Pinitol-containing composition for preventing or treating sensorimotor gating disorders

Abstract

The present invention relates to a pinitol-containing composition for preventing or treating sensorimotor gating disorders, and more specifically, provides a pharmaceutical composition and a health functional food composition for preventing, alleviating, or treating sensorimotor gating disorders, the compositions containing pinitol or a pharmaceutically / sitologically acceptable salt thereof as an active ingredient. The compositions can be used to safely prevent, alleviate, or treat sensorimotor gating disorders without side effects.

Description

Composition for preventing or treating sensorimotor gate disorder containing pinitol

[0001] The present invention relates to a composition containing pinitol for preventing or treating sensorimotor gating disorders, and more particularly, to a pharmaceutical composition and a health functional food composition containing pinitol or a pharmaceutically / foodstuffally acceptable salt thereof for preventing, improving or treating mental or neurological disorders in which sensorimotor gating disorders are observed.

[0002] Sensorimotor gating is the process by which information about various senses, cognition, and behavior is filtered out. One way to measure this sensorimotor gating is through prepulse inhibition (PPI) of the startle reflex. Prepulse inhibition measures the acoustic startle response evoked by a sudden loud sound, either with or without mild prestimulation. The mild prestimulation suppresses the subsequent strong acoustic startle response. Anatomically, the circuit connecting the cerebrum, striatum, putamen, and thalamus (the Cortico-Striatal-Pallido-Thalamic (CSPT) region) is crucial for this mechanism. Neurochemical regulation of PPI is linked to several neurotransmitters, including dopamine, norepinephrine, glutamate, and serotonin. Therefore, numerous studies have investigated the effects of these neurotransmitters on various drug responses in animal models.

[0003] Damage to the sensorimotor gate can be confirmed in various mental illnesses, and is known to be particularly evident in schizophrenia, obsessive-compulsive disorder, autism spectrum disorder (autism), post-traumatic stress disorder (PTSD), Tourette's disorder, and Huntington's disease. In addition, sensorimotor gate damage has been reported to occur in children with 22q gene deletion, children with Fragile X syndrome, adults with Jaspers syndrome, epilepsy, and Lewy body dementia, but it has not been found in Alzheimer's disease, Parkinson's disease, or unipolar depression (Neurotox Res. 2006 Dec; 10(3-4): 211-220, Geyer MA). Therefore, sensorimotor gate damage can be utilized as a physiological marker for the above mental or neurological illnesses. In addition, it can be used to develop treatments for the above diseases.

[0004] Schizophrenia is a mental illness affecting approximately 0.5 to 1% of the population worldwide. It is a widespread, endogenous disorder characterized by changes in thinking, perception, and behavior. Symptoms of schizophrenia are categorized into negative symptoms, characterized by a lack of spontaneous behavior, severe maladjustment, monotonous emotions, interpersonal deficits, and abnormal thinking; positive symptoms, including psychomotor agitation, delusions, auditory hallucinations, and cognitive impairment. The cause of schizophrenia is related to an imbalance of the neurotransmitter dopamine in the brain and damage to the frontal lobe. It is believed to be the result of genetics, prenatal environment, social factors, or substance abuse. Treatment for schizophrenia involves pharmacological treatment, centered on tranquilizers, separate from psychosocial therapy. Conventional antipsychotic medications focus on treating positive symptoms such as hallucinations, delusions, and confusion. Dopamine antagonists are known to be effective, and long-term administration of these medications, often lasting for a year, is essential. Specifically, haloperidol, chlorpromazine, and fluphenazine are used, but these drugs not only have many side effects such as movement disorders, involuntary muscle spasms, emotional dullness, fatigue, lack of drive, and weight gain, but also have the limitation of not being able to treat negative symptoms and cognitive impairment. Recent atypical antipsychotics target the limbic system and treat both positive and negative symptoms with fewer side effects than typical antipsychotics that block dopamine D2 receptors. Examples include clopazine, risperidone, asenapine, olanzapine, and aripiprazole. Although known to have fewer side effects, atypical antipsychotics still have various side effects and can even cause extrapyramidal side effects (Cureus.2019 Nov 14; 11(11):e6152, Zareifopoulos N et al.).

