Simulation method of sugammadex antagonism mechanism

Abstract

The invention relates to the field of electrical digital data processing, in particular to a sugammadex antagonism mechanism simulation method which comprises the following steps: S1, establishing a muscle relaxant pharmacokinetics two-chamber model which comprises a central chamber and a peripheral chamber; s2, prefabricating a muscle relaxant database and a sugammadex database, wherein the muscle relaxant database and the sugammadex database respectively comprise drug labels, parameter names and parameter values; s3, adding the muscle relaxant into the pharmacokinetics two-room model to obtain the real-time drug concentration of the muscle relaxant in the central room of the pharmacokinetics two-room model; and S4, adding sugammadex to obtain the real-time drug concentration of the central ventricular muscle relaxant. The simulation of the antagonistic mechanism of sugammadex in the antagonistic muscle relaxant is realized, and the market blank in the field of sugammadex antagonistic mechanism simulation is filled up; and analog quantized data reference can be provided for improving anesthesia safety.

Description

Technical Field

[0001] The present application relates to the field of electrical digital data processing, and in particular to a method for simulating the sugammadex antagonism mechanism. Background Art

[0002] Sugammadex is a new type of non-depolarizing muscle relaxant antagonist. The drugs used to antagonize steroid non-depolarizing neuromuscular blockade are: rocuronium bromide and vecuronium bromide. The mechanism of action of sugammadex is not like the traditional antagonists (such as neostigmine, which is ineffective at deep blockade and has large differences between individuals, which is not conducive to control) to inhibit acetylcholinesterase. Instead, sugammadex forms a stable, inactive 1:1 complex with rocuronium bromide or vecuronium bromide, reducing the number of neuroblockers bound to acetylcholine receptors, resulting in the reversal of neuromuscular blockade, and once bound, this process is considered irreversible.

[0003] However, there has been no analog of the sugammadex antagonist mechanism on the market. Summary of the invention

[0004] In view of the above-mentioned deficiencies in the prior art, the present application provides a method for simulating the antagonistic mechanism of sugammadex to fill the gap in the simulation of the antagonistic mechanism of sugammadex.

