KR20190128423A - Composition comprising the extract of Patriniae Radix for preventing and treating Attention Deficit Hyperactivity Disorder - Google Patents

Abstract

The present invention relates to a composition for alleviating and treating attention deficit hyperactivity disorder (ADHD). The composition comprising Patriniae radix extract as an active ingredient according to the present invention can effectively prevent, alleviate or treat hyperactivity disorders such as intuition, impulsivity, interpersonal relationships, emotional change, concentration, and restraint by suppressing reuptake activities of neurotransmitters, can minimize side effects such as dependence, growth inhibition and somnipathy as single targets by having various discriminative selectivities with respect to dopamine, norepinephrine and serotonin nervous systems, thereby enabling multiple targets to be elastically adjusted, and can be used safely and consistently without applying severe stimulation to the interior of the body or causing harmful actions since the composition is derived from a natural product.

Description

Composition comprising the extract of Patriniae Radix for preventing and treating Attention Deficit Hyperactivity Disorder}

The present invention relates to a composition for improving and treating attention deficit hyperactivity disorder (ADHD).

Attention Deficit Hyperactivity Disorder (ADHD) is a brain development disorder that manifests itself in the brain's signaling system. Although ADHD has a high prevalence of 5-10%, it is considered to be one of the refractory diseases in the field of cerebral nerve where its causative agent and pathology are not clearly identified. The disease is often diagnosed early in childhood, but recent studies also report a number of late onset ADHD cases (Adgnew-Blais et al., 2016; Caye et al., 2016; Faraone and Biederman, 2016; Moffitt et al 2015). Prevalence rates around 2.2-7.2% for children and adolescents and 2.8-5.0% for adults worldwide (Fayyad et al., 2007, 2016; Polanczyk et al. 2007; Thomas et al., 2015; Willcutt, 2012) Main symptoms include excessive and persistent inattention, hyperactivity, and impulsivity (Aatan Psychiatric Association, 2000). It also leads to dysfunction in areas such as cognition, social interaction, employment, self-management and mobility, and has a high prevalence, and because of its strong correlation with psychotic illness, persistence to adulthood, and lifetime dysfunction, It is recognized as an important disorder around the world (Fayyad et al., 2016).

Currently used drugs include methylphenidate and atomoxetine, which are single targets, causing serious side effects such as dependency, growth inhibition and sleep disorders. Its use is being avoided by guardians.

Despite the 7 trillion won annual ADHD drug market, the current drug is in need of new drug development that has secured efficacy and safety due to the presence of 25% of non-treated patients and various side effects.

Intuition, impulsivity, interpersonal relationships, emotional changes, concentration, and suppression, which are closely related to the symptoms and etiology of ADHD, have complex relationships with the dopamine, norepinephrine, and serotonin nervous systems. The degree of symptoms is different.

Pajanggeun (敗 醬 根) proposed in the present invention refers to the roots of the family Dungalgal or Matariaceae as a plant also referred to as kungjanggeun. It is known that saponin-like ingredient, patlinioside, has hemolytic and local stimulating effects and is mainly used for colon disease, detoxification, postpartum sequelae, prostate treatment, anti-inflammatory, skin disease, hemorrhoids and nervous breakdown.

Related patents include composition and health functional food for treating lung cancer (KR 2011-0027371), prevention and treatment of brain cancer (KR 2011-0012222), pancreatic cancer treatment composition and health functional food (KR 2011-0085596), etc. There is no research related to the use of extracts in improving overaction.

The inventors have developed a natural product that can elastically control multiple targets through the development of substances with various differential selectivity for dopamine, norepinephrine, and serotonin nervous system, and prevent, improve or treat ADHD while minimizing side effects from the initial development stage. I tried to As a result, the present invention was completed by confirming the effect of inhibiting dopamine, norepinephrine, and serotonin transporter's multiple neurotransmitter reuptake activity, and the inhibitory effect on the mouse model.

Accordingly, it is an object of the present invention to provide a composition for the prevention, improvement and treatment of Attention Deficit Hyperactivity Disorder (ADHD), which contains Patriniae radix extract as an active ingredient.

In order to solve the above problems, the present invention provides a pharmaceutical composition for the prevention and treatment of Attention Deficit Hyperactivity Disorder (ADHD) containing the extract Pajakeun ( Patriniae radix ) as an active ingredient.

In addition, the present invention provides a dietary supplement for the prevention and improvement of attention deficit hyperactivity disorder (ADHD) containing the extract of Patriniae radix as an active ingredient.

The composition containing the extract of Paengeungeun as an active ingredient effectively inhibits, improves or treats hyperactivity disorders such as intuition, impulse, interpersonal relationship, emotional change, concentration, and inhibitory ability by inhibiting neurotransmitter reuptake activity. It has an excellent effect.

