AIDS (Acquired Immune Deficiency Syndrome) antibody, syphilis antibody and hepatitis C antibody composite quality control product as well as preparation method and application thereof

Abstract

The invention provides a composite quality control product of an AIDS antibody, a syphilis antibody and a hepatitis C antibody as well as a preparation method and application of the composite quality control product. The composite quality control product comprises an AIDS (Acquired Immune Deficiency Syndrome) antibody, a syphilis antibody, a hepatitis C antibody and the following components: a matrix solution, 1.5 to 3 g / L of Pluronic F68, 0.05 to 0.15% v / v of ProClin 300, 0.1 to 1 g / L of sodium surfactin, 1 to 10 g / L of bovine serum albumin, 1 g / L of alanine, 2 to 5 g / L of trehalose, 0.5 to 1.0 g / L of EDTA (Ethylene Diamine Tetraacetic Acid) and 2 to 5 mmol / L of benzamidine. The matrix liquid comprises a buffer solution and 20-30% v / v human serum. According to the invention, the aggregation and inactivation risk of the antibody in the freezing and thawing process is effectively reduced, the antibody can be repeatedly frozen and thawed for more than three times, the degradation of the antibody at high temperature can be effectively prevented, and the reliability of the quality control product in the transportation and clinical use process is ensured.

Description

Technical Field

[0001] This invention relates to the field of biological testing, and in particular to a composite quality control product containing HIV antibody, syphilis antibody and hepatitis C antibody, its preparation method and application. Background Technology

[0002] Immunological testing of infectious diseases plays an important role in clinical diagnosis, blood transfusion safety, and disease control. To ensure the accuracy and reliability of test results, laboratories usually need to use quality control products containing corresponding markers to monitor the sensitivity, specificity, and stability of the detection system. Currently, commercially available quality control products for infectious diseases mostly use human serum or plasma as a matrix, with a certain concentration of surfactants, preservatives, and stabilizers added to ensure the stability of the antigens or antibodies contained therein during storage and use. For example, some technical solutions use surfactants (such as Tween), protein stabilizers (such as bovine serum albumin), and sugars (such as sucrose) to maintain protein conformation and extend the shelf life of quality control products. However, existing composite quality control products for infectious diseases still have the following problems: (1) Freeze-thaw instability: During repeated freeze-thaw cycles, the activity of some antibodies decreases significantly, leading to attenuation of the detection signal. (2) Insufficient thermal stability: When quality control products are stored under high temperature or fluctuating transportation conditions, the activity of infectious disease markers is easily lost. (3) Limitations of the preservation system: Although traditional preservatives can inhibit microbial growth, they may affect antibody activity and have potential toxicity to the human body. (4) Insufficient coexistence stability of complex antibodies: Anti-HIV (glycoprotein structure), anti-TP (lipoprotein related), and anti-HCV (easily aggregated) have large differences in physicochemical properties, which are prone to degradation in a single liquid phase. Many quality control products are easily degraded during storage and transportation, resulting in changes in composition and concentration, which affects the reliability of the test results. Traditional buffer solutions (such as PBS + fetal bovine serum) only provide basic protection and cannot solve the problems mentioned above, such as freeze-thaw instability, insufficient thermal stability, and toxicity of preservatives, and cannot inhibit the interaction between antibodies.

[0003] Therefore, how to construct a composite quality control product that can maintain stability under various storage conditions while also ensuring antibody activity and detection consistency has become a technical problem that urgently needs to be solved in this field. Summary of the Invention

[0004] To address the shortcomings of existing technologies, this invention proposes a composite quality control product containing HIV antibody, syphilis antibody, and hepatitis C antibody, along with its preparation method and applications. This invention provides a three-item composite quality control product, enabling quality control of all three items in a single experiment.

[0005] This invention achieves high stability and high reliability of composite quality control products for infectious diseases under conditions such as freeze-thaw cycles, heat stress, and long-term storage by optimizing the combination ratio of surfactants, preservatives, stabilizers, and chelating agents. It overcomes the problems of insufficient stability, high toxicity of preservatives, and poor compatibility of multiple markers in the prior art.