[0005] Post-traumatic stress disorder (PTSD) is a psychological trauma that can occur after experiencing an event that causes mental shock, such as physical injury or fear for one's life. It is often accompanied by depression, anxiety disorder, or panic disorder, and in severe cases, symptoms can appear to interfere with social activities, which can lead to serious crimes. Currently, selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) are used to treat PTSD, but these have significant side effects. Candidate substances being developed as treatments, while effective, have a high risk of causing dependence, necessitating the urgent discovery of new materials.

[0006] Obsessive compulsive disorder (OCD) is a general term for a disorder characterized by repetitive, unwanted thoughts and behaviors. Its main symptoms include obsessions, which are distressing thoughts, impulses, or images that repeatedly intrude into consciousness, and compulsive behaviors, which are repetitively performed to reduce anxiety. Compulsive behaviors primarily manifest in the form of cleaning, checking, repetition, ordering, and procrastination. These behaviors are known to be performed repeatedly to relieve anxiety caused by obsessive thoughts, even though the individual knows they are inappropriate and excessive (Clin Psychol Rev. 2017 Jan 16; 52:137-147. Laura MS De Putter et al., J Cent Nerv Syst Dis. 2016 Aug 21; 8:13-29. Rapp AM et al.).

[0007] Autism spectrum disorder (ASD) is a complex developmental disorder characterized by a wide range of symptoms, including repetitive, stereotyped behaviors and difficulties with social interaction and communication. Currently, there are no specific biomarkers available for diagnostic screening or treatment in ASD patients. Stereotypic and repetitive behaviors are triggered by neurochemical changes in the amygdala, cerebellum, hippocampus, and cerebral cortex. In addition to core functions, other common symptoms observed in children include dyskinesias, sleep disturbances, speech delays, gastrointestinal problems, anxiety, irritability, and epilepsy. While there is no established treatment for ASD patients, many patients rely on medications, including those for behavioral problems or for comorbid conditions such as ADHD (Acad Pediatr. 2021; 21(2): 272-279. Rast JE et al.).

[0008] Meanwhile, Tourette syndrome is characterized by motor and vocal tics, which begin before puberty, worsen and remit, and improve in adulthood, but can persist throughout life if left untreated. It has also been reported to be related to problems with the sensorimotor gating system, as reduced PPI is observed compared to normal controls (Biol Psychiatry. 1996; 39(1): 33-41, Castellanos FX et al.). Antipsychotic drugs such as haloperidol and aripiprazole are primarily preferred for the treatment of Tourette's disorder, but the alpha-2 receptor agonist clonidine is also used. However, typical and atypical antipsychotic drugs have poor patient compliance because they cause sedative and extrapyramidal side effects (J Korean Acad Child Adolesc Psychiatry 2014; 25(2): 53-64, Lim MH et al.).

[0009] As such, disorders related to sensorimotor gateway dysfunction have a very wide range of symptoms and various medications such as antidepressants, antipsychotics, and anti-anxiety medications are used to alleviate each symptom, but these medications still have many side effects. In particular, medications for treating schizophrenia or Tourette syndrome can cause extrapyramidal side effects, and medications for treating major depressive disorder used for obsessive-compulsive disorder can significantly reduce medication compliance due to side effects such as sleep disturbances and sexual dysfunction, making drug treatment difficult.

[0010] Accordingly, there is a need for a treatment that restores sensorimotor gateway dysfunction without causing the various side effects mentioned above, such as extrapyramidal side effects, sleep disorders, and sexual dysfunction.

[0011] The purpose of the present invention is to provide a pharmaceutical composition or food composition that can effectively prevent, improve or treat sensorimotor gateway disorders without side effects.

[0012] In order to achieve the above purpose, the present invention provides a pharmaceutical composition for preventing or treating sensorimotor gate disorder, containing pinitol or a pharmaceutically acceptable salt thereof as an active ingredient.

[0013] The present invention provides a health functional food composition for preventing or improving sensorimotor gateway disorders, containing pinitol or a food-related acceptable salt thereof as an active ingredient.

[0014] In addition, the present invention provides a method for treating sensorimotor gateway disorder, comprising administering the pharmaceutical composition to a subject suspected of having sensorimotor gateway disorder.

