Medicine for treating autism and application thereof

Abstract

The invention discloses a medicine for treating autism, application of the medicine for treating autism in preparation of a medicine for improving social competence damage of autism animals or people, and application of the medicine for treating autism in preparation of a medicine for improving anxiety behaviors of autism animals or people. When the high-dose vitamin D is used for intervening autism mice, the method has the advantages of being economical, convenient to take and good in effect, animal experiment evidence is provided for supplementing large-dose VD to intervene autism spectrum disorders in the early stage of clinical experiments, and a new thought is provided for early prevention and treatment of neurodevelopment disorders of clinical children.

Description

Technical Field

[0001] The present invention relates to the technical field of medicines for developmental disorders, and more specifically to a medicine for treating autism and its application. Background Art

[0002] Autism spectrum disorder (ASD) is a serious developmental disorder. Children with ASD will show varying degrees of language communication barriers, stereotyped repetitive behaviors, social skills defects, narrow interests and hobbies, etc. The disease develops in childhood and most patients are unable to take care of themselves. There is no specific treatment drug, and behavioral intervention is ineffective. The disease often persists for life, which not only seriously affects the children's quality of life, but also brings huge burdens to their families and society. Summary of the invention

[0003] To this end, the technical problem to be solved by the present invention is to provide a drug for treating autism and its application, which uses high-dose vitamin D to intervene in autistic mice, has the advantages of being economical, convenient to administer, and having good effects, and provides animal experimental evidence for early clinical trials of supplementing high-dose VD to intervene in autism spectrum disorders, as well as providing new ideas for the early prevention and treatment of clinical children's neurodevelopmental disorders.

[0004] In order to solve the above technical problems, the present invention provides the following technical solutions:

[0005] A drug for autism that includes vitamin D.

[0006] Furthermore, the content of vitamin D in the medicine is 1000-5000 IU / kg.

[0007] Furthermore, the content of vitamin D in the medicine is 5000 IU / kg.

[0008] Use of a drug for treating autism in the preparation of a drug for improving social ability impairment in autistic animals or humans, wherein the drug comprises vitamin D.

[0009] Use of a drug for treating autism in the preparation of a drug for improving anxiety-like behavior of autistic animals or humans, wherein the drug comprises vitamin D.

[0010] The technical solution of the present invention achieves the following beneficial technical effects:

[0011] Oral high-dose vitamin D intervention in autistic mice has the advantages of being economical, easy to administer, and having good effects. It provides animal experimental evidence for early clinical trials of high-dose VD supplementation to intervene in autism spectrum disorders, and provides new ideas for the early prevention and treatment of clinical pediatric neurodevelopmental disorders. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] Figure 1 A schematic diagram of a behavioral room for a three-box social experiment of a drug for treating autism and its application in the present invention;

[0013] Figure 2 A schematic diagram of a drug for treating autism and social ability detection using the drug according to the present invention;

[0014] Figure 3 A schematic diagram of an elevated plus maze device for an elevated plus maze experiment of a drug for treating autism and its application in the present invention;

[0015] Figure 4 A schematic diagram of the results of an elevated plus maze experiment of a drug for treating autism of the present invention and its application. DETAILED DESCRIPTION

[0016] Example

[0017] 1. Building an autism model

[0018] Maternal immune activation (MIA) was simulated by treating C57 mice with a double-stranded RNA (dsRNA) analog polyinosinic:polycytidylic acid (Pol y(I:C)) at 12.5 days of gestation. Maternal separation (MS) was performed starting on the second day after the offspring were born, 3 hours / day, for 14 days, to construct an autism model of maternal immune activation combined with maternal separation.

[0019] 2. Experimental groups:

[0020] Control group (PBS): C57 mice, 6 cases, the mother mice were intraperitoneally injected with the same volume of PBS (injection volume of polyinosinic:polycytidylic acid / g) at 12.5 days of pregnancy, during which the mothers and offspring were fed with ordinary feed (VD 1000I U / kg).

