KR20190127004A - 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, which has less side effects, and has an alleviation and therapeutic effect against on behavior and vocal control disorders due to tic disorders and Tourette′s syndrome. More specifically, the present invention relates to a composition for treating or preventing tic disorders containing an Uncaria rhynchophylla extract.

Description

A pharmaceutical composition having a tic disorder improvement and therapeutic effect

The present invention relates to pharmaceutical compositions having a tic disorder improvement and therapeutic effect.

Tic Disorder and Tourette Syndrome are neurological abnormalities that result in unconscious, repeating uncontrolled sounds or behaviors, with uncontrolled speech and behavioral symptoms. In particular, Tourette syndrome is a case of both the tics and negative symptoms and lasts for more than a year, often left to adults. It usually occurs around 8 years of age, and tic symptoms usually appear on the face and neck, moving down the body and developing into more complex aspects. Negative or motor dysregulation, hypersensitivity to the sensory sensations, etc. may appear as simple or complex, and in severe cases, they may be inherited as vulgar language, sexual language, behavioral disorders, aggressive behavior, etc. Middle cerebral limbic system). It also tends to be associated with other conditions, such as attention deficit hyperactivity disorder, sleep disorders, learning disabilities and stuttering.

Tic disorders are caused by the interaction of genetic and environmental factors during the development of the central nervous system, causing changes in specific areas of the brain, and are known as representative neuropsychiatric disorders that change in various forms throughout the life of an individual. have. In particular, it is associated with abnormalities in the cerebral ancestral-thalamic-cortical (middle-limbic limbic) circuit, and although the genetic cause is not clearly identified, mutations in the SLITRK1 gene, located on chromosome 13q31.1, are thought to be involved. A hypothesis about the genetic cause raises the mutation of the HDC gene located on chromosome 15q21-q22. It is also hypothesized that the smaller the birth weight, the more severe the tics, and that it is caused by environmental factors in the womb during pregnancy. In addition, compared with the general population, various perinatal complications that can cause hypoxia in the newborn's brain in children with tic disorders, abnormal fetal position, long-term pain, premature infants, placental abnormalities, pregnancy addiction, umbilical cord abnormalities, severe vomiting in early pregnancy, and Severe emotional stress during pregnancy was found at a higher frequency. Other hypotheses are the effects of sex hormones (which are more common in boys), psychosocial stress or drugs such as CNS, and streptococcal infections. (Health Care Headquarters homepage, health information-'Tourette syndrome')

Treatment includes drug therapy and behavioral therapy. Experimental therapy includes neurosurgical treatment, but the success of the results is not clear. In particular, in the case of drug treatment, haloperidol, fluphenazine, pimozide, which are typical antipsychotic drugs, are used, but side effects such as discomfort or extracorporeal symptoms and cognitive decline may occur.

Therefore, the present inventors conducted a study on a pharmaceutical composition derived from natural products having fewer side effects, and alleviating and treating tic disorders, Tourette syndrome, and the composition of the present invention is excellent in improving and treating the disease. It confirmed and completed this invention.

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

Accordingly, it is an object of the present invention to provide a pharmaceutical composition derived from natural products, which has little side effects, and has the effect of alleviating and treating tic disorders, negative and behavioral control disorders of Tourette syndrome as extracts of early morning and the like.

In addition, another object of the present invention is to provide a health functional food having an alleviating and improving effect on tic disorders, Tourette syndrome negative and behavioral control disorders.

In order to achieve the above object, the present invention provides a pharmaceutical composition for treating or preventing tic disorders, Tourette syndrome, including extracts of hydrothermal extracts of Uncaria rhynchophylla.

In addition, the composition may be a hot water extract by mixing the Baekjak, the dew and throat and the like to the head.

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

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

On the other hand, the present invention provides a health functional food for preventing or ameliorating tic disorders, Tourette's syndrome, including extracts of hot water extracted from Uncaria rhynchophylla.

