Application of duchenne muscular dystrophy medicine in attention deficit and hyperactivity disorder and product

Abstract

The invention discloses application of a Duchenne muscular dystrophy drug in attention deficit and hyperactivity disorder and a product, and belongs to the technical field of bioengineering. Through a zebra fish attention deficit and hyperactivity disorder model, the inventor team finds that the Duchenne muscular dystrophy medicine has the effects of improving attention deficit and hyperactivity disorder diseases and has statistical significance. Therefore, when the Duchenne muscular dystrophy medicine is applied to preparation of products for treating attention deficit and hyperactivity disorder, a reliable theoretical basis is provided for a new treatment scheme.

Description

Technical Field

[0001] The present invention relates to the application of a class of drugs in attention deficit hyperactivity disorder and products, and particularly to the application of drugs for Duchenne muscular dystrophy in attention deficit hyperactivity disorder and products, belonging to the field of bioengineering technology. Background Art

[0002] Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder mainly characterized by the inability to sustain attention, hyperactivity, and emotional impulsivity. It often occurs in childhood, mostly starting in the preschool period, and is mainly divided into two types: childhood and adolescent ADHD and adult ADHD. The cause is not yet clear, but it is mostly considered to be the combined influence of multiple factors such as genetics and environment. Patients may have learning disabilities, oppositional defiant disorder, mood disorders, adjustment disorders, etc., and may thus have a greater impact on academic performance, work, and social life.

[0003] Currently, the treatment of ADHD mainly adopts a combination of psychological intervention and drug treatment. Among them, for drug treatment, the drugs involved include CFTR enhancers (Ivacaftor and VX-809), narcissus cycline, BzATP triethylammonium salt, cilengitide, guanfacine patch, etc., but there are problems such as large side effects, poor prognosis, and easy emergence of tolerance.

[0004] Therefore, there is a need to provide a drug that can improve attention deficit hyperactivity disorder for reference and theoretical basis for new treatment plans, etc. Summary of the Invention

[0005] In long-term research, the inventor team found through a zebrafish model of attention deficit hyperactivity disorder that drugs for Duchenne muscular dystrophy have the performance of improving attention deficit hyperactivity disorder, and it has statistical significance. Therefore, applying drugs for Duchenne muscular dystrophy to the preparation of products for the treatment of attention deficit hyperactivity disorder provides a reliable reference and theoretical basis for new treatment plans.

[0006] In order to achieve the above technical objectives, the following technical solutions are proposed: The first objective of this technical solution is to propose: the application of drugs for Duchenne muscular dystrophy in the preparation of products for the treatment of attention deficit hyperactivity disorder.

[0007] Further, the drugs for Duchenne muscular dystrophy include deflazacort, prednisone, prednisolone, or vamorolone.

[0008] Furthermore, in the product for treating attention deficit hyperactivity disorder, the final concentration of deflazacort is 100 ng / mL, the final concentration of prednisone is 50 ng / mL, the final concentration of prednisolone is 10 μg / mL, and the final concentration of vamorolone is 1 μM.

[0009] The second objective of this technical solution is to propose a product of a pharmaceutical composition composed of a drug for Duchenne muscular dystrophy or a pharmaceutically acceptable salt thereof as an active ingredient, as well as a pharmaceutically acceptable carrier, diluent, and excipient, wherein the product is a pharmaceutical composition for treating attention deficit hyperactivity disorder.

[0010] Furthermore, the drug for Duchenne muscular dystrophy includes deflazacort, prednisone, prednisolone, or vamorolone.

[0011] Furthermore, in the product for treating attention deficit hyperactivity disorder, the final concentration of deflazacort is 100 ng / mL, the final concentration of prednisone is 50 ng / mL, the final concentration of prednisolone is 10 μg / mL, and the final concentration of vamorolone is 1 μM.

[0012] Adopting this technical solution, the beneficial technical effects are as follows: First, the present invention first applies the drug for Duchenne muscular dystrophy to the preparation of a product for treating attention deficit hyperactivity disorder. This drug for Duchenne muscular dystrophy can significantly restore the abnormal behavioral phenotypes, providing a reliable theoretical basis for a new treatment plan for attention deficit hyperactivity disorder. Second, by establishing an ADHD zebrafish model, the present invention has sufficient evidence and strong theoretical support, and can well exhibit the symptoms and treatment effects of attention deficit hyperactivity disorder. Among them, the experimental means involved are mature technologies in the field, easy to operate, and highly expressive. Moreover, a specific drug for Duchenne muscular dystrophy is selected, which has obvious effects on the treatment of attention deficit hyperactivity disorder and is convenient for popularization and use. Description of the Drawings

