KR20220077706A - Composition for improving, preventing or treating Neuropsychiatry disorders diseases comprising Fraction of agarwood extracts - Google Patents

Abstract

The present invention relates to a composition for preventing, improving, or treating brain neuropsychiatric disorders, comprising a fraction of an extract of aloes agarula as an active ingredient.
The composition comprising the fraction of the extract according to the present invention as an active ingredient was confirmed to have a significant effect of 95% or more reliability in a non-clinical experiment, an animal experiment using rodents, and was also clinically reported for depression and anxiety. The improvement effect such as reduction of nitric oxide (NO), NLRP3 inflammasome, ASC and IL-1β, which is a pharmacological mechanism related to neuropsychiatric disorders as the main symptom, was verified and reduced significantly with a reliability of 95% or more. Identified, it can be usefully used as a composition for preventing, improving or treating brain neuropsychiatric disorders.

Description

Composition for improving, preventing or treating Neuropsychiatry disorders diseases comprising Fraction of agarwood extracts;

The present invention relates to a composition for preventing, improving, or treating brain neuropsychiatric disorders, comprising a fraction of an extract of aloes acupuncture points in the brain as an active ingredient.

Neuropsychiatric disorders, such as major depressive disorder, bipolar disorder, and schizophrenia, whose main symptoms are depression and anxiety disorders, are increasing in incidence and prevalence every year in modern society. This has a profound impact on daily life, leading to a decrease in the quality of life and a high suicide rate.

In this regard, it was reported that the number of patients receiving treatment for depression over the past five years announced by the National Health Insurance Corporation increased from 643,105 in 2016 to 798,427 in 2019, an increase of about 155,322, compared to the first half of 2019. In the first half of the year, the suicide rate among women increased by 43%. In addition, according to statistics on the cause of death by the National Statistical Office, suicide due to depression has been the number one cause of death every year since 2015. appear.

Although the causes of depression and anxiety disorders are diverse, stress is considered to be an important cause. The depression and anxiety disorders may be largely caused by genetic factors and environmental factors such as stress. The detailed mechanisms accompanying these causes include a decrease in neurotransmitters such as dopamine and serotonin, a decrease in the expression of neurotrophic factors, and a decrease in the generation of new neurons related thereto, and the long-term expression of key genes in the nervous system due to the influence of epigenetic mechanisms. Inhibition or increase, changes in energy metabolism of nerve cells, and damage to nerve cells due to accumulation of oxidative stress have been suggested. Recently, it has been suggested that the activity of brain microglia is deeply involved in the pathogenesis of major depressive disorder, and the corresponding research evidence is accumulating.

Depression symptoms currently used in clinical practice are mostly developed and tested through animal models of depressive symptoms. It is understood that all antidepressant drugs have a drug action that enhances drug action at the synapse by inhibiting the breakdown and reuptake of monoamines such as dopamine, serotonin, and norepinephrine, which are neurotransmitters between brain neurons. However, the drug has a large difference in efficacy depending on the patient, so there is a need for the development of a new safe, effective, and no side effect that supplements or replaces these problems.

In addition, a new pharmaceutical approach is required due to problems such as a high recurrence rate and low compliance after discontinuation of medication.

Therefore, it is possible to rapidly improve, prevent or treat depression and anxiety disorders, and there is a demand for extracts from natural herbal medicines that are stable and have no side effects.

On the other hand, research on natural products for neuropsychiatric disorders that are safe for the human body and have no side effects, but with depression and anxiety as the main symptoms, are still being studied, but they are still more effective and have non-clinical and clinically significant effects. The need to develop therapeutic agents that can be used is emerging.

Accordingly, the present inventors, in relation to depression and anxiety disorders, have fewer side effects to the human body than chemically synthesized drugs, and for the prevention, improvement or treatment of brain neuropsychiatric disorders, including active ingredients derived from natural products that can be easily manufactured and ingested Efforts were made to develop a composition.

In this regard, the present invention has been completed by objectively verifying the effect of the extract of the extract on the brain on neuropsychiatric disorders through cell and animal experiments.

Previously, the effect of inhibiting stress-induced oxidative damage in the brain using an extract of acupuncture and ethanol extracts was proven, and the protective effect of a fraction of the extract of the extract against brain neuronal excitability was studied, but there is no applied research on depression and anxiety disorders. .

KR 10-2018-0011625 A KR 10-2018-0112711 A

The main object of the present invention is to provide a composition for preventing, improving, or treating brain neuropsychiatric disorders, comprising a fraction of the extract of aloes amulets as an active ingredient.

Specifically, the object of the present invention is harmless to the human body and through the pharmaceutical mechanisms related to cranial neuropsychiatric disorders, nitric oxide (NO), NLRP3 inflammasome, ASC and IL-1β and inflammatory mechanisms of action, brain neuropsychiatric To provide a pharmaceutical composition for preventing or treating a disorder.

Another object of the present invention is to treat neuropsychiatric disorders in the brain through nitric oxide (NO), NLRP3 inflammasome, ASC and IL-1β, and inflammatory mechanisms, which are harmless to the human body and are a pharmaceutical mechanism related to cranial neuropsychiatric disorders. To provide a health functional food composition for prevention or improvement.

In order to solve the above object, the present invention

As a pharmaceutical composition for the prevention or treatment of neuropsychiatric disorders in the brain, comprising a fraction of the extract of aloes amulets as an active ingredient,

The fraction of the extract of the alopecia extract is a lipophilic fraction showing a peak at a retention time of 28.52 minutes with a coefficient of variation of 0.024% at a UV 280 nm wavelength of high-performance liquid chromatography (HPLC) with a non-polar column Prep It provides a pharmaceutical composition for preventing or treating brain neuropsychiatric disorders, which is obtained by separation and purification by .LC (Recycling 　 Preparative 　 Liquid Chromatograph).

According to an embodiment of the present invention, the fraction of the extract of aloes agar is included in an amount of 0.1 to 1% by weight based on the total weight% of the extract.

According to an embodiment of the present invention, the brain neuropsychiatric disorder is major depressive disorder, bipolar disorder, schizophrenia, panic disorder, autism, obsessive compulsive disorder It may be any one selected from the group consisting of Obsessive-compulsive disorder, eating disorder, visual or auditory hallucination, dysthymia and anxiety disorders .

According to an embodiment of the present invention, the aloes may be derived from plants of the genus Aquilaria.

