CN113317760B

CN113317760B - Olfactory disorder detection kit and preparation method thereof

Info

Publication number: CN113317760B
Application number: CN202110585846.6A
Authority: CN
Inventors: 张昊; 程洋; 付海田; 李子健; 黄乐兮; 胡昌进; 刘宁; 路雅斐; 张耀东; 张淼飒; 喻慧捷; 钟文丽
Original assignee: Jiangnan University
Current assignee: Jiangnan University
Priority date: 2021-05-27
Filing date: 2021-05-27
Publication date: 2022-06-07
Anticipated expiration: 2041-05-27
Also published as: CN113317760A

Abstract

The invention discloses a smell disorder detection kit and a preparation method thereof, and belongs to the field of detection kits. The kit comprises one or more metal wrappings and carriers, wherein the metal wrappings are wrappings consisting of metal wrapped smelly essences, the metal is a metal material which is solid at normal temperature, is molten at human body temperature and is nontoxic to the body surface of a human body, and gallium is preferably selected. The kit adopts a solid material as an odor carrier and is matched with the components of the special essence, so that the purposes of reducing the concentration loss of the odor essence in the transportation and storage processes, improving the detection accuracy, facilitating the use and simplifying the transportation and storage can be achieved, and meanwhile, better performance indexes than similar detection methods can be exerted, and the kit is particularly suitable for Chinese old people, can be widely applied to olfactory disorder detection demand scenes such as olfactory decline symptom detection, early screening of Alzheimer disease, auxiliary diagnosis of Parkinson disease and the like and preparation of related products.

Description

Olfactory disorder detection kit and preparation method thereof

Technical Field

The invention relates to a smell disturbance detection kit and a preparation method thereof, belonging to the field of detection kits.

Background

At the aspect of medical and health in China, the abnormal smell is not paid enough attention, and the research work of human smell in China is still in the initial stage of starting. Olfaction is not a routine physical examination item, and there is no general survey about olfaction capability, and no industry standard to regulate the olfaction status of workers engaged in smell (such as gas repair, fire and explosion prevention, chefs, etc.). On the other hand, in our country, accidents such as gas explosion and gas poisoning frequently occur, and tens of millions of people are afflicted with diseases such as nasal diseases (nasal trauma, allergic rhinitis, nasopharyngeal carcinoma, etc.), neurodegenerative diseases (Alzheimer's disease, AD) and Parkinson's disease, schizophrenia, etc. It has been shown by investigation that allergic rhinitis is about 17.6% in China, i.e., about 2.5 billion patients suffer from allergic rhinitis. During the allergic rhinitis, patients have symptoms of paroxysmal sneeze, watery nasal discharge, nasal obstruction, rhinocnesmus and the like, and some patients have hyposmia. Allergic rhinitis may also cause a variety of diseases including asthma, conjunctivitis, chronic rhinosinusitis, adenoids, secretory otitis media. In neurodegenerative diseases, the prevalence of AD is about 3-7% and the prevalence of PD is about 1.7-2% for people over the age of 60. The diseases have long course, progressive development of the diseases, no effective method for inhibiting the disease progress, high disability rate, more patients in middle and late stages, poor treatment effect and high treatment cost, and bring heavy mental and economic burden to families and society. Therefore, the inspection of the olfaction ability, especially the inspection of the olfaction naming ability has great significance for reducing the accident risk, early diagnosing and intervening partial mental diseases and neurodegenerative diseases and improving the life quality of people.

Olfactory naming test is used to measure the olfactory naming ability of a subject, requiring the subject to select from several options what taste is smelled. Currently in international use is the University of Pennsylvania SmellIdentification Test (UPSIT) in the United states (Doty, Shaman, & Dann, 1984). It contains 4 booklets, each of which has 10 scents (one small area per page containing scent molecules) and corresponding options. The subject swipes a block of each page with a fingernail or stylus to smell a scent, and then chooses to answer.

Currently, the above-mentioned prior olfactive naming Test has some problems to be solved urgently in China, for example, the Test is very expensive to purchase from abroad, and for example, the universal of Pennsylvania SmellIdentification Test (UPSIT) in the United states, the selling price of a single Test is about 200 RMB, and the Test can only be used once by a single person. The high cost makes the test impossible to carry out a large amount of tests and exert the effective value of the test. At present, the existing olfaction test in the domestic market can not directly give out a test result after the test is finished, and professional persons are required to further assist in analyzing and interpreting the test result.

