Method and system for analyzing storage stability of cpG1018 vaccine

Abstract

The application relates to the technical field of data analysis, and relates to a CpG1018 vaccine storage stability analysis method and system, which comprises the following steps: receiving a storage stability analysis instruction, obtaining a freeze-dried product set, redissolving the freeze-dried product to obtain a redissolved product set, sequentially extracting the redissolved product, performing an equal-division operation on the redissolved product to obtain an equal-division product group, performing detection to obtain adjuvant purity, nucleic acid protein ratio and mass deviation, obtaining a physicochemical stable vaccine, obtaining a first experimental solution and a second experimental solution, injecting a preset experimental body with the physicochemical stable vaccine, the first experimental solution and the second experimental solution to obtain reaction characteristics, judging according to a characteristic range and the reaction characteristics to obtain vaccine judgment parameters, and completing analysis of the storage stability of the CpG1018 vaccine according to the vaccine judgment parameters. The application can improve the accuracy of vaccine storage stability analysis.

Description

Technical Field

[0001] This invention relates to the field of data analysis technology, and in particular to an analysis method and system based on the storage stability of CpG1018 vaccine. Background Technology

[0002] With the rapid development of vaccines, the storage stability of vaccines is a key indicator to ensure immunization efficacy and vaccine safety, and an important part of vaccine research and development and quality control. Vaccine storage stability can improve the stability of antigenic and adjuvant components in the vaccine throughout the transportation and storage process, reduce the degradation rate of antigenic and adjuvant components during the transportation and storage process, thereby maintaining the immunogenicity and protective efficacy at the time of planned vaccination.

[0003] Traditional methods for analyzing vaccine stability often focus on single physicochemical indicators or in vitro experiments, lacking a comprehensive assessment of the combined effects of adjuvants and antibiotics after reconstitution. Furthermore, animal studies primarily involve end-stage potency assays, failing to correlate deviations with real-time organismal response characteristics. Therefore, improving the accuracy of vaccine storage stability analysis is a crucial issue that urgently needs to be addressed. Summary of the Invention

[0004] This invention provides an analytical method and system for the storage stability of CpG1018 vaccines, the main purpose of which is to improve the accuracy of vaccine storage stability analysis.

[0005] To achieve the above objectives, the present invention provides an analytical method for the storage stability of CpG1018 vaccine, comprising:

[0006] Receive storage stability analysis instructions, and obtain a set of freeze-dried products according to the storage stability analysis instructions and preset storage parameters. The freeze-dried products include: vaccine adjuvant and vaccine antigen. The vaccine adjuvant is CpG1018 vaccine adjuvant and the vaccine antigen is 13-valent pneumococcal polysaccharide-CRM197 conjugate.

[0007] All freeze-dried products in the freeze-dried product set are re-melted to obtain a re-melted product set;

[0008] Redissolved products are extracted sequentially from the redissolved product set, and the extracted redissolved products are divided into equal parts to obtain equal product groups, wherein the equal parts are divided into three equal parts;

[0009] The adjuvant purity, nucleic acid-to-protein ratio, and quality deviation were obtained by testing the aforementioned aliquots.

[0010] A physicochemically stable vaccine was obtained based on the adjuvant purity, nucleic acid-to-protein ratio, and quality deviation.

[0011] Obtain a first experimental solution and a second experimental solution, wherein the first experimental solution is physiological saline and the second experimental solution is a 13-valent pneumococcal polysaccharide conjugate vaccine;

[0012] The pre-set experimental subjects are injected with the physicochemically stable vaccine, the first experimental solution, and the second experimental solution to obtain reaction characteristics. The vaccine determination parameters are obtained based on the pre-set characteristic range and reaction characteristics. The storage stability of CpG1018 vaccine is analyzed based on the vaccine determination parameters. The experimental subjects include experimental mice and experimental rabbits. The characteristic range includes a first range, a second range, a third range, and a fourth range.

[0013] Optionally, the storage parameters include: storage temperature and storage time, wherein the storage temperature includes: refrigeration temperature, short-term temperature and acceleration temperature, the refrigeration temperature is 2°C to 6°C, the short-term temperature is 23°C to 27°C, the acceleration temperature is 38°C to 42°C, and the storage time includes: 0 months, 1 month, 2 months, 3 months, 6 months, 12 months and 18 months.

[0014] Optionally, the step of using the aliquoted product group for testing to obtain adjuvant purity, nucleic acid-protein ratio, and quality deviation includes:

[0015] The equally divided product groups are identified to obtain the first product, the second product, and the third product;

[0016] A first experimental solid is obtained and dissolved to obtain a first experimental solution, wherein the first experimental solid is triethylamine-acetic acid solid and the liquid used to dissolve the first experimental solid is deionized water;

[0017] The first experimental solution is adjusted using a preset adjustment solution to obtain a first adjusted solution. The adjusted pH value of the first adjusted solution is detected, and the pH difference is calculated based on the adjusted pH value and the preset pH standard value.

[0018] Compare the acid-base difference with the preset acid-base difference threshold;

[0019] If the acid-base difference is greater than the acid-base difference threshold, the first experimental solution is updated using the first adjustment solution, and the process of adjusting the first experimental solution using the preset adjustment solution is returned to the above steps based on the updated first experimental solution until the acid-base difference is less than or equal to the acid-base difference threshold.

[0020] If the acid-base difference is less than or equal to the acid-base difference threshold, then the first adjustment solution is identified as the first target adjustment solution;

[0021] The adjuvant purity is obtained based on the first target adjustment solution, the first product, and the preset second target adjustment solution;

[0022] The nucleic acid-to-protein ratio is obtained based on the second product and the preset comparison solution, and the quality deviation is obtained based on the third product.

[0023] Optionally, obtaining adjuvant purity based on the first target adjustment solution, the first product, and a preset second target adjustment solution includes:

[0024] In-column separation was performed using the first target conditioning solution, the second target conditioning solution, and the first product, and the absorbance value and reading time were obtained using pre-built reading software.

[0025] Using the absorbance value and reading time, an experimental chromatogram was plotted, and the main peak area and overall area were obtained from the experimental chromatogram.

[0026] The adjuvant purity is calculated based on the area of ​​the main peak and the overall area, wherein the adjuvant purity is the ratio of the main peak area to the overall area.

[0027] Optionally, obtaining the nucleic acid-protein ratio based on the second product and a preset comparison solution includes:

[0028] The pre-constructed dual-beam UV-Vis spectrophotometer was preheated, and the preheating time was recorded.

[0029] Compare the preheating time with the preset target time;

[0030] If the preheating time is less than the target time, the current preheating time is obtained, the preheating time is updated using the current preheating time, and the updated preheating time is used to return to the above steps of comparing the preheating time with the preset target time, until the preheating time is greater than or equal to the target time.

[0031] If the preheating time is greater than or equal to the target time, the dual-beam UV-Vis spectrophotometer is confirmed as a measurement device ready for use.

[0032] The second product and the control solution are scanned using the prepared measuring device to obtain a first reading and a second reading, wherein the first reading is the absorbance value corresponding to 260 nm and the second reading is the absorbance value corresponding to 280 nm.

[0033] The nucleic acid-protein ratio is calculated using the first reading and the second reading, wherein the nucleic acid-protein ratio is the first reading divided by the second reading.

[0034] Optionally, the step of injecting a pre-set experimental subject with the physicochemically stable vaccine, the first experimental solution, and the second experimental solution to obtain reaction characteristics includes:

[0035] Based on a preset first experimental subject number and a preset second experimental subject number, a set of experimental mice and a set of experimental rabbits are obtained from the experimental subjects, wherein the first experimental subject number corresponds to the number of experimental mice and the second experimental subject number corresponds to the number of experimental rabbits.

[0036] The experimental mouse set and the experimental rabbit set are allocated according to the physicochemically stable vaccine, the first experimental solution, and the second experimental solution to obtain the physicochemical experimental set, the physiological experimental set, and the binding experimental set. The physicochemical experimental set includes physicochemically tested mice and physicochemically tested rabbits. The physiological experimental set includes physiologically tested mice and physiologically tested rabbits. The binding experimental set includes binding experimental mice and binding experimental rabbits. The number of physicochemically tested mice, physiologically tested mice, and binding experimental mice are the same. The number of physicochemically tested rabbits, physiologically tested rabbits, and binding experimental rabbits are the same.

[0037] The physicochemically stable vaccine, the first experimental solution, and the second experimental solution were used to inject all experimental subjects in the physicochemical experimental set, the physiological experimental set, and the binding experimental set, respectively, to obtain reaction characteristics.

