Kit and system for detecting neurological function state of subject

Abstract

The invention relates to a kit and a system for detecting a neurological function state of a subject. The kit comprises a plurality of small chambers for containing different concentrations of an HCAR2 receptor activator or an HCAR3 receptor activator or an ester aqueous solution thereof. The kit provided by the invention can be used for effectively detecting the neurological function state of a subject by evaluating the sensitivity degree of the subject to the HDAR2 receptor activator or the HDAR3 receptor activator or the ester thereof. The system disclosed by the invention can be used for quickly obtaining a detection result through several simple steps of operation in a short time, realizes multi-scene real-time detection in a ward, a physical examination center, a home and the like, and is an objective, convenient and effective biological detection means for detecting four nerve function states of a subject.

Description

Technical Field

[0001] This invention relates to the field of medical testing technology. Specifically, this invention relates to kits and systems for detecting the neurological functional status of subjects. Background Technology

[0002] Vibration sensory threshold (VPT) is a neurological function state assessment method that tests a patient's sensory threshold for vibration by providing localized vibration, thus aiding in the diagnosis of whether the patient has a neurosensory system disorder.

[0003] Currently, VPT testing is mainly used for the measurement and evaluation of the function of the human peripheral nervous system, diabetic foot, deep sensory impairment caused by the brain's sensory center, deep sensory nerve fiber lesions, and nerve regeneration.

[0004] The general testing procedure for VPT is as follows: (1) The subject remains quiet (sitting or lying down) and waits for the test; (2) The tester operates the VPT testing instrument to apply vibration to the subject; (3) The subject carefully feels the vibration and accurately describes the vibration sensation to the tester; (4) The tester records the instrument display value when the subject can feel the vibration, which is the subject's VPT value. It is evident that VPT testing is easily affected by systematic errors, the instrument's repeatability is poor, and multiple measurements are often required to obtain a test report; its numerical recording relies on the subject's subjective account, lacks objectivity, and is also affected by the subject's cognitive ability.

[0005] Therefore, developing a more objective method for assessing neurological function is of great clinical significance. Summary of the Invention

[0006] One object of the present invention is to provide a method for detecting the neurological function status of a subject, which can be used to objectively, sensitively and conveniently provide early warning of sub-health risks.

[0007] Another object of the present invention is to provide a kit for detecting the neurological functional state of a subject, which can be used in the above-described detection method.

[0008] Another object of the present invention is to provide a system for detecting the neurological functional state of a subject, which can be used to implement the above-described detection method.

[0009] This invention is based on the inventors’ discovery that the degree of reaction between HCAR2 receptor activators and HCAR3 receptor activators and their esters and the subject’s skin is strongly positively correlated with VPT value, and can be used to detect the subject’s neurological function status and provide early warning of sub-health risks.

[0010] Therefore, according to a first aspect, the present invention provides the use of active substances selected from HCAR2 receptor activators, HCAR3 receptor activators, their esters and combinations thereof in the preparation of a kit for detecting the neurological functional status of a subject.

[0011] According to a second aspect, the present invention provides a system for detecting the neurological functional state of a subject, characterized in that it comprises:

[0012] A kit containing active substances selected from HCAR2 receptor activators, HCAR3 receptor activators, their esters, and combinations thereof;

[0013] Reactor;

[0014] Imaging equipment, used to acquire images; and

[0015] Image processing equipment is used to acquire information from images.

[0016] According to a third aspect, the present invention provides a method for detecting the neurological functional state of a subject, characterized in that it comprises the following steps:

[0017] I) Provides a correlation line between the degree of response to stimulation by active substances selected from HCAR2 receptor activators, HCAR3 receptor activators, their esters and combinations thereof and the VPT value;

[0018] II) Determine the degree of response of the subject to the active substance; and

[0019] III) Obtain the VPT value corresponding to the response level value obtained in step II) from the correlation line of step I), thereby obtaining information on the neural functional state.