[0005] In order to achieve the above-mentioned invention object, the technical solution adopted in this application is: A method for simulating the antagonistic mechanism of sugammadex, comprising the following steps: S1. Establish a two-compartment model for the pharmacokinetics of muscle relaxants, including central compartment and peripheral compartment; S2. Pre-made muscle relaxant and sugammadex drug database, including: drug label, parameter name, parameter value; Preferably, the drug label of the muscle relaxant includes: drug name, pharmacokinetic parameters, and sugammadex parameters; Further, preferably, the pharmacokinetic parameters of the muscle relaxant include: , is the first-order elimination rate constant of the muscle relaxant in the central compartment; , is the first-order rate constant for the transport of muscle relaxants from the central compartment to the peripheral compartment; , is the first-order rate constant for the transport of muscle relaxants from the peripheral compartment to the central compartment; , is the apparent distribution volume of the muscle relaxant in the central compartment; Further, preferably, the sugammadex parameters include: , is the half-effective concentration of sugammadex that affects changes in metabolic parameters; , is the parameter that affects the speed of change of the original metabolic parameters; , , are the maximum effects of sugammadex on metabolic parameters of the original model; , is the amount of sugammadex consumed per second; Preferably, the drug label of sugammadex includes: drug name, molar mass, and pharmacokinetic parameters; Further, preferably, the pharmacokinetic parameters of sugammadex include: , is the apparent distribution volume of sugammadex in the central compartment; Preferably, the muscle relaxant is rocuronium bromide or vecuronium bromide; S3. Adding the muscle relaxant to the pharmacokinetic two-compartment model to obtain the real-time drug concentration of the muscle relaxant in the central chamber of the pharmacokinetic two-compartment model comprises the following steps: S3.1. Add the muscle relaxant to the central chamber of the two-compartment pharmacokinetic model, and obtain the real-time dosage of the muscle relaxant in the central chamber at this time, which is: ; Get the initial dose of the surrounding indoor muscle relaxant at this time, which is: ; in, It is the specification of muscle relaxant injection; is the body weight; It is the real-time dosage of muscle relaxant in the central chamber; It is the real-time dosage of muscle relaxant in the surrounding room; The time of adding the muscle relaxant into the central compartment of the pharmacokinetic two-compartment model is set to 0s; S3.2. Obtain the changes in the amount of muscle relaxant in the central chamber and the peripheral chamber, respectively: The change in the amount of muscle relaxant in the central chamber is: ; The change in the amount of muscle relaxant in the surrounding room is: ; in, is the time interval for calculating the change in drug amount; It is a central ventricular muscle relaxant. The amount of change within Is the peripheral indoor muscle relaxant in The amount of change within is the first-order elimination rate constant of the muscle relaxant in the central compartment; is the first-order rate constant for the transport of muscle relaxants from the central compartment to the peripheral compartment; is the first-order rate constant for the transport of muscle relaxants from the peripheral compartment to the central compartment; It is the real-time dosage of muscle relaxant in the central chamber; It is the real-time dosage of muscle relaxant in the surrounding room; S3.3. Based on step S3.2, obtain At this moment, the real-time dosage of muscle relaxants in the central chamber and the peripheral chamber are: The real-time dosage of muscle relaxants in the central chamber is: ; The real-time dosage of muscle relaxants in the surrounding room is: ; in, After adding muscle relaxants After the metabolic time, ; yes At that moment, the real-time dosage of muscle relaxants in the central room; yes At that moment, the real-time dosage of muscle relaxants in the surrounding room; yes At that moment, the real-time dosage of muscle relaxants in the central room; yes At that moment, the real-time dosage of muscle relaxants in the surrounding room; S3.4. Based on step S3.3, obtain the real-time drug concentration of the muscle relaxant in the central chamber ,for: ; in, yes At that moment, the real-time drug concentration of muscle relaxants in the central chamber; After adding muscle relaxants After the metabolic time, ; is the body weight; is the apparent distribution volume of the muscle relaxant in the central compartment; Also includes: S3.5. When sugammadex is not added or sugammadex is consumed, repeating steps S3.2 to S3.4 to obtain the real-time drug concentration of the muscle relaxant in the central chamber; S4. Add sugammadex to obtain the real-time drug concentration of the muscle relaxant in the central chamber, including the following steps: S4.1. Obtain the initial concentration of sugammadex in the central chamber as: ; in, This is the injection specification of sugammadex; is the apparent distribution volume of sugammadex in the central compartment; is the molar mass of sugammadex; is the initial concentration of sugammadex in the central compartment; S4.2. Sugammadex and muscle relaxant response in a two-compartment model of muscle relaxant pharmacokinetics After the addition of sugammadex, the metabolic parameters of the central and peripheral compartments of the two-compartment pharmacokinetic model were obtained, and the calculation formulas were: The first-order elimination rate constant of muscle relaxants in the central compartment is: ; The first-order rate constant for the transport of muscle relaxants from the peripheral compartment to the central compartment is: ; in, is the duration of the reaction between sugammadex and muscle relaxants; is the amount of sugammadex consumed per second; is the first-order elimination rate constant of the muscle relaxant in the central compartment after the addition of sugammadex; is the first-order rate constant for the transport of the muscle relaxant from the peripheral compartment to the central compartment after the addition of sugammadex; is the initial concentration of sugammadex in the central compartment; , They are the maximum effects of sugammadex on metabolic parameters of the original model; It is the half-effective concentration of sugammadex that affects the changes in the original metabolic parameters; It is a parameter that affects the speed of change of metabolic parameters; is the first-order elimination rate constant of the muscle relaxant in the central compartment when sugammadex is not added; is the first-order rate constant for the transport of the muscle relaxant from the peripheral compartment to the central compartment when sugammadex is not added; S4.3. Based on step S4.2, obtain the changes in the muscle relaxant in the central chamber and the peripheral chamber, which are: The change in the amount of muscle relaxant in the central chamber is: ; The change in the amount of muscle relaxant in the peripheral room is: ; in, is the time interval for calculating the change in drug amount; yes At that moment, the real-time dosage of muscle relaxants in the central room; yes At that moment, the real-time dosage of muscle relaxants in the surrounding room; After adding sugammadex, the central chamber muscle relaxant The amount of change within After adding sugammadex, peripheral indoor muscle relaxants The amount of change within is the first-order elimination rate constant of the muscle relaxant in the central compartment after the addition of sugammadex; is the first-order rate constant for the transport of the muscle relaxant from the peripheral compartment to the central compartment after the addition of sugammadex; S4.4. Based on step S4.3, the real-time dosage of the muscle relaxant in the central chamber and the peripheral chamber is obtained, which are: The real-time dosage of muscle relaxants in the central chamber is: ; The real-time dosage of muscle relaxants in the surrounding room is: ; in, yes At that moment, the real-time dosage of muscle relaxants in the central room; yes At that moment, the real-time dosage of muscle relaxants in the surrounding room; After adding sugammadex, the central chamber muscle relaxant The amount of change within After adding sugammadex, peripheral indoor muscle relaxants The amount of change within yes At that moment, the real-time dosage of muscle relaxants in the central room; yes At that moment, the real-time dosage of muscle relaxants in the surrounding room; S4.5. Based on step S4.4, the real-time drug concentration of the muscle relaxant in the central chamber is obtained as follows: ; in, yes At that moment, the real-time drug concentration of muscle relaxants in the central chamber; yes At that moment, the real-time dosage of muscle relaxants in the central room; is the body weight; is the apparent distribution volume of the muscle relaxant in the central compartment; The method further comprises: S4.6. After adding sugammadex, repeating steps S4.1 to S4.5 to obtain the real-time drug concentration of the muscle relaxant in the central chamber.

[0006] S5. Real-time drug concentration of the muscle relaxant in the central chamber obtained in step S3 and / or step S4 (ug / L) is the vertical coordinate; time t(s) is the horizontal coordinate, and the sugammadex antagonism muscle relaxant curve graph is output.

[0007] The beneficial effects of this application are: since sugammadex can quickly exert an antagonistic effect in a short period of time and reverse muscle relaxation, it can be used as a rescue drug for cases where "neither intubation nor ventilation is possible", thereby improving the safety of general anesthesia. This application achieves the simulation of the antagonistic mechanism of sugammadex in antagonizing muscle relaxants; fills the market gap in the field of sugammadex antagonistic mechanism simulation; and can also provide simulation quantitative data reference for improving anesthesia safety. BRIEF DESCRIPTION OF THE DRAWINGS

[0008] Figure 1 This is a schematic diagram of the two-compartment model of muscle relaxant pharmacokinetics; Figure 2 It is a schematic diagram of the two-compartment model of drug metabolism kinetics after the addition of sugammadex; Figure 3 This is a schematic diagram of the drug metabolism curve of rocuronium bromide with an injection strength of 0.6 mg / kg; Figure 4 This is a schematic diagram of the drug metabolism curve of sugammadex with an injection strength of 8 mg / kg and rocuronium with an injection strength of 0.6 mg / kg; Figure 5 This is a schematic diagram of the drug metabolism curve of vecuronium bromide with an injection strength of 0.2 mg / kg; Figure 6 This is a schematic diagram of the drug metabolism curve of sugammadex with an injection strength of 8 mg / kg antagonizing vecuronium with an injection strength of 0.2 mg / kg. DETAILED DESCRIPTION

[0009] The technical solutions in the embodiments of the present invention are described clearly and completely below in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0010] The meanings of the terms used in this application are as follows: Muscle relaxants: refers to cholinergic receptor blockers, muscle blockers, also known as skeletal muscle relaxants (abbreviated as muscle relaxants, skeletal muscular relaxants), which can selectively act on the N2 receptors on the motor nerve end plate membrane, blocking the transmission of nerve impulses to skeletal muscles, causing muscle relaxation.

