KR102096165B1 - A pharmaceutical composition having a tic disorder improvement and therapeutic effect - Google Patents

Abstract

The present invention relates to a pharmaceutical composition derived from a natural product that has less side effects and has mitigation and treatment efficacy against tic disorders, behavioral and speech control disorders caused by Tourette syndrome, and more specifically, includes extracts of Jocar lamp (Uncaria rhynchophylla). It relates to a composition for treating or preventing a tic disorder.

Description

A pharmaceutical composition having a tic disorder improvement and therapeutic effect

The present invention relates to a pharmaceutical composition having a tic disorder improvement and treatment effect.

Tic Disorder and Tourette Syndrome are neurological abnormalities that repeat unconscious, uncontrolled sounds or behaviors, resulting in uncontrollable voice and behavior symptoms. In particular, Tourette syndrome is a case where both motor tics and negative tics appear and persist for more than a year, and often remain as adults. It usually develops around 8 years of age, and tic symptoms usually appear on the face and neck, moving under the body and developing into more complex patterns. Voice control disorders, motor control disorders, and hypersensitivity of sensations appear in a simple or complex manner, and in severe cases, tendency to be inherited in the form of vulgar language, sexual language, behavior disorder, aggressive behavior, etc. Midbrain limbic system). It also tends to be accompanied by other disorders such as attention deficit hyperactivity disorder, sleep disorder, learning disorder, and stuttering.

Tick disorder is a typical neuropsychiatric disorder that occurs when genetic and environmental factors interact and cause changes in specific parts of the brain during the development of the central nervous system. have. In particular, it is associated with abnormalities in the ancestral-thalamic-cortical (central brain limbic system) circuit of the cerebrum, and the genetic cause is not clearly identified, but it is thought that the mutation of the SLITRK1 gene located on chromosome 13q31.1 is related. As a hypothesis for the genetic cause, a mutation of the HDC gene located on chromosome 15q21-q22 has been raised. In addition, the hypothesis that the less birth weight was, the more severe the tick was, which was caused by environmental factors in the womb during pregnancy. In addition, compared to the general population, various perinatal complications that can induce hypoxia in the newborn's brain in children with tic disorders, abnormal fetal position, prolonged analgesia, premature babies, placental abnormalities, gestational poisoning, umbilical cord abnormalities, severe vomiting in early pregnancy and Severe emotional stress during pregnancy was found at a higher frequency. In addition, the hypothesis that the effects of sex hormones (which are more common in boys), psychosocial stress or drugs such as central neurostimulants, streptococcal infections, etc., can be caused are being studied. (Disease Management Headquarters website, Health Information-'Touret Syndrome')

Treatment includes drug therapy and behavioral therapy. Experimental therapy includes neurosurgical therapy, but the success of the results is still unclear. Particularly, in the case of drug treatment, haloperidol, fluphenazine, and pimozide, which are typical antipsychotic drugs, are used, but there may be side effects such as unpleasant feeling, extrapyramidal symptoms, and cognitive decline.

Accordingly, the present inventors conducted a study on a pharmaceutical composition derived from a natural product having less side effects, relief and treatment efficacy against tic disorder, Tourette syndrome, and the composition of the present invention is excellent in improving and treating the disease. Confirmed to complete the present invention.

Republic of Korea Patent Publication No. 1999-027571 Republic of Korea Patent Publication No. 10-2005-0044604

Accordingly, an object of the present invention is to provide a pharmaceutical composition derived from a natural product having less side effects, less tic disorder, negative and behavioral control disorder of Tourette syndrome, and therapeutic efficacy as an extract of Jogu.

In addition, another object of the present invention is to provide a health functional food having relieving and improving efficacy for tic disorders, speech and behavior control disorders of Tourette syndrome.

In order to achieve the above-described problems, the present invention provides a pharmaceutical composition for treating or preventing tic disorders, Tourette syndrome, including extracts of hot water extracted from Jogu lamp (Uncaria rhynchophylla).

In addition, the composition may be a hot water extracted by mixing the medicinal pear, hyssop, and throat with Jojo.