[0020] The reagent kit of this invention can be used safely and non-invasively to reflect the neurological function status of subjects. The system and method of this invention can quickly obtain test results in a short time through a few simple steps, enabling real-time testing in multiple scenarios such as wards, health check centers, and homes. It is an objective, convenient, and effective biological testing method. This invention provides a safe and non-invasive method for reflecting neurological function status, which is simple to operate. Attached Figure Description

[0021] The present invention will now be described and explained in more detail with reference to the accompanying drawings, wherein:

[0022] Figure 1 A reactor with several orifices is schematically shown, where 1 is the reactor and 11 are the orifices.

[0023] Figure 2 The diagram schematically shows a reactor consisting of several patches, where 2 is the reactor and 21 is a patch.

[0024] Figure 3 The correlation line between the response degree value and the mean VPT value under nicotinic acid methyl ester solution stimulation in Example 1 is shown. Detailed Implementation

[0025] Some specific embodiments of the invention are now described for illustrative purposes and not for limitation.

[0026] Reagent test kit

[0027] According to a first aspect, the present invention provides the use of active substances selected from HCAR2 receptor activators, HCAR3 receptor activators, their esters and combinations thereof in the preparation of a kit for detecting the neurological functional status of a subject.

[0028] HCAR2 receptor refers to hydroxycarboxylic acid receptor 2, also known as GPR109A.

[0029] HCAR3 receptor refers to hydroxycarboxylic acid receptor 3, also known as GPR109B.

[0030] In this application, for the sake of simplicity, HCAR2 receptor activators or HCAR3 receptor activators or their esters are sometimes referred to as active compounds.

[0031] Preferably, the active substance is selected from nicotinic acid, methyl nicotinic acid, ethyl nicotinic acid, and combinations thereof.

[0032] Nicotinic acid, methyl nicotinic acid, and ethyl nicotinic acid have the following structures:

[0033]

[0034] Preferably, the active substance in the kit is in the form of an aqueous solution.

[0035] Preferably, the kit comprises an aqueous solution of an active substance with a concentration of 0.1 mM or higher. More preferably, the concentration of the active substance in the aqueous solution is 0.15 mM or higher, or 0.5 mM or higher, or 1 mM or higher, or 3 mM or higher, or 10 mM or higher, or 20 mM or higher.

[0036] Preferably, the concentration of the active substance in the aqueous solution does not exceed 1000 mM.

[0037] The kit includes several chambers to contain aqueous solutions of active substances at several concentrations.

[0038] In this application specification and claims, several may cover one or more.

[0039] In cases comprising more than one chamber, the concentrations of the aqueous solutions of the active substances contained therein may be the same or different.

[0040] In some embodiments, the kit contains at least two aqueous solutions of active substances at different concentrations, with a maximum concentration of at least 20 mM and a concentration decreasing sequentially by 2 to 10 times.

[0041] In some embodiments, the kit contains at least two aqueous solutions of active substances at different concentrations, with a maximum concentration below 100 mM and a concentration decreasing sequentially by 2 to 10 times.

[0042] In some embodiments, the kit contains at least six aqueous solutions of active substances at different concentrations, with a maximum concentration of 60 mM and decreasing by a factor of 3.

[0043] The detection includes:

[0044] I) Provides a correlation line between the response degree value and the VPT value under the stimulation of active substances;

[0045] II) Determine the degree of response of the subject to the active substance; and

[0046] III) Obtain the VPT value corresponding to the response level value obtained in step II) from the correlation line of step I), thereby obtaining information on the neural functional state.

[0047] The subjects were humans.

[0048] In this application, the degree of reaction value refers to the degree of reaction when the skin comes into contact with the active compound, and its determination is described in detail below.

[0049] Further details regarding the testing are described in detail below and may be incorporated herein by reference.

[0050] A system for detecting the neurological functional status of a subject.

