POCT blood glucose quality control product based on PIPES buffer system and preparation method

Abstract

This invention discloses a POCT blood glucose quality control product and its preparation method based on the PIPES buffer system, belonging to the field of in vitro diagnostic point-of-care testing technology. The quality control product consists of the following components: PIPES buffer salts, NaOH, hydrochloric acid, colorimetric reagent, PC300 preservative, Kv500 antibacterial agent, NaCl, glucose, and purified water; the pH value of the quality control product is 7.35~7.45; the quality control product contains no human or animal-derived biological components. This invention uses the PIPES organic buffer system to construct a human serum-like matrix, and is compatible with both GOD and GDH blood glucose meters. Testing on 36 models showed 100% universality; the glucose deviation is only ±4% after 38 months of storage at room temperature (10~35℃), completely eliminating reliance on cold chain logistics.

Description

Technical Field

[0001] This invention belongs to the field of in vitro diagnostic (IVD) point-of-care testing (POCT) technology, specifically relating to a POCT blood glucose quality control product based on the PIPES (piperazine-1,4-diethanesulfonic acid) buffer system and its preparation method. It is applicable to the internal quality control, instrument performance verification and test strip validity verification of portable blood glucose meters and blood glucose test strips in laboratory departments of medical institutions at all levels, community health service centers, physical examination centers, elderly care institutions and home settings. Background Technology

[0002] Diabetes is a prevalent chronic metabolic disease worldwide. According to the International Diabetes Federation (IDF), the number of people with diabetes globally has exceeded 500 million. Point-of-care testing (POCT) blood glucose meters, with their advantages of ease of operation, rapid testing, and small sample volume, have become the core equipment for clinical bedside blood glucose monitoring and home-based blood glucose monitoring for diabetic patients. According to the "Management and Clinical Operation Specifications for Portable Blood Glucose Meters in Medical Institutions (Trial)" (Health Office Medical Administration Document

[2010] No. 209) issued by the National Health Commission, internal quality control must be carried out on blood glucose meters before daily testing. The performance of the quality control products directly determines the accuracy of blood glucose test results and is a key consumable for ensuring the safety of clinical diagnosis and treatment.

[0003] Currently, there are numerous POCT blood glucose meter brands in China, whose detection principles mainly fall into two categories: glucose oxidase (GOD) and glucose dehydrogenase (GDH). These two types of instruments have significantly different requirements for the pH value, ionic strength, osmotic pressure, and tolerance to component interference of the quality control matrix, placing extremely high demands on the universality of the quality control materials. Furthermore, the "Administrative Measures for the Registration and Filing of In Vitro Diagnostic Reagents" (Order No. 48 of the State Administration for Market Regulation) clearly requires IVD reagents to possess good biosafety, batch uniformity, and storage stability.

[0004] Currently available POCT blood glucose control products mainly fall into the following three technical categories: The first category is biologically derived blood matrix quality control products. Chinese invention patent application CN109521201A discloses "a human whole blood matrix quality control product for portable blood glucose meters". This scheme uses human whole blood as matrix, fixes whole blood cells with formaldehyde and glutaraldehyde, and prepares quality control products with three blood glucose concentration levels: high, medium and low. The advantage of this type of product is that the matrix is ​​close to the clinical sample, but it has the following inherent defects: (1) High biosafety risk. Natural blood may carry pathogenic microorganisms such as bacteria, viruses and mycoplasma, which can easily cause cross-infection in the production, use and waste disposal process; (2) Blood contains endogenous glycolytic enzymes, which will accelerate glucose degradation and interfere with the accuracy of the test results; (3) Regulatory compliance risk. According to relevant national regulations, human blood products are prohibited from being privately circulated and traded. Animal serum has large differences in composition between batches, making raw material quality control difficult and product batch consistency difficult to guarantee; (4) It must be stored and transported under refrigeration at 2~8℃ throughout the process. The cold chain cost is high, and remote areas and home users are prone to product failure due to cold chain breakage.