[0015] A composition comprising pinitol or a pharmaceutically / foodstuffally acceptable salt thereof according to the present invention may have an excellent therapeutic or improving effect on diseases related to sensorimotor gateway disorders such as schizophrenia, post-traumatic stress syndrome, or obsessive-compulsive disorder.

[0016] The composition according to the present invention comprises pinitol, which is already used as a raw material for health functional foods, or a pharmaceutically / foodstuffally acceptable salt thereof, and thus can be safely used as a pharmaceutical composition and health functional food composition for preventing, improving, or treating sensorimotor gateway disorders without side effects.

[0017] Figure 1 shows the effect of D-pinitol on the reduction of prestimulus inhibition by MK-801 administration in an animal model of schizophrenia.

[0018] Figures 2 and 3 show the effect of D-pinitol in an animal model of post-traumatic stress syndrome.

[0019] Figure 4 shows the effect of D-pinitol on the bead-burying test, an indicator of post-stress obsessive-compulsive disorder.

[0020] Hereinafter, the present invention will be described in detail.

[0021]

[0022] The inventor of the present invention has completed the present invention by examining various drugs in order to develop a drug for treating mental and neurological diseases such as schizophrenia, obsessive-compulsive disorder, post-traumatic stress disorder, Tourette syndrome, and autism, which are diseases related to sensorimotor gateway disorders, and confirming that D-pinitol or a compound related thereto improves sensorimotor gateway disorders without side effects.

[0023]

[0024] The present invention provides a pharmaceutical composition for preventing or treating sensorimotor gate disorder, containing pinitol or a pharmaceutically acceptable salt thereof as an active ingredient.

[0025] In this specification, "pinitol" refers to cyclitol present in the heartwood of Pinus lambertiana (sugar pine) and most other conifers, the sap of Madagascar gum, senna leaves, etc., and may be named as D-pinitol, 3-O-methyl-D-chiro-inositol, etc.

[0026] The above pinitol can be extracted or manufactured by a method well known in the art, and a commercially available one can be selected and used, but the method or material is not particularly limited.

[0027] The above pinitol can be used in the form of a pharmaceutically or food-wise acceptable salt within the range having the same efficacy.

[0028] As used herein, “pharmaceutically or food-wise acceptable” means a salt that is non-toxic to cells or humans exposed to the composition and has a safety and efficacy profile suitable for administration to humans.

[0029] The above salt may be used in the form of either a basic salt or an acid salt that is pharmaceutically or food-wise acceptable. The basic salt may be used in the form of either an organic basic salt or an inorganic basic salt, and may be selected from the group consisting of sodium salt, potassium salt, calcium salt, lithium salt, magnesium salt, cesium salt, aminium salt, ammonium salt, triethylaminium salt, and pyridinium salt.

[0030] Acid salts are useful as acid addition salts formed by free acids. Inorganic acids and organic acids can be used as free acids, and inorganic acids include hydrochloric acid, hydrobromic acid, sulfuric acid, sulfurous acid, phosphoric acid, diphosphoric acid, nitric acid, etc., and organic acids include citric acid, acetic acid, maleic acid, malic acid, fumaric acid, gluconic acid, methanesulfonic acid, benzenesulfonic acid, camphorsulfonic acid, oxalic acid, malonic acid, glutaric acid, acetic acid, glycolic acid, succinic acid, tartaric acid, 4-toluenesulfonic acid, galacturonic acid, embonic acid, glutamic acid, citric acid, aspartic acid, stearic acid, etc., but are not limited thereto, and all salts formed using various inorganic acids and organic acids commonly used in the art can be included.

[0031] In addition, the above pinitol may include not only the above salts, but also all salts, hydrates, solvates, derivatives, etc. that can be prepared by conventional methods. The addition salts can be prepared by conventional methods, and can be prepared by dissolving in a water-miscible organic solvent such as acetone, methanol, ethanol, or acetonitrile, adding an excess amount of organic base, or adding an aqueous base solution of an inorganic base, and then precipitating or crystallizing. Alternatively, the addition salt can be obtained by evaporating the solvent or the excess base from the mixture and then drying, or by suction filtration of the precipitated salt.

