| ObjectiveThe aim of this study is to prevent and treat corneal neovascularization caused by ocular trauma,to improve the bioavailability of RCG.RCG ophthalmic in situ gel was prepared and its quality was evaluated,at the same time its pharmacodynamics and pharmacokinetics were researched.This paper establish the theoretical foundation for the research and development of new products related to RCG.MethodsPolymer materials which were represented by Carbomer,HPMC(K4M)and Poloxamers were used as the main gel matrix.The dosage and ratio of the main matrix of the ophthalmic in situ gel were determined by investigating the gel forming ability,the viscosity and the phase transition temperature.RCG ophthalmic in situ gel was prepared,its properties,pH,quantitative determination,permeability of isolated corneal,stability,irritation and sterile examination were investigated to evaluate the formulation.32 rats were used as pharmacodynamic models.The rats were divided averagely into four groups,and recorded as low dose group,medium dose group,high dose group and control group.The model of corneal neovascularization in rats was established by suture method.Three research groups were given 25mg/ml,50mg/ml,100mg/ml RCG ophthalmic in situ gel,the amount is 100?l/time,treatment for 12 d.The control group were received saline,the amount is 100?l/time,treatment for 12 d.The length and width of corneal neovascularizationthe were measured under the LYL-II type slit lamp microscope in 3rd,6th,9th and 12 th day.And the pathological tissues of the 4groups were observed.10 healthy rabbits were divided into five groups which recorded as group A(10min),group B(30min),group C(60min),group D(120min)and group E(180min),according to the time of collecting the vitreous in pharmacokinetics experiment.5 groups of rabbits were administered RCG ophthalmic in situ gel,the amount is 200?l,then vitreous were collected at different times.The concentrations of RCG in the cornea,iris,vitreous and aqueous were determined respectively.ResultsThe type of RCG ophthalmic in situ gel was determined as pH sensitive type.The best ratio of formulation was 0.1g Carbopol 940 and 0.4g HPMC(100ml water).The RCG ophthalmic in situ gel was light yellow,clear and transparent liquid,pH value of about 5.5 which was fit for human eyes ranges of tolerance,good stability,no local eye irritation.Sterile examination result met the eye administration's requirements.The results of pharmacodynamic experiment: Corneal neovascular area in rats of low dose group was(12.36±3.39)mm2at the 3rd day.It is little difference compared with the control group which neovascular area was(12.46±4.36)mm2.CNV area of medium dose group and high dose group were both significantly lower than low dose group and control group,which respectively(2.39±3.68)mm2and(2.01±2.96)mm2.After 12 days,CNV area of medium dose group was(5.36±7.12)mm2 and CNV area of high dose group was(4.89±6.59)mm2.Their measurements were bigger than the data on the third day,but lower than the control group significantly.Histopathological results also showed,RCG ophthalmic in situ gel of the concentration above 50 mg/ml can control corneal neovascularization in rats with large range,and inhibit lammatory cell infiltration in corneal tissue.The results of pharmacokinetics experiment: The concentration of drug in the iris increased first and then decreased,and reached the maximum at 60 min,which was(28.2±0.4)?g/ml.The drug concentration in corneal showed a decreasing trend,reached the maximum after 10 min,which was(17.0±0.3)?g/ml.The drug concentration in aqueous humor increased first and thendecreased,and reached the maximum after 60 min,which was(9.3±0.2)?g /ml.The drug concentration in vitreous was stable.After 180 min,the concentration in cornea was the highest,reached(3.1±0.5)?g/ml.ConclusionpH sensitive RCG ophthalmic in situ gel is stable,safe,effective,and has the longest residence time in cornea,this has a positive effect on the treatment of corneal neovascularization. |
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