Nicotinamide-containing intraocular surgery perfusate, preparation method therefor, and use thereof

Abstract

A nicotinamide-containing intraocular surgery perfusate, a preparation method therefor, and use thereof. Use of nicotinamide in an intraocular surgery perfusate. The intraocular surgery perfusate improved using nicotinamide can inhibit corneal endothelial cell damage caused by cataract ultrasonic emulsification surgery treatment, relieve corneal edema caused by cataract ultrasonic emulsification surgery, prevent the number of corneal endothelial cells from being significantly reduced due to surgery, promote the postsurgical recovery of corneal transparency, promote the recovery of the thickness of the cornea to a normal level, maintain the normal density and cellular morphology of the corneal endothelial cells and the regular expression of functional proteins, and reduce complications caused by cataract ultrasonic emulsification surgery. The present invention can provide an effective strategy for the rapid postsurgical recovery of normal visual function in cataract patients.

Description

Intraocular surgical perfusion solution containing nicotinamide, preparation method and application thereof

[0001] This application claims priority to the Chinese patent application filed with the China Patent Office on October 26, 2023, with application number 202311396074.7 and invention name “A niacinamide-containing intraocular surgical irrigation solution, its preparation method and application”, the entire contents of which are incorporated by reference into this application. Technical Field

[0002] The invention belongs to the technical field of drug preparation, and particularly relates to an intraocular surgical perfusion solution containing nicotinamide, a preparation method and application thereof. Background Art

[0003] Cataracts are the world's leading cause of blindness. Currently, most cataract surgeries are performed using phacoemulsification, which uses high-intensity ultrasonic energy to fragment and emulsify the cloudy lens. With advances in surgical equipment and technology, the indications for phacoemulsification have expanded to include mature cataracts with a hard lens nucleus, requiring higher phacoemulsification energy and time. However, excessive phacoemulsification energy, fragmented lens nucleus, and elevated local temperatures can damage corneal endothelial cells (CECs), leading to a significant decrease in CEC numbers, corneal edema, and even endothelial decompensation, necessitating corneal transplantation in severe cases. CECs are located in the innermost layer of the cornea and maintain normal corneal transparency and visual function through their barrier and pump functions. Because adult CECs have a very limited proliferative capacity, they can only repair damage through the expansion and migration of surrounding cells, resulting in a gradual decrease in cell density. When the cell density falls below its critical value (400-500 cells / mm), the cornea becomes overly dense and sluggish. 2 ), which can cause corneal edema and decreased transparency, and in severe cases, can cause corneal blindness. Corneal endothelial cell dysfunction such as corneal endothelial wrinkles and corneal edema caused by phacoemulsification for cataract is common, seriously affecting the patient's visual function recovery. Previous studies have found that corneal endothelial cell dysfunction caused by cataract surgery is the most common cause of penetrating keratoplasty. Cataract surgery has also become the main indication for corneal endothelial transplantation, ranking second only to Fuchs endothelial dystrophy. To date, there is no clinically effective, convenient, feasible and widely promoted treatment strategy for protecting CECs during phacoemulsification for cataract.

[0004] Studies have reported that corneal endothelial damage during phacoemulsification is partially caused by oxidative stress. Hydrogen (H2), a strong reducing agent, dissolved in the irrigating fluid can reduce corneal endothelial damage during phacoemulsification. However, H2 has strong penetrating power and is volatile, making it difficult to retain in the irrigating fluid for long periods of time. Currently, BSS PLUS irrigating fluid, released by Alcon, has shown promise in protecting the corneal endothelium, but it is expensive. Currently, there is a lack of effective and cost-effective products to reduce corneal damage during phacoemulsification.

[0005] Summary of the Invention

[0006] The present invention aims to provide an intraocular perfusion solution containing nicotinamide, its preparation method and application. The novel intraocular perfusion solution obtained by improving and optimizing nicotinamide can be used in cataract phacoemulsification surgery to protect corneal endothelial cells, with good effect and low cost.

