Patent Background
One of the patents for medium-term corneal preservation solution (Application No. CN200410091007.5, filed on November 15, 2004) was submitted by Shandong Eye Institute. The inventors include Dong Xiaoguang, Xie Lixin, and Shi Weiyun.
The patent describes a preservation solution consisting of RPMI1640 medium, chondroitin sulfate, hyaluronic acid, HEPES buffer, dexamethasone, low molecular weight algal polysaccharide, and antibiotics such as tobramycin or vancomycin. The solution is light orange, transparent, and mildly viscous.
The formulation can preserve corneal viability for over two weeks, with stable endothelial cell activity. Its effectiveness in preserving endothelial cells is comparable to Optisol, with superior maintenance of metabolic function over time. Clinically, corneas preserved for more than seven days still maintained endothelial cell density above 2,000 cells/mm² one to four weeks after transplantation.
Technical and Regulatory Evaluation
Product Composition:
The corneal preservation solution consists of cell nutrient medium, stabilizers, antioxidants, preservatives, and sterile water for injection. The nutrient medium includes MEM, F12, M199, non-essential amino acids, sodium pyruvate, and β-mercaptoethanol. Stabilizers include sodium chondroitin sulfate and dextran. Antioxidants include dexamethasone sodium phosphate, (R)-3-hydroxybutyrate, and dexmedetomidine hydrochloride. Amikacin sulfate serves as a preservative. The solution is sterile, produced via filtration and aseptic filling, intended for single-use, with a shelf life of one year.
Indications:
For ex vivo preservation of donor corneas for up to seven days. Available in 10 mL and 20 mL vials.
Although many components are drug-like, the product is classified as a Class III medical device. Its principle is to maintain corneal transparency, provide nutrients, reduce endothelial metabolism, and inhibit bacterial growth.
Performance Studies:
The manufacturer submitted extensive validation, including formulation rationale, technical specifications, comparative studies with Optisol-GS in rabbit corneas, residual cleaning validation, and impurity analyses.
Biocompatibility Testing:
Tests included cytotoxicity, skin sensitization, ocular irritation, acute systemic toxicity, and pyrogenicity. Since chondroitin sulfate sodium is derived from porcine cartilage, biosafety evaluation confirmed acceptable risk, provided donor corneas are rinsed before transplantation, following GB/T 44353.1 and YY/T 0771.1 standards.
Animal Studies:
Rabbit corneas were stored for 1, 7, and 14 days. Observed parameters included endothelial cell density, hexagonality, and cell area. Corneal transplantation was performed after 7, 14, and 25 days of storage. Postoperative assessments at days 1 and 14 examined transparency, endothelial density, and corneal thickness. Results demonstrated feasibility and compliance with design requirements.
Clinical Trials:
A prospective, single-group target-value design trial enrolled 60 patients.
- Primary Endpoints: Donor cornea viability at transplantation (endothelial density ≥2,000 cells/mm²) and graft transparency at 14 days post-op.
- Secondary Endpoints: Endothelial hexagonality at transplantation, endothelial density at 14 days post-op, graft thickness, epithelial healing, and visual recovery.
- Safety Endpoints: Re-graft rate, adverse events, and serious adverse events.
Contraindications:
As trace amounts of amikacin sulfate may remain from manufacturing, patients with known hypersensitivity to amikacin face cross-allergy risks. Physicians must carefully review patient allergy history before use. Inclusion of antibiotics, even at trace levels, remains essential in such solutions.