Spaceflight amino acid immunomodulatory system for microgravity environments and methods of making

Abstract

The present application relates to aerospace medicine and intelligent drug release technology, and provides a kind of aerospace amino acid immunomodulatory system for microgravity environment and preparation method.The scheme solves the problem that existing amino acid immunomodulator cannot be dynamically adjusted according to the real-time state of the body, with real-time detection and control function based on the change of cortisol concentration.The system includes a cortisol detection unit (containing a three-electrode electrochemical sensor of modified gold nanoparticles), a control unit (a 32-bit microcontroller with three-stage threshold judgment), a segmented drug-loaded microcapsule (with a three-cavity structure, loaded with different proportions of amino acids, and made of specific PLGA), and a release control unit (composed of three electromagnetic valves, controlled by a 1kHz PWM signal).It is suitable for maintaining the immune function of astronauts in microgravity environment.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of space medicine and intelligent drug release technology, in particular to a space amino acid immune regulation system for microgravity environment and a preparation method thereof, which is used for maintaining the immune function of astronauts in a microgravity environment. BACKGROUND

[0002] With the rapid development of manned space technology, the health protection of astronauts in a microgravity environment has attracted increasing attention. Studies have shown that the immune function of astronauts in space environment will decrease by 15-25%, mainly manifested as weakened T cell proliferation ability, abnormal cytokine secretion, etc. Cortisol, as an important stress hormone, its concentration change can accurately reflect the body's stress state and immune function level.

[0003] Currently, cortisol detection technology has developed to a certain extent. The existing technology mainly uses cortisol monoclonal antibody functionalized working electrode to detect cortisol concentration by antigen-antibody interaction to produce current change, but this technology is mainly used for environmental control system and does not involve drug release control. Another technology uses G-quadruplex structure change to realize cortisol detection, which has high specificity, but is limited to detection function and lacks subsequent therapeutic intervention ability. There are also various biomarker detection electronic devices based on LC circuit, which can simultaneously detect multiple indicators including cortisol, but the system complexity is high and integration with the treatment system has not been realized.

[0004] In terms of immune regulation drugs, the existing technology mainly uses fixed ratio amino acid preparations. These preparations can enhance immune function to a certain extent, but have the following shortcomings: first, they cannot be dynamically adjusted according to the real-time physiological state of the body, resulting in poor adaptability in different stress stages; second, they lack individualized design and cannot adapt to physiological differences of different individuals; third, the response time is long, usually taking 24-48 hours to take effect, which is difficult to meet the rapid response requirements in special environments such as space.

[0005] In addition, the existing drug release system is mainly in passive control mode, such as time-controlled release or pH response, which lacks active control ability based on physiological indicators. This passive control method cannot achieve precise drug release and is prone to cause drug waste or insufficient dosage, affecting the treatment effect.

[0006] Therefore, it is urgent to develop an intelligent system that can monitor the change of cortisol concentration in real time and automatically adjust the release of amino acids based on the detection results, in order to meet the differentiated immune regulation needs of astronauts in different task stages. SUMMARY

[0007] TECHNICAL PROBLEM

[0008] The technical problem this invention aims to solve is that existing amino acid immunomodulatory agents cannot dynamically adjust according to the body's real-time physiological state, resulting in poor immunomodulatory effects during the three different stages of astronaut launch, on-orbit, and return phases. Specifically, this manifests as follows:

[0009] 1. The lack of integrated real-time detection and release control technology based on changes in cortisol concentration makes it impossible to achieve closed-loop regulation of detection-control-release;

[0010] 2. There is a lack of stage-specific judgment algorithms and differentiated amino acid ratio release technology to address the differences in physiological needs at different task stages;

[0011] 3. Existing carrier systems have long response times (24-48 hours), which cannot meet the adjustment requirements for rapid stress response in aerospace environments.

[0012] Technical solution

[0013] To address the aforementioned technical problems, this invention provides a space amino acid immunomodulation system for microgravity environments. This system integrates three functional modules: cortisol detection, mission-stage cortisol response discrimination algorithm control, and segmented polylactic acid drug-loaded microcapsules for precise release, thereby achieving closed-loop regulation of detection-control-release.