[0032]

[0033] In the present invention, the sensorimotor gateway disorder or a disease related thereto may be selected from the group consisting of schizophrenia, obsessive-compulsive disorder, post-traumatic stress disorder, Tourette syndrome, and autism spectrum disorder.

[0034] According to one embodiment of the present invention, it was confirmed that pinitol can improve schizophrenic symptoms by increasing the prestimulus inhibition rate in an animal model of schizophrenia induced by dizocilpine (MK-801), an NMDA (N-methyl-D-aspartate) inhibitor.

[0035]

[0036] The pharmaceutical composition according to the present invention can be prepared according to conventional methods in the pharmaceutical field. The pharmaceutical composition can be combined with an appropriate pharmaceutically acceptable carrier depending on the formulation, and, if necessary, can be prepared by further including excipients, diluents, dispersants, emulsifiers, buffers, stabilizers, binders, disintegrants, solvents, etc. The appropriate carrier, etc., can be selected differently depending on the dosage form and formulation as long as it does not inhibit the activity and properties of pinitol or a pharmaceutically acceptable salt thereof according to the present invention.

[0037] The pharmaceutical composition according to the present invention can be applied in any dosage form, and more specifically, it can be formulated and used as an oral dosage form, an external preparation, a suppository, and a parenteral dosage form of a sterile injection solution according to a conventional method.

[0038] Among the oral dosage forms, the solid dosage form may be in the form of tablets, pills, powders, granules, capsules, etc., and may be prepared by mixing at least one excipient, such as starch, calcium carbonate, sucrose, lactose, sorbitol, mannitol, cellulose, gelatin, etc. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be included. In addition, in the case of a capsule dosage form, in addition to the above-mentioned substances, a liquid carrier such as fatty oil may be further included.

[0039] Among the above oral dosage forms, liquid dosage forms include suspensions, solutions, emulsions, syrups, etc., and in addition to commonly used simple diluents such as water and liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included.

[0040] The above parenteral formulations may include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, and suppositories. Non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. Suppository bases may include witepsol, macrogol, Tween 61, cacao butter, laurin, glycerogelatin, and the like. Without limitation, any suitable formulation known in the art may be used.

[0041]

[0042] In the pharmaceutical composition according to the present invention, the pharmaceutical composition can be administered in a pharmaceutically effective amount.

[0043] As used herein, “pharmaceutically effective amount” means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment and not causing adverse effects.

[0044] The effective dosage level of the above pharmaceutical composition may be determined differently depending on factors including the purpose of use, the patient's age, sex, weight and health condition, the type and severity of the disease, the activity of the drug, the sensitivity to the drug, the method of administration, the time of administration, the route of administration and the excretion rate, the duration of treatment, the drugs used in combination or concurrently, and other factors well known in the medical field.

[0045] The pharmaceutical composition according to the present invention can be administered to adults at a single or multiple doses of 10 to 2000 mg / kg per day, preferably at a single or multiple doses of 50 to 500 mg / kg, to suppress sensorimotor gateway disorders or related diseases. The above range represents a safe, non-toxic dose.

[0046] The pharmaceutical composition according to the present invention can be administered to any animal that may develop a sensorimotor gateway disorder, and the animal may include, for example, humans and primates, as well as livestock such as cows, pigs, horses, and dogs.

[0047] The pharmaceutical composition according to the present invention can be administered via an appropriate route of administration depending on the formulation form, and can be administered via various routes, either oral or parenteral, as long as it can reach the target tissue. The method of administration is not particularly limited, and can be administered by conventional methods such as oral, rectal, intravenous, intramuscular, or skin application, respiratory inhalation, intrauterine epidural, or intracerebroventricular injection.

[0048]

[0049] The present invention provides a health functional food composition for preventing or improving sensorimotor gateway disorders, containing pinitol or a food-related acceptable salt thereof as an active ingredient.

[0050] In the health functional food composition according to the present invention, the health functional food can be manufactured in the form of powder, granules, tablets, capsules, syrup, or beverage, and there is no limitation on the form that the health functional food can take, and all foods in the conventional sense can be included. For example, beverages and various drinks, fruits and processed foods thereof (canned fruits, jams, etc.), fish, meat and processed foods thereof (ham, bacon, etc.), bread and noodles, cookies and snacks, dairy products (butter, cheese, etc.), etc. are possible, and all functional foods in the conventional sense can be included. In addition, foods used as feed for animals can also be included.

