KR20240111546A - Composition for the improvement or treatment of depression and anxiety disorders containing Menthae Herba volatile fragrance extract as an active ingredient - Google Patents

Abstract

The present invention relates to a composition containing a mentha japonica volatile scent extract as an active ingredient. More specifically, as a result of a mouse behavior evaluation in which the mentha japonica volatile scent extract is intranasally administered, the mentha japonica volatile scent extract tends to increase in penetration into an open space, time spent in the open space, and moving distance in the open space, thereby reducing instability. Since the total moving distance and speed do not decrease, it has been confirmed that side effects such as muscle relaxation or influencing motor functions, for example, by benzodiazepine-based drugs, do not occur. Thus, a pharmaceutical composition containing the mentha japonica volatile scent extract can be provided as an active ingredient can be provided for alleviating or treating depression and anxiety disorders.

Description

Composition for the improvement or treatment of depression and anxiety disorders containing Menthae Herba volatile fragrance extract as an active ingredient}

The present invention relates to a composition for improving or treating depression and anxiety disorders containing peppermint volatile aroma extract as an active ingredient.

Benzodiazepine drugs used for existing acute anxiety disorders are less effective for chronic generalized anxiety disorder, and SSRIs developed as antidepressants cause nausea, nervousness, insomnia, sedation, headache, dry mouth, dizziness, constipation, diarrhea, Side effects such as decreased sexual function, decreased appetite, and sweating may occur.

Menthae Herba can be used to replace the benzodiazepine drug. Menthae Herba is a perennial root of the dicotyledonous plant order Lamiaceae. The plant itself has aroma and is erect and branched at the top. . The main components of peppermint are alpha-pinene (+, -), anisaldehyde, Daucosterol, Eugenol, Linalool, Menthone, (+ )-Neomenthol ((+)-Neomenthol), etc.

Peppermint emits a refreshing and refreshing scent, and has sterilizing and antibacterial effects against microorganisms such as pathogenic fungi, Escherichia coli, and staphylococci that cause eczema and scabies on the skin or scalp. In addition, it has the effect of constricting the mucous membrane and blood vessels of the skin, paralyzing the nerve endings, stopping pain, and stopping itching, giving a unique refreshing feeling to the skin, improving skin diseases, soothing the skin, and having an antioxidant effect. Menthol, the main component of peppermint oil, is used medicinally as a liniment, analgesic, stimulant, or gastric agent, and is used as a flavoring or refreshing agent in toothpaste, candy, jam, cosmetics, cigarettes, etc.

Meanwhile, traditionally, peppermint was often used for oral administration in the form of water extract, but it can bypass the blood-brain barrier, which is the biggest barrier in the delivery of therapeutic agents for the treatment of central nervous system diseases. Intra-nasal delivery is emerging as a new delivery system.

The nasal administration has recently been attracting attention as an alternative route to injection and oral administration due to reasons such as fast drug action time, relatively large absorption surface area, non-invasive method, and avoidance of the first-pass effect in the liver. It does not enter the bloodstream, so it does not enter the body. This method has a low risk of adverse side effects. However, because there are disadvantages such as removal of the drug from mucosal epithelial tissue by mucus, relatively fast mucus replacement time, irritation and toxicity that may occur during repeated administration, attempts to overcome these disadvantages are continuing.

Republic of Korea Patent No. 10-1112578 (registered on January 30, 2012)

The present invention seeks to provide a composition for improving or treating depression and anxiety disorders containing peppermint volatile aroma extract as an active ingredient in order to solve the problems caused by the use of conventional benzodiazepine drugs.

The present invention provides a pharmaceutical composition for improving or treating depression and anxiety disorders containing peppermint volatile aroma extract as an active ingredient.

In addition, the present invention provides a nasal administration preparation for improving or treating depression and anxiety disorders containing peppermint volatile aroma extract as an active ingredient.

According to the present invention, as a result of evaluating the behavior of mice administered intranasally a volatile aroma extract of peppermint, the time spent in the open space and the distance moved in the open space tended to increase, indicating a decrease in instability, and a decrease in the total movement distance and speed. Since it does not cause side effects such as muscle relaxation or affecting motor function like benzodiazepine drugs, the peppermint volatile aroma extract can be effectively used in pharmaceutical compositions for preventing and treating depression. You can.

