Nicotinamide-containing irrigating solution for intraocular surgery and its preparation method and application

Abstract

The present invention belongs to the technical field of drug preparation and relates to a nicotinamide-containing intraocular surgical irrigation solution and its preparation and application. The present invention provides the use of nicotinamide in an intraocular surgical irrigation solution. The present invention uses nicotinamide to improve the intraocular surgical irrigation solution, which can inhibit corneal endothelial cell damage caused by cataract phacoemulsification surgery, reduce corneal edema caused by cataract phacoemulsification surgery, avoid a significant decrease in the number of corneal endothelial cells caused by surgery, promote the recovery of corneal transparency after surgery, promote the recovery of normal corneal thickness, maintain the normal density, cell morphology, and regular expression of functional proteins of corneal endothelial cells, and reduce complications caused by cataract phacoemulsification surgery. The present invention can provide an effective strategy for the rapid recovery of normal visual function in cataract patients after surgery.

Description

[Technical Field]

[0001] This application claims priority from a Chinese patent application filed with the China Patent Office on October 26, 2023, with application number 202311396074.7 and title "Nicotinamide-containing intraocular surgical irrigation solution and its manufacturing method and application," the entire contents of which are incorporated herein by reference. The present invention relates to the field of drug preparation technology, and specifically to a nicotinamide-containing intraocular surgical irrigation solution and its preparation method and application. [Background technology]

[0002] Cataract is the world's first blinding eye disease. Currently, most cataract surgeries are completed using phacoemulsification, which involves using high-intensity ultrasound energy to break down and emulsify the cloudy lens. With advances in surgical equipment and technology, the indications for phacoemulsification have expanded to include mature cataracts with a harder lens nucleus, requiring greater phacoemulsification energy and time. However, excessive phacoemulsification energy, fragmentation of the lens nucleus, and increased local temperature can all damage corneal endothelial cells (CECs), significantly reducing their number and leading to corneal edema and even corneal endothelial dysfunction. In severe cases, corneal transplantation is required. CECs are located at the innermost layer of the cornea and maintain normal corneal transparency and visual function through their barrier and pumping functions. Adult CECs have very limited proliferation capacity; after injury, repair is only possible through the expansion and migration of peripheral cells, resulting in a decline in cell density over time. The cell density reaches its critical value (400-500 cells / mm 2A lower level of corneal endothelial function can cause corneal edema and loss of transparency, leading to corneal blindness in severe cases. Corneal endothelial dysfunction, such as corneal endothelial wrinkling and corneal edema, is common after cataract phacoemulsification, severely impacting patients' visual function recovery. Studies have shown that corneal endothelial cell decompensation caused by cataract surgery is the most common cause of penetrating keratoplasty. Cataract surgery is also a major indication for corneal endothelial transplantation, ranking second only to Fuchs endothelial malnutrition. Currently, there is no effective, convenient, feasible, or widely promoted therapeutic strategy for protecting CECs during cataract phacoemulsification.

[0003] Research has shown that corneal endothelial damage during phacoemulsification is partially caused by oxidative stress. Hydrogen (H2), a powerful reducing agent, dissolves in the irrigation solution and reduces corneal endothelial damage during phacoemulsification. However, H2 has strong permeability and volatility, making it difficult to retain in the irrigation solution for long periods of time. Currently, Alcon's BSS PLUS irrigation solution has demonstrated its ability to protect the corneal endothelium, but it is expensive. Currently, there is a lack of effective, low-cost products that can reduce corneal damage during phacoemulsification. Summary of the Invention [Problem to be solved by the invention]

[0004] The present invention aims to provide a nicotinamide-containing intraocular surgical irrigation solution, its preparation method, and applications. The novel intraocular surgical irrigation solution obtained by improving and optimizing nicotinamide can be used in phacoemulsification surgery for cataracts, and has excellent efficacy in protecting corneal endothelial cells at low cost. [Means for solving the problem]

[0005] The present invention provides the application of nicotinamide in the preparation of irrigating solutions for intraocular surgery.

