Application of xenon for treating autism and testing method of xenon

Abstract

The invention discloses an application of xenon in preparation of a medicament for preventing or treating autism. The volume fraction of xenon in the medicament is 25%. The application of the xenon as the medicine for improving the autism is found for the first time, the problem that a clinical medicine with an exact curative effect on the core behavior of the autism is lacked at present is solved, and through behavioral testing and ANY-maze animal behavioral analysis, 25% of xenon has the effect of improving the self-closing behavior of an autism mouse model and has the advantages of being safe and effective.

Description

Technical Field

[0001] The present invention relates to the technical field of autism treatment, in particular to the technical field of using xenon for treating autism. Background Art

[0002] Autism, also known as Autism Spectrum Disorder (ASD), is a neurological developmental disorder disease characterized by social interaction / communication disorders, repetitive stereotyped behaviors, and restricted interests; its prevalence rate is 1.5% - 2.3%; currently, the clinical treatment of ASD mainly includes behavioral therapy and drug therapy, including risperidone, aripiprazole, clozapine, sertraline, and haloperidol; these treatment methods can partially improve the symptoms of children in aspects such as irritability, hyperactivity, sleep disorders, cognitive function, and language communication; unfortunately, currently only behavioral therapy has a certain effect on the core behaviors of autism, and there is still no drug with a definite effect on the core behaviors of autism.

[0003] Xenon (Xe) is a rare inert gas, which was first applied to the human body in 1951; the safety of xenon as an anesthetic drug is relatively high, it will not have a serious inhibitory effect on the brain and cardiovascular system, nor will it cause serious side effects. When using xenon anesthesia, patients usually recover faster and the recovery period after anesthesia is shorter; generally, the concentration of xenon used for anesthesia is between 40% and 75%, and the xenon concentration within this range can produce an ideal anesthetic effect and has high safety.

[0004] Recent studies have shown that xenon at sub-anesthetic concentrations (<30%) has strong neuroprotective effects and has no obvious side effects even on newborns. The patent document with the publication number CN107569509B discloses the use of xenon or a xenon gas mixture in the preparation of a preparation for treating epilepsy, and this patent does not disclose the use of xenon for treating autism.

[0005] The patent document with the publication number CN110337297A treats anxiety by administering a mixture containing an inert gas, and administers a xenon-oxygen or xenon-oxygen-nitrogen mixture at sub-anesthetic concentrations. This patent provides the use of a mixture containing an inert gas at a sufficient concentration and frequency for preventing panic attacks and / or inhibiting the frequency of panic attacks; when testing this use, a xenon-oxygen mixture is administered to the patient through a face mask. After the treatment is completed, it is necessary to use clinical psychopathological and post-clinical medical record methods, as well as internationally widely used psychological scales to evaluate the treatment of psychosis. Scale evaluations are performed before the start of the therapy (VI) and at the 1st and 6th months after the treatment, using the Zung Self-Rating Anxiety Scale (SAS); this testing method takes too much time, and the test results may be affected by the outside world and cannot well reflect the specific effects of xenon. Summary of the Invention

[0006] The object of the present invention is to solve the problems in the prior art, and to propose the use of xenon for manufacturing a medicament for preventing or treating autism, which can solve the above problems.

[0007] To achieve the above object, the present invention proposes a use of xenon for manufacturing a medicament for preventing or treating autism.

[0008] Preferably, the volume fraction of xenon in the medicament is 15% - 30%, the volume fraction of oxygen is 30% - 40%, and the balance is air or nitrogen.

[0009] Preferably, the volume fraction of xenon in the medicament is 25%.

[0010] The present invention also proposes a verification method for the above use, including the following steps: S1. Construct an autism mouse model; S2. Conduct behavioral tests on the autism mice; S3. Treat the autism mice with the medicament by xenon, Treat for 10 minutes every day, and the treatment cycle is 10 days; the volume fraction of xenon in the medicament is 25%; S4. Conduct behavioral tests and data analysis on the autism mice 2 days after the treatment ends; S5. Conduct behavioral tests and data analysis on the autism mice again 9 days after the treatment ends.

[0011] Preferably, the behavioral tests include novel object recognition test, three - chamber social test, and Y - maze test.