[0007] The present invention provides application of nicotinamide in preparing intraocular surgery perfusion solution.

[0008] Preferably, the intraocular surgery includes phacoemulsification surgery and / or vitrectomy surgery.

[0009] Preferably, the cataract includes one or more of senile cataract, diabetic cataract, cataract in the compensatory stage of corneal endothelial function and cataract in the decompensated stage of corneal endothelial function.

[0010] The present invention also provides an intraocular surgical perfusion solution containing nicotinamide, wherein the intraocular surgical perfusion solution comprises nicotinamide and a balanced salt solution.

[0011] Preferably, the concentration of nicotinamide in the intraocular surgical perfusion solution is 1-5 mM.

[0012] Preferably, the balanced salt solution comprises: a compound electrolyte intraocular irrigation solution or a balanced salt intraocular irrigation solution.

[0013] The present invention also provides a method for preparing the intraocular surgical perfusion solution described in the above technical solution, comprising the following steps: dissolving nicotinamide in a balanced salt solution to obtain an intraocular surgical perfusion solution containing nicotinamide.

[0014] The present invention also provides the use of nicotinamide or the intraocular surgical perfusion solution described in the above technical solution in the preparation of a product having one or more functions as shown in (1) to (7):

[0015] (1) Inhibit corneal endothelial cell damage caused by phacoemulsification;

[0016] (2) Reduce corneal edema caused by phacoemulsification surgery;

[0017] (3) Avoid the significant decrease in the number of corneal endothelial cells caused by phacoemulsification surgery;

[0018] (4) Promote the restoration of normal corneal transparency after phacoemulsification surgery;

[0019] (5) Promote the restoration of normal corneal thickness after phacoemulsification surgery;

[0020] (6) Maintaining normal density, normal cell morphology, and regular expression and distribution of functional proteins in the corneal endothelial cells after phacoemulsification surgery;

[0021] (7) Avoid complications caused by phacoemulsification surgery.

[0022] Preferably, the complications include ocular hypertension and / or endophthalmitis.

[0023] The present invention provides the use of nicotinamide in the preparation of intraocular surgical perfusion fluid. The intraocular surgical perfusion fluid prepared by nicotinamide can be used in phacoemulsification surgery for cataracts, with good effect and low cost. The present invention addresses the clinical bottleneck problems of a significant decrease in the number of CECs, corneal edema, and slow recovery of transparency caused by phacoemulsification surgery for cataracts. Nicotinamide (NAM) is added to the anterior chamber surgical perfusion fluid and applied to phacoemulsification surgery for cataracts to observe its protective effect on the morphology, density, corneal thickness, and transparency of postoperative CECs. Nicotinamide will protect CECs during phacoemulsification surgery for patients with senile cataracts (including the hypermature stage), diabetic cataracts, cataracts with decompensated corneal endothelial function, and cataracts in the compensated stage of corneal endothelial function, thereby avoiding a significant decrease in the number of CECs, reducing complications after phacoemulsification surgery for patients, and promoting rapid recovery of corneal transparency, thereby providing an effective strategy for achieving the treatment of normal visual function in patients. The results of cell experiments showed that NAM treatment can inhibit the apoptosis of corneal endothelial cell line B4G12 cells caused by phacoemulsification operation and promote cell survival; the results of animal experiments showed that compared with the anterior chamber perfusion solution alone, the perfusion solution with the addition of NAM can reduce the corneal edema caused by phacoemulsification surgery in rabbits, inhibit the enlargement of CECs, changes in cell atypia, and abnormal expression of functional proteins ZO1 and ATP1A1, and promote the rapid recovery of corneal transparency; and compared with the control group, no complications such as high intraocular pressure and endophthalmitis were observed in New Zealand white rabbits when the perfusion solution containing NAM was used in phacoemulsification cataract surgery. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0025] FIG1 is a macroscopic photograph of a rabbit cornea one day after phacoemulsification surgery provided by the present invention;

[0026] FIG2 is an Alizarin red staining result of rabbit corneal endothelial cells 7 days after phacoemulsification surgery provided by the present invention;