[0014] The aerospace amino acid immunomodulation system for microgravity environments includes a cortisol detection unit, a control unit, segmented drug-loaded microcapsules, and a release control unit. The cortisol detection unit includes a three-electrode electrochemical sensor. The working electrode surface is modified with gold nanoparticles with a particle size of 15–25 nm. Cortisol antibodies are immobilized on the surface of the gold nanoparticles via thiol-gold bonding. The gold nanoparticles are prepared using a sodium citrate reduction method, specifically by heating a chloroauric acid solution to boiling and then adding sodium citrate solution for reduction. The sensor's operating potential range is -0.15 V to +0.75 V relative to the Ag / AgCl reference electrode. The control unit includes a 32-bit microcontroller used to compare the detected cortisol concentration with three preset thresholds and output a chamber activation signal. The segmented drug-loaded microcapsules are made of polylactic-co-glycolic acid copolymer with a molecular weight of 60,000–70,000 Da and a lactic acid to glycolic acid molar ratio of 75:25. They are internally divided into three independent chambers, each containing an amino acid composition with different proportions. The release control unit includes three solenoid valves, which control the opening of the release ports of the three chambers respectively, and control the release rate through a PWM signal with a frequency of 1kHz.

[0015] Gold nanoparticles were prepared by sodium citrate reduction, and the cortisol antibody density was [missing value]. The sensor's relative detection error does not exceed ±8% per cm². The control unit performs a three-stage threshold judgment: when the cortisol concentration is greater than 350 nmol / L, it outputs a first chamber activation signal; when the cortisol concentration is in the range of 200–350 nmol / L and the system is in orbit, it outputs a second chamber activation signal; and when the cortisol concentration is greater than 280 nmol / L but less than 350 nmol / L and the system is in return phase, it outputs a third chamber activation signal.

[0016] The segmented drug-loaded microcapsules have a cylindrical structure with an outer diameter of 15 mm and a total length of 12 mm. Three chambers are arranged axially: the first chamber has a volume of 0.6 mL, the second 0.9 mL, and the third 0.6 mL. The chambers are separated by a 0.5 mm thick pH-responsive polymer membrane made of poly(methacrylic acid)-co-polyethylene glycol methacrylate, which adjusts permeability in response to pH changes. Each chamber has a 0.2 mm pore size release port. The PWM signal duty cycle ranges from 10% to 90%, corresponding to a release rate of 0.1 to 2.0 mg / min. The release rate is linearly related to the PWM duty cycle, allowing for precise release rate control by adjusting the duty cycle. The control unit also includes an individualized baseline adaptive learning module, which establishes individual baseline values ​​through continuous cortisol concentration monitoring over 48–96 hours. The individualized baseline adaptive learning module calculates stress regulation factors.

[0017]

[0018] in The value ranges from 0.8 to 1.2. The value is between 0.1 and 0.3.

[0019] This invention also provides a control method for a space amino acid immunomodulatory system in a microgravity environment, comprising the following steps: detecting cortisol concentration in body fluids using a gold nanoparticle-modified three-electrode electrochemical sensor, scanning within a potential range of -0.15V to +0.75V using cyclic voltammetry; comparing the detected cortisol concentration value with three preset thresholds and performing a three-stage judgment; calculating a stress regulation factor based on the judgment results; controlling the opening of the solenoid valves of the corresponding chambers in the segmented drug-loaded microcapsules and adjusting the release rate using PWM signals; monitoring changes in cortisol concentration, and stopping release when two consecutive detection results show that the cortisol concentration has returned to within ±20% of the individual baseline value. The method also includes an individualized baseline calibration step, establishing an individual cortisol baseline value by continuously detecting for 48–96 hours before system startup, with the baseline value calculated as the average value after removing the highest and lowest 10% of data.

[0020] This invention also provides a three-stage differentiated amino acid composition, comprising a first-compartment high-intensity immune support composition, a second-compartment maintenance immune support composition, and a third-compartment recovery immune support composition. The first-compartment high-intensity immune support composition contains 20±2 g / L arginine, 15±2 g / L glutamine, and 0.1 g / L sodium ascorbate. The second-compartment maintenance immune support composition contains eight essential amino acids: leucine, isoleucine, valine, threonine, methionine, phenylalanine, tryptophan, and lysine, with a total concentration of 25±3 g / L. The third-compartment recovery immune support composition contains a total concentration of 15±2 g / L branched-chain amino acids, wherein the molar ratio of leucine, isoleucine, and valine is 2.0:1.0:1.0, and 1.0 g / L taurine is added.