[0012] Advantages of the present invention: The present invention discovers for the first time the use of xenon as a drug for improving autism, solves the problem of the lack of clinical drugs with definite curative effects on the core behaviors of autism. Through behavioral tests and ANY - maze animal behavior analysis, 25% xenon has the effect of improving the autistic behavior of the autism mouse model, and has the characteristics of safety and effectiveness.

[0013] The features and advantages of the present invention will be described in detail through examples in combination with the drawings. Brief Description of the Drawings

[0014] Figure 1 is the flow chart of xenon treatment of the present invention; Figure 2 is the schematic diagram of the xenon treatment device of the present invention; Figure 3 is the schematic diagram of the behavioral test of the present invention; Figure 4It is Mef2cL35P of the present invention + / - Schematic diagram of the behavioral results of male mice; Figure 5 It is a schematic diagram of the behavioral results of Mef2cL35P+ / - female mice of the present invention; Figure 6 It is Shank3 of the present invention - / - Schematic diagram of the behavioral results of male mice; Figure 7 It is Shank3 of the present invention - / - Schematic diagram of the behavioral results of female mice. Detailed implementation manners

[0015] Refer to Figures 1 to 7 , a use of xenon for manufacturing a medicament for preventing or treating autism; the volume fraction of xenon in the medicament is 25%, the volume fraction of oxygen is 30%-40%, and the balance is air or nitrogen.

[0016] A mouse autism model was constructed by continuously intraperitoneally injecting valproic acid (VPA) into mouse pups at 6-12 days after birth. It was found that during the intervention with sub-anesthetic concentration of xenon, the social behavior, exploratory behavior and depressive-like behavior of ASD mice were significantly improved; further, a mouse autism model was constructed by intraperitoneally injecting VPA during pregnancy, and the 2-3-week-old autistic mouse pups were intervened with sub-anesthetic concentration of xenon. After 2 weeks (at 4-5 weeks of age), the social deficits and stereotyped behaviors of the mouse pups were still significantly improved; these indicate that the intervention with sub-anesthetic concentration of xenon has a therapeutic effect on the core symptoms of the autism model animals constructed by VPA.

[0017] Verification process: S1. Construct an autism mouse model; 8-week-old Mef2cL35P + / - and Shank3 - / - Autism model mice were purchased from Shanghai Songjiang Research Institute and Beijing Vitalstar Biotechnology Co., Ltd. respectively.

[0018] S2. Conduct behavioral tests on the autism mice; Autism shows symptoms such as social interaction, communication disorders, repetitive stereotyped behaviors, and restricted interests.

[0019] The behavioral tests include novel object recognition test, three-chamber social test, and Y-maze test.

[0020] The experimental procedure for novel object recognition is as follows: The mice are allowed to adapt in the open field for 5 min, and then two objects A1 and A2 with exactly the same size, shape and color are placed. The mice are allowed to become familiar with them for 10 min. After an interval of 1 h, A2 is replaced with an object B with different size, shape and color, and the mice are filmed for 10 min to record their recognition of the new and old objects.

[0021] The calculation formula is: Exploration time of new object / (Exploration time of new object + Exploration time of old object).

[0022] The experimental procedure of the three-chamber social experiment is as follows: The mouse is acclimated in the middle chamber of the three chambers for 5 min. A strange mouse 1 is placed in one of the cages. The transparent baffles on both sides are opened, and the mouse's social stage is recorded by video for 10 min. A strange mouse 2 is placed in the other cage, and the mouse's social difference stage is recorded by video for 10 min.

[0023] The calculation formula is: Exploration time of strange mouse 2 / (Exploration time of strange mouse 1 + Exploration time of strange mouse 2); The experimental procedure of the Y-maze experiment is as follows: A baffle is inserted on one side of the Y-maze. The mouse is placed in the starting arm, explores the open area (starting arm and old arm) for 5 min, and then the mouse is taken out. After an interval of 1 h, the baffle is opened, and the mouse is placed in the starting arm again, and the mouse's Y-maze exploration behavior is recorded by video for 5 min.

[0024] The calculation formula is: Exploration time of new arm / (Exploration time of new arm + Exploration time of old arm).

[0025] After the ANY-maze ethological analysis, the experimental statistical results are obtained. The data is processed using the SAS 9.2 statistical analysis software. If the P value is less than or equal to 0.05, it is considered that there is a difference between the experimental group and the control group.

[0026] After testing, the new object recognition ability, social recognition ability, and desire to explore the new arm of the mouse are all significantly lower than those of wild-type mice.

