Use of composition in preparation of drug

Abstract

A use of a composition in the preparation of a drug. The composition comprises taurine and a β-blocker.

Description

Use of a composition in the manufacture of a medicament TECHNICAL FIELD

[0001] The present application relates to the field of biological medicine, in particular to a composition and its use in treating autism spectrum disorder. BACKGROUND

[0002] Autism spectrum, commonly referred to as autism, is a professional diagnosis of autism spectrum disorder (English: autism spectrum disorders, ASD; or autism spectrum conditions, ASC), which belongs to the syndrome of neurodevelopmental disorders. Its main clinical manifestations are abnormality in the nature of social interaction and communication mode, limitation, stereotypy and repetition of interest and activity content. Some patients also have intellectual deficiency, cognitive development delay or retardation, and loss of acquired developmental skills after a certain period of normal development. The epidemiological survey in 2011 showed that the current incidence of ASD in the world is estimated to be about 1%. In China, there are about 650,000 patients with severe autism, and about 5 million people with mild symptoms.

[0003] There is no specific drug for ASD at present, and the main treatment method is to improve the social interaction ability of patients, master the life skills and learning skills through education and training, and assist with drugs to reduce the symptoms of complications. The anti-psychotic drug has been approved for the treatment of autism. The U.S. FDA approved risperidone in 2006 and aripiprazole in 2009 for the treatment of young ASD patients. This kind of drug mainly regulates the dopamine in the brain, and is used to improve the irritability and aggression of ASD patients. However, recent studies have shown that this kind of drug can cause metabolic abnormalities, extrapyramidal reactions, gastrointestinal symptoms, and some patients also have suicidal ideation and behavior.

[0004] Therefore, there is still a need in the art for methods of treating and reducing the severity and incidence of symptoms associated with autism spectrum disorder. SUMMARY

[0005] The present application provides a combination therapy of taurine and β-receptor blocker, which can treat autism spectrum disorder or improve the related symptoms of patients with autism spectrum disorder. Moreover, the combination therapy of taurine and β-receptor blocker is superior to the use of taurine and β-receptor blocker alone in improving the symptoms of autism spectrum disorder.

[0006] In one aspect, the present application provides a use of a composition in the manufacture of a medicament, wherein the composition comprises taurine and a β-receptor blocker.

[0007] In certain embodiments, wherein the beta-receptor blocker is selected from the group consisting of a beta1 receptor selective beta-receptor blocker, a beta2 receptor selective beta-receptor blocker, a mixed alpha and beta-receptor blocker, and / or a non-selective beta-receptor blocker.

[0008] In certain embodiments, wherein the beta-receptor blocker is selected from the group consisting of Atenolol, Metoprolol, Carvedilol, Labetalol, Propranolol, Bisoprolol, Propafenone, and pharmaceutically acceptable salts thereof.

[0009] In certain embodiments, wherein the beta-receptor blocker is Atenolol or a pharmaceutically acceptable salt thereof. In certain embodiments, wherein the beta-receptor blocker is Metoprolol or a pharmaceutically acceptable salt thereof. In certain embodiments, wherein the beta-receptor blocker is selected from the group consisting of Metoprolol succinate and Metoprolol tartrate. In certain embodiments, wherein the beta-receptor blocker is Carvedilol or a pharmaceutically acceptable salt thereof. In certain embodiments, wherein the beta-receptor blocker is Carvedilol phosphate. In certain embodiments, wherein the beta-receptor blocker is Labetalol or a pharmaceutically acceptable salt thereof. In certain embodiments, wherein the beta-receptor blocker is Labetalol hydrochloride. In certain embodiments, wherein the beta-receptor blocker is Propranolol or a pharmaceutically acceptable salt thereof. In certain embodiments, wherein the beta-receptor blocker is Propranolol hydrochloride. In certain embodiments, wherein the beta-receptor blocker is Bisoprolol or a pharmaceutically acceptable salt thereof. In certain embodiments, wherein the beta-receptor blocker is Bisoprolol fumarate. In certain embodiments, wherein the beta-receptor blocker is Propafenone or a pharmaceutically acceptable salt thereof. In certain embodiments, wherein the beta-receptor blocker is Propafenone hydrochloride.

[0010] In certain embodiments, wherein the mass ratio of taurine and derivatives thereof to the beta-receptor blocker is 80: 1 to 2: 1. In certain embodiments, wherein the mass ratio of taurine and derivatives thereof to the beta-receptor blocker is 40: 1 to 1: 1. In certain embodiments, wherein the mass ratio of taurine and derivatives thereof to the beta-receptor blocker is 80: 1, 40: 1, 20: 1, 200: 15, 8: 1, 100: 15, 4: 1, 16: 5, 2: 1, or 1: 1.

[0011] In certain embodiments, wherein the composition has one or more of the following functions: improving memory impairment, improving social impairment, improving speech and communication impairment, reducing repetitive stereotypic behavior, improving sensory ability deficits, and improving motor ability deficits.

[0012] In certain embodiments, wherein the composition has one or more of the following functions: improving memory impairment in autism spectrum patients, improving social impairment in autism spectrum disorder patients, improving speech communication impairment in autism spectrum disorder patients, reducing repetitive stereotyped behavior in autism spectrum disorder patients, improving sensory ability deficits in autism spectrum disorder patients, improving motor ability deficits in autism spectrum disorder patients, and improving self-care ability in autism spectrum disorder patients.

[0013] In certain embodiments, wherein the composition has one or more of the following functions: rescuing social preference in autism spectrum disorder patients, rescuing social memory in autism spectrum disorder patients, rescuing empathic ability in autism spectrum disorder patients, rescuing spatial memory in autism spectrum disorder patients.

[0014] In certain embodiments, wherein the medicament is used for improving memory impairment, improving social impairment, improving speech communication impairment, reducing repetitive stereotyped behavior, improving sensory ability deficits, and / or improving motor ability deficits.

[0015] In certain embodiments, wherein the medicament is used for treating autism spectrum disorder.

[0016] In certain embodiments, wherein the medicament is used for improving memory impairment in autism spectrum patients, improving social impairment in autism spectrum disorder patients, improving speech communication impairment in autism spectrum disorder patients, reducing repetitive stereotyped behavior in autism spectrum disorder patients, improving sensory ability deficits in autism spectrum disorder patients, improving motor ability deficits in autism spectrum disorder patients, and improving self-care ability in autism spectrum disorder patients.

[0017] In certain embodiments, wherein the medicament comprises a pharmaceutical composition, further comprising a pharmaceutically acceptable carrier.

[0018] In another aspect, the present application provides a composition comprising taurine and a beta-receptor blocker.

[0019] In certain embodiments, wherein the beta-receptor blocker is selected from the group consisting of: Atenolol, Metoprolol, Carvedilol, Labetalol, Propranolol, Bisoprolol, and pharmaceutically acceptable salts thereof.

[0020] In certain embodiments, wherein the beta-receptor blocker is atenolol or a pharmaceutically acceptable salt thereof. In certain embodiments, wherein the beta-receptor blocker is metoprolol or a pharmaceutically acceptable salt thereof. In certain embodiments, wherein the beta-receptor blocker is selected from the group consisting of metoprolol succinate and metoprolol tartrate. In certain embodiments, wherein the beta-receptor blocker is carvedilol or a pharmaceutically acceptable salt thereof. In certain embodiments, wherein the beta-receptor blocker is carvedilol phosphate. In certain embodiments, wherein the beta-receptor blocker is labetalol or a pharmaceutically acceptable salt thereof. In certain embodiments, wherein the beta-receptor blocker is labetalol hydrochloride. In certain embodiments, wherein the beta-receptor blocker is propranolol or a pharmaceutically acceptable salt thereof. In certain embodiments, wherein the beta-receptor blocker is propranolol hydrochloride. In certain embodiments, wherein the beta-receptor blocker is bisoprolol or a pharmaceutically acceptable salt thereof. In certain embodiments, wherein the beta-receptor blocker is bisoprolol fumarate. In certain embodiments, wherein the beta-receptor blocker is propafenone or a pharmaceutically acceptable salt thereof. In certain embodiments, wherein the beta-receptor blocker is propafenone hydrochloride.

[0021] In certain embodiments, wherein the mass ratio of the taurine and derivatives thereof to the beta-receptor blocker is 100: 1 to 1 : 10. In certain embodiments, wherein the mass ratio of the taurine and derivatives thereof to the beta-receptor blocker is 80: 1 to 2: 1. In certain embodiments, wherein the mass ratio of the taurine and derivatives thereof to the beta-receptor blocker is 40: 1 to 1 : 1. In certain embodiments, wherein the mass ratio of the taurine and derivatives thereof to the beta-receptor blocker is 80: 1, 40: 1, 20: 1, 200: 15, 8: 1, 100: 15, 4: 1, 16: 5, 2: 1, or 1 : 1.

[0022] In certain embodiments, wherein the composition has one or more of the following functions: improving memory impairment, improving social impairment, improving speech communication impairment, reducing repetitive stereotyped behavior, improving sensory ability deficiency, and improving motor ability deficiency.

[0023] In certain embodiments, wherein the composition has one or more of the following functions: improving memory impairment in a patient with autism spectrum disorder, improving social impairment in a patient with autism spectrum disorder, improving speech communication impairment in a patient with autism spectrum disorder, reducing repetitive stereotyped behavior in a patient with autism spectrum disorder, improving sensory ability deficiency in a patient with autism spectrum disorder, improving motor ability deficiency in a patient with autism spectrum disorder, and improving self-care ability in a patient with autism spectrum disorder.

[0024] In certain embodiments, wherein the composition has one or more of the following functions: rescues social preference in autism spectrum disorder patients, rescues social memory in autism spectrum disorder patients, rescues empathy in autism spectrum disorder patients, rescues spatial memory in autism spectrum disorder patients.

[0025] In certain embodiments, wherein the composition is a pharmaceutical composition, and comprises a pharmaceutically acceptable carrier.

[0026] In certain embodiments, it comprises administering taurine and a beta-receptor blocker to a subject.

[0027] In certain embodiments, it comprises administering a composition described herein to a subject.

[0028] In another aspect, the present application provides a use of taurine and a beta-receptor blocker for treating autism spectrum disorder.

[0029] In another aspect, the present application provides a use of a composition described herein for treating autism spectrum disorder.

[0030] Other aspects and advantages of the present application can be readily ascertained by one skilled in the art from the following detailed description. Only the preferred embodiments of the application are shown and described in the following detailed description. As will be realized by those skilled in the art, the application is capable of modifications in various obvious aspects, all without departing from the application as recited in the claims. Accordingly, the drawings and descriptions should be regarded as illustrative in nature and not restrictive. BRIEF DESCRIPTION OF DRAWINGS

[0031] The specific features of the application as claimed are set forth in the appended claims. The features and advantages of the application claimed can be better understood from the exemplary embodiments described in detail below, and in conjunction with the accompanying drawings. Brief description of the drawings is as follows:

[0032] Figure 1 shows a schematic diagram of a three-chamber test for social memory test in mice.

[0033] Figure 2 shows a schematic diagram of a pain transfer test in mice.

[0034] Figure 3 shows a schematic diagram of a water maze apparatus used in water maze memory test in mice.

[0035] Figure 4 shows a flow chart of a social experiment in a mouse model of autism.

[0036] Figure 5 shows a flow chart of a social behavior experiment.

[0037] Figure 6 shows the effect of propafenone on the social function of VPA model mice. Mice were subjected to the three-chamber social test to test the social ability of mice. From left to right are wild type control group, VPA model group, propafenone group. Figure 6A, comparison of the exploration time of mice to strange mice and empty restraint cages. Two-way ANOVA was used to analyze the variance. Figure 6B, comparison of the exploration time of mice to strange mice and familiar mice. Two-way ANOVA was used to analyze the variance. (* represents p<0.05, ** represents p<0.01, *** represents p<0.001, **** represents p<0.0001. N=6).

[0038] Figure 7 shows the effect of taurine on the social function of VPA model mice. Mice were subjected to the three-chamber social test to test the social ability of mice. From left to right are wild type control group, VPA model group, taurine group. Figure 7A, comparison of the exploration time of mice to strange mice and empty restraint cages. Two-way ANOVA was used to analyze the variance. Figure 7B, comparison of the exploration time of mice to strange mice and familiar mice. Two-way ANOVA was used to analyze the variance. (* represents p<0.05, ** represents p<0.01, *** represents p<0.001, **** represents p<0.0001. N=6).

[0039] Figure 8 shows the effect of propranolol on the social function of VPA model mice. Mice were subjected to the three-chamber social test to test the social ability of mice. From left to right are wild type control group, VPA model group, propranolol group. Figure 8A, comparison of the exploration time of mice to strange mice and empty restraint cages. Two-way ANOVA was used to analyze the variance. Figure 8B, comparison of the exploration time of mice to strange mice and familiar mice. Two-way ANOVA was used to analyze the variance. (* represents p<0.05, ** represents p<0.01, *** represents p<0.001, **** represents p<0.0001. N=5-6).