In addition, the composition has at least one effect during tic disorder improvement, tension, anxiety, anger improvement, concentration improvement, ADHD improvement, autism improvement or dementia improvement.

In addition, the effective dosage of the composition is 5 to 10g per time based on the powdery crude.

On the other hand, the present invention provides a health functional food for preventing or improving tic disorders, Tourette syndrome, including extracts of hot water extracted from Jogu lamp (Uncaria rhynchophylla).

In addition, the health functional food may include an extract extracted from hot water by mixing the county medicine, hyssop, and throat with Jojo.

The pharmaceutical composition having an improvement and treatment effect of tic disorder of the present invention has an effect of improving tic disorder and improving tension, anxiety, anger, improving concentration, improving ADHA, improving autism, and preventing dementia.

Figure 1 shows the improvement effect on scopolamine-induced neurological disorders and memory loss through the passive evasion test of the present invention.
Figure 2 shows the effect of improving concentration through the water-maze test of the present invention.
Figure 3 shows the effect of alleviating the symptoms of tic disorder and Tourette syndrome by YGTTS of the present invention.

Jogudeung (Uncaria rhynchophylla), also known as Jodeung, belongs to the family Puppetae. The thorny young branch is dried, and the shape is in the form of a fish hook. The small branches are squared, and the needle-shaped branches emerge from the leaf axils and bend down. The leaves are opposite, the cotyledon is large, and the inflorescence runs on the leaf axil. The sakwa is hairy in the shape of a club. The medicinal herb is a branch with a fishing thorn and two curved fishing thorns on the stem of a short branch, sometimes with only one side. It is 1 ~ 3㎝ long, 2㎜ wide, the outer surface is reddish brown to dark reddish brown, and the cross section is long oval to oval and light brown. It mainly suppresses the central nervous system and decreases blood pressure, acts to expand peripheral blood vessels, and is effective as a blood pressure lowering agent.

The present invention relates to a pharmaceutical composition having less side effects, tic disorder improvement and treatment effect with relief and treatment efficacy against tics disorder, speech and behavior control disorder caused by Tourette syndrome, and more specifically, Jo-gu (Uncaria rhynchophylla) It provides a pharmaceutical composition for the treatment or prevention of tic disorders comprising the extract of).

In addition, the present invention can be used to extract the hot water extracted by mixing the county medicinal, hyssop, and throat with Jojo.

In addition, according to the present invention provides a health functional food for preventing or improving tic disorders containing extracts of jogu etc.

The composition of the present invention specifically has the effect of improving one of tension, anxiety, anger, decreased concentration, ADHD, autism or dementia, which is frequently accompanied by tic disorder and tic disorder.

The effective dosage in the present invention can be administered at 5 to 10 g per time, based on powdery coarse, etc., and is preferably administered at 8 g per time.

According to the present invention, the composition may be used as an extract extracted by boiling water with jogu, etc., and preferably may be an extract extracted for 10 to 15 minutes in hot water. Here, it is preferable that the extraction time does not exceed 15 minutes in consideration of the activity change of the active ingredient due to heat.

In addition, the composition of the present invention includes a mixed extract extracted by mixing 8 g of crude bulb, 8 g of earl, 6 g of hyssop, 6 g of neck and 6 g.

Here, as the extraction method of the mixed extract, a generally known extraction method may be used, but it is preferable that the extraction is performed in consideration of a change in activity due to heat such as jojo. For example, a mixture of rooster medicine, hyssop, and throat is immersed in water for 1 to 2 hours in a water heater, and during this time, water is added to the water heater in the water heater during the water bath, and then water is heated for 10 minutes to prepare a mixed extract.

In the present invention, after drying and drying the jojo lamp, a jojo lamp in a crushed powder state may be used. It is advantageous to extract the active ingredient at the time of bathing.

In addition, the present invention provides a pharmaceutical composition for treating Tourette syndrome, obsessive-compulsive disorder, chronic motility spasm disorder, or vocal cord spasm disorder.