In addition, the health functional food may include an extract of hot water extracted by mixing the earl, walnut and throat and the like as an active ingredient.

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

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

Uncaria rhynchophylla, also called lance, is a genus of locusts. Dry thorny sprigs, shaped like fish hooks. The small branches are squared and the hooked branches come out of the leaf axes and bend down. The leaves face each other, the cotyledon is large, and the inflorescence hangs on the leaf axil. A capsule is a club-like hair. Medicinal herbs have a fishing thorn and two curved fishing thorns on the stem of a short branch, sometimes a branch on one side. It is 1 ~ 3㎝ long, 2mm wide, and its outer surface is reddish brown to dark reddish brown, and its cross section is long oval ~ oval and light brown. It mainly suppresses the central nervous system, lowers blood pressure, and works to expand peripheral blood vessels.

The present invention relates to a pharmaceutical composition having fewer side effects, a tic disorder improvement and a therapeutic effect having a mitigating effect and a therapeutic effect on a tic disorder, a Tourette syndrome, and a negative and behavioral control disorder. More specifically, Uncaria rhynchophylla Provided is a pharmaceutical composition for treating or preventing tic disorders.

In addition, the present invention can be used to extract the extract of hot water by mixing the white medicinal herbs, dew and neck and the like.

In addition, according to the present invention provides a health functional food for preventing or improving tic disorders, including extracts of early morning and the like.

The composition of the present invention specifically has an effect of improving one of tic disorders and tension, anxiety, anger, decreased concentration, ADHD, autism or dementia frequently associated with tic disorders.

In the present invention, the effective dose may be administered at 5 to 10 g per dose, based on powdery composition, and preferably at 8 g per dose.

According to the present invention, the composition may be an extract extracted by pouring a bath or the like in water, preferably an extract extracted for 10 to 15 minutes in hot water. Here, the extraction time is preferably not to exceed 15 minutes in consideration of the activity change of the active ingredient by heat.

In addition, the composition of the present invention includes a mixed extract extracted by mixing 8g, 8g, 8g, 6g, 6g, neck and 6g of the head and the like.

Here, the extraction method of the mixed extract may be a generally known extraction method, but is preferably extracted in consideration of the activity change caused by heat, such as light bulbs. For example, it is mixed with Baekjak, dew, throat and water for 1 to 2 hours in a hot water heater, in which the mixture is prepared by injecting the troughs and the like in the hot water for 10 minutes.

In the present invention, the lighting fixtures can be used after washing and drying, the crushed powdery fixtures. This is advantageous for the extraction of the active ingredient at the time of pouring.

The present invention also provides a pharmaceutical composition for treating Tourette syndrome, obsessive compulsive disorder, chronic motility spasm disorder or vocal cord spasm disorder.

As used herein, the term “treatment” means to reverse, alleviate, or prevent the progression of the disorder or condition to which the term applies, or one or more syndromes of that condition or disorder. As used herein, the term "treatment" refers to the action of "treatment" defined immediately above.

The compositions or compounds disclosed herein are also useful for the treatment of Tourette's syndrome, Tourette's disorder, Gildra Tourette's syndrome, or Tourette's syndrome, referred to simply as Tourette 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 disorders are characterized by multiple motor and / or negative ticks that occur for at least 4 weeks less than 12 months. Chronic tic disorders generally include single or multiple motor or negative ticks (but not both) that exist for over a year, and Tourette's syndrome is diagnosed when both motor and negative ticks are present for more than a year. Tick Disorder NOS is diagnosed when a tick is present but does not meet the criteria for any particular tic disorder. The compounds and compositions also include ticks induced as side effects of drug therapy; Ticks associated with autism; And Tourettism (eg, as a result of another disease or condition, sporadic, genetic, or neurodegenerative disorders), Tourette-like symptoms in the absence of Tourette's syndrome.

