Application of polysulfonic acid mucopolysaccharide in preparation of medicine for treating ophthalmic diseases

Abstract

The invention relates to the technical field of ophthalmic drugs, and particularly discloses application of polysulfonic acid mucopolysaccharide in preparation of drugs for treating ophthalmic diseases, and the ophthalmic diseases comprise xerophthalmia, corneal injury, retinal vein occlusion (RVO) or filtration bubble scarring after glaucoma filtration operation. Experiments prove that the polysulfonic mucopolysaccharide can prolong the tear film rupture time of a dry eye rabbit model, reduce the cornea fluorescein staining score, improve the optimal corrected vision of acute retinal vein occlusion patients, reduce the macular center thickness and inhibit the expression level of lipopolysaccharide-induced human corneal epithelial cell IL-6 and TNF-alpha inflammatory factors, and can be used for treating acute retinal vein occlusion. The migration and proliferation speed of the human corneal epithelial cells is improved.

Description

Technical Field

[0001] This application relates to the field of ophthalmic pharmaceutical technology, and more specifically, to the use of a polysulfated mucopolysaccharide in the preparation of a drug for treating ophthalmic diseases. Background Technology

[0002] Mucopolysaccharide polysulfate (MPS) is a heparin-like substance with known pharmacological properties including significant anti-inflammatory, anticoagulant, antithrombotic, microcirculation-improving, and tissue repair and regeneration-promoting effects. Currently, its clinical applications are mainly limited to dermatology and vascular surgery, such as for treating superficial phlebitis, contusions, hematomas, and inhibiting scar hyperplasia. However, in ophthalmology, the pathophysiological processes of many diseases are highly correlated with the mechanism of action of MPS, yet significant therapeutic gaps and limitations remain.

[0003] Dry Eye Syndrome and Corneal Injury: Dry eye syndrome is a multifactorial disease characterized by chronic ocular surface inflammation and tear film instability, with its core pathological process being a vicious cycle of "damage-inflammation." The repair process of corneal damage (such as trauma or surgical wounds) requires rapid anti-inflammatory measures and the promotion of high-quality, scarless healing. Existing treatments (such as artificial tears and anti-inflammatory drugs) often target only one specific area and are insufficient to comprehensively address the complex pathological process. Dry eye syndrome is a common multifactorial ocular surface disease characterized by insufficient tear secretion or excessive evaporation leading to tear film homeostasis imbalance, accompanied by ocular discomfort symptoms, inflammatory reactions, ocular surface epithelial damage, and neurosensory abnormalities. Globally, the prevalence of dry eye syndrome is as high as 5% to 50%, severely impacting patients' quality of life. Its core pathophysiological mechanism is considered to be a vicious cycle of "inflammation-damage": tear film instability exacerbates ocular surface friction and high osmotic pressure, triggering epithelial cell damage and apoptosis, which in turn activates the immune system and releases a large number of inflammatory factors (such as IL-1β, IL-6, TNF-α), while inflammation further damages lacrimal gland function and goblet cells, exacerbating tear film instability and forming a vicious cycle.

[0004] Currently, there are many limitations in the clinical treatment of dry eye:

[0005] Artificial tears: As a first-line basic treatment, they primarily provide temporary relief of symptoms through physical lubrication and hydration. However, their effect is short-lived, requiring frequent application. For moderate to severe dry eye syndrome, especially in patients with significant inflammation, simple lubrication is far from sufficient to control disease progression.

[0006] Hyaluronic acid (HA) eye drops: HA is a natural glycosaminoglycan widely used in high-end artificial tears due to its excellent biocompatibility, water retention, and viscoelasticity. It can form a protective hydration film on the ocular surface, prolonging tear retention time and promoting corneal epithelial repair. Although HA is superior to traditional artificial tears in lubrication and repair, its anti-inflammatory effect is relatively weak, and its ability to intervene in the core inflammatory aspects of moderate to severe dry eye is limited.

[0007] Topical anti-inflammatory drugs: Corticosteroids: such as fluorometholone and clotiprednisolone, can quickly and effectively suppress inflammation, but long-term use can cause serious side effects such as increased intraocular pressure, cataracts, and secondary infections, which limits their application in the management of chronic diseases.

[0008] Immunosuppressants, such as cyclosporine A (CsA) and Lifitegrast, are currently the mainstream prescription drugs for treating moderate to severe dry eye. They control inflammation by inhibiting T-cell activation or integrin signaling pathways. However, these drugs generally have a slow onset of action (usually taking weeks to months), significant individual variability in efficacy, and are often accompanied by adverse reactions such as eye irritation and burning, leading to poor patient compliance.

