Organ preserving fluid as well as preparation method and application thereof

Abstract

The invention relates to the technical field of organ transplantation, in particular to organ preserving fluid as well as a preparation method and application thereof. The organ preserving fluid comprises the following components: histidine; n, N-acetyl histidine monohydrate; vitamin C magnesium stearate; tryptophan; and alpha-ketoglutaric acid; trehalose; sodium chloride; potassium chloride; magnesium chloride * 6H2O; calcium chloride * 2H2O; aspartic acid; l-arginine is selected from L-arginine; glycine; l, L-alanine; eDTA (ethylene diamine tetraacetic acid); in addition, the composition also comprises rosmarinic acid and naringenin. The organ preserving fluid provided by the invention has better oxidation resistance.

Description

Technical Field

[0001] This application relates to the technical field of organ transplantation, and in particular to an organ preservation solution, its preparation method, and its application. Background Technology

[0002] Organ transplantation, as a core treatment for end-stage organ failure, has significantly improved patients' quality of life and prognosis. However, the quality of organ preservation directly determines the success or failure of transplantation surgery—if organ function is impaired during preservation, it will lead to increased rejection after transplantation, delayed recovery of organ function, and even transplantation failure. Currently, the clinical application of cryogenic combined with preservation solutions is widely adopted. This technique slows down cell metabolism by lowering the temperature and uses the components of the preservation solution to maintain intracellular environmental stability and inhibit ischemia-reperfusion injury, thus buying time for organ transplantation.

[0003] Currently, organ preservation solutions are mainly divided into three categories, each with its own advantages and disadvantages: ① UW solution is designed with "hyperosmolarity + antioxidation" as its core, using lacturonic acid to maintain osmotic pressure and glutathione to scavenge free radicals. It is known as the "gold standard" for organ preservation, but its high cost limits its widespread application; ② HTK solution has become the mainstream in clinical practice due to its simple formulation and convenient use, but it lacks antioxidant components and has a low concentration of energy substrates, making it difficult to meet the needs of long-term organ preservation; ③ Modified solutions containing exogenous antioxidants can alleviate oxidative damage to some extent, but many of their antioxidants have poor stability (such as ascorbic acid being easily auto-oxidized) or potential toxicity risks (such as some synthetic antioxidants potentially causing cytotoxicity), making it impossible to achieve a balance between safety and effectiveness.

[0004] The limitations of HTK solution are particularly prominent. Due to its limited antioxidant capacity, organs are susceptible to increased oxidative stress damage during preservation, leading to mitochondrial dysfunction and cell membrane lipid peroxidation, which in turn triggers irreversible apoptosis and necrosis. Simultaneously, insufficient energy substrates further weaken the organ cells' self-repair capabilities, exacerbating the risk of reperfusion injury. Clinical data show that organs such as the liver and kidneys preserved in HTK solution for more than 12 hours have a significantly increased probability of delayed functional recovery after transplantation, and are more prone to adverse events such as biliary complications and acute kidney injury.

[0005] In recent years, with the continuous growth in demand for organ transplantation and the intensification of the donor shortage, the development of efficient, safe, and cost-effective antioxidant preservation solutions has become a common goal of both academia and clinicians. Therefore, in-depth research on the antioxidant properties of organ preservation solutions has significant theoretical and clinical value for promoting the development of organ transplantation medicine. Summary of the Invention

[0006] This application provides an organ preservation solution, its preparation method, and its application.

[0007] Compared to HTK solution (with an antioxidant capacity of only 8.63%), the organ preservation solution provided in this application uses a combination of trehalose and magnesium vitamin C phosphate, and with the synergistic effect of rosmarinic acid and naringenin, it has a superior antioxidant capacity of 69.79%.

[0008] In a first aspect, this application provides an organ preservation solution, which adopts the following technical solution:

[0009] An organ preservation solution comprising the following components at the following concentrations: 20-25 g / L histidine; 4-6 g / L N-acetylhistidine monohydrate; 0.4-0.6 g / L vitamin C; magnesium stearate; 0.3-0.5 g / L tryptophan; 0.1-0.2 g / L α-ketoglutarate; 8-10 g / L trehalose; 0.5-1.5 g / L sodium chloride; 0.5-1 g / L potassium chloride; 1-2 g / L magnesium chloride × 6H₂O; 0.001-0.005 g / L calcium chloride × 2H₂O; 0.5-0.8 g / L aspartic acid; 0.4-0.6 g / L L-arginine; 0.6-0.8 g / L glycine; 0.3-0.5 g / L L-alanine; 0.005-0.02 g / L EDTA; 0.4-1.2 mg / L rosmarinic acid; 0.05-0.4 mg / L naringenin.

