Kit and system for detecting neurological function state of subject

Abstract

The use of an active substance selected from an HCAR2 receptor activator, an HCAR3 receptor activator, an ester thereof, and a combination thereof in the preparation of a kit for detecting a neurological function state of a subject. The kit comprises several small chambers to accommodate different concentrations of aqueous solutions of the HCAR2 receptor activator or the HCAR3 receptor activator or the ester thereof. The kit can be used for effectively detecting the neural neurological state of the subject by means of evaluating the sensitivity of the subject to the HCAR2 receptor activator or the HCAR3 receptor activator or the ester thereof, and can be used for quickly obtaining a detection result by means of a few simple steps in a short time, so that real-time detections in multiple scenarios such as hospital wards, physical examination centers, and homes are achieved.

Description

Kit and system for detecting the neurological function status of a subject Technical Field

[0001] The present invention relates to the field of medical detection technology, and in particular to a kit and a system for detecting the neurological function status of a subject. Background Art

[0002] Vibration Perception Threshold Testing (VPT) is a method for detecting neurological function status. It provides local vibration to detect the patient's perception threshold of vibration, and assists in diagnosing whether the patient has a neurological sensory system disease.

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

[0004] The general process of VPT testing is as follows: (1) The subject remains quiet (sitting or lying down) and waits for the test; (2) The tester operates the VPT tester to apply vibration to the subject; (3) The subject feels the vibration and accurately describes the vibration sensation to the tester when feeling it; (4) The tester records the instrument display value when the subject can feel the vibration, which is the subject's VPT value. It can be seen from this that VPT testing is easily affected by systematic errors, the instrument test repeatability is poor, and it often takes multiple repeated measurements to produce a test report; its digital record relies on the subject's subjective description, lacks a certain degree of objectivity, and is also affected by the subject's cognitive ability.

[0005] Therefore, developing a more objective method to assess neurological functional status is of great clinical significance. Summary of the Invention

[0006] An 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 function status of a subject, which can be used in the above-mentioned 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-mentioned detection method.

[0009] The present invention is based on the following discovery by the inventors: the degree of reaction of HCAR2 receptor activators, HCAR3 receptor activators and their esters with the subject's skin is strongly positively correlated with the 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 use of an active substance selected from HCAR2 receptor activators, HCAR3 receptor activators, esters thereof, and combinations thereof in preparing a kit for detecting the neurological function status of a subject.

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

[0012] A kit comprising an active substance selected from the group consisting of an HCAR2 receptor activator, an HCAR3 receptor activator, an ester thereof, and a combination thereof;

[0013] reactor;

[0014] Imaging equipment for obtaining images; and

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

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

[0017] 1) providing a correlation line between the response degree value and the VPT value under stimulation by an active substance selected from the group consisting of an HCAR2 receptor activator, an HCAR3 receptor activator, an ester thereof, and a combination thereof;

[0018] II) measuring the degree of response of the subject to stimulation by the active substance; and

[0019] III) Obtaining the VPT value corresponding to the reaction degree value obtained in step II) from the correlation line of step I), thereby obtaining the neural function status information.

[0020] The kit of the present invention can be used to safely and noninvasively assess a subject's neurological function. The system and method of the present invention can be used to rapidly obtain test results in a short period of time through a few simple steps, enabling real-time testing in multiple scenarios, such as hospital wards, physical examination centers, and at home. This is an objective, convenient, and effective biological testing method. The present invention provides a safe, noninvasive, and simple-to-use method for assessing neurological function. BRIEF DESCRIPTION OF THE DRAWINGS

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

[0022] FIG1 schematically shows a reactor having several holes, wherein 1 is a reactor and 11 is a hole.

[0023] FIG2 schematically shows a reactor composed of several patches, where 2 is a reactor and 21 is a patch.

[0024] FIG3 shows the correlation line between the reaction degree value and the VPT mean value under the stimulation of methyl nicotinate solution in Example 1. DETAILED DESCRIPTION

[0025] Certain specific embodiments of the present invention will now be described for purposes of illustration and not limitation.