[0006] Preferably, the intraocular surgery comprises cataract phacoemulsification and / or vitrectomy.

[0007] Preferably, the cataract includes one or more of senile cataract, diabetic cataract, cataract during corneal endothelial dysfunction compensation, and cataract during corneal endothelial dysfunction decompensation.

[0008] The present invention further provides a nicotinamide-containing intraocular surgical irrigation solution, the intraocular surgical irrigation solution comprising nicotinamide and a balanced salt solution.

[0009] Preferably, the concentration of nicotinamide in the irrigating solution for intraocular surgery is 1 to 5 mM.

[0010] Preferably, the balanced salt solution comprises a complex electrolyte compound ocular rinse or a balanced salt ocular rinse.

[0011] The present invention also provides a method for preparing the intraocular surgical irrigation solution described in the above technical solution, comprising the step of dissolving nicotinamide in a balanced salt solution to obtain a nicotinamide-containing intraocular surgical irrigation solution.

[0012] The present invention further comprises: (1) Suppresses corneal endothelial cell damage caused by ultrasonic emulsification, (2) Reduce corneal edema caused by phacoemulsification surgery for cataracts; (3) Avoiding the significant decrease in the number of corneal endothelial cells caused by phacoemulsification surgery for cataracts; (4) Promoting the restoration of normal corneal transparency after phacoemulsification surgery for cataracts; (5) Promoting the restoration of normal corneal thickness after phacoemulsification surgery for cataracts; (6) Maintaining the normal density, normal cell morphology, regular expression and normal distribution of functional proteins of corneal endothelial cells after phacoemulsification surgery for cataracts; (7) The use of nicotinamide or the intraocular surgical irrigation solution described in the above technical solutions in the preparation of a product having the functions of one or more of (1) to (7) of avoiding complications caused by ultrasonic emulsification surgery for cataracts is provided.

[0013] Preferably, the complications include ocular hypertension and / or endophthalmitis. [Effects of the Invention]

[0014] The present invention provides the use of nicotinamide in the preparation of intraocular surgical irrigation solutions. The intraocular surgical irrigation solutions prepared with nicotinamide can be used in cataract phacoemulsification surgery, and are highly effective and inexpensive. In this invention, to address the clinical bottlenecks of cataract phacoemulsification surgery, such as a significant decrease in CEC count, corneal edema, and slow recovery of transparency, nicotinamide (NAM) is added to irrigation solutions for anterior chamber surgery and used in cataract phacoemulsification surgery. The resulting protective effects on CEC morphology, density, and corneal thickness and transparency after surgery are observed. Nicotinamide protects CECs and prevents a significant decrease in the number of CECs during cataract phacoemulsification surgery in patients with senile cataract (including hypermature cataract), diabetic cataract, cataract with corneal endothelial dysfunction decompensation, and cataract with corneal endothelial dysfunction compensation, thereby reducing complications after cataract phacoemulsification surgery and promoting the rapid recovery of corneal transparency, providing an effective strategy for treating patients and achieving normal visual function. Cellular studies showed that NAM treatment inhibited the apoptosis of corneal endothelial cell line B4G12 caused by phacoemulsification and promoted cell survival. Animal studies showed that, compared with anterior chamber irrigation solution alone, irrigation solution containing NAM reduced corneal edema caused by phacoemulsification for cataracts, inhibited the increase in CECs, cellular dysmorphic changes, and the abnormal expression of functional proteins ZO1 and ATP1A1, and promoted the rapid recovery of corneal transparency. Furthermore, when NAM-containing irrigation solution was used in phacoemulsification cataract surgery, compared with controls, there were no complications such as high intraocular pressure and endophthalmitis in New Zealand large white rabbits. [Brief explanation of the drawings]

[0015] In order to more clearly describe the embodiments of the present invention or the technical solutions in the prior art, the following will briefly describe the drawings that need to be used in the embodiments. Obviously, the drawings in the following description are only some embodiments of the present invention, and those skilled in the art can further obtain other drawings based on these drawings without any creative efforts.

