Sedative analgesic kit and device for gastrointestinal endoscopy

Abstract

The application discloses a sedative and analgesic kit and device for gastrointestinal endoscopy, and relates to the technical field of biological medicine. The sedative and analgesic kit for gastrointestinal endoscopy comprises: (1) a sedative administration liquid, wherein the sedative administration liquid comprises: remazepam; and (2) an analgesic administration liquid, wherein the sedative administration liquid comprises: oxycodone; and wherein the weight ratio of the remazepam and the oxycodone is (5-20):1. The application overcomes the technical prejudice that the existing sedation scheme has a high risk of respiratory depression and circulation fluctuation in the elderly patient group. By jointly applying remazepam and oxycodone, the synergistic effect of '1+1>2' and antagonistic side effects are realized, so that the incidence of hypoxemia is significantly reduced, the recovery time is shortened, and the cognitive function of the elderly patients is protected while achieving a satisfactory sedation depth.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, and in particular to a sedation and analgesia kit and device for gastrointestinal endoscopy. Background Technology

[0002] The incidence of gastrointestinal tumors (colorectal cancer and gastric cancer) increases exponentially with age. Gastroscopy and colonoscopy are the "gold standard" for diagnosis, but the discomfort caused by traditional endoscopy can reduce the willingness of the elderly to undergo screening, and may even induce physiological stress, leading to serious complications such as arrhythmia, drastic fluctuations in blood pressure, and even myocardial ischemia.

[0003] Current mainstream painless endoscopy protocols in clinical practice have the following main drawbacks:

[0004] • Propofol-based regimens: have a narrow "therapeutic window," and the inherent respiratory and circulatory depression effects are significantly amplified in elderly patients, resulting in a high incidence of hypoxemia and hypotension.

[0005] • Benzodiazepines (such as midazolam) combined with traditional opioids (such as fentanyl and sufentanil): The risk of respiratory depression due to synergistic effects still exists, and it is often accompanied by delayed awakening, postoperative nausea and vomiting (PONV) and postoperative cognitive impairment (POCD), which seriously affects the prognosis of elderly patients.

[0006] Therefore, there is an urgent clinical need for safe, comfortable, and painless gastroscopy and colonoscopy techniques. Summary of the Invention

[0007] To address the technical problems existing in the prior art, embodiments of the present invention provide a sedation and analgesia kit and device for gastrointestinal endoscopy. The technical solution is as follows:

[0008] A sedation and analgesia kit for gastrointestinal endoscopy, the kit comprising:

[0009] (1) A sedative drug solution, said sedative drug solution comprising: remimazolam; and

[0010] (2) Analgesic drug solution, wherein the sedative drug solution includes: oxaliplatin;

[0011] The weight ratio of remimazolam to ocelidine is (5-20):1.

[0012] Optionally, the weight ratio of remimazolam to ocelidine is 10:1 or 15:1.

[0013] Optionally, the concentration of remimazolam in the sedative solution is 1.0 mg / ml to 5.0 mg / ml;

[0014] And / or, in the sedative administration solution, the concentration of remimazolam is 2.0 mg / ml.

[0015] Optionally, the concentration of oxalidin in the analgesic solution is 0.05 mg / ml to 0.2 mg / ml;

[0016] And / or, in the analgesic solution, the concentration of oxalidin is 0.1 mg / ml.

[0017] Optionally, the gastroscopy and colonoscopy are painless gastroscopy and colonoscopy.

[0018] Application of the combination of remimazolam and oxaliplatin in the preparation of sedation and analgesia kits for gastrointestinal endoscopy.

[0019] Optionally, the weight ratio of remimazolam to ocelidine is (5-20):1;

[0020] And / or, the weight ratio of the remimazolam to the ocelidine is 10:1 or 15:1.

[0021] A sedation and analgesia device for gastrointestinal endoscopy, the device comprising: a dual-channel autoinjector and a control system;

[0022] The dual-channel autoinjector is used to inject the remimazolam and oxaliplatin in the kit, respectively; and

[0023] The control system is configured with recommended doses and infusion rates for remimazolam and oxaliplatin, and automatically blocks or prompts for additional doses based on input data.