According to an embodiment of the present invention, the Aquilaria (Aquilaria) genus plants are Aquilaria Lignum (A. Lignum), Aquilaria Cassiana (A. khasiana), Aquilaria Apiculina (A. apiculina), Aquila Lia blillonil (A. blillonil), Aquilaria baneonsis (A. baneonsis), Aquilaria brachyantha (A. brachyantha), Aquilaria cummingiana (A. cunmingiana), Aquilaria filaria (A. filaria) ), Aquilaria grandiflora (A. grandiflora), Aquilaria hilata (A. hilata), Aquilaria microcapa (A. microcapa), Aquilaria rostrata (A. rostrata), Aquilaria agalocha (A) agallocha), Aquilaria malaccensis (A. malaccensis), Aquilaria sinensis (A. sinensis) and Aquilaria crassana (A. crassna), may be any one selected from the group consisting of.

According to one embodiment of the present invention, the extract of the alopecia is made by using one or more solvents selected from chloroform, ether or methylene chloride as a primary extract of the extract using water, C1 to C3 alcohol, or a mixture thereof as a solvent. It may be an extracted extract.

The present invention is a health functional food composition for preventing or improving brain neuropsychiatric disorders comprising a fraction of aloes root extract as an active ingredient,

The fraction of the extract of the alopecia extract is a lipophilic fraction showing a peak at a retention time of 28.52 minutes with a coefficient of variation of 0.024% at a UV 280 nm wavelength of high-performance liquid chromatography (HPLC) with a non-polar column Prep It provides a health functional food composition for preventing or improving brain neuropsychiatric disorders, which is obtained by separation and purification by .LC.

The composition for preventing, improving, or treating brain neuropsychiatric disorders, comprising the fraction of the extract according to the present invention as an active ingredient, exhibits effects on anti-depression and anxiety without showing any toxicity in cytotoxicity, The fraction of the extract can be usefully used as a composition for preventing, improving or treating brain neuropsychiatric disorders having depression and anxiety as the main symptoms.

More specifically, the composition for preventing, improving, or treating brain neuropsychiatric disorders, comprising the fraction of the extract of aloes amulets according to the present invention as an active ingredient, is a non-clinical experiment, an animal experiment using rodents, with a reliability of 95% or more. Efficacy was confirmed, and pharmacological mechanisms related to cranial neuropsychiatric disorders with clinically reported depression and anxiety as main symptoms, nitric oxide (NO), NLRP3 inflammasome, ASC and IL-1β The improvement effect such as a significant reduction in inhibition of 95% or more is verified and confirmed, and it can be usefully used as a composition for prevention, improvement or treatment for brain neuropsychiatric disorders.

Figure 1 shows the peaks for the five fractions (A, B, C, D, E) separated at UV 280 nm wavelength of high-performance liquid chromatography (HPLC) having a non-polar column.
FIG. 2 shows the results of confirming the improvement effect of the E fraction of the extract according to Example 1 in a rodent model of depression and anxiety disorders induced by unpredictable chronic mild stress (UCMS) in relation to neuropsychiatric disorders in the brain. it has been shown
In the results of FIG. 2, ## means that chronic stress was significantly increased with p<0.01 and 99% reliability compared to the normal group (vehicle), and * indicates depression or anxiety compared to the control group, p<0.05, with 95% reliability. means a significant decrease to a significance level of 5%, and ** means a significant decrease in depression or anxiety compared to the control group with p<0.01 and a reliability of 99%.
More specifically, FIGS. 2A and 2B are tail suspension test (TST), FIGS. 2C and 2D are forced swimming test (FST), and FIGS. 2E and 2F are open field test, OFT) analysis results are shown. More specifically, Figure 2A is the immobility duration in the tail suspension method, Figure 2B is the result of the activity duration in the tail suspension method, Figure 2C is the immobility time in the forced swimming method, 2D is the active state time in the forced swimming method, FIG. 2E is the open branch movement distance in the open space method, and FIG. 2F is the stay time in the open branch in the open space method. 2D and 2E show the effect of improving anxiety disorder.
Figure 3A is a graph showing the cytotoxicity results of mouse microglia cell line (BV2 cell) of the E fraction of the extract according to Example 1 of the present invention. Figure 3B is a graph showing the results of the inhibitory effect of nitric oxide (NO) production in a mouse microglia cell line induced with endotoxin (lipopolysaccharide, LPS) in which the fraction E fraction according to Example 1 of the present invention is induced.
Figure 4 is an endotoxin (lipopolysaccharide, LPS)-induced nitric oxide (NO) production inhibitory effect according to the amorrhage fractions (A, B, C, D, E) according to the preparation example of the present invention; is shown graphically.
5A is a graph showing the results of inhibiting the secretion and production of prostaglandin E2 (prostaglandin, PGE ₂ ) of a extract E fraction according to Example 1, and FIG. The protein secretion inhibitory effect of enzymes (inducible nitric oxide synthase, iNOS and cyclooxygenase, COX2) involved in the production of by-products (NO, PGE ₂ ) is shown by Western blot measurement. Figure 5C shows the results of confirming the iNOS and COX2 gene activity inhibitory effect of the amorrhage extract E fraction according to Example 1 by qPCR. Western blot results are shown graphically.
6 shows the results of the inhibitory effect on NF-κB (nuclear factor-κB) activity, which is an inflammatory mechanism of action, of the E fraction of the extract of aloes root according to Example 1. FIG. Figure 6A is the result of measuring the activity of NF-κB by immunofluorescence staining, Figure 6B is the result of measuring the NF-κB transcription promoters P65 and P-P65 activity by Western blot, Figure 6C is the NF-κB signal (signal) is a graph showing the measurement result by Western blot, Figure 6D is a graph showing the P65 activity, a transcription promoter of NF-κB, and Figure 6E is a graph showing the result for Western blot NF-κB activity P-P65 / The results are shown by graphing P65.
7 is a graph showing the inhibitory effect on the secretion of inflammatory cytokines (tumor necrosis factor-α, TNF-α and interleukin-1β, IL-1β) protein and gene secretion of the E fraction of the extract according to Example 1. FIG. 7A is an ELISA assay of TNF-α, FIG. 7B is an ELISA assay of IL-1β, and FIG. 7C shows the results of confirming the gene activity of TNF-α and IL-1β by qPCR.
Figure 8 shows the results of the inhibition of the inflammation control complex (Nod-like receptor family pyrin domain containing 3, NLRP 3, ASC and caspase-1) activity of the extract E fraction according to Example 1. Figure 8A shows the result of measuring the inhibitory effect of the inflammatory regulatory complex by Western blot, Figure 8B shows the measurement result of caspase-1 in the inflammatory regulatory complex by ELISA assay, Figure 8C is the measurement of the inhibitory effect on the inflammatory regulatory complex It is a graph of a Western blot result.

