Synergistic effect method of traditional Chinese medicine dosage gradient scheme in insomnia treatment based on prescription dosage-efficiency theory

Abstract

The invention belongs to the technical field of traditional Chinese medicine individuation, and provides a synergistic effect method of a traditional Chinese medicine dosage gradient scheme in insomnia treatment based on prescription dosage-efficiency science, which comprises the following steps: performing traditional Chinese medicine syndrome differentiation and typing on patients, and matching corresponding basic prescriptions according to syndromes; collecting individual characteristic parameters of a patient, and calculating an initial dose of traditional Chinese medicine according to the individual characteristic parameters; in the treatment cycle, the insomnia severity index and the Pittsburgh sleep quality index are adopted for curative effect evaluation, safety monitoring is conducted in combination with blood routine examination and liver and kidney function detection, and an evaluation result is obtained; according to an evaluation result, combining pharmacokinetic parameters, dynamically adjusting the dosage of the traditional Chinese medicine, and forming a dosage gradient scheme; synchronizing real-time lifestyle intervention and psychotherapy; through deep combination of the traditional Chinese medicine dialectical theory and modern pharmacokinetics, digital modeling and dynamic regulation and control are carried out on the dose-effect relationship of the traditional Chinese medicine, and the accuracy, safety and long-term curative effect of the traditional Chinese medicine for treating insomnia are ensured.

Description

Technical Field

[0001] The present invention belongs to the technical field of personalized traditional Chinese medicine, and in particular is a method for enhancing the synergistic effect of a traditional Chinese medicine dosage gradient scheme in the treatment of insomnia based on prescription and drug dose-effect theory. Background Art

[0002] Currently, traditional Chinese medicine treatments for insomnia mostly use fixed-dose traditional prescriptions, such as Guipi Decoction and Tianwang Buxin Dan, which generally follow the standard dosages in the "Chinese Medicine Formula" or the commonly used dosage ranges in the pharmacopoeia, lacking quantitative consideration of individual patient characteristics. This "one prescription for a thousand people" model ignores the impact of differences in age, weight, constitution, and liver and kidney function on drug metabolism, resulting in dose mismatch issues in approximately 39% of patients (for example, patients with qi deficiency are prone to drug accumulation when taking conventional doses, while patients with phlegm-dampness constitution may have insufficient efficacy due to faster metabolism), which directly affects clinical efficacy.

[0003] Existing technologies for adjusting the dosage of traditional Chinese medicine mostly rely on the subjective experience of physicians, lack a scientific basis based on pharmacokinetic parameters, do not incorporate indicators such as peak blood drug concentration and half-life into dosage decisions, and are unable to accurately evaluate the relationship between drug exposure and efficacy. Contradictions such as "efficacy not achieved but dosage exceeded limit" or "dose insufficient but concentration reached standard" often occur, resulting in prolonged insomnia treatment cycles and an adverse reaction rate as high as 18.3%.

[0004] In addition, traditional programs lack a systematic efficacy-safety evaluation system: they only make qualitative judgments based on symptom improvement, and have not established a linkage mechanism between quantitative indicators such as PSQI and ISI and liver and kidney function monitoring, making it difficult to achieve a dynamic balance between efficacy and safety in dose adjustment; at the same time, the intervention methods are single, and there is a lack of coordinated management of dimensions such as sleep hygiene and psychological cognition, which cannot meet the needs of individualized treatment.

[0005] To this end, those skilled in the art have proposed a method for enhancing the effect of a traditional Chinese medicine dosage gradient scheme in the treatment of insomnia based on the dose-effect theory of prescriptions and medicines, aiming to deeply combine the theory of traditional Chinese medicine syndrome differentiation with modern pharmacokinetics, and to digitally model and dynamically regulate the dose-effect relationship of prescriptions and medicines, so as to ensure the accuracy, safety and long-term efficacy of traditional Chinese medicine in the treatment of insomnia. Summary of the Invention

[0006] In order to solve the above technical problems, the present invention provides a method for enhancing the synergistic effect of a traditional Chinese medicine dosage gradient scheme in the treatment of insomnia based on prescription and drug dose-effect theory, so as to solve the problems raised in the background technology.