[0038] Optionally, the step of injecting all experimental subjects in the physicochemical experimental set, the physiological experimental set, and the binding experimental set with the physicochemically stable vaccine, the first experimental solution, and the second experimental solution respectively to obtain reaction characteristics includes:

[0039] Using the physicochemically stable vaccine, preset injection sites for mice and rabbits, all mice and rabbits in the physicochemical experimental body are injected. After a preset waiting time, physicochemical reaction characteristics are obtained, including: physicochemical weight change, physicochemical rectal temperature, and physicochemical erythema length.

[0040] According to the first experimental solution, the injection sites of experimental mice and experimental rabbits, all physiological experimental mice and physiological experimental rabbits in the physiological experimental body were injected, and after waiting time, physiological response characteristics were obtained, wherein the physiological response characteristics include: physiological weight change and physiological rectal temperature.

[0041] Based on the second experimental solution, the injection sites of the experimental mice and the experimental rabbits, all the experimental mice and experimental rabbits in the binding experimental body were injected, and after waiting time, the binding reaction characteristics were obtained, wherein the binding reaction characteristics included: changes in the weight of the bound animals and the rectal temperature of the bound animals.

[0042] The physicochemical reaction characteristics, physiological reaction characteristics, and binding reaction characteristics are identified as reaction characteristics.

[0043] Optionally, the step of determining vaccine determination parameters based on a preset feature range and reaction characteristics includes:

[0044] The first weight change value and the second weight change value are calculated using the physicochemical weight change, physiological weight change and combined weight change, wherein the first weight change value is the absolute value of the difference between the physicochemical weight change and the physiological weight change, and the second weight change value is the absolute value of the difference between the physicochemical weight change and the combined weight change.

[0045] The first and second weight change values ​​are compared with a preset change threshold.

[0046] If both the first and second weight change values ​​are less than or equal to the change threshold, then the physicochemical weight change is considered a safe weight change.

[0047] If the first and second weight change values ​​are not both less than or equal to the change threshold, then the physical and chemical weight change is identified as an abnormal weight change.

[0048] The first temperature change value and the second temperature change value are calculated using the physicochemical rectal temperature, physiological rectal temperature and combined rectal temperature, wherein the first temperature change value is the change value of the difference between the physicochemical rectal temperature and the physiological rectal temperature, and the second temperature change value is the change value of the difference between the physicochemical rectal temperature and the combined rectal temperature.

[0049] The first temperature change value and the second temperature change value are compared with a preset temperature threshold.

[0050] If both the first temperature change value and the second temperature change value are less than or equal to the temperature threshold, then the physical and chemical rectal temperature is confirmed as the safe rectal temperature.

[0051] If the first temperature change value and the second temperature change value are not both less than or equal to the temperature threshold, then the physical and chemical rectal temperature is identified as an abnormal rectal temperature.

[0052] The length of the physicochemical erythema is determined by using the aforementioned characteristic range to obtain the erythema grade. The safe weight change, abnormal weight change, safe rectal temperature, abnormal rectal temperature, and erythema grade are confirmed as vaccine determination parameters.

[0053] Optionally, the step of determining the length of the physicochemical erythema using the characteristic range to obtain the erythema grade includes:

[0054] The length of the physicochemical erythema is compared with the first, second, third and fourth ranges of the characteristic range, wherein the first range is 0 mm to 2 mm, the second range is 2 mm to 4 mm, the third range is 4 mm to 8 mm, and the fourth range is greater than 8 mm.

[0055] If the length of the physicochemical erythema is within the first range, then the length of the physicochemical erythema is identified as the first level;

[0056] If the length of the physicochemical erythema is within the second range, then the length of the physicochemical erythema is confirmed as the second level;

[0057] If the length of the physicochemical erythema is within the third range, then the length of the physicochemical erythema is confirmed as the third level;

[0058] If the length of the physicochemical erythema is not within the first, second, or third range, then the length of the physicochemical erythema is classified as the fourth level.

[0059] The first, second, third, or fourth level is identified as the erythema level.

[0060] To achieve the above objectives, the present invention also provides an analysis system based on the storage stability of CpG1018 vaccine, comprising:

[0061] The reconstituted product acquisition module is used to receive storage stability analysis instructions and acquire a set of lyophilized products according to the storage stability analysis instructions and preset storage parameters. The lyophilized products include: vaccine adjuvant and vaccine antigen. The vaccine adjuvant is CpG1018 vaccine adjuvant and the vaccine antigen is 13-valent pneumococcal polysaccharide-CRM197 conjugate.

[0062] All freeze-dried products in the freeze-dried product set are re-melted to obtain a re-melted product set;

[0063] The physicochemical parameter detection module is used to sequentially extract reconstituted products from the reconstituted product set, and to perform an equal division operation on the extracted reconstituted products to obtain an equal product group, wherein the equal division is into three equal parts;

[0064] The adjuvant purity, nucleic acid-to-protein ratio, and quality deviation were obtained by testing the aforementioned aliquots.

[0065] A stable vaccine acquisition module is used to acquire a physicochemically stable vaccine based on the adjuvant purity, nucleic acid-protein ratio, and quality deviation.

[0066] The storage stability analysis module is used to obtain a first experimental solution and a second experimental solution, wherein the first experimental solution is physiological saline and the second experimental solution is a 13-valent pneumococcal polysaccharide conjugate vaccine;

[0067] The pre-set experimental subjects are injected with the physicochemically stable vaccine, the first experimental solution, and the second experimental solution to obtain reaction characteristics. The vaccine determination parameters are obtained based on the pre-set characteristic range and reaction characteristics. The storage stability of CpG1018 vaccine is analyzed based on the vaccine determination parameters. The experimental subjects include experimental mice and experimental rabbits. The characteristic range includes a first range, a second range, a third range, and a fourth range.

[0068] To address the above problems, the present invention also provides an electronic device, the electronic device comprising:

[0069] Memory, storing at least one instruction;

[0070] The processor executes the instructions stored in the memory to implement the above-described analysis method based on the storage stability of CpG1018 vaccine.

[0071] To address the aforementioned problems, the present invention also provides a computer-readable storage medium storing at least one instruction, which is executed by a processor in an electronic device to implement the aforementioned analysis method for the storage stability of CpG1018 vaccine.

[0072] To address the problems described in the background art, this invention first receives a storage stability analysis command and obtains a set of lyophilized products based on the received command and storage parameters. The lyophilized products include a vaccine adjuvant and a vaccine antigen. The vaccine adjuvant is CpG1018, and the vaccine antigen is a 13-valent pneumococcal polysaccharide-CRM197 conjugate. By using the storage stability analysis command and standardized storage parameters, it can be ensured that all lyophilized vaccine samples undergo identical storage conditions, eliminating interference from human or environmental variations on subsequent data. Secondly, all lyophilized products in the set are reconstituted to obtain a set of reconstituted products. This reconstitution simulates the actual operation before clinical administration, ensuring a high degree of consistency between the physicochemical and biological test results and the final usage method. Then, reconstituted products are sequentially extracted from the set, and the extracted reconstituted products are divided into three equal portions. The product groups were divided into equal parts for testing to obtain adjuvant purity, nucleic acid-protein ratio, and mass deviation. Each reconstituted sample was divided into three equal parts to ensure parallel samples of the same volume, concentration, and source, providing a basis for consistency in the three tests. By testing adjuvant purity, nucleic acid-protein ratio, and mass deviation, the physicochemical quality of the vaccine can be evaluated from multiple perspectives. Furthermore, based on the adjuvant purity, nucleic acid-protein ratio, and mass deviation, a physicochemically stable vaccine was obtained, realizing automated and repeatable stability determination. Finally, the physicochemically stable vaccine, the first experimental solution, and the second experimental solution were used to inject experimental subjects to obtain reaction characteristics. Based on the characteristic range and reaction characteristics, the vaccine determination parameters were obtained. The storage stability of the CpG1018 vaccine was analyzed based on the vaccine determination parameters. Simultaneous testing was conducted on experimental mice and rabbits, making the storage stability conclusions more universal and predictive, and improving the accuracy of vaccine storage stability analysis. Therefore, this invention can improve the accuracy of vaccine storage stability analysis. Attached Figure Description

[0073] Figure 1A flowchart illustrating an analytical method for the storage stability of CpG1018 vaccine provided in an embodiment of the present invention;

[0074] Figure 2 A functional block diagram of an analysis system for the storage stability of CpG1018 vaccine provided in an embodiment of the present invention;

[0075] Figure 3 This is a schematic diagram of an electronic device for implementing the analysis method based on the storage stability of CpG1018 vaccine, as provided in an embodiment of the present invention.

[0076] Explanation of reference numerals in the attached figures:

[0077] 10. Electronic device; 11. Processor; 12. Memory; 13. Bus.