The term “treatment” in the present invention means to reverse, alleviate or prevent the disorder or condition to which this term applies, or the progression of one or more syndromes of such condition or disorder. The term “treatment” as used in the present invention means the “treatment” action defined immediately above.

The compositions or compounds disclosed herein are also useful for the treatment of Tourette's syndrome, Tourette's disorder, Jildratourette's syndrome, or Tourette's syndrome, simply referred to as Tourette's or TS, in connection with the treatment of tic disorders. The tic disorder may also be a pediatric autoimmune disorder (PANDAS), transient tic disorder, chronic tic disorder, or atypical tic disorder (NOS) associated with streptococcal infection. Transient tic disorder is characterized by multiple motor and / or negative tics that occur for at least 4 weeks, less than 12 months. Chronic tic disorders generally include single or multiple motor or negative tics (but not both) that have been present for over 1 year, and Tourette syndrome is diagnosed when both motor and negative tics are present for over 1 year. Tick Disorder NOS is diagnosed when a tic is present but does not meet the criteria for any particular tic disorder. The present compounds and compositions also include ticks induced as side effects of medication; Ticks associated with autism; And Tourett-like syndrome (eg, as a result of another disease or condition, sporadic, genetic, or neurodegenerative disorder), for the treatment of Tourette-like symptoms in the absence of Tourette syndrome.

The compositions or mixed extracts disclosed in the present invention are also more generally useful in the treatment of movement disorders. These disorders may include stiffness syndrome, chorea (e.g., occurring in Huntington's disease), cirrhosis and / or dystonia, tremor, or Parkinson's disease of any etiology. Movement disorders may also be caused by medication or other stimuli to which the patient has been exposed. For example, the compositions or mixed extracts disclosed herein may be derived from dopamine agonists (e.g., including but not limited to levodopa, levodopa and carbidopa combinations, ropinirole, pramipexole, or pergolide). Dyskinesia and antipsychotic drugs (e.g., without limitation haloperidol, risperidone, olanzapine, cuetiapine, aripiprazole, ziprasidone, paliperidone, iloperidone, perfenazine, metoclopramide, and chlorpromazine) It can be used to alleviate spontaneous dyskinesia induced by).

The compositions and compounds described herein can be administered to a subject who may be referred to as a “patient”. Although clearly intended to treat human patients, the present invention is not so limited. Since the composition will be relatively inexpensive to manufacture, the present invention includes methods of veterinary use (eg, treatment of domestic pets such as cats and dogs). Subjects are effectively treated whenever clinically beneficial results follow. This may mean, for example, complete or remarkable resolution of symptoms of the disorder, a decrease in the frequency of symptoms, a duration of severity, or a slower progression of the disorder. Thus, effective treatment for tic disorders is indicated by a decrease in the number, duration, frequency, or intensity of exercise tics, voice tics, or both exercise and voice tics. Preferably, at a level without significant toxicity in the patient, it can be determined by evaluating the patient's clinical symptoms before and after administration of a known amount of a particular composition.

Any of the methods described herein can include diagnosing a subject with a tic disorder (eg, a patient and more specifically a human patient). After diagnosis or in conjunction with a diagnostic test, the method may include providing the compound or composition described herein to a subject. “Providing” a compound or composition includes direct administration and indirect administration.

A “therapeutically effective amount” of a composition is an amount that causes a significant resolution of a patient's symptoms, a decrease in the frequency, severity, or duration of symptoms, or a slowing of the progression of the disorder. The present invention may also include monitoring patients to help optimize doses and schedules as well as to predict and optimize results.

The methods described herein are useful for the treatment of tics. Ticks can take many forms, but typically consist of simple, repetitive, sequential movements, gestures, and remarks that mimic some of the normal behavior.