[0007] According to a first aspect of the present disclosure, a method for enhancing the synergistic effect of a traditional Chinese medicine dosage gradient scheme in the treatment of insomnia based on prescription-drug dose-effect theory is proposed, comprising the following steps:

[0008] S1. Perform TCM syndrome differentiation on the patient and match the corresponding basic prescription according to the syndrome type;

[0009] S2. Collect individual characteristic parameters of the patient and calculate the initial dose of the traditional Chinese medicine based on the individual characteristic parameters, wherein the individual characteristic parameters include age, weight, physical type, and liver and kidney function indicators;

[0010] S3. During treatment, efficacy was assessed every 7-14 days using the Insomnia Severity Index and the Pittsburgh Sleep Quality Index, and safety was monitored in combination with routine blood tests and liver and kidney function tests to obtain evaluation results.

[0011] S4. Based on the evaluation results and combined with pharmacokinetic parameters, dynamically adjust the dosage of the traditional Chinese medicine to form a dose gradient plan until the optimal therapeutic effect is achieved or intolerable adverse reactions occur;

[0012] S5. Synchronous real-time lifestyle intervention and psychotherapy; the lifestyle intervention includes sleep hygiene guidance, diet management and exercise prescription, and the psychotherapy includes cognitive behavioral therapy.

[0013] Preferably, in step S1, the syndrome type includes at least one of the following syndromes: liver fire disturbing the heart syndrome, phlegm heat disturbing the heart syndrome, heart and spleen deficiency syndrome, heart and kidney disharmony syndrome, or heart and gallbladder qi deficiency syndrome;

[0014] The corresponding basic prescriptions are matched according to the syndrome types, including: Longdan Xiegan Decoction for the syndrome of liver fire disturbing the heart, Huanglian Wendan Decoction for the syndrome of internal disturbance of phlegm and heat, Guipi Decoction for the syndrome of deficiency of both heart and spleen, Tianwang Buxin Dan combined with Liuwei Dihuang Wan for the syndrome of disharmony between heart and kidney, and Anshen Dingzhi Wan combined with Suanzaoren Decoction for the syndrome of deficiency of heart and gallbladder qi.

[0015] Preferably, in step S2, calculating the initial dose of the traditional Chinese medicine according to the individual characteristic parameters includes:

[0016] The standard dosage of the basic prescription is D base , the individualized initial dose is:

[0017] D init =D base ×K age ×K weight ×K ct ×K liver ×K kid

[0018] Among them, K age is the age coefficient, K weight is the weight coefficient, K ct is the body mass coefficient, K liver is the liver function coefficient, K kid is the renal function coefficient.

[0019] Preferably, in step S3, the Insomnia Severity Index and the Pittsburgh Sleep Quality Index are used to evaluate the therapeutic effect. The treatment evaluation period is T, T∈[7,14] days, and the sleep index improvement rate is calculated using the following formula:

[0020]

[0021] Among them, R ISI is the improvement rate of the Insomnia Severity Index, ISI t is the current insomnia severity index, ISI0 is the baseline of the insomnia severity index; R PSQI is the improvement rate of the Insomnia Severity Index, PSQI t is the current Pittsburgh Sleep Quality Index, PSQI0 is the baseline of the Pittsburgh Sleep Quality Index;

[0022] By normalizing the weights, a comprehensive efficacy score is obtained, which is expressed as:

[0023]

[0024] Among them, α and β are the corresponding weight coefficients, ISI th 、PSQI th The thresholds for the Insomnia Severity Index and the Pittsburgh Sleep Quality Index are respectively; combined with blood routine, liver and kidney function tests for safety monitoring, the assessment result A is obtained:

[0025] A=f(E,R liver ,R kidney ,R blood )

[0026] Among them, R liver is the functional risk index, R kidney is the renal function risk index, R blood is the blood system risk index, and f represents the decision function, which is used to map the input parameters to specific decision outputs.

[0027] Preferably, in step S4, according to the type of the evaluation result and in combination with the pharmacokinetic parameters, the PK parameters are selected to dynamically adjust the dosage of the traditional Chinese medicine;

[0028] The conditions for dose escalation are: if the evaluation results A are met at the same time, the dose is increased, and C min <C min-eff That is, the current minimum concentration is less than the target minimum concentration, C max <0.7<C max-safe That is, the current maximum concentration is less than 70% of the safe maximum concentration limit; the calculation increment is:

[0029]

[0030] Among them, 10% is the basic step length, is the half-life correction, Compensation for concentration gap;

[0031] The dose reduction conditions are: if the evaluation result A is met, the dose is reduced or C is met. max >0.9×C max-safe That is, the current maximum concentration exceeds 90% of the safe maximum concentration threshold, which is the toxic load; the reduction range is calculated as:

[0032]

[0033] Among them, 20% is the basic reduction, Penalty for exceeding the limit;

[0034] The dose escalation algorithm is used to form a dose gradient scheme, which is expressed as:

[0035]

[0036] Among them, k is the slope coefficient, and E is the comprehensive score of efficacy, until the best efficacy is achieved or intolerable adverse reactions occur.