[0027] FIG3 is a macroscopic image of the rabbit cornea treated with phacoemulsification provided by the present invention, with or without NAM, 1 to 5 days after surgery;

[0028] FIG4 is a graph showing the changing trend of intraocular pressure in rabbits treated with phacoemulsification for 7 days under the conditions of addition and subtraction of NAM provided by the present invention;

[0029] FIG5 is a graph showing the changing trend of corneal thickness of rabbits treated with phacoemulsification for 7 days under the conditions of addition and subtraction of NAM provided by the present invention;

[0030] FIG6 is a diagram showing the staining of the functional proteins ZO1 and ATP1A1 in rabbit corneal endothelial cells treated with phacoemulsification for 7 days under the conditions of NAM addition and subtraction provided by the present invention; ZO1 is red, ATP1A1 is green, and DAPI is blue;

[0031] FIG7 is a graph showing the effects of NAM and glutamine provided by the present invention on corneal endothelial cells during phacoemulsification;

[0032] FIG8 is a graph showing the morphological results of corneal endothelial cells B4G12 treated with different concentrations of NAM at 1 hour and 24 hours after phacoemulsification, as provided by the present invention. DETAILED DESCRIPTION

[0033] The present invention provides application of nicotinamide in preparing intraocular surgery perfusion solution.

[0034] In the present invention, the intraocular surgery preferably includes phacoemulsification and / or vitrectomy. In the present invention, the cataract preferably includes one or more of senile cataract, diabetic cataract, cataract in the compensatory stage of corneal endothelial function and cataract in the decompensated stage of corneal endothelial function. In the present invention, the senile cataract preferably includes hypermature senile cataract. Nicotinamide (NAM) is the amide form of vitamin B3, which acts as a nicotinamide adenine dinucleotide (NAD+ Nicotinamide is a precursor of nicotinamide (α-amylase), which participates in various cellular biological processes, including cell metabolism, activation of autophagy, resistance to oxidative stress, anti-inflammatory responses, and immune responses to physiological or pathological signals. It improves cell survival and has a strong cytoprotective effect. The present invention discovered that nicotinamide can be used to prepare perfusion solutions for intraocular cataract phacoemulsification surgery and / or vitrectomy surgery.

[0035] The present invention also provides an intraocular surgical irrigation solution containing nicotinamide, comprising nicotinamide and a balanced salt solution. In the present invention, the concentration of nicotinamide in the intraocular surgical irrigation solution is preferably 1 to 5 mM, more preferably 2.5 mM. In the present invention, the balanced salt solution preferably comprises a compound electrolyte intraocular irrigation solution or a balanced salt intraocular irrigation solution, more preferably a compound electrolyte intraocular irrigation solution. The present invention does not particularly limit the source of the balanced salt solution; conventional commercially available products, such as a compound electrolyte intraocular irrigation solution (Shike) or a balanced salt intraocular irrigation solution (Bishi), may be used.

[0036] The intraocular surgical perfusion solution of the present invention can inhibit corneal endothelial cell apoptosis caused by phacoemulsification treatment; reduce corneal edema caused by phacoemulsification surgery for cataracts; avoid a significant decrease in the number of corneal endothelial cells caused by phacoemulsification surgery for cataracts; promote rapid recovery of corneal transparency after phacoemulsification surgery for cataracts; promote recovery of normal corneal thickness after phacoemulsification surgery for cataracts; maintain normal density, normal cell morphology and regular expression and normal distribution of functional proteins of corneal endothelial cells after phacoemulsification surgery for cataracts; and avoid complications (high intraocular pressure and / or endophthalmitis) caused by phacoemulsification surgery for cataracts.

[0037] The present invention also provides a method for preparing the intraocular surgical perfusion solution described in the above technical solution, comprising the following steps: dissolving nicotinamide in a balanced salt solution to obtain an intraocular surgical perfusion solution containing nicotinamide.

