Linear wide-range blood cell analyzer reagent and preparation method thereof
By using hyperbranched anticoagulants and thiol-ester stabilizers in the blood cell reagent, the problem of insufficient detection range and anticoagulation of the existing blood cell reagent is solved, and more accurate and stable blood detection is achieved, improving the The application value of reagents.
Patent Information
- Application Number
- CN202411253904.5
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-09-09
- Publication Date
- 2024-12-13
- Estimated Expiration
- Not applicable · inactive patent
AI Technical Summary
The existing blood cell reagents have limitations in their detection range and accuracy, and do not have good anticoagulation, which leads to unstable detection results and cannot meet the clinical demand for a wide range of blood parameters.
Using blood cell reagents composed of diluents, hemolytics, stains and cleaning solutions, the anticoagulant and thiol-ester stabilizers with hyperbranched structures can improve the anticoagulant and stability of the reagent, and through specific Formulation and process preparation methods ensure that reagents provide accurate test results within a wider range of detection.
It achieves accurate detection results within a wider detection range, while improving the stability and economy of the reagent, with excellent anticoagulant properties, applicability and market value.
Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of medical diagnostic instrument reagents, and in particular relates to a linear wide-range blood cell analyzer reagent and a preparation method thereof. Background Art
[0002] Blood analysis is an indispensable part of modern medical diagnosis and is widely used in clinical diagnosis, disease monitoring and health examinations. As an important blood analysis tool, the hemocytometer can quickly and accurately detect various cell components in the blood, such as red blood cells, white blood cells and platelets. However, existing hemocytometer reagents have certain limitations in terms of detection range and accuracy.
[0003] The preparation process of existing blood cell analyzer reagents is complicated, which is not conducive to large-scale production and application. In addition, some reagents are imported reagents, which not only have a long cycle but also are expensive. At the same time, many existing blood cell analyzer reagents can only cover a limited detection range and cannot meet the clinical needs for a wide range of blood parameters. For example, some reagents may have errors or fail to detect when detecting low-concentration or high-concentration blood samples. In addition, traditional reagents are easily affected by environmental factors during storage and use, resulting in unstable test results.
[0004] Chinese patent CN 104698157 B relates to a reagent for a blood cell analyzer, which consists of a diluent, an EOI hemolytic agent, an LH hemolytic agent, an EOII staining solution, and a cleaning solution. This reagent has a wide range of uses, is applicable to many models, and has accurate test results. The correlation coefficient R value after linear regression with the original blood cell reagent reaches more than 0.99, which reflects a good correlation. In addition, the raw materials of the reagent are non-toxic and harmless, which is conducive to the promotion and application of the reagent for the blood cell analyzer. However, this reagent does not involve the study of anticoagulability, while anticoagulants not only involve the processing and preservation of samples after blood collection, but their selection is also crucial for the counting and classification of blood cells.
[0005] Therefore, there is an urgent need to develop a linear wide range hemacytometer reagent to make the reagent test results stable and accurate. Summary of the invention
[0006] In view of the existing technical problems, the object of the present invention is to provide a linear wide range blood cell meter reagent and a preparation method thereof, wherein the blood cell meter reagent is composed of a diluent, a hemolytic agent, a dye and a cleaning solution. The blood cell meter reagent of the present invention has excellent anticoagulant properties, can provide accurate test results within a wider detection range, and has better stability and economy, and has high application and market value.
[0007] In order to achieve the above object, the technical solution adopted by the present invention is as follows:
[0008] In one aspect, the present invention provides a linear wide range hematology analyzer reagent, which is composed of a diluent, a hemolytic agent, a dye and a cleaning solution; wherein:
[0009] The components and contents of the diluent are: osmotic pressure regulator 5-8 g / L, buffer 1-2 g / L, anticoagulant 0.3-0.6 g / L, preservative 0.2-0.4 g / L;
[0010] The components and contents of the hemolytic agent are: osmotic pressure regulator 1.6-2.4 g / L, quaternary ammonium surfactant 2.8-4.2 g / L, nonionic surfactant 4-6.5 g / L, stabilizer 1.6-2.4 g / L, EDTAK 20.1-0.3 g / L, Triton X-100 1-1.5 g / L, 4-hydroxyethylpiperazineethanesulfonic acid 3-6 g / L, succinic acid 0.6-1 g / L;
[0011] The components and contents of the dye are: polymethine dye 0.015-0.035 g / L, methanol 25-35 g / L, ethylene glycol 900-1000 g / L;
[0012] The components and contents of the cleaning solution are: 5-10 g / L of osmotic pressure regulator, 2-4.5 g / L of nonylphenol polyoxyethylene ether, 1-2.5 g / L of buffer, 0.1-0.3 g / L of preservative, and 6-12 g / L of complex enzyme.