[0040] Figure 9 shows the effect of atenolol on the social function of VPA model mice. Mice were subjected to the three-chamber social test to test the social ability of mice. From left to right are wild type control group, VPA model group, atenolol group. A, comparison of the exploration time of mice to strange mice and empty restraint cages. Two-way ANOVA was used to analyze the variance. B, comparison of the exploration time of mice to strange mice and familiar mice. Two-way ANOVA was used to analyze the variance. (* represents p<0.05, ** represents p<0.01, *** represents p<0.001, **** represents p<0.0001. N=4, 6).

[0041] Figure 10 shows the social function rescue effect of aripiprazole and carvedilol on VPA model mice. Mice were subjected to three-chamber social test to test the social ability of mice. From left to right are wild control group, VPA model group, aripiprazole group, carvedilol group. Figure 10A, comparison of exploration time of mice to strange mice and empty restraint cages. Two-way ANOVA was used to analyze variance. Figure 10B, comparison of exploration time of mice to strange mice and familiar mice. Two-way ANOVA was used to analyze variance. (* represents p<0.05, ** represents p<0.01, *** represents p<0.001, **** represents p<0.0001. N=3, 6).

[0042] Figure 11 shows the social function rescue effect of aripiprazole and atenolol combination, aripiprazole and labetalol combination on VPA model mice. Mice were subjected to three-chamber social test to test the social ability of mice. From left to right are wild control group, VPA model group, aripiprazole+atenolol group, aripiprazole+labetalol group. Figure 11A, comparison of exploration time of mice to strange mice and empty restraint cages. Two-way ANOVA was used to analyze variance. Figure 11B, comparison of exploration time of mice to strange mice and familiar mice. Two-way ANOVA was used to analyze variance. (* represents p<0.05, ** represents p<0.01, *** represents p<0.001, **** represents p<0.0001. N=4, 6).

[0043] Figure 12 shows the social function rescue effect of atenolol and taurine combination, propafenone and taurine combination on VPA model mice. Mice were subjected to three-chamber social test to test the social ability of mice. From left to right are wild control group, VPA model group, atenolol+taurine group, propafenone+taurine group. Figure 12A, comparison of exploration time of mice to strange mice and empty restraint cages. Two-way ANOVA was used to analyze variance. Figure 12B, comparison of exploration time of mice to strange mice and familiar mice. Two-way ANOVA was used to analyze variance. (* represents p<0.05, ** represents p<0.01, *** represents p<0.001, **** represents p<0.0001. N=4, 6).

[0044] Figure 13 shows the rescue effect of metoprolol and taurine combination, metoprolol and taurine on the social function of VPA model mice. The mice were subjected to three-chamber social experiment to test the social ability of the mice. From left to right are wild type control group, VPA model group, metoprolol + taurine group, metoprolol group, taurine group. Figure 13A, comparison of the exploration time of mice to strange mice and empty restraint cages. Two-way ANOVA was used to analyze the variance. Figure 13B, comparison of the exploration time of mice to strange mice and familiar mice. Two-way ANOVA was used to analyze the variance. (* represents p < 0.05, ** represents p < 0.01, *** represents p < 0.001, **** represents p < 0.0001. N = 6).

[0045] Figure 14 shows the rescue effect of metoprolol, metoprolol and taurine combination on the social function of VPA model mice. The mice were subjected to three-chamber social experiment to test the social ability of the mice. From left to right are wild type control group, VPA model group, metoprolol + taurine group, metoprolol group. Figure 14A, comparison of the exploration time of mice to strange mice and empty restraint cages. Two-way ANOVA was used to analyze the variance. Figure 14B, comparison of the exploration time of mice to strange mice and familiar mice. Two-way ANOVA was used to analyze the variance. (* represents p < 0.05, ** represents p < 0.01, *** represents p < 0.001, **** represents p < 0.0001. N = 5).

[0046] Figure 15 shows the rescue of 10 mg / kg metoprolol combination on the social function of Shank3 model mice. The mice were subjected to three-chamber social experiment to test the social ability of the mice. From left to right are wild type control group, VPA model group, aripiprazole group, metoprolol + taurine group, metoprolol group. Figure 15A, comparison of the exploration time of mice to strange mice and empty restraint cages. Two-way ANOVA was used to analyze the variance. Figure 15B, comparison of the exploration time of mice to strange mice and familiar mice. Two-way ANOVA was used to analyze the variance. (* represents p < 0.05, ** represents p < 0.01, *** represents p < 0.001, **** represents p < 0.0001. N = 5).

[0047] Figure 16 shows the flow chart of the experiment of autistic model mice.

[0048] Figure 17 shows the social function rescue of 20 mg / kg metoprolol compound, etc. on VPA model mice. Mice were tested for pain threshold before and after interaction through social paradigm. From left to right are control group, VPA model group, metoprolol + taurine group, taurine group. Two-way ANOVA was used to analyze variance. (* represents p<0.05, ** represents p<0.01, *** represents p<0.001, **** represents p<0.0001. N=6).

[0049] Figure 18 shows the social function rescue of 20 mg / kg metoprolol compound, etc. on Shank3 model mice. Mice were tested for pain threshold before and after interaction through social paradigm. From left to right are wild control group, VPA model group, metoprolol + taurine group, metoprolol group. Two-way ANOVA was used to analyze variance. (* represents p<0.05, ** represents p<0.01, *** represents p<0.001, **** represents p<0.0001. N=6).

[0050] Figure 19 shows the spatial memory rescue of 20 mg / kg metoprolol compound on VPA model mice. After 5 days of water maze training, the memory ability of mice was tested. Figure 19A, time to reach the platform during training of mice. Multiple variance comparison analysis was used. Figure 19B, the proportion of time mice swim in the platform quadrant during the adaptation and test stages. One-way ANOVA was used to analyze variance. Figure 19C, the number of times mice crossed the platform location during the adaptation and test stages. (* represents p<0.05, ** represents p<0.01, *** represents p<0.001. N=6).

[0051] Figure 20 shows the spatial memory rescue of 10 mg / kg metoprolol compound on VPA model mice. After 5 days of water maze training, the memory ability of mice was tested. Figure 20A, time to reach the platform during training of mice. Multiple variance comparison analysis was used. Figure 20B, the number of times mice crossed the platform location during the adaptation and test stages. One-way ANOVA was used to analyze variance. Figure 20C, the proportion of time mice swim in the platform quadrant during the adaptation and test stages. (* represents p<0.05, ** represents p<0.01, *** represents p<0.001. N=6).

[0052] Figure 21 shows the rescue of spatial memory in Shank3 mice by 20 mg / kg metoprolol. After 6 days of water maze training, mice were tested for memory ability. Figure 21A, Time to reach the platform during training of mice. One-way ANOVA was used for statistical variance. Figure 21B, Number of times mice crossed the platform location during the adaptation and test phases. One-way ANOVA was used for statistical variance. Figure 21C, Proportion of time mice swam in the platform quadrant during the adaptation and test phases. (* represents p < 0.05, ** represents p < 0.01, *** represents p < 0.001. N = 6). DETAILED DESCRIPTION

[0053] The present application will be described in greater detail by way of specific embodiments, from which the other advantages and effects of the present application will be more clearly understood.

[0054] DEFINITIONS

[0055] In the present application, the term "taurine" also known as 2-aminoethanesulfonic acid (IUPAC nomenclature) is an amino-containing sulfonic acid. Taurine has a CAS number of 107-35-7 and a molecular formula of C2H7NO3S. "Taurine" and "L-taurine" are used interchangeably to refer to the same organic compound.

[0056] In the present application, the term "beta-blocker" also known as Beta-receptor blocking drug, beta-receptor blocking agent, beta-receptor antagonist, or beta-receptor blocker, beta- blocker, or beta-blocker generally refers to a class of substances that can inhibit the activity of beta-receptors. Beta-blockers can bind to beta-receptors and thereby inhibit their activity. For example, beta-blockers can block the binding of beta-receptors to adrenaline and noradrenaline and thereby inhibit their activity. Beta-blockers can have the effects of slowing heart rate, lowering blood pressure, reducing cardiac contractility, controlling arrhythmia, reducing myocardial oxygen consumption, controlling hyperthyroidism, etc.

[0057] The beta receptors are mainly divided into three subtypes: β1 receptor, β2 receptor and β3 receptor, which have different distribution and function in different tissues and organs. β1 receptor is mainly distributed in the heart and adrenal gland tissue, regulating the beating force and heart rate of the heart, and the release of adrenaline. β2 receptor is widely distributed in various tissues such as bronchial smooth muscle, vascular smooth muscle, liver cells and muscle tissue, etc., participating in the regulation of bronchial dilation, vasodilation, glycogenolysis and other physiological processes. β3 receptor mainly exists in adipocytes and the digestive system, regulating fat metabolism and energy consumption. β-receptor blockers can be divided into 4 categories: ① non-selective β-receptor blockers, which can block both β1 and β2 receptors; ② β1 receptor selective β-receptor blockers, which mainly act on β1-receptors; ③ β2 receptor selective β-receptor blockers, which mainly act on β2-receptors; ④ mixed α and β-receptor blockers, which can act on both β- and α-receptors.

[0058] In the present application, the term "pharmaceutically acceptable salt" generally refers to those salts which are suitable for use in contact with the tissues of humans and animals. Pharmaceutically acceptable salts include acid and base addition salts. The term "pharmaceutically acceptable acid addition salt" generally refers to those pharmaceutically acceptable salts formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, carbonic acid, phosphoric acid, and organic acids selected from aliphatic, cycloaliphatic, aromatic, araliphatic, heterocyclic, carboxylic, and sulfonic classes of organic acids such as formic, acetic, propionic, glycolic, gluconic, lactic, pyruvic, oxalic, malic, maleic, malonic, succinic, fumaric, tartaric, citric, aspartic, ascorbic, glutamic, anthranilic, benzoic, cinnamic, mandelic, embonic, phenylacetic, methanesulfonic, ethanesulfonic, p-toluenesulfonic, and salicylic acids. The term "pharmaceutically acceptable base addition salt" generally refers to those salts which are formed with inorganic or organic bases. Examples of inorganic bases include sodium hydroxide, potassium hydroxide, ammonia, calcium hydroxide, magnesium hydroxide, aluminum hydroxide, ferric hydroxide, zinc hydroxide, copper hydroxide, manganese hydroxide, and aluminum hydroxide. Salts derived from pharmaceutically acceptable organic nontoxic bases include salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines, and basic ion exchange resins such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, 2-diethylaminoethanol, trimethylamine, dicyclohexylamine, lysine, arginine, histidine, caffeine, procaine, hydrabamine, choline, betaine, ethylenediamine, glucosamine, methylglucosamine, theobromine, purines, piperizine, piperidine, N-ethylpiperidine, and polyamine resins. These salts can be formed by procedures well known and described in the art.

[0059] In the present application, the term "pharmaceutical composition" generally refers to a preparation which is in a form suitable for its intended administration to a subject and which is in an effective amount for the biological activity of the active ingredient, and which does not contain additional ingredients which are unacceptable to the subject to which the preparation is to be administered. These preparations can be sterile. The pharmaceutical composition can also include one or more pharmaceutically acceptable carriers. Acceptable ingredients of the pharmaceutical composition are preferably non-toxic to the recipient at the dosages and concentrations employed.

[0060] In the present application, the term "pharmaceutically acceptable carrier" generally refers to any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like that are compatible with pharmaceutical administration. The use of such media and agents for pharmaceutically active substances is well known in the art. Except insofar as any conventional media or agent is incompatible with the active compound, its use in the pharmaceutical compositions of the present application is contemplated.

[0061] In the present application, the term "treatment" generally includes: (1) preventing a subject from developing undesirable symptoms and pathological states, who is predisposed to developing these undesirable symptoms and pathological states, but has not yet been diagnosed with these symptoms and pathological states; (2) inhibiting undesirable symptoms and pathological states, i.e., controlling their development; or (3) improving or relieving undesirable symptoms or pathological states, i.e., causing the above-mentioned undesirable symptoms or pathological states to subside. For example, the treatment of autism spectrum disorders described in the present application can include the relief of symptoms associated with autism spectrum disorders, whether or not the subject is diagnosed with autism spectrum disorders.

[0062] In the present application, the term “autism spectrum disorders (ASD)” also known as “autism spectrum” or “autism” generally refers to a syndrome of neurodevelopmental disorders and its related symptoms. According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) and the International Classification of Diseases, Eleventh Revision (ICD-11), autism is generally understood as a spectrum of disorders. For example, the autism spectrum disorders described herein can include one or more of autism spectrum disorder (ASD), Level 1 ASD, Level 2 ASD, Level 3 ASD, autism (“classic autism”), Asperger syndrome (“high-functioning autism”), pervasive developmental disorder (PDD “atypical autism”), pervasive developmental disorder not otherwise specified (PDD-NOS), childhood disintegrative disorder, developmental disorder related to autism spectrum disorder, speech and language delay (SLD), obsessive-compulsive disorder (OCD), social disorder, intellectual disorder, learning disorder, sensory processing, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), speech disorder, language disorder, social deficiency, social interaction deficiency, repetitive stereotyped behavior (RBB), repetitive stereotyped interest, repetitive stereotyped activity, global developmental delay, or other behavioral, intellectual, or developmental delay.

