KR20200046525A - Composition comprising pirenperone compound for treating fragile x syndrome and related developmental disorders - Google Patents

Abstract

The present invention relates to a composition for preventing, alleviating or treating fragile X syndrome or developmental disorders related to fragile X syndrome, containing pirenperone or a pharmaceutically acceptable salt thereof. Pirenperone in the present invention exhibits effects of alleviating and treating behavior of fragile X syndrome in an animal model lacking of FMR1 genes, which are genes responsible for fragile X syndrome, alleviating repetitive behavior and hyperactivity, alleviates cognitive ability decline, and at the same time relieving impulsiveness. Therefore, pirenperone or the pharmaceutically acceptable salt thereof of the present invention can be developed as a therapeutic agent and functional food for fragile X syndrome or related diseases.

Description

Composition for the treatment of fragile X syndrome and related developmental disorders comprising a pyrenferon compound as an active ingredient {COMPOSITION COMPRISING PIRENPERONE COMPOUND FOR TREATING FRAGILE X SYNDROME AND RELATED DEVELOPMENTAL DISORDERS}

The present invention relates to a composition for the prevention, amelioration or treatment of fragile X syndrome or related developmental disorders comprising pyrenperone or a pharmaceutically acceptable salt thereof.

Fragile X Syndrome (FXS) is caused by a decrease in the Fragile x mental retardation 1 (Fmr1) gene due to amplification of the number of repetitions of the CGG triple base at the 27.3 chromosome position of the X gene. It also causes a lack of FMRP (Fragile X mental retardation protein) produced through encoding. Because it is a disease caused by mutation in the X chromosome, it has a prevalence of about 1.5 times higher in men than in women. Fragile X syndrome has a variety of concomitant diseases, which are primarily associated with cranial nerve disease. Around 50% of the patients have attention deficit hyperactivity disorder (ADHD) or autism, and patients with mental retardation, impulsivity or speech and cognitive impairment are also many.

In order to study the vulnerable X syndrome treatment, mice lacking the cause gene, Fmr1 gene, were invented in 1994 and are still used to a large extent, and the animal model is hyperactivity, lack of sociality, repetitive behavior, anxiety disorder, depending on the strain of the mouse in use. It has phenotypes of various behavioral aspects such as cognitive decline.

Most drugs for the treatment of fragile X syndrome have been studied in group 1 metabolic glutamate receptors or induced amino acid receptors for the treatment of imbalance of glutamate and glutamate receptors. In addition, it targets several proteins, such as MMP9, MAP1B, PSD95, CaMKII, Arc, and STEP, which are involved in FMRP protein.

However, it is usually difficult to show a therapeutic effect on one symptom or fail in clinical practice.

In the present invention, while trying to develop a therapeutic agent capable of obtaining a direct therapeutic effect on various symptoms of fragile X syndrome, pyreneferon reduces repetition or hyperactivity in the animal model fragile X syndrome lacking Fmr1 and decreases cognition. The present invention has been completed by clarifying that it not only improves ability but also improves impulsivity.

Accordingly, the present invention is to provide a composition capable of preventing or treating one or more symptoms according to Fragile X Syndrome (FXS) or related disorders.

However, the technical problem to be achieved by the present invention is not limited to the above-mentioned problems, and other problems not mentioned will be clearly understood by those skilled in the art from the following description.

In order to achieve the above object, the present invention prevents, improves or treats symptoms of Fragile X Syndrome (FXS) or related developmental disorders containing pyrenferon or a pharmaceutically acceptable salt thereof as an active ingredient. It provides a composition for.

The fragile X syndrome may include repetitive behavior, hyperactivity, decreased learning ability, lack of sociality, or impulsiveness.

The vulnerable X syndrome-related developmental disorder is attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), intellectual disability, cognitive impairment, or impulse control Impulse control disorders.

The pyrenferon of the present invention exhibits an effect of improving hyperactivity, cognitive decline, and impulsiveness in the animal model of fragile X syndrome lacking the Fmr1 gene, thus vulnerable to the pyrenferon of the present invention or a pharmaceutically acceptable salt thereof It can be an effective candidate as an agent for improving and treating behavior of X syndrome.

In addition, the present invention can relieve various symptoms with a single drug at a time, and can have an effect without administering various drugs to patients of a young age, thereby reducing side effects associated with administration of many drugs and reducing economic burden.