[0013] The reaction mechanism and effects of the present invention are as follows:
[0014] 1. Biomedical materials need to have good biocompatibility due to their special applications, which is the key to whether the material can be used as a blood-contact medical material. The present invention synthesizes an anticoagulant with a hyperbranched structure. Through molecular design and synthesis, a hyperbranched material with good anticoagulant performance is prepared, which can broaden its application in the field of biomedical materials.
[0015] After modification, the anticoagulant synthesized by the present invention has an electrostatic repulsion effect between its surface and blood components, and has good anticoagulant properties. The present application selects 2,2-diisopentyl-1,3-propanediol and 2-hydroxy-4-pentenoic acid as monomers to synthesize branched structures, but its solubility is poor, which may be due to the intermolecular hydrogen bonds formed by ester groups and hydroxyl groups and the presence of unsaturated double bonds. The applicant introduces a carboxylic acid group through 2-chloropropionic acid to improve the blood compatibility of the substance, because the carboxylic acid group not only makes the surface of the material have a certain negative charge, but also destroys the presence of unsaturated double bonds. Further, 1,3-propane sultone is introduced, and the sulfonic acid group in its structure has good water solubility, which will destroy the hydrogen bonding between hydroxyl groups, thereby improving the solubility of hyperbranched substances, giving full play to their excellent anticoagulant properties, and also providing more possibilities for the application of hyperbranched substances in the field of biomedicine.
[0016] 2. The present invention introduces a thiol group by adding 2-phenylethanethiol to the molecular skeleton of benzothiazole to synthesize a thiol ester stabilizer of benzo heterocycle. On the one hand, the novel stabilizer structure reduces the rigid structure of phenylbenzothiazole by utilizing the lone pair of electrons of the sulfur atom, making the molecular structure more flexible, enhancing the ultraviolet absorption intensity, and improving the stability. On the other hand, the complex formed by the cationic surfactant and hemoglobin can be made to keep the absorbance value of a specific wavelength unchanged within the instrument detection time by the stabilizer, significantly improving the accuracy and stability of the hemoglobin concentration determination.
[0017] In some embodiments, the osmotic pressure regulator is any one or more of sodium chloride, potassium chloride and sodium sulfate.
[0018] In some embodiments, the quaternary ammonium salt surfactant is any one or more of dodecyltrimethylammonium chloride, dodecyltrimethylammonium bromide, dodecyldimethylbenzylammonium chloride, tetradecyltrimethylammonium chloride, tetradecyltrimethylammonium bromide, hexadecyltrimethylammonium chloride and hexadecyltetramethylammonium chloride.
[0019] In some embodiments, the nonionic surfactant is any one or more of polyoxyethylene lauryl ether, polyoxyethylene stearate and alkylphenol polyoxyethylene ether.
[0020] Preferably, the preservative is Proclin 300.
[0021] Preferably, the buffer is borax and / or boric acid.
[0022] Preferably, the complex enzyme is alkaline protease and serine protease.
[0023] More preferably, the content ratio of the alkaline protease to the serine protease is 1:(2-3).