[0063] Autism spectrum disorders and / or its related symptoms can be assessed by a variety of methods known in the art. The Autism Behavior Checklist (ABC Checklist) is one of the most widely used autism assessment scales in China. The ABC Checklist was compiled by Krug in 1978, which lists 57 behavioral characteristics of children with autism, including sensory (Sensory), relating (Relating), body and object use (Body and object use), language (Language), social and self-help (Social and self-help) for children aged 2-14 years. Commonly used scales also include the Autism Diagnostic Observation Schedule (ADOS), the Autism Diagnostic Interview-Revised (ADI-R), the Childhood Autism Rating Scale (CARS), the Social Responsiveness Scale (SRS), the Vineland Adaptive Behavior Scale (Vineland-II), the Ohio Autism Clinical Global Impression Scale (OACIS), the Repetitive Behavior Scale-Revised (RBS-R), and the Yale-Brown Obsessive Compulsive Scale for Children with Autism Spectrum Disorders (CYBOSC-ASD).

[0064] In the present application, the term “memory impairment” generally refers to a condition in which an individual has problems in acquiring, storing, recalling, or utilizing information. Such problems can be temporary or long-term, and can be caused by various reasons, including brain injury, neurological diseases, drug or drug abuse, emotional or mental health problems, etc. Social impairment in individuals with autism spectrum disorder can manifest as one or more of the following: social memory impairment, including difficulty remembering names, faces, emotional states, or social rules of others; nonverbal memory impairment, such as impairment in spatial memory, visual memory, or motor memory, forgetting specific patterns, locations, sequences, or actions; excessive focus on details, difficulty integrating information into meaningful wholes; obsessive interests and attention, excessive investment in specific interests or activities, leading to interference with attention and memory of other information or events; emotional memory impairment, such as difficulty recalling past emotional experiences, or difficulty understanding and expressing emotions. Memory impairment can be assessed by methods known in the art, such as cognitive function tests, standardized memory assessment tools, etc. Commonly used standardized memory assessment tools can include Wechsler Memory Scale, Bradford Cognitive Abilities Scale (BACS), Rey Complex Figure Delayed Memory Test, etc.

[0065] In the present application, the term “social impairment” generally refers to a condition in which an individual avoids or actively seeks to avoid social interaction. Social impairment can include social psychological impairment, social functioning impairment, and / or social anxiety impairment. Social impairment in individuals with autism spectrum disorder can manifest as one or more of the following: lack of use of body language or other nonverbal communication skills, such as lack of eye contact; inability to develop peer relationships appropriate for one's age; weaker interpersonal communication skills than normal individuals, lack of motivation and ability to actively share things, interests, and emotions when communicating with peers; less response in communication, inability to initiate social interaction, difficulty in maintaining a two-way conversation, and even building friendships; lack of motivation to actively participate in social or group activities, preferring to be alone; inability to perceive, understand, and respond to the feelings and needs of others, and to perceive the presence of others; inability to participate in pretend or social imitation games. Social impairment can be assessed by methods known in the art, such as autism behavior checklist (ABC) and Childhood Autism Rating Scale (CARS).

[0066] In the present application, the term "speech and language disorder" generally refers to a neurodevelopmental disorder that affects the ability to communicate verbally. It is characterized by difficulties in language comprehension, expression, or speech that are beyond the range of normal language development. Speech and language disorders can involve multiple aspects, including the pronunciation of language, the use of vocabulary, the understanding and use of grammar, the understanding of semantics, and problems with phonology and fluency. Speech and language disorders in individuals with autism can manifest as one or more of the following: delayed language development or complete lack of ability to understand and express; weak comprehension, only understanding the literal meaning of spoken or written words, and not understanding underlying meanings; inability to understand or misinterpret puns, jokes, idioms, metaphors, or sarcastic remarks; inability to understand the meaning and focus of questions when asked by others, resulting in answering irrelevantly; inability to understand abstract concepts and complex instructions; expression of speech in a manner that is stereotyped, repetitive, direct, or parrot-like; stereotyped and outdated content of speech or words, such as parrot-like conversations, or even self-talk; use of direct words or sentences when communicating with others, and inability to use indirect words or sentences, giving the impression of being impolite or blunt; abnormal use of sentence or sentence structure organization, such as confusion in the use of pronouns such as "you", "I", "he", etc.; incoherent sentences, lack of coherence, repetition; lack of focus in the content of speech or writing; abnormal tone control; flat or abnormal tone; inability to emphasize important words; speaking too loudly or too softly, too fast or too slowly; one-way communication style when conversing with others, lack of communication skills; lack of interest in others' topics, and constantly repeating one's own topics of interest; inappropriate timing of speech, inappropriate response to others' speech; inappropriate speech in specific environments; lack of understanding of when to start, join, or continue a conversation, lack of understanding of turn-taking, difficulty in sustaining a conversation with others; interruption of others' speech during conversation. Speech and language disorders can be assessed by methods known in the art, for example, using standardized language assessment tools, such as the Language Development Test, the Language Comprehension and Expression Test, to assess the level of language ability of an individual.

[0067] In the present application, the term "repetitive stereotypy" generally refers to a persistent, frequent and stereotyped pattern of behavior characteristic that lacks flexibility and variability, and is typically not influenced by environmental or social feedback. Repetitive stereotypy can include one or more of the following: repetition of objects or body movements, including swaying, rocking, spinning, rubbing, flapping, waving; repetition of verbal speech: including repeating a certain word, phrase, sentence, song or part of a conversation, sometimes even repeating one's own or others' speech (also known as echolalia); repetition of interests or activities: for example, strong interest in specific objects or activities, such as flipping objects, arranging objects in neat rows, constantly disassembling and assembling toys, etc.; insistence on sameness or routines: insistence on certain activities, environments or behaviors in daily life, which can cause anxiety or challenges once broken; intense pursuit of special interests: unusual interest and investment in a particular topic, activity or theme, which can occupy a large amount of time and energy. Repetitive stereotypy can be assessed by methods known in the art, such as standardized questionnaires and scales, such as the Repetitive Behavior Scale-Revised (RBS-R) and the like.

[0068] In the present application, the term "sensory ability deficit" generally refers to difficulties and abnormalities in reflecting individual properties of stimuli, also known as "sensory disorder" or "sensory integration disorder". Sensory ability deficit can include hyperesthesia, hypohesia and anesthesias, paracusia and / or interoceptive discomfort. Hyperesthesia generally refers to an abnormally high ability to perceive external stimuli. Hypohesia or anesthesias generally refers to a decrease in the ability to perceive external stimuli. Paracusia generally refers to a false perception of the nature of external stimuli. Interoceptive discomfort generally refers to an unusual discomfort or pain from internal stimuli of the body. Assessment of sensory ability can be assessed by methods known in the art, such as standardized questionnaires and scales, such as sensory integration and praxis tests (SIPT), sensory profile (SP), evaluation of sensory processing (ESP), sensory processing measure (SPM) and the like.

[0069] In the present application, the term "motor ability deficit" generally refers to difficulties or abnormalities in motor control. Motor ability deficit can include motor coordination difficulty, muscle tone abnormality, motor skill developmental delay, motor perception abnormality, and / or motor stereotypy. Motor coordination difficulty generally refers to lack of coordination in performing complex movements or motions, which can manifest as awkward movements or unstable gait. Muscle tone abnormality generally refers to abnormal muscle tone, including muscle hyper-tonicity or hypotonia. This can lead to incoordination and instability in movement. Motor skill developmental delay generally refers to slow progress in learning and mastering basic motor skills. Motor perception abnormality generally refers to impaired ability to perceive and understand movement. Motor stereotypy generally refers to repetitive or stereotyped movement patterns. Assessment of motor ability can be assessed by methods known in the art, such as motor assessment tools and behavioral observation, which can include standardized motor development assessment scales, motion analysis, muscle strength test, and balance assessment, etc.

[0070] In the present application, the term "self-care agency" generally refers to the ability of an individual to perform basic activities of daily living and personal hygiene activities independently, including but not limited to dressing, eating, toileting, mobility and transfer, household activities, etc. Assessment of self-care agency can be assessed by methods known in the art, such as daily observation and standardized questionnaires and scales, which can include Barthel Index, Katz Index, etc.

[0071] In the present application, the term "administered in conjunction with", "co-administered", "co-therapy", "combination therapy" or "combination treatment" generally refers to administration of taurine and its derivatives described in the present application and beta-blockers described in the present application, for example, as respective independent preparations / application (or as a single preparation / application). The co-administration can be simultaneous administration or sequential administration without limitation, but preferably is administration within a period in which both (or all) active agents exert their biological activities simultaneously. The dose and timing of co-administration depend on the type (species, gender, age, body weight, etc.) and severity of the condition of the patient to be treated.

[0072] In the present application, the term "rescue" or "save" generally refers to recovery from or avoidance of a more severe outcome from a severe adverse state. In the present application, the term "improve" or "enhance" generally refers to an elevation of an existing state to a better state. In some instances, the improvement includes the rescue. In the present application, the terms "rescue" and "improve" can be relative, meaning their effects are measured against a specific context and baseline. Different reference points can lead to different evaluation criteria, for example, a comparison can be made to the same subject before and after administration of the composition, e.g., pre- and post-treatment, and if after administration of the composition described herein, certain performance of the subject shows a significant elevation, then the composition is said to "rescue" or "improve" the performance. In the present application, the term "effective amount" or "therapeutically effective amount" generally refers to the amount of an agent sufficient to provide a desired biological result. That result can be a reduction and / or alleviation of the signs, symptoms or causes of a disease, or any other desired biological change. For example, an "effective amount" for therapeutic uses is the amount of a composition comprising a compound as active ingredient required to provide a clinically significant decrease in disease. An appropriate "effective" amount in any individual case can be determined by one of ordinary skill in the art using routine experimentation, and is dependent on the type of disease, its severity, and the age, weight, health, and physical condition of the subject. Thus, the expression "effective amount" generally refers to an amount of active substance that has a therapeutic effect.

[0073] The term "subject" as used herein generally refers to a subject to whom the compositions, the pharmaceutical compositions, the combination therapies, and / or the treatment methods described herein are administered. For example, a subject can include a human or non-human animal in need of prognosis, improvement, prevention, and / or treatment of a disease. For example, the subject can include mammals and non-mammals. Examples of mammals include, but are not limited to, any member of the mammalian class: humans, non-human primates such as chimpanzees and other apes and monkey species; farm animals such as cows, horses, sheep, goats, pigs; domestic animals such as rabbits, dogs, and cats; laboratory animals including rodents, such as rats, mice and guinea pigs, and the like. Examples of non-mammals include, but are not limited to, fruit flies, birds, fish, and the like. In certain embodiments, the mammal is a human. In certain embodiments, the subject described herein is a child.

[0074] As used in the specification and claims, the singular forms "a," "an" and "the" include plural references unless the context clearly dictates otherwise.

[0075] All numerical values or expressions involving quantities of components, etc., as used herein in the specification and claims are understood to be modified in all instances by the term "about," unless expressly indicated otherwise. The term "about" when used before a quantity or a numerical range means that the quantity or the numerical range is an approximation and, as such, the quantity or the numerical range can vary from the stated quantity or numerical range by, for example, ±5. All ranges involving the same component or property are inclusive of the endpoints, which are combinable independently. Since the ranges are continuous, they include every value between the minimum and the maximum values. It is also understood that any numerical range recited in this application is intended to include all sub-ranges of the same entire range.

[0076] When this application refers to range using "comprising" it is understood that the composition, integer or steps of the process claimed, can consist just of the recited range, as well as the recited range extended by the recited minimum and / or maximum limits, and any combination thereof. When this application refers to range using "comprising" it is understood that the composition, integer or steps of the process claimed, can consist just of the recited range, as well as the recited range extended by the recited minimum and / or maximum limits, and any combination thereof. The term "comprising" (and related terms such as "comprise" or "comprises" or "having" or "including") includes those embodiments of the application where the recited features are present "by themselves" or "alone", as well as embodiments where the recited features are present with other features.

[0077] As used herein in the specification and claims, "and / or" means one or the other or both. As used herein in the specification and claims, "or" as used in a list of items prefaced by "at least one of" means one or more items in the list. As used herein in the specification and claims, "or" as used in a list of items prefaced by "one or more of the

[0078] It should be understood that any method, including a method of any of the present application that comprises more than one step, or more than one act, can not necessarily be limited to the order of the steps or acts, unless expressly stated otherwise.

[0079] DETAILED DESCRIPTION

[0080] Compositions

[0081] In one aspect, the present application provides a composition comprising taurine and a beta-blocker.

[0082] In certain embodiments, the mass ratio of taurine to the beta-blocker in the composition can be 100: 1-1: 10, 90: 1-1: 10, 80: 1-1: 10, 70: 1-1: 10, 60: 1-1: 10, 50: 1-1: 10, 40: 1-1: 10, 30: 1-1: 10, 20: 1-1: 10, or 10: 1-1: 10. In certain embodiments, the mass ratio of taurine to the beta-blocker in the composition can be 100: 1-1: 10, 80: 1-2: 1, or 40: 1-1: 1. In certain embodiments, the mass ratio of taurine to the beta-blocker in the composition can be 100: 1, 90: 1, 80: 1, 70: 1, 60: 1, 50: 1, 40: 1, 30: 1, 20: 1, 15: 1, 10: 1, 9: 1, 8: 1, 7: 1, 6: 1, 5: 1, 4: 1, 3: 1, 2: 1, 1: 1, 1: 2, 1: 3, 1: 4, or 1: 5. In certain embodiments, the mass ratio of taurine to the beta-blocker in the composition can be 400: 15, 200: 15, 100: 15, or 16: 5.