[0051] The health functional food composition according to the present invention may be manufactured by further including food additives (food additives) commonly used in the art and other appropriate auxiliary ingredients. Unless otherwise specified, suitability as a food additive may be determined by the specifications and standards for the relevant item, as stipulated in the General Provisions and General Test Methods of the Food Additives Code approved by the Ministry of Food and Drug Safety.

[0052] The above other auxiliary ingredients may additionally contain, for example, flavoring agents, natural carbohydrates, sweeteners, vitamins, electrolytes, coloring agents, pectic acid, alginic acid, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonating agents, etc. In particular, as the natural carbohydrates, monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, sugar alcohols such as xylitol, sorbitol, and erythritol can be used, and as the sweetener, natural sweeteners such as thaumatin and stevia extract, or synthetic sweeteners such as saccharin and aspartame can be used.

[0053] The effective dose of pinitol or a food-based acceptable salt thereof contained in the health functional food according to the present invention can be appropriately adjusted depending on the intended use, such as prevention or improvement of sensorimotor gateway disorders.

[0054] The above composition has the advantage of being made from food and having no side effects that may occur with long-term use of general medicines, and is highly portable, so it can be taken as a supplement for preventing or improving sensorimotor gateway disorders.

[0055]

[0056] In addition, the present invention provides a method for treating sensorimotor gateway disorder, comprising administering the pharmaceutical composition described above to a subject suspected of having sensorimotor gateway disorder.

[0057] The corresponding features can be replaced by those described above.

[0058] Hereinafter, to aid understanding of the present invention, examples will be given in detail. However, the following examples are intended only to illustrate the scope of the present invention and are not intended to limit its scope. These examples are provided to more fully explain the present invention to those of average skill in the art.

[0059] All experimental results were statistically analyzed using one-way ANOVA (one-way analysis of variance) or two-way ANOVA, and when significance was recognized, significance testing was performed at a level of P < 0.05 or lower using the Student-Newman-Keuls Test, Tukey's test, or Bonferroni test.

[0060]

[0061] <Example 1> Confirmation of the effect of D-pinitol on improving schizophrenia-like behavior in an animal model of schizophrenia administered with MK-801.

[0062] 1.1. Purchasing D-pinitol and preparing mice

[0063] D-pinitol was purchased from Sigma-Aldrich (Product Number: 441252, USA) and used in this experiment. The highest dose of D-pinitol used in this experiment, 300 mg / kg, was confirmed to be a safe dose in terms of toxicity.

[0064] Six-week-old ICR mice (26-28 g) to be used in the experiment were supplied by Orient Co., Ltd. (Seoul, Korea) and acclimated to a clean cage at the College of Pharmacy, Kyung Hee University for approximately 5 days. Water and food were provided ad libitum, and temperature (23 ± 1 ℃), humidity (60 ± 10%), and light / dark cycle (12 h) were automatically controlled.

[0065]

[0066] 1.2. Effects of D-pinitol treatment on sensorimotor gate inhibition

[0067] D-Pinitol, described in 1.1 above, was dissolved in 0.9% NaCl solution and orally administered to mice at various doses (30, 100, 300 mg / kg). The control group was administered 0.9% NaCl solution. Each group used 8 to 10 mice, and no fasting was performed.

[0068] This experiment is a neurophysiological and behavioral measurement method for sensorimotor association. In an animal model of schizophrenia, administering an NMDA (N-methyl-D-aspartate) antagonist such as MK-801 (dizocilpine) or a dopamine agonist such as apomorphine prevents prepulse inhibition (Noda et al., 2001; Howes and Kapur, 2009). Based on this fact, we stimulated rats with a strong sound of several decibels in a startle box and measured their responses to determine whether the drug was effective in an animal model of schizophrenia.