[0021] Beneficial effects

[0022] The present invention has the following beneficial effects:

[0023] By integrating an electrochemical sensor modified with gold nanoparticles and a PWM-controlled solenoid valve release system, a closed-loop integrated control of cortisol detection and amino acid release was achieved, reducing the system response time from 24-48 hours in traditional technologies to less than 1.6 hours. This is because the high specific surface area and excellent electron transfer performance of gold nanoparticles improve the sensor's detection sensitivity, while the precisely controlled PWM solenoid valve enables instantaneous release response, resulting in a response speed improvement of over 93.3% compared to existing technologies.

[0024] An innovative three-stage threshold judgment algorithm is adopted, which can automatically switch control strategies according to different stages of the space mission (launch, on-orbit, and return), achieving precise phased immune regulation. By setting differentiated cortisol concentration thresholds of 350 nmol / L during launch, 200-350 nmol / L during on-orbit, and 280-350 nmol / L during return, and combining three amino acid compositions with different ratios, the immune function maintenance rate has been increased from 60% of the traditional technology to over 75%.

[0025] A unique segmented polylactic acid (PLGA) drug-loaded microcapsule three-chamber structure design, utilizing PLGA material with a molecular weight of 60,000-70,000 Da and a lactic acid to glycolic acid molar ratio of 75:25, achieves selective release of three different amino acid ratios. The carrier maintains structural integrity in environments ranging from -20℃ to 60℃, and its structural stability retention rate is greater than 95% within 18 months under simulated aerospace radiation conditions, with an amino acid activity retention rate of no less than 92%, significantly superior to the 70-80% level of existing technologies.

[0026] Introducing a personalized baseline adaptive learning function, individual baseline values ​​are established through continuous 48-96 hours of cortisol concentration monitoring, stress regulators The dynamic calculations can automatically optimize release parameters based on individual differences. The system reliability reaches over 92.5%, with significantly improved adaptability and stability, effectively solving the problem that existing fixed-ratio formulations cannot adapt to individual differences. Attached Figure Description

[0027] Figure 1 This is a schematic diagram of the overall structure of the aerospace amino acid immunomodulation system for microgravity environment of the present invention, showing the integrated configuration of cortisol detection unit, control unit, drug-loaded microcapsule and release control unit;

[0028] Figure 2 This is a flowchart of the control method of the aerospace amino acid immunomodulation system for microgravity environment according to the present invention, which shows the complete control process from detection to release;

[0029] Figure 3 This is a schematic diagram of the three-chamber structure of the segmented polylactic acid drug-loaded microcapsule of the present invention, showing the axial arrangement of the three chambers and the configuration of the release port. Detailed Implementation

[0030] The present invention will now be described in detail with reference to the accompanying drawings and specific embodiments.

[0031] Example 1: Construction of an aerospace amino acid immunomodulatory system for microgravity environments

[0032] like Figure 1 As shown, the aerospace amino acid immunomodulation system for microgravity environments constructed in this embodiment includes the following components:

[0033] Cortisol detection unit 1: A three-electrode electrochemical sensor modified with gold nanoparticles. The working electrode is a 2 mm diameter gold disk electrode, the reference electrode is an Ag / AgCl electrode, and the auxiliary electrode is a platinum wire electrode.

[0034] Preparation of gold nanoparticles: 1 mL of 1% chloroauric acid solution was added to 99 mL of deionized water and heated to boiling. Then, 1 mL of 1% sodium citrate solution was quickly added, and the mixture was boiled for another 15 minutes until the solution turned wine-red. The solution was then cooled to room temperature. The particle size was determined to be 20 ± 3 nm by transmission electron microscopy, and a characteristic absorption peak was observed at 520 nm in the UV-Vis spectrum.

[0035] Antibody fixation: The prepared gold nanoparticle solution was mixed with 11-mercaptoundecanoic acid (final concentration 10 μM) and reacted at room temperature for 2 hours to form a self-assembled monolayer. Then, it was reacted with EDC / NHS activated cortisol antibody (10 μg / mL) for 12 hours, and the antibody fixation density was determined to be 2.5 × 10¹² particles / cm² using a quartz crystal microbalance.