[0010] Rosmarinic acid is a polyphenolic compound whose molecular structure contains multiple phenolic hydroxyl groups (such as the ortho- and tho-diol structures on a benzene ring), giving it strong reducing properties. The phenolic hydroxyl groups can act as hydrogen donors, combining with hydroxyl radicals to terminate free radical chain reactions. The phenolic hydroxyl groups can also react with Fe... 2+ Cu 2+ It promotes the chelation of oxidizing metal ions, inhibits the Fenton reaction, and reduces the generation of ROS (reactive oxygen species).

[0011] Naringenin belongs to the flavonoid family and has a C6 (A ring)-C3-C6 (B ring) flavonoid core. Naringenin donates hydrogen atoms or electrons through its phenolic hydroxyl groups to neutralize reactive oxygen species (ROS), and the conjugated system of its flavonoid core can stabilize free radical intermediates. Furthermore, naringenin can activate the Nrf2 / ARE signaling pathway, promoting the synthesis of endogenous antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPx), thereby enhancing cellular antioxidant capacity.

[0012] In this application, rosmarinic acid and naringenin are added to the organ preservation solution. First, the two may regenerate each other through redox reactions; for example, the oxidation products of rosmarinic acid can be reduced by naringenin, prolonging the duration of antioxidant activity. Second, since the two have different distribution ranges in the preservation solution, they can exert their effects in the extracellular fluid, cell membrane, and intracellular space, respectively, forming a synergistic spatial protection. Furthermore, the anti-inflammatory effect of rosmarinic acid combined with the membrane-protective effect of naringenin can reduce the "oxidative-inflammatory" cascade reaction caused by ischemia-reperfusion during organ preservation, such as inhibiting neutrophil activation and the explosive release of oxygen free radicals, further reducing oxidative damage.

[0013] The organ preservation solution provided in this application can effectively extend the preservation time by reducing ROS damage to cell structures (such as cell membranes, DNA, and proteins), thus delaying organ function decline and providing more time for transplantation.

[0014] The protective solution provided in this application contains EDTA, which has the following advantages: (1) Chelating metal ions: EDTA can bind trace metal ions (such as Fe) in the solution. 2+ Cu 2+ (1) Inhibit its catalytic oxidation reaction; (2) Reduce pigment formation: Reduce solution discoloration by blocking the Maillard reaction catalyzed by metal ions and non-enzymatic browning; (3) Stabilize pH value: EDTA can buffer the effect of trace metal ions on pH and maintain solution stability.

[0015] Optionally, the amount of rosmarinic acid added is 0.6-1.0 mg / L.

[0016] In one specific embodiment, the amount of rosmarinic acid added is 0.4 mg / L, 0.6 mg / L, 0.7 mg / L, 0.8 mg / L, 0.9 mg / L, 1.0 mg / L, or 1.2 mg / L.

[0017] In some specific embodiments, the amount of rosmarinic acid added is 0.4-0.6 mg / L, 0.4-0.7 mg / L, 0.4-0.8 mg / L, 0.4-0.9 mg / L, 0.4-1.0 mg / L, 0.4-1.2 mg / L, 0.7-0.8 mg / L, 0.7-0.9 mg / L, 0.7-1.0 mg / L, 0.7-1.2 mg / L, 0.8-0.9 mg / L, 0.8-1.0 mg / L, 0.8-1.2 mg / L, 0.9-1.0 mg / L, 0.9-1.2 mg / L, or 1.0-1.2 mg / L.

[0018] Optionally, the amount of naringenin added is 0.2-0.3 mg / L.

[0019] In one specific embodiment, the amount of naringenin added is 0.05 mg / L, 0.1 mg / L, 0.2 mg / L, 0.3 mg / L, 0.32 mg / L, or 0.4 mg / L.