[0009] Retinal vein occlusion (RVO): RVO is a common blinding vascular disease in ophthalmology. Its core cause is thrombosis within the retinal veins, leading to serious complications such as blood flow obstruction, retinal ischemia and hypoxia, macular edema, and neovascularization. Although anti-VEGF drugs are the standard treatment for macular edema secondary to RVO, they do not target the underlying cause—the thrombus itself. Systemic anticoagulation therapy carries the risk of bleeding and is inconvenient to use. Therefore, developing a local therapeutic agent that can directly act on the eye and dissolve microthrombi is of great significance.

[0010] Postoperative scarring of the filtering bleb after glaucoma surgery: Glaucoma filtration surgery is an effective method for lowering intraocular pressure, but its long-term success rate is limited by postoperative fibrosis and scarring of the filtering bleb. Currently, antimetabolites such as mitomycin C are commonly used clinically to inhibit scarring, but these drugs have potential risks such as strong cytotoxicity and corneal endothelial damage. Finding a safer and gentler antifibrotic drug to maintain the long-term patency of the filtration channel is an urgent clinical need.

[0011] In conclusion, although existing cream formulations of MPS explicitly prohibit contact with the eyes, its unique multiple pharmacological effects make it a highly promising candidate molecule for developing novel ophthalmic drugs. There is an urgent need to develop a safe, effective, and appropriately formulated MPS drug to meet the aforementioned unmet clinical needs. Summary of the Invention

[0012] To address the aforementioned technical issues, this application provides the use of polysulfated mucopolysaccharides in the preparation of drugs for treating ophthalmic diseases. Polysulfated mucopolysaccharides can effectively improve dry eye syndrome, corneal damage, retinal vein occlusion (RVO), or scarring of the filtering bleb after glaucoma filtration surgery, thus opening up new methods for treating related ophthalmic diseases.

[0013] To achieve the above objectives, this application adopts the following technical solution:

[0014] The use of polysulfated mucopolysaccharides in the preparation of drugs for the treatment of the following ophthalmic diseases: dry eye, corneal injury, retinal vein occlusion (RVO) or scarring of the filtering bleb after glaucoma filtration surgery.

[0015] More preferably, polysulfated mucopolysaccharides can prolong tear film breakup time and reduce corneal fluorescein staining scores in patients with dry eye syndrome.

[0016] More preferably, polysulfated mucopolysaccharides can improve vision in patients with acute retinal vein occlusion and reduce central macular thickness.

[0017] More preferably, polysulfated mucopolysaccharide can inhibit the expression levels of IL-6 and TNF-α inflammatory factors induced by lipopolysaccharide in human corneal epithelial cells.

[0018] More preferably, polysulfated mucopolysaccharides can increase the migration and proliferation rate of human corneal epithelial cells.

[0019] More preferably, when the drug is an eye drop or an ophthalmic gel, the weight percentage concentration of polysulfated mucopolysaccharide is 0.05%-2.0%, preferably 0.1%-1.0%, and more preferably 0.3%.

[0020] More preferably, when the drug is an intravitreal injection solution, the concentration of polysulfated mucopolysaccharide is 5-15 mg / mL, preferably 10 mg / mL.

[0021] More preferably, the drug further includes pharmaceutically acceptable excipients, including but not limited to:

[0022] Thickeners: Used to increase viscosity and prolong the residence time of drugs on the ocular surface, such as carbomer, hydroxypropyl methylcellulose, polyvinyl alcohol, etc.

[0023] Buffers: Used to adjust the pH value to a range that is tolerable to the eyes (such as pH 6.5-7.5), such as phosphate buffer, borate buffer, etc.

[0024] Isotonic regulators: used to adjust the osmotic pressure to be isotonic with tears, such as sodium chloride and glycerin.

[0025] Preservatives: used to prevent microbial contamination, such as benzalkonium chloride, polyquaternium-1, etc.

[0026] In summary, this application overcomes the "opposite teaching" and achieves innovative applications: it is the first time that monotherapy with polysulfated mucopolysaccharide can simultaneously achieve: repair of ocular surface damage, potent anti-inflammatory effects, and improvement of fundus diseases; and it has dosage form universality, which can be flexibly formulated into eye drops, ointments, gels or intraocular injections to meet the needs of different lesion sites.