[0083] The compositions described herein can have one or more of the following functions: improving memory impairment, improving social impairment, improving speech communication impairment, reducing repetitive stereotypic behavior, improving sensory ability deficiency, and improving motor ability deficiency.

[0084] The compositions of taurine and beta-blocker can have better functions and / or reduce side effects compared to using each agent alone. In some cases, the functions of the compositions described herein can be additive (e.g., the functions of the compositions are approximately equal to the sum of the functions of taurine and beta-blocker alone). In some cases, the functions of the compositions described herein can be synergistic (e.g., the functions of the compositions are greater than the sum of the functions of taurine and beta-blocker alone). In some cases, the compositions described herein can have better functions can be an increase in the number of functions (e.g., the compositions can improve multiple symptoms, while taurine and beta-blocker can only improve one symptom). In some cases, the compositions described herein can have better functions can be an increase in the strength of the functions (e.g., the functions of the combination are stronger than the functions of taurine and beta-blocker alone).

[0085] The composition described in the present application can have one or more of the following functions: improving social impairment of autism spectrum disorder patients, improving speech communication impairment of autism spectrum disorder patients, reducing repetitive stereotyped behavior of autism spectrum disorder patients, improving sensory ability deficiency of autism spectrum disorder patients, improving motor ability deficiency of autism spectrum disorder patients, and improving self-care ability of autism spectrum disorder patients. The pharmaceutical composition described in the present application can also have one or more of the following functions: saving the social preference of autism spectrum disorder patients, saving the social memory of autism spectrum disorder patients, saving the empathy ability of autism spectrum disorder patients, saving the spatial memory of autism spectrum disorder patients.

[0086] The composition described in the present application can have a therapeutic effect on autism spectrum disorder. The composition described in the present application can have an improvement effect on one or more related symptoms of autism spectrum disorder patients.

[0087] The function of the composition described in the present application can be detected by methods known in the art. For example, the therapeutic effect of the composition described in the present application on autism spectrum disorder patients can be detected by methods known in the art for diagnosing and / or assessing symptoms of autism spectrum disorder patients. For example, the therapeutic effect of the composition described in the present application on autism spectrum disorder patients can include reducing the autism behavior checklist (ABC) score of autism spectrum disorder patients by more than 5 points, reducing the Childhood Autism Rating Scale (CARS) score of autism spectrum disorder patients by more than 5 points. For example, the therapeutic effect of the composition described in the present application on autism spectrum disorder patients can include reducing the autism behavior checklist (ABC) score of autism spectrum disorder patients to less than 67 points, reducing the Childhood Autism Rating Scale (CARS) score of autism spectrum disorder patients to less than 30 points. The composition described in the present application can have a better therapeutic effect on autism spectrum disorder than taurine or β-receptor blockers alone. For example, the better therapeutic effect can be manifested in an increase in the number of symptoms related to autism spectrum disorder that are improved. For example, the better therapeutic effect can be manifested in an improvement in the degree of improvement in a certain symptom related to autism spectrum disorder.

[0088] Taurine and β-receptor blockers

[0089] The present application relates to the use of taurine and β-receptor blockers.

[0090] Polymorphic forms of different beta-receptor blockers and salts, solvates, esters and prodrugs thereof are intended to be included in the present application. The beta-receptor blockers described in the present application can be any conventional beta-receptor blocker known in the art. Preferably, the beta-receptor blocker is selected from the group of compounds which are known in the art and commercially available under different trade names or can be obtained as described in the literature.

[0091] Non-selective beta-receptor blockers

[0092] In certain embodiments, the beta-receptor blocker can be a non-selective beta-receptor blocker. Examples of non-selective beta-receptor blockers include, but are not limited to, propranolol or a pharmaceutically acceptable salt thereof.

[0093] In certain embodiments, the beta-receptor blocker can be propranolol or a pharmaceutically acceptable salt thereof. For example, the beta-receptor blocker can be propranolol hydrochloride. Propranolol described in the present application generally refers to a drug with a CAS number of 525-66-6, a molecular formula of C 16 H 21 NO2, which can also be referred to as Norsynephrine, Inderal, Nadoxolol, Inderal or 1- isopropylamino-3-(naphthalen-1-yloxy)propan-2-ol. Propranolol hydrochloride described in the present application generally refers to the hydrochloride salt of propranolol, for example, the CAS number of propranolol hydrochloride can be 3506-09-0, the molecular formula can be C 16 H 21 NO2· HC1, which can also be referred to as 1-isopropylamino-3-(1-naphthyloxy)-2-propanol hydrochloride.

[0094] In certain embodiments, the composition described in the present application can comprise taurine and propranolol or a pharmaceutically acceptable salt thereof.

[0095] In certain embodiments, the composition described in the present application can comprise taurine and propranolol. In certain embodiments, the composition described in the present application can comprise taurine and propranolol hydrochloride.

[0096] In certain embodiments, the composition described herein can comprise taurine and propranolol or a pharmaceutically acceptable salt thereof, and the mass ratio of taurine to propranolol or a pharmaceutically acceptable salt thereof in the composition can be 100: 1-1: 10, 90: 1-1: 10, 80: 1-1: 10, 70: 1-1: 10, 60: 1-1: 10, 50: 1-1: 10, 40: 1-1: 10, 30: 1-1: 10, 20: 1-1: 10, or 10: 1-1: 10. In certain embodiments, the mass ratio of taurine to propranolol or a pharmaceutically acceptable salt thereof in the composition can be 100: 1-1: 10, 80: 1-2: 1, or 40: 1-1: 1. In certain embodiments, the mass ratio of taurine to propranolol or a pharmaceutically acceptable salt thereof in the composition can be 100: 1, 90: 1, 80: 1, 70: 1, 60: 1, 50: 1, 40: 1, 30: 1, 20: 1, 15: 1, 10: 1, 9: 1, 8: 1, 7: 1, 6: 1, 5: 1, 4: 1, 3: 1, 2: 1, 1: 1, 1: 2, 1: 3, 1: 4, or 1: 5. In certain embodiments, the mass ratio of taurine to propranolol or a pharmaceutically acceptable salt thereof in the composition can be 400: 15, 200: 15, 100: 15, or 16: 5.

[0097] a β1 receptor-selective β-receptor blocker

[0098] In certain embodiments, the β-receptor blocker can be a β1 receptor-selective β-receptor blocker.

[0099] Examples of a β1 receptor-selective β-receptor blocker include, but are not limited to, atenolol, bisoprolol, and metoprolol.

[0100] In certain embodiments, the β-receptor blocker can be selected from atenolol or a pharmaceutically acceptable salt thereof, bisoprolol or a pharmaceutically acceptable salt thereof, and metoprolol or a pharmaceutically acceptable salt thereof.

[0101] In certain embodiments, the β-receptor blocker can be metoprolol or a pharmaceutically acceptable salt thereof. For example, the β-receptor blocker can be selected from metoprolol succinate and metoprolol tartrate. Metoprolol described herein generally refers to a drug with a CAS number of 51384-51-1, a molecular formula of C 15 H 25 NO3, which can also be referred to as metoprolol, methoprolol, metoprolol, or (±)-1- isopropylamino-3-[p-(2-methoxyethyl)phenoxy]-2-propanol. Metoprolol succinate described herein generally refers to a succinate salt of metoprolol. For example, metoprolol succinate can have a CAS number of 98418-47-4, and a molecular formula of (C 15 H 25NO3)2·C4H6O4, which can also be referred to as 1-isopropylamino-3-[p-(2- methoxyethyl)phenoxy]-2-propanol succinate. Metoprolol tartrate as described herein generally refers to a tartrate salt of metoprolol, for example, the CAS number of metoprolol tartrate can be 56392-17-7, and the molecular formula can be (C 15 H 25 NO3)2·C4H6O4, which can also be referred to as 1-isopropylamino-3-[p-(2- methoxyethyl)phenoxy]-2-propanol succinate. Metoprolol tartrate as described herein generally refers to a tartrate salt of metoprolol, for example, the CAS number of metoprolol tartrate can be 56392-17-7, and the molecular formula can be (C

[0102] In certain embodiments, the composition described herein can comprise taurine and metoprolol or a pharmaceutically acceptable salt thereof.

[0103] In certain embodiments, the composition described herein can comprise taurine and metoprolol or a pharmaceutically acceptable salt thereof.

[0104] In certain embodiments, the composition described herein can comprise taurine and metoprolol or a pharmaceutically acceptable salt thereof, and the mass ratio of taurine to metoprolol or a pharmaceutically acceptable salt thereof in the composition can be 100: 1-1: 10, 90: 1-1: 10, 80: 1-1: 10, 70: 1-1: 10, 60: 1-1: 10, 50: 1-1: 10, 40: 1-1: 10, 30: 1-1: 10, 20: 1-1: 10, or 10: 1-1: 10. In certain embodiments, the mass ratio of taurine to metoprolol or a pharmaceutically acceptable salt thereof in the composition can be 100: 1-1: 10, 80: 1-2: 1, or 40: 1-1: 1. In certain embodiments, the mass ratio of taurine to metoprolol or a pharmaceutically acceptable salt thereof in the composition can be 100: 1, 90: 1, 80: 1, 70: 1, 60: 1, 50: 1, 40: 1, 30: 1, 20: 1, 15: 1, 10: 1, 9: 1, 8: 1, 7: 1, 6: 1, 5: 1, 4: 1, 3: 1, 2: 1, 1: 1, 1: 2, 1: 3, 1: 4, or 1: 5. In certain embodiments, the mass ratio of taurine to metoprolol or a pharmaceutically acceptable salt thereof in the composition can be 400: 15, 200: 15, 100: 15, or 16: 5.

[0105] In certain embodiments, the beta-receptor blocker can be bisoprolol or a pharmaceutically acceptable salt thereof. For example, the beta-receptor blocker can be bisoprolol fumarate. As used herein, bisoprolol generally refers to a drug with a CAS number of 66722-44-9, a molecular formula of C 18 H 31 NO4, which can also be referred to as 1-[4-[[2-(1-methylethoxy)ethoxy]methyl]phenoxy]-3-[(1- methylethyl)amino]-2-propanol. As used herein, bisoprolol fumarate generally refers to a fumarate salt of bisoprolol. For example, bisoprolol fumarate can have a CAS number of 104344-23-2, and a molecular formula of (C 18 H 31 NO4)2·C4H4O4, which can also be referred to as 1-[4-[[2-(1-methylethoxy)ethoxy]methyl]- phenoxy]-3-[(1-methylethyl)amino]-2-propanol fumarate.

[0106] In certain embodiments, the compositions described herein can comprise taurine and bisoprolol or a pharmaceutically acceptable salt thereof.

[0107] In certain embodiments, the compositions described herein can comprise taurine and bisoprolol. In certain embodiments, the compositions described herein can comprise taurine and a bisoprolol pharmaceutically acceptable salt. In certain embodiments, the compositions described herein can comprise taurine and bisoprolol fumarate.

[0108] In certain embodiments, the composition described herein can comprise taurine and bisoprolol or a pharmaceutically acceptable salt thereof, and the mass ratio of taurine to bisoprolol or a pharmaceutically acceptable salt thereof in the composition can be 100:1-1:10, 90:1-1:10, 80:1-1:10, 70:1-1:10, 60:1-1:10, 50:1-1:10, 40:1-1:10, 30:1-1:10, 20:1-1:10, or 10:1-1:10. In certain embodiments, the mass ratio of taurine to bisoprolol or a pharmaceutically acceptable salt thereof in the composition can be 100:1-1:10, 80:1-2:1, or 40:1-1:1. In certain embodiments, the mass ratio of taurine to bisoprolol or a pharmaceutically acceptable salt thereof in the composition can be 100:1, 90:1, 80:1, 70:1, 60:1, 50:1, 40:1, 30:1, 20:1, 15:1, 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, 2:1, 1:1, 1:2, 1:3, 1:4, or 1:5. In certain embodiments, the mass ratio of taurine to bisoprolol or a pharmaceutically acceptable salt thereof in the composition can be 400:15, 200:15, 100:15, or 16:5.

[0109] In certain embodiments, the beta-blocker can be atenolol or a pharmaceutically acceptable salt thereof. Atenolol described herein generally refers to a drug with a CAS number of 29122-68-7, a molecular formula of C 14 H 22 N2O3, which can also be referred to as 4-[3-[(1-methylethyl)amino-2-hydroxy]propoxy]benzeneacetamide. A salt of atenolol described herein, such as a hydrochloride salt of atenolol, generally refers to a complex formed by atenolol and hydrochloric acid. The hydrochloride salt of atenolol has a CAS number of 65277-36-3, a molecular formula of C 14 H 22 N2O3·HCl, which can also be referred to as 4-[3-[(1-methylethyl)amino-2-hydroxy]propoxy]benzeneacetamide hydrochloride.