The compositions or mixed extracts disclosed herein are also more generally useful for the treatment of motor disorders. These disorders may include asterile syndrome, chorea (eg, occurring in Huntington's disease), myoclonus and / or dystonia of any etiology, tremors, or Parkinson's disease. Movement disorders may also be induced 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 a dopamine agonist (e.g., including but not limited to levodopa, levodopa and carbidopa combinations, lopinilol, pramipexole, or pergolide). Dyskinesia and antipsychotic drugs (e.g., but not limited to haloperidol, risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone, paliperidone, iloperidone, perpenazine, metoclopramide, and chlorpromazine It can be used to alleviate spontaneous movement disorder induced by).

The compositions and compounds described herein can be administered to a subject, which can be referred to as a "patient." Although expressly intended to treat human patients, the present invention is not so limited. Since the compositions will be relatively inexpensive to make, the present invention includes methods of veterinary use (eg, treating domestic pets such as cats and dogs). Subjects are effectively treated whenever there is a clinically beneficial outcome. This may mean, for example, the complete or significant resolution of the symptoms of the disorder, the frequency of symptoms, the reduction in the duration of severity, or the slowing of the progression of the disorder. Thus, effective treatment for tic disorders is indicated by a decrease in the number, duration, frequency, or intensity of motor tics, voice tics, or both motor and voice tics. Preferably, at a level where there is no significant toxicity in the patient, it can be determined by evaluating the clinical symptoms of the patient before and after administration of a known amount of a particular composition.

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

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

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

Simple motorized ticks only involve a single muscle or group of muscles, and usually cause short shaking motions (moderate ticks), which can also be slow, resulting in short-lasting abnormal postures (tension abnormal ticks) or static contractions (relaxed ticks). ). Examples of simple eccentric exercise ticks include blinking, nose pulling, and shaking head and limbs. Hypertonic ticks include persistent eye closure (eyelid spasms), ocular deviations, bruising, mouth opening, torticollis, continuous jaw opening, and shoulder rotation. Tension ticks are typically indicated by abdominal contractions, limb openness or limb flexion. Examples of compound movement ticks include shaking your head, bending or turning your body, combing your hair, touching, throwing, hitting, running, kicking, making rude gestures, trimming, vomiting, nausea, smelling objects, catching your genitals, and other things. Making sensational or indecent gestures (obscene behaviors), and other mimicry gestures (echoes).

Simple vocal ticks typically include nasal blow, neck squeal, aching, squealing, screaming, coughing, tailoring, blowing your nose, squeezing your throat, and making sucking sounds. Compound speech ticks are linguistically significant remarks and language expressions such as obscenity, profanity, or other socially inappropriate language or phrases (obsessive compulsions), repetition of other people's language or phrases (echo) , And their remarks in a sentence, in particular the repetition of the last syllable, language or phrase (synonym).

The composition of the present invention may be formulated according to its use. For example, the compound may be formulated to a pharmaceutically acceptable amount in the composition for administration to a patient. These compositions can be prepared according to methods well known in the pharmaceutical art, and can be administered by various routes. Administration may be topical (including ophthalmic or ocular (eg via eye drops)) and mucous membranes (ie, transmucosal), including oral, intranasal, vaginal and rectal delivery, lungs (eg by nebulizers) Inhalation or insufflation of the comprising powder or aerosol), intranasal, epidermal (and transdermal), ocular, or oral. Oral administration is preferred for its convenience in the present invention, but parenteral formulations may also be used, which formulations are administered intravenously, intraarterally, subcutaneously, intraperitoneally or intramuscularly (eg by injection or infusion). Can be. As dopaminergic receptors in the brain are targeted, intracranial (eg, intravertebral or intraventricular) administration may also be considered within the scope of the method. Parenteral administration may be in the form of a single bolus dose or may be, for example, by a continuous perfusion pump. Thus, formulations include depot formulations, including those that are sustained 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, drops, suppositories, sprays, solutions, 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 comprise the active ingredient in combination with one or more pharmaceutically acceptable carriers. In 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, chassis, paper, or other containers. When the excipient acts as a diluent, it may be a solid, semisolid, 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. Thus, the compositions may be used in capsules (e.g. soft or hard gelatin capsules), tablets, pills, powders (e.g. sterile packaging powders), lozenges, cachets, cachets, elixirs, suspensions, emulsions, solutions (Eg, sterile injectable solutions), suppositories, syrups, aerosols (solid or in a liquid medium), or ointments.