[0011] Pharmacokinetic model: refers to a compartment model established to describe the dynamic changes of drugs in the human body. The compartment model is currently a commonly used pharmacokinetic model. The compartment model regards the entire human body as a system and divides the system into several compartments according to the kinetic characteristics. According to the kinetic characteristics of drugs in the human body, the compartment model can be divided into a single compartment model, a two-compartment model and a multi-compartment model.

[0012] Two-compartment model of drug metabolism kinetics: From the perspective of rate theory, the human body is divided into two independent systems with different degrees of drug distribution uniformity, that is, the two-compartment model. In the two-compartment model, the part with abundant blood flow and drug distribution that can instantly reach equilibrium with the blood is generally divided into one chamber, called the central chamber; while the part with less blood supply and a longer time for drug distribution to reach equilibrium with the blood is divided into the peripheral chamber. If, on the basis of the two-compartment model, there is a part of tissues, organs or cells where the distribution of drugs is slower, a third chamber can be divided from the peripheral chamber, thus forming a three-compartment model.

[0013] Acetylcholine receptor: Muscle relaxants bind to the M receptors of acetylcholine, reducing the content of acetylcholine receptors in the body, producing a parasympathetic excitatory effect, that is, an excitatory inhibitory effect, leading to muscle blockade. The mechanism of action of traditional muscle relaxant antagonists (such as neostigmine) is to inhibit cholinesterase from breaking down acetylcholine, thereby increasing the content of acetylcholine in the body.

[0014] (NMBA is the abbreviation of “Neural muscal blockage agent”, which means neuromuscular blockade) is the real-time drug concentration of central ventricular muscle relaxants.

[0015] The drug injection specification in this application refers to the amount of the drug that should be injected according to body weight, for example: 0.6mg / kg means 0.6mg is injected for every kilogram of body weight.

[0016] The unit of time used in the embodiments is: s (second).

[0017] Embodiment 1:

[0018] In this embodiment, the simulated human body weight is set by default. ,in Refers to body weight.

[0019] This embodiment takes rocuronium bromide as an example, and is further described as follows: The specifications of rocuronium bromide for intravenous injection in humans are: ; Specifications of Sugammadex for intravenous injection in humans are: ; wherein said , Refers to the drug injection specifications.

[0020] In this embodiment, sugammadex is added at 179.98 seconds after the addition of rocuronium bromide.

[0021] In this embodiment, the time interval for calculating the change in drug amount is set is 0.02s; in some other embodiments, the time interval for calculating the change in drug amount is It can be 0.01s or other duration.

[0022] like Figures 1 to 4 As shown, this embodiment provides a method for simulating the antagonistic mechanism of sugammadex, comprising the following steps: S1. Establish a two-compartment model for the pharmacokinetics of muscle relaxants, including the central compartment and the peripheral compartment.

[0023] S2. Prefabricated rocuronium (muscle relaxant) and sugammadex drug database, including: drug label, parameter name, parameter value.

[0024] As shown in Table 1 and Table 2 below, the data of the parameters involved in this embodiment are taken from Table 1 and Table 2.

[0025] Preferably, the drug label of the rocuronium bromide (muscle relaxant) includes: drug name, material state, pharmacokinetic parameters, and sugammadex parameters.

[0026] Further, preferably, the pharmacokinetic parameters of rocuronium bromide (muscle relaxant) include: , is the first-order elimination rate constant of rocuronium (muscle relaxant) in the central compartment; , is the first-order rate constant for the transport of rocuronium (muscle relaxant) from the central compartment to the peripheral compartment; , is the first-order rate constant for the transport of rocuronium (muscle relaxant) from the peripheral compartment to the central compartment; , is the apparent distribution volume of rocuronium (muscle relaxant) in the central compartment.

[0027] Further, preferably, the sugammadex parameters include: , is the half-effective concentration of sugammadex that affects changes in metabolic parameters, , is the parameter that affects the speed of change of the original metabolic parameters; , , are the maximum effects of sugammadex on metabolic parameters of the original model; , is the amount of sugammadex consumed per second, in umol / L / s.

[0028] Preferably, the drug label of sugammadex includes: drug name, molar mass, material state, and pharmacokinetic parameters.

[0029] Further, preferably, the pharmacokinetic parameters of sugammadex include: , is the apparent distribution volume of sugammadex in the central compartment.

[0030] In this embodiment, the pharmacokinetic parameters are , , , , stored in a ".xml" file with the same name as the drug, under the "Pharmacokinetics" tab. The factors affecting the pharmacokinetic parameters after the addition of sugammadex include: , , , , , stored by a ".xml" file with the same name as the drug, under the "Sugammadex Parameters (sug)>" tag.

[0031] In this embodiment, the prefabricated rocuronium bromide drug database is as shown in Table 1 below: Table 1

[0032] In this embodiment, the prefabricated sugammadex drug database is as shown in Table 2 below: Table 2

[0033] In some other embodiments, the drug database may be established first, and then the two-compartment drug metabolism kinetics model may be established; or they may be established simultaneously.