In addition, the composition containing the extract of the root muscle of the present invention as an active ingredient has a variety of differential selectivity to the dopamine, norepinephrine, serotonin nervous system can be elastically controlled multiple targets, such as dependency, growth inhibition and sleep disorders as a single target Side effects can be minimized.

In addition, the extract of Pajanggeun of the present invention is derived from natural products without showing toxicity as a result of animal experiments, and safely and continuously without causing serious irritation or harmful effects in the body in addition to the prevention, improvement and treatment efficacy of hyperactivity disorder. Can be used.

1 is a result showing the inhibitory effect of each neurotransmitter transporter by the extract of the root muscle in HEK-293-cell line, Figure 1a is the inhibitory effect of dopamine neurotransmitter reuptake activity, Figure 1b is norepinephrine neurons Delivery material reuptake inhibitory effect inhibitory effect, Figure 1c is a diagram showing the effect of inhibiting serotonin neurotransmitter reuptake activity.
Figure 2 is a result of confirming the inhibitory effect of the excess activity by the extract of the root muscle in the experimental animal, A is the result of confirming the inhibitory effect of hyperactivity in the attention deficit / hyperactivity disorder model (SHR), B is a control group Wistar-Kyoto This is the result of checking the excess behavior of rat (WKY).
3 is a diagram inducing sleep by administering ketamine to the experimental animal and confirming the sleep induction and sleep duration by the extract of the root muscle, A is the sleep time, B is the result of confirming the sleep duration.
Figure 4 is to confirm the toxicity of the extract of the root, Figure 4a is to confirm the weight change of the week, Figure 4b is a picture showing the toxicity of the organ, Figure 4c is to confirm the change in organ weight.

Hereinafter, the present invention will be described in detail.

According to one aspect of the invention, the present invention provides a composition for the prevention, improvement and treatment of Attention Deficit Hyperactivity Disorder (ADHD) containing an extract of Patriniae radix as an active ingredient.

The present inventors have diligently studied the development of ADHD therapeutics without side effects and toxicity using natural extracts. As a result, the effect of inhibiting the reuptake activity of dopamine, norepinephrine, and serotonin transporter of Pasengeun extract and hyperactivity suppression in ADHD animal model The effect was confirmed, and there were no side effects of sleep disorders and cytotoxicity in the experimental animals administered orally the myofascimus extract.

In the present specification, "peanus root extract" includes all of them without particular limitation, as long as it is obtained by extracting an active ingredient from natural root melancholia. For example, the result obtained by putting a package root in water or an organic solvent and eluting an effective component through means, such as standing, stirring, pressurization, or heating, is mentioned. It also includes a lyophilized product obtained by lyophilizing the liquid extract thus obtained. It also includes a powder obtained by grinding such lyophilisate. In addition, any possible means for extracting the active ingredient includes all the extracted extracts, including all the processed after extraction and freeze-drying. Others include extracts obtained by conventional extraction methods such as extraction by baths or room temperature, or by conventional extraction methods described in Chinese medicine or textbooks. In addition, the fraction extract obtained through a special extraction method or various column chromatography methods for separating the specific active compounds.

In one embodiment of the present invention, the mesothelioma extract of the present invention may be obtained by treating with ultrasonic waves after adding a solvent to the melancholia. As the solvent, any pharmaceutically acceptable organic solvent may be used, and water or an organic solvent may be used, but is not limited thereto. For example, purified water, methanol, ethanol, C1-C4 alcohol, acetone, ether, benzene, chloroform, ethyl acetate, including propanol, isopropanol, butanol, etc. ), Methylene chloride, hexane and cyclohexane may be used alone or in combination. Preferably ethanol (alcohol) can be used, more preferably 80 to 95 w / v% ethanol is used.

In one embodiment of the present invention, the mycorrhizal extract of the present invention using 80 ~ 95 w / v% ethanol for 1 to 3 hours after sonication for 10 to 20 minutes at 40 ~ 50 ℃ 25 ~ 35 It may be obtained by repeating times.

In one embodiment of the present invention, the frequency of the ultrasonic wave in the ultrasonic treatment may be 30 ~ 40 kHz, preferably 35 ~ 37 kHz, most preferably 36.5 kHz.

The extract of Pajanggeun of the present invention is increased in extraction efficiency compared to the extract extracted with simply ethanol solvent, and also shows a more excellent effect on the hyperactivity inhibiting activity.

The pharmaceutical composition according to the present invention may further comprise suitable carriers, excipients and diluents commonly used in the manufacture of pharmaceutical compositions.