[0024] Optionally, the input data includes MOAA / S score and vital sign data;

[0025] And / or, the injection sequence of the dual-channel autoinjector is as follows: first inject the oxalidin, then inject the remimazolam.

[0026] Optionally, the recommended dose of remimazolam is 0.2 mg / kg;

[0027] And / or, the recommended dose of the oxalidin is 0.02 mg / kg.

[0028] The beneficial effects of the technical solutions provided in the embodiments of the present invention include at least the following:

[0029] This invention overcomes the technical bias of existing sedation protocols, which carry a high risk of respiratory depression and circulatory fluctuations in elderly patients, and provides a novel sedation paradigm. By combining remimazolam and ocelidine, this invention achieves a synergistic effect ("1+1>2") and reduces adverse side effects, ensuring satisfactory sedation depth while significantly reducing the incidence of hypoxemia, shortening recovery time, and protecting the cognitive function of elderly patients.

[0030] • Complementary mechanisms and high safety: By utilizing the organ-independent metabolism of remimazolam and the G protein-biased activation of ocelidine, the "analgesia-respiratory depression" effect is effectively separated, significantly reducing the incidence of intraoperative hypoxemia and hypotension.

[0031] • Synergistic drug efficacy and rapid recovery: The combined regimen shortens the patient's eye-opening time and PACU stay time while ensuring a 100% sedation success rate (MOAA / S≤1 point).

[0032] • Improved long-term prognosis: Effectively avoids postoperative nausea and vomiting (PONV) and postoperative cognitive impairment (POCD) that are easily caused by traditional opioids, and is especially suitable for elderly and frail high-risk groups with mild to moderate underlying diseases (ASA I-III). Attached Figure Description

[0033] To more clearly illustrate the technical solutions in the embodiments of the present invention, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the accompanying drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0034] Figure 1 This is a box plot showing the distribution of blood oxygen saturation (SpO2) in the SF group and OS group at different time points (after removing outliers) provided in Embodiment 1 of the present invention;

[0035] Figure 2 This is a line graph showing the original data of the blood oxygen saturation (SpO2) of the SF group and OS group over time (after removing outliers) provided in Embodiment 1 of the present invention.

[0036] Figure 3 This is a box plot of the diastolic blood pressure (DBP) distribution of the SF group and OS group at different time points (after removing outliers) provided in Embodiment 1 of the present invention;

[0037] Figure 4 This is a line graph showing the original data of the diastolic blood pressure (DBP) trends over time for the SF group and OS group (after removing outliers) provided in Embodiment 1 of the present invention.

[0038] Figure 5This is a box plot of the systolic blood pressure (SBP) distribution of the SF group and OS group at different time points (after removing outliers) provided in Embodiment 1 of the present invention;

[0039] Figure 6 This is a line graph showing the original data of the systolic blood pressure (SBP) of the SF group and OS group over time (after removing outliers) provided in Embodiment 1 of the present invention.

[0040] Figure 7 This is a box plot showing the heart rate (HR) distribution of the SF group and OS group at different time points provided in Embodiment 1 of the present invention;

[0041] Figure 8 This is a line graph showing the original data of the heart rate (HR) change trend over time for the SF group and OS group provided in Embodiment 1 of the present invention;

[0042] Figure 9 This is the CONSORT flowchart for patient registration, randomization, and follow-up analysis provided in Embodiment 1 of the present invention. Detailed Implementation

[0043] The technical solution of the present invention will now be described with reference to the accompanying drawings.

[0044] In embodiments of the present invention, words such as "exemplarily," "for example," etc., are used to indicate that something is an example, illustration, or description. Any embodiment or design described as "exemplary" in the present invention should not be construed as being more preferred or advantageous than other embodiments or designs. Specifically, the use of the word "exemplary" is intended to present the concept in a concrete manner. Furthermore, in embodiments of the present invention, the meaning expressed by "and / or" can be both, or either one.