[0069] The surprise box consists of a box in which rats can be lightly restrained, a system that can deliver a constant sound stimulus ranging from 5 to 130 dB, equipment to measure animal movement, a program to digitize the measured stimulus, and a sound source and speaker. For each test, rats were allowed to acclimate in the restraint box for 5 minutes, with white noise (70 dB) added as a background sound. Because animals may overreact to stimuli, the animals were acclimated several times with a 120 dB, 40 ms sound stimulus. Then, the animals' responses to each stimulus were measured by giving sound stimuli of 80 to 120 dB. Afterwards, four situations were randomly assigned: 120 dB alone (SS), a prepulse (PP) alone, no stimulus, and a 120 dB sound 40 ms after the prepulse, and each response was measured. After measuring the startle response of the animal to each stimulus, the response ratio between the situation where only 120 dB was stimulated and the situation where 120 dB was stimulated after the pre-stimulus (PS) was measured and the data was analyzed by calculating it using the following mathematical formula 1.

[0070] [Mathematical Formula 1]

[0071] Prestimulus inhibition (PPI) (%) = [(SS - PS) / SS] X 100

[0072]

[0073] The effect of D-pinitol on prestimulus inhibition in an animal model of schizophrenia induced by MK-801 was investigated using mice. In all experiments, the prestimulus inhibition ratio of the group administered only MK-801 was significantly reduced compared to the control group. As shown in Figure 1, the prestimulus inhibition ratio of the group administered only MK-801 was 8.294 ± 6.107 and 16.85 ± 2.139% at PP12 (prestimulus 12 dB higher than white noise) and PP16 (prestimulus 16 dB higher than white noise), respectively, whereas in the group administered 300 mg / kg of D-pinitol, it significantly increased to 28.33 ± 3.591 and 39.42 ± 2.512 (p < 0.05) %, respectively. (mean ± SEM)

[0074]

[0075] <Example 2> Confirmation of the improvement effect of D-pinitol in an animal model of post-traumatic stress syndrome induced by various stresses.

[0076] 2.1. Purchasing D-pinitol and preparing mice

[0077] D-Pinitol and mice were treated in the same manner as in 1.1 above.

[0078]

[0079] 2.2. Improvement of post-traumatic stress disorder by D-pinitol treatment

[0080] D-pinitol, described in 1.1 above, was dissolved in 0.9% NaCl solution and orally administered to mice at various doses (100 mg / kg). The control group was administered 0.9% NaCl solution. Post-traumatic stress disorder (PTSD) animal models were created in mice by applying stress such as 2 h of restraint stress, 20 min of swimming and 5 dives, and anesthesia stress (Chen et al., 2021; Malikowska-Racia, Popik, & Sałat, 2020). After allowing these animals to acquire fear memories, we examined whether D-pinitol administration promoted the extinction of fear memories and normalized them, thereby evaluating the effect of D-pinitol on improving PTSD.

[0081] Fear memory in mice was induced using a conditioned fear response based on Pavlovian conditioning. First, mice were acclimated to an electric shock box (Lafayette Instrument, Lafayette, IN) for 2 minutes, after which they were exposed to 10 seconds of white noise (90 dB; CS; conditioned stimulus). During the last 2 seconds of white noise exposure, a 0.8 mA electric shock (US; unconditioned stimulus) was delivered. This was followed by 60 seconds of no stimulation. This process was repeated five times, and after the final electric shock, the mice were placed in the electric shock box for 60 seconds. All events were recorded using Freeze Frame software (Actimetrics, Wilmette, IL) and subsequently used to measure fear responses (freezing). Fear responses were defined as a state of immobility other than breathing lasting more than 2 seconds, which was automatically calculated by the computer. The effect of D-pinitol on extinction of fear memory and recall of fear memory in mice in which the above fear memory was induced was measured as follows.

[0082] After fear memory formation through conditioning learning, the effect of D-pinitol on the extinction of fear memory was measured as follows when the CS was re-exposed without the US in a box with a floor made of a different material.

[0083] Mice exhibiting post-traumatic stress disorder were divided into two groups, and a control group that was not administered D-pinitol and a group that was orally administered D-pinitol at 100 mg / kg were compared. As shown in Figure 2, when the extinction of fear memory after acquisition of fear memory was compared with the control group, the freezing response was reduced in the D-pinitol-administered group, which was almost similar to the positive control group administered fluoxetine (FLX). This indicates that D-pinitol has an effect of promoting the extinction of fear memory in relation to the inhibition of fear memory extinction observed in post-traumatic stress disorder.