Figure 1 shows the results of measuring the effect of peppermint volatile aroma extract on behavioral changes in mice.

Hereinafter, the present invention will be described in more detail.

As a result of evaluating the behavior of mice administered intranasally with a volatile aroma extract of peppermint, the inventors of the present invention found that the time spent in the open space and the distance moved in the open space tended to increase, indicating a decrease in instability, and a decrease in the total movement distance and speed. The present invention was completed after confirming that side effects such as muscle relaxation or influence on motor function, such as those of benzodiazepine drugs, do not occur.

The present invention can provide a pharmaceutical composition for improving or treating depression and anxiety disorders containing peppermint volatile aroma extract as an active ingredient.

The peppermint volatile aroma extract may be extracted from any one or two or more selected from the group consisting of seeds, leaves, stems, flowers, or fruits of peppermint.

The extraction solvent used for extraction of the peppermint volatile aroma extract is not limited to a specific solvent as long as it is a solvent used for extracting pharmaceutical compositions or herbal medicines. A more preferable extract is an extract soluble in a solvent selected from water, hexane, lower alcohols having 1 to 4 carbon atoms, or mixed solvents thereof.

The peppermint volatile aroma extract may be extracted by a method selected from the group consisting of compression, ultrasonic waves, supercritical solvent extraction, solvent extraction, and steam distillation, and is preferably extracted by steam distillation.

The anxiety disorder is preferably one or more selected from separation or isolation anxiety, paranoia, generalophobia, generalized obsessive-compulsive disorder, nervous anxiety, and panic disorder, but is not limited thereto.

The peppermint volatile aroma extract may be administered to a subject by an intranasal route, and the subject may be a human or non-human animal subject.

The extract of the present invention is administered in a pharmaceutically effective amount. In the present invention, a pharmaceutically effective amount refers to an amount sufficient to treat a disease with a reasonable benefit/risk ratio applicable to medical treatment, and the effective dose level refers to the type and severity of the patient's disease, the activity of the drug, and the It can be determined based on factors including sensitivity, time of administration, route of administration and excretion rate, duration of treatment, concurrently used drugs, and other factors well known in the medical field. The extract of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be administered singly or multiple times. Considering all of the above factors, it is important to administer an amount that can achieve maximum effect with the minimum amount without side effects, and this can be easily determined by a person skilled in the art.

The dosage of the extract of the present invention varies depending on the patient's weight, age, gender, health condition, diet, administration time, administration method, excretion rate, and severity of the disease, and the daily dosage is the amount of peppermint volatile aroma extract. Based on this, it is 10-100 mg/kg/day, preferably 25-50 mg/kg/day, and can be administered 1-6 times a day, but depending on the route of administration, severity of obesity, gender, weight, age, etc. Since it can be increased or decreased, the above dosage does not limit the scope of the present invention in any way.

In addition, the present invention provides a nasal administration preparation for improving or treating depression and anxiety disorders containing peppermint volatile aroma extract as an active ingredient.

The preparation can be administered in various oral and parenteral dosage forms. When formulating the composition, it may be prepared using commonly used diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, and surfactants. You can. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc. These solid preparations are made by adding at least one excipient to the Chunma extract, such as starch, calcium carbonate, and sucrose. ), it can be prepared by mixing lactose or gelatin. Additionally, in addition to simple excipients, lubricants such as magnesium styrate talc can also be used. Liquid preparations for oral use include suspensions, oral solutions, emulsions, and syrups. In addition to the commonly used simple diluents such as water and liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included. . Preparations for parenteral administration may include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate. As a base for suppositories, witepsol, macrogol, tween 61, tween 80, cacao, laurin, glycerogeratin, etc. can be used.

Hereinafter, the present invention will be described in detail through examples to aid understanding. However, the following examples only illustrate the content of the present invention and the scope of the present invention is not limited to the following examples. Examples of the present invention are provided to more completely explain the present invention to those skilled in the art.

<Experimental example>

The following experimental examples are intended to provide experimental examples commonly applied to embodiments according to the present invention.