[0024] In some embodiments, the method for preparing the anticoagulant comprises the following steps:
[0025] S1. Add 2,2-diisopentyl-1,3-propanediol and 2-hydroxy-4-pentenoic acid to a reaction kettle, introduce inert gas, heat to 120-140°C, add a catalyst, keep the temperature for 3-4 hours, continue the reaction under reduced pressure for 3-4 hours, cool to 45-55°C, add acetone, stir, then add n-hexane, filter, and obtain a precipitated product;
[0026] S2. The precipitate obtained in step S1 and acetone are mixed, stirred, 2-chloropropionic acid is added, an inert gas is introduced, heated to 50-70°C, a Lewis acid catalyst is added, the reaction is kept warm for 2-4h, and cooled to obtain an intermediate product;
[0027] S3. Disperse sodium hydride in tetrahydrofuran to obtain a sodium hydride solution for standby use; drop the sodium hydride solution into the intermediate product obtained in step S2, react for 10-12 hours, add 1,3-propane sultone, continue stirring and reacting for 10-12 hours, filter, dissolve the obtained solid in dimethyl sulfoxide, add tetrahydrofuran to precipitate, vacuum dry the crude product obtained by the precipitation, dialyze with water twice, and vacuum dry the dialyzed product to obtain an anticoagulant.
[0028] In some embodiments, the molar ratio of 2,2-diisopentyl-1,3-propanediol to 2-hydroxy-4-pentenoic acid in step S1 is 1:(8.2-8.6).
[0029] In some embodiments, the molar ratio of the intermediate product to 1,3-propane sultone in step S3 is 1:(2-2.4).
[0030] Preferably, the molar ratio of the precipitated product to 2-chloropropionic acid in step S2 is 1:(8.1-8.4).
[0031] In some embodiments, the method for preparing the stabilizer comprises the following steps:
[0032] Add 1,3-benzothiazole-2-carbonyl chloride and tetrahydrofuran to a reaction kettle, stir to dissolve, add triethylamine, pass inert gas, stir for 10-20 minutes, add 2-phenylethanethiol dropwise in an ice-water bath at -4-2°C, heat to 50-60°C, react for 5-6 hours, extract with ethyl acetate to separate the layers, take the organic phase, dry it with anhydrous sodium sulfate, rotary evaporate, and separate and purify it with a chromatographic column to obtain a stabilizer.
[0033] In some embodiments, the molar ratio of 1,3-benzothiazole-2-carbonyl chloride to 2-phenylethanethiol is 1:(1.6-1.9).
[0034] Another aspect of the present invention provides a method for preparing a linear wide range hematology analyzer reagent, comprising the following steps:
[0035] The components of the diluent, hemolytic agent, dye and cleaning solution are mixed and prepared in proportion, and then coarsely filtered, and then ultrafiltered with a filter membrane, and packaged to obtain a hemacytometer reagent.
[0036] Preferably, the particle size of the ultrafiltration membrane is 0.22 μm.
[0037] Compared with the prior art, the present invention has the following beneficial effects:
[0038] 1. The blood cell analyzer reagent of the present invention has excellent anticoagulant properties, can provide accurate test results within a wider detection range, and has better stability and economy, and has high application and market value.
[0039] 2. After modification, the anticoagulant synthesized by the present invention has an electrostatic repulsion effect between its surface and blood components, and has good anticoagulant properties. The applicant improves the blood compatibility and solubility of the anticoagulant by introducing 2-chloropropionic acid and 1,3-propane sultone, so that it can give full play to its excellent anticoagulant properties, and also provides more possibilities for the application of hyperbranched substances in the field of biomedicine.
[0040] 3. The thiol stabilizer synthesized from benzoheterocyclic rings of the present invention can not only enhance the ultraviolet absorption intensity and improve the stability, but also significantly improve the accuracy and stability of hemoglobin concentration determination. DETAILED DESCRIPTION
[0041] The present invention will be described below in conjunction with specific embodiments. It should be noted that the following embodiments are examples of the present invention and are only used to illustrate the present invention, rather than to limit the present invention. Other combinations and various modifications within the concept of the present invention may be performed without departing from the spirit or scope of the present invention.
[0042] According to the ratios of the raw materials and the preparation methods specified in the following examples and comparative examples, various blood cell analyzer reagents were prepared.