Simple motor tics involve only a single muscle or group of muscles, and usually cause short swaying motions (severity tics), which can also be slow, such as short lasting abnormal postures (dysplastic tics) or static contractions (spastic tics) ). Examples of simple locomotor ticks include blinking, nose pulling, and shaking the head and limbs. The dystonia tics include persistent eye closure (eyelid spasm), eye displacement, lice, mouth opening, torticollis, continuous jaw opening, and shoulder turning. Tonic tic is typically indicated by abdominal contraction, limb spreading or limb bending. Examples of complex exercise ticks include shaking the head, bending or turning the torso, combing hair, touching, throwing, hitting, jumping, kicking, making rude gestures, belching, vomiting, nausea, smelling of objects, catching your genitals and other This includes making sensuous or obscene gestures (obscene behavior), and mimicking other gestures (echoing).

Simple voice ticks typically include nasal swelling, throat trimming, sore throating, screaming, yelling, coughing, squeezing, blowing your nose, trimming your throat, and making sucking sounds. Complex phonetic ticks are linguistically meaningful remarks and language expressions, such as obscene, vulgar, or otherwise socially inappropriate language or phrase (obsessive obscene), repetition of another person's language or phrase (echoic) , And repetition (synchronism) of one's remarks in a sentence, especially the last syllable, language, or phrase.

The composition of the present invention can be formulated according to its use. For example, the compound can be formulated to a pharmaceutically acceptable level in the composition for administration to a patient. These compositions can be prepared according to methods well known in pharmaceutical technology, and can be administered by various routes. Administration is topical (including ophthalmic or ocular (e.g. via eye drops) and mucous membranes including oral, intranasal, vaginal and rectal delivery (i.e., transmucosal)), lungs (e.g. by nebulizer) Inhalation or insufflation of the powder or aerosol comprising it may be intranasal, epidermal (and transdermal), ocular, or oral. Oral administration is preferred for its convenience in the present invention, but parenteral formulations can also be used, and such formulations are administered intravenously, intraartely, subcutaneously, intraperitoneally or intramuscularly (e.g., by injection or infusion). Can be. With the targeting of dopamine agonist receptors in the brain, intracranial (e.g., intrathecal or intraventricular) administration may also be considered within the scope of this method. Parenteral administration can be in the form of a single bolus dose, or can be, for example, by a continuous perfusion pump. Thus, formulations include depot formulations, including formulations that are acceptable to the West. For administration by various routes, the compounds described herein can be associated with nanoparticles or microparticles. Pharmaceutical compositions and formulations for topical administration may include transdermal patches, ointments, lotions, creams, gels, droplets, suppositories, sprays, liquids, powders, and the like. Conventional pharmaceutical carriers, aqueous, powder or oil bases, thickeners, and the like may be necessary or desirable.

Pharmaceutical compositions useful in the present invention may include the active ingredient in combination with one or more pharmaceutically acceptable carriers. When preparing pharmaceutical compositions, the active ingredient is typically mixed with excipients, diluted with excipients, or enclosed in such carriers, for example in the form of capsules, tablets, sachets, paper, or other containers. When the excipient acts as a diluent, it can be a solid, semi-solid, or liquid (eg, normal saline or buffered saline, such as phosphate buffered saline), which acts as a vehicle, carrier, or medium for the active ingredient. Accordingly, the composition may be a capsule (e.g., soft or hard gelatin capsule), tablet, pill, powder (e.g., sterile packaging powder), lozenge, sachet, cachet, elixir, suspension, emulsion, solution (Eg, sterile injectable solutions), suppositories, syrups, aerosols (as a solid or in a liquid medium), or in the form of ointments.

These forms may include, for example, up to about 10% by weight of active extract, and for this purpose, a fraction obtained by separating the active ingredient from the extract or the complex extract of the present invention may be used. In other embodiments, these forms may include at least 10% by weight or more of active compound (eg, at least or about 15%, 20%, 25%, 35% or 50% by weight of active compound). As is known in the art, the type of diluent can vary depending on the intended route of administration. The resulting composition can include additional agents, such as colorants, flavors or preservatives. The extract may also be applied to or incorporated into drug delivery devices, such as pumps or patches. The compounds of the invention may be administered alone or in mixtures in the presence of pharmaceutically acceptable excipients selected based on the mode and route of administration. In manufacturing, the active compound can be ground to provide a suitable particle size before being blended with other ingredients. If the active compound is substantially water insoluble, it can be ground to a particle size of less than 200 mesh to improve dissolution. If the active compound is substantially water soluble, the particle size can be adjusted by grinding to provide a substantially uniform distribution in the formulation, for example about 40 mesh.