In addition, the existing olfactory detection method adopting the paper pen recording and manual calculation mode is difficult to meet the requirements of digital data structure and large-scale calculation analysis required by group-level big data mining, and is characterized in that the reference baseline for evaluating olfactory function level cannot be updated in time and the olfactory function characteristics of the contemporary group are difficult to represent due to data filing, complex forward flow of demographic schools and rigid detection maps depicting the group. The assessment results obtained in this way are used as the basis for the risk analysis of related diseases, and the misdiagnosis rate of diseases is increased, thereby causing great physical and mental economic losses for patients and even non-patients and families. Meanwhile, with the popularization of electronic terminals, internet and database servers and the maturity of big data analysis technology, the accumulation of substances and technologies is pushing the olfactory detection to develop towards the direction of popularization, digitization, systematization, electronization and big data, and a novel olfactory function evaluation system based on human olfactory detection is promoted.

Disclosure of Invention

The invention aims to provide a smell disorder detection kit and a preparation method thereof, and the kit obtained by the invention can be used for detecting hyposmia symptoms, early screening of Alzheimer disease and auxiliary diagnosis of Parkinson disease. The kit is easy to carry, has the olfactory test effect equal to or better than that of the existing detection method, and is suitable for popularization and application.

The invention provides a kit for detecting olfactory disorder, which comprises a plurality of metal wrappings and a carrier, wherein the metal wrappings are wrappings formed by wrapping odor essence with metal, and the metal is a metal material which is solid at normal temperature, can be melted at the temperature of a human body and is nontoxic to the body surface of the human body; the flavor essence is prepared from 12 kinds of materials including menthol, garlicin, naringin, acetic acid leaf alcohol ester, nicotine, citric acid, 2-phenethyl alcohol, caffeine, limonene, acetic acid, neohesperidin, and trimethylamine.

In one embodiment of the invention, the metal is preferably metal gallium, and the metal gallium is solid at normal temperature and is used for wrapping the odor essence, and can be heated and melted into liquid after contacting the body surface of a human body to release the odor essence, so that the odor release effect and the preservation effect are facilitated.

In one embodiment of the invention, the carrier is used for mechanically supporting the metal wrap, and the carrier is selected from one or two of filter paper and polypropylene cotton sheets.

In one embodiment of the invention, the odor essence comprises 4 kinds of odors which are familiar to people and are easy to distinguish, including garlic odor, flower odor, mint odor and banana odor, and three concentration gradients are set for each odor; in order to exert the odor release effect to the best in the actual detection process, the invention selects essence substances which are more matched with the odors, and the essence substances are selected from one or more than two of menthol, allicin, naringin, acetic acid leaf alcohol ester, nicotine, citric acid, 2-phenylethyl alcohol, caffeine, limonene, acetic acid, neohesperidin and trimethylamine.

In one embodiment of the present invention, the mass ratio of solvent to fragrance in the odorous fragrance may be any suitable ratio.

In one embodiment of the invention, the kit further comprises a parkinson's disease/alzheimer's disease olfactory impairment auxiliary diagnosis card and/or an odor selection card.

In one embodiment of the present invention, the olfactive impairment auxiliary diagnosis card for parkinson's disease/alzheimer's disease is also referred to as a personal information card, and may include information such as the name, sex, age, and medical history of the subject (mainly, whether or not a nasal disease, allergy history, history of common cold in about 2 weeks, presence or absence of administration of a drug affecting the sense of smell, presence or absence of a nasal trauma surgery history, and the like).

A second object of the present invention is to provide a method for preparing the above kit, comprising: heating and melting the metal to prepare a thin-layer sphere, injecting the odor essence into the sphere by using an injector, transferring the sphere to room temperature, airing, and mounting on a carrier to obtain the kit.

It is a third object of the present invention to provide a detection apparatus comprising the above-described kit.

Compared with the prior art, the invention has the following beneficial effects:

the invention adopts a solid form, and the solid consisting of the metal gallium, the carrier and the flavor essence is used as a key component, namely a smell releaser in the detection kit, so that the kit is simple and convenient to operate, easy to carry, not easy to volatilize and deteriorate, and improves the smell test effect to a certain extent. In addition, the metal gallium can release the odor essence substances after becoming in a liquid state, and the odor essence substances can not be dissolved or adsorbed, so that the release effect of the odor essence substances is improved, and the detection accuracy is favorably improved.

Detailed Description

The present invention is further described below with reference to examples, but the embodiments of the present invention are not limited thereto.

Example 1

(1) Adding 10g of melted metal gallium into a spherical mold, standing for solidification, taking out the solidified metal gallium by using tweezers, and placing the solidified metal gallium on a tray for airing.

