sodium chloride: 0.45g; Ethyl hydroxybenzoate: 0.04g; It is 6.5 that sodium hydroxide is regulated pH value in right amount.
Preparation technology by embodiment 1 prepares with above-mentioned prescription, fill after the assay was approved, and pressure sterilizing is standby.
Embodiment 5 preparation of drug combination of the present invention
Prescription: ganciclovir: 0.01g; Acritamer 940: 0.15g; Hydroxypropyl methylcellulose: 3.0g; Sodium hydrogen phosphate: 0.20g; Sodium dihydrogen phosphate: 0.40g; Sodium chloride: 0.4g; Ethyl hydroxybenzoate: 0.02g; It is 5.5 that sodium hydroxide is regulated pH value in right amount.
Preparation technology by embodiment 1 prepares with above-mentioned prescription, fill after the assay was approved, and pressure sterilizing is standby.
Embodiment 6 preparation of drug combination of the present invention
Prescription: ganciclovir: 0.1g; Acritamer 940: 0.35g; Hydroxypropyl methylcellulose: 3.0g; Sodium hydrogen phosphate: 0.3g; Sodium dihydrogen phosphate: 0.40g; Sodium chloride: 0.55g; Boric acid: 0.02g; It is 5.0 that sodium hydroxide is regulated pH value in right amount.
Preparation technology by embodiment 1 prepares with above-mentioned prescription, fill after the assay was approved, and pressure sterilizing is standby.
Ganciclovir content assaying method in embodiment 7 pharmaceutical compositions of the present invention
Use high performance liquid chromatography (" two appendix V of Chinese pharmacopoeia version in 2000 D) to measure ganciclovir content in the pharmaceutical composition of the present invention.
Chromatographic condition and system suitability test:
Chromatographic condition: with octadecylsilane chemically bonded silica is filler, methanol: water (1: 1) (volume ratio) is mobile phase, and the detection wavelength is 252nm, and flow velocity is 1ml/min, column temperature: 35 ℃.
It is an amount of to the medicine of the present invention that example 4 makes that the assay precision is measured embodiment 1, quantitatively dilutes with mobile phase and make the solution that contains ganciclovir 0.1mg among every 1ml, as need testing solution; It is an amount of that other gets the ganciclovir reference substance, quantitatively dilutes with mobile phase and make the solution that contains ganciclovir 0.1mg among every 1ml, product solution in contrast.Precision is measured need testing solution and each 10 μ l of reference substance solution, injects chromatograph of liquid respectively, the record chromatogram, and with calculated by peak area, that is, result of calculation is: the percent weight in volume of ganciclovir is 0.01%～0.15%w/v by external standard method.
Embodiment 8 best proportioning tests
By embodiment 1-5 being formed ability with the clarity of finished product, pH value, situ-gel and ganciclovir content is index, different prescriptions and technology are investigated and estimated.
Different formulations is investigated the result
Investigate result's 1 prescription, 2 prescriptions, 3 prescriptions 4 of writing out a prescription
Ganciclovir
100.1 99.85 99.90 99.82
(labelled amount %)
PH 6.5 6.0 6.5 5.5
Clarity is qualified
Situ-gel formation ability-+++-
Conclusion: determine that embodiment 2 is optimum formula.
Annotate: the clarity criterion is seen " clarity test detailed rules and regulations and criterion " (WB1-362 (B-121)-91) of Ministry of Public Health promulgation.
Below prove beneficial effect of the present invention by concrete pharmacodynamic experiment.
Experimental example 1 ganciclovir slow release eye drop pharmacokinetics test of the present invention
In order to compare pharmacokinetics and the bioequivalence after the present invention's 0.2% ganciclovir slow release eye drop and 0.2% Eye Drops of Ganciclovir are given the lagophthalmos eye drip.
Experimental technique: adopt healthy no ophthalmic rabbit, behind two kinds of preparation eye drips, get aqueous humor at different time points, adopt high performance liquid chromatography (HPLC), chromatographic column is DAB ODS chromatographic column (OHG4240-92C18 filler, 5 μ m, 4.6mmid * 25cm), column temperature is a room temperature.Mobile phase is 0.05mol/l citric acid soln-acetonitrile (volume ratio is 79: 21), uses triethylamine to regulate pH to 4.0, the concentration of ganciclovir in the rabbit aqueous humor of mensuration different time.