[0027] S3. Use the said medicament to perform xenon treatment on autistic mice. 12 - 15 autistic model mice are subjected to 25% xenon treatment for 10 days, once a day, and the treatment duration each time is 10 minutes. 12 - 15 wild-type mice of the same size are subjected to air treatment for 10 days, once a day, and the treatment duration each time is 10 minutes.

[0028] The xenon treatment is performed using a xenon treatment device. The xenon treatment device includes a treatment chamber. The mouse is placed in the treatment chamber. One side of the treatment chamber is provided with an air inlet, the other side of the chamber is provided with an air outlet. The air inlet is connected to a xenon gas source. A carbon dioxide adsorbent is provided in the treatment chamber, and a gas detector is provided in the treatment chamber.

[0029] In the present invention, the autistic model mouse is placed in the treatment chamber, which does not affect its normal activities, can avoid the influence of the treatment behavior on the experiment, and makes the experimental results more credible.

[0030] S4. After the treatment, behavioral tests and ANY-maze data analysis are performed after an interval of 2 days (i.e., the 13th day).

[0031] S5. Nine days after the treatment ended, the behavioral tests and data analysis were performed on the autistic mice again.

[0032] As Figure 4 , 5 shown, for the 8-week-old Mef2cL35P + / - autistic model mice (separated by male and female), compared with the control group, the results of the behavioral tests showed that the abilities of novel object recognition, social recognition, and the desire to explore new arms were significantly lower than those of wild-type mice.

[0033] After 10 days of treatment with 25% xenon, the duration of each treatment was 10 minutes.

[0034] Two days after the treatment ended (i.e., on the 13th day), the behavioral tests and data analysis were carried out. The data showed that the core behaviors of the autistic model mice were significantly improved.

[0035] Nine days after the treatment ended (i.e., on the 20th day), the behavioral test data showed that the core behaviors of the autistic model mice were significantly improved.

[0036] As Figure 6 , 7 shown, for the 8-week-old Shank3 - / - autistic model mice (separated by male and female), the abilities of novel object recognition, social recognition in the three-chamber social test, and exploration of new arms in the Y-maze were significantly lower than those of C57BL / 6 wild-type mice.

[0037] After 10 days of treatment with 25% xenon, the duration of each treatment was 10 minutes.

[0038] Two days after the treatment ended (i.e., on the 13th day), the behavioral tests and data analysis were carried out. The data showed that the core behaviors of the autistic model mice were significantly improved.

[0039] Nine days after the treatment ended (i.e., on the 20th day), the behavioral test data showed that the core behaviors of the autistic model mice were significantly improved.

[0040] In the situation where there is a lack of drugs to improve the core behaviors of autism at home and abroad, the treatment with the rare gas xenon can become a new breakthrough and innovation point.

[0041] The above embodiments are illustrative of the present invention, not restrictive of the present invention. Any simple transformation of the present invention also falls within the protection scope of the present invention.

Claims

1. Use of xenon in the manufacture of a medicament for preventing or treating autism.

2. The use according to claim 1, characterized in that: In the medicament, the volume fraction of xenon is 15% - 30%, the volume fraction of oxygen is 30% - 40%, and the balance is air or nitrogen.

3. The use according to claim 2, characterized in that: The volume fraction of xenon in the medicament is 25%.

4. The use according to claim 1, wherein: The verification method of the above use includes the following steps: S1. Construct an autism mouse model; S2. Conduct behavioral tests on the autism mice; S3. Treat the autism mice with xenon using the above medicament; Treat for 10 minutes every day, and the treatment cycle is 10 days. The volume fraction of xenon in the medicament is 25%; S4. Conduct behavioral tests and data analysis on the autism mice 2 days after the treatment ends; S5. Conduct behavioral tests and data analysis on the autism mice again 9 days after the treatment ends.

5. The use according to claim 4, wherein: The behavioral tests include novel object recognition test, three - chamber social test and Y - maze test.

6. The use according to claim 4, wherein: In S3, xenon treatment is carried out using a xenon treatment device. The xenon treatment device includes a treatment chamber. The mouse is placed in the treatment chamber. One side of the treatment chamber is provided with an air inlet, the other side of the chamber is provided with an air outlet. The air inlet is connected to a xenon gas source. A carbon dioxide adsorbent is provided in the treatment chamber, and a gas detector is provided in the treatment chamber.

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