[0026] Reagent test kit

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

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

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

[0030] In this application, for simplicity, the HCAR2 receptor activator or HCAR3 receptor activator or ester thereof is sometimes also referred to as an active compound.

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

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

[0033] Preferably, the active substance in the kit is in the form of an aqueous solution.

[0034] Preferably, the kit comprises an aqueous solution of the active substance having a concentration of 0.1 mM or greater. More preferably, the concentration of the active substance in the aqueous solution is 0.15 mM or greater, or 0.5 mM or greater, or 1 mM or greater, or 3 mM or greater, or 10 mM or greater, or 20 mM or greater.

[0035] Preferably, the concentration of the active substance in the aqueous solution does not exceed 1000 mM.

[0036] The kit includes several chambers to contain aqueous solutions of active substances at several concentrations.

[0037] In the specification and claims of this application, number may encompass one or more.

[0038] In case more than one chamber is included, the concentration of the aqueous active substance solution contained therein may be the same or different.

[0039] In some embodiments, the kit comprises at least two aqueous solutions of active substances at different concentrations, with a maximum concentration of at least 20 mM and concentrations decreasing in 2-10 fold increments.

[0040] In some embodiments, the kit comprises at least two aqueous solutions of active substances with different concentrations, with the maximum concentration being below 100 mM and the concentration decreasing in 2-10 fold increments.

[0041] In some embodiments, the kit comprises at least 6 aqueous solutions of active substances with different concentrations, with a maximum concentration of 60 mM and a 3-fold decrease in concentration.

[0042] The detection includes:

[0043] 1) providing a correlation line between the reaction degree value and the VPT value under the stimulation of the active substance;

[0044] II) measuring the degree of response of the subject to stimulation by the active substance; and

[0045] III) Obtaining the VPT value corresponding to the reaction degree value obtained in step ID from the correlation line of step I), thereby obtaining the neural function status information.

[0046] The subject is a human.

[0047] In this application, the reaction level value refers to the reaction level of the skin when it comes into contact with the active compound, the determination of which is described in detail below.

[0048] Additional details regarding detection are described in detail below and may be incorporated herein.

[0049] System for detecting the neurological function status of a subject

[0050] According to a second aspect, the present invention provides a system for detecting a neurological functional state of a subject, characterized in that it comprises:

[0051] A kit comprising an active substance selected from the group consisting of an HCAR2 receptor activator, an HCAR3 receptor activator, an ester thereof, and a combination thereof;

[0052] reactor;

[0053] Imaging equipment for obtaining images; and

[0054] Image processing equipment is used to collect information from images.

[0055] Preferably, the active substance is selected from niacin, methyl nicotinate, ethyl nicotinate, and combinations thereof.

[0056] In some embodiments, the reactor may have several holes for placing the active material.

[0057] The holes may have any shape, preferably circular holes, square holes, rectangular holes, or a combination thereof.

[0058] The holes may have the same or different areas.

[0059] FIG1 schematically shows a reactor having several holes, wherein 1 is a reactor and 11 is a hole.

[0060] In the case of using a reactor having several holes, the reactor is brought into contact with the subject's skin (eg, forearm skin), and then several amounts of the active substance are applied to the holes.

[0061] In some embodiments, the reactor simply consists of a number of patches capable of containing the active substance.

[0062] The patch may have any shape, preferably a circular hole, a square hole, a rectangular hole, or a combination thereof.

[0063] The patches may be of the same or different areas.

[0064] FIG2 schematically shows a reactor composed of several patches, where 2 is a reactor and 21 is a patch.

[0065] In the case of a reactor consisting of several patches, the patches are brought into contact with the subject's skin.

[0066] Preferably, the imaging device comprises:

[0067] a box body constituting a closed space and provided with an entrance for inserting the forearm of the subject; and

[0068] The image acquisition component is used to image the skin of the forearm of the subject inserted into the box and acquire the obtained image.

[0069] Preferably, the image acquisition component can also receive a timed shooting signal, wherein the timed shooting signal is used to trigger the image acquisition component to image the skin of the subject's forearm at a plurality of predetermined time points.

