RU2675407C1 - Method on basis of raman spectroscopy for control of western drugs added to health food products - Google Patents

Abstract

FIELD: instrumentation technology; food industry.SUBSTANCE: invention relates to the field of food quality control and relates to a control method based on Raman spectroscopy of drugs added to health food products. Method includes the steps in which the initial Raman spectroscopic signal is obtained and compared with the reference initial Raman spectroscopic signals of the drug formulations. It is determined that the sample contains drug formulations if the original Raman spectroscopic signal of the sample matches one or more of the reference source Raman spectroscopic signals of the drug formulations. If the original Raman spectroscopic signal of the sample does not coincide with any of the reference original Raman spectroscopic signals of all the compositions of the drugs, then test the enhanced Raman spectrum of the sample and comparing the amplified Raman spectroscopic signal of the sample with the reference amplified Raman spectroscopic signals of the drug formulations to determine if the sample to be controlled contains the drug formulations.EFFECT: technical result is to increase the accuracy and reduce the time spent in the measurements.15 cl, 9 dwg

Description

CROSS REFERENCE TO A RELATED APPLICATION

This application claims advantages on the basis of Chinese patent application No. 201510221524.8 filed on May 4, 2015 with the State Intellectual Property Office of the PRC, the contents of which are fully incorporated into this description by reference.

BACKGROUND OF THE INVENTION

1. The technical field to which the invention relates.

The present invention relates to the field of safety control technology, in particular, to a method for controlling food products, for example, health food products, using Raman spectra to determine whether Western medicines are added to health food products.

2. Description of the prior art.

Some unscrupulous trading organizations illegally add Western medicine formulations to food products (for example, health food products) to increase the effectiveness or speed up the drug effect. However, the compositions of Western medicines often have side effects and are subject to dosing according to the doctor's prescription. Prolonged consumption of such foods can be harmful. Therefore, it is very important to control wellness foods.

Currently, Western medicines illegally added to health food products are mainly detected, for example, by chromatography, mass spectrography. These methods require a long time and therefore do not meet the requirements of rapid control and verification in practical use.

SUMMARY OF THE INVENTION

The present invention is the provision of a method based on Raman spectroscopy for the control of Western medicines added to health food products, which allows you to quickly, efficiently and accurately determine whether the sample to be controlled (for example, health food products), in violation of the law, the compositions of Western medicines.

In this regard, the following embodiments of the present invention are provided.

An embodiment of the present invention provides a method based on Raman spectroscopy for monitoring Western medicines added to health food products, comprising:

(a) measuring the Raman spectrum of the sample to be monitored to obtain an initial Raman spectroscopic signal of the sample to be monitored;

(b) comparing the initial Raman spectroscopic signal of the sample to be monitored with the reference initial Raman spectroscopic signals of one or more compositions of Western medicines to determine whether the original Raman spectroscopic signal of the sample to be monitored is compatible with any of the reference initial Raman spectroscopic signals of the compositions of Western medicines ; and

(c) determining that the sample contains the compositions of Western medicines, if the original Raman spectroscopic signal of the sample to be controlled coincides with one or more of the reference source Raman spectroscopic signals of the compositions of Western medicines; otherwise, testing the amplified Raman spectrum of the sample to be monitored if the initial Raman spectroscopic signal of the sample to be monitored does not coincide with any of the reference initial Raman spectroscopic signals of all compositions of Western medicines,

moreover, testing the enhanced Raman spectrum of the sample to be controlled, contains:

(c1) measuring a mixture of the sample to be controlled and an amplifying agent to obtain an amplified Raman spectroscopic signal of the sample to be controlled; and

(c2) comparing the amplified Raman spectroscopic signal of the sample to be monitored with the reference amplified Raman spectroscopic signals of one or more compositions of Western medicines to determine whether the sample to be controlled contains the compositions of Western medicines.

According to an embodiment, in step (a), the initial Raman spectroscopic signal of the sample to be monitored is obtained by simultaneously measuring the Raman spectrum of the sample to be monitored.

According to an embodiment, step (a) comprises:

(a1) sequentially measuring the Raman spectrum of a sample to be monitored to collect a plurality of Raman spectroscopic signals;

(a2) superimposing a plurality of Raman spectroscopic signals to form a superposition signal; and

(a3) filtering the interfering fluorescence signal from the superposition signal to obtain the original Raman spectroscopic signals of the sample to be monitored.

According to an embodiment, step (a3) comprises:

(a31) obtaining a plurality of numerical sample points of the superposition signal, wherein the number of numerical sample points satisfies the requirement of the sampling theorem;

(a32) calculating an interfering fluorescence signal by the iteration method based on a plurality of numerical sample points of the superposition signal; and

(a33) subtracting the interfering fluorescence signal from the superposition signal.

According to an embodiment, in step (a32), the interfering fluorescence signal is calculated by the iteration method as follows:

based on the fact that {y _n } is the sequence of numerical sample points of the superposition signal, y _n (i) is the value of the i-th numerical sample point in {y _n }, and {y _{n + 1} } is the sequence calculated after one iteration {y _n }, and y _{n + 1} (i) is the value of the i-th numerical sample point in {y _{n + 1} },

where m is a positive integer with an initial value of 1, the aforementioned iteration being repeated until m reaches a predetermined threshold, where m increases by 1 in each iteration.