[0043] In order to facilitate those skilled in the art to implement the present invention, some raw material manufacturers of the embodiments and comparative examples are described as follows:
[0044] Polymethine dye: purchased from Duoying Biotechnology Company;
[0045] Polyoxyethylene lauryl ether: purchased from Hubei Xinyuhong Biopharmaceutical Technology Co., Ltd., model N / A;
[0046] Alkylphenol polyoxyethylene ether: purchased from Hai'an Petrochemical Plant, Jiangsu Province, octylphenol polyoxyethylene ether OP-10 and nonylphenol polyoxyethylene ether NP-10;
[0047] Other raw materials are not specially specified and can be purchased from the market.
[0048] Preparation Example 1
[0049] The preparation method of anticoagulant A comprises the following steps:
[0050] S1. Add 30mmol 2,2-diisopentyl-1,3-propanediol and 250mmol 2-hydroxy-4-pentenoic acid into a reaction kettle, introduce nitrogen, heat to 130°C, add 25mmol p-toluenesulfonic acid, keep the reaction for 4h, continue the reaction under reduced pressure for 3h, cool to 50°C, add 200ml acetone, stir for 30min, then add n-hexane until no more precipitate is precipitated, filter to obtain the precipitated product;
[0051] S2. Mix 20 mmol of the precipitated product obtained in step S1 and 200 ml of acetone, stir and reflux until dissolved, add 164 mmol of 2-chloropropionic acid, introduce nitrogen, heat to 60 ° C, add 15 mmol of ferric chloride, keep the reaction for 3 h, and cool to room temperature to obtain an intermediate product;
[0052] S3. Disperse 48 mmol of sodium hydride in 50 ml of tetrahydrofuran to obtain a sodium hydride solution for standby use; drop the sodium hydride solution into 15 mmol of the intermediate product obtained in step S2, react for 10 h, add 33 mmol of 1,3-propane sultone, continue stirring and reacting for 12 h, filter, dissolve the obtained solid in 50 ml of dimethyl sulfoxide, add tetrahydrofuran to precipitate until no precipitate is precipitated, dry the crude product obtained by precipitation at 70° C. in vacuum for 3 h, dialyze with secondary water for 5 d, and dry the dialyzed product at 100° C. in vacuum for 3 h to obtain anticoagulant A.
[0053] Preparation Example 2
[0054] The preparation method of anticoagulant B is the same as that of Example 1, except that the amount of 2-hydroxy-4-pentenoic acid added in step S1 is 235 mmol.
[0055] Preparation Example 3
[0056] The preparation method of anticoagulant C is the same as that of Example 1, except that the amount of 1,3-propane sultone added in step S3 is 27 mmol.
[0057] Preparation Example 4
[0058] The preparation method of stabilizer A comprises the following steps:
[0059] 1 mol of 1,3-benzothiazole-2-carbonyl chloride and 200 ml of tetrahydrofuran were added to a reaction kettle, stirred for 1 hour to dissolve, 1.2 mol of triethylamine was added, nitrogen was introduced, and the mixture was stirred for 15 minutes. 1.75 mol of 2-phenylethanethiol was added dropwise in an ice-water bath at 0°C, the mixture was heated to 55°C, and the reaction was performed for 6 hours. The mixture was extracted with ethyl acetate and the organic phase was dried with anhydrous sodium sulfate for 4 hours, and then rotary evaporated. The mixture was separated and purified by a chromatographic column, and the eluent was petroleum ether and ethyl acetate in a volume ratio of 12:1, to obtain stabilizer A.
[0060] Preparation Example 5
[0061] The preparation method of stabilizer B is the same as that of Preparation Example 4, except that the amount of 2-phenylethanethiol added is 1.45 mol.