[0070] Preferably, the image processing device includes:

[0071] Image information acquisition component, used for collecting information from images;

[0072] An optional information processing component is used to perform calculations on the information collected from the images.

[0073] The information includes a redness characteristic value of the red and swollen area, such as at least one of the red and swollen skin area and chromaticity.

[0074] For example, you can refer to the description in patent application CN202110707754.0 to collect information on the image.

[0075] The processing may be quantifying the redness and swelling area using algorithm software or calculation formula.

[0076] For example, the information can be processed with reference to the description in patent application CN202110707754.0.

[0077] Optionally, the system further comprises auxiliary tools, such as distance measuring tools, timers, and the like.

[0078] In some embodiments, the system further comprises a distance measuring tool to determine the distance between the active compound contact areas.

[0079] In some embodiments, the system further comprises a timer to control the active compound contact time and / or the interval and total time of image acquisition.

[0080] Method for detecting the neurological function status of a subject

[0081] According to a third aspect, the present invention provides a method for detecting the neurological function state of a subject, characterized in that it comprises the following steps:

[0082] 1) providing a correlation line between the response degree value and the VPT value under stimulation by an active substance selected from the group consisting of an HCAR2 receptor activator, an HCAR3 receptor activator, an ester thereof, and a combination thereof;

[0083] II) measuring the degree of response of the subject to stimulation by the active substance; and

[0084] III) Obtaining the VPT value corresponding to the reaction degree value obtained in step II) from the correlation line of step I), thereby obtaining the neural function status information.

[0085] The subject is a human.

[0086] The active substance is selected from niacin, methyl nicotinate, ethyl nicotinate and combinations thereof.

[0087] The active substance is in the form of an aqueous solution.

[0088] The stimulation is to bring the active substance into contact with the skin at several reaction points.

[0089] The active substance can be placed in a reactor and brought into contact with the skin via the reactor.

[0090] The active substance can also be brought into contact with the skin via a patch containing the active substance.

[0091] Preferably, the skin is forearm skin.

[0092] For example, the aqueous solution of the active substance is dripped into the corresponding hole position on the reactor and flatly applied to the forearm of the volunteer or subject.

[0093] Preferably, the active compound is allowed to contact the skin for 0.5-2 minutes. More preferably, the active compound is allowed to contact the subject's skin for at least 1 minute.

[0094] Preferably, the active substance stimulation conditions in step I) and step II) are the same or similar.

[0095] The active substance stimulation conditions mentioned here include solution concentration and reaction point.

[0096] The same or similar reaction points mean that the reaction points in step I) and step II) correspond to each other or are located in symmetrical parts of the body.

[0097] Preferably, the reaction degree values ​​in step I) and step II) are obtained in the same or similar manner.

[0098] The reaction level and VPT value under the stimulation of the active substance are usually measured after a certain time (0-10 minutes) (eg, immediately, for example, 0.5-10 minutes) after the stimulation is stopped.

[0099] For example, the correlation line can be obtained by the following steps:

[0100] ii) measuring the degree of response of the volunteers under stimulation with the active substance;

[0101] iii) while performing step ii, measuring the VPT value of the volunteer;

[0102] Iiii) performing a correlation analysis on the reaction degree value of step Ii) and the VPT value of step Iii) to obtain a correlation line.

[0103] The volunteers are humans, and the number is at least 10, preferably at least 20. It is understood that volunteers may also be referred to as subjects in step Ii.

[0104] For example, the VPT value can be obtained by methods known in the art. For example, the VPT value can be obtained by using ?

[0105] In steps Ii and II, one or more aqueous solutions of the active substance at different concentrations may be brought into contact with the skin of the subject.

[0106] Preferably, several aqueous solutions of the active substance at different concentrations are brought into contact with the skin of the subject.

[0107] When at least two active substance reaction sites are designated, preferably, the concentration of the active substance aqueous solution at each active substance reaction site is different.