[0020] In some specific embodiments, the amount of naringenin added is 0.05-0.1 mg / L, 0.05-0.2 mg / L, 0.05-0.3 mg / L, 0.05-0.32 mg / L, 0.1-0.2 mg / L, 0.1-0.3 mg / L, 0.1-0.32 mg / L, 0.1-0.4 mg / L, 0.2-0.3 mg / L, 0.2-0.32 mg / L, 0.2-0.4 mg / L, 0.3-0.32 mg / L, 0.3-0.4 mg / L, or 0.32-0.4 mg / L.

[0021] Optionally, the concentration ratio of rosmarinic acid to naringenin is (2.5-5):1.

[0022] Optionally, the concentration ratio of rosmarinic acid to naringenin is (3.5-4.5):1.

[0023] In one specific embodiment, the concentration ratio of rosmarinic acid to naringenin is 16:1, 8:1, 6:1, 5:1, 4.5:1, 4:1, 3.5:1, 3:1, 2.7:1, 2.5:1, or 2:1.

[0024] In some specific embodiments, the concentration ratio of rosmarinic acid to naringenin is (2-2.5):1, (2-2.7):1, (2-3):1, (2-3.5):1, (2-4):1, (2-4.5):1, (2-5):1, (2-6):1, (2-8):1, (2-16):1, (2.5-2.7):1, (2.5-3):1, ( 2.5-3.5): 1, (2.5-4): 1, (2.5-4.5): 1, (2.5-5): 1, (2.5-6): 1, (2.5-8): 1, (2.5-16): 1, (2.7-3): 1, (2.7-3.5): 1, (2.7-4): 1, (2.7-4.5): 1, (2.7-5): 1, (2.7-6): 1, ( 2.7-8): 1, (2.7-16): 1, (3-3.5): 1, (3-4): 1, (3-4.5): 1, (3-5): 1, (3-6): 1, (3-8): 1, (3-16): 1, (3.5-4): 1, (3.5-4.5): 1, (3.5-5): 1, (3.5-6): 1, (3.5-8): 1, (3.5-1 6):1, (4-4.5):1, (4-5):1, (4-6):1, (4-8):1, (4-16):1, (4.5-5):1, (4.5-6):1, (4.5-8):1, (4.5-16):1, (5-6):1, (5-8):1, (5-16):1, (6-8):1, (6-16):1, (8-16):1.

[0025] Optionally, the organ preservation solution has an antioxidant capacity of 69.79%.

[0026] Secondly, this application provides a method for preparing an organ preservation solution, which adopts the following technical solution:

[0027] A method for preparing an organ preservation solution, the method specifically comprising the following steps:

[0028] According to the required proportions of each component, add each component to pure water and stir at 50-60℃ until the solution becomes clear to obtain a mixture.

[0029] Invert the 1000mL high-pressure bottle and fill it with nitrogen gas at a flow rate of 1L / min for 1-2 minutes;

[0030] The mixture was brought to a final volume of 1000 mL, and the pH of the mixture was controlled between 6.85 and 7 by adjusting the ratio of histidine to N-acetylhistidine monohydrate. The mixture was then poured into a 1000 mL autoclave (the beaker used was rinsed repeatedly during the process to ensure no residue remained). The autoclave containing 1000 mL of the mixture was placed in an autoclave and sterilized at 121 °C for 15-20 min to obtain the organ preservation solution.

[0031] The protective solution provided in this application contains nitrogen, which has the following advantages: (1) It can inhibit oxidation reaction: Nitrogen, as an inert gas, can replace oxygen in the solution and reduce oxidation reaction (such as sugar decomposition and amino acid oxidation); (2) It can prevent component degradation: During sterilization and storage, nitrogen protection can reduce the degradation of active ingredients (such as magnesium phosphate of vitamin C and tryptophan); (3) Color control: By reducing oxidation reaction, it inhibits the generation of colored substances such as 5-HMF (5-hydroxymethylfurfural) and avoids the solution from turning yellow.

[0032] Thirdly, this application provides the application of an organ preservation solution in cell, tissue, and organ transplantation.