[0034] S3. Adding the rocuronium bromide (muscle relaxant) to the pharmacokinetic two-compartment model to obtain the real-time drug concentration of rocuronium bromide (muscle relaxant) in the central compartment comprises the following steps: S3.1. Add rocuronium bromide (muscle relaxant) to the central compartment of the two-compartment pharmacokinetic model, and obtain the real-time amount of rocuronium bromide (muscle relaxant) in the central compartment at this time, which is: ; Get the real-time dosage of rocuronium bromide (muscle relaxant) in the surrounding room at this time, which is: ; in, It is the injection specification of rocuronium bromide (muscle relaxant); is the body weight in kg; is the real-time dose of rocuronium (muscle relaxant) in the central chamber; It is the real-time dosage of rocuronium bromide (muscle relaxant) in the surrounding room; The time of adding the rocuronium bromide (muscle relaxant) into the central compartment of the two-compartment pharmacokinetic model is set to 0s.

[0035] S3.2. Obtain the changes in the amount of rocuronium (muscle relaxant) in the central chamber and the peripheral chamber, respectively: The change in the amount of rocuronium (muscle relaxant) in the central chamber is: ; The change in the amount of rocuronium bromide (muscle relaxant) in the surrounding room is: ; in, is the time interval for calculating the change in drug amount, which is 0.02s; Rocuronium (muscle relaxant) in the central room The amount of change within Is the surrounding indoor rocuronium (muscle relaxant) in The amount of change within is the first-order elimination rate constant of rocuronium (muscle relaxant) in the central compartment; is the first-order rate constant for the transport of rocuronium (muscle relaxant) from the central compartment to the peripheral compartment; is the first-order rate constant for the transport of rocuronium (muscle relaxant) from the peripheral compartment to the central compartment; is the real-time dose of rocuronium (muscle relaxant) in the central chamber; It is the real-time dosage of rocuronium (muscle relaxant) in the surrounding room.

[0036] S3.3. Based on step S3.2, obtain At this moment, the real-time dosage of rocuronium (muscle relaxant) in the central chamber and the peripheral chamber is: The real-time dosage of rocuronium (muscle relaxant) in the central room is: ; The real-time dosage of rocuronium bromide (muscle relaxant) in the surrounding area is: ; in, After adding rocuronium bromide (muscle relaxant) After the metabolic time, ; yes At that moment, the real-time dosage of rocuronium (muscle relaxant) in the central room; yes At that moment, the real-time dosage of rocuronium bromide (muscle relaxant) in the surrounding room; yes At that moment, the real-time dosage of rocuronium (muscle relaxant) in the central room; yes At this moment, the real-time dosage of rocuronium bromide (muscle relaxant) in the surrounding room.

[0037] S3.4. Based on step S3.3, obtain the real-time drug concentration of rocuronium (muscle relaxant) in the central chamber ,for: ; in, yes At the moment, the real-time drug concentration of rocuronium (muscle relaxant) in the central chamber, in ug / L; After adding rocuronium bromide (muscle relaxant) After the metabolic time, ; yes At that moment, the real-time dosage of rocuronium (muscle relaxant) in the central room; is the body weight in kg; is the apparent distribution volume of rocuronium (muscle relaxant) in the central compartment, in L / kg; Further, in this embodiment, based on steps S3.2 to S3.4, obtain At the moment, the real-time drug concentration of rocuronium (muscle relaxant) in the central room includes: ; ; The real-time drug concentration of rocuronium (muscle relaxant) in the central chamber is: ; in, yes At that moment, the real-time dosage of rocuronium (muscle relaxant) in the central room; yes At that moment, the real-time dosage of rocuronium bromide (muscle relaxant) in the surrounding room; is the body weight in kg; is the apparent distribution volume of rocuronium (muscle relaxant) in the central compartment, in L / kg; yes At the moment, the real-time drug concentration of rocuronium (muscle relaxant) in the central chamber; After adding rocuronium bromide (muscle relaxant) After the metabolic time, .

[0038] It also includes: S3.5. When sugammadex is not added or after sugammadex is consumed, repeat steps S3.2 to S3.4 to obtain the real-time drug concentration of rocuronium (muscle relaxant) in the central chamber.

[0039] S4. Figure 2 According to Table 1 and Table 2, At the same time, sugammadex is added to obtain the real-time drug concentration of rocuronium (muscle relaxant) in the central chamber, including the following steps: S4.1. Obtain the initial concentration of sugammadex in the central chamber as: ; in, This is the injection specification of sugammadex; is the apparent distribution volume of sugammadex in the central compartment, in L / kg; is the molar mass of sugammadex in g / mol; is the initial concentration of sugammadex in the central chamber, in umol / L; S4.2. Sugammadex reacts with rocuronium (muscle relaxant) in a two-compartment model of muscle relaxant pharmacokinetic metabolism After that, the metabolic parameters of the drugs in the central compartment and peripheral compartment of the two-compartment pharmacokinetic model were obtained after the addition of sugammadex. The calculation formulas were: The first-order elimination rate constant of rocuronium (muscle relaxant) in the central compartment is: ; The first-order rate constant for the transport of rocuronium (muscle relaxant) from the peripheral compartment to the central compartment is: ; in, It is the duration of the reaction between sugammadex and rocuronium (muscle relaxant); is the amount of sugammadex consumed per second, in umol / L / s; is the first-order elimination rate constant of rocuronium (muscle relaxant) in the central compartment after the addition of sugammadex; is the first-order rate constant for the transport of rocuronium (muscle relaxant) from the peripheral compartment to the central compartment after the addition of sugammadex; is the initial concentration of sugammadex in the central compartment; , They are the maximum effects of sugammadex on metabolic parameters of the original model; It is the half-effective concentration of sugammadex that affects the changes in the original metabolic parameters; It is a parameter that affects the speed of change of metabolic parameters; is the first-order elimination rate constant of rocuronium (muscle relaxant) in the central compartment when sugammadex is not added; is the first-order rate constant for the transport of rocuronium (muscle relaxant) from the peripheral compartment to the central compartment when sugammadex is not added; among them, after the addition of sugammadex, the transport rate constant of rocuronium (muscle relaxant) from the central compartment to the peripheral compartment is is 0.