[0037] Compared with the prior art, the present invention has the following beneficial effects:

[0038] 1. The present invention realizes the three-dimensional precise control of syndrome differentiation-dose-metabolism through the linkage between TCM syndrome differentiation and pharmacokinetic parameters, and dynamically monitors liver and kidney function and blood drug concentration, thereby reducing the incidence of adverse reactions. Through the precision of TCM syndrome differentiation, digitalization of dose adjustment and diversification of intervention methods, the present invention realizes the deep integration of modern pharmacokinetics and traditional TCM theory.

[0039] 2. The present invention constructs a dosage gradient scheme for traditional Chinese medicine based on the dose-effect theory of prescriptions and medicines, accurately calculates the initial dose through traditional Chinese medicine syndrome differentiation and individual characteristic parameters, and dynamically adjusts the dosage gradient in combination with pharmacokinetic parameters to achieve refined management and break through the efficacy limitations of traditional fixed doses. BRIEF DESCRIPTION OF THE DRAWINGS

[0040] Figure 1 This is a flow chart of the Chinese medicine dosage gradient synergistic enhancement method of the present invention;

[0041] Figure 2 This is a flowchart of the dosage adjustment decision process in step S4 of the present invention. DETAILED DESCRIPTION

[0042] The following embodiments of the present invention are described in further detail with reference to the accompanying drawings and examples. The following examples are used to illustrate the present invention but are not intended to limit the scope of the present invention.

[0043] Example: As shown in the attached Figure 1 As shown, the present invention provides a method for enhancing the synergistic effect of a traditional Chinese medicine dosage gradient scheme in the treatment of insomnia based on prescription and drug dose-effect theory, comprising the following steps:

[0044] S1. Perform TCM syndrome differentiation on the patient and match the corresponding basic prescription according to the syndrome type; the syndrome type includes at least one of the following: liver fire disturbing the heart syndrome, phlegm heat internal disturbance syndrome, heart and spleen deficiency syndrome, heart and kidney disharmony syndrome, or heart and gallbladder qi deficiency syndrome;

[0045] The corresponding basic prescriptions are matched according to the syndrome types, including: Longdan Xiegan Decoction for the syndrome of liver fire disturbing the heart, Huanglian Wendan Decoction for the syndrome of phlegm-heat disturbing the heart, Guipi Decoction for the syndrome of deficiency of both heart and spleen, Tianwang Buxin Dan combined with Liuwei Dihuang Wan for the syndrome of disharmony between heart and kidney, and Anshen Dingzhi Wan combined with Suanzaoren Decoction for the syndrome of deficiency of heart and gallbladder qi.

[0046] Based on the theory of traditional Chinese medicine, insomnia is divided into five major syndromes, including liver fire disturbing the heart and phlegm-heat disturbing the body. Classic prescriptions are matched to achieve a precise basis for "differentiation and treatment". Corresponding prescriptions are selected according to the pathological mechanisms of different syndromes to improve the targeted use of medication.

[0047] S2. Collect individual characteristic parameters of the patient and calculate the initial dose of traditional Chinese medicine based on these individual characteristic parameters. The individual characteristic parameters include age, weight, physical type, and liver and kidney function indicators. The initial dose of traditional Chinese medicine calculated based on the individual characteristic parameters includes:

[0048] The standard dosage of the basic prescription is D base , the individualized initial dose is:

[0049] D init =D base ×K age ×K weight ×K ct ×K liver ×K kid

[0050] Among them, K age is the age coefficient, K weight is the weight coefficient, K ct is the body mass coefficient, K liver is the liver function coefficient, K kid is the renal function coefficient.

[0051] By collecting the patient's age, weight, physical condition, liver and kidney function and other parameters, the impact of individual differences on drug metabolism is quantified and the initial dose deviation is automatically adjusted.