[0110] In certain embodiments, the composition described herein can comprise taurine, and atenolol and a pharmaceutically acceptable salt thereof.

[0111] In certain embodiments, the composition described herein can comprise taurine and atenolol. In certain embodiments, the composition described herein can comprise taurine and a pharmaceutically acceptable salt of atenolol. In certain embodiments, the composition described herein can comprise taurine and atenolol hydrochloride.

[0112] In certain embodiments, the composition described herein can comprise taurine and atenolol or a pharmaceutically acceptable salt thereof, and the mass ratio of taurine to atenolol or a pharmaceutically acceptable salt thereof in the composition can be 100: 1-1: 10, 90: 1-1: 10, 80: 1-1: 10, 70: 1-1: 10, 60: 1-1: 10, 50: 1-1: 10, 40: 1-1: 10, 30: 1-1: 10, 20: 1-1: 10, or 10: 1-1: 10. In certain embodiments, the mass ratio of taurine to atenolol or a pharmaceutically acceptable salt thereof in the composition can be 100: 1-1: 10, 80: 1-2: 1, or 40: 1-1: 1. In certain embodiments, the mass ratio of taurine to atenolol or a pharmaceutically acceptable salt thereof in the composition can be 100: 1, 90: 1, 80: 1, 70: 1, 60: 1, 50: 1, 40: 1, 30: 1, 20: 1, 15: 1, 10: 1, 9: 1, 8: 1, 7: 1, 6: 1, 5: 1, 4: 1, 3: 1, 2: 1, 1: 1, 1: 2, 1: 3, 1: 4, or 1: 5. In certain embodiments, the mass ratio of taurine to atenolol or a pharmaceutically acceptable salt thereof in the composition can be 400: 15, 200: 15, 100: 15, or 16: 5.

[0113] β2 receptor-selective β-receptor blockers

[0114] In certain embodiments, the β-receptor blocker can be a β2 receptor-selective β-receptor blocker.

[0115] Mixed α and β-receptor blockers

[0116] In certain embodiments, the β-receptor blocker can be a mixed α and β-receptor blocker. Examples of the mixed α and β-receptor blocker include, but are not limited to, carvedilol and labetalol.

[0117] In certain embodiments, the β-receptor blocker can be selected from the group consisting of carvedilol and a pharmaceutically acceptable salt thereof, and labetalol and a pharmaceutically acceptable salt thereof.

[0118] In certain embodiments, the β-receptor blocker can be carvedilol or a pharmaceutically acceptable salt thereof. For example, the β-receptor blocker can be carvedilol phosphate. Carvedilol described herein generally refers to a drug with a CAS number of 72956-09-3, a molecular formula of C 24 H 26N2O4, which can also be referred to as (±)-1-(9H-4-carbazolyloxy)-3-[2-(2- methoxyphenoxy)ethylamino]-2-propanol. Carvedilol phosphate described herein generally refers to a phosphate salt of carvedilol, for example, carvedilol dihydrogen phosphate. For example, carvedilol phosphate can have a CAS number of 610309-89-2 and a molecular formula of C 24 H 26 N2O4» H3PO4» ½ H2O.

[0119] In certain embodiments, the composition described herein can comprise taurine and carvedilol or a pharmaceutically acceptable salt thereof.

[0120] In certain embodiments, the composition described herein can comprise taurine and carvedilol. In certain embodiments, the composition described herein can comprise taurine and a pharmaceutically acceptable salt of carvedilol. In certain embodiments, the composition described herein can comprise taurine and a phosphate salt of carvedilol.

[0121] In certain embodiments, the composition described herein can comprise taurine and carvedilol or a pharmaceutically acceptable salt thereof, and the mass ratio of taurine to carvedilol or a pharmaceutically acceptable salt thereof in the composition can be 100: 1-1: 10, 90: 1-1: 10, 80: 1-1: 10, 70: 1-1: 10, 60: 1-1: 10, 50: 1-1: 10, 40: 1-1: 10, 30: 1-1: 10, 20: 1-1: 10, or 10: 1-1: 10. In certain embodiments, the mass ratio of taurine to carvedilol or a pharmaceutically acceptable salt thereof in the composition can be 100: 1-1: 10, 80: 1-2: 1, or 40: 1-1: 1. In certain embodiments, the mass ratio of taurine to carvedilol or a pharmaceutically acceptable salt thereof in the composition can be 100: 1, 90: 1, 80: 1, 70: 1, 60: 1, 50: 1, 40: 1, 30: 1, 20: 1, 15: 1, 10: 1, 9: 1, 8: 1, 7: 1, 6: 1, 5: 1, 4: 1, 3: 1, 2: 1, 1: 1, 1: 2, 1: 3, 1: 4, or 1: 5. In certain embodiments, the mass ratio of taurine to carvedilol or a pharmaceutically acceptable salt thereof in the composition can be 400: 15, 200: 15, 100: 15, or 16: 5.

[0122] In certain embodiments, the beta-receptor blocker can be labetalol or a pharmaceutically acceptable salt thereof. For example, the beta-receptor blocker can be labetalol hydrochloride. Labetalol described herein generally refers to a drug with a CAS number of 36894-69-6 and a molecular formula of C 19 H 24N2O3, which can also be referred to as labetalol. The labetalol hydrochloride described herein generally refers to the hydrochloride salt of labetalol. For example, the CAS number of labetalol hydrochloride can be 32780-64-6, and its molecular formula can be C 19 H 24 N2O3 HCI, which can also be referred to as 5-[1-hydroxy-2(1-methyl-3- phenylpropylamino)-ethyl] salicylamide hydrochloride.

[0123] In certain embodiments, the compositions described herein can comprise taurine and labetalol or a pharmaceutically acceptable salt thereof.

[0124] In certain embodiments, the compositions described herein can comprise taurine and labetalol. In certain embodiments, the compositions described herein can comprise taurine and a pharmaceutically acceptable salt of labetalol. In certain embodiments, the compositions described herein can comprise taurine and labetalol hydrochloride.

[0125] In certain embodiments, the compositions described herein can comprise taurine and labetalol or a pharmaceutically acceptable salt thereof, and the mass ratio of taurine to labetalol or a pharmaceutically acceptable salt thereof in the composition can be 100:1-1:10, 90:1-1:10, 80:1-1:10, 70:1-1:10, 60:1-1:10, 50:1-1:10, 40:1-1:10, 30:1-1:10, 20:1-1:10, or 10:1-1:10. In certain embodiments, the mass ratio of taurine to labetalol or a pharmaceutically acceptable salt thereof in the composition can be 100:1-1:10, 80:1-2:1, or 40:1-1:1. In certain embodiments, the mass ratio of taurine to labetalol or a pharmaceutically acceptable salt thereof in the composition can be 100:1, 90:1, 80:1, 70:1, 60:1, 50:1, 40:1, 30:1, 20:1, 15:1, 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, 2:1, 1:1, 1:2, 1:3, 1:4, or 1:5. In certain embodiments, the mass ratio of taurine to labetalol or a pharmaceutically acceptable salt thereof in the composition can be 400:15, 200:15, 100:15, or 16:5.

[0126] Substances capable of inhibiting the activity of β-receptors

[0127] The β-receptor blockers described herein can also include substances capable of inhibiting the activity of β-receptors and / or capable of blocking β-receptors. For certain reasons, they are not referred to as "β-receptor blockers" in the art, for example, the inhibition of the activity of β-receptors is not their main function, but as long as they have an inhibitory effect on the activity of β-receptors, they are included in the scope of the β-receptor blockers described herein.

[0128] The inhibiting of the activity of the β-receptor can include blocking the binding of the β-receptor to its ligand. For example, the inhibiting can include reducing the binding of the β-receptor to its ligand by at least 10%, at least 20%, at least 30%, at least 40%, at least 50% relative to the absence of the β-blocker

[0129] In certain embodiments, the β-receptor blocker can include an antiarrhythmic drug having an inhibitory effect on the activity of the β-receptor.

[0130] In certain embodiments, the β-receptor blocker can be propafenone or a pharmaceutically acceptable salt thereof. For example, the β-receptor blocker can be propafenone hydrochloride. As used herein, propafenone generally refers to a drug having a CAS number of 54063-53-5, a molecular formula of C 21 H 27 NO3, which can also be referred to as l-[2-[2-hydroxy-3-(propylamino)- propoxy]phenyl]-3-phenyl-l-propanone. As used herein, propafenone hydrochloride generally refers to a hydrochloride salt of propafenone, for example, having a CAS number of 34183-22-7, a molecular formula of C 21 H 27 NO3-HCl, which can also be referred to as 3-phenyl-l-[2-3-(propylamino)-2- hydroxypropoxy]phenyl-l-propanone hydrochloride.

[0131] In certain embodiments, the composition described herein can comprise taurine and propafenone or a pharmaceutically acceptable salt thereof.

[0132] In certain embodiments, the composition described herein can comprise taurine and propafenone. In certain embodiments, the composition described herein can comprise taurine and a pharmaceutically acceptable salt of propafenone. In certain embodiments, the composition described herein can comprise taurine and propafenone hydrochloride.

[0133] In certain embodiments, the composition described herein can comprise taurine and propafenone, or a pharmaceutically acceptable salt thereof, in a mass ratio of taurine to propafenone, or a pharmaceutically acceptable salt thereof, of 100: 1 to 1: 10, 90: 1 to 1: 10, 80: 1 to 1: 10, 70: 1 to 1: 10, 60: 1 to 1: 10, 50: 1 to 1: 10, 40: 1 to 1: 10, 30: 1 to 1: 10, 20: 1 to 1: 10, or 10: 1 to 1: 10. In certain embodiments, the composition can comprise taurine and propafenone, or a pharmaceutically acceptable salt thereof, in a mass ratio of taurine to propafenone, or a pharmaceutically acceptable salt thereof, of 100: 1 to 1: 10, 80: 1 to 2: 1, or 40: 1 to 1: 1. In certain embodiments, the composition can comprise taurine and propafenone, or a pharmaceutically acceptable salt thereof, in a mass ratio of taurine to propafenone, or a pharmaceutically acceptable salt thereof, of 100: 1, 90: 1, 80: 1, 70: 1, 60: 1, 50: 1, 40: 1, 30: 1, 20: 1, 15: 1, 10: 1, 9: 1, 8: 1, 7: 1, 6: 1, 5: 1, 4: 1, 3: 1, 2: 1, 1: 1, 1: 2, 1: 3, 1: 4, or 1: 5. In certain embodiments, the composition can comprise taurine and propafenone, or a pharmaceutically acceptable salt thereof, in a mass ratio of taurine to propafenone, or a pharmaceutically acceptable salt thereof, of 400: 15, 200: 15, 100: 15, or 16: 5.

[0134] Pharmaceutical composition

[0135] In another aspect, the present application provides a pharmaceutical composition comprising taurine and a beta-receptor blocker. For example, the pharmaceutical composition can further comprise a pharmaceutically acceptable carrier.

[0136] The pharmaceutical composition described herein can include a pharmaceutical product suitable for pharmaceutical use (e.g., treating autism spectrum disorder or improving symptoms associated therewith). The pharmaceutical composition described herein can be a composition comprising a plurality of active ingredients (e.g., taurine and a beta-receptor blocker) and one or more inert ingredients; and any product directly or indirectly obtained by combination, complexation, or aggregation of any two or more ingredients.

[0137] The pharmaceutical composition described herein can have one or more of the following functions: improving memory impairment, improving social impairment, improving speech communication impairment, reducing repetitive stereotyped behavior, improving sensory ability deficiency, and improving motor ability deficiency.

[0138] The pharmaceutical compositions described herein can have one or more of the following functions: ameliorating social impairment in a patient with autism spectrum disorder, ameliorating speech communication impairment in a patient with autism spectrum disorder, reducing repetitive stereotyped behavior in a patient with autism spectrum disorder, ameliorating sensory ability deficiency in a patient with autism spectrum disorder, ameliorating motor ability deficiency in a patient with autism spectrum disorder, and ameliorating self-care ability in a patient with autism spectrum disorder. The pharmaceutical compositions described herein can also have one or more of the following functions: rescuing social preference in a patient with autism spectrum disorder, rescuing social memory in a patient with autism spectrum disorder, rescuing empathic ability in a patient with autism spectrum disorder, rescuing spatial memory in a patient with autism spectrum disorder.

[0139] The pharmaceutical compositions described herein can have a therapeutic effect on autism spectrum disorder. The pharmaceutical compositions described herein can have an ameliorating effect on one or more related symptoms in a patient with autism spectrum disorder.

[0140] Therapeutic methods and uses

[0141] In another aspect, the present application provides use of a composition in the manufacture of a medicament, wherein the composition comprises taurine and a beta-receptor blocker.

[0142] In certain embodiments, the medicament described herein can comprise a pharmaceutical composition. For example, the pharmaceutical composition can further comprise a pharmaceutically acceptable carrier.

[0143] In another aspect, the present application provides a therapeutic method, comprising administering taurine and a beta-receptor blocker to a subject.

[0144] In another aspect, the present application provides a therapeutic method, comprising administering a composition described herein, a medicament described herein, and / or a pharmaceutical composition described herein to a subject.

[0145] In another aspect, the present application provides use of taurine and a beta-receptor blocker for treating autism spectrum disorder.