Concrete steps are: draw the rabbit aqueous humor of different time points behind the medicine, add phosphate buffer (pH=7.4) mixing in the aqueous humor, add the dichloromethane vibration again, 3000rpm is centrifugal, gets organic layer, is transferred to conical centrifuge tube, 50 ℃, dries up standby under the air flow.During the HPLC sample introduction, add mobile phase to centrifuge tube, the vortex dissolving after 3000rpm is centrifugal, is got 20 μ l and is injected the analysis of high performance liquid chromatograph sample introduction fully.Precision takes by weighing the ganciclovir standard substance, formulates the aqueous humor standard curve of ganciclovir.The response rate by analytical method is investigated, the precision experiment of analytical method draws, ganciclovir high-performance liquid chromatogram determination method in the aqueous humor sample of setting up, the aqueous humor endogenous material is disturbed specimen peak not all, average recovery rate: 102.6%, in the daytime and in a few days the relative standard deviation is less than 7.87%, the minimal detectable concentration of ganciclovir is 0.02 μ g/ml in the aqueous humor, and lowest detection is limited to 0.2ng.The range of linearity is 0.05～5.0 μ g/ml.Illustrate that this method meets the analysis requirement of sample, can be used for the Preclinical metabolism and pharmacokinetics study of ganciclovir slow release eye drop.Pharmacokinetic parameters is calculated: t
Max, C
MaxAdopt measured value; Other pharmacokinetic parameters adopt the 3P87 computed in software.With ganciclovir ordinary eye drops control formulation is reference, calculates the relative bioavailability of homemade ganciclovir slow release eye drop test preparation, and its computing formula is: F=(AUC
TestD
Contrast/ AUC
ContrastD
Test) * 100%.
Evaluation of bioequivalence: evaluation of bioequivalence adopts the three-factor analysis of variance of own control, cross-over experiment design and paired data t check to carry out statistical procedures.Pharmacokinetic parameter C to two preparations
Max, AUC
0～∞/ D carries out three-factor analysis of variance and paired data t check (α=0.05).
Experimental result: from aqueous humor concentration-time data as seen, ganciclovir slow release eye drop and Eye Drops of Ganciclovir are the linear kinetics feature substantially in the absorption and the elimination process of healthy white rabbit ophthalmic.10 groups of 50 healthy rabbits intersect at random give homemade ganciclovir slow release eye drop and ganciclovir ordinary eye drops control formulation after, with the ganciclovir ordinary eye drops is reference, and the relative bioavailability of ganciclovir slow release eye drop test preparation is 181.11 ± 6.52%.Pharmacokinetic parameter C
Max, t
Max, t
1/2, MRT, AUC
0～τ, AUC
0～∞Be respectively: 1.11 ± 0.09 μ g/ml and 1.15 ± 0.72 μ g/ml, 30.00 ± 11.55min and 22.00 ± 4.78min, 107.61 ± 16.00min and 52.45 ± 5.21min, 245.56 ± 34.53min and 99.79 ± 7.10min, 178.72 ± 5.26 μ gmin/ml and 99.42 ± 4.57 μ gmin/ml, 253.41 ± 12.73 μ gmin/ml and 100.09 ± 4.30 μ gmin/ml.
Above-mentioned result of the test shows that the ganciclovir slow release eye drop of development is compared with commercially available ganciclovir ordinary eye drops, and aqueous humor concentration rises slowly, concentration change is steady, and drug release time is longer, and peak time obviously postpones, the unit dose peak concentration significantly reduces, and has the slow release drug release characteristic.
With the C after ganciclovir slow release eye drop and the administration of ganciclovir ordinary eye drops control formulation
Max, AUC
0～τ/ D is respectively to laggard capable variance analysis of number conversion and paired data t check (α=0.05).The result shows C
MaxThere was no significant difference (α=0.05), and AUC
0～τ/ D has significant difference (α=0.05), further to C
Max, AUC
0～τ/ D carries out paired data t check, and the result shows that the degree of absorption of ganciclovir slow release eye drop is higher than ganciclovir ordinary eye drops control formulation, the C of self-control ganciclovir slow release eye drop
MaxDecrease t
MaxProlong to some extent, test preparation has sustained releasing character.The 0.2% ganciclovir slow release eye drop that development is described mainly is to control the release of effective ingredient by controlled release preparation technology, thereby the ophthalmic that slows down ganciclovir absorbs, to satisfy long-acting, the purpose of safety of clinical treatment.