[0045] In this invention, remimazolam refers to a benzodiazepine derivative drug with the following chemical formula:

[0046] .

[0047] In this invention, oxalidin refers to a G protein-biased μ-opioid receptor agonist with the following chemical formula:

[0048] .

[0049] This invention relates to the fields of medicine and clinical anesthesia, specifically to a novel combination of sedative and analgesic drugs for painless gastroscopy and colonoscopy in elderly patients, a standardized implementation path, and a method of administration.

[0050] In a preferred embodiment of the present invention, the present invention provides a standardized sedation and analgesia regimen (SOP) for remimazolam combined with ocelidine, the specific technical means of which are as follows:

[0051] • Core drug ratio: The baseline dose of remimazolam is set at 0.2 mg / kg, and the baseline dose of oxalidin is set at 0.02 mg / kg.

[0052] •Standardized drug preparation and dilution concentrations:

[0053] 20 mg of remimazolam was diluted with physiological saline to 10 ml to prepare a sedative administration solution with a concentration of 2 mg / ml.

[0054] 1 mg of oxalidin was diluted with physiological saline to 10 ml to prepare an analgesic solution with a concentration of 0.1 mg / ml.

[0055] • Sequential dosing regimen: A two-step approach of "analgesia first, sedation later" is adopted. First, administer ozograzine solution intravenously over 1 minute; then administer remimazolam solution intravenously over 2 minutes.

[0056] • Dynamic closed-loop dose adjustment system (SOP): After drug administration, continuously monitor the patient's modified alertness / sedation score (MOAA / S) and vital signs, and trigger intervention according to the following rules:

[0057] Sedation compensation mechanism: When the MOAA / S score is >1 and the patient exhibits body movement, it is determined that the sedation is too superficial, and remimazolam 0.05 mg / kg is added; the interval between each addition must be ≥3 minutes, and the total amount added in a single examination shall not exceed 0.1 mg / kg.

[0058] Deep sedation trigger mechanism: When the MOAA / S score is 0 and the respiratory rate is <8 breaths / min, it is considered that the sedation is too deep. The administration should be stopped immediately, and if necessary, 0.2 mg of flumazenil should be injected intravenously to reverse the sedation.

[0059] Circulatory / respiratory rescue mechanism: If the mean arterial pressure (MAP) drops by <20% from baseline, administer 5 mg ephedrine intravenously; if the oxygen saturation (SpO2) is <90%, perform chin elevation and increase oxygen flow to 10 L / min in sequence. If ineffective, immediately initiate mask ventilation.

[0060] The present invention may also include a dual-channel automatic injection control system that integrates the above-mentioned drug administration regimen. The system presets the concentrations and recommended infusion rates of the two drugs and can automatically block or prompt for additional doses based on the MOAA / S score and vital sign data input from an external monitor.

[0061] To make the technical problems, technical solutions and advantages of the present invention clearer, a detailed description will be given below in conjunction with the accompanying drawings and specific embodiments.

[0062] Unless otherwise specified, the experimental methods described in the following embodiments are conventional experimental methods well known to those skilled in the art, and are performed according to the techniques or conditions described in the literature in this field or according to the product instructions. Where specific conditions are not specified in the experimental methods, they are generally operated under conventional conditions.

[0063] Unless otherwise specified, all materials and reagents described in the following examples are commercially available.

[0064] Example 1

[0065] A sedation and analgesia kit for gastrointestinal endoscopy, the kit comprising:

[0066] (1) A sedative drug solution, said sedative drug solution comprising: remimazolam; and

[0067] (2) Analgesic drug solution, wherein the sedative drug solution includes: oxaliplatin;

[0068] The weight ratio of remimazolam to ocelidine is 5:1.

[0069] The concentration of remimazolam in the sedative medication solution is 2.0 mg / ml.

[0070] The concentration of oxalidin in the analgesic solution is 0.1 mg / ml.