[0078] The realization of the objective, functional features and advantages of the present invention will be further explained in conjunction with the embodiments and with reference to the accompanying drawings. Detailed Implementation

[0079] It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.

[0080] This application provides an analysis method for the storage stability of CpG1018 vaccine. The execution entity of this analysis method includes, but is not limited to, at least one of the following electronic devices that can be configured to execute the method provided in this application: a server, a terminal, etc. In other words, the analysis method for the storage stability of CpG1018 vaccine can be executed by software or hardware installed on a terminal device or a server device, and the software can be a blockchain platform. The server includes, but is not limited to, a single server, a server cluster, a cloud server, or a cloud server cluster.

[0081] Reference Figure 1 The diagram shown is a flowchart illustrating an analysis method for the storage stability of CpG1018 vaccine according to an embodiment of the present invention. In this embodiment, the analysis method for the storage stability of CpG1018 vaccine includes:

[0082] S1. Receive storage stability analysis command, and obtain a set of freeze-dried products according to the storage stability analysis command and preset storage parameters. The freeze-dried products include: vaccine adjuvant and vaccine antigen. The vaccine adjuvant is CpG1018 vaccine adjuvant and the vaccine antigen is 13-valent pneumococcal polysaccharide-CRM197 conjugate.

[0083] Explainable, storage stability analysis command refers to a command issued by a person to obtain a set of lyophilized products. For example, if an experimenter needs to obtain a set of lyophilized products and perform storage stability analysis on the obtained set of lyophilized products, the experimenter issues a storage stability analysis command and obtains the lyophilized product set according to the storage stability analysis command and storage parameters. A freeze-dried product set refers to a collection of freeze-dried products obtained according to storage stability analysis instructions and storage parameters. Freeze-dried products refer to the powder obtained after removing moisture from vaccines. Each storage temperature and storage time in the storage parameters corresponds to one freeze-dried product. For example, if the storage temperature is a refrigerated temperature and the storage time is 0 months, then the refrigerated temperature and 0 months correspond to one freeze-dried product, indicating that the freeze-dried product was stored at a refrigerated temperature of 2°C to 6°C for 0 months. If the storage temperature is a short-term temperature and the storage time is 3 months, then the short-term temperature and 3 months correspond to one freeze-dried product, indicating that the freeze-dried product was stored at a short-term temperature of 23°C to 27°C for 3 months.

[0084] In detail, the storage parameters include: storage temperature and storage time, wherein the storage temperature includes: refrigeration temperature, short-term temperature and acceleration temperature, the refrigeration temperature is 2°C to 6°C, the short-term temperature is 23°C to 27°C, the acceleration temperature is 38°C to 42°C, and the storage time includes: 0 months, 1 month, 2 months, 3 months, 6 months, 12 months and 18 months.

[0085] Explainable storage parameters refer to the parameters used for storing vaccines and obtaining corresponding freeze-dried products. Storage parameters include storage temperature and storage time.

[0086] S2. All freeze-dried products in the freeze-dried product set are re-dissolved to obtain a re-dissolved product set.

[0087] Explained, a reconstituted product set refers to a collection of reconstituted products. A reconstituted product is a vaccine obtained by reconstituted lyophilized products. For example, reconstituted lyophilized products stored at refrigeration temperature for 6 months are obtained by reconstituted products stored at refrigeration temperature for 6 months.

[0088] S3. Extract reconstituted products sequentially from the reconstituted product set, and perform an equal division operation on the extracted reconstituted products to obtain an equal product group, wherein the equal division is into three equal parts.

[0089] Explained, an aliquot of a product group refers to a combination of aliquots of a product. Performing an aliquot operation on the extracted reconstituted product means dividing the reconstituted product into three equal volumes. For example, if the reconstituted product is 0.9 ml, performing an aliquot operation on the reconstituted product will yield three 0.3 ml aliquots.

[0090] S4. The adjuvant purity, nucleic acid-protein ratio and quality deviation are obtained by testing the equal product groups.

[0091] In detail, the process of using the aliquoted product group for testing to obtain adjuvant purity, nucleic acid-protein ratio, and quality deviation includes:

[0092] The equally divided product groups are identified to obtain the first product, the second product, and the third product;

[0093] A first experimental solid is obtained and dissolved to obtain a first experimental solution, wherein the first experimental solid is triethylamine-acetic acid solid and the liquid used to dissolve the first experimental solid is deionized water;

[0094] The first experimental solution is adjusted using a preset adjustment solution to obtain a first adjusted solution. The adjusted pH value of the first adjusted solution is detected, and the pH difference is calculated based on the adjusted pH value and the preset pH standard value.

[0095] Compare the acid-base difference with the preset acid-base difference threshold;

[0096] If the acid-base difference is greater than the acid-base difference threshold, the first experimental solution is updated using the first adjustment solution, and the process of adjusting the first experimental solution using the preset adjustment solution is returned to the above steps based on the updated first experimental solution until the acid-base difference is less than or equal to the acid-base difference threshold.

[0097] If the acid-base difference is less than or equal to the acid-base difference threshold, then the first adjustment solution is identified as the first target adjustment solution;

[0098] The adjuvant purity is obtained based on the first target adjustment solution, the first product, and the preset second target adjustment solution;

[0099] The nucleic acid-to-protein ratio is obtained based on the second product and the preset comparison solution, and the quality deviation is obtained based on the third product.

[0100] Explained terms: First product, second product, and third product refer to the products obtained after identifying the three equal products in the equal product group; first experimental solution refers to the solution obtained after dissolving the first experimental solid; adjusted pH value refers to the pH value of the first adjusted solution; standard pH value refers to a manually set value used to calculate the pH difference, optionally 7.0; pH difference threshold refers to a manually set threshold used to determine the pH difference, optionally 0.05; first target adjusted solution refers to the first adjusted solution with a pH difference less than or equal to the pH difference threshold; the first adjusted solution refers to the solution obtained after adjusting the pH of the first experimental solution using an adjusting solution; the adjusting solution refers to a pre-set solution used to adjust the pH of the first experimental solution, optionally acetic acid. The quality deviation obtained based on the third product refers to obtaining the mass spectrometry data of the third product using liquid chromatography-mass spectrometry (LC-MS), obtaining the relative molecular mass of the third product based on the mass spectrometry data, and calculating the quality deviation based on the theoretical molecular mass and the relative molecular mass. The theoretical molecular mass refers to the mass calculated based on the molecular chemical formula, atomic composition, and chemical bonding method of CpG1018. The above-mentioned methods of obtaining the mass spectrometry data of the third product using LC-MS, obtaining the relative molecular mass of the third product based on the mass spectrometry data, and obtaining the theoretical molecular mass are all existing technologies and will not be elaborated here.

[0101] Specifically, obtaining adjuvant purity based on the first target adjustment solution, the first product, and a preset second target adjustment solution includes:

[0102] In-column separation was performed using the first target conditioning solution, the second target conditioning solution, and the first product, and the absorbance value and reading time were obtained using pre-built reading software.

[0103] Using the absorbance value and reading time, an experimental chromatogram was plotted, and the main peak area and overall area were obtained from the experimental chromatogram.

[0104] The adjuvant purity is calculated based on the area of ​​the main peak and the overall area, wherein the adjuvant purity is the ratio of the main peak area to the overall area.

[0105] Explained, in-column separation using the first target adjustment solution, the second target adjustment solution, and the first product refers to substituting the first product into the chromatographic column using the first and second target adjustment solutions. Optionally, the chromatographic column is a C18 reversed-phase column. Reading software refers to the software used to control the HPLC; optionally, the reading software is Agilent ChemStation software. Absorbance value refers to the absorbance value of the first product read by the reading software. Reading time refers to the time taken for the reading software to read the absorbance value. Experimental chromatogram refers to the image plotted based on the reading time and absorbance value. The experimental chromatogram consists of an experimental horizontal axis and an experimental vertical axis; the experimental horizontal axis represents the reading time, and the experimental vertical axis represents the absorbance value. Main peak area refers to the peak with the largest area in the experimental chromatogram, and the total area refers to the sum of the areas of all peaks in the experimental chromatogram. Generally, the second target adjustment solution is an acetonitrile-triethylamine acetic acid mixed solution used in conjunction with the first target adjustment solution. Optionally, the acetonitrile-triethylamine acetic acid mixed solution is obtained by mixing 60% acetonitrile with 40% triethylamine-acetic acid buffer solution.

[0106] Specifically, obtaining the nucleic acid-protein ratio based on the second product and the preset comparison solution includes:

[0107] The pre-constructed dual-beam UV-Vis spectrophotometer was preheated, and the preheating time was recorded.