According to an embodiment, step (a), before step (a1), further comprises:

(a00) measuring the Raman spectrum of a sample to be monitored in advance to collect a single Raman spectroscopic signal; and

(a01) recording the characteristic intensity of the Raman spectrum in the collected single Raman spectroscopic signal, and if the characteristic intensity of the Raman spectrum is sufficient to recognize the Raman characteristic, use a single Raman spectroscopic signal as the initial Raman spectroscopic signal of the sample to be monitored, and go directly to step (b ); if the characteristic intensity of the Raman spectrum is not sufficient to recognize the Raman characteristic, the continuation of steps (a1) - (a3).

According to an embodiment, in step (a01), the characteristic intensity of the Raman spectrum is recorded by searching for the characteristic peak of the Raman spectrum in a single Raman spectroscopic signal; and if the characteristic peak of the Raman spectrum is found, a determination is made that the characteristic intensity of the Raman spectrum is sufficient to recognize the Raman characteristic; if the characteristic peak of the Raman spectrum is not found, a determination is made that the characteristic intensity of the Raman spectrum is not sufficient to recognize the Raman characteristic.

According to an embodiment, in step (a01), the characteristic intensity of the Raman spectrum is recorded by searching for the characteristic peak of the Raman spectrum in a single Raman spectroscopic signal; and if the characteristic peak of the Raman spectrum is found, and the ratio of the intensity of the characteristic peak of the Raman spectrum to the average intensity of a single Raman spectroscopic signal exceeds a predetermined first threshold, a determination is made that the characteristic intensity of the Raman spectrum is sufficient to recognize the Raman characteristic; if the characteristic peak of the Raman spectrum is not found, or the ratio of the intensity of the characteristic peak of the Raman spectrum to the average intensity of a single Raman spectroscopic signal does not exceed a predetermined first threshold, although it is found, a determination is made that the characteristic intensity of the Raman spectrum is not sufficient to recognize the Raman characteristic.

According to an embodiment, the method between step (a2) and step (a3) further comprises:

(ax) recording the characteristic intensity of the Raman spectrum in the superposition signal, and if the characteristic intensity of the Raman spectrum is sufficient to recognize the Raman characteristic, use the superposition signal as the initial Raman spectroscopic signal of the sample to be monitored, and go directly to step (b); if the characteristic intensity of the Raman spectrum is not enough to recognize the Raman characteristic, go to step (a3).

According to an embodiment, in step (ax), the characteristic intensity of the Raman spectrum is recorded by searching for the characteristic peak of the Raman spectrum in the superposition signal; and if the characteristic peak of the Raman spectrum is found, a determination is made that the characteristic intensity of the Raman spectrum is sufficient to recognize the Raman characteristic; if the characteristic peak of the Raman spectrum is not found, a determination is made that the characteristic intensity of the Raman spectrum is not sufficient to recognize the Raman characteristic.

According to an embodiment, in step (ax), the characteristic intensity of the Raman spectrum is recorded by searching for the characteristic peak of the Raman spectrum in the superposition signal; and if the characteristic peak of the Raman spectrum is found, and the ratio of the intensity of the characteristic peak of the Raman spectrum to the average intensity of the superposition signal exceeds a predetermined second threshold, a determination is made that the characteristic intensity of the Raman spectrum is sufficient to recognize the Raman characteristic; if the characteristic peak of the Raman spectrum is not found, or the ratio of the intensity of the characteristic peak of the Raman spectrum to the average intensity of the superposition signal does not exceed a predetermined second threshold, although it is found, a determination is made that the characteristic intensity of the Raman spectrum is not sufficient to recognize the Raman characteristic.

According to an embodiment, in step (b), the step of comparing the initial Raman spectroscopic signal of the sample to be monitored with the reference initial Raman spectroscopic signals of one or more compositions of Western medicines is performed by calculating the similarities between the original Raman spectroscopic signal of the sample to be monitored and the reference initial Raman spectroscopic signal of each composition of Western medicines.

According to an embodiment, in step (c), the step of comparing the amplified Raman spectroscopic signal of the sample to be monitored with the reference amplified Raman spectroscopic signals of one or more compositions of Western medicines is performed by calculating the similarities between the amplified Raman spectroscopic signal of the sample to be monitored and the reference amplified Raman spectroscopic signal of each composition of Western medicines.

According to an embodiment, the method based on Raman spectroscopy further comprises: creating a database of reference source Raman spectroscopic signals of one or more compositions of western medicines before performing step (b); and the creation of a database of reference amplified Raman spectroscopic signals of one or more compositions of Western medicines before the implementation of step (c).

According to an embodiment, a mixture of the sample to be controlled and a reinforcing agent is formed by directly mixing the sample to be controlled with a reinforcing agent or by mixing a solution of the sample to be controlled in water or an organic solvent with a reinforcing agent.

In at least one aspect of the above schemes of embodiments of the present invention, the sample to be monitored can be controlled by combining the original Raman spectra and amplified Raman spectra to determine if it contains Western medicine formulations. Such schemes make it possible to maintain an optimal balance between the accuracy of control and the effectiveness of control to ensure quick and effective control and verification of whether food products, in violation of the law, contain Western medicines.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a flowchart of a method based on Raman spectroscopy for monitoring Western medicines in accordance with an embodiment of the present invention;

FIG. 2 is a flowchart illustrating a process for generating initial Raman spectroscopic signals of a sample to be monitored in accordance with an embodiment of the present invention;

FIG. 3 is a flowchart illustrating a process for filtering out an interfering fluorescence signal from a superposition signal in accordance with an embodiment of the present invention;

FIG. 4 is a graph of a reference initial Raman spectroscopic signal for a standard Sildenafil sample;

FIG. 5 is a graph of a single Raman spectroscopic signal of a Sildenafil sample as an example;

FIG. 6 - FIG. 8 is a graph of a single Raman spectroscopic signal of a sample of a specific health food product, by way of example, and its superposition signals before filtering the interfering fluorescence signal and after filtering out the interfering fluorescence signal; and

FIG. 9 is a graph of an amplified Raman spectroscopic signal of a sample of a specific health food product as an example.