(2) Weighing 10mL of ethanol, putting the ethanol into a 50mL centrifuge tube, adding 0.1g of odor essence, and slightly shaking the centrifuge tube to uniformly dissolve the odor essence;

(3) the essence solution was injected into the metal ball with a syringe.

(4) And transferring the metal ball to room temperature, airing and mounting on filter paper to obtain the kit.

Example 1 contains 12 solid odor blocks, and the odors are menthol, allicin, naringin, folic acid ester, nicotine, citric acid, 2-phenylethyl alcohol, caffeine, limonene, acetic acid, neohesperidin, trimethylamine.

Example 2

(2) Weighing 10mL of ethanol, putting the ethanol into a 50mL centrifugal tube, adding 1g of odor essence, and slightly shaking the centrifugal tube to uniformly dissolve the odor essence;

(3) injecting the essence solution into the metal ball by using an injector;

(4) and transferring the metal ball to room temperature, airing and mounting on a polypropylene cotton piece to obtain the kit.

Example 2 contains 12 solid odor blocks, the odors being menthol, folic acid ester, allicin, 2-phenylethyl alcohol, acetic acid, nicotine, citric acid, caffeine, limonene, neohesperidin, naringin, trimethylamine, respectively.

Example 3

(1) Adding 10g of melted metal gallium into a spherical mold, standing for solidification, taking out the solidified metal gallium by using tweezers, and placing the solidified metal gallium on a tray for airing;

(2) weighing 10mL of ethanol, putting the ethanol into a 50mL centrifuge tube, adding 0.01g of odor essence, and slightly shaking the centrifuge tube to uniformly dissolve the odor essence;

(3) injecting the essence solution into the metal ball by using an injector;

Example 3 contains 12 solid odor blocks, and the odors are menthol, folic acid ester, garlicin, 2-phenylethyl alcohol, acetic acid, nicotine, citric acid, caffeine, limonene, neohesperidin, naringin, and trimethylamine, respectively.

Besides the key solid odor block, the kit of the invention also comprises an auxiliary diagnosis card for olfactory disorder of Parkinson disease/Alzheimer disease and/or an odor selection card, wherein the auxiliary diagnosis card for olfactory disorder of Parkinson disease/Alzheimer disease is also called as a personal information card and can contain the name, sex, age, medical history (mainly including whether a nose disease exists, allergy history, history of common cold in nearly 2 weeks, whether a drug for affecting olfactory sensation is taken or not, whether a nose trauma operation history exists or not), smoking history, existing products, the diagnosis result of the product of the invention and the like, and the specific form can refer to Table 1.

TABLE 1 Parkinson disease/Alzheimer disease dysosmia auxiliary diagnosis card

The scent selection card is a tab which is made for the selected scent and contains correct options and incorrect options, and the specific form can refer to table 2.

TABLE 2 odor selection card

Example 4 comparison of sensitivity and specificity of the detection method of the kit of the present invention and the B-SIT method

1. Aims to verify whether the olfactory detection method has higher sensitivity and specificity, PPV and NPV.

2. Study subject 60 patients with Parkinson's disease and 60 healthy control groups were selected.

(1) PD group, Parkinson disease patients come from outpatient service and ward of subsidiary hospital of south Jiangnan university, are diagnosed as Parkinson disease according to the diagnosis standard of MDS in 2015, are over 50 years old (the calculation of PD clinical precursor stage standard and risk prediction value according to MDS established by the international motion-dependent disease society in 2015 is from 50 years old), and have a sex ratio of 1: 1.

Exclusion criteria: MMSE is lower than 24 points, and olfactory diseases (rhinitis and the like) or nasal trauma and surgical history have the history of cold in nearly two weeks.

(2) The Control group is derived from a Parkinsonism of a Parkinson disease patient and a cohort of Jiangsu aged-care communities, and is matched with the cohort according to the age classification of 1: 1.

The exclusion criteria are that MMSE is less than 24 points, the patients have olfactory diseases (rhinitis and the like) or nose trauma surgical history, the patients have nearly two weeks of cold history, and the patients have clearly diagnosed neurological diseases (PD, AD and the like).

3. Study procedure all subjects received olfactory tests of two week olfactory test procedure, with 20 minutes intervening in each olfactory test procedure.