[0108] Compare the preheating time with the preset target time;

[0109] If the preheating time is less than the target time, the current preheating time is obtained, the preheating time is updated using the current preheating time, and the updated preheating time is used to return to the above steps of comparing the preheating time with the preset target time, until the preheating time is greater than or equal to the target time.

[0110] If the preheating time is greater than or equal to the target time, the dual-beam UV-Vis spectrophotometer is confirmed as a measurement device ready for use.

[0111] The second product and the control solution are scanned using the prepared measuring device to obtain a first reading and a second reading, wherein the first reading is the absorbance value corresponding to 260 nm and the second reading is the absorbance value corresponding to 280 nm.

[0112] The nucleic acid-protein ratio is calculated using the first reading and the second reading, wherein the nucleic acid-protein ratio is the first reading divided by the second reading.

[0113] Explained, the preheating time refers to the manually set time for preheating the dual-beam UV-Vis spectrophotometer; the target time refers to the manually set time required for preheating the dual-beam UV-Vis spectrophotometer, optionally 45 minutes. The current preheating time refers to the time the dual-beam UV-Vis spectrophotometer has been preheated at the current time; preparing the measuring device refers to the dual-beam UV-Vis spectrophotometer when the preheating time is greater than or equal to the target time. Scanning using the prepared measuring device, the second product, and the comparison solution is existing technology and will not be elaborated further. 260nm and 280nm both refer to wavelength. The comparison solution is a reference used to quantify the ratio of vaccine adjuvant and vaccine antigen, and its main function is to calibrate the dual-beam UV-Vis spectrophotometer. Optionally, water excluding vaccine adjuvant and vaccine antigen may be used as the comparison solution.

[0114] S5. Obtain a physicochemically stable vaccine based on the adjuvant purity, nucleic acid-protein ratio, and quality deviation.

[0115] Explained, obtaining a physicochemically stable vaccine based on the adjuvant purity, nucleic acid-protein ratio, and quality deviation refers to determining the adjuvant purity, nucleic acid-protein ratio, and quality deviation according to the adjuvant purity standard, nucleic acid-protein ratio standard, and quality deviation standard. When the adjuvant purity, nucleic acid-protein ratio, and quality deviation meet the adjuvant purity standard, nucleic acid-protein ratio standard, and quality deviation standard, the reconstituted product corresponding to that adjuvant purity, nucleic acid-protein ratio, and quality deviation is confirmed as a physicochemically stable vaccine. The adjuvant purity standard refers to an adjuvant purity greater than or equal to 95%, the nucleic acid-protein ratio standard refers to a nucleic acid-protein ratio between 1.8 and 2.0, including 1.8 and 2.0, and the quality deviation standard refers to a quality deviation between -5 Da and 5 Da, including -5 Da and 5 Da.

[0116] S6. Obtain a first experimental solution and a second experimental solution, wherein the first experimental solution is physiological saline and the second experimental solution is a 13-valent pneumococcal polysaccharide conjugate vaccine.

[0117] Explained, the first and second experimental solutions were used in comparative experiments with physicochemically stable vaccines.

[0118] S7. Inject the pre-set experimental subjects using the physicochemically stable vaccine, the first experimental solution, and the second experimental solution to obtain reaction characteristics. Determine the vaccine determination parameters based on the pre-set characteristic range and reaction characteristics. Analyze the storage stability of the CpG1018 vaccine based on the vaccine determination parameters. The experimental subjects include experimental mice and experimental rabbits, and the characteristic range includes a first range, a second range, a third range, and a fourth range.

[0119] Explainable experimental subjects refer to individuals used to represent the reaction characteristics of physicochemically stable vaccines, the first experimental solution, and the second experimental solution. Among them, experimental mice are female mice aged 6 to 8 weeks and weighing 18 to 20 grams, and experimental rabbits are female rabbits aged 10 to 12 weeks and weighing 2 to 3 kilograms.

[0120] In detail, the injection of the pre-set experimental subject with the physicochemically stable vaccine, the first experimental solution, and the second experimental solution to obtain reaction characteristics includes:

[0121] Based on a preset first experimental subject number and a preset second experimental subject number, a set of experimental mice and a set of experimental rabbits are obtained from the experimental subjects, wherein the first experimental subject number corresponds to the number of experimental mice and the second experimental subject number corresponds to the number of experimental rabbits.

[0122] The experimental mouse set and the experimental rabbit set are allocated according to the physicochemically stable vaccine, the first experimental solution, and the second experimental solution to obtain the physicochemical experimental set, the physiological experimental set, and the binding experimental set. The physicochemical experimental set includes physicochemically tested mice and physicochemically tested rabbits. The physiological experimental set includes physiologically tested mice and physiologically tested rabbits. The binding experimental set includes binding experimental mice and binding experimental rabbits. The number of physicochemically tested mice, physiologically tested mice, and binding experimental mice are the same. The number of physicochemically tested rabbits, physiologically tested rabbits, and binding experimental rabbits are the same.

[0123] The physicochemically stable vaccine, the first experimental solution, and the second experimental solution were used to inject all experimental subjects in the physicochemical experimental set, the physiological experimental set, and the binding experimental set, respectively, to obtain reaction characteristics.

[0124] Explainable, the first experimental subject quantity refers to the number of experimental mice required to conduct experiments on the physicochemically stable vaccine, the first experimental solution, and the second experimental solution; optionally, the first experimental subject quantity is 18. The second experimental subject quantity refers to the number of experimental rabbits required to conduct experiments on the physicochemically stable vaccine, the first experimental solution, and the second experimental solution; optionally, the second experimental subject quantity is 12. The experimental mouse set refers to the set of experimental mice obtained according to the first experimental subject quantity; the experimental rabbit set refers to the set of experimental rabbits obtained according to the second experimental subject quantity; the physicochemical experimental subject set refers to the set of experimental subjects used for the physicochemically stable vaccine; the physiological experimental subject set refers to the set of experimental subjects used for the first experimental solution; the combined experimental subject set refers to the set of experimental subjects used for the second experimental solution; physicochemical experimental mice refer to the experimental mice in the physicochemical experimental subject set; physicochemical experimental rabbits refer to the experimental rabbits in the physicochemical experimental subject set; physiological experimental mice refer to the experimental mice in the physiological experimental subject set; physiological experimental rabbits refer to the experimental rabbits in the physiological experimental subject set; combined experimental mice refer to the experimental mice in the combined experimental subject set; combined experimental rabbits refer to the experimental rabbits in the combined experimental subject set.

[0125] In detail, the method of injecting all experimental subjects in the physicochemical experimental set, the physiological experimental set, and the binding experimental set with the physicochemically stable vaccine, the first experimental solution, and the second experimental solution respectively to obtain reaction characteristics includes:

[0126] Using the physicochemically stable vaccine, preset injection sites for mice and rabbits, all mice and rabbits in the physicochemical experimental body are injected. After a preset waiting time, physicochemical reaction characteristics are obtained, including: physicochemical weight change, physicochemical rectal temperature, and physicochemical erythema length.

[0127] According to the first experimental solution, the injection sites of experimental mice and experimental rabbits, all physiological experimental mice and physiological experimental rabbits in the physiological experimental body were injected, and after waiting time, physiological response characteristics were obtained, wherein the physiological response characteristics include: physiological weight change and physiological rectal temperature.

[0128] Based on the second experimental solution, the injection sites of the experimental mice and the experimental rabbits, all the experimental mice and experimental rabbits in the binding experimental body were injected, and after waiting time, the binding reaction characteristics were obtained, wherein the binding reaction characteristics included: changes in the weight of the bound animals and the rectal temperature of the bound animals.

[0129] The physicochemical reaction characteristics, physiological reaction characteristics, and binding reaction characteristics are identified as reaction characteristics.

[0130] Explainable, the injection site for mice refers to the right iliac hind leg of the mouse, and the injection site for rabbits refers to the right scapula of the rabbit. The waiting time refers to the waiting time after the mice and rabbits are injected according to the injection sites for mice and rabbits. Optional, the waiting time is 4 hours. Physicochemical reaction characteristics refer to the characteristics exhibited by mice and rabbits after the stable vaccine has been injected into them at the injection sites in the mice and rabbits, respectively, and after a waiting period. Physicochemical weight change refers to the physicochemical changes in mice and rabbits after the injection of the stable vaccine and the waiting period. Physicochemical change value refers to the change in weight of mice and rabbits at the time of injection of the stable vaccine and after the waiting period. Physicochemical rectal temperature refers to the rectal temperature of mice and rabbits after the injection of the stable vaccine and the waiting period. Physicochemical erythema length refers to the diameter of the erythema produced after the injection of the stable vaccine in mice and rabbits. Physiological response characteristics refer to the characteristics exhibited by the physiological mice and rabbits after the first experimental solution was injected into them according to the injection sites in the mice and rabbits, and after a waiting period. Physiological weight change refers to the physiological change values ​​of the physiological mice and rabbits after the injection of the first experimental solution and the waiting period. Physiological change value refers to the change in weight of the physiological mice and rabbits at the time of injection of the first experimental solution and after the waiting period. Physiological rectal temperature refers to the rectal temperature of the physiological mice and rabbits after the injection of the first experimental solution and the waiting period. Binding weight change refers to the binding change values ​​of the physiological mice and rabbits after the injection of the second experimental solution and the waiting period. Binding change value refers to the change in weight of the binding mice and rabbits at the time of injection of the second experimental solution and the waiting period. Binding rectal temperature refers to the rectal temperature of the binding mice and rabbits after the injection of the second experimental solution and the waiting period.