[0006] This invention provides a composite quality control product containing HIV antibody, syphilis antibody, and hepatitis C antibody, comprising HIV antibody, syphilis antibody, and hepatitis C antibody, and the following components: Matrix solution, 1.5~3 g / L Pluronic F68, 0.05~0.15% v / v ProClin 300, 0.1~1 g / L sodium subtilisin, 1~10 g / L bovine serum albumin, 1 g / L alanine, 2~5 g / L trehalose, 0.5~1.0 g / L EDTA, 2~5 mmol / L benzomidine; The matrix solution contains a buffer solution and 20–30% v / v human serum.

[0007] In this invention, Pluronic F68, as a nonionic surfactant, can form a protective layer at the solution-gas interface and on the container wall surface, reducing the adsorption and denaturation of antibody molecules at the interface. Simultaneously, it blocks the hydrophobic aggregation between antibody molecules through steric hindrance, thereby effectively maintaining the monomeric state and functional activity of the antibody.

[0008] This invention, by adding sodium subtilis lipopeptide, which has strong interfacial activity, reduces direct contact between proteins and the gas-liquid interface during freeze-thaw or heating processes, forming a protective layer at the solution interface. This reduces the risk of protein aggregation and inactivation, significantly improving antibody stability under repeated freeze-thaw cycles and heat stress. Simultaneously, its surface activity provides an auxiliary hydrophobic barrier on the antibody molecule surface, synergistically enhancing the interfacial protective effect of Pluronic F68.

[0009] In the serum matrix, residual endogenous proteases may be activated during freeze-thaw cycles or heating, thereby accelerating antibody degradation. This invention addresses this by adding benzalkonium chloride, which interacts weakly with negatively charged amino acid residues on the protein surface, thus stabilizing the protein structure to some extent, slowing conformational loosening and denaturation, and helping to reduce antibody degradation and inactivation under freeze-thaw cycles and heat stress.

[0010] In some embodiments, the sodium subtilis lipopeptide is 1 g / L and the benzalkonium chloride is 3 mmol / L. By optimizing the dosage of the two, the present invention enhances the synergistic effect of sodium subtilis lipopeptide and benzalkonium chloride, so that the antibody can maintain its native conformation and avoid enzymatic degradation, thereby achieving a high detection signal intensity under freeze-thaw cycles and high temperature conditions and reducing the deviation value.

[0011] In some embodiments, the buffer solution is a Tris buffer; the low ionic strength of the Tris buffer reduces salting-out effects and metal ion-induced aggregation, which is beneficial for maintaining the monomeric state and long-term homogeneity of the antibody. Furthermore, Tris exhibits good compatibility with trehalose, BSA, EDTA, ProClin 300, and benzalkonium chloride, without precipitation or reaction.

[0012] In some embodiments, the target levels for HIV antibodies, syphilis antibodies, and hepatitis C antibodies are set at a detection signal COI of 2-5. COI (Cut Off Index) is the threshold for the detection system to determine a positive or negative result. This invention sets the target levels for HIV antibodies, syphilis antibodies, and hepatitis C antibodies at COI = 2-5, which ensures stable positive results, avoids detection interference caused by excessively high signals, and more sensitively reflects performance fluctuations in the detection system, thereby achieving both scientific rigor and practicality in quality control products.

[0013] In some embodiments, the composite quality control product is a liquid quality control product. Liquid quality control products are more prone to inactivation than lyophilized quality control products because antibodies and other proteins are in a solution state for extended periods, making them more susceptible to enzyme degradation, temperature fluctuations, and microbial contamination. The stabilizer formulation of this invention, through the synergistic effect of its components, effectively solves the problems of easy aggregation, degradation, and contamination of liquid quality control products during long-term storage, thereby enabling the liquid quality control product to possess stability comparable to or even superior to that of lyophilized products.