[0021] Experimental group 1 (M IA+MS+normal feed): C57 strain mice, 6 cases, 20 mg / kg of polyinosinic: polycytidylic acid (Poly (I:C)) was intraperitoneally injected into the mother mice at 12.5 days of pregnancy, and mother-to-child separation (MS) was performed starting on the second day after the offspring were born, and continued for 14 days, 3 hours / day.

[0022] After the offspring were weaned at 3 weeks of age, the mother and offspring were raised separately. When the mice were 6-8 weeks old, the autism model was verified through animal behavior experiments (three-box social test, elevated plus maze test). During this period, the mother and offspring were fed with ordinary feed (VD 1000I U / kg).

[0023] Experimental Group 2 (M IA+MS+VD5000): C57 mice, 6 cases. After the thrombus was checked in the morning of the next day after cage combination (0.5 days of pregnancy), the mothers were fed with a high-dose vitamin D feed (containing VD 5000I U / kg). At 12.5 days of pregnancy, 20 mg / kg of polyinosinic: polycytidylic acid (Poly (I:C)) was injected intraperitoneally. From the second day after the offspring were born, the mother-infant separation was carried out for 14 days, 3 hours / day.

[0024] After the offspring were weaned at 3 weeks of age, the mother and offspring were raised separately, and the offspring continued to be fed with high-dose vitamin D feed (containing VD 5000I U / kg). When the offspring were 6-8 weeks old, mouse behavioral experiments (three-box social test, elevated plus maze test) were conducted to verify the improvement of autism symptoms.

[0025] 3. Behavioral Implementation Methods

[0026] ①Three-box social experiment:

[0027] The experiment used Figure 1 The 60×40×22cm transparent box shown in the figure was used as the behavioral room. Two removable transparent boards were used to divide the interior of the transparent box into three chambers: S1 area, S2 area, and the middle area between S1 area and S2 area. There was a 5×8cm sliding door on each of the two removable boards. After removing the removable boards, the three chambers were interconnected, and the mice could move freely inside. During the experiment, a metal cage with a restraining function was placed in each of the two chambers in the S1 area and the S2 area. The metal cage was used to place unfamiliar mice. 30 minutes before the start of the experiment, the experimental mice and the unfamiliar mice were transported to the behavioral room to familiarize themselves with the environment. The control group, experimental group 1 mice, and experimental group 2 mice were subjected to the following two-stage experiment.

[0028] Phase 1: Adaptation to the environment. Place a metal cage at the same position in each of the two chambers in the S1 area and the S2 area. Put the same building blocks in the metal cage. Put the experimental mouse in the chamber in the middle area. Open the sliding door and let it move freely for 5 minutes.

[0029] Phase II: Social ability test. The first stranger mouse was placed in the metal cage in the chamber of the S1 area. The stranger mouse was a mouse of the same age and gender from a different litter than the experimental mouse, and was recorded as stranger1. The metal cage with building blocks was still placed in the S2 area, and was recorded as stranger2. Then the experimental mouse was released from the chamber of the middle area, the sliding door was opened, and it was allowed to move freely for 10 minutes and recorded. Then the experimental mouse was sent back to the chamber of the middle area and the sliding door was closed.

[0030] The movement trajectory and distance of the experimental mice, the number of times they entered each chamber, and the exploration time of the unfamiliar mice or the metal cage with building blocks were recorded. During the test, the test environment was kept quiet and the light intensity was 30 Lux. After the experiment, the experimental mice and the unfamiliar mice were put back into the breeding cages, and the experimental equipment was cleaned with 75% ethanol.