[0131] In detail, the determination of vaccine assessment parameters based on preset feature ranges and reaction characteristics includes:

[0132] The first weight change value and the second weight change value are calculated using the physicochemical weight change, physiological weight change and combined weight change, wherein the first weight change value is the absolute value of the difference between the physicochemical weight change and the physiological weight change, and the second weight change value is the absolute value of the difference between the physicochemical weight change and the combined weight change.

[0133] The first and second weight change values ​​are compared with a preset change threshold.

[0134] If both the first and second weight change values ​​are less than or equal to the change threshold, then the physicochemical weight change is considered a safe weight change.

[0135] If the first and second weight change values ​​are not both less than or equal to the change threshold, then the physical and chemical weight change is identified as an abnormal weight change.

[0136] The first temperature change value and the second temperature change value are calculated using the physicochemical rectal temperature, physiological rectal temperature and combined rectal temperature, wherein the first temperature change value is the change value of the difference between the physicochemical rectal temperature and the physiological rectal temperature, and the second temperature change value is the change value of the difference between the physicochemical rectal temperature and the combined rectal temperature.

[0137] The first temperature change value and the second temperature change value are compared with a preset temperature threshold.

[0138] If both the first temperature change value and the second temperature change value are less than or equal to the temperature threshold, then the physical and chemical rectal temperature is confirmed as the safe rectal temperature.

[0139] If the first temperature change value and the second temperature change value are not both less than or equal to the temperature threshold, then the physical and chemical rectal temperature is identified as an abnormal rectal temperature.

[0140] The length of the physicochemical erythema is determined by using the aforementioned characteristic range to obtain the erythema grade. The safe weight change, abnormal weight change, safe rectal temperature, abnormal rectal temperature, and erythema grade are confirmed as vaccine determination parameters.

[0141] Explainable, the change threshold refers to a manually set value used to determine the first and second weight change values; optionally, the change threshold is 8%. Safe weight change refers to the physicochemical weight change when both the first and second temperature change values ​​are less than or equal to the temperature threshold. Abnormal weight change refers to the physicochemical weight change when neither the first nor the second weight change values ​​are equally less than or equal to the change threshold. The temperature threshold is a manually set value used to determine the first and second temperature change values; optionally, the temperature threshold is 1.5℃. Safe rectal temperature refers to the physicochemical rectal temperature when both the first and second temperature change values ​​are less than or equal to the temperature threshold. Abnormal rectal temperature refers to the physicochemical rectal temperature when neither the first nor the second temperature change values ​​are equally less than or equal to the temperature threshold. Vaccine judgment parameters refer to parameters used to determine the storage stability of the CpG1018 vaccine. When the physicochemical weight change is a safe weight change, the physicochemical rectal temperature is a safe rectal temperature, and the erythema grade is level one or two, the storage stability of the CpG1018 vaccine is considered to meet the requirements.

[0142] In detail, the determination of the length of physicochemical erythema using the aforementioned feature range to obtain the erythema grade includes:

[0143] The length of the physicochemical erythema is compared with the first, second, third and fourth ranges of the characteristic range, wherein the first range is 0 mm to 2 mm, the second range is 2 mm to 4 mm, the third range is 4 mm to 8 mm, and the fourth range is greater than 8 mm.

[0144] If the length of the physicochemical erythema is within the first range, then the length of the physicochemical erythema is identified as the first level;

[0145] If the length of the physicochemical erythema is within the second range, then the length of the physicochemical erythema is confirmed as the second level;

[0146] If the length of the physicochemical erythema is within the third range, then the length of the physicochemical erythema is confirmed as the third level;

[0147] If the length of the physicochemical erythema is not within the first, second, or third range, then the length of the physicochemical erythema is classified as the fourth level.

[0148] The first, second, third, or fourth level is identified as the erythema level.

[0149] Explainable, the first, second, third and fourth levels are the levels obtained after judging based on the first, second, third and fourth ranges of the feature range.

[0150] To address the problems described in the background art, this invention first receives a storage stability analysis command and obtains a set of lyophilized products based on the received command and storage parameters. The lyophilized products include a vaccine adjuvant and a vaccine antigen. The vaccine adjuvant is CpG1018, and the vaccine antigen is a 13-valent pneumococcal polysaccharide-CRM197 conjugate. By using the storage stability analysis command and standardized storage parameters, it can be ensured that all lyophilized vaccine samples undergo identical storage conditions, eliminating interference from human or environmental variations on subsequent data. Secondly, all lyophilized products in the set are reconstituted to obtain a set of reconstituted products. This reconstitution simulates the actual operation before clinical administration, ensuring a high degree of consistency between the physicochemical and biological test results and the final usage method. Then, reconstituted products are sequentially extracted from the set, and the extracted reconstituted products are divided into three equal portions. The product groups were divided into equal parts for testing to obtain adjuvant purity, nucleic acid-protein ratio, and mass deviation. Each reconstituted sample was divided into three equal parts to ensure parallel samples of the same volume, concentration, and source, providing a basis for consistency in the three tests. By testing adjuvant purity, nucleic acid-protein ratio, and mass deviation, the physicochemical quality of the vaccine can be evaluated from multiple perspectives. Furthermore, based on the adjuvant purity, nucleic acid-protein ratio, and mass deviation, a physicochemically stable vaccine was obtained, realizing automated and repeatable stability determination. Finally, the physicochemically stable vaccine, the first experimental solution, and the second experimental solution were used to inject experimental subjects to obtain reaction characteristics. Based on the characteristic range and reaction characteristics, the vaccine determination parameters were obtained. The storage stability of the CpG1018 vaccine was analyzed based on the vaccine determination parameters. Simultaneous testing was conducted on experimental mice and rabbits, making the storage stability conclusions more universal and predictive, and improving the accuracy of vaccine storage stability analysis. Therefore, this invention can improve the accuracy of vaccine storage stability analysis.

[0151] like Figure 2 The diagram shown is a functional block diagram of an analysis system based on the storage stability of CpG1018 vaccine provided in an embodiment of the present invention.

[0152] The CpG1018 vaccine storage stability analysis system 100 described in this invention can be installed in an electronic device. Depending on the functions implemented, the CpG1018 vaccine storage stability analysis system 100 may include a reconstituted product acquisition module 101, a physicochemical parameter detection module 102, a stable vaccine acquisition module 103, and a storage stability analysis module 104. The module described in this invention can also be called a unit, which refers to a series of computer program segments that can be executed by the processor of an electronic device and can perform a fixed function, stored in the memory of the electronic device.

[0153] The reconstituted product acquisition module 101 is used to receive storage stability analysis instructions and acquire a set of lyophilized products according to the storage stability analysis instructions and preset storage parameters. The lyophilized products include: vaccine adjuvant and vaccine antigen. The vaccine adjuvant is CpG1018 vaccine adjuvant and the vaccine antigen is 13-valent pneumococcal polysaccharide-CRM197 conjugate.

[0154] All freeze-dried products in the freeze-dried product set are re-melted to obtain a re-melted product set;

[0155] The physicochemical parameter detection module 102 is used to sequentially extract reconstituted products from the reconstituted product set, and perform an equal division operation on the extracted reconstituted products to obtain an equal product group, wherein the equal division is into three equal parts;

[0156] The adjuvant purity, nucleic acid-to-protein ratio, and quality deviation were obtained by testing the aforementioned aliquots.

[0157] The stable vaccine acquisition module 103 is used to acquire a physicochemically stable vaccine based on the adjuvant purity, nucleic acid-protein ratio and quality deviation.