Furthermore, since the fragile X syndrome has homology with various mental development diseases such as cognitive disorder, attention deficit hyperactivity disorder, impulsiveness, and autism, the present invention can be used for the treatment of various brain mental development diseases as well as the fragile X syndrome. .

Figure 1 confirms the effect of improving the hyperactivity of pyrenferon in the animal model lacking the Fmr1 gene, A is a result of confirming the distance of the rat during the same time as an indicator of hyperactivity, and B is an indicator of hyperactivity for the same time This is the result of checking the speed of the rat.
2 is a diagram confirming the effect of improving cognitive ability of pyrenferon in an animal model lacking the Fmr1 gene.
3 is a diagram confirming the effect of alleviating the impulse of pyrenferon in the animal model lacking the Fmr1 gene.
4 is a view confirming the effect of alleviating repetitive behavior of pyrenferon according to the present invention.

Hereinafter, the present invention will be described in more detail.

As described above, the fragile X syndrome is characterized by a decrease in cognitive ability including learning and memory, lack of sociality, difficulty in communication, hyperactivity, etc., and is accompanied by autism, attention deficit hyperactivity disorder, etc. Although it is accompanied by symptoms, a drug that can effectively treat one or more symptoms of fragile X syndrome and related developmental disorders simultaneously has not been reported.

Since pyreneferon according to the present invention exhibits a therapeutic effect against direct or indirect symptoms such as repetitive behavior, hyperactivity, cognitive decline, impulsiveness and anxiety symptoms of fragile X syndrome or related developmental disorders, pyrenferon and its pharmaceuticals The acceptable salt can be usefully used as an active ingredient in the pharmaceutical composition for prevention and treatment of fragile X syndrome and related developmental disorders.

The present invention provides a pharmaceutical composition for the prevention or treatment of developmental disorders related to Fragile X Syndrome (FXS) or Fragile X Syndrome, containing Pirenperone or a pharmaceutically acceptable salt thereof as an active ingredient. .

Specifically, pirenperone (Pirenperone), which is an active ingredient of the composition for the treatment of fragile X syndrome or related developmental disorder of the present invention, is a compound represented by the following Chemical Formula 1, the molecular formula is C ₂₃ H ₂₄ FN ₃ O ₂ , and the molecular weight is 393.462. g / mol. The IUPAC name for pyrenferon is 3- [2- [4- (4-fluorobenzoyl) piperidin-1-yl] ethyl] -2-methylpyrido [1,2-a] pyrimidin-4-one.

[Formula 1]

The pyrenferon of the present invention may include pyrenferon hydrate, pyrenferon derivative, or the like within a range having the same efficacy as the pyrenferon, and may also include a solvent compound or a stereoisomer thereof.

The method for obtaining the pyrenferon is not particularly limited, and a chemically synthesized or commercially available one can be used using a known manufacturing method.

In the present invention, the term "pharmaceutically acceptable salt" or "salt thereof" may be an acid addition salt formed by free acid. Acid addition salts can be prepared by conventional methods, for example, by dissolving the compound in an excess of an aqueous acid solution and precipitating the salt using a water miscible organic solvent such as methanol, ethanol, acetone or acetonitrile. In addition, the same molar amount of the compound and acid or alcohol in water (eg, glycol monomethyl ether) can be heated, and then the mixture is evaporated to dryness, or the precipitated salt can be suction filtered.

As the free acid, an inorganic acid or an organic acid may be used. As a non-limiting example of the inorganic acid, hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, and tartaric acid may be used, and these may be used alone or by mixing two or more. The "pharmaceutically acceptable salt" or "the salt thereof" may be an acid addition salt formed by free acid. Acid addition salts can be prepared by conventional methods, for example, by dissolving the compound in an excess of an aqueous acid solution and precipitating the salt using a water miscible organic solvent such as methanol, ethanol, acetone or acetonitrile. In addition, the same molar amount of the compound and acid or alcohol in water (eg, glycol monomethyl ether) can be heated, and then the mixture is evaporated to dryness, or the precipitated salt can be suction filtered.

The salt of the pyrenferon may include all salts of acidic or basic groups that may be present in the compound of the pyrenferon, unless otherwise indicated. For example, the salt of pyreneferon may include sodium, calcium, and potassium salts of hydroxy groups, and other cosmetically acceptable salts of amino groups include hard bromide, sulfuric acid, hydrogen sulfate, phosphate, and hydrogen phosphate. , Dihydrogen phosphate, acetate, succinate, citrate, tartrate, lactate, mandelate, methanesulfonate (mesylate) and p-toluenesulfonate (tosylate) salts. It can be manufactured through a manufacturing method.