[0016] [Figure 1] 1 is a macroscopic photograph of a rabbit cornea one day after treatment with the phacoemulsification surgery provided by the present invention. [Figure 2] FIG. 10 is a diagram showing the results of Alizarin Red staining of rabbit corneal endothelial cells 7 days after treatment with ultrasonic emulsification surgery provided by the present invention. [Figure 3] 1 shows macroscopic images of the cornea of ​​a rabbit treated with ultrasonic emulsification provided by the present invention, taken 1 to 5 days after surgery under NAM-adjusted conditions. [Figure 4] FIG. 1 is a graph showing the change trend of intraocular pressure in rabbits treated for 7 days with ultrasonic emulsification provided by the present invention under NAM addition and reduction conditions. [Figure 5] FIG. 1 is a graph showing the change trend of the corneal thickness of rabbits treated for 7 days with ultrasonic emulsification provided by the present invention under NAM addition conditions. [Figure 6] 1 shows the staining of functional proteins ZO1 and ATP1A1 in rabbit corneal endothelial cells treated for 7 days with ultrasonic emulsification provided by the present invention under NAM addition conditions, where ZO1 is red, ATP1A1 is green, and DAPI is blue. [Figure 7] FIG. 1 is a graph showing the results of the effects of NAM and glutamine on corneal endothelial cells during ultrasonic emulsification provided by the present invention. [Figure 8] FIG. 10 is a graph showing the morphology results of corneal endothelial cells B4G12 added with different concentrations of NAM provided by the present invention, 1 hour and 24 hours after ultrasonic emulsification treatment. DETAILED DESCRIPTION OF THE INVENTION

[0017] The present invention provides the application of nicotinamide in the preparation of irrigating solutions for intraocular surgery.

[0018] In the present invention, the intraocular surgery preferably includes cataract phacoemulsification surgery and / or vitrectomy surgery. In the present invention, the cataract preferably includes one or more of senile cataract, diabetic cataract, cataract due to corneal endothelial dysfunction compensation, and cataract due to corneal endothelial dysfunction decompensation. In the present invention, the senile cataract preferably includes postmature senile cataract. Nicotinamide (NAM), the amide form of vitamin B3, is a precursor of nicotinamide adenine dinucleotide (NAD+). It is involved in various cell biological processes, such as cellular metabolism, autophagy activation, antioxidative stress, anti-inflammatory activity, and immune response to physiological or pathological signals, and has a strong cytoprotective effect, improving cell viability. The present invention has discovered that nicotinamide can be used to prepare irrigation solutions for intraocular cataract phacoemulsification surgery and / or vitrectomy surgery.

[0019] The present invention also provides a nicotinamide-containing intraocular surgical irrigation solution, which contains 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 contains a complex electrolyte compound intraocular irrigation solution or a balanced salt intraocular irrigation solution, more preferably a complex electrolyte compound intraocular irrigation solution. The present invention does not place any particular restrictions on the source of the balanced salt solution, and conventional commercially available products such as an electrolyte compound intraocular irrigation solution (Sekake) or a balanced salt intraocular irrigation solution (Hise) may be used.

[0020] The intraocular surgery irrigation solution described in the present invention can inhibit corneal endothelial apoptosis caused by phacoemulsification, reduce corneal edema caused by cataract surgery, avoid the significant decrease in the number of corneal endothelial cells caused by phacoemulsification surgery for cataracts, promote the rapid recovery of corneal transparency after phacoemulsification surgery for cataracts, promote the recovery of normal corneal thickness after phacoemulsification surgery for cataracts, maintain the normal density, normal cell morphology, regular expression and normal distribution of functional proteins of corneal endothelial cells after phacoemulsification surgery for cataracts, and avoid complications caused by phacoemulsification surgery for cataracts (e.g., high intraocular pressure and / or endophthalmitis).

[0021] The present invention further provides a method for preparing the intraocular surgical irrigation solution described in the above technical solution, which comprises dissolving nicotinamide in a balanced salt solution to obtain a nicotinamide-containing intraocular surgical irrigation solution.