Hereinafter, the present invention will be described in more detail through preparation examples, examples or test examples including the accompanying drawings. However, the following preparation examples, examples, or test examples are merely references for describing the present invention in detail, and the present invention is not limited thereto, and may be implemented in various forms.

Also, unless defined otherwise, all technical and scientific terms have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used in the description herein is for the purpose of effectively describing particular embodiments only and is not intended to limit the present invention.

Also, the singular forms used in the specification and appended claims may also be intended to include the plural forms unless the context specifically dictates otherwise.

In addition, the singular form of a term used in the present invention may be interpreted as including a plural form unless otherwise indicated.

In addition, in the present invention, the unit of % used unclearly without special mention means % by weight.

The present invention relates to a composition for preventing, improving, or treating brain neuropsychiatric disorders, comprising a fraction of an extract of aloes acupuncture points in the brain as an active ingredient.

Since the composition of the present invention contains a fraction separated from the extract of amphitheater, which is a natural plant material, as an active ingredient, there is no side effect to the human body even when administered in excess.

Hereinafter, the present invention will be described in detail.

As a pharmaceutical composition for the prevention or treatment of neuropsychiatric disorders in the brain, comprising a fraction of the extract of aloes amulets as an active ingredient,

The fraction of the extract of the alopecia extract is a lipophilic fraction showing a peak at a retention time of 28.52 minutes with a coefficient of variation of 0.024% at a UV 280 nm wavelength of high-performance liquid chromatography (HPLC) with a non-polar column Prep It provides a pharmaceutical composition for preventing or treating brain neuropsychiatric disorders, which is obtained by separation and purification by .LC (Recycling 　 Preparative 　 Liquid Chromatograph).

The fraction of the extract of alopecia extract may be included in an amount of 0.1 to 1% by weight based on the total weight% of the extract, preferably 0.1 to 0.5% by weight, but is not limited thereto.

In the present invention, 'fraction' refers to a result obtained by performing fractionation to separate a specific component or a specific group of components from a mixture or extract containing various components, and the fraction of the extract of alopecia extract is a non-polar column. At a UV 280 nm wavelength of high-performance liquid chromatography (HPLC) with a lipophilic fraction showing a peak at a retention time of 28.52 minutes with a coefficient of variation of 0.024% at a UV 280 nm wavelength with Prep.LC, the fraction obtained by separating and purifying It may mean a lipophilic material, which is included in 0.1 to 1% by weight, more preferably 0.1 to 0.5% by weight, based on the total weight% of the extract have.

The aloes are derived from plants of the genus Aquilaria, and the plants of the genus Aquilaria are Aquilaria lignum (A. Lignum), Aquilaria cassiana (A. khasiana), Aquilaria apicurina ( A. apiculina), aquilaria blillonil (A. blillonil), aquilaria baneonsis (A. baneonsis), aquilaria brachyantha (A. brachyantha), aquilaria cummingiana (A. cunmingiana), aquilaria Aquilaria (A. filaria), Aquilaria grandiflora (A. grandiflora), Aquilaria hilata (A. hilata), Aquilaria microcapa (A. microcapa), Aquilaria rostrata (A. rostrata), Aquila Ria agallocha (A. agallocha), Aquilaria malaccensis (A. malaccensis), Aquilaria sinensis (A. sinensis) and Aquilaria crassana (A. crassna), any one selected from the group consisting of can be have.

The Aquilaria Lignum is a resin deposited on the heartwood of aloes tree belonging to the family Thymelaeaceae. It is prescribed to purify the mind and calm the mind by alleviating anger and to keep the spirit alive.

The extract may be an extract obtained by first extracting aloes agarose with water, C1 to C3 alcohol, or a mixture thereof as a solvent, and using one or more solvents selected from chloroform, ether, or methylene chloride to extract secondary extracts, preferably may be methylene chloride. Preferably, it may be one in which aloesae is first extracted with 30% ethanol extract, and 99% methylene chloride is secondarily extracted.

The brain neuropsychiatric disorder is major depressive disorder, bipolar disorder, schizophrenia, panic disorder, autism, obsessive-compulsive disorder, It may be any one selected from the group consisting of eating disorder, visual or auditory hallucination, dysthymia and anxiety disorders, but is not limited thereto. The neuropsychiatric disorder is characterized by depression and anxiety as main symptoms, and is not limited as long as it is a disease having depression and anxiety as main symptoms.

In the present invention, 'prevention' refers to suppressing the occurrence of diseases or diseases in individuals who have not been diagnosed with neuropsychiatric disorders, but are prone to these neuropsychiatric disorders.

In the present invention, 'treatment' refers to any action in which the symptoms of neuropsychiatric disorders in the brain are improved, suppressed, reduced, or advantageously changed by the administration of the composition of the present invention.

The pharmaceutical composition of the present invention may be prepared by using a pharmaceutically suitable and physiologically acceptable adjuvant in addition to the active ingredient, and the adjuvant includes an excipient, a disintegrant, a sweetener, a binder, a coating agent, a swelling agent, a lubricant, and a lubricant. agent or flavoring agent, etc. may be used.

The pharmaceutical composition may be preferably formulated as a pharmaceutical composition by including one or more pharmaceutically acceptable carriers in addition to the active ingredients described above for administration.

The pharmaceutical dosage form of the composition according to the present invention may be used in the form of a pharmaceutically acceptable salt thereof, and may be used alone or in combination with other pharmaceutically active compounds as well as in an appropriate group.

Formulations of the pharmaceutical composition may be granules, powders, tablets, coated tablets, capsules, suppositories, solutions, syrups, juices, suspensions, emulsions, drops or injectables. For example, for formulation in the form of a tablet or capsule, the active ingredient may be combined with an orally, non-toxic, pharmaceutically acceptable inert carrier such as ethanol, glycerol, water, and the like. In addition, if desired or required, suitable binders, lubricants, disintegrants and color-developers may also be included in the mixture. Suitable binders include, but are not limited to, starch, gelatin, natural sugars such as glucose or beta-lactose, corn sweeteners, natural and synthetic gums such as acacia, tracacanth or sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride, and the like. Disintegrants include, but are not limited to, starch, methyl cellulose, agar, bentonite, xanthan gum, and the like.