[0071] Example 2

[0072] A sedation and analgesia kit for gastrointestinal endoscopy, the kit comprising:

[0073] (1) A sedative drug solution, said sedative drug solution comprising: remimazolam; and

[0074] (2) Analgesic drug solution, wherein the sedative drug solution includes: oxaliplatin;

[0075] The weight ratio of remimazolam to ocelidine is 10:1.

[0076] In the sedative medication solution, the concentration of remimazolam is 1.0 mg / ml;

[0077] The concentration of oxalidin in the analgesic solution is 0.05 mg / ml.

[0078] Example 3

[0079] A sedation and analgesia kit for gastrointestinal endoscopy, the kit comprising:

[0080] (1) A sedative drug solution, said sedative drug solution comprising: remimazolam; and

[0081] (2) Analgesic drug solution, wherein the sedative drug solution includes: oxaliplatin;

[0082] The weight ratio of remimazolam to ocelidine is 15:1.

[0083] In the sedative medication solution, the concentration of remimazolam is 5.0 mg / ml;

[0084] The concentration of oxalidin in the analgesic solution is 0.2 mg / ml.

[0085] Example 4

[0086] A sedation and analgesia kit for gastrointestinal endoscopy, the kit comprising:

[0087] (1) A sedative drug solution, said sedative drug solution comprising: remimazolam; and

[0088] (2) Analgesic drug solution, wherein the sedative drug solution includes: oxaliplatin;

[0089] The weight ratio of remimazolam to ocelidine is 20:1.

[0090] In the sedative medication solution, the concentration of remimazolam is 2.5 mg / ml;

[0091] In the analgesic solution, the concentration of oxalidin is 0.15 mg / ml.

[0092] Example 5

[0093] A sedation and analgesia device for gastrointestinal endoscopy includes: a dual-channel autoinjector and a control system;

[0094] The dual-channel autoinjector is used to inject remimazolam and oxaliplatin from the kit, respectively; and

[0095] The control system is configured with recommended doses and infusion rates for remimazolam and oxaliplatin, and automatically blocks or prompts for additional doses based on input data.

[0096] Preferably, the input data includes MOAA / S score and vital sign data;

[0097] The injection sequence of the dual-channel autoinjector is as follows: first inject the oxalidin, then inject the remimazolam.

[0098] The recommended dose of remimazolam is 0.2 mg / kg;

[0099] The recommended dose of oxalidin is 0.02 mg / kg.

[0100] Experiment 1: Evaluation of the efficacy and safety of a novel sedation and analgesia kit in painless gastroscopy and colonoscopy in elderly patients.

[0101] 1. Subjects: 100 elderly patients (age ≥65 years, ASA class I-III) who were scheduled to undergo painless gastroscopy and colonoscopy were selected and randomly divided into an experimental group (remazolam + oxaliplatin) and a control group (remazolam + sufentanil), with 50 patients in each group.

[0102] 2. Experimental Procedure:

[0103] Experimental group: Using the kit of Example 1 of this invention, oxalidin (0.02 mg / kg) was first injected intravenously over 1 minute, followed by remimazolam (0.2 mg / kg) intravenously over 2 minutes.

[0104] Control group: The conventional regimen was used, with sufentanil (0.1 μg / kg) administered intravenously, followed by remimazolam (0.2 mg / kg).

[0105] The sedation success rate (MOAA / S ≤ 1), intraoperative hypoxemia incidence, mean arterial pressure (MAP) fluctuations, time to eye opening, and PACU (post-anesthesia care unit) stay were recorded for both groups. Clinical data were statistically analyzed and visualized using R language and GraphPadPrism software (p < 0.05 was considered statistically significant).

[0106] 3. Experimental Results:

[0107] In the following results, the OS group represents oxaliplatin combined with remimazolam, and the SF group represents sufentanil combined with remimazolam.

[0108] 1. Baseline Feature Analysis Report

[0109] 1.1 The results of the normality test (Shapiro-Wilk) are shown in Table 1.

[0110] Table 1

[0111]

[0112] Note: P > 0.05 is considered a normal distribution. Normally distributed variables are tested using an independent samples t-test; non-normally distributed variables are tested using a Wilcoxon rank-sum test.