[0022] The present invention (1) suppresses damage to corneal endothelial cells caused by ultrasonic emulsification treatment, (2) Reduce corneal edema caused by phacoemulsification surgery for cataracts; (3) Avoiding the significant decrease in the number of corneal endothelial cells caused by phacoemulsification surgery for cataracts; (4) Promoting the recovery of normal corneal transparency after phacoemulsification surgery for cataracts; (5) Promoting the restoration of normal corneal thickness after phacoemulsification surgery for cataracts; (6) Maintaining the normal density, normal cell morphology, regular expression and normal distribution of functional proteins of corneal endothelial cells after phacoemulsification surgery for cataracts; (7) The use of nicotinamide or the intraocular surgical irrigation solution described in the above technical solutions in the preparation of a product having the functions of one or more of (1) to (7) for avoiding complications caused by phacoemulsification surgery for cataracts. In the present invention, the complications preferably include intraocular pressure and / or endophthalmitis.

[0023] In the present invention, the product preferably contains a drug. Test results show that NAM treatment can inhibit apoptosis caused by phacoemulsification and promote cell survival, and the effect is concentration-dependent. NAM-containing intraocular surgical irrigation solution can protect the transparency and normal thickness of the cornea treated by phacoemulsification surgery, maintain the normal density, cell morphology, and regular expression of functional proteins of corneal endothelial cells, and does not cause obvious side effects such as increased intraocular pressure or endophthalmitis.

[0024] The present invention does not impose any particular limitations on the method of use of the intraocular surgical irrigation solution, and the usual method of use of intraocular surgical irrigation solutions for cataract ultrasonic emulsification surgery, such as electrolyte compound intraocular irrigation solution (Sekake), which is well known to those skilled in the art, may be adopted.

[0025] To further illustrate the present invention, the nicotinamide-containing intraocular surgical irrigation solution provided by the present invention and its manufacturing method and application will be described in detail below with reference to the drawings and examples, but they should not be construed as limitations on the scope of protection of the present invention.

[0026] Example 1 Electrolyte compound intraocular irrigation solution (Shike, Shenyang Xingqi Ophthalmic Co., Ltd.) was prepared according to the specifications (Part I of the electrolyte compound intraocular irrigation solution: 480 ml sterile solution containing sodium chloride, potassium chloride, magnesium sulfate, and sodium bicarbonate; Part II: 20 ml sterile solution containing glucose and calcium chloride). A sterile syringe was used to transfer the solution from Part II to the solution from Part I, and the two were gently mixed to obtain a compound electrolyte compound intraocular irrigation solution. NAM was then added until the concentration of NAM in the irrigation solution reached 1-5 mM, based on the previous method, to obtain a nicotinamide-containing intraocular surgical irrigation solution.

[0027] Example 2 The materials and methods include animal-level verification and cell-level verification, and the specific details are as follows:

[0028] (1) Animal experiments: NAM-containing perfusion solution protected rabbit CECs from damage caused by ultrasonic emulsification surgery. Animals: New Zealand large white rabbits (age 1.5 years, weight 5-7 kg) were purchased from Jinan Xilingjiao Biological Co., Ltd. The New Zealand large white rabbits were kept in a pathogen-free environment in the animal room of the Affiliated Ophthalmology Institute of Shandong First Medical University. Animal model: Mydriasis was performed three times with 0.5% compound tropicamide eye drops. Rabbits were anesthetized with 20 mg / kg xylazine hydrochloride injection intramuscularly and 3% pentobarbital sodium injection (15 mg / kg) via auricular vein. The right eye of each rabbit was subjected to ultrasonic emulsification to remove the crystalline lens using an Otokonken ultrasonic emulsification system (Signature, AMO, USA). The left eye was used 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 capsulorhexis was made in the center of the anterior lens capsule, with a capsulorhexis diameter of approximately 5.0 mm. Next, ultrasonic emulsification was performed to absorb and remove the lens contents, including the lens nucleus and residual lens cortex, with ultrasonic energy set to 30-50% and ultrasonic duration set to 4-6 min. After the surgery was completed, tobramycin-dexamethasone ophthalmic ointment was applied into the conjunctival sac of New Zealand large white rabbits. Irrigation solution: 1mM NAM-containing balanced salt solution (compound electrolyte intraocular irrigation solution, Shike, Shenyang Xingqi Ophthalmic Co., Ltd.): NAM was added to the balanced salt solution until the concentration of NAM in the irrigation solution reached 1mM. 2.5mM NAM-containing balanced salt solution: NAM was added to the balanced salt solution until the concentration of NAM in the irrigation solution reached 2.5mM. 5mM NAM-containing balanced salt solution: NAM was added to the balanced salt solution until the concentration of NAM in the irrigation solution reached 5mM. Control group using only balanced salt solution: An equal volume of PBS was added to the balanced salt solution. Immunofluorescence staining: The expression of functional proteins ZO1 and ATP1A1 was detected by immunofluorescence. Alizarin red staining: Whole corneas from New Zealand rabbits were harvested and fixed in sterile saline solution. Using an ophthalmic microscope, the corneas were cut into four pieces and laid flat. After staining with Alizarin red stain for 2 minutes, the corneas were washed at least three times with sterile saline. The corneas were covered with a glass coverslip and images were collected under a microscope to observe changes in the corneal endothelial cells of the New Zealand rabbits. All experiments were repeated at least three times. Endothelial cell density, variation index, and hexagonal ratio were measured using Alizarin red-stained New Zealand rabbit corneal images. Two blinded observers used an endothelial microscope, and 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. Slit-lamp photography: A slit lamp was used to observe and record changes in corneal transparency in New Zealand rabbits. Corneal thickness detection: Corneal thickness was analyzed and measured using optical coherence tomography (OCT). Central corneal thickness was measured, and at least three New Zealand rabbits were measured at each time point. Outcome of rabbit corneal endothelial cell damage caused by ultrasonic emulsification treatment: We performed phacoemulsification surgery on the phacoemulsification lens using New Zealand large white rabbits. Compared to normal rabbits, the operated rabbits showed thickened corneal edema one day after surgery (Figure 1, macroscopic photograph of a cornea treated with phacoemulsification one day after surgery). Corneal tissue was collected seven days after phacoemulsification and stained with Alizarin Red for corneal endothelial cell stretching. Unlike the dense, regular corneal endothelial cell morphology of normal rabbits, the corneal endothelial cell morphology of the rabbits treated with phacoemulsification was increased, with increased atypia and decreased cell density (Figure 2, Alizarin Red staining of corneal endothelial cell 7 days after phacoemulsification surgery). NAM-containing irrigation solution protects rabbit corneal endothelial cells from ultrasonic emulsification-induced damage: We performed phacoemulsification surgery using New Zealand large white rabbits. During surgery, we used intraocular irrigation solution containing NAM for irrigation, with a control group using only balanced salt solution as the irrigant. When only irrigation solution was used during surgery, the cornea edema, loss of transparency, and increase in corneal thickness occurred one day after surgery. By five days, corneal transparency and thickness had gradually returned to normal. However, in the NAM-containing intraocular irrigation group, the rabbits' corneas maintained their transparency and thickness after one day, and by five days after surgery, the corneas remained transparent and maintained normal thickness (Figure 3, macroscopic images of the corneas of rabbits treated with phacoemulsification and NAM-containing irrigation solution, 1 to 5 days after surgery).