[0013] Figure 1 It is a result diagram showing that the drug for Duchenne muscular dystrophy - deflazacort in Example 3 can significantly reduce the swimming distance of the larvae of the ADHD zebrafish model; Figure 2 It is a result diagram showing that the drug for Duchenne muscular dystrophy - deflazacort in Example 3 can significantly reduce the swimming speed of the larvae of the ADHD zebrafish model; Figure 3 It is a result diagram showing that the drug for Duchenne muscular dystrophy - deflazacort in Example 3 can significantly reduce the number of mirror attacks of the adult fish of the ADHD zebrafish model; Figure 4Result graph showing that deflazacort, a drug for Duchenne muscular dystrophy in Example 3, can significantly reduce the learning time of adult fish in the ADHD zebrafish model and improve their learning ability; Figure 5 Result graph showing that prednisone, a drug for Duchenne muscular dystrophy in Example 4, can significantly reduce the swimming distance of juvenile fish in the ADHD zebrafish model; Figure 6 Result graph showing that prednisone, a drug for Duchenne muscular dystrophy in Example 4, can significantly reduce the swimming speed of juvenile fish in the ADHD zebrafish model; Figure 7 Result graph showing that prednisone, a drug for Duchenne muscular dystrophy in Example 4, can significantly reduce the number of mirror attacks of adult fish in the ADHD zebrafish model; Figure 8 Result graph showing that prednisone, a drug for Duchenne muscular dystrophy in Example 4, can significantly reduce the learning time of adult fish in the ADHD zebrafish model and improve their learning ability; Figure 9 Result graph showing that prednisolone, a drug for Duchenne muscular dystrophy in Example 5, can significantly reduce the swimming distance of juvenile fish in the ADHD zebrafish model; Figure 10 Result graph showing that prednisolone, a drug for Duchenne muscular dystrophy in Example 5, can significantly reduce the swimming speed of juvenile fish in the ADHD zebrafish model; Figure 11 Result graph showing that prednisolone, a drug for Duchenne muscular dystrophy in Example 5, can significantly reduce the number of mirror attacks of adult fish in the ADHD zebrafish model; Figure 12 Result graph showing that prednisolone, a drug for Duchenne muscular dystrophy in Example 5, can significantly reduce the learning time of adult fish in the ADHD zebrafish model and improve their learning ability; Figure 13 Result graph showing that vamorolone, a drug for Duchenne muscular dystrophy in Example 6, can significantly reduce the swimming distance of juvenile fish in the ADHD zebrafish model; Figure 14 Result graph showing that vamorolone, a drug for Duchenne muscular dystrophy in Example 6, can significantly reduce the swimming speed of juvenile fish in the ADHD zebrafish model; Figure 15 Result graph showing that vamorolone, a drug for Duchenne muscular dystrophy in Example 6, can significantly reduce the number of mirror attacks of adult fish in the ADHD zebrafish model; Figure 16 Result graph showing that vamorolone, a drug for Duchenne muscular dystrophy in Example 6, can significantly reduce the learning time of adult fish in the ADHD zebrafish model and improve their learning ability. Detailed implementation method

[0014] The present invention will be further described below through specific embodiments, but this is not a limitation of the present invention. Those skilled in the art can make various modifications or improvements according to the basic idea of the present invention, but as long as they do not depart from the basic idea of the present invention, they are within the scope of the present invention.

[0015] In the following examples, the ADHD zebrafish model involved is from Soochow University and was constructed by per1b gene mutation. For details, see "Circadian Modulation of Dopamine Levels and Dopaminergic Neuron Development Contributes to Attention Deficiency and Hyperactive Behavior, DOI: 10.1523 / JNEUROSCI.2551-14.2015".

[0016] Example 1 For known Duchenne muscular dystrophy drugs, this example proposes a new use, that is, using Duchenne muscular dystrophy drugs for attention deficit and hyperactivity disorder, specifically including the application of Duchenne muscular dystrophy drugs in the preparation of products for the treatment of attention deficit and hyperactivity disorder.

[0017] Among them, the Duchenne muscular dystrophy drugs include deflazacort. Preferably, in the product for the treatment of attention deficit and hyperactivity disorder, the final concentration of deflazacort is 100 ng / mL; The Duchenne muscular dystrophy drugs include prednisone. Preferably, in the product for the treatment of attention deficit and hyperactivity disorder, the final concentration of prednisone is 50 ng / ml; The Duchenne muscular dystrophy drugs include prednisolone. Preferably, in the product for the treatment of attention deficit and hyperactivity disorder, the final concentration of prednisolone is 10 μg / mL; The Duchenne muscular dystrophy drugs include vamorolone. Preferably, in the product for the treatment of attention deficit and hyperactivity disorder, the final concentration of vamorolone is 1 μM.

[0018] Example 2 This example provides a product for the treatment of attention deficit and hyperactivity disorder, specifically: a product of a pharmaceutical composition composed of a Duchenne muscular dystrophy drug or a pharmaceutically acceptable salt thereof as an active ingredient, and a pharmaceutically acceptable carrier, diluent and excipient, and this product is a pharmaceutical composition.