[0038] The present invention also provides the use of nicotinamide or the intraocular surgical perfusion solution described in the above technical solution in the preparation of a product having one or more functions as shown in (1) to (7):

[0039] (1) Inhibit corneal endothelial cell damage caused by phacoemulsification;

[0040] (2) Reduce corneal edema caused by phacoemulsification surgery;

[0041] (3) Avoid the significant decrease in the number of corneal endothelial cells caused by phacoemulsification surgery;

[0042] (4) Promote the restoration of corneal transparency to normal brightness after phacoemulsification surgery;

[0043] (5) Promote the restoration of normal corneal thickness after phacoemulsification surgery;

[0044] (6) Maintaining normal density, normal cell morphology, and regular expression and distribution of functional proteins in the corneal endothelial cells after phacoemulsification surgery;

[0045] (7) Avoiding complications caused by phacoemulsification surgery. In the present invention, the complications preferably include elevated intraocular pressure and / or endophthalmitis.

[0046] In the present invention, the product preferably includes a drug. Experimental results demonstrate that NAM treatment inhibits cell apoptosis and promotes cell survival in a concentration-dependent manner following phacoemulsification. Intraocular perfusion solutions containing NAM can maintain the transparency and normal thickness of the cornea treated with phacoemulsification, maintaining normal corneal endothelial cell density, morphology, and regular expression and distribution of functional proteins, without significantly causing side effects such as increased intraocular pressure and endophthalmitis.

[0047] The present invention does not specifically limit the method of using the intraocular surgical irrigation solution, and conventional methods for using intraocular surgical irrigation solutions during cataract phacoemulsification surgery known to those skilled in the art can be used, such as compound electrolyte intraocular irrigation solution (Sekko).

[0048] To further illustrate the present invention, a nicotinamide-containing intraocular perfusion solution, a preparation method thereof, and applications thereof are described in detail below with reference to the accompanying drawings and examples. However, these should not be construed as limiting the scope of protection of the present invention.

[0049] Example 1

[0050] Compound electrolyte intraocular irrigation solution (Sike, Shenyang Xingqi Eye Pharmaceutical Co., Ltd.) was prepared according to the instructions (Part I of the compound electrolyte intraocular irrigation solution: 480 ml of sterile solution, the main components of which include sodium chloride, potassium chloride, magnesium sulfate, and sodium bicarbonate; Part II: 20 ml of sterile solution, the main components of which include glucose and calcium chloride). Part II of the solution was transferred into Part I of the solution using a sterile syringe, and the two were gently shaken to mix to obtain the compound electrolyte intraocular irrigation solution. NAM was then added to the above solution until the concentration of NAM in the irrigation solution was 1-5 mM to obtain an intraocular surgical irrigation solution containing nicotinamide.

[0051] Example 2

[0052] Materials and methods include animal-level validation and cell-level validation, the details of which are as follows:

[0053] (I) Animal experiment: NAM-containing perfusion solution protected rabbit CECs from damage caused by phacoemulsification surgery.

[0054] Animals: New Zealand white rabbits (age, 1.5 years; weight, 5-7 kg) were purchased from Jinan Xilingjiao Biological Co., Ltd. New Zealand white rabbits were housed in a pathogen-free environment in the animal room of the Institute of Ophthalmology, Shandong First Medical University.

[0055] Animal Model: Mydriasis was dilated three times with 0.5% compound tropicamide eye drops. Rabbits were first sedated with an intramuscular injection of 20 mg / kg xylazine hydrochloride and anesthetized with 15 mg / kg 3% sodium pentobarbital through the auricular vein. Phacoemulsification of the right eye of each rabbit was performed using the Alendronate phacoemulsification system (Signature, AMO, USA). The left eye served as the normal eye. A 3.0 mm clear corneal tunnel incision was made at the 11-12 o'clock position, and a continuous circular capsulotomy (approximately 5.0 mm in diameter) was performed in the center of the anterior lens capsule. Phacoemulsification of the lens contents, including the nucleus and residual lens cortex, was then performed using phacoemulsification with ultrasound power settings of 30-50% for 4-6 minutes. Following the procedure, tobramycin-dexamethasone ointment was applied to the conjunctival sac of the New Zealand white rabbits.