These forms may include, for example, up to about 10% by weight of the active extract, for this purpose it is possible to use fractions that separate the active ingredient from the extract or complex extract of the present invention. 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 may vary depending on the intended route of administration. The resulting composition may comprise additional agents such as colorants, flavors or preservatives. The extract may also be applied to or included in drug delivery devices such as pumps or patches. The compounds of the present invention may be administered alone or in admixture in the presence of a pharmaceutically acceptable excipient selected based on the mode and route of administration. In preparation, the active compound may be ground to provide the appropriate particle size before blending with other ingredients. If the active compound is substantially water insoluble, it may 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 comprise one or more of lubricants such as talc, magnesium stearate, and mineral oils, wetting agents, emulsifying and suspending agents, preservatives such as methyl- and propylhydroxy-benzoate, 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 compositions of the present invention may be formulated in unit dosage form, each dosage comprising an extract of hydrothermally extracted from 5 to 10 g of powdered light, such as 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 10 ml to about 100 ml, about 20 ml to about 200 ml, about 30 ml to about 150 ml, about 40 ml to about 100 ml, about 250 ml to about 500 ml, about 300 ml to about 450 ml, about 300 ml to about 400 ml, or about 50 ml to about 100 ml It may be formulated in unit dosage forms of various active ingredients.

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

The composition can be sterilized or sterile filtered by conventional sterilization techniques. The aqueous solution can be packaged or lyophilized for use as is. The lyophilized formulation can then be combined with the sterile aqueous carrier prior to administration.

The proportions and concentrations of the compounds of the present invention in pharmaceutical compositions may vary depending on a number of factors, including dosage, chemical properties (eg, hydrophobicity), and route of administration. For example, a compound of the present invention may 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 dosage of a composition of the present invention may be, for example, the specific use for which the treatment is to be made, the nature of the formulation, the manner and / or route of administration of the compound, the health and condition of the patient (eg, body size, 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 a bulbous light extract for oral administration. Dosage will depend on variables such as the extent and type of disease or disorder, the overall health state of the particular patient, the relative biological potency of the selected compound, the formulation of the excipient, 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 ingested as needed. For example, the compound may be taken up to 5 times a day, 3 times a day, twice a day, once a day, or once a week for 4 weeks to several months or years, or once a month It may be administered once a year for 3 to 12 months or years, or for 5 years, 10 years or more. It can also vary depending on the type of disorder and the degree of symptoms. For example, the extract or complex extract of the present invention may be administered daily, weekly, monthly, or once or twice, three times, up to five times a year, preferably three times daily. Extracts or combination extracts of the present invention may also be administered in conjunction with other therapies, including non-pharmacologic, pharmacological and surgical treatments. Exemplary non-pharmacological treatments include relief and environmental modifications, identification and avoidance of triggers, and cognitive behavioral therapy.

Pharmaceutical compositions for improving or treating tic disorders of the present invention may also be present in concomitant disease conditions such as Tourette syndrome, ADHD, tension, anxiety, anger, depression, eating or sleeping disorders, or OCD (if present in patients given these conditions). ) For the treatment of). In addition, it may be administered for improving concentration, improving autism, preventing and improving dementia.