[0033] In summary, this application includes at least one of the following beneficial technical effects:

[0034] (1) Antioxidant capacity: Compared with HTK solution (antioxidant capacity is only 8.63%), the organ preservation solution provided in this application uses a combination of trehalose and magnesium vitamin C phosphate, and with the synergistic effect of rosmarinic acid and naringenin, it has better antioxidant capacity, which can reach 69.79%.

[0035] (2) In terms of low temperature protection: HTK solution has a general ability to inhibit ice crystals. In comparison, the organ protection solution provided in this application has a better low temperature protection performance.

[0036] (3) Energy supply: Compared with HTK solution which only relies on α-ketoglutarate for energy, the organ preservation solution provided in this application can support longer preservation time.

[0037] (4) Sterilization stability: HTK solution is prone to yellowing after high-temperature sterilization, which may be accompanied by degradation of active ingredients; in contrast, the organ preservation solution provided in this application can significantly reduce the discoloration problem.

[0038] (5) Cost and accessibility: HTK solution is expensive; while the organ preservation solution provided in this application has a lower production cost and is suitable for large-scale promotion. Detailed Implementation

[0039] Before describing the embodiments of this application in detail, it should be understood that the terminology used herein is for the purpose of describing a particular embodiment only. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the term pertains.

[0040] It should be noted that the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of technical features indicated. Therefore, a feature defined as "first" or "second" may explicitly or implicitly include one or more of that feature. Furthermore, in the description of this application, unless otherwise stated, "multiple" means two or more.

[0041] The endpoints and any values ​​of the ranges disclosed in this application are not limited to the precise ranges or values, and such ranges or values ​​should be understood to include values ​​close to such ranges or values. For numerical ranges, the endpoint values ​​of the various ranges, the endpoint values ​​of the various ranges and individual point values, and individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed herein.

[0042] In this application, the terms "comprising" or "including" are open-ended expressions, meaning they include the content specified in this application but do not exclude other aspects.

[0043] This application provides an organ preservation solution. It comprises the following components at the following concentrations: 20-25 g / L histidine; 4-6 g / L N-acetylhistidine monohydrate; 0.4-0.6 g / L vitamin C; magnesium stearate; 0.3-0.5 g / L tryptophan; 0.1-0.2 g / L α-ketoglutarate; 8-10 g / L trehalose; 0.5-1.5 g / L sodium chloride; 0.5-1 g / L potassium chloride; 1-2 g / L magnesium chloride × 6H₂O; 0.001-0.005 g / L calcium chloride × 2H₂O; 0.5-0.8 g / L aspartic acid; 0.4-0.6 g / L L-arginine; 0.6-0.8 g / L glycine; 0.3-0.5 g / L L-alanine; 0.005-0.02 g / L EDTA; 0.4-1.2 mg / L rosmarinic acid; 0.05-0.4 mg / L naringenin.

[0044] To make the objectives, technical solutions, and advantages of this application clearer, the technical solutions in the embodiments of this application will be clearly and completely described below. All other embodiments obtained by those skilled in the art based on the embodiments of this application without inventive effort are within the scope of protection of this application. The embodiments described below are exemplary and are only used to explain this application, and should not be construed as limiting this application.

[0045] Where specific techniques or conditions are not specified in the examples, they shall be performed in accordance with the techniques or conditions described in the literature in this field or in accordance with the product instructions. Reagents or instruments whose manufacturers are not specified are all commercially available conventional products.

[0046] In this embodiment, the rosmarinic acid used was purchased from Sigma-Aldrich, CAS No.: 20283-92-5, ≥98%; the naringenin used was purchased from Sigma-Aldrich, CAS No.: 67604-48-2, 98%.

[0047] The present application will be further described in detail below with reference to the embodiments and test results.

[0048] Example

[0049] Example 1

[0050] This embodiment provides an organ preservation solution.

[0051] The specific component ratios of the above organ preservation solution are as follows:

[0052] 22.31 g / L histidine; 5.46 g / L N-acetylhistidine monohydrate; 0.52 g / L vitamin C; magnesium stearate; 0.4085 g / L tryptophan; 0.1842 g / L α-ketoglutarate; 9.5 g / L trehalose; 1.053 g / L sodium chloride; 0.746 g / L potassium chloride; 1.6264 g / L magnesium chloride × 6H2O; 0.002 g / L calcium chloride × 2H2O; 0.6655 g / L aspartic acid; 0.5226 g / L L-arginine; 0.7507 g / L glycine; 0.4455 g / L L-alanine; 0.01 g / L EDTA; 0.4 mg / L rosmarinic acid; 0.05 mg / L naringenin.