[0056] Perfusion solution: balanced salt solution containing 1 mM NAM (referring to compound electrolyte intraocular irrigation solution, Shike, Shenyang Xingqi Eye Pharmaceutical Co., Ltd.): NAM was added to the balanced salt solution until the concentration of NAM in the perfusion solution was 1 mM; balanced salt solution containing 2.5 mM NAM: NAM was added to the balanced salt solution until the concentration of NAM in the perfusion solution was 2.5 mM; balanced salt solution containing 5 mM NAM: NAM was added to the balanced salt solution until the concentration of NAM in the perfusion solution was 5 mM; balanced salt solution alone control group: an equal amount of PBS was added to the balanced salt solution.

[0057] Immunofluorescence staining: Immunofluorescence was used to detect the expression of functional proteins ZO1 and ATP1A1.

[0058] Alizarin red staining: The whole cornea of ​​the New Zealand rabbit was collected and fixed in sterile saline solution. The cornea was cut into four petals using ophthalmic microscissors to flatten the cornea. The cornea was stained with alizarin red solution for 2 minutes, and then the cornea was washed at least 3 times with sterile saline. Cover with a coverslip, observe the changes in the endothelial cells of the New Zealand rabbit cornea under a microscope and collect images. All experiments were repeated at least 3 times. The endothelial cell density, coefficient of variation, and hexagonal ratio were measured using images of the New Zealand rabbit cornea stained with alizarin red. Two blinded observers used endothelial microscopy, and the cell density was normalized to the area of ​​each image in square millimeters. For each image, an area containing at least 60 cells was selected.

[0059] Slit lamp photography: Use a slit lamp to observe and record changes in corneal transparency of New Zealand rabbits.

[0060] Corneal thickness detection: Optical coherence tomography (OCT) was used to analyze and measure corneal thickness. The central corneal thickness was measured, and no less than 3 New Zealand rabbits were measured at each time point.

[0061] Results of phacoemulsification surgery-induced corneal endothelial cell damage in rabbits:

[0062] Phacoemulsification surgery was performed on New Zealand white rabbits. Compared with normal rabbits, rabbits that underwent surgery showed corneal edema and thickening one day after surgery (Figure 1, Gross image of the cornea one day after phacoemulsification). Corneal tissue was collected 7 days after phacoemulsification and stained with alizarin red for the corneal endothelium. Unlike the dense and regular corneal endothelial cell morphology of normal rabbits, the corneal endothelial cells in rabbits treated with phacoemulsification were enlarged, more atypia, and had a decreased cell density (Figure 2, Alizarin red staining of corneal endothelial cells 7 days after phacoemulsification).

[0063] NAM-containing perfusion solution protected rabbit corneal endothelial cell damage caused by phacoemulsification surgery.

[0064] Phacoemulsification surgery was performed on New Zealand white rabbits, using intraocular perfusate containing NAM for irrigation. A control group using perfusate containing balanced salt solution alone served as a control. The perfusate alone resulted in corneal edema, decreased transparency, and increased corneal thickness one day after surgery. These corneal transparency and thickness gradually returned to normal within five days. However, in the group treated with intraocular perfusate containing NAM, corneal transparency and thickness were preserved after one day, and remained transparent and normal in thickness five days after surgery (Figure 3). Gross images of phacoemulsified rabbit corneas treated with NAM perfusate plus or minus NAM perfusate, from one to five days after surgery).