[0108] For example, at least two aqueous solutions of the active substance with different concentrations are used to contact the skin of volunteers or subjects, with a maximum concentration of at least 20 mM, such as 0.50-0.1 M, and the concentrations are decreased by 2-10 times.

[0109] For example, at least two aqueous solutions of the active substance with different concentrations are used to contact the skin of volunteers or subjects, with the maximum concentration being 100 mM and the concentration decreasing by 10 times.

[0110] For example, at least 6 aqueous solutions of the active substance with different concentrations are used to contact the skin of the subject, with the maximum concentration being 60 mM and the concentration decreasing by 3 times.

[0111] For example, steps Ii) and II) can be performed as follows:

[0112] Several points on the arms of several volunteers or subjects are designated as active substance reaction points. Aqueous solutions of the active substance at several concentrations are contacted with each reaction point for a certain period of time. After the contact is stopped for a certain period of time (0-10 minutes) (preferably immediately), the erythema area at each reaction point is measured once or multiple times. The sum of the erythema area measured once or multiple times is used as the reaction degree value.

[0113] Preferably, at least two active substance reaction points are designated for erythema area measurement.

[0114] When at least two active substance reaction sites are designated, preferably, the concentration of the active substance aqueous solution at each active substance reaction site is different. For example, at least two aqueous solutions of the active substance with different concentrations are contacted with the subject's skin, with a maximum concentration of at least 20 mM and a decreasing concentration of 2-10 times.

[0115] For example, at least two aqueous solutions of the active substance with different concentrations are used to contact the skin of the subject, with the maximum concentration being 100 mM and the concentration decreasing by 10 times.

[0116] For example, at least 6 aqueous solutions of the active substance with different concentrations are used to contact the skin of the subject, with the maximum concentration being 60 mM and the concentration decreasing by 3 times.

[0117] The erythema area can be obtained by acquiring images of each reaction point and then quantifying the redness and swelling area using image processing software such as algorithm software.

[0118] Acquiring an image of the subject's skin can be performed by an imaging device.

[0119] Skin images were collected 0-10 minutes after the end of contact between the skin and the active substance.

[0120] Preferably, the skin image is collected immediately after the contact between the skin and the active substance ends.

[0121] Preferably, the skin is imaged for at least 30 seconds, for example, 30 seconds to 20 minutes, by the imaging device. The image acquisition frequency can be several images per minute, for example, 1 image / minute or 6 images / minute (i.e., 1 image / 10 seconds).

[0122] The image acquisition is performed perpendicular to the skin in contact with the active substance.

[0123] The erythema area information can be obtained from the image by using an image processing device.

[0124] For example, you can refer to the description in patent application CN202110707754.0 to extract and analyze the skin reaction characteristics of the subject to obtain erythema area information.

[0125] For example, in some embodiments, the reaction extent value is obtained as follows:

[0126] (1) The software uses the first photo as the base image to locate the reaction area and skin base color;

[0127] (2) Starting from the second photo, the software identifies the reddened area on each photo based on the color change of each photo relative to the base image, and quantifies the area of ​​each reddened area;

[0128] (3) Add up the area values ​​of the reddened areas on each photo to obtain the reaction degree value.

[0129] It is understandable that for different subjects, step I) only needs to be performed once, and steps II) and III) only need to be performed for different subjects.

[0130] The method according to the present invention is a non-invasive detection method, which can detect the neurological function status of a subject.

[0131] The present invention provides a method for evaluating the neurological function status, which uses the skin reaction under the stimulation of active substances as a macroscopic manifestation of the VPT value level. By evaluating the erythema area at the stimulation position, the VPT value of the subject can be reflected.

[0132] By displaying the subcutaneous VPT level as a macroscopic response, the present invention makes the test results easier to interpret, objective, and less susceptible to the subject's cognitive abilities. The method of the present invention is non-invasive and painless, and the test is simple to perform, making it easy for staff to accurately implement. Furthermore, the test cost of the present invention is low. This application provides at least the following embodiments:

[0133] Embodiment 1: Use of an active substance selected from HCAR2 receptor activators, HCAR3 receptor activators, esters thereof, and combinations thereof in preparing a kit for detecting the neurological function status of a subject.