[0019] Among them, in a product for the treatment of attention deficit and hyperactivity disorder, the final concentration of deflazacort is 100 ng / mL; In a product for the treatment of attention deficit and hyperactivity disorder, the final concentration of prednisone is 50 ng / ml; In a product for the treatment of attention deficit hyperactivity disorder (ADHD), the final concentration of prednisolone is 10 μg / mL; In a product for the treatment of attention deficit hyperactivity disorder (ADHD), the final concentration of vamorolone is 1 μM.

[0020] Example 3 Based on Examples 1-2, this example proposes: using the ADHD zebrafish model to discuss the use of deflazacort in the larvae and adult fish of the ADHD zebrafish model, as follows: I. Deflazacort for the larvae of the ADHD zebrafish model 1. Add deflazacort (from MCE) to the embryo medium of the fertilized eggs of the ADHD zebrafish model, and set it as the experimental group. Among them, the final concentration of deflazacort is 100 ng / mL. Continuously treat and culture for 5 days; 2. Use wild-type zebrafish (WT) and the ADHD zebrafish model as control groups respectively, and perform embryo culture under the same conditions. Among them, deflazacort is not added, and continuously treat and culture for 5 days; 3. On the 6th day of culture, detect the swimming distance and swimming speed of the corresponding larvae in the experimental group and the two control groups; The results show that: using deflazacort can significantly reduce the swimming distance and swimming speed of the larvae of the ADHD zebrafish model (as Figure 1-2 shown).

[0021] II. Deflazacort for the adult fish of the ADHD zebrafish model, as follows: 1. Inject deflazacort (from MCE) into the abdominal cavity of the adult fish (6 months) of the ADHD zebrafish model, and set it as the experimental group. Among them, the injection method refers to atg7-Based Autophagy Activation Reverses Doxorubicin-Induced Cardiotoxicity, DOI: 10.1161 / CIRCRESAHA.121.319104, and the injection amount of deflazacort is 2 mg / kg; 2. Use wild-type zebrafish (WT) and the ADHD zebrafish model as control groups respectively, and do not inject deflazacort; 3. One day after the experimental group is injected, detect the learning ability of the adult fish; at the same time, detect the learning ability of the corresponding adult fish in the two control groups; The results show that: injecting deflazacort can significantly reduce the number of mirror attacks of the adult fish of the ADHD zebrafish model, reduce the learning time, and improve its learning ability (as Figure 3-4 shown).

[0022] Example 4 Based on Examples 1-2, this example proposes: Using the ADHD zebrafish model, discuss the use of prednisone in the larvae and adult fish of the ADHD zebrafish model, specifically as follows: I. Prednisone for the larvae of the ADHD zebrafish model 1. Add prednisone (from MCE) to the embryo medium of the fertilized eggs of the ADHD zebrafish model to set up an experimental group, where the final concentration of prednisone is 50 ng / ml. Continuously treat and culture for 5 days; 2. Use wild-type zebrafish (WT) and the ADHD zebrafish model as control groups respectively, and perform embryo culture under the same conditions, where prednisone is not added, and continuously treat and culture for 5 days; 3. On the 6th day of culture, detect the swimming distance and swimming speed of the corresponding larvae in the experimental group and the two control groups; The results show that: Using prednisone can significantly reduce the swimming distance and swimming speed of the larvae of the ADHD zebrafish model (as Figure 5-6 shown).

[0023] II. Prednisone for the adult fish of the ADHD zebrafish model, specifically as follows: 1. Intraperitoneally inject prednisone (from MCE) into the adult fish (6 months old) of the ADHD zebrafish model to set up an experimental group, where the injection method refers to atg7-Based Autophagy Activation Reverses Doxorubicin-Induced Cardiotoxicity, DOI: 10.1161 / CIRCRESAHA.121.319104, and the injection dose of prednisone is 2 mg / kg; 2. Use wild-type zebrafish (WT) and the ADHD zebrafish model as control groups respectively, and do not inject prednisone; 3. One day after the experimental group is injected, detect the learning ability of the adult fish; at the same time, detect the learning ability of the corresponding adult fish in the two control groups; The results show that: Injecting prednisone can significantly reduce the number of mirror attacks of the adult fish of the ADHD zebrafish model, reduce the learning time, and improve its learning ability (as Figure 7-8 shown).