[0014] In some embodiments, the pH of the composite quality control is 7.3 to 7.5. This invention controls the pH of the composite quality control within the range of 7.3 to 7.5, which maintains the conformational stability of the antibody, synergistically inhibits enzyme degradation, balances the effects of each stabilizer, and avoids interference with the detection system, thereby significantly improving the overall stability and detection consistency of the liquid composite quality control.

[0015] The present invention also provides a method for preparing the composite quality control product, comprising the following steps: S1: Prepare the matrix solution by adding Pluronic F68, ProClin 300, sodium subtilis lipopeptide, bovine serum albumin, alanine, trehalose, EDTA, and benzalkonium chloride to obtain solution 1; S2: Add HIV antibody, syphilis antibody and hepatitis C antibody to solution 1 described in S1 to obtain the composite quality control product of the infectious disease marker.

[0016] The present invention also provides the application of the aforementioned composite quality control material in the preparation of a reagent kit for detecting biomarkers of infectious diseases.

[0017] In summary, compared with the prior art, the present invention achieves the following technical effects: (1) The composite quality control product of the present invention effectively reduces the risk of antibody aggregation and inactivation during the freeze-thaw process, and can be repeatedly frozen and thawed four times or more; when stored at 2~8℃ after opening, the deviation is not higher than 10% for more than 30 days; it can effectively prevent antibody degradation at high temperature, and ensure the reliability of the quality control product during transportation and clinical use.

[0018] (2) The present invention can effectively inhibit the growth of microorganisms and ensure the safety and stability of the quality control products after long-term use after opening.

[0019] (3) The composite quality control product of the present invention can be used in immunoblotting, enzyme-linked immunosorbent assay (ELISA), and chemiluminescence immunoassay (CIA). It has strong adaptability and can meet the clinical quality control needs of different detection platforms.

[0020] (4) The composite quality control product of the present invention uses inactivated raw materials and excipients in its preparation process, eliminating the hazards of various potential pathogenic microorganisms. The quality control product is in liquid form and can be stored at -15°C or below for 24 months. It can not only be used for quality control of these three antibody detection processes simultaneously, providing accurate basis for the diagnosis of clinical diseases, but also has good uniformity and stability, which can meet the detection needs of infectious disease markers in the market, reduce clinical operations, and save costs. Detailed Implementation

[0021] To enable those skilled in the art to better understand the present invention, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort should fall within the scope of protection of the present invention.

[0022] This invention provides a formulation for a composite quality control stabilizer containing HIV antibodies, syphilis antibodies, and hepatitis C antibodies. The three infectious disease antibodies include: human immunodeficiency virus antibody (Anti-HIV), hepatitis C virus antibody (Anti-HCV), and Treponema pallidum antibody (Anti-TP).

[0023] This invention relates to a multi-item composite quality control product, designed to achieve quality control of multiple infectious disease items in a single experiment. This quality control product can meet the quality control needs of mainstream instrument and reagent manufacturers (such as Roche, Abbott, Mindray, YHLO, and Maccura Biotechnology) in infectious disease detection systems. This composite quality control product has good clinical applicability and is easy to promote and develop.

[0024] The present invention provides a composite quality control product for infectious disease biomarkers: The preparation of the composite quality control sample includes the following steps: Matrix pretreatment: Sterilize 20-30% (v / v) human serum through a 0.22μm filter membrane, add 25mM Tris buffer (pH 7.4) to 70-80% of the total volume, mix with magnetic stirring, and adjust the pH to 7.4±0.1.

[0025] Stabilizer addition: Dissolve Pluronic F68 (1.5-3 g / L), sodium subtilis lipopeptide (0.1-1.0 g / L), BSA (bovine serum albumin) (1-10 g / L), trehalose (2-5 g / L), EDTA (0.5-1.0 g / L), and alanine (1 g / L) in sequence; add ProClin 300 (0.05-0.15% v / v) and benzoamide (2-5 mmol / L), then adjust the pH to 7.4±0.1 to bring the volume to a final volume; sterilize with a 0.22 μm filter membrane; then store at 2-8℃ for later use.