[0052] S3. During treatment, the Insomnia Severity Index and the Pittsburgh Sleep Quality Index were used to evaluate the efficacy every 7-14 days. Safety monitoring was performed in combination with blood routine tests and liver and kidney function tests to obtain the evaluation results. The Insomnia Severity Index and the Pittsburgh Sleep Quality Index were used to evaluate the efficacy. The treatment evaluation cycle was T, T∈[7,14] days. The sleep index improvement rate was calculated using the following formula:

[0053]

[0054] Among them, R ISI is the improvement rate of the Insomnia Severity Index, ISI t is the current insomnia severity index, ISI0 is the baseline of the insomnia severity index; R PSQI is the improvement rate of the Insomnia Severity Index, PSQI t is the current Pittsburgh Sleep Quality Index, PSQI0 is the baseline of the Pittsburgh Sleep Quality Index;

[0055] By normalizing the weights, a comprehensive efficacy score is obtained, which is expressed as:

[0056]

[0057] Among them, α and β are the corresponding weight coefficients, ISI th 、PSQI th The thresholds for the Insomnia Severity Index and the Pittsburgh Sleep Quality Index are respectively; combined with blood routine, liver and kidney function tests for safety monitoring, the assessment result A is obtained:

[0058] A=f(E,R liver ,R kidney ,R blood )

[0059] Among them, R liver is the functional risk index, R kidney is the renal function risk index, R blood is the blood system risk index, and f represents the decision function, which is used to map the input parameters to specific decision outputs.

[0060] The efficacy is evaluated every 7-14 days using PSQI and ISI scores, combined with blood routine and liver and kidney function tests for safety, to objectively quantify the treatment response, detect abnormal liver and kidney function, and reduce the incidence of adverse reactions.

[0061] S4, as attached Figure 2 As shown, according to the type of evaluation results and combined with pharmacokinetic parameters, PK parameters are selected to dynamically adjust the dosage of traditional Chinese medicine;

[0062] The conditions for dose escalation are: if the evaluation results A are met at the same time, the dose is increased, and Cmin <C min-eff That is, the current minimum concentration is less than the target minimum concentration, C max <0.7<C max-safe That is, the current maximum concentration is less than 70% of the safe maximum concentration limit; the calculation increment is:

[0063]

[0064] Among them, 10% is the basic step length, is the half-life correction, Compensation for concentration gap;

[0065] The dose reduction conditions are: if the evaluation result A is met, the dose is reduced or C is met. max >0.9×C max-safe That is, the current maximum concentration exceeds 90% of the safe maximum concentration threshold, which is the toxic load; the reduction range is calculated as:

[0066]

[0067] Among them, 20% is the basic reduction, Penalty for exceeding the limit;

[0068] The dose escalation algorithm is used to form a dose gradient scheme, which is expressed as:

[0069]

[0070] Among them, k is the slope coefficient, and E is the comprehensive score of efficacy, until the best efficacy is achieved or intolerable adverse reactions occur.

[0071] The dosage is adjusted dynamically by gradient formula to ensure that the blood drug concentration is maintained within the therapeutic window C max <0.7<C max-safe To avoid cumulative toxicity or insufficient dosage, the time to achieve therapeutic effect is shortened through this adjustment mechanism.

[0072] S5. Simultaneous real-time lifestyle intervention and psychotherapy; lifestyle intervention includes sleep hygiene guidance, diet management and exercise prescription, and psychotherapy includes cognitive behavioral therapy.

[0073] Integrate sleep hygiene guidance, diet management, exercise prescription and CBT-I therapy to form a "drug-behavior-cognitive" synergistic intervention, strengthen treatment compliance, correct insomnia-related bad habits, and reduce the recurrence rate of insomnia through joint intervention.

[0074] From the above, we can see that introducing pharmacokinetic parameters into the dosage adjustment of traditional Chinese medicine will form a quantitative system of traditional Chinese medicine syndrome differentiation + modern pharmacology, and establishing a dual-driven adjustment formula based on efficacy and safety, so that dosage adjustment can be transformed from qualitative judgment to quantitative calculation; at the same time, multiple indicators are integrated to achieve real-time optimization of treatment plans through decision-making functions, and CBT-I therapy is combined with traditional Chinese medicine time therapy to form a drug-behavior-cognition synergistic system to fill the gap in the lack of psychological intervention in traditional Chinese medicine.

[0075] Experimental example:

[0076] Experimental purpose: To verify the effectiveness and safety of a dose gradient regimen based on TCM syndrome differentiation and pharmacokinetics in the treatment of insomnia, and to compare the clinical differences with traditional fixed-dose therapy.

[0077] Subjects:

[0078] Inclusion criteria: Insomnia diagnosis criteria of Traditional Chinese Medicine Internal Medicine, ISI ≥ 7 points and PSQI ≥ 7 points, disease duration ≥ 2 weeks, age 18-65 years, syndrome differentiation of heart and spleen deficiency or heart and kidney disharmony.

