CN-121978291-A - Chemical property analysis method for evaluating consistency of medicine quality

CN121978291ACN 121978291 ACN121978291 ACN 121978291ACN-121978291-A

Abstract

The invention relates to the technical field of medicine detection and discloses a chemical property analysis method for evaluating the consistency of medicine quality, which comprises the steps of adjusting physical and chemical parameters of a fluid in a controlled flow field to induce transient dissociation response of the medicine, collecting an absorbance data sequence and a complex impedance signal sequence, mapping a first-order difference value and a complex impedance phase angle of absorbance data to a two-dimensional physical and chemical parameter distribution domain, thereby extracting a physical and chemical response distribution point set, converting the point set into state nodes according to a grid division rule, and further counting the migration frequency and direction among the nodes to construct a physical and chemical state transfer map.

Inventors

WANG YIQUN
YAN XINGYI
ZHANG YONGLI

Assignees

西安吉泰医药科技有限公司

Dates

Publication Date: 20260505
Application Date: 20260408

Claims (9)

1. The chemical property analysis method for evaluating the consistency of the medicine quality is characterized by comprising the following steps of: step S1, in a closed controlled flow field, adjusting the pH value, the ionic strength and the surfactant concentration of an analysis fluid according to a preset time sequence, and inducing a to-be-detected medicine to generate transient dissociation response along with the environmental change of the fluid; s2, acquiring an absorbance data sequence and a complex impedance signal sequence which characterize the drug to be tested in transient dissociation response through a detection unit consisting of an ultraviolet absorbance sensor and an impedance sensor; S3, extracting a first-order difference value from the absorbance data sequence, mapping the first-order difference value and a complex impedance phase angle in the complex impedance signal sequence as coordinate components to a two-dimensional physicochemical parameter distribution domain, and extracting a physicochemical response distribution point set formed by correlation points of the first-order difference value and the complex impedance phase angle at the same sampling time; s4, dividing the two-dimensional physical and chemical parameter distribution domain into a plurality of discrete physical and chemical state areas according to a preset grid dividing rule, and defining the physical and chemical state areas in which physical and chemical response distribution point sets fall as state nodes representing specific chemical states; And S5, counting the migration direction and migration frequency between the state nodes at adjacent moments, and constructing a physical and chemical state transfer map representing the dynamic evolution topological characteristics of the chemical properties of the to-be-detected medicine so as to realize the deep evaluation of the medicine quality through the consistency comparison of the map structures.
2. The chemical property analysis method for evaluating the quality consistency of the medicine according to claim 1 is characterized by further comprising the following steps of S6, converting grid coordinate attributes of all state nodes in a physical and chemical state transition map and migration frequency information among adjacent nodes into a specific coded character sequence according to a preset topological serialization rule to generate a dynamic track characteristic character string used for representing the dynamic characteristics of the medicine, S7, taking the dynamic track characteristic character string as a retrieval key value, matching in a preset standard medicine fingerprint database through an inverted index mechanism, retrieving a reference map subset corresponding to the medicine to be tested, S8, calculating sub-graph isomorphic matching degree between the physical and chemical state transition map and all reference maps in the reference map subset, and outputting a chemical property consistency evaluation result of the medicine to be tested and a reference preparation according to the sub-graph isomorphic matching degree.
3. The chemical property analysis method for evaluating the consistency of medicine quality according to claim 1, wherein in the step S1, an acidic buffer solution, an alkaline buffer solution and a simulated gastrointestinal fluid are alternately injected into a closed controlled flow field according to a preset frequency through a high-precision plunger pump set, so as to construct a disturbance flow field with a dynamic concentration gradient.
4. The chemical property analysis method for evaluating consistency of medicine quality according to claim 1, wherein in step S2, the sampling frequency of the signal collected by the detection unit is not lower than 100Hz, and the complex impedance signal sequence comprises a complex impedance phase angle sequence and a complex impedance amplitude sequence which change with time.
5. A chemical property analysis method for drug quality consistency assessment according to claim 1, wherein the physicochemical state transition profile comprises a state switching path formed by directional arcs, and a weight matrix for storing residence time of the physicochemical response distribution point set in each discrete physicochemical state region.
6. The chemical property analysis method for evaluating consistency of medicine quality according to claim 2, wherein in step S6, the topological serialization rule comprises extracting maximum connected components in the physical and chemical state transition map, extracting critical evolution paths in the maximum connected components by using a depth-first traversal algorithm, and mapping coordinate components of all state nodes on the critical evolution paths into feature characters.
7. The method for analyzing chemical properties for evaluating consistency of pharmaceutical quality according to claim 2, wherein in step S7, the inverted index mechanism comprises splitting a dynamic track character string into a plurality of feature segments with fixed length, and searching a standard graph with the largest number of feature segments in a standard pharmaceutical fingerprint database as a member of a reference graph subset.
8. The chemical property analysis method for evaluating the consistency of medicine quality according to claim 2, wherein in the step S8, the calculation process of the isomorphic matching degree of the subgraph comprises the steps of extracting the topological feature vector of the physical and chemical state transfer map and calculating the Euclidean distance between the topological feature vector and the basic feature vector of the reference map.
9. The chemical property analysis method for evaluating the consistency of medicine quality according to claim 2, wherein in step S8, when the consistency evaluation result is output, if the isomorphic matching degree of the subgraph is higher than a preset similarity threshold, it is determined that the in vitro dissociation behavior of the medicine to be tested is consistent with that of the reference preparation.