[0036] Sensor performance testing: The operating potential range is -0.15V to +0.75V, and detection is performed using cyclic voltammetry at a scan rate of 50mV / s. The detection accuracy is ±7.2%, the detection range is 138~550nmol / L, and the linear correlation coefficient is [not specified].

[0037] Control Unit 2: Built on an STM32F407 microcontroller, operating at 168MHz, with a built-in 32-bit ARM Cortex-M4 core. The control unit executes a three-stage threshold judgment algorithm: during launch, a cortisol concentration threshold greater than 350 nmol / L activates a high-intensity immune support mode; during the on-orbit phase, a cortisol concentration threshold between 200 and 350 nmol / L activates a maintenance immune support mode; and during the return phase, a cortisol concentration threshold greater than 280 nmol / L and less than 350 nmol / L activates a recovery immune support mode.

[0038] Personalized baseline adaptive learning module: Establishes individual baseline values ​​through continuous cortisol concentration monitoring for 48–96 hours. Baseline establishment algorithm: Collects cortisol concentration data every 90 minutes for 72 consecutive hours, totaling 48 data points; calculates the 25th percentile of the data. and the 75th percentile Outlier removal; baseline calculation:

[0039]

[0040] The formula for calculating the stress regulation factor is:

[0041]

[0042] Segmented drug-loaded microcapsules 3: The drug-loaded microcapsules are cylindrical structures with an outer diameter of 15 mm and a total length of 12 mm. They are made of PLGA material with a molecular weight of 65,000 Da and a molar ratio of lactic acid to glycolic acid of 75:25.

[0043] Preparation process: PLGA was dissolved in dichloromethane to prepare a 10% w / v solution using a solvent evaporation method. This solution was then emulsified in an aqueous polyvinyl alcohol (PVA) solution and magnetically stirred at 500 rpm for 4 hours at room temperature. A segmented injection molding process was used: first, the bottom chamber was prepared, cured, and then a pH-responsive diaphragm was installed. The middle and top chambers were then prepared sequentially. Laser drilling technology was used to machine a 0.2 mm diameter release port on the sidewall of each chamber.

[0044] The microcapsule is divided into three independent chambers arranged axially. The first chamber has a volume of 0.6 mL, the second chamber has a volume of 0.9 mL, and the third chamber has a volume of 0.6 mL. The chambers are separated by a 0.5 mm thick pH-responsive polymer membrane made of polymethacrylate-co-polyethylene glycol methacrylate.

[0045] Release control unit 4: Includes three independent miniature solenoid valves, each controlling the release port of a drug-loaded microcapsule chamber. Solenoid valve specifications: Operating voltage DC 5V, rated current 50mA, response time ≤30ms. PWM control parameters: Control signal frequency 1kHz, duty cycle range 10%-90%, release rate control equation:

[0046]

[0047] Example 2: Preparation of a three-stage differentiated amino acid composition

[0048] First-compartment high-intensity immune support composition:

[0049] Raw material specifications: L-arginine hydrochloride (purity ≥98%, Sigma-Aldrich); L-glutamine (purity ≥99%, Sigma-Aldrich); sodium ascorbate (purity ≥99%).

[0050] Preparation process: Weigh 20.0g of L-arginine hydrochloride, 15.0g of L-glutamine, and 0.1g of sodium ascorbate; add 800mL of deionized water and stir magnetically to dissolve; adjust the pH to 7.0±0.1 with 1M NaOH solution; add 2.0g of mannitol to adjust the osmotic pressure to 290±10mOsm / kg; bring the volume to 1000mL and filter through a 0.22μm filter membrane for sterilization.

[0051] Quality control: Amino acid content was determined by HPLC: arginine 19.8±0.4 g / L, glutamine 14.9±0.3 g / L; pH 7.0±0.1; osmotic pressure 290±10 mOsm / kg.

[0052] Second-compartment maintenance immune support composition:

[0053] Raw material specifications: All eight essential amino acids are L-type, with a purity ≥98%. Weigh each amino acid according to the following ratio: leucine 3.5g, isoleucine 1.8g, valine 2.5g, threonine 1.5g, methionine 1.2g, phenylalanine 2.8g, tryptophan 0.5g, and lysine hydrochloride 2.2g.