In the present invention, "prophylaxis" refers to all actions that inhibit or delay the onset of the administration of the composition.

In the present invention, "improvement" or "treatment" means any action in which the symptoms of the disease are improved or beneficially altered by administration of the composition.

In the present invention, "vulnerable X syndrome" is preferably one or more symptoms selected from the group consisting of repetitive behavior, hyperactivity, decreased learning ability, lack of sociality, impulsiveness and anxiety, but is not limited thereto. Any symptoms reported as symptoms of fragile X syndrome can be included.

In the present invention, "vulnerable X syndrome-related developmental disorder" is Attention deficit hyperactivity disorder (ADHD), Autism spectrum disorder (ASD), Intellectual disability, Cognitive disorder (Cognitive) It is preferable to include any one or more developmental disorders selected from the group consisting of impairment, impulse control disorder and anxiety disorder, but is not limited thereto, and as a accompanying disorder or disease of fragile X syndrome Any of those reported can be included.

The autistic categorical disorders include Autistic disorder, Rett's disorder, Asperger's syndrome and Pervasive developmental disorder-not otherwise specified (PDD-NOS) You can.

In the present invention, the "vulnerable X syndrome-related developmental disorder", it is preferable to include any one or more symptoms selected from the group consisting of repetitive behavior, hyperactivity, decreased learning ability, lack of sociality, impulsiveness and anxiety symptoms. It is not limited, and any symptom that is reported as a symptom of "vulnerable X syndrome-related disorder" may be included.

In a specific embodiment of the present invention, the present inventors confirmed the change in hyperactivity according to the presence or absence of pyrenferon in mice lacking the Fmr1 gene, a vulnerable X syndrome model, and the increased hyperactivity of the Fmr1 gene deficient group was administered pyrenferon. Afterwards, it was confirmed that it improved to a level similar to that of the normal control (A and B in FIG. 1).

In addition, the present inventors confirmed that another phenotype of the fragile X syndrome confirmed the effect of pyrenferon administration on cognitive decline, and the cognitive ability was restored to a level similar to that of the normal control group in the group administered pyrenferon (FIG. 2). ).

In addition, since the present inventors reported impulsiveness in patients with fragile X syndrome, they confirmed the effect of alleviating impulse by pyrenferon. As a result, it was confirmed that the impulsive tendency shown in the group lacking the Fmr1 gene was restored to the normal level by administration of pyrenferon (FIG. 3).

Next, as a result of conducting a self-grooming test to confirm the therapeutic effect of pyrenferon on another phenotype of fragile X syndrome, repetitive behavior (homology), Fmr1 gene-deficient mice exhibited repeated behavior of grooming repeatedly. In comparison, it was confirmed that the degree of grooming was decreased in the experimental group administered with pyrenferon and recovered to show the level of grooming repetition at a level similar to that of the normal control group (FIG. 4).

When the composition of the present invention is used as a pharmaceutical, a pharmaceutical composition containing pyrenferon or a pharmaceutically acceptable salt thereof as an active ingredient may be formulated and administered in various oral or parenteral dosage forms as follows. However, it is not limited thereto.

Formulations for oral administration include, for example, tablets, pills, hard / soft capsules, liquids, suspensions, emulsifiers, syrups, granules, elixirs, etc. These formulations are diluents (e.g. lactose, dext, in addition to active ingredients). Rose, sucrose, mannitol, sorbitol, cellulose and / or glycine), lubricants (eg silica, talc, stearic acid and its magnesium or calcium salts and / or polyethylene glycols). Tablets may also contain a binder such as magnesium aluminum silicate, starch paste, gelatin, methylcellulose, sodium carboxymethylcellulose and / or polyvinylpyrrolidine, and optionally, such as starch, agar, alginic acid or its sodium salt. Disintegrants or boiling mixtures and / or absorbents, colorants, flavors, and sweeteners.

The pharmaceutical composition containing the pyrenferon of the present invention or a pharmaceutically acceptable salt thereof as an active ingredient may be administered parenterally, and parenteral administration may be administered by subcutaneous injection, intravenous injection, intramuscular injection, or intrathoracic injection. It depends on the method. At this time, in order to formulate a formulation for parenteral administration, a pharmaceutical composition containing pyreneferon or a pharmaceutically acceptable salt thereof as an active ingredient is mixed with water together with a stabilizer or a buffer to prepare a solution or suspension, and this is used as an ampoule or It can be prepared in a vial unit dosage form. The composition may be sterile and / or contain preservatives, stabilizers, hydrating or emulsifying accelerators, adjuvants such as salts and / or buffers for the control of osmotic pressure, and other therapeutically useful substances. It can be formulated according to the chemical or coating method.