[0029] A comparative analysis of postoperative corneal intraocular pressure (IOP) in rabbits treated with NAM-containing irrigating solution and those treated with NAM-containing irrigating solution revealed that NAM treatment did not cause a pathological increase in IOP within 7 days after surgery. The trends in IOP change between the two groups were consistent compared to the control group. Cataract phacoemulsification surgery caused a brief increase in IOP, which returned to baseline levels after 3 days and did not exceed the normal range (Figure 4, diagram of changes in IOP in rabbits treated with phacoemulsification for 7 days under NAM-containing irrigating solution conditions). At the same time, compared to the increased corneal thickness in the control group, the corneal thickness in rabbits treated with NAM-containing irrigating solution was lower than that of the control group on postoperative day 1, but after 3 days, the corneal thickness returned to normal levels, demonstrating a faster recovery rate than the control group (Figure 5, diagram of changes in corneal thickness in rabbits treated with phacoemulsification for 7 days under NAM-containing irrigating solution conditions).

[0030] At the same time, corneal tissues from both groups were collected 7 days after surgery and stained for corneal endothelial cells in stretched preparations. Results showed that in the control group, the barrier function protein ZO1 in corneal endothelial cells was increased in cell enlargement and atypia, and the expression and localization of the pump function protein ATP1A1 were disrupted. However, ZO1 staining of rabbit corneal endothelial cells treated with NAM-containing irrigation solution showed regular cell morphology and normal expression and distribution of ATP1A1 (Figure 6, functional protein staining diagram for rabbit corneal endothelial cells treated with ultrasonic emulsification for 7 days under NAM conditions: ZO1 red, ATP1A1 green, DAPI blue).

[0031] Furthermore, literature has previously reported that glutamine (Gln) has a protective effect on mouse corneal endothelial cells treated with elevated intraocular pressure. In this study, Gln was added to the irrigation solution as a control and applied to a rabbit phacoemulsification surgery model. Figure 7 shows the effects of NAM and Gln on corneal endothelial cells during phacoemulsification provided by the present invention. 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-treated group were also edematous. The corneal thickness recovery was rapid in the NAM-treated group, but slower in the Gln-treated group. These results suggest that NAM has a protective effect on corneal endothelial cells during phacoemulsification, and that Gln has a protective effect on mouse corneal endothelial cells during phacoemulsification, but its protective effect on corneal endothelial cells during phacoemulsification is not as significant.

[0032] In summary, the NAM-containing irrigation solution can promote rapid recovery of corneal transparency and normal thickness after ultrasonic emulsification surgery, maintain the normal density of corneal endothelial cells, normal cell morphology, and regular expression and normal distribution of functional proteins, without causing any obvious side effects such as increased intraocular pressure or endophthalmitis.

[0033] (2) Cellular experiments: NAM inhibited the damage to in vitro cultured B4G12 cells caused by ultrasonic emulsification. Preparation of in vitro cultured cells: Human CEC line B4G12 was selected and cultured. The original medium was discarded, 3 mL of PBS buffer was added, and a 6.0 cm cell Petri dish was gently rocked and washed twice. The PBS buffer was discarded. 1.0 mL of trypsinase was added, completely covering the bottom of the Petri dish, and the dish was placed in an incubator for 5 min. The Petri dish was gently rocked and tapped, and observed under a microscope to confirm that the adherent cells had turned into suspended round cells. In a clean bench, 1.5 mL of complete medium (containing 1.5 mL of FBS and 0.5 mL of penicillin-streptomycin solution per 50 mL of human corneal endothelial cell basal medium (H-SFM, Creative Bioarray, New York, USA)) was added to the bottle to suspend the pancreatin-digested cells. The bottom of the bottle was gently blown with a pipette head to fully suspend the cells. The cell suspension was transferred to a 15 mL centrifuge tube and centrifuged at 1200 rpm for 5 min. After centrifugation, discard the supernatant, add 3 mL of complete medium to the centrifuge tube, and gently blow the tube evenly to resuspend the cells thoroughly. The cell density was 1 × 10 5 The cells were then inoculated into a 48-well cell culture plate, cultured for 24 hours, and then prepared for the experiment. Experimental Grouping: 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-containing medium: NAM was added to the medium until the concentration of NAM in the medium reached 1 mM based on the complete medium. (2) 2.5 mM NAM-containing medium: NAM was added to the medium until the concentration of NAM in the medium reached 2.5 mM based on the complete medium. (3) 5 mM NAM-containing medium: NAM was added to the medium until the concentration of NAM in the medium reached 5 mM based on the complete medium. Ultrasonic emulsification: The culture medium was aspirated and replaced with balanced salt solution. An Aodi ultrasonic emulsification instrument (CataRhex Swisstech, Oertli Instrumente AG, Switzerland) was prepared and tested. The ultrasonic needle was inserted into the balanced salt solution in the perforated culture plate, and the ultrasonic energy was set to 20-40% and the ultrasonic time was set to 20-30 seconds. The balanced salt solution was then replaced with the culture medium from the previous four groups and placed in an incubator for 1, 6, 12, and 24 hours. After that, the cells were observed under a microscope and photographed to record their condition. NAM treatment protects human CECs from damage and apoptosis caused by ultrasonic emulsification: A human corneal endothelial cell line was subjected to ultrasonic emulsification with a duration of 20 seconds and an ultrasonic energy of 30%. The changes in the corneal endothelial cells were observed 1 hour and 24 hours after ultrasonic emulsification using 1 mM, 2.5 mM, and 5 mM NAM (2.5 mM). The results showed that NAM treatment inhibited ultrasonic emulsification-induced apoptosis and promoted cell survival, with a concentration-dependent effect (Figure 8, showing the changes in corneal endothelial cell morphology 1 hour and 24 hours after ultrasonic emulsification using different concentrations of NAM).