[0031] ②Elevated plus maze test:

[0032] The experimental device used Figure 3 The elevated plus maze shown in the figure consists of a middle connecting platform (10×10 cm), two open arms and two closed arms. The arm length of the open arm and the closed arm is 30 cm and the arm width is 6 cm. There are 15 cm high wall panels on both sides of the closed arm. The color of the device is gray and opaque, and the height is 50 cm from the ground. 30 minutes before the start of the experiment, the experimental mice were transported to the behavior room to familiarize themselves with the environment. During the experiment, the control group (PBS), experimental group 1 (M IA+MS+ordinary feed) mice and experimental group 2 (M IA+MS+VD5000) mice were placed on the middle connecting platform with their backs to the experimenters and allowed to explore freely. The situations of the control group (PBS), experimental group 1 (M IA+MS+ordinary feed) mice and experimental group 2 (M IA+MS+VD5000) mice entering the open arms and closed arms within 10 minutes were recorded respectively.

[0033] During the test, the environment was kept quiet and the light intensity was 30 Lux. At the end of the experiment, the experimental device was cleaned with 75% ethanol.

[0034] 4. Experimental results

[0035] ① The second phase of the three-box social experiment tested the social ability of mice. The results are as follows Figure 2 As shown in the figure, ** represents a statistical P value <0.01, *** represents a statistical P value <0.001, the smaller the P value, the more significant the difference in the activity time of the experimental mice in the S1 and S2 areas. In the control group, normal mice were obviously more interested in the mice in the S1 area during the social ability detection phase, rather than the empty cages in the S2 area. There was no difference in the activity time of the experimental mice in the S1 area (stranger1) and the S2 area (stranger2) in the experimental group 1 (M IA+MS+ordinary feed), indicating that the experimental mice in the experimental group 1 had autism-like manifestations of impaired social ability.

[0036] The activity time of mice in experimental group 2 (M IA+MS+VD5000) in the S1 area (stranger1) was significantly higher than that in the S2 area (stranger2), indicating that after the intervention of high-dose VD in autistic mice, the social ability impairment of the mice was improved.

[0037] ② The elevated plus maze test was used to detect whether the animals had anxiety-like behaviors. Figure 4 As shown in the figure, the proportion of time that the mice in experimental group 1 (MIA+MS+ordinary diet) spent on the open arms was significantly lower than that in the control group (PBS), indicating that the mice in experimental group 1 (MIA+MS+ordinary diet) had anxiety-like behavior. The proportion of time that the mice in experimental group 2 (MIA+MS+VD5000) spent on the open arms was significantly higher than that in experimental group 1 (MIA+MS+ordinary diet), indicating that the anxiety behavior of the autism model mice after high-dose vitamin D intervention was significantly improved.

[0038] After behavioral verification, it was found that autistic mice treated with high-dose vitamin D showed significant improvements in social skills, anxiety symptoms, etc.

[0039] Therefore, using oral high-dose vitamin D to intervene in autistic mice has the advantages of being economical, convenient to administer, and having good effects. It provides animal experimental evidence for the early supplementation of high-dose VD in clinical trials to intervene in autism spectrum disorders, and provides new ideas for the early prevention and treatment of clinical neurodevelopmental disorders in children.

[0040] Obviously, the above embodiments are merely examples for the purpose of clear explanation, and are not intended to limit the implementation methods. For those skilled in the art, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to list all the implementation methods here. The obvious changes or modifications derived therefrom are still within the scope of protection of the claims of this patent application.

Claims

1. A drug for treating autism, characterized in that: Including vitamin D.

2. The drug for treating autism according to claim 1, characterized in that: The content of vitamin D in the medicine is 1000-5000 IU / kg.

3. The drug for treating autism according to claim 2, characterized in that: The content of vitamin D in the medicine is 5000 IU / kg.

4. Use of a drug for treating autism in the preparation of a drug for improving the social ability impairment of autistic animals or humans, characterized in that: The drug includes vitamin D.

5. Use of a drug for treating autism in the preparation of a drug for improving anxiety-like behavior in autistic animals or humans, characterized in that: The drug includes vitamin D.

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