In the composition formulated as a liquid solution, acceptable pharmaceutical carriers are sterile and biocompatible, and include saline, sterile water, Ringer's solution, buffered saline, albumin injection, dextrose solution, maltodextrin solution, glycerol, ethanol and One or more of these components may be mixed and used, and other conventional additives such as antioxidants, buffers, and bacteriostats may be added as needed. In addition, diluents, dispersants, surfactants, binders and lubricants may be additionally added to form an injectable formulation such as an aqueous solution, suspension, emulsion, etc., pills, capsules, granules or tablets.

Furthermore, by using the method disclosed in Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA by an appropriate method in the art, it can be preferably formulated according to each disease or component.

The pharmaceutical composition of the present invention may be administered orally or parenterally, and in the case of parenteral administration, it may be administered by intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, transdermal administration, etc., preferably oral administration.

A suitable dosage of the pharmaceutical composition of the present invention varies depending on factors such as formulation method, administration mode, age, weight, sex, pathological condition, food, administration time, administration route, excretion rate and response sensitivity of the patient, and is preferred. The dosage varies depending on the condition and weight of the patient, the severity of the disease, the drug form, the route and duration of administration, but may be appropriately selected by those skilled in the art.

However, for a desirable effect, the fraction of the present invention is preferably administered at 0.0001 to 100 mg/kg per day, preferably 0.001 to 100 mg/kg. Most preferably, it is administered at 50 to 100 mg/kg. Administration may be administered once a day, or may be administered in several divided doses. The above dosage does not limit the scope of the present invention in any way.

The composition of the present invention may be administered to mammals such as rats, mice, livestock, and humans by various routes. Any mode of administration can be envisaged, for example by oral, rectal or intravenous, intramuscular, subcutaneous or intracerebrovascular injection.

The pharmaceutical composition of the present invention may be prepared in a unit dose form by formulating using a pharmaceutically acceptable carrier or excipient, or may be prepared by internalizing it in a multi-dose container. At this time, the formulation may be in the form of a solution, suspension, or emulsion in oil or aqueous medium, or may be in the form of an extract, powder, granule, tablet or capsule, and may additionally include a dispersant or stabilizer.

The present invention is a health functional food composition for preventing or improving brain neuropsychiatric disorders, comprising a fraction of an extract of aloes amulet as an active ingredient,

The fraction of the extract of the alopecia extract is a lipophilic fraction showing a peak at a retention time of 28.52 minutes with a coefficient of variation of 0.024% at a UV 280 nm wavelength of high-performance liquid chromatography (HPLC) with a non-polar column Prep It provides a health functional food composition for preventing or improving brain neuropsychiatric disorders, which is obtained by separation and purification by .LC.

In the present invention, 'health functional food' refers to food manufactured and processed by methods such as extraction, concentration, purification, mixing, etc. of specific ingredients as raw materials or in food raw materials for the purpose of health supplementation, It refers to a food designed and processed to sufficiently exert biological control functions such as biological defense, regulation of biological rhythm, prevention and recovery of disease, etc., and the composition for health food is related to disease prevention and recovery function can be performed.

The health functional food composition is not limited as long as it can be ingested to prevent or improve brain neuropsychiatric disorders.

When the composition of the present invention is used as a food additive, the fraction may be added as it is or used together with other foods or food ingredients, and may be appropriately used according to a conventional method. The mixed amount of the active ingredient may be suitably determined according to its intended use (prevention, health or therapeutic treatment). In general, in the production of food or beverage, the fraction of the present invention is added in an amount of 15 parts by weight or less, preferably 10 parts by weight or less, based on the raw material. However, in the case of long-term intake for health and hygiene or health control, the amount may be less than the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount above the above range. .

There is no particular limitation on the type of the food. Examples of foods to which the fraction can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea, drinks, There are alcoholic beverages and vitamin complexes, and it refers to all health foods in the ordinary sense.

When the composition of the present invention is used as a health drink, it may contain various flavoring agents or natural carbohydrates as an additional component like a conventional drink. The above-mentioned natural carbohydrates are monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclotenstrin, and sugar alcohols such as xylitol, sorbitol and erythritol. As the sweetener, natural sweeteners such as taumatine and stevia extract, synthetic sweeteners such as saccharin and aspartame, and the like can be used. The proportion of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 g of the composition of the present invention.

In addition to the above, the composition of the present invention includes various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, It may contain a carbonation agent used in carbonated beverages, and the like. In the gourd, the composition of the present invention may contain flesh for the production of natural fruit juices and vegetable beverages. These components may be used independently or in combination. Although the proportion of these additives is not very important, the composition of the present invention is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight.

Hereinafter, the present invention will be described in detail through Preparation Examples, Examples and Test Examples. However, these examples are for illustrating the present invention, and the scope of the present invention is not to be construed as being limited by these examples, and it will be appreciated by those skilled in the art that various changes or modifications can be made within the spirit and scope of the present invention. it is self-evident

[Preparation Example 1] Detecting agaric fractions

Aquilariae Lignum is a powdery aloes obtained from a herbal pharmaceutical company (Dae Han Bio Pharm Inc., Gyeonggi-do, Korea) approved by the Ministry of Food and Drug Safety.

First, 10 g of powder aloes were stirred and extracted with 200 mL of 30% ethanol at room temperature (25° C.) for 72 hours. After stirring, the precipitate was settled in a centrifuge (5000rpm 30min), and the supernatant was filtered with a 300-mesh filter paper (filter paper: Advantac, Tokyo Roshi Kaisah, Tokyo, Japan) 50mm, and the filtered liquid (fillterate) was circulated After concentration in an evaporator, it was freeze-dried. The yield of the final extract was 6.42% (w/w) and stored at -80°C for later use.

After mixing 5 g of the prepared aloes root extract powder with 200 g of 99% methylene chloride, the mixture was stirred at room temperature for 24 hours, followed by solvent extraction. The methylene chloride extract of aloes hyang was filtered through a 0.2 μm nylon filter, washed twice with methylene chloride, and the filtrate was collected. The collected filtrate was again dissolved in 100 mL of distilled water, the aqueous layer was removed, and the methylene chloride layer was dried over sodium sulfate. The volatile components were removed with a rotary concentrator to obtain 0.62 g of a yellow concentrate (methylene chloride extract). The final yield of re-extraction with methylene chloride was 0.79% (w/w).