[0005] Chinese invention patent CN109387643B discloses another blood matrix-based blood glucose quality control product scheme, which uses human serum or animal serum as a matrix and adds glucose and conventional stabilizers. This scheme also suffers from the aforementioned issues of biosafety, regulatory compliance, and cold chain dependence, and is only compatible with some whole blood glucose meters, exhibiting significant matrix interference with GDH principle instruments.

[0006] The second category is ordinary inorganic buffer matrix quality control products. Chinese invention patent application CN111856023A discloses "a portable blood glucose quality control product and its preparation method". The method uses a buffer solution composed of disodium hydrogen phosphate and potassium dihydrogen phosphate as the matrix solution, and adds glucose, Proclin300 preservative, neomycin sulfate and carmine pigment. This type of product has no biosafety risks, but its defects are also significant: (1) The buffer capacity of the phosphate buffer system is limited, and pH drift is easy to occur at room temperature. The physicochemical parameters are significantly different from human serum; (2) The phosphate buffer system is not compatible with the reaction system of GOD principle blood glucose meters and cannot be adapted to most GOD principle instruments; (3) The antibacterial effect of the single preservative system is limited, and the shelf life at room temperature is still short, and it cannot achieve long-term storage without cold chain; (4) It can only be adapted to a few brands of blood glucose meters and has insufficient versatility.

[0007] The third category is brand-specific analog matrix quality control products. These products are customized by instrument manufacturers, with formulas specifically adapted to their own models, offering zero versatility. Users need to purchase multiple quality control products from corresponding brands, resulting in high usage and management costs.

[0008] In summary, current technologies lack a universal quality control product that is compatible with both GOD and GDH, the two mainstream enzymatic principles, and most mainstream POCT blood glucose meters on the market; a pure chemical matrix quality control product that completely eliminates biological components, thereby removing biosafety and regulatory compliance risks at the source; and a quality control product that can be stored stably at room temperature for extended periods, completely eliminating reliance on cold chains. Therefore, developing a POCT blood glucose quality control product that combines broad-spectrum versatility, high biosafety, and long-term stability at room temperature has significant clinical application value and market demand. Summary of the Invention

[0009] The purpose of this invention is to address three major industry pain points of existing POCT blood glucose control products: weak versatility, high biosafety risks, and the necessity of cold chain storage. This invention provides a POCT blood glucose control product based on the PIPES buffer system and its preparation method. This invention uses the PIPES organic buffer system to replace the traditional phosphate and Tris buffer systems, constructing a fully chemical matrix with physicochemical parameters simulating human serum, enabling universal compatibility with multiple brands and multi-enzyme blood glucose meters. It contains no human / animal biological components throughout the process, eliminating biosafety and regulatory risks. A two-component antibacterial stabilization system of PC300 and Kv500 is incorporated, achieving long-term stable storage at room temperature (10~35℃). To achieve the above objectives, this invention adopts the following technical solution.

[0010] In a first aspect, this invention provides a POCT blood glucose control product based on a PIPES buffer system. The control product comprises the following components: PIPES buffer salts, NaOH, hydrochloric acid, a colorimetric reagent, PC300 preservative, Kv500 antibacterial agent, NaCl, glucose, and purified water. The pH value of the control product is 7.35–7.45. The control product contains no human or animal-derived biological components. The role of NaOH and hydrochloric acid is to precisely control the pH value of the control product; the amount of NaOH added is typically 0.4–20 g / L, and the amount of hydrochloric acid added is typically 0.5–25 mL / L.

[0011] Further, the concentration of the PIPES buffer salt is 2~40 mmol / L (corresponding to a weighing amount of 0.6~12 g / L). PIPES (piperazine-1,4-diethanesulfonic acid, molecular formula C8H) 18 N2O6S2 (molecular weight 302.37, CAS number 5625-37-6) has an effective buffering range of pH 6.1~7.5, a pKa of 6.8 at 25℃, and a pKa close to physiological pH at 37℃. PIPES has advantages such as chemical stability, non-chelation of metal ions, low ion interference, and small pKa change with temperature. Its buffering range precisely covers the human serum pH range (7.35~7.45), and it is compatible with both GOD and GDH enzymatic reaction systems. It is the core technology foundation for realizing the universality of dual-enzyme blood glucose meters.