[0146] In another aspect, the present application provides use of a composition described herein and / or a pharmaceutical composition described herein for treating autism spectrum disorder.

[0147] The therapeutic methods described herein can comprise a combination therapy of taurine and a beta-receptor blocker. For example, a combination therapy for autism spectrum disorder or related symptoms.

[0148] The therapeutic methods described herein can have better therapeutic effects on autism spectrum disorders relative to the effects of taurine or beta-blockers alone. For example, the better therapeutic effects can be manifested in an increase in the number of autism spectrum disorder-related symptoms improved. For example, the better therapeutic effects can be manifested in an increase in the degree of improvement of certain autism spectrum disorder-related symptoms.

[0149] The combination therapy described herein can include simultaneous administration of the taurine described herein and the beta-blocker described herein in the same or different dosage forms, or separate administration of the taurine described herein, the beta-blocker described herein (e.g., sequentially). Thus, the taurine and the beta-blocker can be administered simultaneously in a single formulation. Alternatively, the taurine and the beta-blocker can be formulated for separate administration, and administered simultaneously or sequentially (e.g., the taurine is administered within about 30 minutes prior to administration of the beta-blocker).

[0150] For example, the taurine described herein can be administered first, and then (e.g., then immediately) the beta-blocker described herein is administered, or vice versa. In certain embodiments, the beta-blocker described herein is administered prior to administration of the taurine. In certain embodiments, the beta-blocker described herein is administered after administration of the taurine. In certain embodiments, the taurine described herein and the beta-blocker described herein are administered simultaneously.

[0151] In certain embodiments, the dose of the taurine described herein and / or the beta-blocker is calculated based on body weight, e.g., mg / kg body weight. For example, the dose of the taurine described herein and / or the beta-blocker can be 5 mg / kg to 500 mg / kg.

[0152] In certain embodiments, the total dose of taurine and beta-blocker can be 55 mg / kg - 1000 mg / kg based on the dose administered to a murine animal model. In certain embodiments, the total dose of taurine and beta-blocker can be 205 mg / kg - 505 mg / kg based on the dose administered to a murine animal model. In certain embodiments, the dose of taurine can be 50 mg / kg - 500 mg / kg and the dose of beta-blocker can be 5 mg / kg - 200 mg / kg based on the dose administered to a murine animal model. In certain embodiments, the dose of taurine can be 500 mg / kg, 450 mg / kg, 400 mg / kg, 350 mg / kg, 300 mg / kg, 250 mg / kg, 200 mg / kg, 150 mg / kg, 100 mg / kg, or 50 mg / kg and the dose of beta-blocker can be 5 mg / kg, 10 mg / kg, 15 mg / kg, 20 mg / kg, 30 mg / kg, 40 mg / kg, 50 mg / kg, 60 mg / kg, 70 mg / kg, 80 mg / kg, 90 mg / kg, 100 mg / kg, 150 mg / kg, or 200 mg / kg based on the dose administered to a murine animal model.

[0153] Administration doses for different subjects, for example, between humans and non-human animals, can be scaled according to ways known in the art. A scaling factor for scaling mouse doses to human doses can be used for a routine method of extrapolating human doses based on doses administered to a murine animal model: human dose / kg = mouse dose / kg x 12. See Freireich et al., Cancer Chemother Rep. 50, 219-244 (1966). Drug doses can also be given in mg per square meter of body surface area, as this method achieves a better correlation with certain metabolic and excretory functions than does body weight. In addition, body surface area can be used as a common characteristic for drug dosing in adults and children, as well as in different animal species. See Freireich et al., Cancer Chemother Rep. 50, 219-244 (1966).

[0154] Suitable methods for administering the compositions of the presently disclosed subject matter to an individual include, but are not limited to, systemic administration, parenteral administration, oral delivery, buccal delivery, subcutaneous administration, inhalation, intratracheal instillation, transdermal delivery, local injection. The mode of administration used according to the methods described herein depends on a variety of factors including, but not limited to, the drug and / or carrier used, the severity of the condition being treated, and the metabolic or elimination mechanisms of the active agents after administration.

[0155] Without wishing to be bound by any theory, the examples below are merely intended to illustrate the methods, compositions, and uses of the present application and are not intended to limit the scope of the present application.

[0156] Examples

[0157] Instrumentation and reagent supplies

[0158] Mouse spatial memory test pool, mouse plantar mechanical allodynia device, three-chamber test device, ANY-maze mouse behavior automatic recording software, camera.

[0159] Test subjects

[0160] - Autism model mice

[0161] Two-month-old C57BL6 / J mice were subcutaneously injected with VPA at a dose of 600 mg / kg at E12.5. Male mice among the mouse pups were valproate autism mice, and showed symptoms of autism after 40 days of birth. The experiment was performed 11 days after administration.

[0162] - Shank3 transgenic mice

[0163] Shank family genes are pathogenic genes of congenital ASD, and the mutation rate of Shank3 gene is about 2%. The genotype of Shank3 mice is B6.129-Shank3 tm2Gfng / J, JAX number 017688. Knockout of Shank3 gene leads to abnormal protein expression, and the animals show symptoms of autism. The experiment was started at 1 month of age.

[0164] Operation flow

[0165] 1. Mouse modeling and drug administration

[0166] 1.1 VPA purchase and use

[0167] Sodium valproate, CAS number: 1069-66-5, purchased from Aladdin. 0.594 g of VPA powder was weighed, 9.94 ml of 0.9% NaCl was added, and vortexed to obtain a clear solution, obtaining a VPA solution of 59.76 mg / ml. Subcutaneous injection was performed on pregnant mice at E12.5, and the injection amount was 600 mg / kg.

[0168] 1.2 Source of test drugs

[0169] Propranolol was purchased from Selleck Company. Carvedilol, labetalol, propafenone, taurine, atenolol were purchased from Aladdin. Metoprolol was purchased from MCE. Bisoprolol was purchased from Beijing Huasu Pharmaceutical Co., Ltd. Solvent PBS was purchased from Bayerdi Company.

[0170] 1.3 Drug preparation method

[0171] Weigh an appropriate amount of drug and place it in a mortar. Add a small amount of solvent (PBS) and grind. After pouring out, rinse the grinder with solvent three times and then dilute to the desired concentration with solvent. After dispensing, store in a -20°C refrigerator in the dark.

[0172] 1.4 Administration method and administration time

[0173] According to the body weight of rats and mice and the purpose of the experiment, the drug was fed according to the designed concentration. The feeding dose is shown in each example. The prepared drug solution and solvent were taken out from the -20°C refrigerator and restored to room temperature. The drug solution or normal saline was orally gavaged into the mouse stomach with a gavage needle. In the single-dose feeding experiment, gavage was performed at 9:00 am every day, once a day. The experimental animals were given a certain amount of drug, and the model group and wild type control group were given a certain amount of solvent. The behavior experiment started after a specified time of administration. The drug was continuously administered every day during the behavior experiment until the end of the experiment.

[0174] 2. Behavior test

[0175] 2.1 Mouse social memory test

[0176] The 1-meter-long and 40-centimeter-wide open field was evenly divided into three areas. A restraint cage was placed in the center of the first and third areas (as shown in Figure 1, the left side is defined as cage A and the right side is defined as cage B). Within a 5-centimeter range from the restraint cage (A-1; B-1 area).

[0177] The test environment was kept at room temperature of 25 degrees and humidity of 30-40%, in a quiet environment without strong light and irrelevant personnel.

[0178] Adaptation period: On the first day, no mice were placed in cages A and B. The experimental mice were placed in the middle of the open field with their heads facing the inner wall of the open field for 30 minutes to adapt to the open field environment. After cleaning the cages, the next group of animals was adapted.

[0179] Social preference test: The test was performed the next day. A stranger mouse was placed in the home cage of the test mouse. The test mouse was placed in the middle of the open field with its head facing the inner wall of the open field for 10 minutes. The movement trajectory and time of the mouse were recorded automatically using Anymaze software and a camera. The time spent by the animal within 5 cm of the home cage was calculated. The animal was considered to exhibit social preference if it spent time within 5 cm of the home cage. After each group of animals was tested, the cage was cleaned before the next group of animals was tested.

[0180] Social memory test: The social memory test was performed 4 hours after the social preference test. A familiar mouse was placed in the home cage of the test mouse, and a stranger mouse was placed in the home cage of the test mouse. The test mouse was placed in the middle of the open field with its head facing the inner wall of the open field for 10 minutes. The time spent by the animal within 5 cm of the home cage was calculated. After each group of animals was tested, the cage was cleaned before the next group of animals was tested.

[0181] 2.2 Mouse pain transfer experiment

[0182] As shown in FIG. 2, the pain threshold test used different thickness Von Frey fiber filaments to stimulate the mouse foot. The results were recorded using the classic "up and down" method, and the 50% withdrawal threshold of the mouse was calculated according to the formula. The pain tester was 40 cm high, the home cage was 10*10*5 cm, and different fiber filaments (specifications: 0.008 g, 0.02 g, 0.04 g, 0.07 g, 0.16 g, 0.4 g, 0.6 g, 1 g) were tested in turn.

[0183] The pain tester was placed on the operating table, and the test mouse was fixed in the pain tester with the home cage. (The bottom was illuminated with a desk lamp to illuminate the foot) After the mouse was calm for 2-3 hours, the test was performed. First, select a fiber filament with a suitable mouse pain threshold zero value (0.07 g) as the first filament to start testing in turn. The fiber filament was continuously pressed against the bottom of the mouse foot, and the fiber filament was bent at an angle of 45° to the foot. If the test mouse showed a pain response within 5 seconds, an "X" was recorded on the record table, otherwise an "O" was recorded. Each mouse was tested 6 times, with a 1-minute interval between each test. According to the reaction pattern of the mouse, the parameters were determined by referring to the table, and the 50% PWT value (paw withdrawal threshold) was calculated according to the formula for statistical analysis.

[0184] After the mouse pain threshold baseline was tested, the mouse was cohabited with the CFA pain mouse for 24 hours, and the mouse pain threshold was tested again for comparison.

[0185] 2.3 Mouse water maze memory test

[0186] The mouse spatial memory test pool is a circular barrel as shown in Figure 3, with a water maze diameter of 1.2 meters, divided into ABCD four quadrants. Different shaped markers are set at 3 o'clock, 6 o'clock, 9 o'clock and 12 o'clock on the barrel wall, and a platform is set at the midpoint of the line connecting 6 o'clock and 9 o'clock, which is 2 cm below the water surface. Fill the barrel with water and dye it white with milk so that the platform is not visible. The experimental animals are trained four times a day, with an interval of 1 hour, and each time for 1 minute. The mice are placed in the water at 4 o'clock, 3 o'clock, 2 o'clock and 1 o'clock, and allowed to swim in the pool to find the platform position. If the animal does not find the platform position within 1 minute, it will be artificially guided to the platform to remember the platform position. Training lasts for 4-6 days, and the swimming trajectory of the mouse is automatically recorded using a camera. The ANY-maze software is used to analyze the swimming trajectory and swimming time of the mouse. On the last day, the platform is removed and the mouse is allowed to swim freely for 1 minute, and its movement trajectory is recorded.

[0187] During the training phase of the mice, the time required for the mice to find the platform is calculated, and the learning curve of the mice is plotted. The shorter the time required for the mice to find the platform (Escape latency), the stronger the spatial learning and memory ability of the mice.

[0188] During the free swimming phase of the mice after the platform is removed, the swimming trajectory of the mice is analyzed, and the number of times the platform position is crossed (Number of crossing) and the time spent in the B quadrant (Time in right quadrant) are calculated. The more times the mice cross the platform position and the longer the time spent in the B quadrant, the stronger the spatial learning and memory ability of the mice.

[0189] 3. Data analysis

[0190] Data processing and plotting were performed using GraphPad 8 and SPSS 25.0, and statistical differences were compared by repeated measures ANOVA and one-way ANOVA. All data are expressed as mean ± standard error. *, P < 0.05, **, P < 0.01, ***, P < 0.001, ****, P < 0.0001.

[0191] Example 1 Drug rescue of social deficits in VPA autism model mice

[0192] This example shows that the combination of taurine and beta-blocker administration has a better rescue effect on social deficits in VPA autism model mice than when they are administered alone.

[0193] C57BL6 / J mice were used to model VPA. Offspring mice were fed once a day for 11 consecutive days starting at 40 days of age (doses were adjusted according to clinical doses), and then social experiments were performed to test the effect of the drug on the rescue of memory deficits in autism mice.

[0194] 1.1 Single drug: rescue effect of 50 mg / kg propafenone, 30 mg / kg propranolol, 200 mg / kg taurine, 200 mg / kg atenolol, 3 mg / kg aripiprazole, 125 mg / kg carvedilol.

[0195] 1.1.1 In the social preference test, the VPA model group (P = 0.9905) showed no significant difference in the time spent in the two restraint cages, showing social impairment; the wild control group (P < 0.0001) and the propafenone group (P = 0.0011) showed significant social preference, as the time spent in the restraint cage with a strange mouse was significantly higher than the time spent in the empty restraint cage. In the social memory test, the wild control group (P < 0.0001) showed significant social memory, as the time spent in the restraint cage with a strange mouse was significantly higher than the time spent in the restraint cage with a familiar mouse; the VPA model group (P > 0.9999) and the propafenone group (P = 0.9995) showed no significant difference in the time spent in the two restraint cages, showing social memory impairment. The results are shown in Table 1 and Figure 6, and feeding 50 mg / kg propafenone for 11 days can rescue the social preference impairment of autistic mice, but cannot rescue the social memory impairment.