[0053] The preparation method of the above-mentioned organ preservation solution specifically includes the following steps:

[0054] According to the required proportions of each component, add each component to 500ml of pure water and stir at 50℃ until the solution is clear to obtain a mixture.

[0055] Invert the 1000mL high-pressure bottle and fill it with nitrogen gas at a flow rate of 1L / min for 2 minutes;

[0056] The mixture was brought to a final volume of 1000 mL, and the pH of the mixture was controlled between 6.85 and 7 by adjusting the ratio of histidine to N-acetylhistidine monohydrate. The mixture was then poured into a 1000 mL autoclave (the beaker used was rinsed repeatedly during the process to ensure no residue remained). The autoclave containing 1000 mL of the mixture was placed in an autoclave and sterilized at 121 °C for 15 min to obtain the organ preservation solution.

[0057] Example 2-12

[0058] Examples 2-12 each provide an organ preservation solution. The difference between these examples and Example 1 lies in the concentrations of rosmarinic acid and naringenin, as shown in Table 1. All other components and operating procedures remain the same as in Example 1.

[0059] The differences between Examples 1-12 are as follows:

[0060] The difference between Examples 1-7 is the concentration of rosmarinic acid.

[0061] The difference between Example 4 and Examples 8-12 is the concentration of naringenin.

[0062] Table 1. Addition details and antioxidant test results of some components in the examples and comparative examples.

[0063]

[0064]

[0065] Comparative Example

[0066] Comparative Example 1

[0067] This comparative example provides an organ preservation solution. It differs from Example 4 in that it does not contain rosmarinic acid and naringenin, as detailed in Table 1. All other components and operating procedures remain the same as in Example 1.

[0068] Comparative Example 2

[0069] This comparative example provides an organ preservation solution. It differs from Example 4 in that it does not contain rosmarinic acid, as detailed in Table 1. All other components and operating procedures remain the same as in Example 1.

[0070] Comparative Example 3

[0071] This comparative example provides an organ preservation solution. It differs from Example 4 in that it does not contain naringenin, as detailed in Table 1. All other components and operating procedures remain the same as in Example 1.

[0072] Comparative Example 4

[0073] This comparative example provides an organ preservation solution, which is the HTK preservation solution used in the prior art.

[0074] The aforementioned HTK protective solution specifically includes components at the following concentrations:

[0075] 0.089% Sodium chloride; 0.077% Potassium chloride; 0.072% Magnesium chloride × 6H2O; 4.091% Histidine·HCl·H2O, Histidine; 0.014% Tryptophan; 0.525% Mannitol; <1 mg / L Calcium chloride × 2H2O; 0.001% 2-Ketoglutarate-H2-potassium; Balance: Water.

[0076] The preparation method of the above-mentioned organ preservation solution is the same as that in Example 1.

[0077] Performance test results

[0078] The DPPH free radical scavenging rate of the organ preservation solutions in the above examples and comparative examples was measured to determine their antioxidant performance.

[0079] (1) Principle Analysis

[0080] DPPH (2,2-diphenyl-1-picrylhydrazine) is a stable nitrogen-centered free radical. Its ethanol solution is deep purple and has a characteristic absorption peak at 517 nm. In the presence of antioxidants, the hydrogen atoms or electrons they contain can pair with the DPPH free radical, reducing it to the colorless DPPH-H, causing the solution to decolorize. The degree of decolorization is positively correlated with the free radical scavenging ability of the antioxidant. By measuring the change in absorbance, the scavenging rate of the antioxidant can be quantitatively calculated.

[0081] (2) Operating Procedures (Spectrophotometer Method)

[0082] The system consisted of three components: a blank control group (2 mL ethanol + 2 mL DPPH stock solution (0.1 mmol / L)) and a control group (2 mL sample diluent (organ preservation solution diluted 50, 80, and 100 times with ethanol) + 2 mL ethanol (instead of DPPH) and a sample group (2 mL sample diluent (organ preservation solution diluted 50, 80, and 100 times with ethanol) + 2 mL DPPH stock solution and a sample group). Each group was replicated three times to minimize error.