[0012] Furthermore, the volume fraction of the PC300 preservative is 0.01%~0.5%, and the volume fraction of the Kv500 antibacterial agent is 0.01%~0.5%. PC300 (ProClin 300) is a broad-spectrum chemical preservative, the main active ingredient of which is isothiazolinone compounds, which have good inhibitory effects on bacteria, fungi, and yeasts. Kv500 is a long-acting antibacterial agent, and when used in combination with PC300, it can produce a synergistic antibacterial effect, significantly broadening the antibacterial spectrum and prolonging the antibacterial effect, which is a key technical means to achieve long-term storage at room temperature.

[0013] Furthermore, the NaCl concentration is 0.01%~5%, used to adjust the osmotic pressure of the quality control sample to 280~320 mOsm / L, which is equivalent to the osmotic pressure of human serum (280~310 mOsm / L). Precise osmotic pressure matching can reduce matrix differences between the quality control sample and clinical samples, improving the accuracy of test results and instrument compatibility.

[0014] Furthermore, the color developer is any one of the water-soluble inert food colorings selected from orange-yellow, lemon yellow, or amaranth, and the mass fraction of the color developer is 0.01% to 0.2%. The color developer is used only for visual identification, making the solution appear uniformly orange-yellow, which facilitates users' intuitive judgment of whether the reagent is turbid, deteriorated, or mispackaged. It does not participate in any biochemical reaction and has no matrix interference with the detection system.

[0015] Furthermore, the glucose concentration is one of three levels: low (2.5 mmol / L), medium (5.6 mmol / L), and high (16.0 mmol / L), corresponding to anhydrous glucose volumes of 0.4504 g / L, 1.0089 g / L, and 2.8826 g / L, respectively. This three-level design covers the entire clinical range of hypoglycemia, normoglycemia, and hyperglycemia, meeting the general design requirements for IVD quality control products and comprehensively validating the blood glucose meter's detection performance across different concentration ranges.

[0016] Secondly, the present invention provides a method for preparing the above-mentioned POCT blood glucose quality control product, comprising the following steps: (1) Container and solvent preparation: Take a clean container, add purified water to 75-85% of the final volume, and stir at room temperature for later use; (2) PIPES dissolution: Weigh out PIPES powder according to the formula, add it to purified water in batches, stir until completely mixed, then add NaOH solid and stir to dissolve to obtain clear basic buffer solution; (3) Preliminary acid-base adjustment: Add hydrochloric acid dropwise, monitor in real time with a precision pH meter, calibrate the pH to 7.35~7.45, and stir to mix well; (4) Addition of functional components: Add color developer, PC300 preservative, Kv500 antibacterial agent and NaCl in sequence while stirring, and then add anhydrous glucose standard and stir until completely dissolved; (5) Make up to volume and mix: Add purified water to make up to the target volume and continue stirring; (6) Filtration and sterilization: Vacuum filtration is performed using a 0.22μm aqueous sterile filter membrane, and the filtrate is collected into a sterile storage bottle; (7) Let it stand and mature: Let it stand at room temperature in a sealed container. Visually inspect the solution to ensure it is uniform, clear and free of turbidity or precipitate. (8) Quantitative dispensing: Dispense into brown light-proof bottles and seal.

[0017] Furthermore, the stirring speed in step (1) is 200~300 r / min; the 0.22μm aqueous sterile filter membrane in step (6) is a polyethersulfone filter membrane.

[0018] This preparation method is completed entirely in a standard clean area, requiring no biosafety level workshop. The process is simple, production costs are low, and the product meets sterility standards. A room-temperature stepwise dissolution process is employed to avoid the degradation of glucose and preservatives caused by high temperatures. 0.22μm membrane filtration is a key quality control step, effectively removing environmental microorganisms and ensuring the product meets microbiological standards.