DETAILED DESCRIPTION OF EMBODIMENTS

Specific embodiments of the present invention will be described in detail below with reference to the accompanying drawings. In the description, identical or similar reference numerals represent identical or similar components. It should be noted that the embodiments described here serve only to illustrate the general principle of the present invention, but not the limitations of the present invention.

The Raman spectrum is a vibrational spectrum of molecules that allows you to identify molecules and can be used to control substances, even to control substances in trace amounts. The Raman spectrum can be used to quickly and effectively control whether food products, in violation of the law, contain Western medicines.

In FIG. 1 is a flowchart of a method based on Raman spectroscopy for monitoring Western medicines added to health food products in accordance with an embodiment of the present invention. The method may include the following steps:

step 100: measuring the Raman spectrum of the sample to be monitored to obtain an initial Raman spectroscopic signal of the sample to be monitored;

step 200: comparing the initial Raman spectroscopic signal of the sample to be monitored with the reference initial Raman spectroscopic signals of one or more compositions of Western medicines to determine whether the original Raman spectroscopic signal of the sample to be monitored matches any of the reference initial Raman spectroscopic signals of the compositions of Western medicines ; and

step 300: determining that the sample contains compositions of Western medicines, if the original Raman spectroscopic signal of the sample to be controlled coincides with one or more of the reference source Raman spectroscopic signals of the compositions of Western medicines; otherwise, testing the amplified Raman spectrum of the sample to be monitored if the initial Raman spectroscopic signal of the sample to be monitored does not coincide with any of the reference initial Raman spectroscopic signals of all compositions of Western medicines.

The testing step of the amplified Raman spectrum of the sample to be controlled may further comprise:

step 301: measuring the mixture of the sample to be controlled and an amplifying agent to obtain an amplified Raman spectroscopic signal of the sample to be controlled; and

step 302: comparing the amplified Raman spectroscopic signal of the sample to be monitored with the reference amplified Raman spectroscopic signals of one or more compositions of Western medicines to determine whether the sample to be controlled contains the compositions of Western medicines.

In the above embodiments, the original Raman spectrum and the amplified Raman spectrum are used together. The original Raman spectrum means a Raman spectroscopic signal obtained by measuring the Raman spectrum of a sample to be monitored directly. The amplified Raman spectrum means a Raman spectroscopic signal obtained by measuring the Raman spectrum of a mixture of a sample to be controlled and an amplifying agent. The terms “reference source Raman spectroscopic signal” and “reference amplified Raman spectroscopic signal”, respectively, represent the original Raman spectroscopic signal and the amplified Raman spectroscopic signal obtained by measuring a standard or reference sample of any of the compositions of Western medicines.

The above methods allow you to effectively and accurately control whether Western medicines are added to the sample to be controlled. On the one hand, since a small amount of Western medicines cannot actually increase the effectiveness or speed up the drug effect, the content of Western medicines illegally added to a food product (for example, health food products) usually exceeds 1%. Thus, results can often be obtained by comparing the initial Raman spectrum obtained by direct measurement of the sample to be controlled with the reference Raman spectrum. This allows you to quickly control the illegally added compositions of Western medicines, which, in particular, is suitable for quick control and verification in practical use. On the other hand, in a number of cases, it can be very difficult to obtain accurate control results only by means of the initial Raman spectrum, therefore, according to the above described embodiment, a sample in which a search for the compositions of Western medicines by comparing the initial Raman spectrum with the reference Raman spectrum did not yield results, is additionally controlled based on the amplified Raman spectrum. This ensures the accuracy of the test results. Compared to the method involving the use of only the amplified Raman spectrum, the method according to the embodiments of the present invention allows to increase the control speed and reduce costs.

As an example, in the above step 100, the initial Raman spectroscopic signal of the sample to be monitored can be obtained by measuring the Raman spectrum of the sample to be monitored at one time. This provides the most convenient and fastest method, which is especially useful for increasing the effectiveness of control.

However, on the other hand, when a sample is controlled based on its Raman spectrum, fluorescence can interfere with control. Fluorescence can be created by a sample to be controlled, or can be created by other objects, for example, a container. The fluorescence spectrum can cover the range of the Raman spectrum in the frequency band and its intensity often significantly exceeds the intensity of the Raman spectrum. Thus, when a sample is controlled based on its Raman spectrum, if the Raman spectroscopic signal collected from the sample contains a relatively strong fluorescence signal, it may not be possible to correctly extract the characteristic peaks from the Raman spectroscopic signal to recognize an object to be monitored, for example, Western medicines, added to wellness foods. In the case when Western medicines are added to a food product (for example, health food products), since the composition of the food product itself can be very complex, for example, it may contain certain additives in addition to the main composition, fluorescent interference often occurs for some samples. In order to better meet the control requirements of multiple foods (e.g., health foods), it is preferable to eliminate such an obstacle.

In FIG. 2 is a flowchart illustrating a process for generating initial Raman spectroscopic signals of a sample to be monitored in accordance with an embodiment of the present invention. By way of example, the aforementioned step 100 may include:

step 110: sequentially measuring the Raman spectrum of the sample to be monitored to collect a plurality of Raman spectroscopic signals;

step 120: superimposing a plurality of Raman spectroscopic signals to generate a superposition signal; and

step 130: filtering the interfering fluorescence signal from the superposition signal to obtain the original Raman spectroscopic signals of the sample to be monitored.