[0083] Incubate the solutions in the above groups at room temperature (25℃) in the dark for 30 min. Using a 1 cm cuvette, zero the sample group and measure the absorbance of the control group and the sample group at a wavelength of 517 nm.

[0084] (3) Calculation of clearance rate

[0085] The formula for calculating the clearance rate is as follows: Clearance rate (%) = (1-A) 样品组 -A 空白组 ) / A 对照组 ×100%.

[0086] Among them, A 样品组 The absorbance is the result of the reaction between the sample dilution and the DPPH stock solution. A 空白组 The absorbance is for the blank group (containing only ethanol and DPPH stock solution). A 对照组 The absorbance is the result of the reaction between the sample dilution and ethanol (excluding interference from the sample's own color).

[0087] (4) Test results

[0088] The test results are shown in Table 1.

[0089] As shown in Table 1, the organ preservation solution provided in this application uses a combination of trehalose and magnesium vitamin C phosphate. With the synergistic effect of rosmarinic acid and naringenin, it has a better antioxidant capacity, which can reach 69.79%.

[0090] The organ preservation solution provided in this application is significantly superior to HTK preservation solution in terms of antioxidant capacity. At the same time, the solution discoloration problem is solved through the synergistic effect of nitrogen and EDTA. It also has good low-temperature protection, energy supply and sterilization capabilities, and has broad market prospects.

[0091] In the description of this specification, the references to terms such as "one embodiment," "some embodiments," "example," "specific example," or "some examples," etc., indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of this application. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples. Moreover, without contradiction, those skilled in the art can combine and integrate the different embodiments or examples described in this specification, as well as the features of different embodiments or examples.

[0092] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of this application, and are not intended to limit them. Although this application has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of this application.

Claims

1. An organ preservation solution, characterized in that, The organ preservation solution comprises the following components at the following concentrations: 20-25 g / L histidine; 4-6 g / L N-acetylhistidine monohydrate; 0.4-0.6 g / L vitamin C magnesium stearate; 0.3-0.5 g / L tryptophan; 0.1-0.2 g / L α-ketoglutarate; 8-10 g / L trehalose; 0.5-1.5 g / L sodium chloride; 0.5-1 g / L potassium chloride; 1-2 g / L magnesium chloride × 6H₂O; 0.001-0.005 g / L calcium chloride × 2H₂O; 0.5-0.8 g / L aspartic acid; 0.4-0.6 g / L L-arginine; 0.6-0.8 g / L glycine; 0.3-0.5 g / L L-alanine; 0.005-0.02 g / L EDTA; 0.4-1.2 mg / L rosmarinic acid; 0.05-0.4 mg / L naringenin.

2. The organ preservation solution according to claim 1, characterized in that, The amount of rosmarinic acid added is 0.6-1.0 mg / L.

3. The organ preservation solution according to claim 1, characterized in that, The amount of naringenin added is 0.2-0.3 mg / L.

4. The organ preservation solution according to claim 1, characterized in that, The concentration ratio of rosmarinic acid to naringenin is (2.5-5):

1.

5. The organ preservation solution according to claim 1, characterized in that, The concentration ratio of rosmarinic acid to naringenin is (3.5-4.5):

1.

6. The organ preservation solution according to claim 1, characterized in that, The organ preservation solution has an antioxidant capacity of 69.79%.

7. A method for preparing an organ preservation solution according to any one of claims 1-6, characterized in that, The preparation method is specifically as follows: According to the required proportions of each component, add each component to pure water and stir at 50-60℃ until the solution becomes clear to obtain a mixture. Invert the 1000mL high-pressure bottle and fill it with nitrogen gas at a flow rate of 1L / min for 1-2 minutes; The mixture was brought to a final volume of 1000 mL, and the pH of the mixture was controlled between 6.85 and 7 by adjusting the ratio of histidine to N-acetylhistidine monohydrate. The mixture was then poured into a 1000 mL autoclave, and the autoclave containing the 1000 mL mixture was placed in an autoclave and sterilized at 121 °C for 15-20 min to obtain the organ preservation solution.

8. The use of an organ preservation solution according to any one of claims 1-6 in cell, tissue and organ transplantation.

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