[0065] By comparing and analyzing the corneal intraocular pressure of rabbits after surgery in the control group and the group treated with NAM perfusion solution, it was found that NAM treatment did not cause a pathological increase in intraocular pressure within 7 days after surgery. Compared with the control group, the trend of intraocular pressure changes in the two groups was consistent, indicating that cataract phacoemulsification surgery causes a transient increase in intraocular pressure, which basically returns to the baseline level after 3 days, and the increase in intraocular pressure does not exceed the normal range (Figure 4, Changes in intraocular pressure of rabbits treated with phacoemulsification for 7 days under the conditions of adding or subtracting NAM perfusion solution). At the same time, compared with the increased corneal thickness in the control group, the corneal thickness of rabbits treated with NAM perfusion solution was lower than that of the control group one day after surgery, and the corneal thickness basically returned to normal levels after 3 days. The recovery rate of corneal thickness was better than that of the control group (Figure 5, Changes in corneal thickness of rabbits treated with phacoemulsification for 7 days under the conditions of adding or subtracting NAM).

[0066] At the same time, corneal tissue was collected from both groups 7 days after surgery for corneal endothelial cell flat-mount staining. The results showed that in the control group, the barrier function protein ZO1 of the corneal endothelial cells showed enlargement and increased atypia, and the expression and localization of the pump function protein ATP1A1 were disordered. However, ZO1 staining of the corneal endothelial cells of the rabbits in the NAM-containing perfusate treatment group showed regular cell morphology and normal expression and distribution of ATP1A1 (Figure 6, functional protein staining of rabbit corneal endothelial cells treated with NAM for 7 days; ZO1 red, ATP1A1 green, DAPI blue).

[0067] In addition, existing literature reports that glutamine (Gln) has a protective effect on the corneal endothelial cells of mice treated with high intraocular pressure. In the present invention, Gln is added to the perfusion solution as a control and applied to a rabbit lens phacoemulsification surgery model. Figure 7 is a graph showing the effects of NAM and Gln provided by the present invention on corneal endothelial cells during phacoemulsification. The results showed that 2 days after surgery, the corneas of the rabbits in the NAM-treated group were transparent, while the corneas of the rabbits in the Gln group were still edematous, and the corneal thickness of the NAM-treated group recovered quickly, while the corneal thickness of the Gln group recovered more slowly. This suggests that NAM has a protective effect on corneal endothelial cells when used in phacoemulsification, and although Gln has a protective effect on mouse corneal endothelial cells during high intraocular pressure treatment, it has a poor protective effect on corneal endothelial cells during phacoemulsification.

[0068] The above results show that NAM-containing perfusion solution can promote the rapid recovery of corneal transparency and normal thickness after phacoemulsification surgery, maintain the normal density of corneal endothelial cells, normal cell morphology and regular expression and normal distribution of functional proteins, and does not obviously cause side effects such as increased intraocular pressure and endophthalmitis.

[0069] (2) Cell experiment: NAM inhibited the damage of B4G12 cells cultured in vitro induced by phacoemulsification.

[0070] In vitro cell culture preparation: Select the human CECs line B4G12 for culture. Discard the existing culture medium and add 3 mL of PBS buffer. Gently shake a 6.0 cm cell culture dish, rinse twice, and discard the PBS buffer. Add 1.0 mL of trypsin, completely covering the bottom of the dish, and place in an incubator for 5 minutes. Gently shake the dish and observe under a microscope. Adherent cells will become suspended, round cells. On a clean bench, add 1.5 mL of complete culture medium [Human Corneal Endothelial Cell Basal Medium (H-SFM, Creative Bioarray, New York, USA) containing 1.5 mL of FBS and 0.5 mL of penicillin-streptomycin solution per 50 mL] to the flask to stop trypsinization. Gently pipette the tip of the flask to fully suspend the cells. Transfer the cell suspension to a 15 mL centrifuge tube and centrifuge at 1200 rpm for 5 minutes. After centrifugation, discard the supernatant and add 3 mL of complete culture medium to the centrifuge tube. Gently pipette and evenly vortex to fully resuspend the cells. 5 The cells were seeded into 48-well cell culture plates and cultured for 24 hours before preparation for the experiment.