[0051] According to a second aspect, the present invention provides a system for detecting the neurological functional state of a subject, characterized in that it comprises:

[0052] A kit containing active substances selected from HCAR2 receptor activators, HCAR3 receptor activators, their esters, and combinations thereof;

[0053] Reactor;

[0054] Imaging equipment, used to acquire images; and

[0055] Image processing equipment is used to acquire information from images.

[0056] Preferably, the active substance is selected from nicotinic acid, methyl nicotinic acid, ethyl nicotinic acid, and combinations thereof.

[0057] In some embodiments, the reactor may have several pores for placing the active material.

[0058] The hole can have any shape, preferably a circular hole, a square hole, a rectangular hole, or a combination thereof.

[0059] The holes may have the same or different areas.

[0060] Figure 1 A reactor with several orifices is schematically shown, where 1 is the reactor and 11 are the orifices.

[0061] When using a reactor with several pores, the reactor is brought into contact with the subject's skin (e.g., forearm skin), and then a certain amount of the active substance is applied into the pores.

[0062] In some embodiments, the reactor simply consists of a number of patches capable of containing the active material.

[0063] The patch can have any shape, preferably a circular hole, a square hole, a rectangular hole, or a combination thereof.

[0064] The patches may have the same or different areas.

[0065] Figure 2 The diagram schematically shows a reactor consisting of several patches, where 2 is the reactor and 21 is a patch.

[0066] In a reactor consisting of several patches, the patches are brought into contact with the subject's skin.

[0067] Preferably, the imaging device includes:

[0068] The box, which forms a sealed space, has an entrance for the subject's forearm to enter; and

[0069] An image acquisition component is used to image and acquire the skin of the subject's forearm that is inserted into the box.

[0070] Preferably, the image acquisition component can also receive timed imaging signals. The timed imaging signals are used to trigger the image acquisition component to image the subject's forearm skin at multiple predetermined time points.

[0071] Preferably, the image processing device includes:

[0072] Image information acquisition component, used to acquire information from images;

[0073] Optional information processing components are used to perform calculations on the information acquired from the image.

[0074] The information includes redness characteristics of the swollen area, such as at least one of the following: area of ​​skin redness and swelling, and color intensity.

[0075] For example, information acquisition of images can be performed by referring to the method described in patent application CN202110707754.0.

[0076] The processing can involve quantifying the red and swollen area using algorithm software or calculation formulas.

[0077] For example, the information can be processed in accordance with the method described in patent application CN202110707754.0.

[0078] Optionally, the system may also include auxiliary tools, such as distance measuring tools, timers, etc.

[0079] In some embodiments, the system also includes a ranging tool to determine the distance between contact areas of the active compound.

[0080] In some embodiments, the system further includes a timer to control the contact time of the active compound and / or the interval between image acquisitions and the total time.

[0081] Methods for detecting the neurological functional status of subjects

[0082] According to a third aspect, the present invention provides a method for detecting the neurological functional state of a subject, characterized in that it comprises the following steps:

[0083] I) Provides a correlation line between the degree of response to stimulation by active substances selected from HCAR2 receptor activators, HCAR3 receptor activators, their esters and combinations thereof and the VPT value;

[0084] II) Determine the degree of response of the subject to the active substance; and

[0085] III) Obtain the VPT value corresponding to the response level value obtained in step II) from the correlation line of step I), thereby obtaining information on the neural functional state.

[0086] The subjects were human.

[0087] The active substance is selected from nicotinic acid, methyl nicotinic acid, ethyl nicotinic acid, and combinations thereof.

[0088] The active substance is in the form of an aqueous solution.

[0089] The stimulation refers to bringing the active substance into contact with the skin at several reaction points.

[0090] The active substance can be placed in a reactor and then brought into contact with the skin via the reactor.

[0091] The active ingredients can also be brought into contact with the skin through patches containing them.

[0092] Preferably, the skin refers to the skin of the forearm.