Some examples of suitable excipients are lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia gum, calcium phosphate, alginate, tragacanth, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose , Water, syrup, methylcellulose, and other cellulose derivatives. The formulation may further include one or more of lubricants, such as talc, magnesium stearate, and mineral oil, wetting agents, emulsifying and suspending agents, preservatives, such as methyl- and propylhydroxy-benzoates, sweeteners, and flavoring agents. . Pharmaceutical compositions can be formulated to provide rapid, sustained, or delayed release of the active ingredient after administration to a patient by using procedures known in the art.

The composition of the present invention may be formulated in a unit dosage form, and each dose includes extracts of hot water extracted from 5-10 g, such as powdered coarse, for example, about 0.1 ml to about 500 ml. For example, the extract of the present invention is about 0.1ml to about 50ml, about 0.1ml to about 40ml, about 0.1ml to about 20ml, about 0.1ml to about 10ml, about 0.2ml to about 20ml, about 0.3ml to about 15ml , About 0.4 ml to about 10 ml, about 0.5 ml to about 1 ml; About 0.5 ml to about 100 ml, about 0.5 ml to about 50 ml, about 0.5 ml to about 30 ml, about 0.5 ml to about 20 ml, about 0.5 ml to about 10 ml, about 0.5 ml to about 5 ml; About 1 ml to about 50 ml, about 1 ml to about 30 ml, about 1 ml to about 20 ml, about 1 ml to about 10 ml, about 1 ml to about 5 ml; About 5 ml to about 50 ml, about 5 ml to about 20 ml, about 5 ml to about 10 ml; About 10ml to about 100ml, about 20ml to about 200ml, about 30ml to about 150ml, about 40ml to about 100ml, about 250ml to about 500ml, about 300ml to about 450ml, about 300ml to about 400ml, or about 50ml to about 100ml, etc. It can be formulated in unit dosage form of various active ingredients.

The term “unit dosage form” refers to physically discrete units suitable as unitary dosages for human subjects and other mammals, each unit being mixed with a suitable pharmaceutical excipient to calculate the active substance calculated to provide the desired therapeutic effect. It includes the expected amount of.

The composition may be sterilized or filtered by conventional sterilization techniques. Aqueous solutions can be packaged for use as is or lyophilized. Thereafter, the lyophilized formulation can be formulated with a sterile aqueous carrier prior to administration.

The proportions and concentrations of the compounds of the invention in a pharmaceutical composition can vary depending on a number of factors including dosage, chemical properties (eg, hydrophobicity), and route of administration. For example, the compounds of the present invention can be provided in an aqueous physiological buffer solution comprising about 0.1 to about 10% (w / v) of the compound for parenteral administration. "About" means plus or minus 10% of the stated value.

The therapeutic dose of the composition of the present invention is, for example, the specific use for which the treatment is made, the nature of the formulation, the mode and / or route of administration of the compound, the health and condition of the patient (e.g., body weight, body weight, surface area, age and Sex, and other drugs administered), and the judgment of the attending clinician. For example, the compound of the present invention may be provided with 8 g of crude bulb extract per time for oral administration. Dosage will depend on variables such as the extent and type of disease or disorder, the overall health of a particular patient, the relative biological efficacy of the selected compound, the formulation of the excipients, and the route of administration thereof.

The frequency of administration may vary and includes single or multiple doses per dose. The composition can also be taken as needed. For example, the compound can be taken up to 5 times a day, 3 times a day, 2 times a day, once a day, or once a week for 4 weeks to months or years, or once a month It may be administered once a year for 3 to 12 months or years, or for 5 or 10 years or more. In addition, it may vary depending on the type of progression or the severity of the disorder. For example, the extract or complex extract of the present invention can be administered daily, weekly, monthly, or once or twice, three times, up to five times per year, and is preferably administered three times daily. The extracts or complex extracts of the present invention may also be administered in combination with other treatments including non-pharmacological treatment, pharmacological treatment and surgical treatment. Exemplary non-pharmacological treatments include relief and environmental modification, identification and avoidance of triggers, and cognitive behavioral therapy.