[0034] The above embodiments provide a detailed description of the present invention, but are only a part of the embodiments of the present invention, not all of the embodiments. People can also obtain other embodiments based on these embodiments without any creative effort, all of which fall within the protection scope of the present invention.

Claims

1. Application of nicotinamide in the preparation of irrigation solutions for intraocular surgery.

2. 2. The application of claim 1, wherein the intraocular surgery comprises cataract phacoemulsification and / or vitrectomy.

3. The application of claim 2, characterized in that the cataract includes one or more of the following: senile cataract, diabetic cataract, cataract during corneal endothelial dysfunction compensation period, and cataract during corneal endothelial dysfunction decompensation period.

4. 1. A nicotinamide-containing irrigating solution for intraocular surgery, the irrigating solution for intraocular surgery comprising nicotinamide and a balanced salt solution.

5. 5. The irrigation solution for intraocular surgery according to claim 4, wherein the concentration of nicotinamide in the irrigation solution for intraocular surgery is 1 to 5 mM.

6. 5. The irrigating solution for intraocular surgery according to claim 4, wherein the balanced salt solution comprises a complex electrolyte compound intraocular irrigation solution or a balanced salt intraocular irrigation solution.

7. 7. A method for preparing the irrigation solution for intraocular surgery according to claim 4, comprising the step of dissolving nicotinamide in a balanced salt solution to obtain a nicotinamide-containing irrigation solution for intraocular surgery.

8. (1) Suppressing corneal endothelial cell damage caused by ultrasonic emulsification; (2) Reduce corneal edema caused by phacoemulsification surgery for cataracts; (3) Avoiding the significant reduction in the number of corneal endothelial cells caused by phacoemulsification surgery for cataracts; (4) Promoting the restoration of normal corneal transparency after phacoemulsification surgery for cataracts; (5) Promoting the restoration of normal corneal thickness after phacoemulsification surgery for cataracts; (6) Maintaining the normal density, normal cell morphology, and regular expression and normal distribution of functional proteins of corneal endothelial cells after phacoemulsification surgery for cataract; (7) Use of nicotinamide or the intraocular surgical irrigation solution according to any one of claims 4 to 6 in the preparation of a product having the function of avoiding complications caused by ultrasonic emulsification surgery for cataracts, as set forth in one or more of (1) to (7).

9. 9. The application of claim 8, wherein the complications include ocular hypertension and / or endophthalmitis.

10. A method for using the intraocular irrigation solution according to any one of claims 4 to 6, characterized in that it comprises a step of protecting corneal endothelial cells when performing cataract ultrasonic emulsification surgery and / or vitrectomy surgery using the intraocular irrigation solution.

Images