[0093] For example, an aqueous solution of the active substance is added dropwise to the corresponding pore on the reactor and then smoothly applied to the forearm of the volunteer or subject.

[0094] Preferably, the active substance is exposed to the skin for 0.5-2 minutes. More preferably, the active compound is exposed to the subject's skin for at least 1 minute.

[0095] Preferably, the active substance stimulation conditions in steps I) and II) are the same or similar.

[0096] The active substance stimulation conditions mentioned here include solution concentration and reaction point.

[0097] The same or similar reaction points refer to the reaction points in steps I) and II) corresponding to each other or located in symmetrical parts of the body.

[0098] Preferably, the reaction degree values ​​in steps I) and II) are obtained in the same or similar ways.

[0099] The response degree and VPT value under the stimulation of active substances are usually measured some time after the stimulation is stopped (0-10 minutes) (e.g., immediately, e.g., 0.5-10 minutes later).

[0100] For example, the correlation line can be obtained through the following steps:

[0101] Ii) Determine the degree of response of volunteers to the stimulation of active substances;

[0102] (ii) While performing step Ii, the VPT value of the volunteers was measured;

[0103] Iiii) Perform a correlation analysis on the response degree value in step Ii) and the VPT value in step Iii) to obtain the correlation line.

[0104] The volunteers are people, numbering at least 10, preferably at least 20. It is understood that volunteers may also be referred to as subjects in step Ii.

[0105] For example, the VPT value can be obtained by methods known in the art. For example, the VPT value can be obtained using an instrument.

[0106] In steps Ii and II, one or more aqueous solutions of the active substance at different concentrations may be brought into contact with the subject's skin.

[0107] Preferably, several aqueous solutions of active substances of different concentrations are brought into contact with the subject's skin.

[0108] When at least two active substance reaction sites are specified, preferably, the concentration of the active substance aqueous solution is different at each active substance reaction site.

[0109] For example, at least two different concentrations of the active substance aqueous solution were applied to the skin of volunteers or subjects, with a maximum concentration of at least 20 mM, such as 0.50-0.1 M, decreasing by 2-10 times in succession.

[0110] For example, at least two different concentrations of the active substance aqueous solution were applied to the skin of volunteers or subjects, with a maximum concentration of 100 mM and decreasing by 10 times in succession.

[0111] For example, at least six different concentrations of the active substance aqueous solution were applied to the subject's skin, with the maximum concentration being 60 mM and decreasing by a factor of 3.

[0112] For example, steps Ii) and II) can be performed in the following manner:

[0113] Several points were designated as reaction points on one arm of each of several volunteers or subjects. Several concentrations of aqueous solutions of the active substance were applied to each reaction point for a certain period of time. After the contact was stopped for a certain period of time (0-10 minutes) (preferably immediately), the erythema area under each reaction point was measured once or multiple times. The erythema area measured once or the sum of the erythema areas measured multiple times was taken as the reaction degree value.

[0114] Preferably, for the determination of erythema area, at least two active substance reaction sites are specified.

[0115] When at least two active substance reaction sites are specified, preferably, the concentration of the active substance aqueous solution is different at each active substance reaction site. For example, at least two different concentrations of the active substance aqueous solution are applied to the subject's skin, with a maximum concentration of at least 20 mM and a decreasing concentration of 2-10 times.

[0116] For example, at least two different concentrations of the active substance aqueous solution were applied to the subject's skin, with a maximum concentration of 100 mM and decreasing by 10 times in succession.

[0117] For example, at least six different concentrations of the active substance aqueous solution were applied to the subject's skin, with the maximum concentration being 60 mM and decreasing by a factor of 3.

[0118] The area of ​​erythema can be obtained by acquiring images of each reaction point and then quantifying the swollen area using image processing software such as algorithm software.

[0119] Skin images of the subjects can be acquired using imaging equipment.

[0120] Skin images were acquired 0-10 minutes after the skin had finished contacting the active substance.