[0158] The storage stability analysis module 104 is used to obtain a first experimental solution and a second experimental solution, wherein the first experimental solution is physiological saline and the second experimental solution is a 13-valent pneumococcal polysaccharide conjugate vaccine;

[0159] The pre-set experimental subjects are injected with the physicochemically stable vaccine, the first experimental solution, and the second experimental solution to obtain reaction characteristics. The vaccine determination parameters are obtained based on the pre-set characteristic range and reaction characteristics. The storage stability of CpG1018 vaccine is analyzed based on the vaccine determination parameters. The experimental subjects include experimental mice and experimental rabbits. The characteristic range includes a first range, a second range, a third range, and a fourth range.

[0160] In detail, the modules in the CpG1018 vaccine storage stability analysis system 100 described in this embodiment of the invention employ the same methods as described above. Figure 1 The analytical method based on the storage stability of CpG1018 vaccine described herein uses the same technical means and can produce the same technical effect, so it will not be repeated here.

[0161] like Figure 3 The diagram shown is a schematic representation of an electronic device for implementing an analysis method based on the storage stability of CpG1018 vaccine, according to an embodiment of the present invention.

[0162] The electronic device 1 may include a processor 10, a memory 11 and a bus 12, and may also include a computer program stored in the memory 11 and executable on the processor 10, such as an analysis method program based on the storage stability of CpG1018 vaccine.

[0163] The memory 11 includes at least one type of readable storage medium, such as flash memory, portable hard drive, multimedia card, card-type memory (e.g., SD or DX memory), magnetic memory, magnetic disk, optical disk, etc. In some embodiments, the memory 11 can be an internal storage unit of the electronic device 1, such as the portable hard drive of the electronic device 1. In other embodiments, the memory 11 can be an external storage device of the electronic device 1, such as a plug-in portable hard drive, smart media card (SMC), secure digital card (SD), flash card, etc., equipped on the electronic device 1. Furthermore, the memory 11 includes both internal storage units and external storage devices of the electronic device 1. The memory 11 can be used not only to store application software and various types of data installed on the electronic device 1, such as the code of an analysis method program based on the storage stability of CpG1018 vaccine, but also to temporarily store data that has been output or will be output.

[0164] In some embodiments, the processor 10 may be composed of integrated circuits, such as a single packaged integrated circuit or multiple integrated circuits with the same or different functions, including combinations of one or more central processing units (CPUs), microprocessors, digital processing chips, graphics processors, and various control chips. The processor 10 is the control unit of the electronic device, connecting various components of the entire electronic device through various interfaces and lines. It executes programs or modules stored in the memory 11 (e.g., analysis methods for the storage stability of CpG1018 vaccine), and calls data stored in the memory 11 to perform various functions of the electronic device 1 and process data.

[0165] The bus 12 can be a peripheral component interconnect (PCI) bus or an extended industry standard architecture (EISA) bus, etc. The bus 12 can be divided into an address bus, a data bus, a control bus, etc. The bus 12 is configured to realize the connection and communication between the memory 11 and at least one processor 10, etc.

[0166] Figure 3 Only electronic devices with components are shown; it will be understood by those skilled in the art that... Figure 3 The structure shown does not constitute a limitation on the electronic device 1, and may include fewer or more components than shown, or combine certain components, or have different component arrangements.

[0167] For example, although not shown, the electronic device 1 may also include a power supply (such as a battery) to power the various components. Preferably, the power supply can be logically connected to the at least one processor 10 through a power management device, thereby enabling functions such as charging management, discharging management, and power consumption management. The power supply may also include one or more DC or AC power supplies, recharging devices, power fault detection circuits, power converters or inverters, power status indicators, and other arbitrary components. The electronic device 1 may also include various sensors, Bluetooth modules, Wi-Fi modules, etc., which will not be described in detail here.

[0168] Furthermore, the electronic device 1 may also include a network interface. Optionally, the network interface may include a wired interface and / or a wireless interface (such as a Wi-Fi interface, a Bluetooth interface, etc.), which is typically used to establish communication connections between the electronic device 1 and other electronic devices.

[0169] Optionally, the electronic device 1 may further include a user interface, which may be a display, an input unit (such as a keyboard), and optionally, a standard wired interface or a wireless interface. Optionally, in some embodiments, the display may be an LED display, a liquid crystal display, a touch-sensitive liquid crystal display, or an OLED (Organic Light-Emitting Diode) touchscreen, etc. The display may also be appropriately referred to as a screen or display unit, used to display information processed in the electronic device 1 and to display a visual user interface.

[0170] The analysis method program based on the storage stability of CpG1018 vaccine stored in the memory 11 of the electronic device 1 is a combination of multiple instructions. When run in the processor 10, it can achieve the following:

[0171] Receive storage stability analysis instructions, and obtain a set of freeze-dried products according to the storage stability analysis instructions and preset storage parameters. The freeze-dried products include: vaccine adjuvant and vaccine antigen. The vaccine adjuvant is CpG1018 vaccine adjuvant and the vaccine antigen is 13-valent pneumococcal polysaccharide-CRM197 conjugate.

[0172] All freeze-dried products in the freeze-dried product set are re-melted to obtain a re-melted product set;

[0173] Redissolved products are extracted sequentially from the redissolved product set, and the extracted redissolved products are divided into equal parts to obtain equal product groups, wherein the equal parts are divided into three equal parts;

[0174] The adjuvant purity, nucleic acid-to-protein ratio, and quality deviation were obtained by testing the aforementioned aliquots.

[0175] A physicochemically stable vaccine was obtained based on the adjuvant purity, nucleic acid-to-protein ratio, and quality deviation.

[0176] Obtain a first experimental solution and a second experimental solution, wherein the first experimental solution is physiological saline and the second experimental solution is a 13-valent pneumococcal polysaccharide conjugate vaccine;

[0177] The pre-set experimental subjects are injected with the physicochemically stable vaccine, the first experimental solution, and the second experimental solution to obtain reaction characteristics. The vaccine determination parameters are obtained based on the pre-set characteristic range and reaction characteristics. The storage stability of CpG1018 vaccine is analyzed based on the vaccine determination parameters. The experimental subjects include experimental mice and experimental rabbits. The characteristic range includes a first range, a second range, a third range, and a fourth range.

[0178] Specifically, the processor 10's implementation method for the above instructions can be found in [reference needed]. Figures 1 to 3 The descriptions of the relevant steps in the corresponding embodiments are not repeated here.

[0179] Furthermore, if the modules / units integrated in the electronic device 1 are implemented as software functional units and sold or used as independent products, they can be stored in a computer-readable storage medium. The computer-readable storage medium can be volatile or non-volatile. For example, the computer-readable medium may include: any entity or device capable of carrying the computer program code, a recording medium, a USB flash drive, a portable hard drive, a magnetic disk, an optical disk, a computer memory, or a read-only memory (ROM).

[0180] The present invention also provides a computer-readable storage medium storing a computer program, which, when executed by a processor of an electronic device, can perform the following:

[0181] Receive storage stability analysis instructions, and obtain a set of freeze-dried products according to the storage stability analysis instructions and preset storage parameters. The freeze-dried products include: vaccine adjuvant and vaccine antigen. The vaccine adjuvant is CpG1018 vaccine adjuvant and the vaccine antigen is 13-valent pneumococcal polysaccharide-CRM197 conjugate.

[0182] All freeze-dried products in the freeze-dried product set are re-melted to obtain a re-melted product set;

[0183] Redissolved products are extracted sequentially from the redissolved product set, and the extracted redissolved products are divided into equal parts to obtain equal product groups, wherein the equal parts are divided into three equal parts;

[0184] The adjuvant purity, nucleic acid-to-protein ratio, and quality deviation were obtained by testing the aforementioned aliquots.

[0185] A physicochemically stable vaccine was obtained based on the adjuvant purity, nucleic acid-to-protein ratio, and quality deviation.

[0186] Obtain a first experimental solution and a second experimental solution, wherein the first experimental solution is physiological saline and the second experimental solution is a 13-valent pneumococcal polysaccharide conjugate vaccine;

[0187] The pre-set experimental subjects are injected with the physicochemically stable vaccine, the first experimental solution, and the second experimental solution to obtain reaction characteristics. The vaccine determination parameters are obtained based on the pre-set characteristic range and reaction characteristics. The storage stability of CpG1018 vaccine is analyzed based on the vaccine determination parameters. The experimental subjects include experimental mice and experimental rabbits. The characteristic range includes a first range, a second range, a third range, and a fourth range.

[0188] In the embodiments provided by this invention, it should be understood that the disclosed devices, systems, and methods can be implemented in other ways. For example, the system embodiments described above are merely illustrative, and actual implementations may have other classification methods.

[0189] The modules described as separate components may or may not be physically separate. The components shown as modules may or may not be physical units; that is, they may be located in one place or distributed across multiple network units. Some or all of the modules can be selected to achieve the purpose of this embodiment according to actual needs.