[0019] Thirdly, the present invention provides the application of the above-mentioned POCT blood glucose quality control product in the internal quality control of POCT blood glucose meters. The quality control product is applicable to portable blood glucose meters based on both glucose oxidase (GOD) and glucose dehydrogenase (GDH) principles, and is used for blood glucose meter performance verification, test strip validity verification, and internal quality control.

[0020] Furthermore, the quality control products are stored and used at room temperature (10~35℃) without the need for cold chain transportation or refrigerated storage, and the shelf life at room temperature is not less than 36 months.

[0021] Compared with the prior art, the present invention has the following beneficial effects: (1) Broad-spectrum compatibility, compatible with most POCT blood glucose meters on the market. This invention uses the PIPES organic buffer system to replace the traditional phosphate and Tris buffer system, precisely adjusting the pH to the standard range of human serum (7.35~7.45), and its physicochemical properties are highly compatible with the two mainstream enzyme detection systems, GOD and GDH. Verified by testing on 36 mainstream POCT blood glucose meters on the market, the universality of this invention reaches 100%, while 6 instruments showed matrix interference errors with traditional human serum matrix control products, and 9 blood glucose meters showed abnormal recognition errors with conventional phosphate buffer control products. This invention eliminates the need for separate brand purchases, significantly reducing usage and management costs.

[0022] (2) The fully chemically synthesized matrix reduces biosafety risks at the source and ensures strong compliance. The formulation of this invention does not contain any human or animal-derived blood / serum / plasma, blood cells, or other biological components, and is prepared entirely using pharmacopoeia-grade and analytical-grade chemical reagents. On the one hand, it eliminates the risk of pathogenic microorganisms and cross-infection at the source, and the waste liquid can be treated as ordinary chemical waste liquid without having to comply with the medical biological waste management regulations; on the other hand, it avoids the regulatory restrictions on the circulation of blood products, ensuring batch uniformity of raw materials and minimal batch-to-batch differences in products, fully complying with the registration compliance requirements for IVD in vitro diagnostic reagents. At the same time, it contains no endogenous glycolytic enzymes, avoiding non-specific glucose degradation and improving detection accuracy.

[0023] (3) A multi-layered synergistic stabilizing system enables long-term storage at room temperature, completely eliminating reliance on cold chain. PIPES buffer salts have a much stronger resistance to pH drift than phosphates; the combination of PC300 and Kv500, two broad-spectrum antibacterial and preservative agents, synergistically inhibits the growth of bacteria and mold at room temperature; the system contains no endogenous degrading enzymes, and the inert components slow down glucose oxidation. After 38 months of continuous storage testing at 10~35℃, the glucose concentration deviation of the product of this invention was only -4%~+4%, the solution properties remained unchanged, and the performance was stable; while traditional human serum matrix quality control products showed rapid glucose degradation, turbidity, and microbial growth after 6 months, becoming completely ineffective; conventional phosphate buffer quality control products showed glucose attenuation of more than 15% after about 12 months of stability. This invention can be stored for a long time at room temperature of 10~35℃ without the need for cold chain transportation and refrigerated storage, making it suitable for homes, primary clinics, outdoor and other scenarios without refrigeration.

[0024] (4) Stable properties, high recognizability, and excellent repeatability of quality control results. The addition of inert orange-yellow as a colorimetric agent results in a uniform solution color, which can be used to visually determine whether the reagent is turbid or deteriorated; the whole components have excellent solubility, and there is no layering or sedimentation during long-term storage. The intra-batch and inter-batch precision meets the standard of GB / T 19634 "General Technical Conditions for Self-Test Blood Glucose Monitoring Systems". The quality control data fluctuates little and the results are reliable. Detailed Implementation

[0025] The technical solution of the present invention will be clearly and completely described below. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of them. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the protection scope of the present invention.