[0054] Preparation process: Add 800 mL of deionized water and heat in a 50°C water bath to aid dissolution; cool to room temperature and adjust the pH to 7.0 ± 0.2 using a disodium hydrogen phosphate / sodium dihydrogen phosphate buffer system; add mannitol to adjust to isotonicity and bring the volume to 1000 mL; filter through a 0.22 μm membrane for sterilization.

[0055] Third-compartment restorative immune support composition:

[0056] Raw material specifications: L-leucine, L-isoleucine, L-valine (purity ≥98%); taurine (purity ≥99%).

[0057] Preparation process: Accurately weigh 7.5g of L-leucine, 3.75g of L-isoleucine, 3.35g of L-valine, and 1.0g of taurine; verify the molar ratio of branched-chain amino acids: leucine (57.2mmol): isoleucine (28.6mmol): valine (28.6mmol) = 2.0:1.0:1.0; add 800mL of deionized water and stir to dissolve at room temperature; adjust the pH to 7.0±0.2 and the osmotic pressure to isotonic; filter to sterilize.

[0058] Example 3: System Performance Testing and Verification

[0059] Detection accuracy verification experiment:

[0060] Using cortisol standard solution (Sigma-Aldrich, purity ≥98%), a concentration gradient was set: 138, 200, 280, 350, 450, 550 nmol / L, with each concentration point tested 10 times. Test conditions: 37°C, pH 7.4 phosphate buffer.

[0061]

[0062] Statistical analysis: Overall detection accuracy ±7.2%, linear correlation coefficient The detection limit is 10 nmol / L, and the quantitation limit is 30 nmol / L.

[0063] Response time test experiment:

[0064] The simulated cortisol concentration increased instantaneously from 200 nmol / L to 400 nmol / L in an environment of 37°C and 60% relative humidity, repeated 20 times. Time points were recorded: moments of cortisol concentration change. min; the sensor detected a change. min; Data processing complete min; Decision completion min; Solenoid valve response min; Carrier begins to release The total response time is 94±6 min, which is far superior to the 24-48 hours of traditional technologies.

[0065] Carrier stability test experiment:

[0066] Accelerated stability test conditions: 40°C / 75%RH, test period of 18 months, test indicators: amino acid content, carrier integrity, release characteristics.

[0067]

[0068] Results analysis: After 18 months, the average retention rates of amino acids were 92.8% (arginine) and 90.5% (glutamine), the integrity of the carrier structure was maintained at 96.2%, and the changes in release characteristics were within acceptable ranges.

[0069] Example 4: Evaluation of the effect of enhancing immune function

[0070] Experimental design: Commercial human peripheral blood mononuclear cell line (PBMC, purchased from ATCC) was used. Experimental groups: blank control group, conventional preparation group, and the present invention group. Evaluation indicators: T cell proliferation rate and cytokine secretion level.

[0071] PBMC culture: Resuspend in RPMI-1640 medium and adjust cell density to 2×10⁶ cells / year. 6 / mL, cultured in 96-well plates, 100μL of cell suspension per well.

[0072] Experimental treatments: The blank control group was treated with only culture medium; the conventional formulation group was treated with a fixed ratio of amino acid mixture (total concentration 20 g / L); the group of the present invention was treated with three different compositions according to the simulated cortisol concentration.

[0073] T cell proliferation assay: PHA stimulant (final concentration 10 μg / mL) was added, and the cells were cultured at 37°C and 5% CO2 for 72 hours. CCK-8 reagent was then added, and the OD450 value was detected.

[0074]

[0075] Note: * indicates a statistically significant difference compared to the conventional formulation group (p<0.05).

[0076] Statistical analysis: The T cell proliferation rate of the first chamber group of the present invention was increased by 9.2% (p<0.05) compared with the traditional preparation group, and the IL-2 secretion level was increased by an average of 4.0% (p<0.05).

[0077] Immune function maintenance rate test: The effectiveness of immune function maintenance is assessed by monitoring T cell proliferation capacity for 7 consecutive days. The immune function maintenance rate is defined as:

[0078]

[0079]

[0080] Note: * indicates a statistically significant difference compared to the conventional formulation group (p<0.01).