In addition, the dosage of the composition of the present invention to the human body may vary depending on the patient's age, body weight, sex, dosage form, health status and disease degree, and is generally based on an adult patient having a body weight of 60 kg. 0.001 to 1,000 mg / day, preferably 0.01 to 500 mg / day, and may be dividedly administered once to several times a day at regular time intervals according to the judgment of a doctor or pharmacist.

In another aspect, the present invention provides a health functional food composition for preventing or improving symptoms of Fragile X Syndrome (FXS) or related disorders containing pyrenferon or a salt thereof as an active ingredient.

The specific contents of the pyrenferon are as described above.

In the present invention, the term "health functional food" refers to food prepared and processed in the form of tablets, capsules, powders, granules, liquids and pills, etc. using ingredients or ingredients having useful functionality for the human body. Here, the term 'functional' means to obtain a useful effect for health use such as adjusting nutrients or physiological effects on the structure and function of the human body. The health functional food of the present invention can be manufactured by a method conventionally used in the art, and at the time of manufacture, it may be prepared by adding raw materials and ingredients commonly added in the art. In addition, the formulation of the health functional food can also be prepared without limitation as long as the formulation is recognized as a health functional food. The health functional food composition of the present invention has the advantage that there is no side effect or the like that may occur when taking the food as a raw material, unlike a general drug, and has excellent portability, and is effective in alleviating symptoms of fragile X syndrome or related developmental disorders thereof It can be consumed as an adjuvant to promote.

In the health functional food for prevention or improvement of fragile X syndrome or related developmental disorder according to the present invention, when the pyrenferon is used as an additive of a health functional food, it can be added as it is or used with other foods or food ingredients, It can be suitably used according to a conventional method. The mixing amount of the active ingredient can be appropriately determined according to each purpose of use such as prevention, health or treatment.

The formulation of the dietary supplement can be in the form of powders, granules, pills, tablets, capsules, as well as in the form of regular food or beverages.

The type of the food is not particularly limited, and examples of foods to which the substance can be added include dairy products including meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, and ice cream. , Various soups, beverages, teas, drinks, alcoholic beverages and vitamin complexes, and may include all foods in the ordinary sense.

The mixing amount of the active ingredient can be appropriately determined according to its purpose of use (for prevention or improvement). In general, the amount of the compound in the health food can be added to 0.1 to 90 parts by weight of the total food weight. However, in the case of long-term intake for health and hygiene purposes or for health control purposes, the amount may be below the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount above the above range.

Among the functional foods according to the present invention, the beverage may contain various flavoring agents or natural carbohydrates, etc., as additional components, like a conventional beverage. The above-mentioned natural carbohydrates may be monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, and polysaccharides such as dextrin and cyclodextrin, sugar alcohols such as xylitol, sorbitol, and erythritol. Natural sweeteners such as Martin and Stevia extract, and synthetic sweeteners such as saccharin and aspartame can be used. The ratio of the natural carbohydrate may be about 0.01 to 0.04 g per 100 mL of the beverage according to the present invention, preferably about 0.02 to 0.03 g.

In addition to the above, the health functional food for prevention or improvement of fragile X syndrome or related developmental disorders according to the present invention includes various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, and protective properties It may contain colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, and carbonation agents used in carbonated drinks. In addition, the health functional food composition for preventing or improving fragile X syndrome or related developmental disorders of the present invention may contain flesh for the preparation of natural fruit juice, fruit juice beverages and vegetable beverages. These ingredients may be used independently or in combination. The ratio of these additives is not limited, but is generally selected from 0.01 to 0.1 parts by weight compared to 100 parts by weight of the functional food of the present invention.

Hereinafter, the present invention will be described in more detail through examples. These examples are only for illustrating the present invention, it will be apparent to those skilled in the art that the scope of the present invention is not to be construed as limited by these examples.

[Example]

Example 1. Preparation of experimental animals and drugs

Approximately 22g to 24g of 5-week-old Fmr1 knockout mice (Jackson Laboratory, USA) were purchased and allowed to freely consume water and feed while adapting to an environment with a temperature of 23 ± 2 ℃, a humidity of 55 ± 10% and a contrast cycle of 12 hours. After breeding (Konkuk University Laboratory Animal Center), it was used for the experiment.