[0026] The raw materials used in the embodiments of this invention are all analytical grade or pharmacopoeia-grade purification reagents: PIPES (piperazine-1,4-diethanesulfonic acid, CAS No. 5625-37-6, purity ≥99%), NaOH (analytical grade), hydrochloric acid (analytical grade, 36%~38%), orange yellow (food grade, water soluble), PC300 (ProClin 300, commercial preservative), Kv500 (commercial long-acting antibacterial agent), NaCl (analytical grade), anhydrous glucose (standard, purity ≥99.5%), and purified water (conductivity ≤18.2MΩ·cm).

[0027] Example 1: Preparation of low-level (2.5 mmol / L) POCT blood glucose control material This embodiment prepares a low-level blood glucose control sample. The PIPES concentration is set at the lower limit of 2 mmol / L (corresponding to a weighing volume of 0.6 g / L), and the pH is set at the lower limit of 7.35. The specific formulation and preparation steps are as follows: Formula (1L system): PIPES 0.6g, NaOH 0.4g, hydrochloric acid 0.5mL, orange yellow 1mL, PC300 0.1mL, Kv500 0.1mL, NaCl 0.1g, anhydrous glucose 0.4504g, and purified water to a final volume of 1L.

[0028] Preparation steps: (1) Take a 1L sterile volumetric flask, add 800mL of purified water, and stir magnetically at 200r / min at room temperature for later use.

[0029] (2) Weigh 0.6g of PIPES powder, add it to purified water in batches, stir for 10min until completely mixed, then add 0.4g of NaOH solid, stir for 15min to dissolve and obtain clear basic buffer solution.

[0030] (3) Add 0.5 mL of hydrochloric acid dropwise, monitor the pH in real time with a precision pH meter, calibrate the pH to 7.35, and stir for 10 min to mix well.

[0031] (4) While stirring, add 1 mL of orange yellow, 0.1 mL of PC300, 0.1 mL of Kv500 and 0.1 g of NaCl in sequence. Stir for 5 min after each addition of a component, then add 0.4504 g of anhydrous glucose standard and stir until completely dissolved.

[0032] (5) Add purified water to bring the volume to 1L and stir continuously for 60min.

[0033] (6) Vacuum filtration was performed using a 0.22μm PES aqueous sterile filter membrane, and the filtrate was collected into a sterile storage bottle.

[0034] (7) After standing at room temperature for 1 hour in a sealed container, visually inspect the solution to ensure it is uniformly orange-yellow, clear, and free of turbidity and precipitate.

[0035] (8) Use an aseptic filling machine to dispense into brown light-proof plastic bottles, 2mL / bottle, and seal immediately after dispensing.

[0036] Performance Testing: The product in this embodiment has a pH of 7.35, an osmotic pressure of 282 mOsm / L, and a uniform orange-yellow clear liquid appearance. It was tested with 10 different brands of POCT blood glucose meters (5 based on GOD and 5 based on GDH principles). The glucose levels ranged from 2.3 to 2.7 mmol / L, with a recovery rate of 92% to 108%. All instruments functioned correctly without any errors.

[0037] Example 2: Preparation of a medium-level (5.6 mmol / L) POCT blood glucose control sample In this embodiment, a medium-level blood glucose control sample was prepared. The PIPES concentration was set at the midpoint of the range, 20 mmol / L (corresponding to a weighing volume of 6 g / L), and the pH was set at the midpoint of the range, 7.40. The specific formula and preparation steps are as follows: Formula (1L system): PIPES 6g, NaOH 4g, hydrochloric acid 4mL, orange yellow 5mL, PC300 1mL, Kv500 1mL, NaCl 9g, anhydrous glucose 1.0089g, and purified water to a final volume of 1L.

[0038] Preparation steps: (1) Take a 1L sterile volumetric flask, add 800mL of purified water, and stir magnetically at 250r / min at room temperature for later use.

[0039] (2) Weigh 6g of PIPES powder, add it to purified water in batches, stir for 15min until completely mixed, then add 4g of NaOH solid, stir for 15min to dissolve and obtain clear basic buffer solution.

[0040] (3) Add 4 mL of hydrochloric acid dropwise, monitor the pH in real time with a precision pH meter, calibrate the pH to 7.40, and stir for 10 min to mix well.