[0026] Antibody complexation and aliquoting: Add Anti-HIV / Anti-TP / Anti-HCV to the mixture and mix until the target titer is reached (weak positive: COI=2-5); aliquot and store at -20℃.

[0027] The formulations for different preparation examples are shown in Table 1: Table 1

[0028] Preparation Example 1 Specific preparation method: Matrix pretreatment: 25% (v / v) human serum was sterilized through a 0.22 μm filter membrane, and 25 mM Tris buffer (pH 7.4) was added to 70-80% of the total volume. The mixture was magnetically stirred and the pH was adjusted to 7.4 ± 0.1.

[0029] Stabilizer addition: Dissolve Pluronic F68 2g / L, BSA (bovine serum albumin) 0.5g / L, trehalose 2.5g / L, EDTA 0.5g / L, and alanine 1g / L sequentially. Add ProClin 300 0.10% v / v and benzoamide 3mmol / L, then adjust the pH to 7.4±0.1. Sterilize with a 0.22μm filter membrane and store at 2-8℃ for later use.

[0030] Antibody compounding and dispensing: Add Anti-HIV / Anti-TP / Anti-HCV to the mixture and mix until the target titer of the three analytes is 3.0; dispense and store at -20℃.

[0031] Preparation Example 2 Specific preparation method: Matrix pretreatment: Sterilize 20% (v / v) human serum through a 0.22 μm filter membrane; add 25 mM Tris buffer (pH 7.4) to 70-80% of the total volume, mix with magnetic stirring, and adjust the pH to 7.4 ± 0.1.

[0032] Stabilizer addition: Dissolve Pluronic F68 1.5 g / L, BSA 1 g / L, trehalose 5.0 g / L, EDTA 1.0 g / L, and alanine 1.0 g / L sequentially; add ProClin 300 0.15% v / v and benzoamide 5 mmol / L, then adjust the pH to 7.4 ± 0.1; sterilize with a 0.22 μm filter membrane; then store at 2-8℃ for later use.

[0033] Antibody compounding and dispensing: Add Anti-HIV / Anti-TP / Anti-HCV to the mixture and mix until the target titer of the three analytes is 3.0; dispense and store at -20℃.

[0034] Preparation Example 3 Specific preparation method: Matrix pretreatment: Sterilize 30% (v / v) human serum through a 0.22 μm filter membrane; add 25 mM Tris buffer (pH 7.4) to 70-80% of the total volume, mix with magnetic stirring, and adjust the pH to 7.4 ± 0.1.

[0035] Stabilizer addition: Dissolve Pluronic F68 3.0 g / L, BSA 1 g / L, trehalose 2.0 g / L, EDTA 0.5 g / L, and alanine 1 g / L sequentially; add ProClin 300 0.05% v / v and benzoamide 2 mmol / L, then adjust the pH to 7.4 ± 0.1; sterilize with a 0.22 μm filter membrane; then store at 2-8℃ for later use.

[0036] Antibody complexation and aliquoting: Add Anti-HIV / Anti-TP / Anti-HCV to the mixture and mix until the three analytes reach the target titer COI=3.0; aliquot and store at -20℃.

[0037] Preparation Example 4 Specific preparation method: Matrix pretreatment: Sterilize 25% (v / v) fetal serum through a 0.22 μm filter membrane; add 25 mM Tris buffer (pH 7.4) to 70-80% of the total volume, mix with magnetic stirring, and adjust the pH to 7.4 ± 0.1.

[0038] Stabilizer addition: Dissolve TW20 1.0% v / v, BSA 10g / L, sucrose 1g / L, EDTA 0.5g / L, and NaN 3 1.0g / L in sequence, then adjust the pH to 7.4±0.1; sterilize with a 0.22μm filter membrane; then store at 2-8℃ for later use.

[0039] Antibody complexation and aliquoting: Add Anti-HIV / Anti-TP / Anti-HCV to the mixture and mix until the three analytes reach the target titer COI=3.0; aliquot and store at -20℃.