[0190] Furthermore, the functional modules in the various embodiments of the present invention can be integrated into one processing unit, or each unit can exist physically separately, or two or more units can be integrated into one unit. The integrated unit can be implemented in hardware or in the form of hardware plus software functional modules.

[0191] It will be apparent to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above, and that the present invention can be implemented in other specific forms without departing from the spirit or essential characteristics of the present invention.

[0192] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit it. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention.

Claims

1. An analytical method for CpG 1018 vaccine storage stability, characterized by, The method comprises: receiving a storage stability analysis instruction, obtaining a freeze-dried product set according to the storage stability analysis instruction and a preset storage parameter, wherein the freeze-dried product comprises a vaccine adjuvant and a vaccine antigen, the vaccine adjuvant is a CpG1018 vaccine adjuvant, and the vaccine antigen is a 13-valent pneumococcal polysaccharide-CRM197 conjugate; re-dissolving all freeze-dried products in the freeze-dried product set to obtain a re-dissolved product set; extracting re-dissolved products from the re-dissolved product set in sequence and performing aliquoting on the extracted re-dissolved products to obtain an aliquot product group, wherein the aliquoting is three aliquoting; detecting the aliquot product group to obtain adjuvant purity, nucleic acid protein ratio and mass deviation, wherein the mass deviation is calculated according to a theoretical molecular mass and a relative molecular mass, and the theoretical molecular mass is a mass calculated according to a molecular chemical formula, atomic composition and chemical bond connection method of the CpG1018; obtaining a physicochemical stable vaccine according to the adjuvant purity, the nucleic acid protein ratio and the mass deviation; wherein obtaining the physicochemical stable vaccine according to the adjuvant purity, the nucleic acid protein ratio and the mass deviation means judging the adjuvant purity, the nucleic acid protein ratio and the mass deviation according to adjuvant purity standards, nucleic acid protein ratio standards and mass deviation standards, and when the adjuvant purity, the nucleic acid protein ratio and the mass deviation meet the adjuvant purity standards, the nucleic acid protein ratio standards and the mass deviation standards, the re-dissolved product corresponding to the adjuvant purity, the nucleic acid protein ratio and the mass deviation is confirmed as the physicochemical stable vaccine; obtaining a first experimental solution and a second experimental solution, wherein the first experimental solution is normal saline, and the second experimental solution is a 13-valent pneumococcal polysaccharide conjugate vaccine; injecting a preset experimental body with the physicochemical stable vaccine, the first experimental solution and the second experimental solution to obtain a reaction characteristic, judging according to a preset characteristic range and the reaction characteristic to obtain a vaccine judgment parameter, and completing analysis of the storage stability of the CpG1018 vaccine according to the vaccine judgment parameter, wherein the experimental body comprises experimental mice and experimental rabbits, the characteristic range is used to judge a physicochemical erythema length to obtain an erythema grade, the physicochemical erythema length refers to the size of the diameter of the erythema generated after the experimental mice and the experimental rabbits are injected with the physicochemical stable vaccine, and the characteristic range comprises a first range, a second range, a third range and a fourth range.

2. The method of claim 1, wherein the CpG 1018 vaccine stability is analyzed based on the amount of CpG 1018 in the vaccine. The storage parameter comprises a storage temperature and a storage time, wherein the storage temperature comprises a refrigeration temperature, a short-term temperature and an accelerated temperature, the refrigeration temperature is 2-6°C, the short-term temperature is 23-27°C, the accelerated temperature is 38-42°C, and the storage time comprises 0 months, 1 month, 2 months, 3 months, 6 months, 12 months and 18 months.

3. The method for analyzing the storage stability of a CpG 1018 vaccine according to claim 2, wherein The detection of the aliquot product group to obtain the adjuvant purity, the nucleic acid protein ratio and the mass deviation comprises: labeling the aliquot product group to obtain a first product, a second product and a third product; Obtaining a first experimental solid, and dissolving the first experimental solid to obtain a third experimental solution, wherein the first experimental solid is triethylamine-acetic acid solid, and a liquid used for dissolving the first experimental solid is deionized water; Adjusting the third experimental solution by using a preset adjusting solution to obtain a first adjusting solution, detecting an adjusted pH value of the first adjusting solution, and calculating a pH difference value according to the adjusted pH value and a preset pH standard value; Comparing the pH difference value with a preset pH difference value threshold; If the pH difference value is greater than the pH difference value threshold, updating the third experimental solution by using the first adjusting solution, and returning to the step of adjusting the third experimental solution by using the preset adjusting solution until the pH difference value is less than or equal to the pH difference value threshold; If the pH difference value is less than or equal to the pH difference value threshold, confirming the first adjusting solution as a first target adjusting solution; Obtaining an adjuvant purity according to the first target adjusting solution, a first product and a preset second target adjusting solution; Obtaining a nucleic acid protein ratio according to the second product and a preset comparative solution, and obtaining a quality deviation based on the third product.

4. The analytical method for the storage stability of CpG1018 vaccine as described in claim 3, characterized in that, The method for obtaining the adjuvant purity according to the first target adjusting solution, the first product and the preset second target adjusting solution comprises: Performing in-column separation by using the first target adjusting solution, the second target adjusting solution and the first product, and performing reading by using a pre-constructed reading software to obtain an absorbance value and a reading time; Drawing an experimental chromatogram by using the absorbance value and the reading time, and obtaining a main peak area and a total area from the experimental chromatogram; Calculating the adjuvant purity according to the main peak area and the total area, wherein the adjuvant purity is the main peak area to the total area.

5. The method of claim 4, wherein the CpG 1018 vaccine stability is analyzed based on the amount of CpG 1018 in the vaccine. The method for obtaining the nucleic acid protein ratio according to the second product and the preset comparative solution comprises: Preheating a pre-constructed double-beam ultraviolet-visible spectrophotometer, and recording a preheating time; Comparing the preheating time with a preset target time; If the preheating time is less than the target time, obtaining a current preheating time, updating the preheating time by using the current preheating time, and returning to the step of comparing the preheating time with the preset target time by using the updated preheating time until the preheating time is greater than or equal to the target time; If the preheating time is greater than or equal to the target time, confirming the double-beam ultraviolet-visible spectrophotometer as a ready-to-measure device; Scanning the second product and the comparative solution by using the ready-to-measure device to obtain a first reading and a second reading, wherein the first reading is an absorbance value corresponding to 260 nm, and the second reading is an absorbance value corresponding to 280 nm; Calculating the nucleic acid protein ratio according to the first reading and the second reading, wherein the nucleic acid protein ratio is the first reading to the second reading.

6. The method of claim 5, wherein the CpG 1018 vaccine stability is analyzed based on the amount of CpG 1018 in the vaccine. The method for obtaining the reaction characteristics by using the physicochemical stable vaccine, the first experimental solution and the second experimental solution comprises: Obtaining a set of experimental mice and a set of experimental rabbits from the experimental bodies based on a preset number of first experimental bodies and a preset number of second experimental bodies, wherein the number of first experimental bodies corresponds to the number of experimental mice, and the number of second experimental bodies corresponds to the number of experimental rabbits; According to the physicochemical stable vaccine, the first experimental solution, the second experimental solution, the experimental mouse set and the experimental rabbit set are distributed to obtain a physicochemical experimental body set, a physiological experimental body set and a combined experimental body set, wherein the physicochemical experimental body set includes physicochemical experimental mice and physicochemical experimental rabbits, the physiological experimental body set includes physiological experimental mice and physiological experimental rabbits, and the combined experimental body set includes combined experimental mice and combined experimental rabbits, and the number of physicochemical experimental mice, physiological experimental mice and combined experimental mice is the same, and the number of physicochemical experimental rabbits, physiological experimental rabbits and combined experimental rabbits is the same; The physicochemical stable vaccine, the first experimental solution and the second experimental solution are used to inject all experimental bodies in the physicochemical experimental body set, the physiological experimental body set and the combined experimental body set respectively to obtain reaction characteristics.

