Study Of GZ-009 Eye Drops

Diabetic retinopathy(DR)is the most common complication of diabetes,and pathological changes of retinal microvessels occur in patients.The current treatments for diabetic retinopathy include surgery,panretinal photocoagulation,and drug therapy(antibodies,hormones).These treatments are mainly aimed at proliferative diabetic retinopathy,and there is currently no treatment for non-proliferative diabetic retinopathy.It has been reported that the expression of soluble epoxide hydrolase(s EH)is increased in the retina of patients with non-proliferative diabetic retinopathy.Oral s EH inhibitors can improve the retinal capillary barrier function and delay the progression of diabetic retinopathy.Therefore,in this subject,s EH inhibitor GZ-009 eye drops were prepared by inclusion technology,and the therapeutic effect of ocular administration on nonproliferative diabetic retinopathy was investigated.Preparation of eye drops: Screening solubilizers based on the properties of the formulation and the solubility of GZ-009.Screening the types and amount of metalion chelating agents based on the content of GZ-009 and related substances,and determining the p H value of the formulation.Using the antibacterial effect to screen the dosage of benzalkonium chloride,and Na Cl isotonic equivalent method was used to adjust the osmotic pressure.Screening the stirring time,speed,and sterilization method of the preparation process by using the properties of the preparation,the dissolution of GZ-009,and the content as indicators.The final prescription of eye drops are: 0.1%GZ-009,10%hydroxypropyl-β-cyclodextrin,0.1%EDTA,0.015%benzalkonium chloride,0.67%Na Cl,and the p H was adjusted to 6.5±0.5.The preparation process was as follows:GZ-009 and auxiliary materials were stirred at a speed of 500 r/min for 24 hours,filtered and sterilized,and then aseptically divided into eye drop bottles.The properties of the prepared eye drops were colorless clear liquid,The p H value was 7.0±0.5,the content was100±2%,the osmotic pressure was 290～320 m Osmol/kg,and the chemical stability was good.Pharmacodynamic experiments: A rat model of diabetic retinopathy was successfully established.The s EH activity in the retina,the number of capillary free pericytes in the digest preparations,the distribution of fluorescein in the retina,the diameter of the capillaries in the fluorescein fundus angiography,and the leakage of blood vessels after the injection of Evans Blue were used as evaluation indicators to investigate the therapeutic effect of GZ-009 eye drops on DR.The results showed that: compared with the model group,the activity of s EH in the retina of the eye drops treatment group was reduced,the number of free pericytes in the retinal vascular digest preparations was reduced,and no acellular capillary segment appeared,Meanwhile,the distribution of fluorescein in fluorescein fundus angiography was nonuniform,capillary diameter irregularities was eased,and retinal capillary leakage was reduced.All these results indicated that GZ-009 eye drops could alleviate the degree of diabetic retinopathy.The above results showed that GZ-009 eye drops were prepared to achieve local eye administration by solubilizing cyclodextrin,which can alleviate non-value-added diabetic retinopathy.it provided experiment basis for the development,administration route and indication selection of GZ-009 preparation.