Aids antibody, syphilis antibody and hepatitis c antibody complex quality control product and preparation method and application thereof

Abstract

The application provides a complex quality control product of HIV antibody, syphilis antibody and hepatitis C antibody and a preparation method and application thereof. The complex quality control product comprises HIV antibody, syphilis antibody and hepatitis C antibody and the following components: a matrix liquid, 1.5-3 g / L Pluronic F68, 0.05-0.15 % v / v ProClin 300, 0.1-1 g / L sodium mycobacterial lipopeptide, 1-10 g / L bovine serum albumin, 1 g / L alanine, 2-5 g / L trehalose, 0.5-1.0 g / L EDTA and 2-5 mmol / L benzamidine; the matrix liquid comprises a buffer and 20-30 % v / v human serum. The application effectively reduces the aggregation and inactivation risk of the antibodies in the freeze-thaw process, can be repeatedly freeze-thawed more than three times, can effectively prevent the degradation of the antibodies under high temperature, and ensures the reliability of the quality control product in the transportation and clinical use process.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of biological testing, in particular to an AIDS antibody, syphilis antibody and hepatitis C antibody complex quality control product and a preparation method and application thereof. BACKGROUND

[0002] Immunological detection of infectious diseases plays an important role in clinical diagnosis, blood transfusion safety and disease prevention and control. In order to ensure the accuracy and reliability of the detection results, the laboratory usually needs to use quality control products containing corresponding markers to monitor the sensitivity, specificity and stability of the detection system. At present, the commercially available infectious disease quality control products are mostly based on human serum or plasma, and a certain concentration of surfactants, preservatives and stabilizers are added to ensure the stability of the contained antigens or antibodies during storage and use. For example, some technical solutions use surfactants (such as Tween), protein stabilizers (such as bovine serum albumin) and sugar substances (such as sucrose) to maintain protein conformation and extend the shelf life of the quality control product. However, the existing infectious disease complex quality control products still have the following problems: (1) freeze-thaw instability: during repeated freeze-thaw processes, the activity of some antibodies decreases significantly, resulting in attenuation of the detection signal. (2) Insufficient thermal stability: when the quality control product is stored at high temperature or under transportation fluctuation conditions, the activity of the infectious disease markers is easily lost. (3) Limitations of the preservative system: although traditional preservatives can inhibit microbial growth, they may affect the activity of antibodies and have potential toxicity to the human body. (4) Insufficient stability of coexisting complex antibodies: the physicochemical properties of anti-HIV (glycoprotein structure), anti-TP (lipoprotein related) and anti-HCV (easy to aggregate) are quite different, and they are prone to many problems in a single liquid phase. During storage and transportation, the quality control product is prone to degradation, resulting in changes in composition and concentration, which affects the reliability of the detection results. Traditional buffers (such as PBS + calf serum) only provide basic protection and cannot solve the problems of freeze-thaw instability, insufficient thermal stability and preservative toxicity mentioned above, and cannot inhibit the interaction between antibodies.

[0003] Therefore, how to construct a complex quality control product that can maintain stability under various storage conditions and also consider antibody activity and detection consistency has become a technical problem that needs to be solved in the field. SUMMARY

[0004] In view of the defects in the prior art, the present application provides an AIDS antibody, syphilis antibody and hepatitis C antibody complex quality control product and a preparation method and application thereof. The present application is a three-item complex quality control product, which can realize quality control of three items at one time.

[0005] The application realizes high stability and high reliability of the infectious disease composite quality control product under the conditions of freeze-thaw cycle, heat stress and long-term storage by optimizing the combination ratio of surfactants, preservatives, stabilizers and chelating agents, and overcomes the problems of insufficient stability, high toxicity of preservatives and poor compatibility of multiple markers in the prior art.

[0006] The application provides a composite quality control product of HIV antibody, syphilis antibody and hepatitis C antibody, which comprises HIV antibody, syphilis antibody and hepatitis C antibody and the following components:

[0007] The matrix liquid, 1.5-3 g / L Pluronic F68, 0.05-0.15% v / v ProClin 300, 0.1-1 g / L sodium iturin, 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;

[0008] The matrix liquid comprises a buffer and 20-30% v / v human serum.

[0009] In the application, Pluronic F68 as a non-ionic surfactant can form a protective layer on the solution-gas interface and the surface of the container wall, reduce the adsorption and denaturation of antibody molecules on the interface, and block the hydrophobic aggregation between antibody molecules through steric hindrance, so that the monomer state and functional activity of the antibody are effectively maintained.