[0121] Preferably, skin images are acquired immediately after the skin has come into contact with the active substance.

[0122] Preferably, images of the skin are acquired using an imaging device for at least 30 seconds, for example, from 30 seconds to 20 minutes. The image acquisition frequency can be several frames per minute, for example, 1 frame / minute or 6 frames / minute (i.e., 1 frame / 10 seconds).

[0123] The image acquisition is performed perpendicular to the skin in contact with the active substance.

[0124] Information about the erythema area can be obtained from an image using image processing equipment.

[0125] For example, one can refer to the extraction and analysis of the subject's skin reaction characteristics as described in patent application CN202110707754.0 to obtain information on the erythema area.

[0126] For example, in some implementations, the degree of reaction value is obtained as follows:

[0127] (1) The software uses the first photo as the base image to locate the reaction area and the skin background color;

[0128] (2) Starting from the second photo, the software identifies the reddened areas in each photo based on the color change of each photo relative to the background image, and quantifies the area of ​​each reddened area.

[0129] (3) Add up the area values ​​of the reddened areas in each photo to get the reaction degree value.

[0130] Understandably, only step I needs to be performed once for different subjects, and steps II and III only need to be performed for different subjects.

[0131] The method according to the present invention is a non-invasive detection method that can detect the neurological function status of a subject.

[0132] This invention provides a method for assessing neurological function, which uses the skin response to stimulation by active substances as a macroscopic manifestation of VPT value level. By assessing the erythema area at the stimulation site, the VPT value of the subject can be reflected.

[0133] This invention presents subcutaneous VPT levels as a macroscopic response, making the test results easier to interpret and providing an objective response less susceptible to influence by the subject's cognitive abilities. The method is non-invasive and painless, with simple operation, allowing for accurate implementation by staff. Furthermore, the testing cost is low. This application provides at least the following embodiments:

[0134] Implementation Method 1: Use of active substances selected from HCAR2 receptor activators, HCAR3 receptor activators, their esters and combinations thereof in the preparation of a kit for detecting the neurological functional status of a subject.

[0135] Embodiment 2: According to the use described in Embodiment 1, the active substance is selected from nicotinic acid, methyl nicotinic acid, ethyl nicotinic acid, and combinations thereof.

[0136] Embodiment 3: The use according to Embodiment 1 or 2, characterized in that the active substance is in the form of an aqueous solution.

[0137] Embodiment 4: The use according to any one of Embodiments 1 to 3, characterized in that the kit comprises a plurality of chambers for containing aqueous solutions of active substances of a plurality of concentrations.

[0138] Embodiment 5: The use according to any one of Embodiments 1 to 4, characterized in that the kit contains an aqueous solution of an active substance at a concentration of 0.1 mM or more, 0.15 mM or more, 0.5 mM or more, 1 mM or more, 3 mM or more, 10 mM or more, or 20 mM.

[0139] Embodiment 6: The use according to any one of Embodiments 1 to 5, characterized in that the kit contains an aqueous solution of the active substance at a concentration not exceeding 1000 mM.

[0140] Implementation Method 7: According to the use described in Implementation Method 4, the kit contains at least two aqueous solutions of active substances at different concentrations, with a maximum concentration of at least 20 mM and a concentration decreasing sequentially by 2 to 10 times.

[0141] Implementation Method 8: According to the use described in Implementation Method 4, the kit contains at least two aqueous solutions of active substances at different concentrations, with the maximum concentration being below 100 mM and decreasing sequentially by 2 to 10 times.

[0142] Implementation Method 9: According to the use described in Implementation Method 4, the kit contains at least 6 aqueous solutions of active substances at different concentrations, with a maximum concentration of 60 mM and decreasing by a factor of 3.