Pharmaceutical compositions for the improvement or treatment of tic disorders of the present invention may also be used in comorbid conditions such as Tourette's syndrome, ADHD, tension, anxiety, anger, depression, eating or sleep disorders, or OCD (when these conditions are present in a given patient) ). In addition, it can be administered to improve concentration, improve autism, prevent and improve dementia.

 For example, therapeutic agents useful for ADHD include, but are not limited to, methylphenidate as a stimulant, atomoxetine as a non-stimulant, and therapeutic agents useful for depression and OCD are, but are not limited to, selective serotonin reuptake inhibitors (SSRIs), venlafaxine, monoamine oxy Multidrug inhibitors, and atypical antidepressants, buproprion as a dopamine-reuptake inhibitor. Therapeutic agents useful for sleep disorders include all barbiturates, all benzodiazepines, and other non-benzodiazepine-sedative-hypnotics and all sedative antihistamines and can be administered simultaneously.

The compositions described herein are suitable for the treatment of tic disorders with information and instructions for use (e.g., label, other printed material, or information delivery by other media (e.g., audio or visual media)). It can be packaged in a container. Accordingly, packaged products and kits packaged in sterile containers comprising extracts or complex extracts of the invention and instructions for use described herein will be within the scope of the invention. As a container containing the extract or the complex extract of the present invention, a vial, a jar, a bottle, a bag, or the like may be included. In addition, the article of manufacture may further include, for example, packaging materials, instructions for use, syringes, buffers, or other modulating reagents for the treatment or monitoring of conditions that require prevention or treatment. Instructions for use may be associated with the container (e.g., attached to the container) and describe how the internal composition should be administered (e.g., frequency and route of administration), indications for it, and other uses. You can. The composition may be prepared for administration in a unit of an appropriate dose, and may include a pharmaceutically acceptable adjuvant, carrier or other diluent and / or additional therapeutic agent as described above. Alternatively, the compound can be provided in a concentrated form along with a diluent and a description of the dilution.

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

<Example 1> Test of crude bulb extract

The equipment and test methods used in the Examples of the present invention are as follows.

All compounds used for enzyme testing and animal testing were purchased from Sigma-Aldrich (St. Louis, MO, USA).

The Gemini evasion system (San Diego Instruments, USA) was used to perform the passive evasion test and the Morris water-maze test adopted the Smart Junior Video-tracking System (Panlab, Spain). The fluorescent microplate reader adopted Gemini EM (Molecular Devices, USA). The H-13C-NMR spectrum was measured and recorded with a Varian UNITY INOVA 500 spectrophotometer (500 MHz, Varian Inc., Palo Alto, CA, USA) and tetramethylsilane was used as an internal standard. GC-MS was measured with HP6890 series II (Hewlett Packard, USA) and FAB-MS was measured using JMS-700 (Jeol, Japan).

Animal testing was conducted under standard environmental conditions (room temperature: 21 ± 2 ° C., relative humidity: 50% to 60%. Day and night cycle: 12 hours, etc.) in 8 week old male ICR mice with an average weight of 28.5 g. Experiments in the present invention are internationally recognized, such as the European Community Guidelines (EEC Directive of 1986; 86/609 / EEC) or US Guidelines (NIH publication # 85-23, 1985 revision) in the use and management of laboratory animals. It was implemented according to the established principles.

As a positive control group, haloperidol, pimozide, aripiprazole, risperidone or ziprasidone, which are known to relieve tic disorder and Tourette syndrome, were selected, and haloperidol was used.

<Example 2> Natural medicine extraction and separation

2-1 Preparation of crude bulb extract

It was purchased from Saerom Pharmaceuticals of Korea, washed, dried, and crushed, dried, dried, and then boiled in water for 10 minutes to obtain a brown extract.