[0041] (4) While stirring, add 5 mL of orange yellow, 1 mL of PC300, 1 mL of Kv500 and 9 g of NaCl in sequence. Stir for 5 min after each addition of a component, then add 1.0089 g of anhydrous glucose standard and stir until completely dissolved.

[0042] (5) Add purified water to bring the volume to 1L and stir continuously for 60min.

[0043] (6) Vacuum filtration was performed using a 0.22μm PES aqueous sterile filter membrane, and the filtrate was collected into a sterile storage bottle.

[0044] (7) Let it stand at room temperature for 1 hour in a sealed container, and then visually inspect it to ensure it passes inspection.

[0045] (8) Dispense into brown light-proof plastic bottles, 3mL / bottle, and seal.

[0046] Performance Testing: The product in this embodiment has a pH of 7.40, an osmotic pressure of 298 mOsm / L, and is a uniform, clear, orange-yellow liquid. It was tested with 36 mainstream POCT blood glucose meters on the market (covering brands such as Roche, Johnson & Johnson, Abbott, Sinocare, Acron, Bayer, and Yuwell, including both GOD and GDH principles). All 36 instruments recognized the glucose normally, achieving 100% compatibility, with a glucose recovery rate ranging from 95% to 105%. After 38 months of continuous storage at 10–35°C, the glucose concentration deviation was -4% to +4%, and the solution properties remained unchanged.

[0047] Example 3: Preparation of high-level (16.0 mmol / L) POCT blood glucose control material This embodiment prepares a high-level blood glucose control product. The PIPES concentration is set at the upper limit of the range of 40 mmol / L (corresponding to a weighing volume of 12 g / L), and the pH is set at the upper limit of the range of 7.45. The specific formula and preparation steps are as follows: Formula (1L system): PIPES 12g, NaOH 20g, hydrochloric acid 25mL, orange yellow 10mL, PC300 5mL, Kv500 5mL, NaCl 50g, anhydrous glucose 2.8826g, and purified water to a final volume of 1L.

[0048] Preparation steps: (1) Take a 1L sterile volumetric flask, add 800mL of purified water, and stir magnetically at 300r / min at room temperature for later use.

[0049] (2) Weigh 12g of PIPES powder, add it to purified water in batches, stir for 20min until completely mixed, then add 20g of NaOH solid, stir for 15min to dissolve and obtain clear basic buffer solution.

[0050] (3) Add 25 mL of hydrochloric acid dropwise, monitor the pH in real time with a precision pH meter, calibrate the pH to 7.45, and stir for 10 min to mix well.

[0051] (4) While stirring, add 10 mL of orange yellow, 5 mL of PC300, 5 mL of Kv500 and 50 g of NaCl in sequence. Stir for 5 min after each addition of a component, then add 2.8826 g of anhydrous glucose standard and stir until completely dissolved.

[0052] (5) Add purified water to bring the volume to 1L and stir continuously for 60min.

[0053] (6) Vacuum filtration was performed using a 0.22μm PES aqueous sterile filter membrane, and the filtrate was collected into a sterile storage bottle.

[0054] (7) Let it stand at room temperature for 1 hour in a sealed container, and then visually inspect it to ensure it passes inspection.

[0055] (8) Dispense into brown light-proof plastic bottles, 5mL / bottle, and seal.

[0056] Performance Testing: The product in this embodiment has a pH of 7.45, an osmotic pressure of 318 mOsm / L, and a uniform, clear, orange-yellow liquid appearance. Tested with 10 different brands of POCT blood glucose meters, the glucose levels ranged from 15.2 to 16.8 mmol / L, with a recovery rate of 95% to 105%. All instruments recognized the glucose levels normally without any errors.