1. Preparation of Volatile aromatic extract of Menthae Herba

600 g of menthae Herba was hydrogen distilled for 4 hours using a steam distillation solvent extraction (SDE) apparatus, and the distilled oil was captured in n-hexane (Duksan Chemical, Gyeonggi-do). The oil was dehydrated using a separatory funnel, and n-hexane was evaporated. The amount of oil obtained was 4.35 g, and the oil was stored at -20 °C for further use.

2. Animal testing

Ten 7-week-old male ICR mice weighing 25-29 g were obtained from Koatech Lab Animal Inc. (Seoul) and acclimatized for 6 days before behavioral testing. All mice had contact with water and commercial pellet chow (5L79, PMI Nutrition, St Louis, MO, USA). All mice were randomly divided into two groups: control group (Con, n=6) and peppermint volatile aroma extract group (MHEO, n=4), which were treated with vehicle (saline and Tween 80, 3% v/v) and peppermint volatile aroma extract group (MHEO, n=4). (25 mg/kg) was provided each. On the day of the experiment, all animals were habituated for 2 h before receiving a 10 μL intranasal dose. Thirty minutes after treatment, a behavioral assessment (Open Field Test (OFT)) was performed.

<Example> Behavioral evaluation (Open Field Test (OFT))

Behavioral assessment was used to observe changes in movement of mice exposed to a novel environment after oil administration. The behavioral assessment site is a 30x30x30 cm black box with a camera mounted on top for recording and scoring video along with tracking software. After 2 hours of acclimatization in the evaluation location, each mouse was placed in the center of the box for a period of free movement of 20 minutes. All boxes were cleaned with 70% concentration ethanol after every experiment to remove unpleasant odors and urine and feces. The time spent in the open space, the distance moved in the open space, and the total distance moved (cm) were analyzed using Smart V3.0 software (Panlab Harvard Apparatus, MA, USA), and are shown in Figure 1.

As a result of the behavioral evaluation, mice administered intranasally with 25 mg/kg of peppermint volatile aroma extract showed little difference in total distance moved compared to the control group, but the time and percentage of distance moved in the open space were significantly higher than those treated with peppermint volatile aroma extract. As the significant increase was confirmed in mice, it can be confirmed that there are no side effects such as muscle relaxation or effect on motor function like benzodiazepine drugs.

As the specific parts of the present invention have been described in detail above, it is clear to those skilled in the art that these specific techniques are merely preferred embodiments and do not limit the scope of the present invention. something to do. Accordingly, the actual scope of the present invention will be defined by the appended claims and their equivalents.

Claims (10)

A pharmaceutical composition for improving or treating depression and anxiety disorders comprising peppermint volatile aroma extract as an active ingredient. The pharmaceutical composition according to claim 1, wherein the peppermint volatile aroma extract is extracted from any one or two or more selected from the group consisting of seeds, leaves, stems, flowers, or fruits of peppermint. The pharmaceutical composition according to claim 1, wherein the extraction solvent of the volatile aroma extract of peppermint is water, hexane, lower alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof. The pharmaceutical composition according to claim 3, wherein the peppermint volatile aroma extract is extracted by steam distillation. The pharmaceutical composition according to claim 1, wherein the anxiety disorder is one or more selected from separation or isolation anxiety, paranoia, generalophobia, generalized obsessive-compulsive disorder, nervous anxiety disorder, and panic disorder. The pharmaceutical composition according to claim 1, wherein the peppermint volatile aroma extract is administered to the subject by intranasal route. The pharmaceutical composition according to claim 6, wherein the subject is a human or non-human animal subject. The pharmaceutical composition according to claim 1, wherein the peppermint volatile aroma extract is administered at a dosage of 25-50 mg/kg/day. An intranasal preparation for improving or treating depression and anxiety disorders containing peppermint volatile aroma extract as an active ingredient. The method of claim 9, wherein the preparation is selected from the group consisting of tablets, pills, powders, granules, capsules, suspensions, oral solutions, emulsions, syrups, sterilized aqueous solutions, non-aqueous solvents, freeze-dried preparations, and suppositories. Intranasal preparation for improving or treating depression and anxiety disorders.