[0040] Preparation Example 5 Specific preparation method: Matrix pretreatment: 25% (v / v) human serum was sterilized by passing it through a 0.22 μm filter membrane; 25 mM Tris buffer (pH 7.4) was added to 70-80% of the total volume, and the mixture was magnetically stirred to adjust the pH to 7.4 ± 0.1.

[0041] Stabilizer addition: Dissolve Pluronic F68 2.0 g / L, BSA 5 g / L, trehalose 2.5 g / L, EDTA 0.5 g / L, and alanine 1 g / L sequentially; add ProClin 300 0.05% v / v and benzoamide 3 mmol / L, then adjust the pH to 7.4 ± 0.1; sterilize with a 0.22 μm filter membrane; then store at 2-8℃ for later use.

[0042] Antibody compounding and dispensing: Add Anti-HIV / Anti-TP / Anti-HCV to the mixture until the target titer is 3.0; dispense and store at -20°C.

[0043] Preparation Example 6 Specific preparation method: Matrix pretreatment: 25% (v / v) human serum was sterilized by passing it through a 0.22 μm filter membrane; 25 mM Tris buffer (pH 7.4) was added to 70-80% of the total volume, and the mixture was magnetically stirred to adjust the pH to 7.4 ± 0.1.

[0044] Stabilizer addition: Dissolve 0.5 g / L of sodium subtilis lipopeptide, 5 g / L of BSA, 2.5 g / L of trehalose, 0.5 g / L of EDTA, and 1 g / L of alanine in sequence. Add ProClin 300 0.10% v / v and benzoamide 3 mmol / L, then adjust the pH to 7.4 ± 0.1. Sterilize with a 0.22 μm filter membrane and store at 2-8℃ for later use.

[0045] Antibody complexation and aliquoting: Add Anti-HIV / Anti-TP / Anti-HCV to the mixture and mix until the three analytes reach the target titer COI=3.0; aliquot and store at -20℃.

[0046] Preparation Example 7 Specific preparation method: Matrix pretreatment: 25% (v / v) human serum was sterilized by passing it through a 0.22 μm filter membrane; 25 mM Tris buffer (pH 7.4) was added to 70-80% of the total volume, and the mixture was magnetically stirred to adjust the pH to 7.4 ± 0.1.

[0047] Stabilizer addition: Dissolve Pluronic F68 2g / L, BSA 5g / L, trehalose 2.5g / L, EDTA 0.5g / L, and alanine 1g / L in sequence, then add ProClin 300 0.10% v / v and benzoamide 3mmol / L, then adjust the pH to 7.4±0.1. Sterilize with a 0.22μm filter membrane, and then store at 2-8℃ for later use.

[0048] Antibody complexation and aliquoting: Add Anti-HIV / Anti-TP / Anti-HCV to the mixture and mix until the three analytes reach the target titer COI=3.0; aliquot and store at -20℃.

[0049] The products obtained from the preparation steps of Examples 1 to 7 were subjected to performance verification through the following experiments.

[0050] Preparation Example 8 Specific preparation method: Matrix pretreatment: 25% (v / v) human serum was sterilized through a 0.22 μm filter membrane, and 25 mM Tris buffer (pH 7.4) was added to 70-80% of the total volume. The mixture was magnetically stirred and the pH was adjusted to 7.4 ± 0.1.

[0051] Stabilizer addition: Dissolve BSA 5g / L, trehalose 2.5g / L, EDTA 0.5g / L, and alanine 1g / L sequentially, then add ProClin 300 0.10% v / v and benzoamide 3mmol / L, then adjust the pH to 7.4±0.1. Sterilize with a 0.22μm filter membrane, and then store at 2-8℃ for later use.

[0052] Antibody compounding and dispensing: Add Anti-HIV / Anti-TP / Anti-HCV to the mixture and mix until the target titer of the three analytes is 3.0; dispense and store at -20℃.

[0053] Preparation Example 9 Specific preparation method: Matrix pretreatment: 25% (v / v) human serum was sterilized through a 0.22 μm filter membrane, and 25 mM Tris buffer (pH 7.4) was added to 70-80% of the total volume. The mixture was magnetically stirred and the pH was adjusted to 7.4 ± 0.1.

