CN-122005434-A - ROS responsive hydrogel eye drop preparation, preparation method thereof and application thereof in cornea disease treatment

Abstract

The invention relates to the technical fields of biomedical engineering and drug delivery systems, in particular to an ROS responsive hydrogel eye drop preparation, a preparation method thereof and application thereof in cornea disease treatment. Aiming at the problems of short ocular surface residence time, low bioavailability and the like of the existing eye drop preparation, the invention adds glycyrrhizic acid to be used as a skeleton of ROS responsive hydrogel TPG on the basis of polyvinyl alcohol, and the obtained hydrogel eye drop has injectability, shear thinning property and thixotropic property, is suitable for being used as eye drops, can effectively prolong the ocular surface residence time, and can regulate the immune microenvironment of keratitis by inhibiting the neutrophil inflammation amplification process related to HMGB 1.

Inventors

• ZHANG RUIPING
• WANG YANAN
• CAO BING
• Dong Zhuorui
• CUI DANDAN

Assignees

• 山西医科大学

Dates

Publication Date

20260512

Application Date

20260130

Claims (7)

1. 1. An ROS-responsive hydrogel eye drop preparation is characterized in that polyvinyl alcohol and glycyrrhizic acid are taken as frameworks, and cross-linking is carried out through an ROS-responsive cross-linking agent TSPBA.
2. 2. A method of preparing the ROS-responsive hydrogel eye-drop formulation of claim 1, comprising the steps of: Step 1, dissolving N, N, N, N-tetramethyl-1, 3-propanediamine and 4-bromomethyl phenylboronic acid in a solvent, stirring for reaction, settling and collecting TSPBA solids after the reaction is finished, and dissolving TSPBA solids to obtain TSPBA aqueous solution; And 2, uniformly mixing TSPBA aqueous solution, polyvinyl alcohol aqueous solution and glycyrrhizic acid aqueous solution to obtain TPG hydrogel, namely the ROS responsive hydrogel eye drop preparation.
3. 3. The method for preparing the ROS-responsive hydrogel eye-drop formulation as claimed in claim 2, wherein the stirring reaction in the step 1 is carried out at 60 ℃ for 12 hours.
4. 4. The method for preparing the ROS-responsive hydrogel eye drop preparation of claim 2, wherein the TSPBA aqueous solution, the polyvinyl alcohol aqueous solution, and the glycyrrhizic acid aqueous solution have mass fractions of 15% wt% -30%, 7% wt%, and 0.25% wt%, respectively.
5. 5. The method of claim 4, wherein the volume ratio of TSPBA aqueous solution, polyvinyl alcohol aqueous solution and glycyrrhizic acid aqueous solution is 1:1:1.
6. 6. Use of the ROS-responsive hydrogel eye-drop formulation of claim 1 for the manufacture of a medicament for the treatment of bacterial keratitis.
7. 7. A hydrogel eye drop comprising the ROS-responsive hydrogel eye drop formulation of claim 1.

Description

ROS responsive hydrogel eye drop preparation, preparation method thereof and application thereof in cornea disease treatment Technical Field The invention relates to the technical fields of biomedical engineering and drug delivery systems, in particular to an ROS responsive hydrogel eye drop preparation, a preparation method thereof and application thereof in cornea disease treatment. Background Bacterial keratitis is one of the main causes of corneal blindness. The disease usually has rapid onset and severe progression, is liable to damage cornea stroma and cornea thinning, and can cause cornea perforation and permanent vision impairment. At present, bacterial keratitis is mainly treated by locally dripping an antibiotic eye drop clinically, and commonly used medicines comprise ciprofloxacin, tobramycin and the like. The treatment mode has the advantages of simple and convenient operation, quick response and the like, and is widely used clinically. However, the existing methods of antibiotic eye drop treatment have obvious technical drawbacks, mainly in that firstly, the drugs are extremely susceptible to blinking and tear washout after ocular surface administration, and are rapidly cleared, resulting in short corneal residence time and difficulty in maintaining stable local drug concentrations. Second, the cornea itself has multiple physiological barrier structures, and the drug permeation into the cornea is less efficient. Hydrophilic drugs are susceptible to obstruction by tight junctions of the corneal epithelium, while hydrophobic drugs are diffusion limited in the highly aqueous corneal stroma, resulting in a low proportion of drug entering the corneal stroma and aqueous humor, which makes it difficult to form effective bactericidal concentrations at the affected site. In addition, bacteria persist and are prone to induce excessive host inflammatory responses. During infection, neutrophils recruit large amounts of reactive oxygen species and produce the extracellular capture Network (NETs) of neutrophils, which, while helping to kill bacteria, overactivation destroys the corneal stroma structure and creates an inflammatory amplification effect through high mobility group box 1 (HMGB 1) mediated inflammatory signaling pathways, further exacerbating corneal tissue damage. The inflammatory reaction not only can destroy ordered arrangement of cornea collagen, resulting in formation of cornea scar and reduced transparency, but also can weaken biomechanical property of cornea, increase risk of cornea dilatation, edema and even perforation, and seriously affect treatment prognosis. Therefore, a new ophthalmic treatment technology is needed, which can synergistically regulate and control excessive inflammatory reaction induced by bacterial infection, particularly inhibit the HMGB1 mediated inflammatory amplification process, while prolonging the retention time of the ocular surface of the drug and improving the effective concentration of the drug in the cornea. The technology is based on effectively controlling bacterial infection, and reduces secondary damage of inflammation to cornea structure, thereby being beneficial to protecting cornea transparency and biomechanical integrity and improving the overall treatment effect and safety of bacterial keratitis. Disclosure of Invention Aiming at the problems of short ocular surface residence time, low bioavailability and the like of the existing eye drop preparation, the invention provides an ROS responsive hydrogel eye drop preparation, a preparation method thereof and application thereof in cornea disease treatment. According to the invention, the glycyrrhizic acid is added on the basis of the polyvinyl alcohol to be used as the skeleton of the ROS responsive hydrogel TPG, and the obtained hydrogel eye drops have injectability, shear thinning characteristic and thixotropic property, are suitable for being used as eye drops, and can effectively prolong the retention time of the ocular surface. TPG hydrogels can modulate the keratitis immune microenvironment by inhibiting the HMGB 1-related neutrophil inflammatory amplification process. The invention adopts the following technical scheme to achieve the aim: In a first aspect, the present invention provides an ROS-responsive hydrogel eye drop formulation, comprising polyvinyl alcohol and glycyrrhizic acid as a backbone, crosslinked by ROS-responsive crosslinking agent TSPBA. In a second aspect, the present invention provides a method for preparing the ROS-responsive hydrogel eye-drop formulation of claim 1, comprising the steps of: Step 1, dissolving N, N, N, N-tetramethyl-1, 3-propanediamine and 4-bromomethyl phenylboronic acid in a solvent, stirring for reaction, settling and collecting TSPBA solids after the reaction is finished, and dissolving TSPBA solids to obtain TSPBA aqueous solution; And 2, uniformly mixing TSPBA aqueous solution, polyvinyl alcohol aqueous solution and glycyrrhizic acid aqueous solution