1 mg of the methylene chloride extract was dissolved in 1 mL of 100% methanol and filtered through a 0.2 μm nylon filter. Then, 10 μL of the filtrate was injected into an HPLC analyzer using a C18 column to perform fingerprint analysis, and the results are shown in FIG. 1A.

At this time, the column flow rate was 1 mL/min, and the mobile phase conditions were performed using (A) distilled water and (B) acetonitrile as follows: 0 to 0.01 min, 30 % B (isocratic elution); 0.01 to 10 min, 0.01 to 40 % B (linear gradient elution); 10 to 15 min, 40 to 50 % B (linear gradient elution); 15 to 30 min, 50 to 60 % B (linear gradient elution); 30 to 40 min, 100% B (linear gradient elution); and 40 to 50 min (isocratic elution). This was detected with a UV detector. As a result, the five main peaks at a total UV wavelength of 280 nm have a coefficient of variation of 0.024%, with retention times of 8.13 min (fraction A), 13.80 min (fraction B), 17.70 min (fraction C), and 20.92 min (D). fraction) and 28.52 min (E fraction).

[Example 1] Separation of fractions of extract

In order to separate the active ingredient, it was attempted to separate the E fraction, which is the most effective among the HPLC peaks of the five major (A, B, C, D and E fractions) of Preparation Example 1.

To this end, first, 75 mg of the methylene chloride extract was dissolved in 1.5 mL of methanol and filtered through a 0.2 μm nylon filter. Then, 2000 μL of the filtrate was prep. Injected into the LC instrument. At this time, the column flow rate was set to 30 mL/min, and the results are shown in FIG. 1 . Mobile phase conditions were performed using (A) distilled water and (B) methanol as follows: 0 to 0.01 min, 50 % B (isocratic elution); 0.01 to 10 min, 0.01 to 55 % B (linear gradient elution); 10 to 15 min, 55 to 65 % B (linear gradient elution); 15 to 30 min, 65 to 75 % B (linear gradient elution); 30 to 40 min, 100% B (linear gradient elution); and 40 to 50 min (isocratic elution). It was detected with a wavelength of 190-700 nm on a photodiode array detector. Then, 2.2 mg of a yellow E fraction was obtained after removing the volatile components with a rotary concentrator.

[Test Example 1] Depression improvement effect was confirmed through the tail suspension test (TST) and forced swimming test (FST) in a rodent model with respect to the extract E fraction

The depressive behavior evaluation scale was confirmed in the rodent model with respect to the fraction E of the extract of the amorrhage of Example 1 by using the tail suspension method and the forced swimming method.

Thirty eight-week-old male mice (BALB/c 22-24g) were divided into 5 groups of 6 mice each (normal group, control group, low concentration group of E fraction extracted from agaropsis, a group with high concentration of fraction E fraction extracted from apricots, and a positive control group). Normal group (Vehicle) and control group (chronic stress, unpredictable chronic mild stress induction group, UCMS) treated with distilled water, low concentration group (Chronic stress induction E fraction E fraction 40mg/kg treated group, ALF 40mg/kg), aloes root extract E fraction high concentration group (Chronic stress induction E fraction E fraction 80mg/kg treatment group, ALF 80mg/kg), positive control group (N-acetyl-cysteine (NAC) 100mg/kg treatment group, NAC 100mg/kg after chronic stress induction) kg) and was orally administered for 3 weeks. Except for the normal group, various stresses such as restraint, fasting, and isolation were randomly assigned and applied for 3 weeks in the control group. On the day after the last stress application, TST was observed by using the tail suspension test (TST) for 6 minutes by hanging the tail of the test subject on the top of a 30 x 30 x 50 cm plastic square device. Behavioral observation images were taken using a video camera connected to the software (Smart 3.0, Panlab SL, Barcelona, Spain).

2A shows the immobility duration in the tail suspension method, and FIG. 2B shows the results of the activity duration in the tail suspension method. In the result of FIG. 2A, it was found that the immobility state was significantly reduced with a confidence level of 95% compared to the control group in the high concentration group of the extract E fraction of Example 1, and in the result of FIG. 2B, the activity state was a confidence level of 95 compared to the control group %, it was confirmed that depression was significantly improved at the confidence level of 95% through the tail suspension method, immobility time confirmation and activity time confirmation results.

The day after TST, in order to confirm with the forced swimming method, 50 x 20 x 30 cm cylindrical plastic equipment was filled with water at 25 °C to a height of 23 cm, and each experimental subject was observed for 6 minutes. Filmed using a connected video camera. The results are shown in Figures 2C and D. 2C shows the immobility time in the forced swimming method, and FIG. 2D shows the results of the active state time in the forced swimming method. In the result of FIG. 2C, it was found that the immobility state was significantly reduced with a reliability of 99% compared to the control group in the high concentration group of the fraction E fraction of Example 1, and in the low concentration group of the fraction E fraction of Example 1, compared to the control group Therefore, it was found that the immobility was significantly reduced with a reliability of 95%. In addition, in the result of FIG. 2D, it was confirmed that the time of the active state significantly increased with a reliability of 99% in both the low concentration group and the high concentration group of the extract E fraction of Example 1 above. In addition, in the positive control group, it was confirmed that the active state time was increased to a level of 95% confidence. In the forced swimming method results of FIGS. 2C and 2D, it was confirmed that depression was significantly improved at a confidence level of 95% or higher.

As such, it was confirmed that, through the results of the tail suspension method and the forced swimming method using the randomization, the E-fraction of the extract E of Example 1 improved depression with a confidence level of 95%.

[Test Example 2] Anxiety behavior observation through the open space method in a rodent model with respect to the E fraction of the extract

Anxiety behavior evaluation scale was confirmed in the rodent model with respect to the fraction E of the extract of the amphitheater 1 of Example 1 using the open space method.

The day after FST, to measure anxious behavior by the open field test (OFT), it was placed in a plastic box of 30 x 40 x 30 cm and observed for 5 minutes for each experimental subject. 3.0). The results are shown in Figures 2E and F. 2E shows the results for the distance traveled by the open branch in the open space method, and FIG. 2F shows the results for the time spent in the open branch in the open space method.