In the prior art, the signal intensity of the Raman spectrum, in the General case, can be increased by increasing the exposure time. However, in the practically used instrument of Raman spectroscopy, the intensity of the simultaneously collected Raman spectroscopic signal is limited in order to avoid an adverse effect on the life of the device due to too much light power. According to an embodiment of the present application, the Raman spectrum of the sample to be monitored is measured sequentially, and a plurality of collected Raman spectroscopic signals can be superimposed on each other to increase the signal intensity, which avoids the aforementioned adverse effect. The term “plurality” may represent, for example, two, three, four, five, ten, fifteen, fifty, etc.

By superimposing a plurality of Raman spectroscopic signals, the signal intensity can be increased to simplify the elimination of the interfering fluorescence signal. By way of example, as shown in FIG. 3, the step of filtering the interfering fluorescence signal from the superposition signal may comprise the following steps: a step 131 of obtaining a plurality of numerical sample points of the superposition signal, the number of numerical sample points meeting the requirement of the sampling theorem; step 132 of calculating the interfering fluorescence signal by the iteration method based on a plurality of numerical sample points of the superposition signal; and step 133 of subtracting the interfering fluorescence signal from the superposition signal.

To calculate the interfering fluorescence signal, the superposition signal must be expressed in discrete numerical form. If the superposition signal is a continuous model curve, it needs to be converted into a discrete numerical formula through a sampling process. However, in practice, a superposition signal is often expressed in discrete numerical form. In this case, you only need to directly obtain the numerical sample points. To guarantee the accuracy of discrete signals, the number of sample points should satisfy the requirement of the sampling theorem.

The fluorescence signal changes slowly and smoothly compared to the Raman characteristic signal. By way of example, the interfering fluorescence signal can be calculated by iteration as follows:

based on the fact that {y _n } is the sequence of numerical sample points of the superposition signal, y _n (i) is the value of the i-th numerical sample point in {y _n }, and {y _{n + 1} } is the sequence calculated after one iteration {y _n }, and y _{n + 1} (i) is the value of the i-th numerical sample point in {y _{n + 1} },

уравнение (1)

equation (1)

where m is a positive integer with an initial value of 1, the aforementioned iteration being repeated until m satisfies a predetermined threshold condition, where m is incremented by 1 in each iteration. The interference signal of fluorescence can be obtained through the above iterative calculation.

In the above equation (1), "min [..., ...]" denotes a minimum selection operation. Obviously, the sequence number of the numerical point in each iterative calculation must satisfy the condition that im> 0 and i + m do not exceed the full length of the sequence {y _n }. If a numerical point does not satisfy the condition, its value may remain equal to the initial value in the iterative calculation.

By way of example, a predetermined threshold m is determined depending on the smoothness of the superposition signal. For example, when two points spaced 2 × m in the iterative result sequence have a wave number width that is greater than the minimum peak width but less than the fluorescence envelope width, it can be determined that m satisfies a predetermined threshold condition.

By way of example, in order to further increase the accuracy of the calculation, the superposition signal can be subjected to a logarithmic transformation or quadratic transformation before performing the above iterative calculation.

Although in the above example, the calculation of the interfering fluorescence signal is explained with reference to the iterative method presented in equation (1) and equation (2), it should be understood that this is not necessary. Methods for solving a smooth spectrum signal in the prior art can also be used to solve the aforementioned interfering fluorescence signal, but the method can be more complicated and lead to a decrease in computational efficiency.

According to the method described above, the interfering fluorescence signal can be filtered from the original Raman spectroscopic signal to increase the accuracy of the control. This is especially useful for a sample with strong fluorescence noise and a weak Raman spectroscopic signal. In FIG. 6-8 show an example of eliminating an interfering fluorescence signal using the above method. In FIG. Figure 6 shows a single Raman spectroscopic signal obtained by directly measuring the Raman spectrum of a sample of a specific health food product. From FIG. 6, it is very difficult to find information about a signal having significant characteristics. In FIG. 7 shows a signal obtained by superimposing a plurality of Raman spectroscopic signals obtained by successive measurements. Compared to FIG. 6, in FIG. 7 shows some characteristics of the signal. In FIG. Figure 8 shows the original Raman spectroscopic signal obtained by eliminating the interfering fluorescence signal from the superposition signal. From FIG. 8 that the signal has a pure characteristic intensity. Thus, the above-described method for eliminating fluorescence interference can effectively increase the characteristic intensity of the signal to provide a good basis for its comparison with the reference Raman spectroscopic signals.

To ensure the aforementioned process of filtering out the interfering fluorescence signal from the superposition signal, a fluorescence interference eliminating device can be used. A device may include: a module for obtaining a plurality of numerical sample points of a superposition signal, a module for calculating an interfering fluorescence signal by an iteration method based on a plurality of numerical sample points of a superposition signal, and a module for subtracting an interfering fluorescence signal from a superposition signal. A device for eliminating fluorescence interference can be implemented, for example, in the form of electronic equipment, firmware or software.