7. The method of claim 6, wherein the CpG 1018 vaccine stability is analyzed based on the amount of CpG 1018 in the vaccine. The physicochemical stable vaccine, the first experimental solution and the second experimental solution are used to inject all experimental bodies in the physicochemical experimental body set, the physiological experimental body set and the combined experimental body set respectively to obtain reaction characteristics. The physicochemical stable vaccine, the preset experimental mouse injection position and the preset experimental rabbit injection position are used to inject all physicochemical experimental mice and physicochemical experimental rabbits in the physicochemical experimental body set, and after a preset waiting time, physicochemical reaction characteristics are obtained, wherein the physicochemical reaction characteristics include physicochemical body weight change, physicochemical rectal temperature and physicochemical erythema length. The first experimental solution, the experimental mouse injection position and the experimental rabbit injection position are used to inject all physiological experimental mice and physiological experimental rabbits in the physiological experimental body set, and after a waiting time, physiological reaction characteristics are obtained, wherein the physiological reaction characteristics include physiological body weight change and physiological rectal temperature. Based on the second experimental solution, the experimental mouse injection position and the experimental rabbit injection position, all combined experimental mice and combined experimental rabbits in the combined experimental body set are injected, and after a waiting time, combined reaction characteristics are obtained, wherein the combined reaction characteristics include combined body weight change and combined rectal temperature. The physicochemical reaction characteristics, the physiological reaction characteristics and the combined reaction characteristics are confirmed as reaction characteristics.

8. The method of claim 7, wherein the CpG 1018 vaccine stability is analyzed based on the amount of CpG 1018 in the vaccine. The physicochemical stable vaccine, the first experimental solution and the second experimental solution are used to inject all experimental bodies in the physicochemical experimental body set, the physiological experimental body set and the combined experimental body set respectively to obtain reaction characteristics. The physicochemical stable vaccine, the first experimental solution and the second experimental solution are used to inject all experimental bodies in the physicochemical experimental body set, the physiological experimental body set and the combined experimental body set respectively to obtain reaction characteristics. The physicochemical stable vaccine, the preset experimental mouse injection position and the preset experimental rabbit injection position are used to inject all physicochemical experimental mice and physicochemical experimental rabbits in the physicochemical experimental body set, and after a preset waiting time, physicochemical reaction characteristics are obtained, wherein the physicochemical reaction characteristics include physicochemical body weight change, physicochemical rectal temperature and physicochemical erythema length. The first experimental solution, the experimental mouse injection position and the experimental rabbit injection position are used to inject all physiological experimental mice and physiological experimental rabbits in the physiological experimental body set, and after a waiting time, physiological reaction characteristics are obtained, wherein the physiological reaction characteristics include physiological body weight change and physiological rectal temperature. Based on the second experimental solution, the experimental mouse injection position and the experimental rabbit injection position, all combined experimental mice and combined experimental rabbits in the combined experimental body set are injected, and after a waiting time, combined reaction characteristics are obtained, wherein the combined reaction characteristics include combined body weight change and combined rectal temperature. The physicochemical reaction characteristics, the physiological reaction characteristics and the combined reaction characteristics are confirmed as reaction characteristics. The physicochemical stable vaccine, the first experimental solution and the second experimental solution are used to inject all experimental bodies in the physicochemical experimental body set, the physiological experimental body set and the combined experimental body set respectively to obtain reaction characteristics. The physicochemical stable vaccine, the first experimental solution and the second experimental solution are used to inject all experimental bodies in the physicochemical experimental body set, the physiological experimental body set and the combined experimental body set respectively to obtain reaction characteristics. The physicochemical stable vaccine, the preset experimental mouse injection position and the preset experimental rabbit injection position are used to inject all physicochemical experimental mice and physicochemical experimental rabbits in the physicochemical experimental body set, and after a preset waiting time, physicochemical reaction characteristics are obtained, wherein the physicochemical reaction characteristics include physicochemical body weight change, physicochemical rectal temperature and physicochemical erythema length. The first experimental solution, the experimental mouse injection position and the experimental rabbit injection position are used to inject all physiological experimental mice and physiological experimental rabbits in the physiological experimental body set, and after a waiting time, physiological reaction characteristics are obtained, wherein the physiological reaction characteristics include physiological body weight change and physiological rectal temperature. Based on the second experimental solution, the experimental mouse injection position and the experimental rabbit injection position, all combined experimental mice and combined experimental rabbits in the combined experimental body set are injected, and after a waiting time, combined reaction characteristics are obtained, wherein the combined reaction characteristics include combined body weight change and combined rectal temperature. The physicochemical reaction characteristics, the physiological reaction characteristics and the combined reaction characteristics are confirmed as reaction characteristics. The physicochemical stable vaccine, the first experimental solution and the second experimental solution are used to inject all experimental bodies in the physicochemical experimental body set, the physiological experimental body set and the combined experimental body set respectively to obtain reaction characteristics. The first temperature change value and the second temperature change value are calculated by using the physicochemical rectal temperature, the physiological rectal temperature and the combined rectal temperature, wherein the first temperature change value is a change value of a difference between the physicochemical rectal temperature and the physiological rectal temperature, and the second temperature change value is a change value of a difference between the physicochemical rectal temperature and the combined rectal temperature; The first temperature change value and the second temperature change value are compared with a preset temperature threshold value; If the first temperature change value and the second temperature change value are both less than or equal to the temperature threshold value, the physicochemical rectal temperature is confirmed as a safe rectal temperature; If the first temperature change value and the second temperature change value are not both less than or equal to the temperature threshold value, the physicochemical rectal temperature is confirmed as an abnormal rectal temperature; The physicochemical erythema length is determined by using the characteristic range to obtain an erythema grade, and the safe body weight change, the abnormal body weight change, the safe rectal temperature, the abnormal rectal temperature and the erythema grade are confirmed as vaccine determination parameters.

9. The method of claim 8, wherein the CpG 1018 vaccine stability is analyzed based on the amount of CpG 1018 in the vaccine formulation. The determination of the physicochemical erythema length by using the characteristic range to obtain an erythema grade comprises: The physicochemical erythema length is compared with a first range, a second range, a third range and a fourth range of the characteristic range, wherein the first range is 0 mm to 2 mm, the second range is 2 mm to 4 mm, the third range is 4 mm to 8 mm, and the fourth range is greater than 8 mm; If the physicochemical erythema length is in the first range, the physicochemical erythema length is confirmed as a first grade; If the physicochemical erythema length is in the second range, the physicochemical erythema length is confirmed as a second grade; If the physicochemical erythema length is in the third range, the physicochemical erythema length is confirmed as a third grade; If the physicochemical erythema length is not in the first range, the second range or the third range, the physicochemical erythema length is confirmed as a fourth grade; The first grade, the second grade, the third grade or the fourth grade is confirmed as an erythema grade.

10. An analytical system for the stability of CpG 1018 vaccine based on, The system comprises: The re-dissolved product obtaining module is configured to receive a storage stability analysis instruction, and obtain a set of freeze-dried products according to the storage stability analysis instruction and preset storage parameters, wherein the freeze-dried products comprise a vaccine adjuvant and a vaccine antigen, the vaccine adjuvant is a CpG1018 vaccine adjuvant, and the vaccine antigen is a 13-valent pneumococcal polysaccharide-CRM197 conjugate; All the freeze-dried products in the set of freeze-dried products are re-dissolved to obtain a set of re-dissolved products; The physicochemical parameter detection module is configured to sequentially extract re-dissolved products from the set of re-dissolved products, and perform an equal division operation on the extracted re-dissolved products to obtain an equal division product group, wherein the equal division is three equal divisions; The equal division product group is detected to obtain an adjuvant purity, a nucleic acid protein ratio and a mass deviation, wherein the mass deviation is calculated according to a theoretical molecular mass and a relative molecular mass, and the theoretical molecular mass is a mass calculated according to a molecular chemical formula, atomic composition and chemical bond connection method of the CpG1018; The stable vaccine obtaining module is configured to obtain a physicochemical stable vaccine according to the adjuvant purity, the nucleic acid protein ratio and the mass deviation. The physicochemical stable vaccine is determined according to the adjuvant purity, the nucleic acid protein ratio and the mass deviation. When the adjuvant purity, the nucleic acid protein ratio and the mass deviation meet the adjuvant purity standard, the nucleic acid protein ratio standard and the mass deviation standard, the redissolved product corresponding to the adjuvant purity, the nucleic acid protein ratio and the mass deviation is confirmed as the physicochemical stable vaccine. The storage stability analysis module is configured to obtain a first experimental solution and a second experimental solution. The first experimental solution is normal saline, and the second experimental solution is a 13-valent pneumococcal polysaccharide conjugate vaccine. The physicochemical stable vaccine, the first experimental solution and the second experimental solution are used to inject a preset experimental body to obtain a reaction characteristic. The preset characteristic range and the reaction characteristic are determined to obtain a vaccine determination parameter. The vaccine determination parameter is used to analyze the storage stability of the CpG1018 vaccine. The experimental body includes experimental mice and experimental rabbits. The characteristic range is used to determine a physicochemical erythema length to obtain an erythema grade. The physicochemical erythema length refers to the size of the diameter of the erythema generated after the experimental mice and the experimental rabbits are injected with the physicochemical stable vaccine. The characteristic range includes a first range, a second range, a third range and a fourth range.

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