[0010] In the application, sodium iturin with strong interface activity is added, which can reduce the direct contact of proteins with the gas-liquid interface during freeze-thaw or heating, form a protective layer on the solution interface, reduce the risk of protein aggregation and inactivation, and significantly improve the stability of the antibody under repeated freeze-thaw and heat stress conditions. Meanwhile, the surface active property of sodium iturin can provide an auxiliary hydrophobic barrier on the surface of the antibody molecule, and synergistically enhance the interface protection effect of Pluronic F68.

[0011] In the serum matrix, residual endogenous proteases may be activated during freeze-thaw or heating, thereby accelerating the degradation of the antibody. In the application, benzamidine is added to weakly interact with the negatively charged amino acid residues on the surface of the protein, thereby stabilizing the protein structure to some extent, slowing down the conformational loosening and denaturation, and helping to reduce the degradation and inactivation of the antibody under freeze-thaw and heat stress.

[0012] In some embodiments, the bacitracin sodium is 1 g / L, and the formamidine is 3 mmol / L; by optimizing the dosages of the two, the synergistic effect of bacitracin sodium and formamidine is improved, so that the antibody can maintain the native conformation and avoid enzymatic degradation, thereby realizing the maintenance of a high detection signal intensity under freeze-thaw cycles and high-temperature conditions, and reducing the bias value.

[0013] In some embodiments, the buffer is a Tris buffer; the Tris buffer has a low ionic strength, can reduce the salting-out effect and metal ion-induced aggregation, and is conducive to maintaining the monomer state and long-term uniformity of the antibody. In addition, Tris has good compatibility with trehalose, BSA, EDTA, and ProClin 300 and formamidine, and no precipitation or reaction occurs.

[0014] In some embodiments, the target levels of the HIV antibody, the syphilis antibody, and the hepatitis C antibody are a detection signal COI = 2-5. COI (Cut Off Index) is the threshold for the detection system to determine positive / negative. The target levels of the HIV antibody, the syphilis antibody, and the hepatitis C antibody are set to COI = 2-5 in the present application, which can ensure that the detection result is stably positive, avoid detection interference caused by excessively high signals, and more sensitively reflect the performance fluctuation of the detection system, thereby realizing the scientificity and practicality of the quality control product.

[0015] In some embodiments, the composite quality control product is a liquid quality control product. The liquid quality control product is more prone to inactivation than the freeze-dried quality control product, because the antibody and other proteins are in a solution state for a long time and are greatly affected by enzymatic degradation, temperature fluctuations, microbial contamination, and the like. The stabilizer formula of the present application can effectively solve the problems of aggregation, degradation, and contamination of the liquid quality control product during long-term storage through the synergistic effect of the components, thereby enabling the liquid quality control product to have stability comparable to or even better than that of freeze-dried products.

[0016] In some embodiments, the pH of the composite quality control product is 7.3-7.5. The pH of the composite quality control product is controlled in the range of 7.3-7.5 in the present application, which can maintain the conformational stability of the antibody, synergistically inhibit enzymatic degradation, take into account the effects of the stabilizers, and avoid interference with the detection system, thereby significantly improving the overall stability and detection consistency of the liquid composite quality control product.

[0017] The present application also provides a preparation method of the composite quality control product, comprising the following steps:

[0018] S1: preparing a base solution, adding Pluronic F68, ProClin 300, bacitracin sodium, bovine serum albumin, alanine, trehalose, EDTA, and formamidine to obtain solution 1;

[0019] S2: adding HIV antibody, syphilis antibody and hepatitis C antibody in the solution 1 in S1 to obtain the infectious disease marker composite quality control product.

[0020] The application further provides application of the composite quality control product in preparation of an infectious disease marker detection kit.

[0021] Compared with the prior art, the application achieves the following technical effects:

[0022] (1) The composite quality control product effectively reduces the risk of aggregation and inactivation of the antibodies in the freeze-thaw process, can be repeatedly frozen and thawed four times or more, has a deviation of no more than 10% when stored at 2-8 DEG C for more than 30 days after opening, and can effectively prevent degradation of the antibodies at high temperatures, thereby ensuring the reliability of the quality control product in the transportation and clinical use process.

[0023] (2) The application can effectively inhibit the growth of microorganisms, thereby ensuring the safety and stability of the quality control product in long-term use after opening.