By way of example, the aforementioned step 100 may further comprise optional steps indicated by the dashed portion in FIG. 2. For example, step 100 may, before step 110, further comprise:

step 101: measuring the Raman spectrum of the sample to be monitored in advance to collect a single Raman spectroscopic signal; and

step 102: recording the characteristic intensity of the Raman spectrum in the collected single Raman spectroscopic signal. If the characteristic intensity of the Raman spectrum determined in step 102 is sufficient to recognize the Raman characteristic, a single Raman spectroscopic signal is directly used as the initial Raman spectroscopic signal of the sample, and step 200, i.e. a single Raman spectroscopic signal is compared directly with the reference source Raman spectroscopic signals of one or more compositions of Western medicines; if the characteristic intensity of the Raman spectrum is not sufficient to recognize the Raman characteristic, steps 110-130 continue to be performed. This can increase the monitoring efficiency by eliminating the subsequent steps of performing sequential measurements and filtering out the fluorescence noise when the interfering fluorescence signal is weak for the sample to be monitored and will not affect Raman spectroscopy.

In the above embodiments of the present invention, three registration methods are actually synthesized, i.e. a method for recording a single source Raman spectroscopic signal, a method for recording superimposed source Raman spectroscopic signals, and a method for recording an amplified Raman spectroscopic signal. Three registration methods are used sequentially to provide the best balance between registration efficiency and accuracy.

By way of example, in the above step 102, the characteristic intensity of the Raman spectrum can be recorded by searching for the characteristic peak of the Raman spectrum in a single Raman spectroscopic signal; and if the characteristic peak of the Raman spectrum is found, it will be determined that the characteristic intensity of the Raman spectrum is sufficient to recognize the Raman characteristic; if the characteristic peak of the Raman spectrum is not found, it will be determined that the characteristic intensity of the Raman spectrum is insufficient to recognize the Raman characteristic.

In another example, alternatively, at the above step 102, the characteristic intensity of the Raman spectrum is recorded by searching for the characteristic peak of the Raman spectrum in a single Raman spectroscopic signal; and if the characteristic peak of the Raman spectrum is found, and the ratio of the intensity of the characteristic peak of the Raman spectrum to the average intensity of a single Raman spectroscopic signal exceeds a predetermined first threshold, it will be determined that the characteristic intensity of the Raman spectrum is sufficient to recognize the Raman characteristic; if the characteristic peak of the Raman spectrum is not found, or the ratio of the intensity of the characteristic peak of the Raman spectrum to the average intensity of a single Raman spectroscopic signal does not exceed a predetermined first threshold, although it is found, it will be determined that the characteristic intensity of the Raman spectrum is not sufficient to recognize the Raman characteristic.

The aforementioned average intensity of a single Raman spectroscopic signal characterizes a combination of the characteristic intensity of the Raman spectrum and the intensity of the interfering fluorescence signal. Thus, the ratio of the intensity of the characteristic peak of the Raman spectrum to the average intensity of the Raman spectroscopic signal reflects the contrast ratio between the intensity of the characteristic peak of the Raman spectrum and the intensity of the interfering fluorescence signal. The first threshold can be determined depending on the accuracy of the device, calculation errors, etc., for example, it can be defined as 0.5, 1, 3, etc.

By way of example, as shown in FIG. 2, between step 120 and step 130, the method may further comprise: step 12x of recording the Raman spectrum characteristic intensity in the superposition signal, and if the Raman spectrum characteristic intensity is sufficient to recognize the Raman characteristic, the superposition signal is used as the initial Raman spectroscopic signal of the sample to be monitored , and transfer directly to step 200; if the characteristic intensity of the Raman spectrum is not enough to recognize the Raman characteristic, go to step 130. In the case where the characteristic intensity of the Raman spectrum and the intensity of the interfering fluorescence signal are low, the Raman characteristic, for example, the characteristic peak of the Raman spectrum, can be correctly found in the Raman spectroscopic signal after increasing the total intensity of the Raman spectroscopic signal by successive measurements Nij and superimposing signals. Thus, in the aforementioned step 12x, unnecessary calculation of the interfering fluorescence signal can be avoided to increase computational efficiency.

As an example, in step 12x, the characteristic intensity of the Raman spectrum is recorded by searching for the characteristic peak of the Raman spectrum in the superposition signal; and if the characteristic peak of the Raman spectrum is found, it will be determined that the characteristic intensity of the Raman spectrum is sufficient to recognize the Raman characteristic; if the characteristic peak of the Raman spectrum is not found, it will be determined that the characteristic intensity of the Raman spectrum is insufficient to recognize the Raman characteristic.

In another example, in step 12x, the characteristic intensity of the Raman spectrum is recorded by searching for the characteristic peak of the Raman spectrum in the superposition signal; and if the characteristic peak of the Raman spectrum is found, and the ratio of the intensity of the characteristic peak of the Raman spectrum to the average intensity of the superposition signal exceeds a predetermined second threshold, it will be determined that the characteristic intensity of the Raman spectrum is sufficient to recognize the Raman characteristic; if the characteristic peak of the Raman spectrum is not found, or the ratio of the intensity of the characteristic peak of the Raman spectrum to the average intensity of the superposition signal does not exceed a predetermined second threshold, although it is found, it will be determined that the characteristic intensity of the Raman spectrum is not sufficient to recognize the Raman characteristic.

Similar to the aforementioned step 102, the aforementioned average intensity of the Raman spectroscopic signal characterizes a combination of the characteristic intensity of the Raman spectrum and the intensity of the interfering fluorescence signal. Thus, the ratio of the intensity of the characteristic peak of the Raman spectrum to the average intensity of the Raman spectroscopic signal reflects the contrast ratio between the intensity of the characteristic peak of the Raman spectrum and the intensity of the interfering fluorescence signal. The second threshold can be determined depending on the accuracy of the instrument, calculation errors, etc., for example, it can be defined as 0.5, 1, 3, etc. The aforementioned second threshold may be equal to the first threshold or may differ from the first threshold.