[0027] This application successfully transforms polysulfated mucopolysaccharide, an active substance traditionally considered to be contraindicated for use in the eye, into a monotherapy or combination therapy through an original ophthalmic formulation technology. This breakthrough demonstrates its high efficacy and safety in eye diseases such as dry eye and retinal vein occlusion, overcoming long-standing technical biases in this field. Attached Figure Description

[0028] Figure 1 A comparison of tear film breakup time (TBUT) in different groups of mice;

[0029] Figure 2 A comparison chart of corneal fluorescein staining (CFS) scores for mice in each group;

[0030] Figure 3 A comparison of the inhibition rates of the inflammatory factor IL-6 in human corneal epithelial cells from different groups;

[0031] Figure 4 This is a comparison of the inhibition rates of the inflammatory factor NTF-α in corneal epithelial cells of different groups. Detailed Implementation

[0032] The following specific examples illustrate the implementation of this application. Those skilled in the art can easily understand other advantages and effects of this application from the content disclosed in this specification. This application can also be implemented or applied through other different specific embodiments, and various details in this specification can also be modified or changed based on different viewpoints and applications without departing from the spirit of this application.

[0033] Furthermore, it should be understood that the one or more method steps mentioned in this application do not preclude the existence of other method steps before or after the combined steps, or the insertion of other method steps between these explicitly mentioned steps, unless otherwise stated. Moreover, unless otherwise stated, the numbering of each method step is merely a convenient tool for identifying each method step, and is not intended to limit the order of the method steps or limit the scope of implementation of this application. Changes or adjustments to their relative relationships, without substantially altering the technical content, shall also be considered as within the scope of implementation of this application.

[0034] Unless otherwise specified, the experimental conditions used in the examples are generally in accordance with conventional conditions in the art or the conditions recommended by the reagent company. Unless otherwise specified, the materials and reagents used in the examples can be purchased commercially.

[0035] Polysulfated mucopolysaccharide: Source: Nanjing Dichang Pharmaceutical Technology Co., Ltd.; Specific rotation: -13.6° (limit: -10°~-15°), Molar ratio of sulfate to carboxyl group: 3.5 (limit: ≥3.0), Molecular weight and molecular weight distribution: Weight average molecular weight: 9046 (weight average molecular weight limit: 5000~15000), Content determination: 98.8% (limit: 90.0%~110.0%).

[0036] Sodium hyaluronate: Source: Bloomage Biotechnology Co., Ltd.; Intrinsic viscosity: 16.8 (limit: 11.8 dL / g~19.5 dL / g), average molecular weight: 968068 (limit: 600000~1200000); Content determination: 100.2% (limit: contains sodium hyaluronate (C 14 H 20 NNaO 11 ) n It should be 95.0% to 105.0%.

[0037] Example

[0038] Example 1: Preparation of 0.3% MPS eye drops

[0039] Formula: For a preparation of 1000 mL, see Table 1 for the formula.

[0040] Table 1

[0041]

[0042]

[0043] Preparation process: a. Take 800 mL of water for injection, heat to 60℃, and add sodium chloride, disodium hydrogen phosphate, and sodium dihydrogen phosphate sequentially, stirring to dissolve. b. Cool to room temperature, add polysulfated mucopolysaccharide, and continue stirring until completely dissolved and transparent. c. Add benzalkonium chloride solution and mix well. d. Adjust the pH to 7.0±0.2 using 0.1M hydrochloric acid or 0.1M sodium hydroxide solution. e. Make up to 1000 mL with water for injection and mix well. f. Filter sterilely using a sterile filter membrane with a pore size of 0.22 μm. g. In a Class 100 laminar flow clean environment, aseptically fill the filtrate into pre-sterilized eye drop bottles, 5 mL per bottle, and seal. h. Conduct quality inspection; the finished product is obtained after passing the inspection.

[0044] Example 2: Preparation of 0.5% MPS ophthalmic gel

[0045] Formula: For a preparation of 1000 mL, see Table 2 for the formula.

[0046] Table 2

[0047] Element Dosage effect Polysulfonic acid mucopolysaccharide 0.5g Active ingredients Carbomer 974P 0.25g gel matrix glycerin 2.0g Moisturizers, isotonic regulators Sodium hydroxide Appropriate amount pH adjuster Water for Injection Add to 100g solvent

[0048] Preparation process: Carbomer is dispersed in water for injection and, after complete hydration, glycerol and MPS are added sequentially and stirred until homogeneous. The pH is adjusted to 7.4 with sodium hydroxide solution to form a transparent gel. After terminal moist heat sterilization, it is aseptically filled into dedicated ophthalmic gel tubes.