All animals used wild type (WT) with normal expression of FMRP and KO male mice lacking FMRP expression (inducing Fragile X Syndrome (FXS)), and dosing and experiments were conducted according to age. Dosing was conducted at the same time. Behavioral experiments were conducted 30 minutes after dosing. 50-ug / kg pyrenferon (P126, Sigma Aldrich) in knock-out mice lacking FMRP expression (Example 1), wild-type mice and knock-out lacking FMRP expression The mice were divided into groups that received 0.25% DMSO, and were prepared as 6 animals per group. For the drug administration group, pyrenferon was dissolved in 0.25% DMSO and then administered intraperitoneally at a dose of 50 ug / kg. Meanwhile, 0.25% DMS0 was administered intraperitoneally to the control group.

Example 2. Confirmation of the effect of improving the hyperactivity of pyrenferon in vulnerable X syndrome experimental animals (A, B in FIG. 1)

To confirm the therapeutic effect of pyrenferon on hyperactivity, one of the phenotypes of fragile X syndrome and related developmental disorders, the presence or absence of pyrenferon administration through an open field test in an animal model lacking the Fmr1 gene in a 5 week old male The excessive behavioral changes were confirmed.

Specifically, the mice were placed in an open field box of 40 × 40 × 30 cm, and the behavioral tendencies of the mice were recorded for 25 minutes to confirm the total travel time and speed. The conditions of the experimental group and control are as follows [Table 1]. The experimental group dissolved the 50 ug / kg pyrenferon in 0.25% dimethyl sulfoxide 30 minutes before the experiment, and then intraperitoneally administered it and conducted an open field test.

division Mark Population
(Mari) Fmr1 gene lack Travel distance speed Normal control WT 6 Х 10000 cm Approx. 6 cm / s Control
(Solvent administration) Fmr1 KO 6 ○ 12500 cm 8 cm / s Experimental group
(50 ug / kg pyrenferon) KO + Drug 6 ○ 10000 cm Approx. 6 cm / s

As a result, as shown in [Table 1] and [FIG. 1], the group lacking the Fmr1 gene (control) in the total moving distance and the moving speed, which are the figures of the hyperactivity, moved a large distance at a high speed for the same time period, and were normal. Compared to the control group, the tendency for hyperactivity was recorded while recording a significantly higher value, whereas the group administered with pyrenferon (experimental group) showed a tendency to have no hyperactivity characteristic than the mice lacking the Fmr1 gene, and the hyperactivity was similar to the normal control group. It was confirmed to be relaxed.

Example 3. Confirmation of cognitive improvement effect of pyrenferon in vulnerable X syndrome experimental animals (FIG. 2)

Next, a Y-maze experiment was conducted to confirm the therapeutic effect of pyrenferon on cognitive decline, another phenotype of fragile X syndrome and related developmental disorders.

Specifically, the rats were placed in a Y-shaped labyrinth space, and cognitive ability experiments were conducted for 8 minutes. The Y maze device is composed of three arms, and each branch has a length of 50 cm, a width of 10 cm, and a height of 20 cm, and each branch is disposed at a constant angle of 120 ° to each other. Before starting the behavioral experiment, each mouse was placed in the Y-maze and allowed to adapt in the environment for 10 minutes. The mouse was then positioned in the center of the Y maze to face the intersection of both arms in a randomly selected direction, allowing the maze to be explored for 8 minutes. The number of movements in three different directions was calculated as a percentage of the total number of movements. The conditions of the experimental group and control are as follows [Table 2].

division Mark Population
(Mari) Fmr1 gene lack Degree of movement in other directions (%) Normal control WT 6 X About 60% Control
(Solvent administration) Fmr1 KO 6 ○ About 40% Experimental group
(50 ug / kg pyrenferon) KO + Drug 6 ○ About 55%

As a result, as shown in [Table 2] and [FIG. 2], the mice lacking the Fmr1 gene (control) had a degree of movement in different directions compared to the total direction of movement, about 40% of the total, compared to the normal control group. It was confirmed that it had a low cognitive ability, and the group administered with pyrenferon (experimental group) showed a cognitive ability of 55%, confirming that the cognitive ability was restored to a level similar to that of the normal control group.

Example 4. Confirmation of the effect of improving the impulsivity of pyrenferon in fragile X syndrome experimental animals (FIG. 3)

Next, in order to confirm the therapeutic effect of pyrenferon on impulsivity, another phenotype of fragile X syndrome and related developmental disorders, an elevated plus maze (EPM) experiment was conducted.