In the above embodiments, the average intensity can be determined, for example, as the arithmetic mean or geometric mean of the signal intensity.

As an example, at step 200, the step of comparing the original Raman spectroscopic signal of the sample to be controlled with the reference source Raman spectroscopic signals of one or more compositions of Western medicines is carried out by calculating the similarities between the original Raman spectroscopic signal of the sample to be controlled and the reference source Raman spectroscopic a signal of each composition of western medicines. If the similarity exceeds the third threshold, it will be determined that the initial Raman spectroscopic signal of the sample to be controlled coincides with the reference initial Raman spectroscopic signal of the composition of Western medicines; if the similarity does not exceed the third threshold, it will be determined that the initial Raman spectroscopic signal of the sample to be monitored does not coincide with the reference initial Raman spectroscopic signal of the composition of Western medicines.

The similarity can be calculated in several ways, for example, according to the correlation algorithm, the maximum likelihood algorithm, the absolute value algorithm. For example, we denote the initial Raman spectroscopic signal of a certain composition of Western medicines added to health food products as A (x), and the initial Raman spectroscopic signal of the sample to be monitored as B (x). By way of example, according to the maximum likelihood algorithm, the similarity between the original Raman spectroscopic signal of a certain composition and the original Raman spectroscopic signal of the sample to be controlled can be calculated according to equation (2):

уравнение (2)

equation (2)

where Corr denotes the similarity between the original Raman spectroscopic signal of a certain composition and the original Raman spectroscopic signal of the sample to be monitored, and ʺ • ʺ denotes the scalar product operation.

In another example, according to the correlation algorithm, A (x) and B (x) can be sampled, respectively, to obtain n sample points, respectively, i.e. A ₁ , A ₂ , ..., A _n and B ₁ , B ₂ , ..., B _n . Thus, the Corr similarity between the original Raman spectroscopic signal of a certain composition and the original Raman spectroscopic signal of the sample to be monitored can be calculated according to equation (3):

equation (3)

where ʺ • ʺ denotes the scalar product operation.

In another example, according to the absolute value algorithm, A (x) and B (x) can also be discretized, respectively, to obtain n sample points, respectively, i.e. A ₁ , A ₂ , ..., A _n and B ₁ , B ₂ , ..., B _n . Thus, the Corr similarity between the original Raman spectroscopic signal of a certain composition and the original Raman spectroscopic signal of the sample to be monitored can be calculated according to equation (4):

уравнение (4)

equation (4)

The above similarity calculation can be performed for the entire Raman spectroscopic signal, or can be performed locally for the part of the Raman spectroscopic signal where the characteristic portion is contained.

In the present application, the term “characteristic region” means a critical region of a Raman spectroscopic signal of a certain composition of Western medicines or a sample to be controlled, allowing one to distinguish its Raman spectroscopic signal from Raman spectroscopic signals of the compositions of other substances. For example, a characteristic portion may be one or more of characteristic (s) peak (s), characteristic (s) troughs (s), inflection points, etc.

In the case where the initial Raman spectroscopic signal of a certain composition of Western medicines includes the characteristic peak (s), the above similarity can be calculated by weight based on the position (s) of the peak (s), the width of the peak (s) and / or height () peak (s) for characteristic peak (s). By way of example, before calculating the similarity, the characteristic peak (s) can be searched and ordered. In the case where the characteristic peaks of the initial Raman spectroscopic signal or the amplified Raman spectroscopic signal of a certain composition of Western medicines are comparatively noticeable, the calculation of similarities in practice can even be simplified to determine the similarities directly by searching whether the original Raman spectroscopic signal or the amplified Raman spectroscopic signal of the sample to be controlled, characteristic (e) peak (s) corresponding to (e) characteristic the peak (s) of the initial Raman spectroscopic signal or the amplified Raman spectroscopic signal of a certain composition of Western medicines in one or more positions.

By way of example, in step 300, the step of comparing the amplified Raman spectroscopic signal of the sample to be monitored with the reference amplified Raman spectroscopic signals of one or more Western medicine formulations (which can be added to health food products) is performed by calculating the similarities between the amplified Raman spectroscopic the signal of the sample to be monitored, and the reference amplified Raman spectroscopic signal of each composition of the western physician cops. If the similarity exceeds the fourth threshold, it will be determined that the sample to be controlled contains the composition of Western medicines; if the similarity does not exceed the fourth threshold, it will be determined that the sample to be controlled does not contain the composition of Western medicines.

The third threshold may be equal to the fourth threshold or may differ from the fourth threshold. The third threshold and the additional threshold can be set depending on factors such as practical requirements for monitoring and the accuracy of monitoring devices.

The similarity between the amplified Raman spectroscopic signal of a certain composition of Western medicines and the amplified Raman spectroscopic signal of a sample to be controlled can be calculated similarly to the above calculation of the similarity between the initial Raman spectroscopic signal of a certain composition of Western medicines and a sample to be controlled, therefore, a detailed description will be omitted here. It should be noted that only some examples of calculating similarities were given above, and other methods for calculating similarities known to those skilled in the art are acceptable.

As an example, a method based on Raman spectroscopy for monitoring Western medicines added to health food products, according to an embodiment of the present invention, may further include: creating a database of reference raw Raman spectroscopic signals of one or more compositions of Western medicines before step 200 Similarly, a method based on Raman spectroscopy for monitoring Western medicines added to health food products, with according to an embodiment of the present invention, may also include: creating a database of reference amplified Raman spectroscopic signals of one or more compositions of western medicines before step 300.