In the result of FIG. 2E, it was found that the movement distance of the open branches was significantly increased with a reliability level of 99% compared to the control group in both the low-concentration group and the high-concentration group of the extract E fraction of Example 1 above.

In addition, in the result of FIG. 2F, the positive control group showed an increase in the residence time in the open branch with 99% reliability compared to the control group, and both the low concentration group and the high concentration group of the aloes root extract E fraction stayed at a reliability level of 99% compared to the control group. It was confirmed that this significantly increased.

As a result of confirming the anxiety behavior evaluation scale using the open space method using randomization, it was confirmed that anxiety was significantly improved with a reliability of 99%.

[Test Example 3] Confirmation of cytotoxicity and nitric oxide (NO) in brain microglia cell lines

In order to confirm the safety of the E fraction of the extract according to the present invention, cytotoxicity was confirmed through cell viability in brain microglia.

Nitric oxide (NO) is a gaseous substance that exists in the body, and has very high reactivity such as nitrate (NO3 -), nitrite (NO2 -), peroxynitrite (ONOO -), and 3-nitrotyrosine. It is easily converted into an intermediate. When NO is produced excessively, NO or its intermediates induce nitrooxidative stress that causes the transformation of DNA, proteins and lipids constituting cells. In particular, due to dysfunction of various proteins necessary for cell survival, cell dysfunction and apoptosis occur as a result. Also, neurons are particularly vulnerable to NO. This is because NO induces excitatory toxicity in neurons, and its cytotoxicity increases when it is present together with superoxide produced by microglia. Therefore, excessive production of NO causes neuronal cell death. In addition, the NO causes brain neurological disorders such as schizophrenia due to an abnormal nitric oxide system in the brain. In this regard, in order to evaluate the inhibitory effect of the composition on the activity of brain microglia, which plays an important role in the onset of brain neuropsychiatric disorders, and its mediated by-product production, the agarose extract E fraction of Example 1 on microglia (ALF 0.5, 1, 2.5 ug/mL) and NAC as a positive control were treated to confirm cytotoxicity. The cells were further cultured for 24 hours, and then treated with the E fraction of the extract E and NAC, and the results were confirmed at absorbance at 540 nm after 24 hours.

The results for drug cytotoxicity to BV2 microglia are graphically shown in FIG. 3A . In addition, the results of inhibition of nitric oxide overproduction according to LPS-induced microglia overactivity are shown in FIG. 3B. As shown in the result of FIG. 3A , the cell viability of the fraction E of the extract of Example 1 was 90% or more, confirming that it was not toxic and was safe. In addition, as shown in the result of Figure 3B, it was confirmed that the fraction E of the extract of Example 1 inhibited the overproduction of nitrogen monoxide.

[Test Example 4] Confirmation of inhibition of nitric oxide production in brain microglia cell lines

In the same manner as in Test Example 3, the brain microglia were treated with LPS, and then the nitric oxide production inhibitory effect of the extract fraction (5ug/mL) of the preparation example was confirmed.

As shown in the results of FIG. 4 , the A, B, C, D, and E fractions of the extracts A, B, C, D, and E exhibited an inhibitory effect on nitric oxide production only in the fraction E of the extract of Example 1, and the extracts A, B , C, D, and E fractions, it was confirmed that when all mixed and treated with 25 ug/mL, the nitrogen monoxide production inhibitory effect according to the E fraction of the extract of Example 1. As such, the synergistic effect of inhibiting the production of nitrogen monoxide was confirmed when the fractions of the extract of aloes root were mixed.

[Test Example 5] PGE2 and iNOS / COX2 inhibitory effect confirmed in brain microglia cell line

The results of inhibition of the composition of the present invention on iNOS involved in nitric oxide synthesis as a brain inflammatory mediating by-product, PGE2, another by-product, and COX2, an enzyme involved in its production, are shown in FIGS. 5A, 5B, 5C and 5D. .

Figure 5A is a graph showing the results of inhibition of secretion and production of prostaglandin _E2 (prostaglandin, PGE ₂ ), Figure 5B is an enzyme (inducible nitric oxide synthase, iNOS and The results of Western blot measurement of the protein secretion inhibitory effect of cyclooxygenase, COX2) are shown. Figure 5C shows the results of confirming the iNOS and COX2 gene activity inhibitory effect of the amorrhage extract E fraction according to Example 1 by qPCR. Western blot results are shown graphically.

As shown in FIG. 5A , the PGE2 reduction effect was confirmed in the E fraction (ALF 0.5, 1, 2.5 ug/ml treatment test group) of the extract of Example 1 above. In addition, as shown in the result of FIG. 5B, when iNOS and COX were confirmed by western blot, a reduction effect was confirmed in the E fraction of the extract of Example 1 compared to the control (Vehicle). In addition, as shown in the result of FIG. 5C , at the gene level (qPCR), as a result of confirming the reduction effect of the E fraction of the aloes root extract of Example 1 on the iNOS and COX2 compared to the Housekeeping gene GAPDH, the result was 99% of p < 0.01. It was confirmed that it decreased with reliability. In addition, as shown in the result of FIG. 5D , as a result of checking for housekeeping 　 gene actin at the protein level (Western blot), it was confirmed that iNOS and COX2 were concentration-dependently reduced with a reliability of 95%.

[Test Example 6] Confirmation of NF-κB activity in brain microglia

Regarding brain neuropsychiatric disorders, the activity of NF-κB as a transcription factor related to the synthesis of inflammatory mediators in the brain was confirmed by immunofluorescence staining and western blot whether or not nuclear translocation of brain microglia was performed. The results of the adjustment for the fraction E of the extract of aloes root in Example 1 are shown in FIGS. 6A, 6B, 6C, and 6D.

Figure 6A is the result of measuring the activity of NF-κB by immunofluorescence staining, Figure 6B is the result of measuring the NF-κB transcription promoters P65 and P-P65 activity by Western blot, Figure 6C is the NF-κB signal (signal) is a result of Western blot measurement, Figure 6D is a graph showing the P65 activity, a transcription promoter of NF-κB, for Western blot, Figure 6E is a P-P65 / P65 graph of NF-κB activity the results are shown.

As shown in FIG. 6A, it was confirmed that the NF-κB activity reducing effect was significantly reduced in the fraction E of the extract E of Example 1 above.