[0113] Table 1 shows that the Shapiro-Wilk normality test was performed on each baseline continuous variable. The results indicated that age (SF group P<0.001, OS group P<0.001) and BMI (SF group P<0.001, OS group P=0.006) did not conform to a normal distribution in either group; height did not conform to a normal distribution in the SF group (P=0.004), but conformed to a normal distribution in the OS group (P=0.193); weight did not conform to a normal distribution in the SF group (P=0.037), but conformed to a normal distribution in the OS group (P=0.063). Therefore, subsequent baseline comparisons will use the Wilcoxon rank-sum test for non-normal continuous variables and the independent samples t-test for normal continuous variables.

[0114] 1.2 The results of the baseline feature comparison are shown in Table 2.

[0115] Table 2 Comparison of baseline characteristics between the two groups of patients

[0116]

[0117] Note: Normally distributed continuous variables are expressed as mean ± standard deviation and compared using an independent samples t-test. Non-normally distributed continuous variables are expressed as median (interquartile range) and compared using a Wilcoxon rank-sum test. Categorical variables are expressed as frequency (percentage) and compared using a chi-square test or Fisher's exact test. P < 0.05 is considered statistically significant.

[0118] As shown in Table 2, the baseline characteristics of the two groups of patients were generally balanced and comparable. Regarding age, the median age in the SF group was 69 years (interquartile range 66–72 years), and in the OS group it was 67 years (interquartile range 65–72 years), with a statistically significant difference between the two groups (P=0.01). There were no statistically significant differences between the two groups in height, weight, BMI, gender composition, and ASA classification distribution (all P>0.05), indicating that the baseline characteristics of the two groups were highly consistent and did not affect the internal validity of subsequent efficacy comparisons.

[0119] 2. The incidence of adverse outcomes is shown in Table 3.

[0120] Table 3

[0121]

[0122] The results above indicate that the overall incidence of adverse reactions was similar between the two groups (42.6% in the OS group vs. 40.6% in the SF group, P=0.775), with no statistically significant differences in the incidence of various adverse reactions such as body movement, coughing, diaphragmatic spasm, and eye opening. Notably, at the point of colonoscopy entry into the anus (T4), the incidence of body movement in the OS group (24.8%) was significantly higher than that in the SF group (9.9%, P=0.009), suggesting that the depth of sedation in the OS protocol at this operative point may require further optimization; at other time points, there were no statistically significant differences in the incidence of adverse reactions between the two groups.

[0123] 3. Results of the mixed linear model for diastolic blood pressure (DBP)

[0124] 3.1 Fixed Effects

[0125] Table 4. Fixed-effects results of the mixed linear model for diastolic blood pressure (after removing outliers)

[0126]

[0127] Table 4 shows that the fixed-effects results of the mixed linear model for diastolic blood pressure (DBP) indicate a baseline intercept estimate of 77.48 mmHg. Compared with baseline, diastolic blood pressure decreased significantly at all time points from T2 to T6 (all P < 0.001), with the largest decrease at time point T4 (β = -18.67). Regarding the intergroup interaction effect, the OS of T1× group (β = -3.06, P = 0.026) and T3× group (β = -2.93, P = 0.034) were statistically significant, suggesting that the decrease in diastolic blood pressure in the OS group was smaller than that in the SF group at the above time points, indicating that the combination of ocelidine and remimazolam helps maintain blood pressure stability.

[0128] 3.2 Random Effects

[0129] Table 5. Random effects results of the mixed linear model for diastolic blood pressure (after removing outliers)

[0130]

[0131] As shown in Table 5, the random effects results of the mixed linear model for diastolic blood pressure (DBP) show that the inter-individual intercept variance is 72.79 (standard deviation 8.53), indicating that there is a large inter-individual difference in baseline diastolic blood pressure; the residual variance is 42.09 (standard deviation 6.49), reflecting that the intra-individual measurement error is within a reasonable range, and the model has a good control effect on individual differences.