[0084] Furthermore, we sought to determine whether D-pinitol administration modulated the recall of fear memories the next day. As shown in Figure 3, the control group still retained fear memories, exhibiting increased freezing responses. However, the D-pinitol-administered group exhibited decreased freezing responses, similar to the fluoxetine-administered group, the positive control group. This suggests that D-pinitol has an effect of promoting the extinction of fear memories observed in post-traumatic stress disorder.

[0085]

[0086] <Example 3> Confirmation of the effect of improving obsessive-compulsive disorder using the marble burying test.

[0087] 3.1. Purchasing D-pinitol and preparing mice

[0088] D-Pinitol and mice were treated in the same manner as in 1.1 above.

[0089]

[0090] 3.2. Improvement of obsessive-compulsive disorder by D-pinitol treatment

[0091] When rodents are placed in cages lined with marbles, they exhibit a habit of burying the marbles, especially if they suffer from mental disorders such as obsessive-compulsive disorder. When treated with an OCD medication, the number of marbles hidden by the rodents significantly decreases. Using this simple experimental method (bead hiding), obsessive-compulsive disorder, repetitive behaviors, and impulsive behaviors can be identified in rodents (Cogn Affect Behav Neurosci. 2016 Jun;16(3):551-60. Wolmarans de W et al.).

[0092] D-pinitol described in 1.1 above was dissolved in 0.9% NaCl solution and orally administered to mice at various doses (10, 30, 100 mg / kg), and 0.9% NaCl solution was administered to the control group.

[0093] A bedding layer 5 cm high was placed in the cage, and 20 marbles were arranged in a 4 × 5 pattern on top. The mice were then placed in the cage containing the marbles and their behavior was observed for 30 minutes. After 30 minutes, the remaining marbles were photographed, and the number of marbles buried in the bedding was recorded. The number of marbles was counted only when two-thirds of the marbles were buried in the bedding. The greater the number of hidden marbles, the more repetitive behavior was increased. The average number of hidden marbles of the mice in each group is shown in Figure 4 below.

[0094] As shown in Figure 4, the group administered D-pinitol showed a significant decrease in the number of hidden beads compared to the vehicle-administered control group, indicating an improvement in repetitive behavior. In contrast, the WT group, a normal animal, showed no significant behavioral effects due to drug administration. This demonstrates that D-pinitol can effectively prevent or treat obsessive-compulsive disorder, which manifests as repetitive behavior.

[0095]

[0096] <Preparation Example 1> Preparation of a mountain ash

[0097] D-pinitol 100 mg

[0098] 100 mg of lactose

[0099] 10 mg of talc

[0100] The above ingredients are mixed and filled into a sealed bag to produce a powder.

[0101]

[0102] <Preparation Example 2> Preparation of tablets

[0103] D-pinitol 100 mg

[0104] 100 mg of corn starch

[0105] 100 mg of lactose

[0106] Magnesium stearate 2 mg

[0107] After mixing the above ingredients, tablets are manufactured by pressing them according to the usual tablet manufacturing method.

[0108]

[0109] <Preparation Example 3> Preparation of capsules

[0110] D-pinitol 100 mg

[0111] 3 mg of crystalline cellulose

[0112] 14.8 mg of lactose

[0113] Magnesium stearate 0.2 mg

[0114] The above ingredients are mixed according to the conventional capsule manufacturing method and filled into a gelatin capsule to manufacture a capsule.

[0115]

[0116] <Preparation Example 4> Preparation of injection

[0117] D-pinitol 100 mg

[0118] Mannitol 180 mg

[0119] 2974 mg of sterile distilled water for injection

[0120] Na2HPO4,12H2O 26 mg

[0121] According to the manufacturing method of a conventional injection, it is manufactured with the above ingredient content per 1 ampoule (2 ml).