[0081] Example 5: Fabrication and Testing of a Time-Programmed Control System

[0082] System configuration: The three-chamber carrier design and solenoid valve control unit of the present invention are retained, but the cortisol detection function is removed and replaced with a preset time program for release: the first chamber is released after 0-24 hours, the second chamber is released after 24-168 hours, and the third chamber is released after 168 hours.

[0083] Preparation method: The same drug-loaded microcapsule preparation process as in Example 1 was used, but the control unit was changed to a timer controller based on an RTC clock to activate the solenoid valve of the corresponding chamber according to a preset time schedule.

[0084] Performance testing:

[0085]

[0086] Release accuracy test method: The matching degree between the actual released amino acid concentration and the expected concentration is detected by HPLC. Drug utilization test method: The percentage of effectively released drug relative to the total load is calculated.

[0087] Comparative Example 1: Fixed-ratio amino acid preparation

[0088] Preparation method: According to the standard formula of commercially available immune-enhancing amino acid preparations, a fixed ratio of amino acid mixture was prepared: arginine 8g / L, glutamine 6g / L, leucine 2g / L, isoleucine 1g / L, valine 1g / L, other amino acids 2g / L, and a total concentration of 20g / L.

[0089]

[0090] Results analysis: Fixed-ratio formulations, unable to adjust to actual physiological states, exhibit poor adaptability under different stress stages. The system of this invention achieves more precise immunomodulatory effects through real-time detection and dynamic adjustment.

[0091] As can be seen from the above embodiments and comparative examples, the aerospace amino acid immunomodulation system for microgravity environments of the present invention significantly outperforms existing technologies in terms of detection accuracy, response time, and immune enhancement effect, effectively meeting the differentiated immunomodulation needs of astronauts at different mission stages. The system's innovation lies in the integrated detection of cortisol and amino acid release, the intelligent control of the mission-stage cortisol response discrimination algorithm, and the differentiated release design of segmented polylactic acid drug-loaded microcapsules. The synergistic effect of these technical features has produced unexpected technical results, making significant technological contributions to the fields of aerospace medicine and intelligent drug release technology.

Claims

1. A space-based amino acid immunomodulatory system for microgravity environments, characterized in that, The system comprises a cortisol detection unit 1, a control unit 2, segmented drug-loaded microcapsules 3, and a release control unit 4. The cortisol detection unit 1 includes a three-electrode electrochemical sensor. The working electrode surface is modified with gold nanoparticles with a particle size of 15–25 nm. Cortisol antibodies are immobilized on the surface of the gold nanoparticles via thiol-gold bonding. The sensor's operating potential range is -0.15 V to +0.75 V relative to the Ag / AgCl reference electrode. The control unit 2 includes a 32-bit microcontroller used to compare the detected cortisol concentration with three preset thresholds and output a chamber activation signal. The segmented drug-loaded microcapsules 3 are made of polylactic acid-glycolic acid copolymer with a molecular weight of 60,000–70,000 Da and a lactic acid to glycolic acid molar ratio of 75:

25. They are internally divided into three independent chambers, each containing an amino acid composition with different proportions. The release control unit 4 includes three solenoid valves that control the opening of the release ports of the three chambers, and the release rate is controlled by a 1 kHz PWM signal. The control unit 2 performs a three-stage threshold judgment: when the cortisol concentration is greater than 350 nmol / L, it outputs a first chamber activation signal; when the cortisol concentration is in the range of 200 to 350 nmol / L and it is in the on-orbit period, it outputs a second chamber activation signal; and when the cortisol concentration is greater than 280 nmol / L and less than 350 nmol / L and it is in the return period, it outputs a third chamber activation signal. The three-stage differentiated amino acid composition includes a first-compartment high-intensity immune support composition, a second-compartment maintenance immune support composition, and a third-compartment recovery immune support composition. The first-compartment high-intensity immune support composition contains arginine at a concentration of 20±2 g / L, glutamine at a concentration of 15±2 g / L, and sodium ascorbate at a concentration of 0.1 g / L. The second-compartment maintenance immune support composition contains eight essential amino acids: leucine, isoleucine, valine, threonine, methionine, phenylalanine, tryptophan, and lysine, with a total concentration of 25±3 g / L. The third-compartment recovery immune support composition contains a total concentration of branched-chain amino acids of 15±2 g / L, wherein the molar ratio of leucine, isoleucine, and valine is 2.0:1.0:1.0, and taurine at a concentration of 1.0 g / L is added.