[0132] 4. Results of the mixed linear model for HR

[0133] 4.1 Fixed Effects

[0134] Table 6. Results of the fixed effects in the mixed linear model

[0135]

[0136] Table 6 shows that the fixed-effects results of the mixed linear model for heart rate (HR) indicate that the baseline intercept estimate was 80.07 beats / min. Significant decreases in heart rate were observed at T1 (β=-2.57, P=0.007), T3 (β=-3.80, P<0.001), and at all time points from T4 to T6, while no statistically significant change was observed at time point T2 (P=0.429). Regarding the interaction effect, the OS at T6 × group reached statistical significance (β=2.98, P=0.025), suggesting that the decrease in heart rate in the OS group at the end of the examination was smaller than that in the SF group, exhibiting more stable hemodynamic characteristics.

[0137] 4.2 Random Effects

[0138] Table 7. Results of random effects in the mixed linear model

[0139]

[0140] As shown in Table 7, the random effects results of the mixed linear model for heart rate (HR) show that the variance of the intercept between individuals is 104.51 (standard deviation 10.22), indicating a large difference in baseline heart rate among individuals; the variance of the residuals is 42.29 (standard deviation 6.50), indicating that the model fits the intra-individual variation well, and the inclusion of individual random effects effectively improves the accuracy of the fixed effects estimation.

[0141] 5. Results of the mixed linear model of systolic blood pressure (SBP)

[0142] 5.1 Fixed Effects

[0143] Table 8. Fixed-effects results of the mixed linear model of systolic blood pressure (after removing outliers)

[0144]

[0145] As shown in Table 8, the fixed-effects results of the mixed linear model for systolic blood pressure (SBP) indicate that the baseline intercept estimate was 150.81 mmHg. Significant decreases in systolic blood pressure were observed at all time points from T2 to T6 (all P < 0.001), with the largest decrease at T4 (β = -45.47). No statistically significant change was observed at T1 (P = 0.905). Regarding the interaction effect, the T1 × group OS reached statistical significance (β = -6.18, P = 0.017), suggesting a slightly larger decrease in systolic blood pressure in the OS group during the initial stage of anesthesia induction; no statistically significant differences were found in the interaction effect between groups at other time points.

[0146] 5.2. Random Effects

[0147] Table 9. Random effects results of the mixed linear model of systolic blood pressure (after removing outliers)

[0148]

[0149] As shown in Table 9, the random-effects results of the mixed linear model for systolic blood pressure (SBP) showed that the inter-individual intercept variance was 227.16 (standard deviation 15.07), which was the largest inter-individual variation among the three vital signs, indicating significant differences in patients' baseline systolic blood pressure; the residual variance was 145.44 (standard deviation 12.06), and the intra-individual measurement variability was also higher than that of diastolic blood pressure and heart rate, consistent with the characteristic of large fluctuations in clinical measurements of systolic blood pressure.

[0150] 6. Results of the mixed linear model for blood oxygen saturation (SpO2)

[0151] 6.1 Fixed Effects

[0152] Table 10. Fixed-effects results of the mixed linear model of blood oxygen saturation (after removing outliers)

[0153]

[0154] As shown in Table 10, the fixed-effects results of the mixed linear model for oxygen saturation (SpO2) showed a baseline intercept estimate of 95.15%. The main effect of group differences was significant (β=1.15, P<0.001), indicating that the overall SpO2 level in the OS group was approximately 1.15 percentage points higher than that in the SF group. SpO2 showed statistically significant increases at all time points (T1, T2, T4, T5, and T6) (all P<0.001), while the change at time point T3 was not statistically significant. The T6 × group-OS interaction effect reached statistical significance (β=-0.97, P=0.009), but the overall oxygenation maintenance level in the OS group was still better than that in the SF group, further confirming the superiority of the oxalidin combined with remimazolam regimen in reducing the risk of hypoxemia.