[0071] Experimental groups: In vitro cell experiments included a control group and experimental treatment groups with different concentrations of NAM. Control group: Complete medium was used; experimental treatment groups: (1) 1 mM NAM medium: NAM was added to the complete medium to achieve a NAM concentration of 1 mM; (2) 2.5 mM NAM medium: NAM was added to the complete medium to achieve a NAM concentration of 2.5 mM; (3) 5 mM NAM medium: NAM was added to the complete medium to achieve a NAM concentration of 5 mM.

[0072] Phacoemulsification: Remove the culture medium and replace it with a balanced salt solution. Prepare and debug the CataRhex instrument (CataRhex Swisstech, Oertli Instrumente AG, Switzerland). Insert the phacoemulsification needle into the balanced salt solution in the culture plate. Use ultrasonic energy of 20-40% for 20-30 seconds. Then, replace the balanced salt solution with the four culture media described above. Continue culturing in an incubator for 1, 6, 12, and 24 hours. Observe the cells under a microscope and take photos to record their status.

[0073] NAM treatment protected human CECs from damage and apoptosis induced by phacoemulsification.

[0074] Human corneal endothelial cells were phacoemulsified for 20 seconds at 30% ultrasonic energy. Changes in corneal endothelial cells were observed 1 hour and 24 hours after phacoemulsification at 1 mM, 2.5 mM, and 5 mM NAM. The results showed that NAM treatment inhibited phacoemulsification-induced cell apoptosis and promoted cell survival in a concentration-dependent manner (Figure 8). Morphological changes in corneal endothelial cells at 1 hour and 24 hours after phacoemulsification were observed at different NAM concentrations.

[0075] Although the above embodiment provides a detailed description of the present invention, it is only a part of the embodiments of the present invention, not all of the embodiments. People can also obtain other embodiments based on this embodiment without creativity, and these embodiments all fall within the scope of protection of the present invention.

Claims

1. Application of nicotinamide in the preparation of intraocular surgical perfusion solution.

2. The use according to claim 1, characterized in that: The intraocular surgery includes cataract phacoemulsification surgery and / or vitrectomy surgery.

3. The use according to claim 2, characterized in that: The cataract includes one or more of senile cataract, diabetic cataract, cataract in the compensatory stage of corneal endothelial function and cataract in the decompensated stage of corneal endothelial function.

4. An intraocular surgical perfusion solution containing nicotinamide, characterized in that: The intraocular surgical irrigation solution comprises nicotinamide and a balanced salt solution.

5. The intraocular surgery perfusion solution according to claim 4, characterized in that: The concentration of nicotinamide in the intraocular surgery perfusion solution is 1-5 mM.

6. The intraocular surgery perfusion solution according to claim 4, characterized in that: The balanced salt solution includes: a compound electrolyte intraocular irrigation solution or a balanced salt intraocular irrigation solution.

7. The method for preparing the intraocular surgical perfusion solution according to any one of claims 4 to 6, characterized in that: The method comprises the following steps: dissolving nicotinamide in a balanced salt solution to obtain an intraocular surgical irrigation solution containing nicotinamide.

8. Use of nicotinamide or the intraocular surgical perfusion solution according to any one of claims 4 to 6 in the preparation of a product having the functions as shown in one or more of (1) to (7): (1) Inhibit corneal endothelial cell damage caused by phacoemulsification; (2) Reduce corneal edema caused by phacoemulsification surgery; (3) Avoid the significant decrease in the number of corneal endothelial cells caused by phacoemulsification surgery; (4) Promote the restoration of normal corneal transparency after phacoemulsification surgery; (5) Promote the restoration of normal corneal thickness after phacoemulsification surgery; (6) Maintain normal density, normal cell morphology, and regular expression and distribution of functional proteins of corneal endothelial cells after phacoemulsification surgery; (7) Avoid complications caused by phacoemulsification surgery.

9. The use according to claim 8, characterized in that: Such complications include ocular hypertension and / or endophthalmitis.

10. The method for using the intraocular perfusion solution according to any one of claims 4 to 6, characterized in that: The following steps are involved: During cataract phacoemulsification surgery and / or vitrectomy surgery, the intraocular perfusion solution is used to protect corneal endothelial cells during the surgery.

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