2. The aerospace amino acid immunomodulation system for microgravity environments according to claim 1, characterized in that, The gold nanoparticles were prepared by sodium citrate reduction, and the cortisol antibody density was [missing value]. The sensor's relative detection error does not exceed ±8%, with each element per cm².

3. The aerospace amino acid immunomodulation system for microgravity environments according to claim 1, characterized in that, The segmented drug-loaded microcapsule 3 has a cylindrical structure with an outer diameter of 15 mm and a total length of 12 mm. The three chambers are arranged along the axial direction, with the first chamber having a volume of 0.6 mL, the second chamber having a volume of 0.9 mL, and the third chamber having a volume of 0.6 mL.

4. A space amino acid immunomodulatory system for microgravity environments according to claim 3, characterized in that, The chambers are separated by a pH-responsive polymer membrane with a thickness of 0.5 mm, and each chamber is equipped with a release port with a pore size of 0.2 mm.

5. A space amino acid immunomodulatory system for microgravity environments according to claim 1, characterized in that, The duty cycle of the PWM signal ranges from 10% to 90%, corresponding to a release rate of 0.1 to 2.0 mg / min. The control unit 2 also includes an individualized baseline adaptive learning module, which establishes an individual baseline value through continuous monitoring of cortisol concentration for 48 to 96 hours.

6. A space amino acid immunomodulatory system for microgravity environments according to claim 5, characterized in that, The individualized baseline adaptive learning module calculates stress regulation factors. in The value ranges from 0.8 to 1.

2. The value is 0.1 to 0.

3.

7. The control method for a space amino acid immune regulation system in a microgravity environment according to claim 1, characterized in that, Includes the following steps: Step 1: The concentration of cortisol in body fluids was detected by a three-electrode electrochemical sensor modified with gold nanoparticles, and the cyclic voltammetry was used to scan the potential range from -0.15V to +0.75V. Step 2: Compare the detected cortisol concentration with three preset thresholds. When the cortisol concentration is greater than 350 nmol / L, it is determined to be a high stress state during the launch phase. When the cortisol concentration is in the range of 200-350 nmol / L and is in the on-orbit phase, it is determined to be a moderate stress state during the on-orbit phase. When the cortisol concentration is greater than 280 nmol / L and less than 350 nmol / L and is in the return phase, it is determined to be a stress state during the return phase. Step 3: Calculate stress regulation factors based on the judgment results in The value ranges from 0.8 to 1.

2. The value is 0.1 to 0.

3. Step 4: Control the opening of the solenoid valves of the corresponding chambers in the segmented drug-loaded microcapsules, and adjust the release rate within the range of 0.1 to 2.0 mg / min using PWM signals; Step 5: Monitor changes in cortisol concentration. Stop the release when two consecutive test results show that the cortisol concentration has returned to within ±20% of the individual's baseline value.

8. The control method according to claim 7, characterized in that, The method also includes an individualized baseline calibration step, in which individual cortisol baseline values ​​are established by continuous detection for 48 to 96 hours before system startup. The baseline value is calculated by averaging the data after removing the highest and lowest 10%.

9. A three-stage differentiated amino acid composition for use in the system of claim 1, characterized in that, The vaccine comprises a first-compartment high-intensity immune support composition, a second-compartment maintenance immune support composition, and a third-compartment recovery immune support composition. The first-compartment high-intensity immune support composition contains arginine at a concentration of 20±2 g / L, glutamine at a concentration of 15±2 g / L, and sodium ascorbate at a concentration of 0.1 g / L. The second-compartment maintenance immune support composition contains eight essential amino acids—leucine, isoleucine, valine, threonine, methionine, phenylalanine, tryptophan, and lysine—at a total concentration of 25±3 g / L. The third-compartment recovery immune support composition contains a total concentration of branched-chain amino acids of 15±2 g / L, wherein the molar ratio of leucine, isoleucine, and valine is 2.0:1.0:1.0, and taurine at a concentration of 1.0 g / L is added.

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