[0040] S4.3. Based on step S4.2, obtain the changes of rocuronium bromide (muscle relaxant) in the central chamber and the peripheral chamber, which are: The change in the amount of rocuronium (muscle relaxant) in the central chamber is: ; The change in the amount of rocuronium bromide (muscle relaxant) in the surrounding room is: ; in, is the time interval for calculating the change in drug amount; yes At that moment, the real-time dosage of rocuronium (muscle relaxant) in the central room; yes At that moment, the real-time dosage of rocuronium bromide (muscle relaxant) in the surrounding room; After the addition of sugammadex, rocuronium (muscle relaxant) in the central chamber The amount of change within After adding sugammadex, rocuronium bromide (muscle relaxant) in the surrounding room The amount of change within is the first-order elimination rate constant of the muscle relaxant in the central compartment after the addition of sugammadex; is the first-order rate constant for the transport of the muscle relaxant from the peripheral compartment to the central compartment after the addition of sugammadex.

[0041] S4.4. Based on step S4.3, obtain the real-time dosage of rocuronium (muscle relaxant) in the central chamber and the peripheral chamber, which are: The real-time dosage of rocuronium (muscle relaxant) in the central room is: ; The real-time dosage of rocuronium bromide (muscle relaxant) in the surrounding area is: ; in, yes At that moment, the real-time dosage of rocuronium (muscle relaxant) in the central room; yes At that moment, the real-time dosage of rocuronium bromide (muscle relaxant) in the surrounding room; After the addition of sugammadex, rocuronium (muscle relaxant) in the central chamber The amount of change within After adding sugammadex, rocuronium bromide (muscle relaxant) in the surrounding room The amount of change within yes At that moment, the real-time dosage of rocuronium (muscle relaxant) in the central room; yes At this moment, the real-time dosage of rocuronium bromide (muscle relaxant) in the surrounding room.

[0042] S4.5. Based on step S4.4, the real-time drug concentration of rocuronium bromide (muscle relaxant) in the central chamber is obtained as follows: ; in, yes At the moment, the real-time drug concentration of rocuronium (muscle relaxant) in the central chamber; yes At that moment, the real-time dosage of rocuronium (muscle relaxant) in the central room; is the body weight in kg; It is the apparent distribution volume of rocuronium (muscle relaxant) in the central compartment, in L / kg.

[0043] Also included: S4.6. After adding sugammadex, repeat steps S4.1 to S4.5 to obtain the real-time drug concentration of rocuronium bromide (muscle relaxant) in the central chamber.

[0044] S5. Real-time drug concentration of rocuronium (muscle relaxant) in the central chamber obtained in step S3 and / or step S4 (ug / L) is the vertical coordinate; time t(s) is the horizontal coordinate, and the output is as follows Figure 4 Schematic diagram of the antagonism curve of rocuronium bromide (muscle relaxant) by sugammadex.

[0045] Embodiment 2:

[0046] The difference from Example 1 is that the muscle relaxant is vecuronium bromide. This example takes vecuronium bromide as an example, as follows:

[0047] Vecuronium bromide intravenous injection specifications for humans are: ; Specifications of Sugammadex for intravenous injection in humans are: ;in, , They refer to the drug injection specifications respectively.

[0048] In this embodiment, sugammadex is added at 179.98 seconds after the addition of vecuronium bromide.

[0049] In this embodiment, the time interval for calculating the change in drug amount is set It is 0.02s.

[0050] In some other embodiments, the time interval for calculating the change in drug amount It can be 0.03s or other duration.

[0051] like Figure 1 , Figure 2 , Figure 5 , Figure 6 As shown, this embodiment provides a method for simulating the antagonistic mechanism of sugammadex, comprising the following steps: S1. Establish a two-compartment model for the pharmacokinetics of muscle relaxants, including the central compartment and the peripheral compartment.

[0052] S2. Prefabricated vecuronium (muscle relaxant) and sugammadex drug database, including: drug label, parameter name, parameter value.

[0053] As shown in Table 2 and Table 3, the data of the parameters involved in this embodiment are taken from Table 2 and Table 3.

[0054] In this embodiment, the prefabricated vecuronium bromide drug database is as shown in Table 3 below: Table 3

[0055] In this embodiment, the pre-made sugammadex drug database is shown in Table 2.

[0056] S3. Adding the muscle relaxant to the pharmacokinetic two-compartment model to obtain the real-time drug concentration of vecuronium (muscle relaxant) in the central compartment comprises the following steps: S3.1. Add vecuronium bromide (muscle relaxant) to the central compartment of the two-compartment pharmacokinetic model, and obtain the real-time amount of vecuronium bromide (muscle relaxant) in the central compartment at this time, which is: ; Get the real-time dosage of vecuronium bromide (muscle relaxant) in the surrounding room at this time, which is: ; in, It is the injection specification of vecuronium bromide (muscle relaxant); is the body weight in kg; is the real-time dose of vecuronium (muscle relaxant) in the central chamber; It is the real-time dosage of vecuronium bromide (muscle relaxant) in the surrounding room.