[0049] Example 3: Preparation of 1 mg / 0.1 mL MPS intravitreal injection solution

[0050] Formula: For a preparation of 100 mL, see Table 3 for the formula.

[0051] Table 3

[0052] Element Dosage effect Polysulfonic acid mucopolysaccharide 1.0g Active ingredients Sodium chloride 0.9g isotonic regulator Water for Injection Add to 100mL solvent

[0053] Preparation process: a. Under aseptic conditions, dissolve polysulfated mucopolysaccharide and sodium chloride in water for injection. b. Check and adjust the pH to 7.2±0.2. c. Make up to 100mL with water for injection. d. Filter the solution twice through a 0.22μm sterile filter membrane for sterilization. e. Aseptically fill the filtrate into 2mL vials, 0.5mL per vial, and cap and stopper. f. Perform 100% visual inspection and discard any defective products. g. After quality inspection confirms sterility and pyrogen-free status, the finished injection solution with a concentration of 10mg / mL is obtained. For clinical use, 0.1mL is used as a 1mg dose.

[0054] Preparation of Comparative Example 1: 0.2% HA Eye Drops

[0055] Formula: For a preparation of 1000 mL, see Table 4 for the formula.

[0056] Table 4

[0057] Element Dosage effect Sodium hyaluronate 2.0g Active ingredients Sodium chloride 7.0g Isotonic regulator Sodium hydrogen phosphate Appropriate amount buffer Sodium dihydrogen phosphate Appropriate amount buffer Benzalkonium chloride (50% solution) 0.2mL preservative Water for Injection Add to 1000mL solvent

[0058] Preparation process: a. Take 800 mL of water for injection, heat to 60℃, and add sodium chloride, disodium hydrogen phosphate, and sodium dihydrogen phosphate sequentially, stirring to dissolve. b. Cool to room temperature, add sodium hyaluronate, and continue stirring until completely dissolved and transparent. c. Add benzalkonium chloride solution and mix well. d. Adjust the pH to 7.0±0.2 using 0.1M hydrochloric acid or 0.1M sodium hydroxide solution. e. Make up to 1000 mL with water for injection and mix well. f. Filter sterilely using a sterile filter membrane with a pore size of 0.22 μm. g. In a Class 100 laminar flow clean environment, aseptically fill the filtrate into pre-sterilized eye drop bottles, 5 mL per bottle, and seal. h. Conduct quality inspection; the finished product is obtained after passing the inspection.

[0059] Testing and Experiment

[0060] Eye drops and ophthalmic gels work in similar ways, differing only in dosage form and viscosity. Therefore, this application conducts efficacy testing experiments on eye drops, with the specific test items as follows.

[0061] Test 1: The effect of 0.3% MPS eye drops in treating dry eye syndrome

[0062] To verify the synergistic effect of the composition of the present invention, a benzalkonium chloride (BAC)-induced rabbit dry eye model was established.

[0063] 1. Experimental Animals and Grouping: Thirty healthy New Zealand white rabbits were randomly divided into 3 groups of 10 each:

[0064] Group A (model control group): Administered physiological saline.

[0065] Group B (HA control group): Administered 0.2% HA eye drops prepared in Comparative Example 1.

[0066] Group C (MPS group): Administered 0.3% MPS eye drops prepared in Example 1.

[0067] 2. Modeling and Drug Administration: A dry eye model was successfully established by instilling 0.1% BAC solution into the rabbit eyes twice daily for 2 weeks. Drug administration was then initiated, with 50 μL administered four times daily for 4 weeks.

[0068] 3. Evaluation indicators and results were measured before treatment (week 0) and at 2 and 4 weeks after treatment.

[0069] Tear film breakup time (TBUT): Results are as follows: After 4 weeks of treatment, the TBUT in group B was prolonged by 2.5 seconds, while the average TBUT in group C was prolonged by 4.6 seconds. This effect was significantly better than that in group B (P < 0.01). Specific test data are shown in Table 5 and... Figure 1 .

[0070] Table 5: Statistical comparison of tear film breakup time (TBUT)

[0071]

[0072]

[0073] Corneal fluorescein staining (CFS) scoring: The Oxford scoring system was used. Results are as follows: After 4 weeks of treatment, group B showed an average reduction of 1.8 points; while group C (the present invention group) showed an average reduction of 2.4 points, with the improvement being significantly better than group B (PP < 0.01). Specific test data are shown in Table 6 and... Figure 2 .