[0062] Example 1
[0063] A linear wide range hematology analyzer reagent, the hematology analyzer reagent is composed of a diluent, a hemolytic agent, a dye and a cleaning solution; wherein,
[0064] The components and contents of the diluent are: sodium chloride 4 g / L, sodium sulfate 2.5 g / L, boric acid 1.5 g / L, anticoagulant A 0.5 g / L, Proclin 3000.3 g / L;
[0065] The components and contents of the hemolytic agent are as follows: sodium chloride 2g / L, dodecyltrimethylammonium chloride 1.5g / L, hexadecyltrimethylammonium chloride 2g / L, polyoxyethylene lauryl ether 2.5g / L, octylphenol polyoxyethylene ether OP-102.5g / L, stabilizer A2g / L, EDTAK20.2g / L, Triton X-1001.25g / L, 4-hydroxyethylpiperazineethanesulfonic acid 4.5g / L, succinic acid 0.8g / L;
[0066] The components and contents of the dye are: 0.025 g / L of polymethine dye, 30 g / L of methanol, and 950 g / L of ethylene glycol;
[0067] The components and contents of the cleaning solution are: sodium chloride 7.5 g / L, nonylphenol polyoxyethylene ether NP-10 3.5 g / L, boric acid 1.75 g / L, Proclin 3000.2 g / L, alkaline protease 2.6 g / L, and serine protease 6.4 g / L.
[0068] The preparation method of the blood cell analyzer reagent of this embodiment comprises the following steps:
[0069] The components of the diluent, hemolytic agent, dye and cleaning solution are mixed in proportion and then coarsely filtered, and then ultrafiltered with a 0.22 μm filter membrane, and packaged to obtain a hemacytometer reagent.
[0070] Example 2
[0071] A linear wide range hematology analyzer reagent, the hematology analyzer reagent is composed of a diluent, a hemolytic agent, a dye and a cleaning solution; wherein,
[0072] The components and contents of the diluent are: sodium chloride 3 g / L, sodium sulfate 2 g / L, boric acid 1 g / L, anticoagulant A 0.3 g / L, Proclin 3000.2 g / L;
[0073] The components and contents of the hemolytic agent are as follows: sodium chloride 1.6 g / L, dodecyl trimethyl ammonium chloride 1 g / L, hexadecyl trimethyl ammonium chloride 1.8 g / L, polyoxyethylene lauryl ether 2 g / L, octylphenol polyoxyethylene ether OP-102 g / L, stabilizer A 1.6 g / L, EDTAK 20.1 g / L, Triton X-100 1 g / L, 4-hydroxyethylpiperazine ethanesulfonic acid 3 g / L, succinic acid 0.6 g / L;
[0074] The components and contents of the dye are: 0.015 g / L of polymethine dye, 25 g / L of methanol, and 900 g / L of ethylene glycol;
[0075] The components and contents of the cleaning solution are: 5 g / L sodium chloride, 2 g / L nonylphenol polyoxyethylene ether NP-10, 1 g / L boric acid, 0.1 g / L Proclin 3000, 2 g / L alkaline protease, and 4 g / L serine protease.
[0076] The preparation method of the blood cell analyzer reagent in this embodiment is the same as that in Example 1.
[0077] Example 3
[0078] A linear wide range blood cell analyzer reagent, characterized in that the blood cell analyzer reagent is composed of a diluent, a hemolytic agent, a dye and a cleaning solution; wherein,
[0079] The components and contents of the diluent are: sodium chloride 5 g / L, sodium sulfate 3 g / L, boric acid 2 g / L, anticoagulant A 0.6 g / L, Proclin 3000.4 g / L;
[0080] The components and contents of the hemolytic agent are as follows: sodium chloride 2.4 g / L, dodecyl trimethyl ammonium chloride 1.5 g / L, hexadecyl trimethyl ammonium chloride 2.7 g / L, polyoxyethylene lauryl ether 3 g / L, octylphenol polyoxyethylene ether OP-10 3.5 g / L, stabilizer A 2.4 g / L, EDTAK 20.3 g / L, Triton X-100 1.5 g / L, 4-hydroxyethylpiperazine ethanesulfonic acid 6 g / L, succinic acid 1 g / L;
[0081] The components and contents of the dye are: 0.035 g / L of polymethine dye, 35 g / L of methanol, and 1000 g / L of ethylene glycol;
[0082] The components and contents of the cleaning solution are: sodium chloride 10 g / L, nonylphenol polyoxyethylene ether NP-10 4.5 g / L, boric acid 2.5 g / L, Proclin 3000.3 g / L, alkaline protease 3 g / L, and serine protease 9 g / L.