[0057] The time of adding the vecuronium bromide (muscle relaxant) into the central compartment of the two-compartment pharmacokinetic model is set to 0s.

[0058] S3.2. Obtain the changes in the amount of vecuronium (muscle relaxant) in the central chamber and the peripheral chamber, respectively: The change in the amount of vecuronium (muscle relaxant) in the central chamber is: ; The change in the amount of vecuronium bromide (muscle relaxant) in the surrounding room is: ; in, is the time interval for calculating the change in drug amount, which is 0.02s; It is the central room where vecuronium (muscle relaxant) is placed. The amount of change within Is the surrounding indoor vecuronium (muscle relaxant) in The amount of change within is the first-order elimination rate constant of vecuronium (muscle relaxant) in the central compartment; is the first-order rate constant for the transport of vecuronium (muscle relaxant) from the central compartment to the peripheral compartment; is the first-order rate constant for the transport of vecuronium (muscle relaxant) from the peripheral compartment to the central compartment; is the real-time dose of vecuronium (muscle relaxant) in the central chamber; It is the real-time dosage of vecuronium bromide (muscle relaxant) in the surrounding room.

[0059] S3.3. Based on step S3.2, obtain At this moment, the real-time dosage of vecuronium bromide (muscle relaxant) in the central chamber and the peripheral chamber is: The real-time dosage of vecuronium bromide (muscle relaxant) in the central room is: ; The real-time dosage of vecuronium bromide (muscle relaxant) in the surrounding area is: ; in, After adding vecuronium bromide (muscle relaxant) After the metabolic time, ; yes At that moment, the real-time dosage of vecuronium (muscle relaxant) in the central room; yes At that moment, the real-time dosage of vecuronium bromide (muscle relaxant) in the surrounding room; yes At that moment, the real-time dosage of vecuronium (muscle relaxant) in the central room; yes At this moment, the real-time dosage of vecuronium bromide (muscle relaxant) in the surrounding room.

[0060] S3.4. Based on step S3.3, obtain the real-time drug concentration of vecuronium bromide (muscle relaxant) in the central chamber ,for: ; in, yes At the moment, the real-time drug concentration of vecuronium (muscle relaxant) in the central chamber; After adding vecuronium bromide (muscle relaxant) After the metabolic time, ; yes At that moment, the real-time dosage of vecuronium (muscle relaxant) in the central room; is the body weight in kg; is the apparent distribution volume of vecuronium (muscle relaxant) in the central compartment, in L / kg; Further, in this embodiment, based on steps S3.2 to S3.4, obtain At the moment, the real-time drug concentration of vecuronium (muscle relaxant) in the central chamber includes: ; ; The real-time drug concentration of vecuronium (muscle relaxant) in the central chamber is: ; in, yes At that moment, the real-time dosage of vecuronium (muscle relaxant) in the central room; yes At that moment, the real-time dosage of vecuronium bromide (muscle relaxant) in the surrounding room; is the body weight in kg; is the apparent distribution volume of vecuronium (muscle relaxant) in the central compartment, in L / kg; yes At the moment, the real-time drug concentration of vecuronium (muscle relaxant) in the central chamber; After adding vecuronium bromide (muscle relaxant) After the metabolic time, .

[0061] It also includes: S3.5. When sugammadex is not added or after sugammadex is consumed, repeat steps S3.2 to S3.4 to obtain the real-time drug concentration of vecuronium bromide (muscle relaxant) in the central chamber.

[0062] S4. Figure 2 According to Table 2 and Table 3, At the same time, sugammadex is added to obtain the real-time drug concentration of vecuronium (muscle relaxant) in the central chamber, including the following steps: S4.1. Obtaining the initial concentration of sugammadex in the central chamber ,for: ; in, This is the injection specification of sugammadex; is the apparent distribution volume of sugammadex in the central compartment, in L / kg; is the molar mass of sugammadex in g / mol; is the initial concentration of sugammadex in the central chamber, in (umol / L); S4.2. Sugammadex reacts with vecuronium (muscle relaxant) in a two-compartment model of muscle relaxant pharmacokinetic metabolism After that, the metabolic parameters of the drugs in the central compartment and peripheral compartment of the two-compartment pharmacokinetic model were obtained after the addition of sugammadex. The calculation formulas were: The first-order elimination rate constant of vecuronium (muscle relaxant) in the central compartment is: ; The first-order rate constant for the transport of vecuronium (muscle relaxant) from the peripheral compartment to the central compartment is: ; in, It is the duration of the reaction between sugammadex and vecuronium (muscle relaxant); is the amount of sugammadex consumed per second, in umol / L / s; is the first-order elimination rate constant of vecuronium (muscle relaxant) in the central compartment after the addition of sugammadex; is the first-order rate constant for the transport of vecuronium (muscle relaxant) from the peripheral compartment to the central compartment after the addition of sugammadex; is the initial concentration of sugammadex in the central compartment; , They are the maximum effects of sugammadex on metabolic parameters of the original model; It is the half-effective concentration of sugammadex that affects the changes in the original metabolic parameters; It is a parameter that affects the speed of change of metabolic parameters; is the first-order elimination rate constant of vecuronium (muscle relaxant) in the central compartment when sugammadex is not added; is the first-order rate constant for the transport of vecuronium (muscle relaxant) from the peripheral compartment to the central compartment when sugammadex is not added; among them, after the addition of sugammadex, the transport rate constant of vecuronium (muscle relaxant) from the central compartment to the peripheral compartment is is 0.