[0054] Stabilizer addition: Dissolve Pluronic F68 1.5 g / L, BSA 5 g / L, trehalose 2.5 g / L, EDTA 0.5 g / L, and alanine 1 g / L sequentially. Add ProClin 300 0.10% v / v and benzoamide 3 mmol / L, then adjust the pH to 7.4 ± 0.1. Sterilize with a 0.22 μm filter membrane and store at 2-8℃ for later use.

[0055] Antibody compounding and dispensing: Add Anti-HIV / Anti-TP / Anti-HCV to the mixture and mix until the target titer of the three analytes is 3.0; dispense and store at -20℃.

[0056] Preparation Example 10 Specific preparation method: Matrix pretreatment: 25% (v / v) human serum was sterilized through a 0.22 μm filter membrane, and 25 mM Tris buffer (pH 7.4) was added to 70-80% of the total volume. The mixture was magnetically stirred and the pH was adjusted to 7.4 ± 0.1.

[0057] Stabilizer addition: Dissolve Pluronic F68 3.0 g / L, BSA 5 g / L, trehalose 2.5 g / L, EDTA 0.5 g / L, and alanine 1 g / L sequentially. Add ProClin 300 0.10% v / v and benzoamide 3 mmol / L, then adjust the pH to 7.4 ± 0.1. Sterilize with a 0.22 μm filter membrane and store at 2-8℃ for later use.

[0058] Antibody compounding and dispensing: Add Anti-HIV / Anti-TP / Anti-HCV to the mixture and mix until the target titer of the three analytes is 3.0; dispense and store at -20℃.

[0059] Test Example 1: Uniformity Test Examples 1-10 involve taking one bottle of each product and testing it 10 times consecutively, and taking ten bottles of prepared quality control products and testing them continuously. Calculate the mean values ​​of the test results between and within bottles, the standard deviations of the results within and between bottles, and the coefficient of variation (CV) between and within bottles. A CV < 8% indicates good homogeneity.

[0060] Table 2 Summary of Uniformity Data for Examples 1-10

[0061] Table 2 shows that the intra-vial and inter-vial CVs of the three antibodies in Examples 1, 2, 3, 9, and 10 were all <8%, with Example 1 being the best; the intra-vial CVs of Anti-HCV in Examples 4, 5, 6, and 7 were >8%; and the intra-vial and inter-vial CVs of the three analytes in Example 8 were >8%, indicating that the formulation of the present invention exhibits better dispersibility and uniformity, more stable detection results, and excellent uniformity and dispersion of the quality control products.

[0062] Test Example 2: Stability Test at Room Temperature After Opening After reconstituted the composite quality control samples from Examples 1-10, the antibody markers were tested at 0H, 8H, 24H, 2D, and 3D at room temperature. The tests were repeated three times, and the average value and the deviation (%) from 0H at each time point were calculated. A deviation within 10% indicates good room temperature stability.

[0063] Table 3 Summary of room temperature stability data for Examples 1-10

[0064] Table 3 shows that the test deviations of the three antibodies in Examples 1, 2, 3, 9, and 10 at all points under room temperature conditions were within 10%, maintaining good stability. The test deviations of the three analytes in Examples 4, 5, and 6 at room temperature for one day were <-10%, with Example 8 exhibiting the worst short-term stability. This indicates that the stabilizer formulation of the present invention can effectively delay the decay of antibody activity and maintain good detection performance under room temperature conditions.

[0065] Test Example 3: Stability at 2-8°C after opening After reconstituted the composite quality control samples of Examples 1 to 10, the antibody marker values ​​were tested at 0D, 3D, 7D, 10D, 14D, 21D, and 28D at 2-8℃. The tests were repeated 3 times, and the average value and the deviation (%) from 0D at each time point were calculated. A deviation within 10% indicates good stability at 2-8℃.