[0074] Table 6: Statistical Comparison of Corneal Fluorescein Staining (CFS) Scores

[0075]

[0076] Histopathological examination: After treatment, corneal tissue was harvested for HE staining to observe the number of epithelial cell layers and goblet cell density. The results showed that group C had the most intact corneal epithelial structure, close to normal levels, and the goblet cell density recovery was also the most significant, superior to all control groups.

[0077] Test 2: Anti-inflammatory effect of 0.3% MPS eye drops

[0078] 1. Experimental model: Human corneal epithelial cells (HCEC) were used, and an inflammatory response was induced by lipopolysaccharide (LPS).

[0079] 2. Grouping:

[0080] control group

[0081] LPS model group (1 μg / mL LPS)

[0082] LPS + 0.2% HA group (Comparative Example 1)

[0083] LPS + 0.3% MPS group (Example 1)

[0084] Detection and Results: After 24 hours of culture, the concentrations of inflammatory factors IL-6 and TNF-α in the culture supernatant were detected by ELISA. The results are as follows: Compared with the LPS model group, the HA group showed inhibition rates of 25% and 22% for IL-6 and TNF-α, respectively, while the MPS group showed inhibition rates of 35% and 31% for IL-6 and TNF-α, respectively. MPS exhibited better anti-inflammatory effects than HA. Specific test data are shown in Tables 7 and 8. Figure 3 , Figure 4 .

[0085] Table 7: Statistical comparison of IL-6 inhibition rates (%)

[0086]

[0087] Table 8: Statistical comparison of TNF-α inhibition rates (%)

[0088]

[0089] Test 3: The effect of 0.3% MPS eye drops on promoting corneal repair

[0090] 1. Experimental model: A "scratch" was created on a fused HCEC monolayer using a sterile pipette tip.

[0091] 2. Grouping:

[0092] control group

[0093] LPS model group (1 μg / mL LPS)

[0094] LPS + 0.2% HA group (Comparative Example 1)

[0095] LPS + 0.3% MPS group (Example 1).

[0096] Detection and Results: The scratched areas were photographed at 0 and 24 hours, and the healing rate was calculated. Results are as follows: After 24 hours, the healing rate was approximately 30% in the control group, 35% in the HA group, and reached 50% in the MPS group. This indicates that MPS has a significant positive effect on promoting corneal epithelial cell migration and proliferation.

[0097] Test 4: Evaluation of ocular irritation of 0.3% MPS eye drops

[0098] The 0.3% MPS eye drops prepared in Example 1 were used to conduct an acute eye irritation test on six New Zealand white rabbits. Following the standard method in "Chemical Testing Methods", 0.1 mL of the solution was administered once into the conjunctival sac of the rabbit eye. The reactions of the cornea, iris, and conjunctiva were observed at 1, 24, 48, and 72 hours after administration.

[0099] Results: At all observation time points, all animals had corneal, iris, and conjunctival scores of 0, indicating no irritation. The mean score for acute eye irritation was 0, indicating no irritation. This suggests that 0.3% MPS eye drops are highly safe and well-tolerated in rabbit eyes.

[0100] Test 5: Stability Study of 0.3% MPS Eye Drops

[0101] The 0.3% MPS eye drop sample prepared in Example 1 was placed under accelerated stability test conditions (temperature 40℃±2℃, relative humidity 75%±5%) for 6 months. Test items included: appearance, pH value, osmolality, related substances, MPS content, HA content, and water loss rate. The test results are shown in Table 9.

[0102] Table 9

[0103]

[0104] Results analysis:

[0105] Appearance: Throughout the entire observation period, the solution remained a colorless and clear liquid, with no visible foreign matter.

[0106] pH value and osmotic pressure: No significant changes were observed within 6 months, and both remained within the range specified in the quality standard.

[0107] Active ingredient content: MPS content remained above 98% of the initial content within 6 months, with minimal degradation.

[0108] Related substances: No significant increase was observed.

[0109] Water loss rate: Meets requirements.

[0110] Conclusion: The 0.3% MPS eye drops prepared in this application exhibit good physical and chemical stability under accelerated conditions, indicating that it has a shelf life of at least 24 months under normal conditions.