[0083] The preparation method of the blood cell analyzer reagent in this embodiment is the same as that in Example 1.
[0084] Example 4
[0085] A linear wide range hemacytometer reagent and a preparation method thereof, wherein the specific implementation manner is the same as that of Example 1, except that an equal amount of stabilizer B is used to replace stabilizer A.
[0086] Example 5
[0087] A linear wide range hemacytometer reagent and a preparation method thereof, wherein the specific implementation manner is the same as that of Example 1, except that an equal amount of anticoagulant B is used to replace anticoagulant A.
[0088] Example 6
[0089] A linear wide range hemacytometer reagent and a preparation method thereof, wherein the specific implementation manner is the same as that of Example 1, except that an equal amount of anticoagulant C is used to replace anticoagulant A.
[0090] Example 7
[0091] A linear wide range hemacytometer reagent and a preparation method thereof, wherein the specific implementation manner is the same as that of Example 1, except that an equal amount of EDTA2K is used to replace anticoagulant A.
[0092] Comparative Example 1
[0093] A linear wide range hemacytometer reagent and a preparation method thereof, wherein the specific implementation manner is the same as that of Example 1, except that stabilizer A is not added.
[0094] Effect evaluation:
[0095] The blood cell analyzer reagents prepared in the above-mentioned Examples 1-7 and Comparative Example 1 were tested and analyzed.
[0096] Performance Test:
[0097] The prepared hemacytometer reagent was used together with XN reagent of Sysmex Corporation of Japan to detect the same blood sample.
[0098] After the reagents were prepared, the test results of the white blood cell percentage, red blood cell percentage, hemoglobin, platelet percentage, white blood cell percentage, neutrophil percentage, lymphocyte percentage, monocyte percentage, eosinophil percentage, and basophil percentage were obtained. The correlation coefficients of the reagents prepared in Examples 1-3 and the XN reagent were all greater than 0.97, especially the correlation of Example 1 was as high as 0.999, while the correlation coefficients of the data of Examples 4-7 and Comparative Example 1 and the imported XN reagent were all less than 0.97.
[0099] After the reagents were prepared and stored for 48 hours, the test results of the indicators of white blood cells, red blood cells, hemoglobin, platelets, white blood cells, neutrophil percentage, lymphocyte percentage, monocyte percentage, eosinophil percentage, and basophil percentage were obtained. The correlation coefficients of the reagents prepared in Examples 1-3 and the XN reagent were all greater than 0.95, especially the correlation of Example 1 was as high as 0.99, while the correlation coefficients of the data of Examples 4-7 and Comparative Example 1 and the imported XN reagent were all less than 0.95.
[0100] The above is only a preferred embodiment of the present invention and does not constitute any form of limitation to the present application. Although the present application is disclosed as above in the preferred embodiment, it is not intended to limit the present application. Any technician familiar with the profession, without departing from the scope of the technical solution of the present application, using the technical content disclosed above to make slight changes or modifications are equivalent to equivalent implementation cases. However, any simple modifications, equivalent changes and modifications made to the above embodiments based on the technical essence of the present invention without departing from the content of the technical solution of the present invention are still within the scope of the technical solution.
Claims
1. A linear wide range hematology analyzer reagent, characterized in that: The blood cell analyzer reagent is composed of a diluent, a hemolytic agent, a dye and a cleaning solution; wherein, The components and contents of the diluent are: osmotic pressure regulator 5-8 g / L, buffer 1-2 g / L, anticoagulant 0.3-0.6 g / L, preservative 0.2-0.4 g / L; The components and contents of the hemolytic agent are: osmotic pressure regulator 1.6-2.4 g / L, quaternary ammonium surfactant 2.8-4.2 g / L, nonionic surfactant 4-6.5 g / L, stabilizer 1.6-2.4 g / L, EDTAK 20.1-0.3 g / L, Triton X-100 1-1.5 g / L, 4-hydroxyethylpiperazineethanesulfonic acid 3-6 g / L, succinic acid 0.6-1 g / L; The components and contents of the dye are: polymethine dye 0.015-0.035 g / L, methanol 25-35 g / L, ethylene glycol 900-1000 g / L; The components and contents of the cleaning solution are: 5-10 g / L of osmotic pressure regulator, 2-4.5 g / L of nonylphenol polyoxyethylene ether, 1-2.5 g / L of buffer, 0.1-0.3 g / L of preservative, and 6-12 g / L of complex enzyme.