[0134] Embodiment 2: The use according to embodiment 1, characterized in that the active substance is selected from nicotinic acid, methyl nicotinate, ethyl nicotinate and combinations thereof.

[0135] Embodiment 3: The use according to embodiment 1 or 2, characterized in that the active substance is in the form of an aqueous solution.

[0136] Embodiment 4: The use according to any one of embodiments 1 to 3, characterized in that the kit comprises several chambers to accommodate aqueous solutions of active substances of several concentrations.

[0137] Embodiment 5. The use according to any one of embodiments 1 to 4 is characterized in that the kit contains an aqueous solution of active substance with 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.

[0138] 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.

[0139] Embodiment 7: The use according to embodiment 4 is characterized in that the kit contains at least two aqueous solutions of active substances with different concentrations, with a maximum concentration of at least 20 mM and a concentration decreasing in 2-10 times order.

[0140] Embodiment 8: The use according to embodiment 4 is characterized in that the kit contains at least two aqueous solutions of active substances with different concentrations, with a maximum concentration of less than 100 mM and a concentration decreasing in 2-10 times order.

[0141] Embodiment 9: The use according to embodiment 4 is characterized in that the kit contains at least 6 aqueous solutions of active substances with different concentrations, with a maximum concentration of 60 mM and a 3-fold concentration decreasing in sequence.

[0142] Embodiment 10: The use according to any one of embodiments 1 to 9, characterized in that the detection comprises:

[0143] 1) providing a correlation line between the relative VPT value and the response degree value under the stimulation of the active compound;

[0144] II) determining the degree of response of the subject to stimulation by the active compound; and

[0145] III) Obtaining the relative VPT value corresponding to the reaction degree value obtained in step II) from the correlation line of step I), thereby obtaining the neural function status information.

[0146] Embodiment 11: A system for detecting a subject's neurological function state, characterized in that it comprises:

[0147] A kit comprising an active compound selected from the group consisting of an HCAR2 receptor activator, an HCAR3 receptor activator, an ester thereof, and a combination thereof;

[0148] reactor;

[0149] Imaging equipment for obtaining images; and

[0150] Image processing equipment is used to collect information from images and optionally process them.

[0151] Embodiment 12. The system according to embodiment 11, wherein the active compound is selected from niacin, methyl nicotinate, ethyl nicotinate, and combinations thereof.

[0152] Embodiment 13. The system according to embodiment 11 or 12, characterized in that the reactor has a plurality of holes for placing the active compound, and the holes have any shape, preferably circular holes, square holes, rectangular holes, or a combination thereof.

[0153] Embodiment 14. The system according to embodiment 11 or 12, characterized in that the reactor is composed of a plurality of patches capable of accommodating the active compound, and the patches have any shape, preferably circular holes, square holes, rectangular holes, or a combination thereof.

[0154] Embodiment 15: The system according to any one of embodiments 11 to 14, wherein the imaging device comprises:

[0155] A box body, which forms a closed space and is provided with an entrance for a person's forearm to be inserted into; and

[0156] The image acquisition component is used to image the skin of the forearm of a person extending into the box and acquire the resulting image.

[0157] Embodiment 16: The system according to embodiment 15 is characterized in that the image acquisition component can receive a timed shooting signal.

[0158] Embodiment 17: The system according to any one of Embodiments 11 to 16, wherein the image processing device comprises:

[0159] Image information acquisition component, used for collecting information from images;

[0160] An optional information processing component is used to perform calculations on the information collected from the images.

[0161] Embodiment 18: A system according to any one of embodiments 11 to 17, characterized in that the information includes at least one selected from the group consisting of skin redness and swelling area and color.

[0162] Embodiment 19: A method for detecting a subject's neurological function state, characterized in that it comprises the following steps:

[0163] 1) providing a correlation line between the response degree value and the VPT value under stimulation by an active substance selected from the group consisting of an HCAR2 receptor activator, an HCAR3 receptor activator, an ester thereof, and a combination thereof;

[0164] II) measuring the degree of response of the subject to stimulation by the active substance; and

[0165] III) Obtaining the VPT value corresponding to the reaction degree value obtained in step II) from the correlation line of step I), thereby obtaining the neural function status information.