In FIG. Figure 4 shows the reference initial Raman spectroscopic signal of a standard sample of the composition of Western medicines (Sildenafil). In FIG. 5 shows the initial Raman spectroscopic signal of a sample of a specific health food product. In FIG. 5, the characteristic peaks in the initial Raman spectroscopic signal are indicated by arrows. By the process described in the above embodiments, it can be determined that the reference source Raman spectroscopic signal shown in FIG. 4 coincides with the Raman spectroscopic signal shown in FIG. 5. Thus, a sample of a healthy food product contains an illegal composition of Western medicines (Sildenafil).

By way of example, a mixture of a sample to be controlled and a reinforcing agent is formed by directly mixing the sample to be controlled with a reinforcing agent or by mixing a solution of the sample to be controlled in water or an organic solvent with a reinforcing agent. In FIG. 9 shows a representative amplified Raman spectroscopic signal of a sample of a specific health food product. In FIG. 9, the characteristic peaks in the amplified Raman spectroscopic signal are indicated by arrows. It can also be compared with the reference amplified Raman spectroscopic signal of a standard sample of a certain composition of Western medicines to determine whether the sample to be controlled contains the composition of Western medicines. Details of the process will be omitted here.

According to embodiments of the present invention, by way of example, the enhancing agent may comprise any material selected from metal nanoparticles, metal nanowires, metal nanoclusters, carbon nanotubes or carbon nanoparticles having a size in the range of 1-1000 nm, or any combination thereof. In another example, the reinforcing agent may include metallic nanomaterials. The enhancing agent may additionally contain, in addition to the metal nanomaterial, chlorine ions, bromine ions, sodium ions, potassium ions and / or sulfate radical ions. For example, the metal may include any of gold, silver, copper, magnesium, aluminum, iron, cobalt, nickel, palladium or platinum, or any combination thereof. In a mixture of the sample to be controlled and the reinforcing agent, the molecules of the compositions of the western medicines can attach to the surface of the material of the reinforcing agent, and the electromagnetic field of the surface of the material of the reinforcing agent can increase the Raman spectroscopic signals of the compositions of western medicines.

By way of example, Raman spectrum data can be obtained by directing the light emitted by a laser to a sample to be monitored, and emitting light emitted from Raman scattering by a sample to be monitored by a laser, and performing spectral analysis to obtain a Raman spectroscopic signal.

According to embodiments of the present invention, the sample to be controlled may be a sample of a health food product.

Although the present invention is explained with reference to the drawings, the embodiments shown in the drawings are illustrative only, but are not intended to limit the present invention.

Although some embodiments of the general principle of the invention are illustrated and explained, those skilled in the art can propose modifications and variations of these embodiments without going beyond the principles and essence of the general principle of the invention. The scope of the present invention is defined in the following claims and their equivalents.

Claims (33)

1. A method based on Raman spectroscopy for the control of medicines added to health food products, comprising stages in which: (a) measuring the Raman spectrum of the sample to be monitored to obtain an initial Raman spectroscopic signal of the sample to be monitored; (b) comparing the initial Raman spectroscopic signal of the sample to be monitored with the reference initial Raman spectroscopic signals of one or more drug compositions to determine whether the original Raman spectroscopic signal of the sample to be controlled is compatible with any of the reference initial Raman spectroscopic signals of the medication; and (c) it is determined that the sample contains drug compositions if the initial Raman spectroscopic signal of the sample to be controlled coincides with one or more of the reference source Raman spectroscopic signals of the drug composition; otherwise, the amplified Raman spectrum of the sample to be tested is tested if the initial Raman spectroscopic signal of the sample to be controlled does not match any of the reference source Raman spectroscopic signals of all drug compositions, moreover, testing the enhanced Raman spectrum of the sample to be controlled contains sub-steps in which: (c1) measuring a mixture of the sample to be controlled and an amplifying agent to obtain an amplified Raman spectroscopic signal of the sample to be controlled; and (c2) comparing the amplified Raman spectroscopic signal of the sample to be monitored with the reference amplified Raman spectroscopic signals of one or more drug compositions to determine whether the sample to be controlled contains drug compositions. 2. A method based on Raman spectroscopy according to claim 1, wherein in step (a) the initial Raman spectroscopic signal of the sample to be monitored is obtained by measuring the Raman spectrum of the sample to be monitored simultaneously. 3. The method based on Raman spectroscopy according to claim 1, in which step (a) comprises sub-steps in which: (a1) sequentially measuring the Raman spectrum of a sample to be monitored to collect a plurality of Raman spectroscopic signals; (a2) superimpose a plurality of Raman spectroscopic signals to form a superposition signal; and (a3) filtering the interfering fluorescence signal from the superposition signal to obtain the original Raman spectroscopic signals of the sample to be monitored. 4. A method based on Raman spectroscopy according to claim 3, in which step (a3) comprises sub-steps in which: (a31) a plurality of numerical sample points of the superposition signal are obtained, the number of numerical sample points satisfying the requirement of the sampling theorem; (a32) calculating the interfering fluorescence signal by the iteration method based on a plurality of numerical sample points of the superposition signal; and (a33) subtracting the interfering fluorescence signal from the superposition signal. 5. The method based on Raman spectroscopy according to claim 4, wherein in step (a32) the interfering fluorescence signal is calculated by iteration as follows: based on the fact that {y _n } is the sequence of numerical sample points of the superposition signal, y _n (i) is the value of the i-th numerical sample point in {y _n }, and {y _{n + 1} } is the sequence calculated after one iteration {y _n }, and y _{n + 1} (i) is the value of the i-th numerical sample point in {y _{n + 1} },