[0079] Exclusion criteria: patients with severe liver and kidney dysfunction (ALT>2×ULN or Cr>1.5×ULN), mental illness, pregnant women and lactating women.

[0080] Sample size: A prospective randomized controlled trial was conducted, with a total of 120 patients enrolled and randomly divided into: gradient dose group (Group A): 60 patients, who received the dose gradient regimen of Example 1 + synchronous intervention; fixed dose group (Group B): 60 patients, who received the standard dose of the basic prescription + synchronous intervention.

[0081] Experimental period:

[0082] Treatment period: 8 weeks, with dose adjustment and efficacy evaluation every 14 days;

[0083] Follow-up period: 6 months after the end of treatment, and the stability of therapeutic efficacy was evaluated every 3 months.

[0084] Experimental methods:

[0085] Implementation steps of the gradient dose group (Group A):

[0086] S1. Syndrome differentiation and prescription: Guipi Decoction is suitable for the syndrome of deficiency of both heart and spleen, and the standard dosage of the basic prescription is D base It contains 15g of Astragalus, 12g of Codonopsis, 10g of Angelica, etc. (refer to the 2025 edition of the Chinese Pharmacopoeia).

[0087] S2. Calculation of initial dose: Take a 45-year-old patient weighing 60 kg, with Qi deficiency and normal liver function as an example: D init =D base ×Kage ×K weight ×K ct ×K liver ×K kid

[0088] Among them, K age =0.9 (45-year-old correction factor), K weight =1.0(standard weight), K ct =0.9 (Qi deficiency reduced by 10%), K liver =1.0 (normal liver function), D init =15×0.9×1.0×0.9×1.0=12.15g (initial dose of Astragalus).

[0089] S3-S4, Dose adjustment: If the PSQI improvement rate in week 2 = 25% (<30%) and C max <0.7<C max-safe , increasing by 10% gradient:

[0090] The adjusted Astragalus dosage = 12.15 × 1.1 = 13.365 g (take 13.4 g).

[0091] S5. Synchronous intervention: Take Guipi Decoction 90 minutes before bedtime, cooperate with sleep hygiene guidance, and combine with CBT-I stimulation control therapy.

[0092] Fixed-dose group (Group B) control: Guipi Decoction Astragalus was fixed at 15g and Codonopsis pilosula was 12g, without dose adjustment. Other synchronous intervention measures were the same as Group A.

[0093] Experimental results: The results of the efficacy comparison are shown in the following table:

[0094]

[0095] As shown above, the dose-gradient regimen significantly improved the efficacy of insomnia treatment compared to fixed-dose therapy, with a 37% improvement in PSQI and an effective rate of 88.3%. It was particularly effective in shortening sleep onset time and reducing nighttime awakenings. The dynamic adjustment mechanism reduced the incidence of adverse reactions by 36%, all of which were mild and reversible, validating the scientific validity of the dual-driven "efficacy-safety" approach. Furthermore, dose-gradient adjustment allowed blood drug concentrations to accurately approach the therapeutic window, confirming the feasibility of using pharmacokinetic parameters to guide TCM dosage optimization.

[0096] It will be understood that in the development of any actual embodiment, as in any engineering or design project, numerous implementation-specific decisions may be made. Such a development effort may be complex and time-consuming, but for those of ordinary skill having the benefit of this disclosure, the development effort will be a routine task of design, fabrication, and production without undue experimentation.

[0097] It should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit the present invention. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solutions of the present invention may be modified or replaced by equivalents without departing from the spirit and scope of the technical solutions of the present invention, which should all be included in the scope of the claims of the present invention.

Claims

1. A method for enhancing the synergistic effect of a traditional Chinese medicine dosage gradient scheme in the treatment of insomnia based on prescription and drug dose-effect theory, characterized in that: The following steps are involved: S1. Perform TCM syndrome differentiation on the patient and match the corresponding basic prescription according to the syndrome type; S2. Collect individual characteristic parameters of the patient and calculate the initial dose of the traditional Chinese medicine based on the individual characteristic parameters, wherein the individual characteristic parameters include age, weight, physical type, and liver and kidney function indicators; S3. During treatment, efficacy was assessed every 7-14 days using the Insomnia Severity Index and the Pittsburgh Sleep Quality Index, and safety was monitored in combination with routine blood tests and liver and kidney function tests to obtain evaluation results. S4. Based on the evaluation results and combined with pharmacokinetic parameters, dynamically adjust the dosage of the traditional Chinese medicine to form a dose gradient plan until the optimal therapeutic effect is achieved or intolerable adverse reactions occur; S5. Synchronous real-time lifestyle intervention and psychotherapy; the lifestyle intervention includes sleep hygiene guidance, diet management and exercise prescription, and the psychotherapy includes cognitive behavioral therapy.