[0057] Example 4: Alternative color developer (tartrazine) This embodiment verifies the alternative colorimetric reagent, using tartrazine instead of orange-yellow, with the remaining component ratios the same as in Example 2. Formulation (1L system): PIPES 6g, NaOH 4g, hydrochloric acid 4mL, tartrazine 5mL, PC300 1mL, Kv500 1mL, NaCl 9g, anhydrous glucose 1.0089g, diluted to 1L with purified water, pH calibrated to 7.40. Preparation method is the same as in Example 2.

[0058] Performance Testing: The product in this embodiment is a uniform lemon-yellow clear liquid with a pH of 7.40 and an osmotic pressure of 298 mOsm / L. Tested on 10 POCT blood glucose meters, the glucose recovery rate was 95%–104%, and all instruments recognized the sample normally. This proves that lemon yellow can be used as an equivalent alternative to orange-yellow, only changing the appearance color without affecting the detection performance.

[0059] Comparative Example 1: Traditional human serum matrix quality control products Using normal human serum as a matrix, glucose at the same concentration (5.6 mmol / L) and 0.1% Proclin300 preservative as in Example 2 were added and prepared according to industry standard processes, requiring refrigerated storage at 2~8℃.

[0060] Comparative test results: (1) Model compatibility: Among 36 POCT blood glucose meters tested, 6 instruments (Johnson & Johnson OneTouch, Roche Smart Navigation, Roche EasyTouch, Ritek GM700SB, Roche Vitality, etc.) reported "abnormal blood sample" or "abnormal sample" errors and could not perform normal testing; (2) Biosafety: Trace amounts of bacteria were detected, posing a risk of biological contamination; (3) Stability at room temperature: Under storage conditions of 10~35℃, glucose rapidly degraded in the 6th month (deviation -13%~-15%), resulting in turbidity and microbial growth, and the instrument became completely ineffective.

[0061] Comparative Example 2: Standard Phosphate Buffer Quality Control Using potassium dihydrogen phosphate / disodium hydrogen phosphate as a buffer system (pH 6.8), glucose at the same concentration (5.6 mmol / L) and 0.2% Proclin300 preservative as in Example 2 were added to prepare a quality control sample of the same concentration, which was then stored at room temperature.

[0062] Comparative test results: (1) Model universality: Among the 36 POCT blood glucose meters tested, 9 instruments (Sannuo Jinzhun+, Sannuo Jinzhun, Tonghua Dongbao 333D, Aike Yiyou, etc.) showed "test strip abnormality" or recognition abnormality error; (2) Biosafety: There is no biological risk, but the universality does not meet the standard; (3) Stability at room temperature: Under storage conditions of 10~35℃, the glucose decay exceeds 15% after about 12 months of stabilization period, and the decay reaches 23%~28% after 38 months.

[0063] The product of Example 2 of this invention was subjected to a systematic comparative test with Comparative Examples 1 and 2. The test items included model versatility, biosafety, and room temperature stability. The results are as follows: 1. Model compatibility test (36 POCT blood glucose meters on the market were selected, covering both GOD and GDH principles, and mainstream domestic and imported brands): Example 2 of this invention: All 36 instruments tested showed normal results, demonstrating 100% universality; Comparative Example 1 (Human Serum Matrix): Six blood glucose meters reported matrix interference errors, with a universality of 83.3%. Comparative Example 2 (Phosphate Buffer): 9 blood glucose meters reported abnormal errors, with a general compatibility of 75.0%.

[0064] 2. Biosafety testing (microbial limit testing, pathogen screening): Example 2 of the present invention: No bacteria, mold, or pathogenic microorganisms were detected, and there was no biosafety risk; Comparative Example 1: Trace amounts of bacteria were detected, indicating a potential risk of biological contamination; Comparative Example 2: No biological risks, but the universality does not meet the standards.

[0065] 3. Room temperature stability test (continuous storage at 10~35℃ for 38 months, with periodic testing of glucose content): Example 2 of the present invention: The glucose concentration deviation was only -4% to +4% within 38 months, the solution properties remained unchanged, and the performance was stable; Comparative Example 1: In the 6th month, glucose rapidly degraded (deviation -13% to -15%), resulting in turbidity, microbial growth, and complete inactivation; Comparative Example 2: After a stabilization period of approximately 12 months, glucose levels decreased by more than 15%, and by 38 months, the decrease reached 23% to 28%.