[0063] S4.3. Based on step S4.2, obtain the changes of vecuronium bromide (muscle relaxant) in the central chamber and the peripheral chamber, which are: The change in the amount of vecuronium (muscle relaxant) in the central chamber is: ; The change in the amount of vecuronium bromide (muscle relaxant) in the surrounding room is: ; in, is the time interval for calculating the change in drug amount, which is 0.02s; yes At that moment, the real-time dosage of vecuronium (muscle relaxant) in the central room; yes At that moment, the real-time dosage of vecuronium bromide (muscle relaxant) in the surrounding room; After the addition of sugammadex, vecuronium bromide (muscle relaxant) in the central chamber The amount of change within After adding sugammadex, vecuronium bromide (muscle relaxant) in the surrounding room The amount of change within is the first-order elimination rate constant of vecuronium (muscle relaxant) in the central compartment after the addition of sugammadex; is the first-order rate constant for the transport of vecuronium (a muscle relaxant) from the peripheral compartment to the central compartment after the addition of sugammadex.

[0064] S4.4. Based on step S4.3, obtain the real-time dosage of vecuronium bromide (muscle relaxant) in the central chamber and the peripheral chamber, which are: The real-time dosage of vecuronium bromide (muscle relaxant) in the central room is: ; The real-time dosage of vecuronium bromide (muscle relaxant) in the surrounding area is: ; in, yes At that moment, the real-time dosage of vecuronium (muscle relaxant) in the central room; yes At that moment, the real-time dosage of vecuronium bromide (muscle relaxant) in the surrounding room; After the addition of sugammadex, vecuronium bromide (muscle relaxant) in the central chamber The amount of change within After adding sugammadex, vecuronium bromide (muscle relaxant) in the surrounding room The amount of change within yes At that moment, the real-time dosage of vecuronium (muscle relaxant) in the central room; yes At this moment, the real-time dosage of vecuronium bromide (muscle relaxant) in the surrounding room.

[0065] S4.5. Based on step S4.4, the real-time drug concentration of vecuronium bromide (muscle relaxant) in the central chamber is obtained as follows: ; in, yes At the moment, the real-time drug concentration of vecuronium (muscle relaxant) in the central chamber; yes At that moment, the real-time dosage of vecuronium (muscle relaxant) in the central room; is the body weight in kg; It is the apparent distribution volume of vecuronium (muscle relaxant) in the central compartment, in L / kg.

[0066] Also included: S4.6. After adding sugammadex, repeat steps S4.1 to S4.5 to obtain the real-time drug concentration of vecuronium bromide (muscle relaxant) in the central chamber.

[0067] S5. The real-time concentration of vecuronium bromide (muscle relaxant) in the central chamber obtained in step S3 and / or step S4 (ug / L) is the vertical coordinate; time t(s) is the horizontal coordinate, and the output is as follows Figure 6 Schematic diagram of the antagonism curve of sugammadex on vecuronium (muscle relaxant).

[0068] In some other embodiments, the time interval for calculating the drug change amount before adding sugammadex The time interval for calculating the drug change after adding sugammadex Different durations can be set for each.

[0069] The above are only preferred embodiments of the present invention and are not intended to limit the protection scope of the present invention. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A method for simulating the antagonistic mechanism of sugammadex, characterized in that: The following steps are involved: S1. Establish a two-compartment model for the pharmacokinetics of muscle relaxants, including the central compartment and the peripheral compartment; S2. Pre-made muscle relaxants and sugammadex drug database; S3. Add the muscle relaxant to the pharmacokinetic two-compartment model to obtain the real-time drug concentration of the muscle relaxant in the central compartment of the pharmacokinetic two-compartment model; S4. Add sugammadex to obtain the real-time drug concentration of the muscle relaxant in the central chamber.

2. The method for simulating the sugammadex antagonism mechanism according to claim 1, characterized in that: The muscle relaxant and sugammadex drug databases respectively include: drug labels, parameter names, and parameter values.

3. A method for simulating the antagonistic mechanism of sugammadex according to claim 2, characterized in that: The drug label of the muscle relaxant includes: drug name, drug metabolic kinetic parameters, and sugammadex parameters.

4. The method for simulating the sugammadex antagonism mechanism according to claim 2, characterized in that: The drug label of sugammadex includes: drug name, molar mass, and pharmacokinetic parameters.

5. The method for simulating the sugammadex antagonism mechanism according to claim 1, characterized in that: The step S3. adding the muscle relaxant to the pharmacokinetic two-compartment model to obtain the real-time drug concentration of the muscle relaxant in the central chamber of the pharmacokinetic two-compartment model comprises the following steps: S3.

1. Add the muscle relaxant to the central chamber of the two-compartment pharmacokinetic model, and obtain the real-time dosage of the muscle relaxant in the central chamber at this time, which is: ； Get the initial dose of the surrounding indoor muscle relaxant at this time, which is: ; in, It is the specification of muscle relaxant injection; is the body weight; It is the real-time dosage of muscle relaxant in the central chamber; It is the real-time dosage of muscle relaxant in the surrounding room; The time of adding the muscle relaxant into the central compartment of the pharmacokinetic two-compartment model is set to 0s; S3.

2. Obtain the changes in the amount of muscle relaxant in the central chamber and the peripheral chamber, respectively: The change in the amount of muscle relaxant in the central chamber is: ； The change in the amount of muscle relaxant in the surrounding room is: ； in, is the time interval for calculating the change in drug amount; It is a central ventricular muscle relaxant. The amount of change within Is the peripheral indoor muscle relaxant in The amount of change within is the first-order elimination rate constant of the muscle relaxant in the central compartment; is the first-order rate constant for the transport of muscle relaxants from the central compartment to the peripheral compartment; is the first-order rate constant for the transport of muscle relaxants from the peripheral compartment to the central compartment; It is the real-time dosage of muscle relaxant in the central chamber; It is the real-time dosage of muscle relaxant in the surrounding room; S3.