On the basis of one serving, 8 g of jojo lamp was boiled for 10 minutes in 100 ml of water in a water heater to prepare a jogu lamp extract.

2-2 Preparation of mixed extracts such as jojo

Natural medicines purchased from Saerom Pharmaceutical in Korea were used.

After washing, dried and crushed coarse bulbs were mixed with 8 g of earl, 8 g of whistle, and 6 g of neck and 6 g to prepare a mixed extract of coarse bulb.

For the mixed extract, primary extract was prepared by first pouring 8 g of rooster, 6 g of hyssop, 6 g of throat and 6 g of throat and 200 ml of water in a water heater for 1 hour and 30 minutes. The mixture was secondarily heated for a minute to obtain 100 ml of a brown mixed extract.

<Example 3> Manual evasion test

Passive evasion testing is performed using a two-compartment box with a light / noise system and an electrical grid layer in each compartment. Prior to the training test, each sample was administered orally once. Scopolamine was administered intraperitoneally 1 hour after each administration. After 30 minutes the training test was performed in the following steps.

Each mouse is placed in the light / noise compartment of the test box. After 15 seconds, light and noise are applied until the mice escape to the adjacent grid bottom partition. When the mice move to a neighboring partition, the guillotine door automatically closes, and at the same time, an electric shock (3.0 mA, for 3 seconds) is applied to the grid layer. Mice that did not enter the electroshock compartment within 120 seconds are excluded from the experiment. The maintenance test is performed 24 hours after the training test is over. At this time, the test is performed under the same conditions as described above. The time taken to move from one partition to another was recorded step by step, the maximum cut-off time was set to 300 seconds, and the escape time was measured.

Figure 1 shows the improvement effect on scopolamine-induced neurological disorder and memory loss through the passive evasion test of the present invention.

As shown in Fig. 1, the effect of increasing memory was confirmed through the present invention.

<Example 4> Morris water-maze test

The water-maze test was conducted by the Morris method. This test is performed using a cylindrical water bath, which is filled with water at a depth of 27 cm at 22 ° C. The escape platform (diameter: 10 cm) is the destination of the mouse and one of the waterway quadrants is immersed in the surface of the water.

In the previous training test, each sample (200 ml / kg of crude bulb extract and crude bulb mixture extract, scopolamine, haloperidol 2.5 mg / kg) is administered orally for 7 days. Scopolamine (1.0 mg / kg) is administered intraperitoneally 1 hour after the administration is completed. After 30 minutes, the training test is performed in the following steps.

Put each mouse in water and try to find an escape platform. The whole process is observed by a video tracking system.

When the mice successfully reach the platform, they are allowed to stay on the platform for 10 seconds. However, if the mouse cannot find the platform within 150 seconds, place the mouse on the platform for 10 seconds. The residence test is conducted 24 hours after the training test is completed and is performed under the same conditions as above. The time taken for the mouse to escape from the water to the platform is measured as the escape time and recorded so that the maximum cut-off time is within 300 seconds.

Figure 2 shows the effect of improving concentration through the water-maze test of the present invention.

As shown in Figure 2, it was confirmed that the present invention has an effect on improving concentration.

<Example 5> Alleviate symptoms of tic disorder patient group

A clinical program was conducted to test the safety and activity of extracts from hot water extracts of dried bulbs in 30 subjects aged 8 to 17 years, in the patient group with a tic disorder lasting more than one year.

The multi-center, open label, and non-random studies in 30 subjects aged 8 to 17 years were selected to evaluate the stability and activity of extracts and mixed extracts, respectively, of hot water extracted from jojo, etc. in subjects with tic disorders.

Eligible subjects began treatment period of 8 weeks using the extract prepared in the above example, and attended the clinic every other week (phone contact every other week). Evaluation was performed at each visit. Follow-up visits were made over the phone over the week to record any adverse events. The extract was administered orally at 100 mg / 1 time, 3 times / day for 8 weeks.

As a control group, haloperidol, which is known to relieve tic disorder and Tourette syndrome, was used.