Specifically, the EPM is made of acrylic and consists of a cross (+) maze 40 cm above the floor. Of the four passages in the maze, two passages facing each other are open (open arm), and two opposite passages are surrounded by a wall 20 cm high (closed arm). The central platform was 8 cm in width and height, and the mouse was placed on the central platform at the start of the experiment to allow the maze to be freely explored for 5 minutes. Thereafter, for 8 minutes, the time the mouse stayed in the open arm and the closed arm was analyzed. This experiment in a plus (+)-shaped space consists of two spaces facing each other, either open spaces or closed spaces, which means that if you go to an open space more than normal, the impulsivity increases. It means that anxiety symptoms are expressed when sexuality is reduced and excessive (Pineda et al., 2014). This experiment measured which space the rat stayed in more.

division Mark Population
(Mari) Fmr1 gene lack Time in the open space Time stayed in a closed space Normal control WT 6 X About 80 seconds About 300 seconds Control
(Solvent administration) Fmr1 KO 6 ○ About 150 seconds About 250 seconds Experimental group
(50 ug / kg pyrenferon) KO + Drug 6 ○ About 80 seconds About 330 seconds

As a result, as shown in [Table 3] and [FIG. 3], it was confirmed that the mice lacking the Fmr1 gene (control) showed high impulse from the time in the open space was increased by about 2 times compared to the normal control group. On the other hand, in the group administered with pyrenferon (experimental group), it was confirmed that the impulse propensity was restored to a normal level since the time in the open space was the same as the normal control group.

Example 5. Confirmation of the effect of improving pyreneferon repeat behavior (homology) in fragile X syndrome experimental animals (FIG. 4)

Next, a self-grooming test was conducted to confirm the therapeutic effect of pyrenferon on recurrent behavior (homologism), another phenotype of fragile X syndrome and related developmental disorders. Mice usually show grooming of their body, but in autism spectrum disorder model mice, including fragile X syndrome, grooming may be excessive, leading to severe hair loss and body injury. It is said to be. Based on this fact, in order to confirm the therapeutic effect of pyrenferon homology in mice lacking the Fmr1 gene, the effect of improving grooming was confirmed. Specifically, mice lacking the Fmr1 gene were placed in an unarmoured cage (42 cmХ29 cmХ19 cm) and acclimatized for 10 minutes. Then, the grooming time was measured for 10 minutes to confirm the degree of repetitive action. The conditions and population of the experimental group and the control group are shown in [Table 4] below. For the significance test, one-way ANOVA was performed, and bonferroni`s post hoc test was used for the post-test.

division Mark Population
(Mari) Fmr1 gene lack Grooming time Normal control WT 6 X About 86.67 seconds Control
(Solvent administration) Fmr1 KO 6 ○ About 123.3 seconds Experimental group
(50 ug / kg pyrenferon) KO + Drug 6 ○ About 75 seconds

As a result, as shown in [Table 4] and [FIG. 4], the Fmr1 gene-deficient rats showed that the grooming was repeatedly repeated, and the degree of grooming was decreased in the experimental group administered pyrenferon, and It was confirmed that recovery was performed to show the grooming repeat level at a similar level (FIG. 4).

Claims (6)

A pharmaceutical composition for the prevention or treatment of developmental disorders related to Fragile X Syndrome (FXS) or Fragile X syndrome, containing Pirenperone or a pharmaceutically acceptable salt thereof as an active ingredient.
According to claim 1,
The fragile X syndrome is a pharmaceutical composition comprising repetitive behavior, hyperactivity, decreased learning ability, lack of sociality, impulsiveness or anxiety.
According to claim 1,
The vulnerable X syndrome-related developmental disorders include attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), intellectual disability, cognitive impairment, and impulse control A pharmaceutical composition having at least one selected from the group consisting of impulse control disorders and anxiety disorders.
Health functional food for preventing or improving symptoms of Fragile X Syndrome (FXS) or related disorders containing pyrenferon or a salt thereof as an active ingredient.
According to claim 4,
The fragile X syndrome is a health functional food that includes repetitive behavior, excessive behavior, decreased learning ability, impulsiveness or anxiety due to lack of sociality.
The method of claim 4 or 5,
The vulnerable X syndrome-related developmental disorders include attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), intellectual disability, cognitive impairment, and impulse control A health functional food selected from the group consisting of impulse control disorders and anxiety disorder.

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