6B is a western blot for the dimer of RelA(P65) acting as a transcriptional promoter among various forms such as NF-κB homo, hetero dimer, etc. As a result, the activity was significantly reduced in P-P65 (Phosphorylation-P65) of the nucleus It was confirmed that the effect appeared. In addition, as shown in FIG. 6C, as a result of graphing and confirming the Western results for the NF-κB signal, it was confirmed that the NF-κB signal was decreased in a concentration-dependent manner.

Also, as shown in FIG. 6D , when graphing P65 in the cytosolic and nucleus, the Housekeeping gene for NF-κB activity compared to actin and lamnin B1, P<0.05 or more, the reliability was significantly reduced to 95%. confirmed that.

In addition, when it was confirmed as P-P65/P65 as NF-κB activity, it was confirmed that it was significantly reduced with a reliability of 99% in the E fraction of the extract of Example 1 (ALF 1ug/mL).

[Test Example 7] Identification of inflammatory cytokines (TNF-α, IL-1β) in brain microglia

Inhibition of brain inflammatory cytokines was confirmed for the fraction E of the extract of Example 1 for brain inflammatory cytokines (TNF-α, IL-1β) secreted into the culture medium according to brain microglia hyperactivity.

7A is an ELISA assay of TNF-α, FIG. 7B is an ELISA assay of IL-1β, and FIG. 7C shows the results of confirming the gene activity of TNF-α and IL-1β by qPCR.

As a result of confirming the brain inflammatory cytokines, TNF-α, IL-1β secreted from the cell media using ELISA as shown in FIGS. 7A and 7B, it was confirmed that the brain inflammatory cytokines were significantly reduced in IL-1β. did In addition, using qPCR, as a result of confirming gene activity, it was confirmed that the brain inflammatory cytokines were significantly reduced in IL-1β.

[Test Example 8] Confirmation of the inhibitory effect of the inflammatory regulatory complex in brain microglia cell lines

NLRP3 inflammasome, NLRP3 (Nod-like receptor family pyrin domain containing 3) inflammasome is a cytosolic sensor (intracellular sensor) linking psychological stress and depression. . Also, among inflammatory cytokines, the NLRP3 inflammasome pathway, known as an IL-1β-specific pathology, acts in a caspase-1 activity-dependent manner. In addition, ASC (adapter apoptosis-associated speck-like) is an adapter protein of the NLR3 inflammaome, and when the NLRP3 inflammasome is activated, it is redistributed from the nucleus to the cytoplasm to form a large nuclear peripheral structure in the cell. Clinically, the IL-1β and NLR3 inflammaome are increased in patients with neuropsychiatric disorders. As such, the NLRP3 inflammasome interacts with IL-1β, ASC and caspase-1 as key intracellular sensors in neuropsychiatric disorders including depression and anxiety. The activities of NLRP3 inflammasome, IL-1β, ASC and caspase-1, which are inflammatory complexes, were measured using Western blot or enzyme-linked immunosorbent assay (ELISA) techniques. Control results of the composition of the present invention are shown in Figures 8A, 8B, and 8C.

Figure 8A shows the result of measuring the inhibitory effect of the inflammatory regulatory complex by Western blot, Figure 8B shows the measurement result of caspase-1 in the inflammatory regulatory complex by ELISA assay, Figure 8C is the measurement of the inhibitory effect on the inflammatory regulatory complex It is a graph of a Western blot result.

As shown in the results of Figure 8A, as a result of confirming at the protein level by Western blot, in the test group treated with the extract E fraction (ALF) of Example 1, NLRP3 inflammasome, ASC and IL-1β were significantly reduced Confirmed. In addition, as shown in FIG. 8B , as a result of confirming caspase-1 by using ELISA, it was confirmed that the caspase-1 was significantly reduced in the fraction E fraction (ALF) of the extract of Example 1 (ALF) with a reliability of 99%. In addition, FIG. 8C shows that when confirmed by graphing the Western results, NLRP3 inflammasome, ASC and It was confirmed that IL-1β was significantly reduced.

Hereinafter, a formulation example of a composition comprising the fraction of the extract of the present invention as an active ingredient will be described, but the present invention is not intended to limit it, but to describe it in detail.

<Formulation Example 1> Preparation of pharmaceutical formulations

1. Preparation of tablets

A tablet containing the fraction of the extract of the present invention obtained in the above Example as an active ingredient was prepared as follows. Lactose, starch and gelatinized corn starch were mixed with the fraction of the extract of aloes root, added with an appropriate volume of purified water, and granulated into a powder. After drying the granules, they were mixed with magnesium stearate and compressed to prepare tablets. The components of the tablet are as follows.

Fraction of aloes extract 5.0 mg

Lactose BP 150.0 mg

Starch BP 30.0 mg

Gelatinized Corn Starch BP 15.0 mg

magnesium stearate 1.0 mg

2. Preparation of capsules

A capsule containing the fraction of the extract of the present invention as an active ingredient was prepared as follows. A certain amount of the excipient and magnesium stearate of the fractions of the extract of the present invention were mixed. The obtained mixture was filled in gelatin capsules to prepare capsules.

The components of the capsule are as follows.

Fraction of aloes extract 5.0 mg

starch 1500 100.0 mg

Magnesium Stearate BP 1.0 mg

3. Preparation of injections

An injection containing the fraction of the extract of the present invention as an active ingredient was prepared as follows.

Dissolve the E fraction of the aloes root extract in an appropriate volume of sodium chloride BP for injection, and adjust the pH of the resulting solution to pH 3.5 with dilute hydrochloric acid BP, then adjust the volume with sodium chloride BP for injection and mix thoroughly did. The solution was filled in a 5 ml type I ampoule made of clear glass, sealed under an upper grid of air by dissolving the glass, and then sterilized by autoclaving at 120° C. for 15 minutes or more to obtain an injection.

Fraction of aloes extract 200 μg/ml

dilute hydrochloric acid BP until pH 3.5

Magnesium Stearate BP up to 1ml

4. Preparation of pills

After mixing the following components, it was prepared so as to be 4 g per ring according to the general method.

Fraction of aloes extract 0.5 g

lactose 1.5 g

glycerin 1 g

xylitol 0.5 g

5. Preparation of liquid formulations

According to a conventional liquid preparation method, each component is added and dissolved in purified water, lemon flavor is added, and the following ingredients are mixed. did

Fraction of aloes extract 5 mg

Lee Seonghwadang 10 g

mannitol 5 g

Appropriate amount of purified water

6. Preparation of powder

After mixing the following components, the powder was prepared by filling in an airtight cloth.