[0024] Example 5 Based on Examples 1-2, this example proposes: Using the ADHD zebrafish model, discuss the use of prednisolone in the larvae and adult fish of the ADHD zebrafish model, specifically as follows: I. Prednisolone for the larvae of the ADHD zebrafish model 1. Add prednisolone (from MCE) to the embryo medium of the fertilized eggs of the ADHD zebrafish model to set up an experimental group, where the final concentration of prednisolone is 10 μg / mL. Continuously treat and culture for 5 days; 2. Use wild-type zebrafish (WT) and the ADHD zebrafish model as control groups respectively, and conduct embryo culture under the same conditions, where prednisolone is not added, and continuously treat and culture for 5 days; 3. On the 6th day of culture, detect the swimming distance and swimming speed of the corresponding larvae in the experimental group and the two control groups; The results show that: Using prednisolone can significantly reduce the swimming distance and swimming speed of the larvae of the ADHD zebrafish model (as Figure 9-10 shown).

[0025] II. Prednisolone is used for the adult fish of the ADHD zebrafish model, specifically as follows: 1. Inject prednisolone (from MCE) into the abdominal cavity of the adult fish (6 months old) of the ADHD zebrafish model to set up an experimental group. The injection method refers to atg7-Based Autophagy Activation Reverses Doxorubicin-Induced Cardiotoxicity, DOI: 10.1161 / CIRCRESAHA.121.319104, and the injection dose of prednisolone is 2 mg / kg; 2. Use wild-type zebrafish (WT) and the ADHD zebrafish model as control groups respectively, and do not inject prednisolone; 3. One day after the experimental group is injected, detect the learning ability of the adult fish; at the same time, detect the learning ability of the corresponding adult fish in the two control groups; The results show that: Injecting prednisolone can significantly reduce the number of mirror attacks of the adult fish of the ADHD zebrafish model, reduce the learning time, and improve its learning ability (as Figure 11-12 shown).

[0026] Example 6 Based on Examples 1-2, this example proposes: Using the ADHD zebrafish model, discuss the use of vamorolone for the larvae and adult fish of the ADHD zebrafish model, specifically as follows: I. Vamorolone is used for the larvae of the ADHD zebrafish model 1. Add vamorolone (from MCE) to the embryo medium of the fertilized eggs of the ADHD zebrafish model to set up an experimental group, where the final concentration of vamorolone is 1 μM. Continuously treat and culture for 5 days; 2. Another, using wild-type zebrafish (WT) and the ADHD zebrafish model as control groups respectively, embryo culture was carried out under the same conditions. Among them, vamorolone was not added, and the culture was continuously treated for 5 days; 3. On the 6th day of culture, the swimming distance and swimming speed of the corresponding larvae in the experimental group and the two control groups were detected; The results showed that: the use of vamorolone could significantly reduce the swimming distance and swimming speed of the larvae of the ADHD zebrafish model (as Figure 13-14 shown).

[0027] II. Vamorolone was used in adult ADHD zebrafish models as follows: 1. Adult ADHD zebrafish models (6 months old) were intraperitoneally injected with vamorolone (from MCE Company) to set up the experimental group. Among them, the injection method referred to atg7-Based Autophagy Activation Reverses Doxorubicin-Induced Cardiotoxicity, DOI: 10.1161 / CIRCRESAHA.121.319104, and the injection dose of vamorolone was 2 mg / kg; 2. Using wild-type zebrafish (WT) and the ADHD zebrafish model as control groups respectively, neither was injected with vamorolone; 3. One day after the experimental group was injected, the learning ability of the adult fish was detected; at the same time, the learning ability of the corresponding adult fish in the two control groups was detected; The results showed that: injecting vamorolone could significantly reduce the number of mirror attacks of the adult fish of the ADHD zebrafish model, reduce the time of its learning, and improve its learning ability (as Figure 15-16 shown).

Claims

1. Use of Duchenne muscular dystrophy drugs in the preparation of products for the treatment of attention deficit and hyperactivity disorder.

2. The use according to claim 1, characterized in that: The Duchenne muscular dystrophy medications include deflazacort, prednisone, prednisolone or vamololone.

3. The use according to claim 2, characterized in that: In the product for treating attention deficit hyperactivity disorder, the final concentration of deflazacort is 100 ng / mL, the final concentration of prednisone is 50 ng / ml, the final concentration of prednisolone is 10 μg / mL, and the final concentration of vamololone is 1 μM.

4. A product of a pharmaceutical composition comprising a Duchenne muscular dystrophy drug or a pharmaceutically acceptable salt thereof as an active ingredient, and a pharmaceutically acceptable carrier, diluent and excipient, wherein: The product is a pharmaceutical composition for treating attention deficit hyperactivity disorder.

5. The product according to claim 4, characterized in that: The Duchenne muscular dystrophy medications include deflazacort, prednisone, prednisolone or vamololone.

6. The product according to claim 5, characterized in that: In the product for treating attention deficit hyperactivity disorder, the final concentration of deflazacort is 100 ng / mL, the final concentration of prednisone is 50 ng / ml, the final concentration of prednisolone is 10 μg / mL, and the final concentration of vamololone is 1 μM.

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