[0166] Embodiment 20: The method according to embodiment 19, characterized in that the active substance is selected from niacin, methyl nicotinate, ethyl nicotinate and combinations thereof.

[0167] Embodiment 21. The method according to embodiment 19 or 20, characterized in that the active substance is in the form of an aqueous solution.

[0168] Embodiment 22. The method according to any one of embodiments 19 to 21, wherein the stimulation comprises contacting the active substance with the skin at a plurality of reaction points.

[0169] Embodiment 23. The method according to embodiment 22, characterized in that the stimulation comprises contacting the active substance with the skin for 0.5-2 minutes.

[0170] Embodiment 24: The method according to any one of embodiments 19 to 23, characterized in that the reaction degree value and the VPT value under the stimulation of the active substance are measured 0-10 minutes after the stimulation is stopped.

[0171] Embodiment 25: The method according to any one of embodiments 19 to 24, wherein the correlation line can be obtained by the following steps:

[0172] ii) measuring the degree of response of the volunteers under stimulation with the active substance;

[0173] iii) while performing step ii, measuring the VPT value of the volunteer;

[0174] Iiii) performing a correlation analysis on the reaction degree value of step Ii) and the VPT value of step Iii) to obtain a correlation line.

[0175] Embodiment 26. The method according to embodiment 25 is characterized in that at least two aqueous solutions of the active substance with different concentrations are used to contact the skin of the volunteer or subject, with the maximum concentration being at least 20 mM and the concentration decreasing in sequence by 2-10 times.

[0176] Embodiment 27: The method according to embodiment 25, characterized in that steps Ii) and II) can be performed in the following manner:

[0177] Several points on one arm of each subject are designated as active substance reaction points. Aqueous solutions of the active substance at several concentrations are brought into contact with each reaction point for a predetermined period of time. After the contact period has ceased, preferably immediately, the erythema area at each reaction point is measured once or multiple times. The sum of the erythema area measured once or multiple times is used as the reaction degree value.

[0178] Embodiment 28. The method according to embodiment 25, characterized in that in step 1i) and step 1D, the reaction degree value is obtained by:

[0179] (1) The software uses the first photo as the base image to locate the reaction area and skin base color;

[0180] (2) Starting from the second photo, the software identifies the reddened area on each photo based on the color change of each photo relative to the base image, and quantifies the area of ​​each reddened area;

[0181] (3) Add up the area values ​​of the reddened areas on each photo to obtain the reaction degree value.

[0182] The descriptions of various features in this application can be combined with each other if they are not contradictory, and all fall within the scope of protection requested by this application.

[0183] The terms “include” and “comprising” used in the present application encompass the case where the application further includes or comprises other elements not explicitly mentioned as well as the case where the application consists of the mentioned elements.

[0184] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which the invention belongs. When the definition of a term in this specification conflicts with the meaning commonly understood by those skilled in the art to which the invention belongs, the definition described in this article shall prevail.

[0185] Unless otherwise indicated, all numerical values ​​expressing quantities of ingredients and the like used in the specification and claims are to be understood as being modified by the term “about.” Accordingly, unless indicated to the contrary, the numerical parameters set forth herein are approximations that can vary depending upon the desired properties sought to be obtained.

[0186] Example

[0187] The following will further illustrate the concept and technical effects of the present invention in conjunction with the 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 herein are for illustrative purposes only and the scope of the present invention is not limited thereto.

[0188] Example 1

[0189] 1) Provide a correlation line between the reaction level value and the VPT value

[0190] Ii) Determination of the reaction level of volunteers under stimulation of methyl nicotinate aqueous solution

[0191] Twenty volunteers were invited to designate six points within an area on one arm of each volunteer as active compound reaction points. Aqueous solutions of 60mM, 20mM, 6.67mM, 2.22mM, 0.74mM, and 0.25mM nicotinate methyl ester were applied to the reaction points via a patch, and the patch was removed after 1 minute.