Description

Chemical property analysis method for evaluating consistency of medicine quality Technical Field The invention belongs to the technical field of medicine detection, and particularly relates to a chemical property analysis method for evaluating consistency of medicine quality. Background The method has applicability in processing a quasi-static balanced preparation system, provides a basic evaluation criterion for standardized quality control of medicines, and provides a basic evaluation criterion for the standard evaluation criterion, wherein an oral solid preparation faces physical and chemical environment evolution in gastrointestinal transit, and relates to pH gradient change, ionic strength fluctuation and fluid shear force change, a high molecular auxiliary material system generates microscopic responses such as local supersaturation, mesogenic transformation or gel layer ablation when the boundary condition is mutated, the transient effective concentration of an active ingredient at a key absorption part is directly determined, a static buffer is set as a test environment in the existing analysis mode, the measurement frequency is low, the physical quantity of feedback is limited to the time sequence accumulation of the whole concentration, and the loss of the evaluation mode reflects the transient characteristics of the real interaction mechanism of auxiliary materials and the active ingredient. The physical structure of the detection equipment is limited, the characterization logic and the analysis method of the complex preparation release process are deficient, for example, the Chinese patent application with publication number CN116525137A discloses a quality consistency evaluation method of a traditional Chinese medicine compound preparation, a medicine absorption bionic system is established to be combined with a real-time unmarked dynamic cell analysis system, the medicine effect consistency is evaluated by utilizing a cell index evolution curve along with time, the scheme realizes the integral evaluation from the biological effect level, but in the bottom engineering logic, the cell response belongs to a secondary signal and is limited by the physiological inertia of a biological detection source and the signal hysteresis effect, the sampling resolution can not map the transient dissociation action of the millisecond preparation, the biological evaluation system can not decouple the physical scattering interference of complex matrixes, the microscopic evolution track of the preparation in a phase space is difficult to restore, and the principle feature perception defect exists when the chemical preparation with complex release feature is evaluated. Therefore, how to capture and analyze the transient physicochemical evolution track under the controlled disturbance and construct a dynamic evaluation mechanism with topology fidelity and retrieval capability becomes the technical problem to be solved by the invention. Disclosure of Invention The invention provides a chemical property analysis method for evaluating consistency of medicine quality, which comprises the following steps: step S1, in a closed controlled flow field, adjusting the pH value, the ionic strength and the surfactant concentration of an analysis fluid according to a preset time sequence, and inducing a to-be-detected medicine to generate transient dissociation response along with the environmental change of the fluid; s2, acquiring an absorbance data sequence and a complex impedance signal sequence which characterize the drug to be tested in transient dissociation response through a detection unit consisting of an ultraviolet absorbance sensor and an impedance sensor; S3, extracting a first-order difference value from the absorbance data sequence, mapping the first-order difference value and a complex impedance phase angle in the complex impedance signal sequence as coordinate components to a two-dimensional physicochemical parameter distribution domain, and extracting a physicochemical response distribution point set formed by correlation points of the first-order difference value and the complex impedance phase angle at the same sampling time; s4, dividing the two-dimensional physical and chemical parameter distribution domain into a plurality of discrete physical and chemical state areas according to a preset grid dividing rule, and defining the physical and chemical state areas in which physical and chemical response distribution point sets fall as state nodes representing specific chemical states; And S5, counting the migration direction and migration frequency between the state nodes at adjacent moments, and constructing a physical and chemical state transfer map representing the dynamic evolution topological characteristics of the chemical properties of the to-be-detected medicine so as to realize the deep evaluation of the medicine quality through the consistency comparison of the map structures. Preferably, the method