[0196] Table 1 Rescue effect of propafenone

[0197] 1.1.2 In the social preference test, the wild control group (P < 0.0001) and the taurine group (P < 0.0001) showed significant social preference, as the time spent in the restraint cage with a strange mouse was significantly higher than the time spent in the empty restraint cage; the VPA model group (P = 0.9897) showed no significant difference in the time spent in the two restraint cages, showing social impairment. In the social memory test, the wild control group (P < 0.0001) showed significant social memory, as the time spent in the restraint cage with a strange mouse was significantly higher than the time spent in the restraint cage with a familiar mouse; the VPA model group (P = 0.3164) and the taurine group (P > 0.9999) showed no significant difference in the time spent in the two restraint cages, showing social memory impairment. The results are shown in Table 2 and Figure 7, and feeding 200 mg / kg taurine for 11 days can rescue the social preference impairment of autistic mice, but cannot rescue the social memory impairment.

[0198] Table 2 Rescue effect of taurine

[0199] 1.1.3 In the social preference test, the wild control group (P<0.0001) and the propranolol group (P=0.0006) mice spent significantly more time in the home cage with a stranger mouse than in the empty cage, showing a significant social preference; the VPA model group (P=0.3503) spent no significant difference in time in the two cages, showing social deficits. In the social memory test, the wild control group (P=0.0005) spent significantly more time in the home cage with a stranger mouse than in the familiar mouse cage, showing significant social memory. The VPA model group (P=0.9302) and the propranolol group (P=0.9999) spent no significant difference in time in the two cages, showing social memory deficits. The results are shown in Table 3 and Figure 8, and 30 mg / kg propranolol feeding for 11 days can rescue the social preference deficits of autistic mice, but cannot rescue the social memory deficits.

[0200] Table 3 Rescue effect of propranolol

[0201] 1.1.4 In the social preference test, the wild control group (P<0.0001) mice spent significantly more time in the home cage with a stranger mouse than in the empty cage, showing a significant social preference; the VPA model group (P=0.8929) and the atenolol group (P=0.5275) spent no significant difference in time in the two cages, showing social deficits. In the social memory test, the wild control group (P<0.0001) and the atenolol group (P<0.0001) spent significantly more time in the home cage with a stranger mouse than in the familiar mouse cage, showing significant social memory. The VPA model group (P=0.5047) spent no significant difference in time in the two cages, showing social memory deficits. The results are shown in Table 4 and Figure 9, and 200 mg / kg atenolol feeding for 11 days can rescue the social memory deficits of autistic mice, but cannot rescue the social preference deficits.

[0202] Table 4 Rescue effect of atenolol

[0203] 1.1.5 In the social preference test, the wild control group (P<0.0001), the aripiprazole group (P<0.0001), and the carvedilol group (P=0.0002) mice spent significantly more time in the home cage of the unfamiliar mouse than in the empty cage, showing a significant social preference; the VPA model group (P=0.9239) spent no significant difference in time in the two cages, showing social deficits. In the social memory test, the wild control group (P<0.0001) and the aripiprazole group (P=0.0005) spent significantly more time in the home cage of the unfamiliar mouse than in the familiar mouse, showing significant social memory. The VPA model group (P=0.9998) and the carvedilol group (P=0.9975) spent no significant difference in time in the two cages, showing social memory deficits. The results are shown in Table 5 and Figure 10, and 3 mg / kg aripiprazole fed for 11 days can rescue the social preference and social memory deficits of autistic mice. 125 mg / kg carvedilol fed for 11 days can rescue the social preference of autistic mice, but cannot rescue the social memory deficits.

[0204] Table 5 Rescue effect of aripiprazole, carvedilol

[0205] 1.2 Test the combination of the two drugs: aripiprazole 3 mg / kg + atenolol 100 mg / kg, aripiprazole 3 mg / kg + labetalol 100 mg / kg.

[0206] In the social preference test, the wild control group (P<0.0001), the aripiprazole 3 mg / kg+atenolol 200 mg / kg group (P=0.0045), the mice spent significantly more time in the tethered cage with a strange mouse than in the empty tethered cage, showing obvious social preference; the VPA model group (P=0.9995), the aripiprazole 3 mg / kg+ labetalol 100 mg / kg group (P=0.1253) spent no significant time in the two tethered cages, showing social deficits. In the social memory test, the wild control group (P=0.0042), the aripiprazole 3 mg / kg+ labetalol 100 mg / kg group (P<0.0001), spent significantly more time in the tethered cage with a strange mouse than in the familiar mouse, showing significant social memory. The VPA model group (P=0.8776), the aripiprazole 3 mg / kg+ atenolol 200 mg / kg group (P=0.7887) spent no significant time in the two tethered cages, showing social memory deficits. The results are shown in Table 6 and Figure 11, and feeding aripiprazole 3 mg / kg+ atenolol 100 mg / kg for 11 days can rescue the social preference deficits of autistic mice but cannot rescue the social memory deficits. Feeding aripiprazole 3 mg / kg+ labetalol 100 mg / kg for 11 days can rescue the social memory deficits of autistic mice but cannot rescue the social preference deficits.

[0207] Table 6 Rescue effect of aripiprazole+atenolol, aripiprazole+labetalol combination

[0208] 1.3 Modify the social time for testing. Let the mice explore freely for 20 minutes in the phase of testing social preference. Test the rescue effect of atenolol 200 mg / kg+taurine 200 mg / kg, propafenone 50 mg / kg+taurine 200 mg / kg.

[0209] In the social preference test, the wild control group (P<0.0001), the atenolol 200mg / kg+taurine 200mg / kg group (P<0.0001), the propafenone 50mg / kg+taurine 200mg / kg group (P<0.0001) mice spent significantly more time in the home cage of the unfamiliar mouse than in the empty cage, showing obvious social preference; the VPA model group (P=0.9963) spent no significant time in the two cages, showing social defects. In the social memory test, the wild control group (P=0.0122), the atenolol 200mg / kg+taurine 200mg / kg group (P=0.0023), the propafenone 50mg / kg+taurine 200mg / kg group (P=0.0035) spent significantly more time in the unfamiliar mouse cage than in the familiar mouse cage, showing significant social memory. The VPA model group (P=0.9439) spent no significant time in the two cages, showing social memory defects. The results are shown in Table 7 and Figure 12, and feeding atenolol 200mg / kg+taurine 200mg / kg, propafenone 50mg / kg+taurine 200mg / kg for 11 days can rescue the social preference defects and social memory defects of autistic mice.

[0210] Table 7 Rescue effect of atenolol+taurine, propafenone+taurine combination

[0211] 1.4 Modify the social time for testing. Let the mice explore freely for 20 minutes during the phase of testing social preference. Test the rescue effect of 20mg / kg metoprolol+400mg / kg taurine, 20mg / kg metoprolol, 400mg / kg taurine

[0212] In the social preference test, the wild control group (P<0.0001), the 20 mg / kg metoprolol + 400 mg / kg taurine group (P<0.0001), and the 400 mg / kg taurine group (P<0.0001) mice spent significantly more time in the home cage of the unfamiliar mouse than in the empty cage, showing obvious social preference; the VPA model group (P>0.9999) and the 20 mg / kg metoprolol group (P=0.8735) showed no significant difference in time spent in the two cages, showing social deficits. In the social memory test, the wild control group (P=0.0008), the 20 mg / kg metoprolol + 400 mg / kg taurine group (P=0.0003), the 20 mg / kg metoprolol group (P=0.0260), and the 400 mg / kg taurine group (P=0.0005) spent significantly more time in the unfamiliar mouse cage than in the familiar mouse cage, showing significant social memory. The VPA model group (P=0.9487) showed no significant difference in time spent in the two cages, showing social memory deficits. The results are shown in Table 8 and FIG. 13, and feeding 20 mg / kg metoprolol + 400 mg / kg taurine and 400 mg / kg taurine for 11 days can rescue the social preference and social memory deficits of autistic mice. Feeding 20 mg / kg metoprolol for 11 days can rescue the social memory deficits of autistic mice, but cannot rescue the social preference deficits. The 20 mg / kg metoprolol + 400 mg / kg taurine group showed a greater difference in mouse-cage exploration time in the social preference test, and the rescue effect was better.

[0213] Table 8 Rescue effect of metoprolol and / or taurine

[0214] 1.5 Test the rescue effect of 5mg / kg metoprolol + 400mg / kg taurine, 5mg / kg metoprolol, fed twice a day. In the social preference test, the wild control group (P<0.0001), the 5mg / kg metoprolol + 400mg / kg taurine group mice spent significantly more time in the tethered cage with a strange mouse than in the empty tethered cage, showing obvious social preference; the VPA model group (P=0.9773), the 5mg / kg metoprolol group (P>0.9999) spent no significant difference in time in the two tethered cages, showing social deficits. In the social memory test (Figure 9.19B), the wild control group (P=0.0221), the 5mg / kg metoprolol + 400mg / kg taurine group (P<0.0001) spent significantly more time in the tethered cage with a strange mouse than in the familiar mouse, showing significant social memory. The VPA model group (P>0.9999), the 5mg / kg metoprolol group (P=0.8515) spent no significant difference in time in the two tethered cages, showing social memory deficits. The results are shown in Table 9 and Figure 14, and 5mg / kg metoprolol fed twice a day for 11 days cannot rescue the social preference and social memory deficits of autistic mice, and 5mg / kg metoprolol + 400mg / kg taurine fed twice a day for 11 days can rescue the social preference and social memory deficits of autistic mice.

[0215] Table 9 Rescue effect of metoprolol and / or taurine fed twice a day

[0216] Example 2 Drug rescue of social memory deficits in Shank3 model mice

[0217] This example tests the rescue effect of 3mg / kg aripiprazole, 10mg / kg metoprolol + 400mg / kg taurine, 10mg / kg metoprolol.

[0218] In the social preference test, the wild control group (P<0.0001), the 10mg / kg metoprolol + 400mg / kg taurine group (P<0.0001) mice spent significantly more time in the tethered cage with a strange mouse than in the empty tethered cage, showing obvious social preference; the Shank3 model group (P=0.9997), the 3mg / kg aripiprazole group (P=0.1729), the 10mg / kg metoprolol group (P=0.8991) spent no significant difference in time in the two tethered cages, showing social deficits.

[0219] In the social memory test, the wild control group (P=0.0003), the 10 mg / kg metoprolol + 400 mg / kg taurine group (P=0.0006), and the 10 mg / kg metoprolol group (P=0.0068) had significantly higher stay time in the strange mouse's restraint cage than in the familiar mouse's restraint cage, showing significant social memory. The Shank3 model group (P=0.9906) and the 3 mg / kg aripiprazole group (P=0.7842) had no significant difference in stay time in the two restraint cages, showing social memory defects.

[0220] As shown in Table 10 and Figure 15, feeding 10 mg / kg metoprolol + 400 mg / kg taurine for 11 days can rescue the social preference and social memory defects of autistic mice. Feeding 10 mg / kg metoprolol for 11 days can rescue the social memory defects of autistic mice, but cannot rescue the social preference defects.

[0221] Table 10 Metoprolol 10 mg / kg, metoprolol 10 mg / kg + taurine 400 mg / kg

[0222] Example 3 Drug rescue of autistic mice's attachment ability defects

[0223] After completing the social behavior experiment, the pain transfer and water maze experiment were performed in turn. The experimental procedure is shown in Figure 16.

[0224] 3.1 Test the rescue effect of 20 mg / kg metoprolol + 400 mg / kg taurine, 400 mg / kg taurine on VPA autistic mice. The wild control group (P=0.0034), the 20 mg / kg metoprolol + 400 mg / kg taurine group (P=0.0031), and the 400 mg / kg taurine group (P=0.0860) had significantly lower pain threshold after interaction than before, showing obvious attachment ability; the VPA model group (P=0.1694) had no significant difference in pain threshold before and after interaction, showing attachment defects.

[0225] As shown in Table 11 and Figure 17, feeding 20 mg / kg metoprolol + 400 mg / kg taurine, 400 mg / kg taurine for 17 days can rescue the attachment defects of autistic mice. The significant threshold reduction produced by 20 mg / kg metoprolol + 400 mg / kg taurine after interaction is higher than that of the 400 mg / kg taurine group, indicating better rescue effect.

[0226] Table 11 20 mg / kg metoprolol, 20 mg / kg metoprolol + 400 mg / kg taurine

[0227] 3.2 Test the rescue effect of 20mg / kg metoprolol + 400mg / kg taurine, 20mg / kg metoprolol on Shank3 autistic mice. Wild control group (P=0.0004), 20mg / kg metoprolol + 400mg / kg taurine group (P=0.0041) mice showed significant empathy ability as their pain threshold after interaction was significantly lower than the baseline level; VPA model group (P=0.8884), 20mg / kg metoprolol group (P=0.7549) showed empathy deficiency as their pain threshold had no significant difference before and after interaction.