[0143] Embodiment 10: The use according to any one of Embodiments 1 to 9, characterized in that the detection includes:

[0144] I) Provides a correlation line between the relative VPT value and the degree of response value under stimulation by the active compound;

[0145] II) Determine the degree of response of the subject to the stimulation of the active compound; and

[0146] III) Obtain the relative VPT value corresponding to the response level value obtained in step II) from the correlation line of step I), thereby obtaining information on the neural functional state.

[0147] Implementation Method 11: A system for detecting the neurological functional state of a subject, characterized in that it comprises:

[0148] A kit containing active compounds selected from HCAR2 receptor activators, HCAR3 receptor activators, their esters, and combinations thereof;

[0149] Reactor;

[0150] Imaging equipment, used to acquire images; and

[0151] Image processing equipment is used to acquire information from images and optionally process it.

[0152] Embodiment 12: The system according to Embodiment 11, wherein the active compound is selected from nicotinic acid, methyl nicotinic acid, ethyl nicotinic acid, and combinations thereof.

[0153] Embodiment 13: The system according to Embodiment 11 or 12 is characterized in that the reactor has a plurality of holes for placing the active compound, the holes having any shape, preferably circular holes, square holes, rectangular holes, or combinations thereof.

[0154] Embodiment 14. The system according to Embodiment 11 or 12 is characterized in that the reactor consists of a plurality of patches capable of containing the active compound, the patches having any shape, preferably circular holes, square holes, rectangular holes, or combinations thereof.

[0155] Embodiment 15: The system according to any one of Embodiments 11 to 14, characterized in that the imaging device comprises:

[0156] The box, which forms a sealed space, has an entrance for a person to insert their forearm; and

[0157] An image acquisition component is used to image and acquire the skin of a person's forearm that has been inserted into the box.

[0158] Implementation Method 16: The system according to Implementation Method 15 is characterized in that the image acquisition component can receive timed shooting signals.

[0159] Embodiment 17. The system according to any one of Embodiments 11 to 16, characterized in that the image processing device comprises:

[0160] Image information acquisition component, used to acquire information from images;

[0161] Optional information processing components are used to perform calculations on the information acquired from the image.

[0162] Embodiment 18: The system according to any one of Embodiments 11 to 17, wherein the information includes at least one selected from the area and color of skin redness and swelling.

[0163] Implementation Method 19: A method for detecting the neurological functional state of a subject, characterized by comprising the following steps:

[0164] I) Provides a correlation line between the degree of response to stimulation by active substances selected from HCAR2 receptor activators, HCAR3 receptor activators, their esters and combinations thereof and the VPT value;

[0165] II) Determine the degree of response of the subject to the active substance; and

[0166] III) Obtain the VPT value corresponding to the response level value obtained in step II) from the correlation line of step I), thereby obtaining information on the neural functional state.

[0167] Implementation Method 20: The method according to Implementation Method 19, wherein the active substance is selected from nicotinic acid, methyl nicotinic acid, ethyl nicotinic acid, and combinations thereof.

[0168] Implementation Method 21: The method according to Implementation Method 19 or 20, wherein the active substance is in the form of an aqueous solution.

[0169] Embodiment 22: The method according to any one of Embodiments 19 to 21, characterized in that the stimulation comprises bringing an active substance into contact with the skin at several reaction points.

[0170] Implementation Method 23: The method according to Implementation Method 22, wherein the stimulation comprises contacting the active substance with the skin for 0.5-2 minutes.

[0171] Implementation Method 24: The method according to any one of Implementation Methods 19 to 23, characterized in that the response degree value and VPT value under the stimulation of the active substance are measured 0-10 minutes after the stimulation is stopped.

[0172] Implementation Method 25: The method according to any one of Implementation Methods 19 to 24, characterized in that the correlation line can be obtained by the following steps:

[0173] Ii) Determine the degree of response of volunteers to the stimulation of active substances;

[0174] (ii) While performing step Ii, the VPT value of the volunteers was measured;

[0175] Iiii) Perform a correlation analysis on the response degree value in step Ii) and the VPT value in step Iii) to obtain the correlation line.