2. The method for enhancing the synergistic effect of a Chinese medicine dosage gradient regimen based on prescription and drug dose-effect theory in the treatment of insomnia according to claim 1, characterized in that: In step S1, the syndrome type includes at least one of the following syndromes: liver fire disturbing the heart syndrome, phlegm heat disturbing the heart syndrome, heart and spleen deficiency syndrome, heart and kidney disharmony syndrome, or heart and gallbladder qi deficiency syndrome; The corresponding basic prescriptions are matched according to the syndrome types, including: Longdan Xiegan Decoction for the syndrome of liver fire disturbing the heart, Huanglian Wendan Decoction for the syndrome of internal disturbance of phlegm and heat, Guipi Decoction for the syndrome of deficiency of both heart and spleen, Tianwang Buxin Dan combined with Liuwei Dihuang Wan for the syndrome of disharmony between heart and kidney, and Anshen Dingzhi Wan combined with Suanzaoren Decoction for the syndrome of deficiency of heart and gallbladder qi.

3. The method for enhancing the synergistic effect of a Chinese medicine dosage gradient scheme based on prescription and drug dose-effect theory in the treatment of insomnia according to claim 1, characterized in that: In step S2, calculating the initial dose of the traditional Chinese medicine according to the individual characteristic parameters includes: The standard dosage of the basic prescription is D base , the individualized initial dose is: D init =D base ×K age ×K weight ×K ct ×K liver ×K kid Among them, K age is the age coefficient, K weight is the weight coefficient, K ct is the body mass coefficient, K liver is the liver function coefficient, K kid is the renal function coefficient.

4. The method for enhancing the synergistic effect of a Chinese medicine dosage gradient regimen based on prescription and drug dose-effect theory in the treatment of insomnia according to claim 1, characterized in that: In step S3, the Insomnia Severity Index and the Pittsburgh Sleep Quality Index are used to evaluate the therapeutic effect. The treatment evaluation period is T, T∈[7,14] days. The sleep index improvement rate is calculated using the following formula: Among them, R ISI is the improvement rate of the Insomnia Severity Index, ISI t is the current insomnia severity index, ISI0 is the baseline of the insomnia severity index; R PSQI is the improvement rate of the Insomnia Severity Index, PSQI t is the current Pittsburgh Sleep Quality Index, PSQI0 is the baseline of the Pittsburgh Sleep Quality Index; By normalizing the weights, a comprehensive efficacy score is obtained, which is expressed as: Among them, α and β are the corresponding weight coefficients, ISI th 、PSQI th The thresholds for the Insomnia Severity Index and the Pittsburgh Sleep Quality Index are respectively; combined with blood routine, liver and kidney function tests for safety monitoring, the assessment result A is obtained: A=f(E,R liver ,R kidney ,R blood ) Among them, R liver is the functional risk index, R kidney is the renal function risk index, R blood is the blood system risk index, and f represents the decision function, which is used to map the input parameters to specific decision outputs.

5. The method for enhancing the synergistic effect of a Chinese medicine dosage gradient regimen based on prescription and drug dose-effect theory in the treatment of insomnia according to claim 1, characterized in that: In step S4, according to the type of the evaluation result and in combination with the pharmacokinetic parameters, PK parameters are selected to dynamically adjust the dosage of the traditional Chinese medicine; The conditions for dose escalation are: if the evaluation results A are met at the same time, the dose is increased, and C min <C min-eff That is, the current minimum concentration is less than the target minimum concentration, C max <0.7<C max-safe That is, the current maximum concentration is less than 70% of the safe maximum concentration limit; the calculation increment is: Among them, 10% is the basic step length, is the half-life correction, Compensation for concentration gap; The dose reduction conditions are: if the evaluation result A is met, the dose is reduced or C is met. max >0.9×C max-safe That is, the current maximum concentration exceeds 90% of the safe maximum concentration threshold, which is the toxic load; the reduction range is calculated as: Among them, 20% is the basic reduction, Penalty for exceeding the limit; The dose escalation algorithm is used to form a dose gradient scheme, which is expressed as: Among them, k is the slope coefficient, and E is the comprehensive score of efficacy, until the best efficacy is achieved or intolerable adverse reactions occur.

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