The activity of the extract was measured using the following clinical evaluation scale: (1) Yale Global Tic Severity Scale (YGTSS; data based on this rating system is presented below); (2) ADHD self-report symptom checklist (ASRS); (3) Yale-Brown Obsessive Compulsive Scale (YBOCS); (4) Premonitory Urge for Tics Scale (PUTS-1); (5) HAM-D; And Clinical Global Impression-Improvement and Severity Scale (CGI). The demographics of the study population were as follows. Thirty subjects were found to have tic disorders, and fatigue, insomnia, nausea, sedation, headache, restlessness, anxiety, muscle spasms, and discomfort were identified.

Sporadic changes were observed in laboratory tests, but had no clinical significance. Likewise, there were no clinically significant changes in vital signs.

The change in YGTSS score between baseline evaluation and evaluation at the patient's last visit is summarized in FIG. 3 for 30 patients who completed the experiment. Figure 3 shows the effect of alleviating the symptoms of tic disorders by YGTTS of the present invention.

As shown in Figure 3, in these patients, the bulbous extract and mixed extract had a very statistically significant (paired t-test p <0.001) decrease in YGTSS score (motor, negative, and total severity scores). The intention to process the analysis of the entire population (n = 30) indicates that statistically significant changes are evident even when data from all 30 patients are included.

The improvement of the YGTSS score was consistent with a significant change in the Clinical Overall Severity (CGI-S) score, and 18 out of 30 patients (60%) had at least 50% change in their score (p≤≤0.01 Student's t test). Showed.

In order to test the stability and activity of extracts and mixed extracts of crude bulbs through this test, we investigated them in vitro, and observed behaviors through animal models and clinical trials.

Among the tested samples, extracts and mixed extracts of hot water extracted from jojo, etc. were shown to improve tic disorder, speech and behavior control disorder, tension, anxiety, and anger disorders of Tourette syndrome, improving concentration, improving ADHD, as shown in Table 1 below. , It was confirmed that it has an effect on improving autism, preventing and improving dementia. These results suggest that there is an active substance that improves tic disorder and Tourette syndrome in hot water extracts such as jogu.

In addition, it can be confirmed that the effect of improving the tic disorder and Tourette syndrome is increased compared to the single hot water extract of Jogu et al. It was found that the active substance for improving tic disorder and Tourette syndrome was qualitatively increased due to the count extract, hyssop, and throat of the mixed extract.

As described above, the pharmaceutical composition derived from a natural product having a tic disorder improvement and treatment effect according to the present invention has been described in detail with respect to specific embodiments of the invention, but those skilled in the art to understand the spirit of the present invention are within the scope of the same idea. By adding, changing, or deleting other components, other backward inventions or other embodiments included within the scope of the inventive concept may be easily proposed. Therefore, it should be understood that the embodiments described above are illustrative in all respects and not restrictive. The scope of the present invention is indicated by the scope of the claims, which will be described later, rather than the detailed description above, and all the changed or modified forms derived from the meaning and scope of the claims and their equivalent concepts are included in the scope of the present invention. It should be interpreted as.

Claims (6)

Pharmaceutical composition for the treatment or prevention of tic disorders or Tourette syndrome, including extracts of hot water extracted from a mixture of Jogu-deung (Uncaria rhynchophylla), rooster medicine, hyssop, and throat. delete The method of claim 1,
The composition is a pharmaceutical composition for the treatment or prevention of tic disorder or Tourette syndrome, which additionally has at least one effect during tic disorder improvement, tension, anxiety, anger improvement, concentration improvement, ADHD improvement, autism improvement or dementia improvement. The method of claim 1,
The effective dosage of the composition is 5 to 10 g per time, based on the powdery composition before extraction, pharmaceutical composition for the treatment or prevention of tic disorder or Tourette syndrome. Health functional food for preventing or improving tic disorders or Tourette syndrome, including extracts of hot water extracted from a mixture of Jogu-deung (Uncaria rhynchophylla), county medicine, hyssop, and throat. delete

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