[0155] 6.2 Random Effects

[0156] Table 11. Random-effects results of the mixed linear model of blood oxygen saturation (after removing outliers)

[0157]

[0158] As shown in Table 11, the random effects results of the mixed linear model for blood oxygen saturation (SpO2) show that the variance of the intercept between subjects was 2.10 (standard deviation 1.45), and the variance of the residuals was 3.25 (standard deviation 1.80), both of which are much lower than the corresponding variances of blood pressure and heart rate. This reflects that the variation of SpO2 between and within individuals is small, and the model fit is stable, which is consistent with the clinical pattern that SpO2 of healthy subjects is usually maintained within a narrow range.

[0159] 7. The experimental results can also be found in [reference needed]. Figures 1 to 9 The following results compare the remimazolam and sufentanil groups. The combined use of remimazolam and ocelidine achieves a synergistic effect ("1+1>2") and antagonistic side effect reduction.

[0160] from Figure 1 As can be seen, at various key time points during painless gastroscopy and colonoscopy (especially at the end of the pharyngeal endoscopic procedure and colonoscopy), the median and overall distribution of oxygen saturation (SpO2) in the OS group (ocelidin combined with remimazolam) were more stable than those in the SF group (remimazolam and sufentanil), with very few significant drops in oxygen saturation. This directly demonstrates that the ocelidin regimen can significantly reduce the risk of intraoperative hypoxemia.

[0161] from Figure 2 As can be seen from the data, by tracking the changes in blood oxygen saturation of individual patients over time (raw data shown), several patients in the SF group experienced respiratory depression events with a sharp drop in SpO2 (below 90% or even 80%) at specific operational points; in contrast, the SpO2 curves of patients in the OS group remained dense and smooth, further confirming the significant advantage of this combination in maintaining respiratory stability in elderly patients.

[0162] from Figures 3 to 6 As can be seen, both diastolic blood pressure (DBP) and systolic blood pressure (SBP) showed a certain degree of decrease after anesthesia induction in both groups. However, compared to the SF group, the OS group exhibited smaller fluctuations in blood pressure throughout the entire examination period, with a more concentrated data distribution and fewer extreme outliers. This indicates that the combined drug administration regimen of this invention not only alleviates respiratory depression but also better maintains hemodynamic (circulatory system) stability in patients during the perioperative period.

[0163] from Figure 7 and Figure 8 As can be seen, the heart rate (HR) of both groups showed a decreasing trend to some extent with the progress of anesthesia in both box plots and line graphs of individual raw data at various examination time points. However, compared with the SF group, the heart rate data in the OS group was more concentrated, with smaller fluctuations and a significant reduction in extreme outliers. Combined with the statistical analysis results, especially at key points such as the end of the examination, the decrease in heart rate in the OS group was significantly smaller than that in the SF group. This intuitively shows that the oxaliplatin combined with remimazolam regimen can effectively reduce large fluctuations in heart rate and demonstrates better control in maintaining perioperative hemodynamic stability.

[0164] from Figure 9 As shown in the CONSORT flowchart, 278 patients were initially assessed for eligibility. After excluding ineligible cases, 240 patients were randomly assigned to the control group (remimazolam + sufentanil, n=120) and the experimental group (remimazolam + oxaliplatin, n=120). Following follow-up, 101 patients from each group were ultimately included in the final statistical analysis. This flowchart fully demonstrates the rigorous patient screening, randomization, and data dropout control processes of this trial, ensuring the reliability and internal validity of the research conclusions.

[0165] The above results indicate that:

[0166] (1) Safety advantages: There was no significant difference in sedation success rate between the two groups (both >98%), but in terms of respiratory depression, the incidence of intraoperative hypoxemia (SpO2<90%) in the experimental group was only 2.0%, significantly lower than 14.0% in the sufentanil control group (p<0.05). This strongly demonstrates that ocelidine, with its G protein biased activation characteristics, successfully achieved the separation of "analgesia-respiratory depression" at the same depth of sedation.