[0066] Experimental conclusion: This invention is significantly superior to the two existing mainstream products in terms of three core indicators: versatility, biosafety, and room temperature stability.

[0067] Although embodiments of the present invention have been shown and described above, it is understood that these embodiments are exemplary and should not be construed as limiting the present invention. Those skilled in the art can make changes, modifications, substitutions, and alterations to the above embodiments within the scope of the present invention without departing from its principles and spirit. The scope of protection of the present invention is defined by the claims and their equivalents.

Claims

1. A POCT blood glucose control product based on the PIPES buffer system, characterized in that, The quality control product consists of the following components: PIPES buffer salt, NaOH, hydrochloric acid, colorimetric reagent, PC300 preservative, Kv500 antibacterial agent, NaCl, glucose, and purified water; the pH value of the quality control product is 7.35~7.45; the quality control product does not contain any human or animal biological components.

2. The POCT blood glucose quality control product according to claim 1, characterized in that, The concentration of the PIPES buffer salt is 2~40 mmol / L.

3. The POCT blood glucose quality control product according to claim 1, characterized in that, The volume fraction of the PC300 preservative is 0.01%~0.5%, and the volume fraction of the Kv500 antibacterial agent is 0.01%~0.5%.

4. The POCT blood glucose quality control product according to claim 1, characterized in that, The mass concentration of NaCl is 0.01% to 5%.

5. The POCT blood glucose quality control product according to claim 1, characterized in that, The color developer is any one of the water-soluble inert food colorings selected from orange-yellow, lemon yellow, or amaranth, and the mass fraction of the color developer is 0.01% to 0.2%.

6. The POCT blood glucose quality control product according to claim 1, characterized in that, The glucose concentration is one of the following three levels: low level 2.5 mmol / L, medium level 5.6 mmol / L, and high level 16.0 mmol / L.

7. The method for preparing the POCT blood glucose quality control product according to any one of claims 1 to 6, characterized in that, Includes the following steps: (1) Container and solvent preparation: Take a clean container, add purified water to 75-85% of the final volume, and stir at room temperature for later use; (2) PIPES dissolution: Weigh out PIPES powder according to the formula, add it to purified water in batches, stir until completely mixed, then add NaOH solid and stir to dissolve to obtain clear basic buffer solution; (3) Preliminary acid-base adjustment: Add hydrochloric acid dropwise, monitor in real time with a precision pH meter, calibrate the pH to 7.35~7.45, and stir to mix well; (4) Addition of functional components: Add color developer, PC300 preservative, Kv500 antibacterial agent and NaCl in sequence while stirring, and then add anhydrous glucose standard and stir until completely dissolved; (5) Make up to volume and mix: Add purified water to make up to the target volume and continue stirring; (6) Filtration and sterilization: Vacuum filtration is performed using a 0.22μm aqueous sterile filter membrane, and the filtrate is collected into a sterile storage bottle; (7) Let it stand and mature: Let it stand at room temperature in a sealed container. Visually inspect the solution to ensure it is uniform, clear and free of turbidity or precipitate. (8) Quantitative dispensing: Dispense into brown light-proof bottles and seal.

8. The manufacturing method according to claim 7, characterized in that, The stirring speed in step (1) is 200~300 r / min; the 0.22μm aqueous sterile filter membrane in step (6) is a polyethersulfone filter membrane.

9. The application of the POCT blood glucose quality control material as described in any one of claims 1 to 6 in the internal quality control of POCT blood glucose meters, characterized in that, The quality control material is applicable to both portable blood glucose meters based on glucose oxidase and glucose dehydrogenase principles, and is used for blood glucose meter performance verification, test strip validity verification, and internal quality control.

10. The application according to claim 9, characterized in that, The quality control products are stored and used at room temperature (10-35°C) without the need for cold chain transportation or refrigeration. The shelf life at room temperature is no less than 36 months.