[0122]

[0123] <Preparation Example 5> Preparation of liquid

[0124] D-pinitol 100 mg

[0125] 10 g of isoflavonoids

[0126] 5 g of mannitol

[0127] Appropriate amount of purified water

[0128] According to the usual method of manufacturing a liquid, each ingredient is added to purified water and dissolved, an appropriate amount of lemon zest is added, the above ingredients are mixed, purified water is added, and the total volume is adjusted to 100 ml. The liquid is then filled into a brown bottle and sterilized to manufacture the liquid.

[0129]

[0130] <Preparation Example 6> Manufacturing of health food

[0131] D-pinitol 100 mg

[0132] Vitamin mixture appropriate amount

[0133] Vitamin A acetate 70 μg

[0134] Vitamin E 1.0 mg

[0135] Vitamin B1 0.13 mg

[0136] Vitamin B2 0.15 mg

[0137] Vitamin B6 0.5 mg

[0138] Vitamin B12 0.2 μg

[0139] Vitamin C 10 mg

[0140] 10 μg of biotin

[0141] Nicotinamide 1.7 mg

[0142] 50 μg of folic acid

[0143] Calcium pantothenate 0.5 mg

[0144] Appropriate amount of mineral mixture

[0145] 1.75 mg of ferrous sulfate

[0146] 0.82 mg of zinc oxide

[0147] Magnesium carbonate 25.3 mg

[0148] 15 mg of monobasic potassium phosphate

[0149] 55 mg of dibasic calcium phosphate

[0150] Potassium citrate 90 mg

[0151] 100 mg of calcium carbonate

[0152] Magnesium chloride 24.8 mg

[0153] The composition ratio of the above vitamin and mineral mixture is a preferred example of a mixture of ingredients suitable for relatively healthy foods, but the mixing ratio may be arbitrarily modified, and the above ingredients may be mixed according to a conventional health food manufacturing method, granules may be manufactured, and used to manufacture a health food composition according to a conventional method.

[0154]

[0155] <Preparation Example 7> Manufacturing a health drink

[0156] D-pinitol 100 mg

[0157] 1000 mg of citric acid

[0158] 100 g of oligosaccharide

[0159] 2 g of plum concentrate

[0160] 1 g of taurine

[0161] Add purified water to make a total of 900 ml

[0162] The above ingredients are mixed according to a conventional health drink manufacturing method, then stirred and heated at 85°C for about 1 hour, the resulting solution is filtered, placed in a sterilized 2-liter container, sealed and sterilized, and then stored in a refrigerator, and then used to manufacture the health drink composition of the present invention.

[0163]

[0164] The above composition ratio is a preferred example of a mixture of ingredients relatively suitable for a preferred beverage, but the mixing ratio may be arbitrarily modified according to regional and national preferences such as demand class, demand country, and intended use.

[0165]

[0166] While specific aspects of the present invention have been described in detail above, it should be apparent to those skilled in the art that these specific descriptions merely represent preferred embodiments and are not intended to limit the scope of the present invention. In other words, the substantial scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A pharmaceutical composition for preventing or treating sensorimotor gate disorder, containing pinitol or a pharmaceutically acceptable salt thereof as an active ingredient.

2. In paragraph 1, The above sensorimotor gateway disorder is, A pharmaceutical composition characterized in that it is selected from the group consisting of schizophrenia, obsessive-compulsive disorder, post-traumatic stress disorder, Tourette syndrome, and autism spectrum disorder.

3. In paragraph 1, The above pharmaceutical composition, A pharmaceutical composition characterized in that it is used in a dosage of 10 to 2000 mg / kg.

4. In paragraph 1, The above pharmaceutical composition, A pharmaceutical composition characterized in that it is formulated in a dosage form selected from the group consisting of tablets, capsules, solutions, syrups, suspensions, and injections.

5. A health functional food composition for preventing or improving sensorimotor gateway disorder, containing pinitol or a food-related acceptable salt thereof as an active ingredient.

6. In paragraph 5, The above sensorimotor gateway disorder is, A health functional food composition characterized by being selected from the group consisting of schizophrenia, obsessive-compulsive disorder, post-traumatic stress syndrome, Tourette syndrome, and autism spectrum disorder.

7. A method for treating sensorimotor gateway disorder, comprising administering a pharmaceutical composition according to any one of claims 1 to 4 to a subject suspected of having sensorimotor gateway disorder.

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