[0176] Implementation Method 26: The method according to Implementation Method 25 is characterized in that at least two aqueous solutions of active substances of different concentrations are applied to the skin of volunteers or subjects, with a maximum concentration of at least 20 mM and a concentration decreasing sequentially by 2 to 10 times.

[0177] Implementation Method 27: The method according to Implementation Method 25 is characterized in that steps Ii) and II) can be performed in the following manner:

[0178] Several points were designated as active substance reaction points on one arm of each subject. Several concentrations of aqueous solutions of the active substance were applied to each reaction point for a certain period of time. After the contact was stopped for a certain period of time, preferably immediately, the erythema area under each reaction point was measured once or multiple times. The erythema area measured once or the sum of the erythema areas measured multiple times was taken as the reaction degree value.

[0179] Implementation Method 28: The method according to Implementation Method 25 is characterized in that, in steps Ii) and II), the degree of reaction value is obtained by:

[0180] (1) The software uses the first photo as the base image to locate the reaction area and the skin background color;

[0181] (2) Starting from the second photo, the software identifies the reddened areas in each photo based on the color change of each photo relative to the background image, and quantifies the area of ​​each reddened area.

[0182] (3) Add up the area values ​​of the reddened areas in each photo to get the reaction degree value.

[0183] The descriptions of each feature in this application can be combined with each other as long as they do not contradict each other, and all of them fall within the scope of protection claimed in this application.

[0184] The terms "comprising" and "including" as used in this application cover situations where other elements not explicitly mentioned are also included, as well as situations where the elements mentioned are constituted.

[0185] Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. In the event of any discrepancy between the definitions of terms in this specification and their commonly understood meaning by one of ordinary skill in the art to which this invention pertains, the definitions set forth herein shall prevail.

[0186] Unless otherwise stated, all numerical values ​​of the quantities of expressed components, etc., used in the specification and claims are to be understood as being modified by the term "about". Therefore, unless otherwise indicated, the numerical parameters set forth herein are approximate values ​​that can be varied to obtain the desired performance as needed.

[0187] Example

[0188] The following will further illustrate the concept and technical effects of the present invention with reference to embodiments, so that those skilled in the art can fully understand the purpose, features, and effects of the present invention. Those skilled in the art will understand that the embodiments described herein are merely illustrative, and the scope of the present invention is not limited thereto.

[0189] Example 1

[0190] I) Provide a correlation line between the degree of reaction value and the VPT value.

[0191] Ii) Determine the degree of response of volunteers to nicotinic acid methyl ester aqueous solution.

[0192] Twenty volunteers were invited to designate six points on one of their arms as reaction sites for the active compound. 60mM, 20mM, 6.67mM, 2.22mM, 0.74mM and 0.25mM aqueous solutions of methyl nicotinic acid were applied to the reaction sites through patches, and the patches were removed after 1 minute.

[0193] After removing the patch, volunteers placed their arms into the imaging device, and photography was immediately initiated, taking one photo every 10 seconds for a total of 10 minutes. The software used the first photo as a base image to locate the reaction area and the skin's background color. Starting with the second photo, the software identified the reddened areas in each photo based on the color changes relative to the base image and quantified the area of ​​each reddened area. The area values ​​of the reddened areas in each photo were summed to obtain the reaction severity value.

[0194] IIi) Measure the VPT value of volunteers.

[0195] Simultaneously with the nicotinic acid methyl ester skin reaction in step Ii), the VPT values ​​of the first toe of the right foot, the dorsum of the right foot, the first toe of the left foot, and the dorsum of the left foot were measured using routine VPT testing. The average value of the four locations was taken as the vibration perception threshold of the subject (i.e., the volunteer).

[0196] (ii) Obtain the correlation line between the degree of reaction in step (ii) and the VPT value in step (ii).