[0066] Table 4 Summary of stability data for Examples 1-10 at 2-8℃ after opening

[0067] In Table 4, the test deviations of the three antibodies in Examples 1, 2, 3, 9, and 10 at all points under 2-8℃ conditions were within 10%; the test deviations of the three analytes in Examples 4, 5, 6, 7, and 8 at 2-8℃ for 14 days were greater than 10%, with Example 8 showing the worst stability. This indicates that the composite system of the present invention has good long-term storage performance under 2-8℃ conditions.

[0068] Test Example 4: Stability after Freeze-Thaw Cycles After reconstituted the composite quality control samples from Examples 1 to 10, they were thawed and tested separately. The antibody marker values ​​were tested 0, 1, 2, 3, and 4 times. The tests were repeated 3 times, and the average value and the deviation (%) between each test and the 0th test were calculated. A deviation within 10% indicates good freeze-thaw stability.

[0069] Table 5 Summary of freeze-thaw stability test data

[0070] In Table 5, Examples 1, 2, 3, 9, and 10 can be frozen and thawed at least four times, indicating that the quality control products of the present invention can maintain the integrity and detection activity of the antibodies after repeated freeze-thaw cycles, demonstrating excellent freeze-thaw stability. Specifically, in Example 1, after four freeze-thaw cycles, the deviation of each analyte raw material was less than 5%, indicating that the component formulation of Example 1 was optimal. In contrast, in Examples 4-8, after three freeze-thaw cycles, the deviation of each analyte raw material was greater than 10%, indicating poor freeze-thaw stability.

[0071] Test Example 5: Thermal Stability Evaluation After reconstitution of the composite quality control samples (Example 1-10), antibody marker values ​​were measured at 37°C on days 0, 3, 7, 10, and 14. The tests were repeated three times, and the average value and the deviation (%) from day 0 were calculated. A deviation within 10% indicates good thermal stability. The results are shown in Tables 6-8. Table 6

[0072] Table 7

[0073] Table 8

[0074] In Tables 6-8, the deviations of each test point in Examples 1, 2, 3, 9, and 10 compared to 0d are all less than 10%, with Example 1 showing the lowest deviation value at 3.44%. This indicates that the stabilizer formulation of the present invention can effectively enhance the thermal stability of the quality control products, ensuring their reliability even under adverse storage conditions.

[0075] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A complex quality control product of HIV antibody, syphilis antibody and hepatitis C antibody, characterized in that, The infectious disease marker complex quality control product comprises the following components: a matrix solution, 1.5-3 g / L Pluronic F68, 0.05-0.15% v / v ProClin 300, 0.1-1 g / L sodium mycobacterium cell wall extract, 1-10 g / L bovine serum albumin, 1 g / L alanine, 2-5 g / L trehalose, 0.5-1.0 g / L EDTA, 2-5 mmol / L benzamidine; the matrix solution comprises a buffer and 20-30% v / v human serum.

2. The composite quality control of claim 1, wherein, the sodium mycobacterium cell wall extract is 1 g / L, and the benzamidine is 3 mmol / L.

3. The composite quality control of claim 1, wherein, the buffer is a Tris buffer.

4. The composite quality control of claim 1, wherein, the target level of the HIV antibody, the syphilis antibody and the hepatitis C antibody is a detection signal COI=2-5.

5. The composite quality control of claim 1, wherein, the complex quality control product is a liquid quality control product.

6. The composite quality control of claim 1, wherein, the pH of the complex quality control product is 7.3-7.

5.

7. A method for preparing a composite quality control according to any one of claims 1 to 6, characterized in that, The method comprises the following steps: S1: preparing a matrix solution, adding Pluronic F68, ProClin 300, sodium mycobacterium cell wall extract, bovine serum albumin, alanine, trehalose, EDTA and benzamidine to obtain a solution 1; S2: adding HIV antibody, syphilis antibody and hepatitis C antibody to the solution 1 in S1 to obtain the infectious disease marker complex quality control product.

8. Use of the complex quality control product in any one of claims 1-6 in the preparation of an infectious disease marker detection kit.

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