The pharmaceutical dosage forms of the compositions of the present invention may be used in the form of their pharmaceutically acceptable salts, and may be used alone or in combination with other pharmaceutically active compounds as well as in a suitable collection. The salt is not particularly limited as long as it is pharmaceutically acceptable. For example, hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, hydrofluoric acid, hydrobromic acid, formic acid acetic acid, tartaric acid, lactic acid, citric acid, fumaric acid, maleic acid, succinic acid, methanesulfonic acid , Benzene sulfonic acid, toluene sulfonic acid, naphthalene sulfonic acid and the like can be used.

The pharmaceutical compositions according to the present invention may be used in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, oral formulations, ointments, creams, external preparations, suppositories, and sterile injectable solutions. It may be used in formulated in any form suitable for pharmaceutical formulations.

In the compositions according to the invention, the preferred dosage of the extract of the invention depends on the subject's age, sex, weight, symptoms, extent of disease, drug form, route of administration and duration, but may be appropriately selected by those skilled in the art. have. However, for the desired effect, the composition of the present invention is preferably administered at 0.001 to 500 mg / kg body weight per day. Administration may be administered once a day or may be divided several times. In addition, the dosage may be increased or decreased depending on age, sex, weight, degree of disease, route of administration, and the like. Therefore, the above dosage does not limit the scope of the present invention in any aspect.

The composition according to the present invention can be administered to mammals such as rats, mice, livestock, humans by various routes, such as parenteral, oral, and all modes of administration can be expected, for example, oral, rectal Or by intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebroventricular injection.

On the other hand, the composition according to the present invention, there is no serious toxicity and side effects can be used with confidence even for long-term use for the purpose of prevention.

The composition according to the present invention may contain 0.001 to 99.9% by weight of the extract as an active ingredient in the total weight of the composition. This is because the effect can be expected to be 0.001% by weight or more, it is difficult to exceed 99.9% by weight due to the presence of impurities.

On the other hand, in the case of formulating the extract of the present invention into tablets, capsules, chewing tablets, small bags, granules, powders, liquid solutions, suspensions, dispersions, emulsions, syrups and the like for the purpose of oral administration, gum arabic, Binders such as corn starch, microcrystalline cellulose or gelatin, excipients such as dicalcium phosphate or lactose, disintegrants such as alginic acid, corn starch or potato starch, lubricants such as magnesium stearate, sweeteners such as sucrose or saccharin and Flavoring agents such as peppermint, methyl salicylate or fruit flavors may be included, and when the dosage unit form is a capsule, liquid carriers such as polyethylene glycol or fatty oil may be included in addition to the above components.

The present invention also provides a health functional food composition comprising an extract and a food acceptable additive. Food composition according to the present invention, for example, chewing gum, caramel products, candy, ice cream, various foods such as confectionery, soft drinks, mineral water, beverage products such as alcoholic beverages, health functional foods including vitamins and minerals, etc. Can be.

At this time, the amount of the extract in the food may be added to 0.001 to 99.9% by weight of the total food weight, in the beverage may be added in a ratio of 0.001 to 0.1 g, more preferably 0.05 to 0.1 g based on 100 ml. .

The beverage containing the extract of the present invention is not particularly limited to other ingredients except for containing the extract or the compound derivative as essential ingredients in the indicated proportions, and contains various flavors or natural carbohydrates as additional ingredients, such as ordinary drinks. can do.

In addition to the above, the functional food composition of the present invention includes various nutrients, vitamins, minerals (electrolytes), synthetic flavors such as synthetic and natural flavors, colorants and enhancers (such as cheese and chocolate), pectic acid and salts thereof, alginic acid And salts thereof, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like. In addition, the functional food compositions of the present invention may contain fruit flesh for the production of natural fruit juices and fruit juice beverages and vegetable beverages. These components can be used independently or in combination. The proportion of such additives is not so critical but is usually selected in the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.

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

Example 1.Preparation of Root Root Extract

The extract of Paengeun root used in the present invention was supplied from Korea Plant Extract Bank of Korea Research Institute of Bioscience and Biotechnology and used for experiments. It is a herbal sample extracted by sonication (SD-ULTRASONIC CLEANER, SDN-900H) at a frequency of 36.5 kHz for 10 hours 3 days a day. The extracted material was filtered using a non-fluorescent cotton as a filter paper, concentrated using a rotary evaporator, N-1000SWD (EYELA) at 45 ℃. The concentrated sample was dried using Modul spin 40 of Biotron coporation for 24 hours at -70 ℃. The dried extract was stored in a -4 ° C low temperature room as the original sample.