[0197] Pearson correlation analysis was used to correlate the response scores of volunteers at the six concentrations with the mean VPT, and the correlation lines and correlation coefficients were obtained.

[0198] Figure 3 The correlation curve between the response degree values ​​and the mean VPT values ​​under nicotinic acid methyl ester solution stimulation is shown. From Figure 3 It can be seen that there is a significant negative correlation between the nicotinic acid methyl ester response score and the mean VPT score in volunteers (p<0.001).

[0199] II) Measuring the subject's response to nicotinic acid methyl ester aqueous solution stimulation.

[0200] As described in step Ii, the degree of response to the same nicotinic acid methyl ester aqueous solution was measured on one arm of 12 subjects.

[0201] Table 1 lists the response levels of the 12 subjects at various concentrations of methyl nicotinic acid aqueous solution.

[0202] III) Obtaining information on neural functional status

[0203] The VPT value corresponding to the response level value obtained in step II) is obtained from the correlation line in step I), thereby obtaining information on the neural functional state.

[0204] Table 1 lists the VPT values ​​(VPT inference values) corresponding to each response level of the above 12 subjects.

[0205] verify

[0206] The subject's VPT value was measured simultaneously with step II).

[0207] Specifically, the VPT values ​​of the first toe of the right foot, the instep of the right foot, the first toe of the left foot, and the instep of the right foot were measured using VPT detection, and the average value of the four locations was taken.

[0208] Table 1 lists the mean VPT (i.e., measured VPT values) of the above 12 subjects at various concentrations of methyl nicotinic acid aqueous solution.

[0209] Table 1

[0210]

[0211] *: VPT relative error = (|VPT inferred value – VPT actual value|) / VPT measured value * 100%

[0212] The foregoing descriptions are merely exemplary embodiments or examples of the present invention and are not intended to limit the invention. Those skilled in the art will recognize that the present invention can be modified and varied in many ways. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principle of the present invention are included within the scope of the claims of this application.

Claims

1. Use of active substances selected from HCAR2 receptor activators, HCAR3 receptor activators, their esters and combinations thereof in the preparation of kits for detecting the neurological functional status of subjects.

2. The use according to claim 1, characterized in that, The active substance is selected from nicotinic acid, methyl nicotinic acid, ethyl nicotinic acid, and combinations thereof.

3. The use according to claim 1 or 2, characterized in that, The active substance is in the form of an aqueous solution.

4. The use according to any one of claims 1 to 3, characterized in that, The kit includes several chambers to contain aqueous solutions of active substances at several concentrations.

5. The use according to any one of claims 1 to 4, characterized in that, The kit contains an aqueous solution of the active substance at a concentration of 0.1 mM or higher, 0.15 mM or higher, 0.5 mM or higher, 1 mM or higher, 3 mM or higher, 10 mM or higher, or 20 mM.

6. The use according to any one of claims 1 to 5, characterized in that, The kit contains an aqueous solution of the active substance at a concentration not exceeding 1000 mM.

7. The use according to claim 4, characterized in that, The kit contains at least two aqueous solutions of active substances at different concentrations, with a maximum concentration of at least 20 mM and concentrations decreasing sequentially from 2 to 10 times.

8. The use according to claim 4, characterized in that, The kit contains at least two aqueous solutions of active substances at different concentrations, with the maximum concentration below 100 mM and the concentration decreasing sequentially from 2 to 10 times.

9. The use according to claim 4, characterized in that, The kit contains at least six different concentrations of active ingredient aqueous solutions, with a maximum concentration of 60 and decreasing by a factor of 3.

10. The use according to any one of claims 1 to 9, characterized in that, The detection includes: I) Provides a correlation line between the relative VPT value and the degree of response value under stimulation by the active compound; II) Determine the degree of response of the subject to the stimulation of the active compound; and III) Obtain the relative VPT value corresponding to the response level value obtained in step II) from the correlation line of step I), thereby obtaining information on the neural functional state.

Images