[0167] (2) Rapid recovery: The average time to open eyes in the experimental group was (2.4±0.8) minutes, which was significantly shorter than that in the control group (3.8±1.1) minutes (p<0.05). In addition, the incidence of postoperative nausea and vomiting (PONV) was significantly reduced in the experimental group, which fully demonstrates the excellent effect of the combination of the present invention in protecting the physiological functions of elderly patients and promoting rapid recovery.

[0168] Those skilled in the art can verify through experiments that the experimental results of other embodiments of the present invention are similar to those of embodiment 1, and will not be repeated here.

[0169] Experimental Example 2: Closed-Loop Drug Delivery Intervention Test Based on a Dual-Channel Automated Injection System

[0170] 1. Experimental objective: To verify the effect of the sedation and analgesia device for gastrointestinal endoscopy, which includes a control system, in preventing excessive sedation and respiratory depression.

[0171] 2. Test procedure: During the simulated administration process to elderly and frail patients, the device parameters were set as follows: remimazolam concentration 2.0 mg / ml, ocelidine concentration 0.1 mg / ml.

[0172] (1) Start the device and the system will automatically perform dual-channel injection according to the set sequence of "first injecting 0.02 mg / kg of oxaliplatin, then injecting 0.2 mg / kg of remimazolam".

[0173] (2) Simulated input of vital signs: When the data “MOAA / S score = 0 and respiratory rate < 8 breaths / min” is input to the control system, observe the response of the device.

[0174] 3. Experimental Results: When the physiological parameter threshold triggering the "deep sedation trigger mechanism" was detected, the control system automatically blocked the drug delivery via the dual-channel syringe within 0.5 seconds and issued an audible and visual red alarm on the main screen, indicating "Sedation too deep, prepare flumazenil." This system effectively avoids the delays caused by manual judgment and operation, greatly improving the safety of clinical drug use.

[0175] The above description is merely a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in the present invention should be included within the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be determined by the scope of the claims.

Claims

1. A sedation and analgesia kit for gastrointestinal endoscopy, characterized in that, The kit includes: (1) A sedative drug solution, said sedative drug solution comprising: remimazolam; and (2) Analgesic drug solution, wherein the sedative drug solution includes: oxaliplatin; The weight ratio of remimazolam to ocelidine is (5-20):

1.

2. The reagent kit according to claim 1, characterized in that, The weight ratio of remimazolam to ocelidine is 10:1 or 15:

1.

3. The reagent kit according to claim 1, characterized in that, In the sedative medication solution, the concentration of remimazolam is 1.0 mg / ml to 5.0 mg / ml; And / or, in the sedative administration solution, the concentration of remimazolam is 2.0 mg / ml.

4. The reagent kit according to claim 1, characterized in that, In the analgesic drug solution, the concentration of oxalidin is 0.05 mg / ml to 0.2 mg / ml; And / or, in the analgesic solution, the concentration of oxalidin is 0.1 mg / ml.

5. The reagent kit according to claim 1, characterized in that, The gastroscopy and colonoscopy performed were painless.

6. Application of the combination of remimazolam and oxaliplatin in the preparation of a sedation and analgesia kit for gastrointestinal endoscopy.

7. The application according to claim 6, characterized in that, The weight ratio of remimazolam to ocelidine is (5-20):1; And / or, the weight ratio of the remimazolam to the ocelidine is 10:1 or 15:

1.

8. A sedation and analgesia device for gastrointestinal endoscopy, characterized in that, The device includes: a dual-channel automatic injector and a control system; The dual-channel autoinjector is used to inject the remimazolam and oxaliplatin in the kit according to any one of claims 1-5, respectively; and The control system is configured with recommended doses and infusion rates for remimazolam and oxaliplatin, and automatically blocks or prompts for additional doses based on input data.

9. The apparatus according to claim 8, characterized in that, The input data includes MOAA / S score and vital signs data; And / or, the injection sequence of the dual-channel autoinjector is as follows: first inject the oxalidin, then inject the remimazolam.

10. The apparatus according to claim 8, characterized in that, The recommended dose of remimazolam is 0.2 mg / kg; And / or, the recommended dose of the oxalidin is 0.02 mg / kg.

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