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

The compositions described herein are suitable together with information and instructions for use (e.g., transfer of information by label, other printed material, or other media (e.g., audio or visual media)) as a therapy for treating tic disorders. Can be packaged in a container. Thus, packaged products and kits packaged in sterile containers comprising the extract or complex extract of the present invention and instructions for use described herein will be within the scope of the present invention. As a container containing an extract or complex extract of the present invention, it may include a vial, a jar, a bottle, a bag, and the like. In addition, the article of manufacture may further comprise, for example, packaging materials, instructions for use, syringes, buffers, or other modulating reagents for the treatment or monitoring of conditions requiring prophylaxis or treatment. Instructions for use may be associated with the container (eg attached to the container) and describe the manner in which the composition inside should be administered (eg the frequency and route of administration), indications for this, and other uses. Can be. The composition may be prepared for administration in appropriate dosage units and may comprise a pharmaceutically acceptable adjuvant, carrier or other diluent and / or additional therapeutic agent as described above. Alternatively, the compound may be provided in concentrated form with a description of the diluent and dilution.

Hereinafter, the present invention will be described in more detail with reference to Examples. These examples are only for illustrating 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 Extracts of Head Light

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

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

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

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

As a positive control, haloperidol, pimozide, aripiprazole, risperidone, or ziprasidone, which are known as tic disorders and Tourette syndrome relievers, were selected, of which haloperidol was used.

Example 2 Natural Herb Extraction and Separation

2-1 Preparation of Headlight Extract

Purified, dried, and pulverized crude bulbs, which were purchased from Salom Pharmaceuticals, Korea, were extracted with hot water for 10 minutes, and a brown extract was obtained.

On the basis of the amount of once, 8 g of light bulbs were warmed with 100 ml of water for 10 minutes in a water heater to prepare extracts of light bulbs.

2-2 Preparation of Mixed Extracts

We used natural herbs purchased from Salom Pharmaceutical in Korea.

After washing, dried and crushed 8 g of light bulbs, 8 g of Baekjak, 6 g of dew, 6 g of neck and 6 g were mixed and mixed to prepare a mixed extract of light bulbs.

The mixed extract was prepared by firstly distilling 8 g of Baekjak, 6 g of dew, 6 g of throat, 6 g of neck and 200 g of water and 200 ml of water for 1 hour and 30 minutes in a water heater, and then adding 8 g of light bulbs to the primary extract. Secondary warming for a minute gave 100 ml of a brown mixed extract.

Example 3 Manual Avoidance Test

Passive avoidance tests are carried out using a two-part compartment box with a light / noise system and an electric grid layer in each compartment. Prior to the training trial, each sample was administered orally once. Scopolamine was intraperitoneally administered 1 hour after the end of each administration. After 30 minutes the training test was carried out in the following steps.

Place each mouse in the light / noise compartment of the test box. After 15 seconds, light and noise are applied until the mice escape to the neighboring grid bottom partition. When the mice move to neighboring compartments, the guillotine door automatically closes, and at the same time an electric shock (3.0 mA, 3 seconds) is applied to the grid layer. Mice that do not enter the electroshock compartment within 120 seconds are excluded from the experiment. The maintenance test is performed 24 hours after the end of the training test. At this time, the test should be carried out under the same conditions. The time taken to move from one partition to the other was recorded in stages, the maximum cut-off time was 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 avoidance 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 carried out using a cylindrical water bath, which is filled with water 27 cm deep at 22 ° C. The escape platform (diameter: 10 cm) is the mouse's destination and one of the waterway quadrants is submerged on the surface of the water.

In the previous training test, each sample (200ml / kg of headlight and mixed extract of headlight, scopolamine, haloperidol 2.5mg / kg) is administered orally for 7 days. One hour after the end of the administration, scopolamine (1.0 mg / kg) is intraperitoneally administered. After 30 minutes, the training test is carried out in the following steps.

Place each mouse in the water to find an escape platform. The whole process is observed by the video tracking system.

Once the mice successfully reach the platform, they will be on the platform for 10 seconds. However, if the mouse doesn't find a platform within 150 seconds, it will stay on the platform for 10 seconds. The retention test is carried out 24 hours after the end of the training test and under the same conditions as above. The time it takes 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 concentration improvement effect through the water-maze test of the present invention.

As shown in FIG. 2, the present invention was confirmed to have an effect on improving concentration.