Experimental Example 1. Determination of neurotransmitter reuptake inhibitory effect of dopamine, norepinephrine, serotonin transporter by treatment with extract of Pa root muscle

The transporter cDNA is transfected into the HEK-293 cell line. For transient transfection, the transfected cDNA (3 μg / 100 mm dish, PEI: 10 μl) subcloned in pCDNA 3.1 (Zeo) is transfected into a 100 mm culture dish. The next day the cells were seeded again in 24 well plates. Thereafter, the medium was removed and 200 μl of each of the root muscle extracts diluted in the buffer was added and incubated at 37 ° C. for 15 minutes. Then 100 μl buffer containing 20-30 nM [3H] -DA (dopamine) was added and incubated at 37 ° C. for 5 minutes. In the case of NE and 5-HT, cells transformed with NE or 5-HT transporter cDNA were used, and [3H] -NE (norepinephrine) or [3H] -5-HT (serotonin) was used as a substrate. (FIG. 1). The reaction solution was quickly removed, washed three times with 1 ml cold chilled buffer, dissolved in 0.5 ml of 1% SDS, and then measured for activity.

As a result of experiments on the inhibitory effect of dopamine reuptake, GBR12909 (vanoxerine) positive control group, which is known as dopamine reuptake inhibitor, showed about 85% inhibitory effect compared to vehicle control group. . Experimental results on the inhibitory effect of norepinephrine resorption showed a norepinephrine reuptake inhibitory effect similar to the positive control group (Fig. 2b). As a result of the serotonin reuptake inhibitory effect, venlafaxine, a positive control, showed about 60% of serotonin reuptake inhibitory effect, and the myofascissus showed about 90% inhibition effect compared to the control group. Better inhibitory efficacy was shown (FIG. 2C).

Experimental Example 2. Confirmation of the inhibitory effect of the excessive action by the extract of the root muscle in the experimental animal (A, B of Figure 2)

50 mg / kg or 10% tween 80 of the root muscle extract was administered orally to the three-week-old Attention Deficit Hyperactivity Disorder (ADHD) model, SHR, and the control group, Wistar-Kyoto Rat (WKY). The open field test (OFT), which measures distance and time traveled in a wide box for 10 minutes, confirmed the effect of suppressing excess behavior.

Experimental results in SHR, the animal model of ADHD, showed 350 cm and 40 seconds less movement in the PA group than the vehicle on the first day of administration. On the 7th day, 400 cm and 50 seconds less in the PA group than the vehicle. (A in FIG. 2).

The control group, Wistar-Kyoto rat (WKY), showed no significant difference between the two groups on the first day of administration. 2, B).

Experimental Example 3. Confirmation of the sleep disorder side effects by the extract of Pa root muscle in the experimental animal (Fig. 3)

Four-week-old mice were ingested 50 mg / kg of Pa root muscle extract or Geuncho root extract (positive control of sleep, 10 mg / kg) by oral administration for one week, followed by intraperitoneal injection of ketamine 100 mg / kg in 5-week-old mice. To induce sleep. If the ketamine-treated mice showed their stomachs and turned upside down, they fell asleep, and the mice that showed their stomachs and turned upside down were considered to be completely awake from sleep.

As a result of confirming the sleep induction and sleep duration effect by the extract of Paengeun root, there was no difference in the sleep induction time and duration as compared to the negative control group, it was confirmed that there is no effect on sleep induction effect, sleep time enhancement effect or sleep disorder. (FIG. 3).

Experimental Example 4. Confirmation of the toxicity of the extract of Paengeuneun (Fig. 4)

As a result of measuring the weight change during the period of injecting 50 mg / kg of Pa root muscle extract in 4 weeks old mice, it was confirmed that there was no weight change between the groups (FIG. 4A). After 7 days, the brain, lung, heart, thymus, liver, kidney, spleen, and testis were extracted from the 5 week-old mice, and the change in organ weight was not found. No statistically significant changes were observed (Fig. 4B and C).

There was no difference in body weight, organ weight, and organ changes for the control group, the extract of Pa root muscle, and the positive control group for one week.

Claims (6)

A pharmaceutical composition for the prevention and treatment of Attention Deficit Hyperactivity Disorder (ADHD) containing the extract of Patriniae radix as an active ingredient. The method of claim 1,
The patch root extract is characterized in that the ultrasonic wave extract, composition. The method of claim 2,
The ultrasonic wave extract of Pajanggeun is characterized in that obtained by repeating 1 to 3 hours standing 25 to 35 times a day after sonication for 10 to 20 minutes at 40 ~ 50 ℃ using 80 ~ 95 w / v% ethanol, Composition. The method of claim 1,
The effective amount of the mycorrhizal extract is characterized in that 0.001 ~ 500 mg / kg, the composition. Health functional food for the prevention and improvement of attention deficit hyperactivity disorder (ADHD) containing the extract of Patriniae radix as an active ingredient. The method of claim 5,
The health functional food is characterized in that selected from the group consisting of beverages, meat, chocolate, foods, confectionery, pizza, ramen, other noodles, gums, candy, ice cream, alcoholic beverages, vitamin complexes and health supplements, Nutraceutical.

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