[0192] After removing the patch, the volunteer placed their arm into the imaging device, which immediately started capturing images every 10 seconds for 10 minutes. The software used the first image as a base image to locate the reaction area and the underlying skin color. Starting with the second image, 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 ​​for the reddened areas in each photo were summed to obtain the reaction severity value.

[0193] iii) Determination of the VPT value of volunteers

[0194] Simultaneously with the nicotinate methyl ester skin reaction in step Ii), the VPT values ​​of the first toe of the right foot, the right dorsum of the foot, the first toe of the left foot, and the left dorsum of the foot were measured by conventional VPT testing, and the average of the test values ​​at the four locations was taken as the vibration perception threshold of the subject (i.e., the volunteer).

[0195] iii) Obtaining a correlation line between the reaction degree value of step ii) and the VPT value of step iii)

[0196] Pearson correlation analysis was used to correlate the response values ​​of the volunteers at the six concentrations with the VPT mean, and the correlation line and correlation coefficient were obtained.

[0197] Figure 3 shows the correlation between the reaction degree values ​​and the VPT mean values ​​under stimulation with methyl nicotinate solution. Figure 3 shows that there is a significant negative correlation between the methyl nicotinate reaction degree values ​​and the VPT mean values ​​of the volunteers (p < 0.001).

[0198] II) Determination of the subject's response to stimulation with methyl nicotinate aqueous solution

[0199] As described in step Ii, the reaction level values ​​to the same nicotinate methyl ester aqueous solution stimulation were measured on one arm of 12 subjects.

[0200] Table 1 lists the reaction levels of the 12 subjects at various concentrations of the nicotinate methyl ester aqueous solution.

[0201] III) Obtaining neurological function status information

[0202] The VPT value corresponding to the reaction degree value obtained in step II) is obtained from the correlation line in step I), thereby obtaining the neural function status information.

[0203] Table 1 lists the VPT values ​​(VPT value inference values) corresponding to the reaction levels of the 12 subjects mentioned above.

[0204] verify

[0205] The VPT value of the subject is measured simultaneously with step II).

[0206] Specifically, the VPT values ​​of the first toe of the right foot, the right dorsum of the foot, the first toe of the left foot, and the right dorsum of the foot were measured through VPT detection, and the average value of the four positions was taken.

[0207] Table 1 lists the average VPT values ​​(ie, the actual VPT values) of the 12 subjects at various concentrations of the nicotinate methyl ester aqueous solution.

[0208] Table 1

[0209] *: VPT relative error = (|VPT estimated value - VPT actual value|) / VPT measured value * 100%

[0210] The above merely describes exemplary embodiments or examples of the present invention and is not intended to limit the present invention. It will be apparent to those skilled in the art that various modifications and variations of the present invention are possible. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention are intended to be included within the scope of the claims of this application.

Claims

Use of an active substance selected from HCAR2 receptor activators, HCAR3 receptor activators, esters thereof, and combinations thereof in the preparation of a kit for detecting the neurological function status of a subject.

2. The use according to claim 1, characterized in that, The active substance is selected from nicotinic acid, methyl nicotinate, ethyl nicotinate, 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. Use according to any one of claims 1 to 3, characterized in that, The kit includes a number of compartments for accommodating aqueous solutions of the active substance at a number of 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 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.

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 the active substance at different concentrations, with the maximum concentration being at least 20 mM, and the concentrations decreasing successively by a factor of 2 - 10.

8. The use according to claim 4, wherein The kit contains at least two aqueous solutions of the active substance at different concentrations, with the maximum concentration being 100 mM or less, and the concentrations decreasing successively by a factor of 2 - 10.

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

10. The use according to any one of claims 1 to 9, characterized in that, The detection includes: I) Providing a correlation line of the relative VPT value and the response degree value under the stimulation of the active compound; II) Measuring the response degree value of the subject under the stimulation of the active compound; and III) Obtaining the relative VPT value corresponding to the response degree value obtained in step II) from the correlation line in step I), thereby obtaining neurological function status information.

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