By above-mentioned pharmacokinetics test explanation, drug use ganciclovir of the present invention, carbomer, hydroxypropyl methylcellulose and the ophthalmic preparation adjuvant of pharmaceutically using always are that the eye of feedstock production has reached the slow release effect with slow releasing preparation, slow release eye drop of the present invention is liquid clear liquid, because the physical property (poorly water-soluble) of ganciclovir, the needs of clinical indication, quantitatively use, principal agent ganciclovir consumption is little, the bioavailability height, inherent quality is controlled, increase stability of formulation, reduce the stimulation of medicine to eyes, effect is remarkable, the use that proves absolutely slow releasing preparation of the present invention is a kind of safety, effective route of administration provides a kind of new application method for clinical.
Claims (9)
1, a kind of anti-viral pharmaceutical compositions that is used for eye is characterized in that: it is to be active component by ganciclovir, the eye slow releasing preparation that carbomer, hydroxypropyl methylcellulose and ophthalmic preparation adjuvant pharmaceutically commonly used or complementary composition are made.
2, the anti-viral pharmaceutical compositions that is used for eye according to claim 1, it is characterized in that: described carbomer is: Acritamer 940, Carbopol 941, carbomer 934.
3, the anti-viral pharmaceutical compositions that is used for eye according to claim 2, it is characterized in that: described carbomer is: Acritamer 940.
4, the anti-viral pharmaceutical compositions that is used for eye according to claim 1 is characterized in that: wherein the percent weight in volume of ganciclovir is 0.01%～0.15%w/v.
5, the anti-viral pharmaceutical compositions that is used for eye according to claim 1, it is characterized in that: described carbomer and hydroxypropyl methylcellulose, its weight proportion is 0.1～0.5: 1.0～4.0, and carbomer mixes the percent weight in volume that accounts for pharmaceutical composition with hydroxypropyl methylcellulose be 1.1%～4.5%w/v.
6, the anti-viral pharmaceutical compositions that is used for eye according to claim 5, it is characterized in that: described carbomer and hydroxypropyl methylcellulose, its weight proportion is: 0.40: 1.30, carbomer mixes the percent weight in volume that accounts for pharmaceutical composition with hydroxypropyl methylcellulose be 1.7%w/v.
7, the anti-viral pharmaceutical compositions that is used for eye according to claim 1 is characterized in that: described eye is an eye drop with slow releasing preparation.
8, the anti-viral pharmaceutical compositions that is used for eye according to claim 7 is characterized in that: the pH value of described eye drop is 5～6.5.
9, the described preparation method that is used for the anti-viral pharmaceutical compositions of eye of claim 7 is characterized in that:
A, carbomer is added the water for injection swelling, mix, form clear solution with pharmaceutically acceptable ophthalmic preparation adjuvant;
B, get ganciclovir and add the 0.1mol/L sodium hydroxide solution, heating makes it dissolving, with the swelling thing mix homogeneously of a step gained, adds water for injection, regulates pH value with sodium hydroxide, the packing of sterilizing through after the assay was approved, promptly.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100361658C (en) * | 2005-06-15 | 2008-01-16 | 刘继东 | In situ-forming eye gel composition of ganciclovir and preparation method thereof |
| US9486530B1 (en) * | 2013-08-30 | 2016-11-08 | Exela Pharma Sciences, LLC | Ganciclovir compositions and related methods |
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| WO1993017664A1 (en) * | 1992-03-02 | 1993-09-16 | Alcon Laboratories, Inc. | Combinations of cellulosic polymers and carboxy vinyl polymers and their use in pharmaceutical compositions |
| ITMI991453A1 (en) * | 1999-07-01 | 2001-01-01 | Farmila Farma Milano | OPHTHALMIC COMPOSITIONS IN THE FORM OF AQUEOUS GEL |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100361658C (en) * | 2005-06-15 | 2008-01-16 | 刘继东 | In situ-forming eye gel composition of ganciclovir and preparation method thereof |
| US9486530B1 (en) * | 2013-08-30 | 2016-11-08 | Exela Pharma Sciences, LLC | Ganciclovir compositions and related methods |
| US11723978B2 (en) | 2013-08-30 | 2023-08-15 | Exela Pharma Sciences, LLC | Ganciclovir compositions and related methods |
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