[0024] (3) The composite quality control product can be used for immunoblotting, enzyme-linked immunoassay, and chemiluminescence immunoassay, has strong adaptability, and can meet the clinical quality control needs of different detection platforms.

[0025] (4) The composite quality control product uses inactivated raw materials and accessories in the preparation process, thereby eliminating the hazards of various potential pathogenic microorganisms. The quality control product is in liquid form, has a storage condition of-15 DEG C or below, and has a time of 24 months. The quality control product can be used for quality control of the detection processes of the three antibodies at the same time, provides accurate basis for the diagnosis of clinical diseases, has good uniformity and stability, can meet the detection needs of infectious disease markers on the market, reduces clinical operation, and saves cost. DETAILED DESCRIPTION

[0026] In order for those skilled in the art to better understand the application, the technical solutions in the embodiments of the application will be described clearly and completely below. Obviously, the described embodiments are only a part of the embodiments of the application, rather than all the embodiments of the application. Based on the embodiments in the application, all other embodiments obtained by those skilled in the art without creative labor should belong to the protection scope of the application.

[0027] The application provides a formula of an HIV antibody, syphilis antibody and hepatitis C antibody composite quality control product stabilizer. The three infectious disease antibodies include: human immunodeficiency virus antibody (Anti-HIV), hepatitis C virus antibody (Anti-HCV) and syphilis spirochete antibody (Anti-TP).

[0028] The present application relates to a kind of multi-project composite quality control product, to realize the quality control of multiple infectious disease projects by one experiment.The quality control product can meet the quality control needs of mainstream instrument and reagent manufacturer (such as Roche, Abbott, Shenzhen Mai Rui, Yaguilong, Mike biology, etc.) in infectious disease detection system.The composite quality control product has good clinical practicability, and is convenient for promotion and development.

[0029] The infectious disease marker composite quality control product of the present application includes the following steps:

[0030] The preparation of the composite quality control product includes the following steps:

[0031] Matrix pretreatment: 20-30% (v / v) human serum is sterilized by 0.22 μm filter membrane, 25 mM Tris buffer (pH 7.4) is added to a total volume of 70-80%, and the pH is adjusted to 7.4±0.1.

[0032] Stabilizer addition: Pluronic F68 (1.5-3 g / L), sodium subtilisin 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), alanine (1 g / L) are sequentially dissolved; ProClin 300 (0.05-0.15% v / v) and benzalkonium (2-5 mmol / L) are added, and the pH is adjusted to 7.4±0.1 after constant volume adjustment; 0.22 μm filter membrane sterilization; and then placed at 2-8℃ for standby.

[0033] Antibody complexing and sub-packaging: Anti-HIV / Anti-TP / Anti-HCV is added to the mixed solution, and the target titer (weak positive: COI=2-5) is adjusted by mixing; sub-packaging, and stored at -20℃.

[0034] Different preparation examples are shown in Table 1:

[0035] Table 1

[0036]

[0037] Preparation Example 1

[0038] Specific preparation scheme:

[0039] Matrix pretreatment: 25% (v / v) human serum is sterilized by 0.22 μm filter membrane, 25 mM Tris buffer (pH 7.4) is added to a total volume of 70-80%, and the pH is adjusted to 7.4±0.1.

[0040] Stabilizer addition: Dissolve Pluronic F68 2 g / L, Mycosubtilin Sodium 0.5 g / L, BSA (Bovine Serum Albumin) 5 g / L, Trehalose 2.5 g / L, EDTA 0.5 g / L, Alanine 1 g / L, respectively, add ProClin 300 0.10% v / v and Benzenemethylamidine 3 mmol / L, then adjust the volume to the final volume and the pH to 7.4±0.1; sterilize with 0.22 μm filter membrane; then store at 2-8℃ for standby.

[0041] Antibody complexing and sub-packaging: Add Anti-HIV / Anti-TP / Anti-HCV to the mixed solution, mix and adjust to the target potency of three analytes COI=3.0; sub-package, store at -20℃.

[0042] Preparation Example 2

[0043] Specific preparation scheme:

[0044] Matrix pretreatment: Sterilize 20% (v / v) human serum with 0.22 μm filter membrane; add 25 mM Tris buffer (pH 7.4) to a total volume of 70-80%, mix well with magnetic stirring, and adjust the pH to 7.4±0.1.