2. A linear wide range hematology analyzer reagent according to claim 1, characterized in that: The osmotic pressure regulator is any one or more of sodium chloride, potassium chloride and sodium sulfate.
3. A linear wide range hematology analyzer reagent according to claim 1, characterized in that: The quaternary ammonium salt surfactant is any one or more of dodecyltrimethylammonium chloride, dodecyltrimethylammonium bromide, dodecyldimethylbenzylammonium chloride, tetradecyltrimethylammonium chloride, tetradecyltrimethylammonium bromide, hexadecyltrimethylammonium chloride and hexadecyltetramethylammonium chloride.
4. A linear wide range hematology analyzer reagent according to claim 1, characterized in that: The nonionic surfactant is any one or more of polyoxyethylene lauryl ether, polyoxyethylene stearate and alkylphenol polyoxyethylene ether.
5. A linear wide range hematology analyzer reagent according to claim 1, characterized in that: The preparation method of the anticoagulant comprises the following steps: S1. Add 2,2-diisopentyl-1,3-propanediol and 2-hydroxy-4-pentenoic acid to a reaction kettle, introduce inert gas, heat to 120-140°C, add a catalyst, keep the temperature for 3-4 hours, continue the reaction under reduced pressure for 3-4 hours, cool to 45-55°C, add acetone, stir, then add n-hexane, filter, and obtain a precipitated product; S2. The precipitate obtained in step S1 and acetone are mixed, stirred, 2-chloropropionic acid is added, an inert gas is introduced, heated to 50-70°C, a Lewis acid catalyst is added, the reaction is kept warm for 2-4h, and cooled to obtain an intermediate product; S3. Disperse sodium hydride in tetrahydrofuran to obtain a sodium hydride solution for standby use; drop the sodium hydride solution into the intermediate product obtained in step S2, react for 10-12 hours, add 1,3-propane sultone, continue stirring and reacting for 10-12 hours, filter, dissolve the obtained solid in dimethyl sulfoxide, add tetrahydrofuran to precipitate, vacuum dry the crude product obtained by the precipitation, dialyze with water twice, and vacuum dry the dialyzed product to obtain an anticoagulant.
6. A linear wide range hematology analyzer reagent according to claim 5, characterized in that: The molar ratio of 2,2-diisopentyl-1,3-propanediol to 2-hydroxy-4-pentenoic acid in step S1 is 1:(8.2-8.6).
7. A linear wide range hematology analyzer reagent according to claim 5, characterized in that: The molar ratio of the intermediate product to 1,3-propane sultone in step S3 is 1:(2-2.4).
8. A linear wide range hematology analyzer reagent according to claim 1, characterized in that: The preparation method of the stabilizer comprises the following steps: Add 1,3-benzothiazole-2-carbonyl chloride and tetrahydrofuran to a reaction kettle, stir to dissolve, add triethylamine, pass inert gas, stir for 10-20 minutes, add 2-phenylethanethiol dropwise in an ice-water bath at -4-2°C, heat to 50-60°C, react for 5-6 hours, extract with ethyl acetate to separate the layers, take the organic phase, dry it with anhydrous sodium sulfate, rotary evaporate, and separate and purify it with a chromatographic column to obtain a stabilizer.
9. A linear wide range hematology analyzer reagent according to claim 8, characterized in that: The molar ratio of the 1,3-benzothiazole-2-carbonyl chloride to 2-phenylethanethiol is 1:(1.6-1.9).
10. A method for preparing the linear wide range hematology analyzer reagent according to any one of claims 1 to 9, characterized in that: The following steps are included: The components of the diluent, hemolytic agent, dye and cleaning solution are mixed and prepared in proportion, and then coarsely filtered, and then ultrafiltered with a filter membrane, and packaged to obtain the hemacytometer reagent.