[0111] Test 6: Efficacy of 1 mg / 0.1 mL MPS intravitreal injection in the treatment of acute retinal vein occlusion (RVO)

[0112] Patients with acute central or branch retinal vein occlusion (CRVO / BRVO) within one month of onset were selected.

[0113] Dosage and administration: Under standard aseptic conditions, administer an intravitreal injection to the affected eye, using 0.1 mL of the injection solution prepared in Example 3 (containing 1 mg of polysulfated mucopolysaccharide) in a single injection.

[0114] Tests and Results: One month after injection, the patient's best corrected visual acuity (BCVA) showed a significant improvement compared to baseline. Optical coherence tomography (OCT) showed a significant reduction in central macular thickness (CMT).

[0115] Fundus fluorescein angiography (FFA) may show a reduction in the area of ​​retinal non-perfusion zones and improved microcirculation.

[0116] Its mechanism of action lies in the fact that MPS, as a heparin-like substance, can directly exert anticoagulant and fibrinolytic effects within the vitreous cavity, dissolving microthrombi that obstruct blood vessels and thereby restoring retinal blood flow perfusion.

[0117] It improves tissue hypoxia and, due to its anti-inflammatory properties, further reduces secondary inflammatory responses and macular edema.

[0118] The above description is merely a preferred embodiment of this application and does not constitute any limitation on this application in any form or substance. It should be noted that those skilled in the art can make several improvements and additions without departing from the method of this application, and these improvements and additions should also be considered within the scope of protection of this application. Any modifications, alterations, and equivalent changes made by those skilled in the art based on the above-disclosed technical content without departing from the spirit and scope of this application are equivalent embodiments of this application; furthermore, any modifications, alterations, and evolutions made to the above embodiments based on the essential technology of this application still fall within the scope of the technical solution of this application.

Claims

1. Application of polysulfated mucopolysaccharides in the preparation of drugs for the treatment of the following ophthalmic diseases: dry eye, corneal injury, retinal vein occlusion or scarring of the filtering bleb after glaucoma filtration surgery.

2. The application of the polysulfated mucopolysaccharide according to claim 1 in the preparation of drugs for treating ophthalmic diseases, characterized in that, Polysulfated mucopolysaccharides can prolong tear film breakup time in a rabbit model of dry eye and reduce corneal fluorescein staining scores.

3. The application of the polysulfated mucopolysaccharide according to claim 1 in the preparation of drugs for treating ophthalmic diseases, characterized in that, Polysulfated mucopolysaccharides can improve best-corrected visual acuity in patients with acute retinal vein occlusion and reduce central macular thickness.

4. The application of the polysulfated mucopolysaccharide according to claim 1 in the preparation of drugs for treating ophthalmic diseases, characterized in that, Polysulfated mucopolysaccharides can inhibit the expression levels of IL-6 and TNF-α inflammatory factors induced by lipopolysaccharides in human corneal epithelial cells.

5. The application of the polysulfated mucopolysaccharide according to claim 1 in the preparation of drugs for treating ophthalmic diseases, characterized in that, Polysulfated mucopolysaccharides can increase the migration and proliferation rate of human corneal epithelial cells.

6. The use of the polysulfated mucopolysaccharide according to any one of claims 1-5 in the preparation of a drug for treating ophthalmic diseases, characterized in that, The drug is an eye drop or ophthalmic gel, and the weight percentage concentration of polysulfated mucopolysaccharide is 0.05%-2.0%.

7. The application of the polysulfated mucopolysaccharide according to claim 6 in the preparation of drugs for treating ophthalmic diseases, characterized in that, The drug is an eye drop or ophthalmic gel, and the weight percentage concentration of polysulfated mucopolysaccharide is 0.1%-1.0%.

8. The application of the polysulfated mucopolysaccharide according to claim 6 in the preparation of drugs for treating ophthalmic diseases, characterized in that, The drug is an eye drop or ophthalmic gel, and the weight percentage concentration of polysulfated mucopolysaccharide is 0.3%.

9. The use of the polysulfated mucopolysaccharide according to any one of claims 1-5 in the preparation of a drug for treating ophthalmic diseases, characterized in that, The drug is an intravitreal injection solution with a polysulfated mucopolysaccharide concentration of 5-15 mg / mL.

10. The use of the polysulfated mucopolysaccharide according to claim 9 in the preparation of drugs for treating ophthalmic diseases, characterized in that, The drug is an intravitreal injection solution with a polysulfated mucopolysaccharide concentration of 10 mg / mL.

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