[0045] Stabilizer addition: Dissolve Pluronic F68 1.5 g / L, Mycosubtilin Sodium 0.1 g / L, BSA 1 g / L, Trehalose 5.0 g / L, EDTA 1.0 g / L, Alanine 1.0 g / L, respectively; add ProClin 300 0.15% v / v and Benzenemethylamidine 5 mmol / L, then adjust the volume to the final volume and the pH to 7.4±0.1; sterilize with 0.22 μm filter membrane; then store at 2-8℃ for standby.

[0046] Antibody complexing and sub-packaging: Add Anti-HIV / Anti-TP / Anti-HCV to the mixed solution, mix and adjust to the target potency of three analytes COI=3.0; sub-package, store at -20℃.

[0047] Preparation Example 3

[0048] Specific preparation scheme:

[0049] Matrix pretreatment: Sterilize 30% (v / v) human serum with 0.22 μm filter membrane; add 25 mM Tris buffer (pH 7.4) to a total volume of 70-80%, mix well with magnetic stirring, and adjust the pH to 7.4±0.1.

[0050] Stabilizer addition: Dissolve Pluronic F68 3.0 g / L, BSA 1 g / L, sucrose 1 g / L, EDTA 0.5 g / L, NaN3 1.0 g / L in sequence; adjust pH to 7.4±0.1 after constant volume; sterilize with 0.22 μm filter; store at 2-8 °C for standby.

[0051] Antibody complexing and sub-packaging: Add Anti-HIV / Anti-TP / Anti-HCV to the mixture, mix and adjust to the target potency of three analytes to COI=3.0; sub-package, store at -20 °C.

[0052] Preparation Example 4

[0053] Specific preparation scheme:

[0054] Matrix pretreatment: Sterilize 25% (v / v) bovine serum with 0.22 μm filter; add 25 mM Tris buffer (pH 7.4) to a total volume of 70-80%, mix well with magnetic stirring, and adjust pH to 7.4±0.1.

[0055] Stabilizer addition: Dissolve TW20 1.0% v / v, BSA 10 g / L, sucrose 1 g / L, EDTA 0.5 g / L, NaN3 1.0 g / L in sequence; adjust pH to 7.4±0.1 after constant volume; sterilize with 0.22 μm filter; store at 2-8 °C for standby.

[0056] Antibody complexing and sub-packaging: Add Anti-HIV / Anti-TP / Anti-HCV to the mixture, mix and adjust to the target potency of three analytes to COI=3.0; sub-package, store at -20 °C.

[0057] Preparation Example 5

[0058] Specific preparation scheme:

[0059] Matrix pretreatment: Sterilize 25% (v / v) bovine serum with 0.22 μm filter; add 25 mM Tris buffer (pH 7.4) to a total volume of 70-80%, mix well with magnetic stirring, and adjust pH to 7.4±0.1.

[0060] Stabilizer addition: Dissolve Pluronic F68 3.0 g / L, BSA 1 g / L, sucrose 1 g / L, EDTA 0.5 g / L, NaN3 1.0 g / L in sequence; adjust pH to 7.4±0.1 after constant volume; sterilize with 0.22 μm filter; store at 2-8 °C for standby.

[0061] Antibody complexing and aliquoting: Anti-HIV / Anti-TP / Anti-HCV was added to the mixture to the target potency COI = 3.0; aliquoted and stored at -20°C.

[0062] Preparation Example 6

[0063] Specific preparation scheme:

[0064] Matrix pretreatment: 25% (v / v) human serum was sterilized by 0.22 μιη filter membrane; 25 mM Tris buffer (pH 7.4) was added to a total volume of 70-80%, and the mixture was stirred by magnetic stirring, and the pH was adjusted to 7.4±0.1.

[0065] Stabilizer addition: 0.5 g / L of iturin sodium, 5 g / L of BSA, 2.5 g / L of trehalose, 0.5 g / L of EDTA, and 1 g / L of alanine were sequentially dissolved, 0.10% v / v of ProClin 300 and 3 mmol / L of benzalkonium were added, and the pH was adjusted to 7.4±0.1 after constant volume adjustment; sterilized by 0.22 μιη filter membrane; and stored at 2-8°C for standby.

[0066] Antibody complexing and aliquoting: Anti-HIV / Anti-TP / Anti-HCV was added to the mixture to the target potency COI = 3.0; aliquoted and stored at -20°C.

[0067] Preparation Example 7

[0068] Specific preparation scheme:

[0069] Matrix pretreatment: 25% (v / v) human serum was sterilized by 0.22 μιη filter membrane; 25 mM Tris buffer (pH 7.4) was added to a total volume of 70-80%, and the mixture was stirred by magnetic stirring, and the pH was adjusted to 7.4±0.1.