Fraction of aloes extract 0.5 mg

lactose 100 mg

talc 10 mg

<Production Example 2> Preparation of health functional food

manufacturing of health food

Fraction of aloes extract 5 mg

vitamin mixture appropriate amount

vitamin A acetate 70 μg

vitamin E 1 mg

vitamin 0.13 mg

vitamin B2 0.15 mg

vitamin B2 0.5 mg

vitamin B12 0.2 μg

vitamin C 10 mg

biotin 0.2 μg

Nicontinamide 1.7 mg

folic acid 50 mg

Pantothenic acid knife? 0.5 mg

mineral mixture appropriate amount

ferrous sulfate 1.75 mg

zinc oxide 0.82 mg

magnesium carbonate 25.3 mg

monobasic calcium phosphate 15 mg

dicalcium phosphate 55 mg

potassium citrate 90 mg

calcium carbonate 100 mg

magnesium chloride 24.8 mg

The composition ratio of the vitamin and mineral mixture was prepared by mixing components suitable for relatively healthy food as a preferred manufacturing example, but the mixing ratio may be arbitrarily modified. The granules can be prepared and used in the preparation of health food compositions according to a conventional method.

2. Manufacture of health drinks

Fraction of aloes extract 5.0 mg

citric acid 1000 mg

oligosaccharide 100 g

Plum Concentrate 2g

Taurine 1 g

Total 900ml with purified water

After mixing the above ingredients according to the usual manufacturing method of health drinks, after stirring and heating at 85° C. for about 1 hour, the resulting solution is filtered and acquired in a sterilized 2 liter (ℓ) container, sealed and sterilized, and then stored in a refrigerator. Thus, it was used to prepare a health drink composition according to the present invention. Although the composition ratio is prepared by mixing ingredients suitable for relatively favorite beverages in a preferred embodiment, the mixing ratio may be arbitrarily modified according to regional and national preferences such as demand class, demanding country, and use.

As such, the extract of aloes root extract has an inflammatory mechanism and an oxidative stress improvement effect on cranial nerve disorders including depression and anxiety disorders, so it can be usefully used as a pharmaceutical composition or health functional food composition for effectively preventing and treating brain neuropsychiatric disorders. have.

In particular, in the non-clinical experiment, animal experiments using rodents, a significant effect of 95% or more of the reliability of the extract of aloes root extract according to the present invention was confirmed, and also clinically reported neuropsychiatric disorder with depression and anxiety as the main symptoms. Improvement effects such as significant inhibition and reduction of nitric oxide (NO), NLRP3 inflammasome, ASC and IL-1β, which are related pharmacological mechanisms, have been verified and confirmed, preventing brain neuropsychiatric disorders, It can be usefully used as a composition for improvement or treatment.

So far, we have looked at preferred examples and test examples for the present invention. Those of ordinary skill in the art to which the present invention pertains will understand that the present invention can be implemented in a modified form without departing from the essential characteristics of the present invention. Therefore, the disclosed embodiments are to be considered in an illustrative rather than a restrictive sense. The scope of the present invention is indicated in the claims rather than the foregoing description, and all differences within an equivalent scope should be construed as being included in the present invention.

Claims (8)

As a pharmaceutical composition for the prevention or treatment of brain neuropsychiatric disorders comprising a fraction of the extract of aloes amulets as an active ingredient,
The fraction of the extract of the alopecia extract is a lipophilic fraction showing a peak at a retention time of 28.52 minutes with a coefficient of variation of 0.024% at a UV 280 nm wavelength of high-performance liquid chromatography (HPLC) with a non-polar column Prep .LC (Recycling Preparative Liquid Chromatograph) will be obtained by separation and purification, a pharmaceutical composition for preventing or treating brain neuropsychiatric disorders. According to claim 1,
A pharmaceutical composition for preventing or treating neuropsychiatric disorders in the brain, wherein the fraction of the extract is contained in an amount of 0.1 to 1% by weight based on the total weight% of the extract. According to claim 1,
The brain neuropsychiatric disorder is major depressive disorder, bipolar disorder, schizophrenia, panic disorder, autism, obsessive-compulsive disorder, Eating disorder, visual or auditory hallucination, dysthymia, and anxiety disorder, any one selected from the group consisting of, for the prevention or treatment of neuropsychiatric disorders pharmaceutical composition. According to claim 1,
The Aquillaria (Aquilaria) genus plant is derived from the, a pharmaceutical composition for the prevention or treatment of neuropsychiatric disorders in the brain. 5. The method of claim 4,
The Aquilaria (Aquilaria) genus plants are Aquilaria Lignum (A. Lignum), Aquilaria Cassiana (A. khasiana), Aquilaria Apiculina (A. apiculina), Aquilaria blillonil (A. blillonil) , Aquilaria baneonsis (A. baneonsis), Aquilaria brachyantha (A. brachyantha), Aquilaria cummingiana (A. cunmingiana), Aquilaria filaria (A. filaria), Aquilaria grandiflora (A) . (A. malaccensis), Aquilaria sinensis (A. sinensis) and Aquilaria crassana (A. crassna), any one selected from the group consisting of, a pharmaceutical composition for the prevention or treatment of neuropsychiatric disorders in the brain. According to claim 1,
The extract of alopecia is an extract obtained by first extracting the extract with water, C1 to C3 alcohol, or a mixture thereof as a solvent with one or more solvents selected from chloroform, ether, or methylene chloride. A pharmaceutical composition for preventing or treating a disorder. As a health functional food composition for preventing or improving brain neuropsychiatric disorders comprising a fraction of aloes root extract as an active ingredient,
The fraction of the extract of the alopecia extract is a lipophilic fraction showing a peak at a retention time of 28.52 minutes with a coefficient of variation of 0.024% at a UV 280 nm wavelength of high-performance liquid chromatography (HPLC) with a non-polar column Prep A health functional food composition for preventing or improving brain neuropsychiatric disorders, which is obtained by separation and purification by .LC. 8. The method of claim 7,
A health functional food composition for preventing or improving brain neuropsychiatric disorders, wherein the fraction of the extract is comprised in an amount of 0.1 to 1% by weight based on the total weight% of the extract.

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