, where m is a positive integer with an initial value of 1, the aforementioned iteration being repeated until m reaches a predetermined threshold, where m increases by 1 in each iteration. 6. The method based on Raman spectroscopy according to claim 3, in which step (a), before step (a1), further comprises sub-steps, in which: (a00) pre-measuring the Raman spectrum of the sample to be monitored to collect a single Raman spectroscopic signal; and (a01) register the characteristic intensity of the Raman spectrum in the collected single Raman spectroscopic signal, and if the characteristic intensity of the Raman spectrum is sufficient to recognize the Raman characteristic, use the single Raman spectroscopic signal as the initial Raman spectroscopic signal of the sample to be monitored, and proceed immediately to step (b ); if the characteristic intensity of the Raman spectrum is not enough to recognize the Raman characteristic, then steps (a1) - (a3) are continued. 7. The method based on Raman spectroscopy according to claim 6, in which at step (a01) the characteristic intensity of the Raman spectrum is recorded by searching for the characteristic peak of the Raman spectrum in a single Raman spectroscopic signal; and if the characteristic peak of the Raman spectrum is found, it is determined that the characteristic intensity of the Raman spectrum is sufficient to recognize the Raman characteristic; if the characteristic peak of the Raman spectrum is not found, it is determined that the characteristic intensity of the Raman spectrum is not sufficient to recognize the Raman characteristic. 8. The method based on Raman spectroscopy according to claim 6, in which at step (a01) the characteristic intensity of the Raman spectrum is recorded by searching for the characteristic peak of the Raman spectrum in a single Raman spectroscopic signal; and if the characteristic peak of the Raman spectrum is found, and the ratio of the intensity of the characteristic peak of the Raman spectrum to the average intensity of a single Raman spectroscopic signal exceeds a predetermined first threshold, it is determined that the characteristic intensity of the Raman spectrum is sufficient to recognize the Raman characteristic; if the characteristic peak of the Raman spectrum is not found, or the ratio of the intensity of the characteristic peak of the Raman spectrum to the average intensity of a single Raman spectroscopic signal does not exceed a predetermined first threshold, although it is found, it is determined that the characteristic intensity of the Raman spectrum is not sufficient to recognize the Raman characteristic. 9. A method based on Raman spectroscopy according to claim 3, wherein the method between step (a2) and step (a3) further comprises a sub-step in which: (ax) register the characteristic intensity of the Raman spectrum in the superposition signal, and if the characteristic intensity of the Raman spectrum is sufficient to recognize the Raman characteristic, use the superposition signal as the initial Raman spectroscopic signal of the sample to be monitored, and proceed immediately to step (b); if the characteristic intensity of the Raman spectrum is not enough to recognize the Raman characteristic, go to step (a3). 10. The method based on Raman spectroscopy according to claim 9, wherein in step (ax) the characteristic intensity of the Raman spectrum is recorded by searching for the characteristic peak of the Raman spectrum in the superposition signal; and if the characteristic peak of the Raman spectrum is found, it is determined that the characteristic intensity of the Raman spectrum is sufficient to recognize the Raman characteristic; if the characteristic peak of the Raman spectrum is not found, it is determined that the characteristic intensity of the Raman spectrum is not sufficient to recognize the Raman characteristic. 11. The method based on Raman spectroscopy according to claim 9, wherein in step (ax) the characteristic intensity of the Raman spectrum is recorded by searching for the characteristic peak of the Raman spectrum in the superposition signal; and if the characteristic peak of the Raman spectrum is found, and the ratio of the intensity of the characteristic peak of the Raman spectrum to the average intensity of the superposition signal exceeds a predetermined second threshold, it is determined that the characteristic intensity of the Raman spectrum is sufficient to recognize the Raman characteristic; if the characteristic peak of the Raman spectrum is not found, or the ratio of the intensity of the characteristic peak of the Raman spectrum to the average intensity of the superposition signal does not exceed a predetermined second threshold, although it is found, it is determined that the characteristic intensity of the Raman spectrum is not sufficient to recognize the Raman characteristic. 12. The method based on Raman spectroscopy according to claim 1, wherein, in step (b), the step of comparing the initial Raman spectroscopic signal of the sample to be monitored with the reference initial Raman spectroscopic signals of one or more drug compositions is carried out by calculating the similarities between the original Raman spectroscopy spectroscopic signal of the sample to be monitored, and the reference reference Raman spectroscopic signal of each composition of medicines. 13. The method based on Raman spectroscopy according to claim 1, wherein, in step (c), the step of comparing the amplified Raman spectroscopic signal of the sample to be monitored with the reference amplified Raman spectroscopic signals of one or more drug compositions is carried out by calculating the similarities between the amplified Raman spectroscopy spectroscopic signal of the sample to be monitored, and a reference amplified Raman spectroscopic signal of each composition of medicines. 14. A method based on Raman spectroscopy according to claim 1, further comprising the steps of: creating a database of reference initial Raman spectroscopic signals of one or more compositions of medicines before step (b); and create a database of reference amplified Raman spectroscopic signals of one or more compositions of medicines before the implementation of step (c). 15. A method based on Raman spectroscopy according to any one of paragraphs. 1-14, in which a mixture of the sample to be controlled and a reinforcing agent is formed by directly mixing the sample to be controlled with a reinforcing agent or by mixing a solution of the sample to be controlled in water or an organic solvent with a reinforcing agent.

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