[0070] Stabilizer addition: 2 g / L of Pluronic F68, 5 g / L of BSA, 2.5 g / L of trehalose, 0.5 g / L of EDTA, and 1 g / L of alanine were sequentially dissolved, 0.10% v / v of ProClin 300 and 3 mmol / L of benzalkonium were added, and the pH was adjusted to 7.4±0.1 after constant volume adjustment; sterilized by 0.22 μιη filter membrane; and stored at 2-8°C for standby.

[0071] Antibody complexing and aliquoting: Anti-HIV / Anti-TP / Anti-HCV was added to the mixture to the target potency COI = 3.0; aliquoted and stored at -20°C.

[0072] The products produced in the production step of Preparation Examples 1 to 7 were subjected to performance verification, and the following experiments were performed.

[0073] Preparation Example 8

[0074] Specific preparation scheme:

[0075] Matrix pretreatment: 25% (v / v) human serum was sterilized by 0.22 μm filter membrane, 25 mM Tris buffer (pH 7.4) was added to a total volume of 70-80%, and the mixture was stirred by magnetic stirring, and the pH was adjusted to 7.4±0.1.

[0076] Stabilizer addition: BSA 5 g / L, trehalose 2.5 g / L, EDTA 0.5 g / L, alanine 1 g / L were sequentially dissolved, ProClin 300 0.10% v / v and benzamidine 3 mmol / L were added, and the pH was adjusted to 7.4±0.1 after constant volume adjustment; 0.22 μm filter membrane sterilization; and then stored at 2-8°C for standby use.

[0077] Antibody complexing and sub-packaging: Anti-HIV / Anti-TP / Anti-HCV was added to the mixed solution, and the mixture was adjusted to a target titer of three analytes COI=3.0; sub-packaged, and stored at -20°C.

[0078] Preparation Example 9

[0079] Specific preparation scheme:

[0080] Matrix pretreatment: 25% (v / v) human serum was sterilized by 0.22 μm filter membrane, 25 mM Tris buffer (pH 7.4) was added to a total volume of 70-80%, and the mixture was stirred by magnetic stirring, and the pH was adjusted to 7.4±0.1.

[0081] Stabilizer addition: Pluronic F68 1.5 g / L, sodium subtilisin lipopeptide 1.0 g / L, BSA 5 g / L, trehalose 2.5 g / L, EDTA 0.5 g / L, alanine 1 g / L were sequentially dissolved, ProClin 300 0.10% v / v and benzamidine 3 mmol / L were added, and the pH was adjusted to 7.4±0.1 after constant volume adjustment; 0.22 μm filter membrane sterilization; and then stored at 2-8°C for standby use.

[0082] Antibody complexing and sub-packaging: Anti-HIV / Anti-TP / Anti-HCV was added to the mixed solution, and the mixture was adjusted to a target titer of three analytes COI=3.0; sub-packaged, and stored at -20°C.

[0083] Preparation Example 10

[0084] Specific preparation scheme:

[0085] Matrix pretreatment: 25% (v / v) human serum was sterilized by 0.22 μm filter membrane, added to 25 mM Tris buffer (pH 7.4) to a total volume of 70-80%, mixed evenly by magnetic stirring, and adjusted to pH 7.4±0.1.

[0086] Stabilizer addition: Pluronic F68 3.0 g / L, sodium mycobacterial lipopeptide 0.1 g / L, BSA 5 g / L, trehalose 2.5 g / L, EDTA 0.5 g / L, alanine 1 g / L were sequentially dissolved, added with ProClin 300 0.10% v / v and benzamidine 3 mmol / L, and then adjusted to volume and pH 7.4±0.1; sterilized by 0.22 μm filter membrane; and then placed at 2-8°C for standby.

[0087] Antibody complexing and sub-packaging: Anti-HIV / Anti-TP / Anti-HCV was added to the mixed solution, mixed and adjusted to a target titer of three analytes COI=3.0; sub-packaged, and stored at -20°C.

[0088] Test Example 1 Uniformity Test

[0089] Examples 1-10 were tested continuously for 10 times by taking one bottle each time, and the prepared quality control samples were continuously detected, the mean value of the detection values between bottles and within bottles, the standard deviation between bottles and within bottles, and the coefficient of variation between bottles and within bottles were calculated. The CV between bottles and within bottles is less than 8%, indicating good uniformity.