3. Based on step S3.2, obtain At this moment, the real-time dosage of muscle relaxants in the central chamber and the peripheral chamber are: The real-time dosage of muscle relaxants in the central chamber is: ； The real-time dosage of muscle relaxants in the surrounding room is: ； in, After adding muscle relaxants After the metabolic time, ; yes At that moment, the real-time dosage of muscle relaxants in the central room; yes At that moment, the real-time dosage of muscle relaxants in the surrounding room; yes At that moment, the real-time dosage of muscle relaxants in the central room; yes At that moment, the real-time dosage of muscle relaxants in the surrounding room; S3.

4. Based on step S3.3, obtain the real-time drug concentration of the muscle relaxant in the central chamber ,for: ； in, yes At that moment, the real-time drug concentration of muscle relaxants in the central chamber; After adding muscle relaxants After the metabolic time, ; is the body weight; It is the apparent distribution volume of the muscle relaxant in the central compartment.

6. The method for simulating the sugammadex antagonism mechanism according to claim 5, characterized in that: It also includes: S3.

5. When sugammadex is not added or after sugammadex is consumed, repeating steps S3.2 to S3.4 to obtain the real-time drug concentration of the muscle relaxant in the central chamber.

7. The method for simulating the sugammadex antagonism mechanism according to claim 1, characterized in that: The step S4. adding sugammadex to obtain the real-time drug concentration of the muscle relaxant in the central chamber comprises the following steps: S4.

1. Obtain the initial concentration of sugammadex in the central chamber as: ； in, This is the injection specification of sugammadex; is the apparent volume of distribution of sugammadex in the central compartment; is the molar mass of sugammadex; is the initial concentration of sugammadex in the central compartment; S4.

2. Sugammadex and muscle relaxant response in a two-compartment model of muscle relaxant pharmacokinetics After the addition of sugammadex, the metabolic parameters of the central and peripheral compartments of the two-compartment pharmacokinetic model were obtained, and the calculation formulas were: The first-order elimination rate constant of muscle relaxants in the central compartment is: ； The first-order rate constant for the transport of muscle relaxants from the peripheral compartment to the central compartment is: ； in, is the duration of the reaction between sugammadex and muscle relaxants; is the amount of sugammadex consumed per second; is the first-order elimination rate constant of the muscle relaxant in the central compartment after the addition of sugammadex; is the first-order rate constant for the transport of the muscle relaxant from the peripheral compartment to the central compartment after the addition of sugammadex; is the initial concentration of sugammadex in the central compartment; , They are the maximum effects of sugammadex on metabolic parameters of the original model; It is the half-effective concentration of sugammadex that affects the changes in the original metabolic parameters; It is a parameter that affects the speed of change of metabolic parameters; is the first-order elimination rate constant of the muscle relaxant in the central compartment when sugammadex is not added; is the first-order rate constant for the transport of the muscle relaxant from the peripheral compartment to the central compartment when sugammadex is not added; S4.

3. Based on step S4.2, obtain the changes in the muscle relaxant in the central chamber and the peripheral chamber, which are: The change in the amount of muscle relaxant in the central chamber is: ； The change in the amount of muscle relaxant in the peripheral room is: ； in, is the time interval for calculating the change in drug amount; yes At that moment, the real-time dosage of muscle relaxants in the central room; yes At that moment, the real-time dosage of muscle relaxants in the surrounding room; After adding sugammadex, the central chamber muscle relaxant The amount of change within After adding sugammadex, peripheral indoor muscle relaxants The amount of change within is the first-order elimination rate constant of the muscle relaxant in the central compartment after the addition of sugammadex; is the first-order rate constant for the transport of the muscle relaxant from the peripheral compartment to the central compartment after the addition of sugammadex; S4.

4. Based on step S4.3, the real-time dosage of the muscle relaxant in the central chamber and the peripheral chamber is obtained, which are: The real-time dosage of muscle relaxants in the central chamber is: ； The real-time dosage of muscle relaxants in the surrounding room is: ； in, yes At that moment, the real-time dosage of muscle relaxants in the central room; yes At that moment, the real-time dosage of muscle relaxants in the surrounding room; After adding sugammadex, the central chamber muscle relaxant The amount of change within After adding sugammadex, peripheral indoor muscle relaxants The amount of change within yes At that moment, the real-time dosage of muscle relaxants in the central room; yes At that moment, the real-time dosage of muscle relaxants in the surrounding room; S4.

5. Based on step S4.4, the real-time drug concentration of the muscle relaxant in the central chamber is obtained as follows: ； in, yes At that moment, the real-time drug concentration of muscle relaxants in the central chamber; yes At that moment, the real-time dosage of muscle relaxants in the central room; is the body weight; It is the apparent distribution volume of the muscle relaxant in the central compartment.

8. The method for simulating the sugammadex antagonism mechanism according to claim 7, characterized in that: Also includes: S4.

6. After adding sugammadex, repeat steps S4.1 to S4.5 to obtain the real-time drug concentration of the muscle relaxant in the central chamber.

9. A method for simulating the sugammadex antagonism mechanism according to any one of claims 1 to 8, characterized in that: The muscle relaxant is rocuronium bromide or vecuronium bromide.

10. A method for simulating the sugammadex antagonism mechanism according to any one of claims 1 to 8, characterized in that: Also includes: S5. The real-time drug concentration of the muscle relaxant in the central chamber obtained in step S3 and / or step S4 is used as the ordinate; With time as the horizontal axis, output the curve graph of sugammadex antagonism to muscle relaxants.

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