[0228] As shown in Table 12 and Figure 18, feeding 20mg / kg metoprolol + 400mg / kg taurine for 17 days can rescue the empathy deficiency of autistic mice.

[0229] Table 12 20mg / kg metoprolol, 20mg / kg metoprolol + 400mg / kg taurine

[0230] Example 4 Drug rescue of autistic mice water maze memory deficiency

[0231] 4.1 Test the rescue effect of 20mg / kg metoprolol + 400mg / kg taurine, 400mg / kg taurine on VPA autistic model. As training progressed, the time for mice to find the platform significantly shortened over time, with significant differences between groups (intra-group comparison, F=32.112, P=0.000; inter-group comparison, F=2.960, P=0.057). Relative to the wild control group, the autistic model group showed obvious memory deficiency (day2, P=0.848; day3, P=0.103; day4, P=0.007; day5, P=0.138).

[0232] 20mg / kg metoprolol + 400mg / kg taurine feeding can significantly shorten the time for the model group to find the platform (day2, P=0.362; day3, P=0.049; day4, P=0.035; day5, P=0.434), indicating that it can rescue the memory of autistic mice.

[0233] Table 13 20mg / kg metoprolol + 400mg / kg taurine

[0234] As shown in Table 13 and Figure 19, 20mg / kg metoprolol + 400mg / kg taurine can rescue the spatial memory deficiency of VPA autistic mice, while the 400mg / kg taurine group has no rescue effect.

[0235] 4.2 Test 10 mg / kg metoprolol + 400 mg / kg taurine, 10 mg / kg metoprolol rescue effect on VPA autism model. As training proceeds, the time for mice to find the platform significantly shortened over time, with significant differences between groups (intra-group comparison, F = 18.839, P = 0.000; inter-group comparison, F = 14.963, P = 0.000). Relative to the wild control group, the autism model group showed a significant memory deficit (day 1, P = 0.381; day 2, P = 0.072; day 3, P = 0.012; day 4, P = 0.000; day 5, P = 0.000).

[0236] 10 mg / kg metoprolol + 400 mg / kg taurine feeding can significantly shorten the time for the model group to find the platform (day 1, P = 0.427; day 2, P = 0.349; day 3, P = 0.003; day 4, P = 0.007; day 5, P = 0.000), and significantly increase the swimming time in the target quadrant (P = 0.0163), indicating that it can rescue the memory of autistic mice. 10 mg / kg metoprolol feeding can significantly shorten the time for the model group to find the platform (day 1, P = 0.934; day 2, P = 0.046; day 3, P = 0.211; day 4, P = 0.060; day 5, P = 0.001), and significantly increase the swimming time in the target quadrant (P = 0.0340), indicating that it can rescue the memory of autistic mice.

[0237] Table 14 10 mg / kg metoprolol + 400 mg / kg taurine

[0238] As shown in Table 14 and Figure 20, 10 mg / kg metoprolol + 400 mg / kg taurine, 10 mg / kg metoprolol can rescue the spatial memory deficit of VPA autistic mice. 10 mg / kg metoprolol + 400 mg / kg taurine has a rescue effect on days 3-5, and 10 mg / kg metoprolol only has a rescue effect on day 5. The 10 mg / kg metoprolol + 400 mg / kg taurine group reached the platform time lower than the 10 mg / kg metoprolol group, indicating that the compound has a better rescue effect.

[0239] 4.3 Test 20mg / kg metoprolol + 400mg / kg taurine, 20mg / kg metoprolol rescue effect on Shank3 autism model. As training proceeded, the time for mice to find the platform was significantly shortened over time, with significant differences between groups (intra-group comparison, F=10.853, P=0.000; inter-group comparison, F=14.963, P=0.000). Relative to the wild control group, the autism model group showed a significant memory deficit (day 1, P=0.232; day 2, P=0.848; day 3, P=0.053; day 4, P=0.013; day 5, P=0.003; day 6, P=0.000).

[0240] 20mg / kg metoprolol + 400mg / kg taurine feeding can significantly shorten the time for the model group to find the platform (day 1, P=0.134; day 2, P=0.469; day 3, P=0.403; day 4, P=0.200; day 5, P=0.084; day 6, P=0.001), significantly increase the number of times the platform position is crossed (P=0.0430), and significantly increase the swimming time in the target quadrant (P=0.0046), indicating that it can rescue the memory of autistic mice.

[0241] Table 15 20mg / kg metoprolol + 400mg / kg taurine

[0242] As shown in Table 15 and Figure 21, 20mg / kg metoprolol + 400mg / kg taurine can rescue the spatial memory deficit of Shank3 autistic mice.

Claims

1. Use of a composition in the manufacture of a medicament, wherein the composition comprises taurine and a beta-receptor blocker.

2. The use according to claim 1, wherein the beta-receptor blocker is selected from the group consisting of a beta 1 receptor selective beta-receptor blocker, a beta 2 receptor selective beta-receptor blocker, a mixed alpha and beta-receptor blocker and / or a non-selective beta-receptor blocker.

3. The use according to any one of claims 1-2, wherein the beta-receptor blocker is selected from the group consisting of Atenolol, Metoprolol, Carvedilol, Labetalol, Propranolol, Bisoprolol, Propafenone, and pharmaceutically acceptable salts thereof.

4. The use according to any one of claims 1-3, wherein the beta-receptor blocker is Atenolol or a pharmaceutically acceptable salt thereof.

5. The use according to any one of claims 1-3, wherein the beta-receptor blocker is Metoprolol or a pharmaceutically acceptable salt thereof.

6. The use according to claim 5, wherein the beta-receptor blocker is selected from the group consisting of Metoprolol succinate and Metoprolol tartrate.

7. The use according to any one of claims 1-3, wherein the beta-receptor blocker is Carvedilol or a pharmaceutically acceptable salt thereof.

8. The use according to claim 7, wherein the beta-receptor blocker is Carvedilol phosphate.

9. The use according to any one of claims 1-3, wherein the beta-receptor blocker is Labetalol or a pharmaceutically acceptable salt thereof.

10. The use according to claim 9, wherein the beta-receptor blocker is Labetalol hydrochloride.

11. The use according to any one of claims 1-3, wherein the beta-receptor blocker is Propranolol or a pharmaceutically acceptable salt thereof.

12. The use according to claim 11, wherein the beta-receptor blocker is Propranolol hydrochloride.

13. The use according to any one of claims 1-3, wherein the beta-receptor blocker is Bisoprolol or a pharmaceutically acceptable salt thereof.

14. The use according to claim 13, wherein the beta-receptor blocker is Bisoprolol fumarate.

15. The use according to any one of claims 1-3, wherein the beta-receptor blocker is Propafenone or a pharmaceutically acceptable salt thereof.

16. The use according to claim 15, wherein the beta-receptor blocker is Propafenone hydrochloride.

17. The use according to any one of claims 1-16, wherein the mass ratio of taurine to the beta-receptor blocker is 40:1-1:

1.

18. The use according to any one of claims 1-17, wherein the mass ratio of taurine to the beta-receptor blocker is 40:1-1:

1.

19. The use of any one of claims 1-18, wherein the mass ratio of the taurine to the beta-blocker is 80: 1, 40: 1, 20: 1, 200: 15, 8: 1, 100: 15, 4: 1, 16: 5, 2: 1, or 1:

1.

20. The use of any one of claims 1-19, wherein the composition has one or more of the following functions: improving memory impairment, improving social impairment, improving speech communication impairment, reducing repetitive stereotypic behavior, improving sensory ability deficits, improving motor ability deficits, and improving self-care ability.

21. The use of any one of claims 1-20, wherein the composition has one or more of the following functions: improving memory impairment in a patient with autism spectrum disorder, improving social impairment in a patient with autism spectrum disorder, improving speech communication impairment in a patient with autism spectrum disorder, reducing repetitive stereotypic behavior in a patient with autism spectrum disorder, improving sensory ability deficits in a patient with autism spectrum disorder, improving motor ability deficits in a patient with autism spectrum disorder, and / or improving self-care ability in a patient with autism spectrum disorder.

22. The use of any one of claims 1-21, wherein the composition has one or more of the following functions: rescuing social preference in a patient with autism spectrum disorder, rescuing social memory in a patient with autism spectrum disorder, rescuing empathic ability in a patient with autism spectrum disorder, rescuing spatial memory in a patient with autism spectrum disorder.

23. The use of any one of claims 1-22, wherein the medicament is for improving memory impairment, improving social impairment, improving speech communication impairment, reducing repetitive stereotypic behavior, improving sensory ability deficits, improving motor ability deficits, and / or improving self-care ability.

24. The use of any one of claims 1-23, wherein the medicament is for treating autism spectrum disorder.

25. The use of any one of claims 1-24, wherein the medicament is for improving memory impairment in a patient with autism spectrum disorder, improving social impairment in a patient with autism spectrum disorder, improving speech communication impairment in a patient with autism spectrum disorder, reducing repetitive stereotypic behavior in a patient with autism spectrum disorder, improving sensory ability deficits in a patient with autism spectrum disorder, improving motor ability deficits in a patient with autism spectrum disorder, and / or improving self-care ability in a patient with autism spectrum disorder.

26. The use of any one of claims 1-25, wherein the medicament comprises a pharmaceutical composition further comprising a pharmaceutically acceptable carrier.

27. A composition comprising taurine and a beta-blocker.

28. The composition of claim 27, wherein the beta-blocker is selected from the group consisting of Atenolol, Metoprolol, Carvedilol, Labetalol, Propranolol, Bisoprolol, and pharmaceutically acceptable salts thereof.

29. The composition of any one of claims 27-28, wherein the beta-receptor blocker is atenolol or a pharmaceutically acceptable salt thereof.

30. The composition of any one of claims 27-28, wherein the beta-receptor blocker is metoprolol or a pharmaceutically acceptable salt thereof.

31. The composition of claim 30, wherein the beta-receptor blocker is selected from the group consisting of metoprolol succinate and metoprolol tartrate.

32. The composition of any one of claims 27-28, wherein the beta-receptor blocker is carvedilol or a pharmaceutically acceptable salt thereof.

33. The composition of claim 32, wherein the beta-receptor blocker is carvedilol phosphate.

34. The composition of any one of claims 27-28, wherein the beta-receptor blocker is labetalol or a pharmaceutically acceptable salt thereof.

35. The composition of claim 34, wherein the beta-receptor blocker is labetalol hydrochloride.

36. The composition of any one of claims 27-28, wherein the beta-receptor blocker is propranolol or a pharmaceutically acceptable salt thereof.

37. The composition of claim 36, wherein the beta-receptor blocker is propranolol hydrochloride.

38. The composition of any one of claims 27-28, wherein the beta-receptor blocker is bisoprolol or a pharmaceutically acceptable salt thereof.

39. The composition of claim 38, wherein the beta-receptor blocker is bisoprolol fumarate.

40. The composition of any one of claims 27-28, wherein the beta-receptor blocker is propafenone or a pharmaceutically acceptable salt thereof.

41. The composition of claim 40, wherein the beta-receptor blocker is propafenone hydrochloride.

42. The composition of any one of claims 27-41, wherein the mass ratio of the taurine to the beta-receptor blocker is 80: 1-2:

1.

43. The composition of any one of claims 27-42, wherein the mass ratio of the taurine to the beta-receptor blocker is 40: 1-1:

1.

44. The composition of any one of claims 27-43, wherein the mass ratio of the taurine to the beta-receptor blocker is 80: 1, 40: 1, 20: 1, 200: 15, 8: 1, 100: 15, 4: 1, 16: 5, 2: 1, or 1:

1.

45. The composition of any one of claims 24-44, wherein the composition has one or more of the following functions: improving memory impairment, improving social impairment, improving speech and communication impairment, reducing repetitive stereotypic behavior, improving sensory ability deficits, and improving motor ability deficits.

46. The composition of any one of claims 27-45, wherein the composition has one or more of the following functions: improving memory impairment in a patient with autism spectrum disorder, improving social impairment in a patient with autism spectrum disorder, improving speech communication impairment in a patient with autism spectrum disorder, reducing repetitive stereotyped behavior in a patient with autism spectrum disorder, improving sensory ability deficits in a patient with autism spectrum disorder, improving motor ability deficits in a patient with autism spectrum disorder, and improving self-care ability in a patient with autism spectrum disorder.

47. The composition of any one of claims 27-46, wherein the composition has one or more of the following functions: rescuing social preference in a patient with autism spectrum disorder, rescuing social memory in a patient with autism spectrum disorder, rescuing empathic ability in a patient with autism spectrum disorder, rescuing spatial memory in a patient with autism spectrum disorder.

48. The composition of any one of claims 27-47, wherein the composition is a pharmaceutical composition and comprises a pharmaceutically acceptable carrier.

49. A method of treating autism spectrum disorder, comprising administering taurine and a beta-receptor blocker to a subject.

50. A method of treating autism spectrum disorder, comprising administering the composition of any one of claims 27-48 to a subject.

51. Use of taurine and a beta-receptor blocker for treating autism spectrum disorder.

52. Use of the composition of any one of claims 27-48 for treating autism spectrum disorder.

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