Example 5 Symptom Relief

A clinical program was conducted to test the safety and activity of hot water extracts from 30 patients aged between 8 and 17 years old.

The multicenter, open label, and non-randomized studies were performed on 30 subjects aged 8 to 17 years of age to evaluate the stability and activity of the extracts and mixed extracts of the hydrothermal extracts in the subjects with tic disorders.

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

As a control, haloperidol, known as a tic disorder and Tourette syndrome relieving agent, was used.

The activity of the extracts was measured using the following clinical evaluation scales: (1) Yale Global Tic Severity Scale (YGTSS; data based on this scoring 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 identified as having tic disorders, and fatigue, insomnia, nausea, sedation, headache, restlessness, anxiety, muscle spasms, and discomfort were identified.

Sporadic changes were observed in laboratory tests, but did not have clinical significance. Likewise, there was no clinically significant change in vital signs.

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

In these patients, as shown in FIG. 3, the morninglight extract and mixed extract developed a very statistically significant (paired t-test p <0.001) reduction of YGTSS score (exercise, negative, and total severity score). The intention to process the analysis of the total population (n = 30) indicates that statistically significant changes are evident even when data from all 30 patients are included.

The improvement in the YGTSS score was consistent with a significant change in the overall clinical severity (CGI-S) score, with 18 of 30 patients (60%) changing at least 50% or more in their score (p ≦ 0.01 Student's t test). Indicated.

This test was conducted in vitro to test the stability and activity of the bulbous extract and mixed extract, and behavior was observed through animal models and clinical trials.

Among the tested samples, extracts and mixed extracts of hot water, etc. were found to improve tic disorders, negative and behavioral control disorders of Tourette syndrome, tension, anxiety, and anger disorders, as shown in Table 1, improved concentration, and improved ADHD. It has been shown to be effective in improving autism, preventing and improving dementia. These results suggest that there is an active substance that improves tic disorders and Tourette's syndrome in hydrothermal extracts such as early morning and the like.

In addition, it can be seen that the mixed extract extracted by mixing Baekjak, ridiculous, throat and the like in the early morning, the effect of improving the tic disorder and Tourette syndrome compared to the single hot water extract, such as early morning. It can be seen that qualitatively increase the active substance for improving tic disorder and Tourette syndrome due to the ear extract, dew and throat of the mixed extract.

As described above, the natural-derived pharmaceutical composition having a tic disorder improvement and therapeutic effect according to the present invention has been described in detail with reference to specific embodiments of the present invention, those skilled in the art to understand the spirit of the present invention within the scope of the same idea By adding, modifying, or deleting other elements, other embodiments that fall within the scope of the present invention or other inventive concepts may be easily proposed. Therefore, it should be understood that the embodiments described above are exemplary in all respects and not restrictive. The scope of the invention is indicated by the following claims rather than the foregoing description, and all changes or modifications derived from the meaning and scope of the claims and their equivalents are included in the scope of the invention. Should be interpreted as

Claims (6)

A pharmaceutical composition for treating or preventing tic disorders, Tourette syndrome, comprising extracts of hot water extracted from Uncaria rhynchophylla. According to claim 1,
The composition is extracted from the hydrothermal extract by mixing the Earl, the dew and the neck and the like in the composition of the tics disorders, Tourette syndrome treatment or prevention pharmaceutical composition. According to claim 1,
The composition is a pharmaceutical composition for treating or preventing tic disorders, Tourette syndrome further having at least one effect of improving tic disorders, improving tension, anxiety, anger, improving concentration, improving ADHD, improving autism or improving dementia. According to claim 1,
Effective dosage of the composition is 5 to 10g per dose based on powdery composition, tic disorders, Tourette syndrome treatment or prevention pharmaceutical composition. Health functional food for preventing or improving tic disorder, Tourette syndrome, including extract of hot water extracted from Uncaria rhynchophylla. The method of claim 5,
The health functional food is a health functional food comprising an extract of hot water extracted by mixing the Earl, the dew and neck and the like as an active ingredient.

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