4. The olfactory test method comprises the following steps: methods based on the kit of the invention (example 1) and the U.S. B-SIT method. The U.S. B-SIT method was performed with reference to the test card front specification. The test method of the invention comprises the following steps:

(1) firstly, a subject fills in a personal information card according to the self condition to ensure that no cold exists and no corresponding disease exists in the nose;

(2) the product detection agent has 12 detection card strips in total, a subject takes out the detection card strips which are independently packaged in sequence from the minimum number (No. 1), bends three times along the virtual line on the package, opens the package bag, takes out the detection card strips, places the bending positions at the positions 2-3 cm below nostrils for smelling, and fills in answer cards (the answer cards are required to be filled according to the truest condition, otherwise, the final diagnosis result is influenced); the used detection card strips are thrown into the sealing bag (the accuracy of the test is interfered when the used detection card strips are directly thrown aside), and finally the used detection card strips are uniformly thrown into the garbage can; the next test is carried out after about 10 seconds;

(3) and checking the result. All odors are required to be completely finished, and if the odor can be smelled during the test, the odor selection is carried out, and if the odor cannot be smelled, the test of the next numbered card strip is directly carried out. The total score was calculated as the test result, and the full score was 48. Further note that: the detection is carried out in a ventilated and odor-free environment.

The scoring criteria were: no. 1-4 can smell the taste for 3 points, and can not smell the taste for no point, if can smell the taste, then the taste selection is carried out, which kind of taste can be accurately selected for 3 points, and no point can be determined; no. 5-8 can smell the taste for 2 points, and can not smell the taste for no point, if can smell the taste, then the taste selection is carried out, which kind of taste can be accurately selected for 2 points, and no point can be determined; no. 9-12 can smell 1 point of taste, and can not smell no point, if can smell taste, then make taste selection, can accurately select which kind of taste is 1 point, and can not definitely obtain point. The final full score was 48. The diagnosis standard is that the olfaction is normal if the score is higher than 32 points, the olfaction disorder is diagnosed if the score is lower than 32 points, the diagnosis method can be used as one of the support standards for the confirmed diagnosis of the Parkinson's disease and can also be used as an auxiliary basis for the prediction of the risk of the Alzheimer's disease, and the risk of the Parkinson's disease or the Alzheimer's disease progressing within several years is higher than that of a tester with normal olfaction.

In addition, in order to verify whether the kit has higher sensitivity and specificity and performance indexes such as PPV (positive predictive value) and NPV (negative predictive value), the kit and the American B-SIT method are respectively adopted to carry out olfaction tests on a Parkinson disease patient group and a healthy control group.

5. Statistical analysis was done using SPSS 19.0.

6. The results are shown in Table 3.

TABLE 3 test results

The results in the table show that the sensitivity and specificity of the kit can respectively reach 83.3% and 91.7%, and the positive predictive value PPV and the negative predictive value NPV can respectively reach 90.9% and 84.6%. Compared with the American B-SIT product and the golden pamidren, the kit provided by the invention can achieve the same effect on diagnosis of the Parkinson disease, but has better specificity, positive predicted value and negative predicted value. As both the Parkinson disease and the Alzheimer disease are neurodegenerative diseases and the olfactory system is pathologically changed in the pathogenesis, the Parkinson disease and the Alzheimer disease have similar olfactory disorder expression, and the embodiment can be expanded to olfactory decline or obstacle diseases such as the Alzheimer disease.

Although the present invention has been described with reference to the preferred embodiments, it should be understood that various changes and modifications can be made therein by those skilled in the art without departing from the spirit and scope of the invention as defined in the appended claims.

Claims

1. The olfactory disorder detection kit is characterized by comprising a plurality of metal wrappings and carriers, wherein the metal wrappings are wrappings formed by metal wrapped odor essence, and the metal is a metal material which is solid at normal temperature, can be melted at the temperature of a human body and is nontoxic to the body surface of the human body; the odor essence is 12 kinds of the following components, such as menthol, garlicin, naringin, acetic acid leaf alcohol ester, nicotine, citric acid, 2-phenethyl alcohol, caffeine, limonene, acetic acid, neohesperidin, and trimethylamine.

2. The olfactory disorder detection kit of claim 1 wherein the metal is gallium metal.

3. The olfactory disorder detection kit of claim 1 wherein the support is for mechanically supporting the metal wrap and is selected from one or both of filter paper and polypropylene cotton sheet.

4. The olfactory disorder detection kit of claim 1, wherein the mass ratio of solvent to perfume in the odorous perfume can be any suitable ratio.

5. The olfactory disorder detection kit of claim 1, further comprising a Parkinson's disease/Alzheimer's disease olfactory disorder auxiliary diagnostic card and/or an odor selection card.

6. The method for producing the kit for detecting an olfactory disorder as claimed in any of claims 1 to 5, which comprises: heating and melting the metal to prepare a thin-layer sphere, injecting the odor essence into the sphere by using an injector, transferring the sphere to room temperature, airing, and mounting on a carrier to obtain the kit.

7. A detection device comprising the olfactory disorder detection kit according to any one of claims 1 to 5.