[0090] Table 2 Uniformity data summary of Examples 1-10

[0091]

[0092] The results in Table 2 show that the CV between bottles and within bottles of the three antibodies in Examples 1, 2, 3, 9, and 10 is less than 8%, among which Example 1 is the best; the CV within bottles of Anti-HCV in Examples 4, 5, 6, and 7 is greater than 8%; the CV between bottles and within bottles of the three analytes in Example 8 is greater than 8%, indicating that the formula of the application exhibits better dispersity and uniformity, and the detection results are more stable, and the uniformity and dispersity effect of the quality control sample are excellent.

[0093] Test Example 2 Open-bottle room temperature stability evaluation

[0094] After reconstituting the complex quality control samples of Examples 1-10, the antibody markers were tested at 0H, 8H, 24H, 2D, and 3D under room temperature conditions, repeated testing 3 times, the average value was calculated, and the deviation (%) of each time from 0H was calculated. The deviation is within 10%, indicating good room temperature stability.

[0095] Table 3 Room temperature stability data summary of Examples 1-10

[0096]

[0097] The results in Table 3 show that the test deviations of the three antibodies in Examples 1, 2, 3, 9, and 10 at each point under room temperature conditions are within 10%, and good stability is maintained; the test deviations of the three analytes in Examples 4, 5, and 6 under room temperature conditions for 1 day are less than -10%, among which the short-term stability of Example 8 is the worst. This indicates that the stabilizer formula of the application can effectively delay the decay of antibody activity, and still maintain good detection performance under room temperature conditions.

[0098] Test Example 3 Stability at 2-8°C after opening

[0099] After reconstituting the complex quality control samples of Examples 1-10, the antibody marker values were tested under 2-8°C conditions at 0D, 3D, 7D, 10D, 14D, 21D, and 28D, and the test was repeated 3 times to calculate the average value and the deviation (%) of each time from the 0D. A deviation within 10% indicates good stability at 2-8°C.

[0100] Table 4 Stability data summary of Examples 1-10 at 2-8°C after opening

[0101]

[0102] In Table 4, the test deviations of the three antibodies in Examples 1, 2, 3, 9, and 10 at each point under 2-8°C conditions are within 10%; the test deviations of the three analytes in Examples 4, 5, 6, 7, and 8 under 2-8°C conditions for 14 days are greater than 10%, among which the stability of Example 8 is the worst. This indicates that the complex system of the application has good long-term storage performance under 2-8°C conditions.

[0103] Test Example 4 Stability of freeze-thaw cycles

[0104] After reconstituting the complex quality control samples of Examples 1-10, the antibody marker values were tested after thawing, and the test was repeated 3 times to calculate the average value and the deviation (%) of each time from the 0th time. A deviation within 10% indicates good freeze-thaw cycle stability.

[0105] Table 5 Stability test data summary of freeze-thaw cycles

[0106]

[0107] In Table 5, Examples 1, 2, 3, 9, and 10 can be freeze-thawed at least 4 times, indicating that the quality control product of the present application can maintain the integrity and detection activity of the antibody after repeated freeze-thawing, and has excellent freeze-thawing stability. Among them, Example 1 has a deviation of each analyte raw material of less than 5% after freeze-thawing 4 times, indicating that the component formula of Example 1 is optimal. In Examples 4-8, the deviation of each analyte raw material is greater than 10% after freeze-thawing 3 times, and the freeze-thawing stability is poor.

[0108] Test Example 5 Thermal stability evaluation

[0109] After reconstituting the composite quality control products of Examples 1-10, the antibody marker values were determined at 37°C on day 0, day 3, day 7, day 10, and day 14, respectively, and the average value was calculated, and the deviation (%) of each day from day 0 was calculated. The deviation is within 10%, indicating good thermal stability. The results are shown in Tables 6-8.

[0110] Table 6

[0111]

[0112] Table 7

[0113]

[0114] Table 8

[0115]

[0116] In Tables 6-8, the deviation of each test point of Examples 1, 2, 3, 9, and 10 compared with 0d is less than 10%, and the deviation value of Example 1 is the lowest, which is 3.44%. It indicates that the stabilizer formula of the present application can effectively enhance the thermal stability of the quality control product, and ensure the reliability of the quality control product under adverse storage conditions.

[0117] The above description is only the preferred embodiment of the present application, and is not intended to limit the present application. Any modification, equivalent replacement, improvement, etc. made within the spirit and principles of the present application shall be included in the protection scope of the present application.

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 lipopeptide, 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 lipopeptide 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 lipopeptide, 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 an 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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