KR20220102809A - Composition for Preventing or Improving Anxiety Disorder Comprising Linalyl Acetate - Google Patents

Abstract

The present invention relates to a composition for preventing or alleviating anxiety disorders comprising linalyl acetate as an active component, and specifically, the present invention relates to a pharmaceutical composition for preventing or treating anxiety disorders comprising linalyl acetate as an active component, and a health functional food composition for preventing or alleviating anxiety disorder comprising linalyl acetate as the active component. By confirming that an anxiety relief effect of a group administered with linalyl acetate of the present invention to a subject through inhalation is significantly superior to the anxiety relief effect of the group not administered with linalyl acetate, so that the linalyl acetate of the present invention has an effect of being able to be usefully used in the pharmaceutical and health functional food industries for the purpose of preventing, alleviating or treating anxiety disorders.

Description

A composition for preventing or improving anxiety disorder comprising linalyl acetate as an active ingredient {Composition for Preventing or Improving Anxiety Disorder Comprising Linalyl Acetate}

The present invention relates to a composition for preventing or improving anxiety disorders comprising linyl acetate as an active ingredient.

Anxiety disorder is a state of anxiety and restlessness that occurs in the absence of brain disease or other mental illness. Anxiety disorder is the most common mental disorder among modern people, and includes generalized anxiety disorder, social anxiety disorder, post-traumatic stress disorder, and panic disorder. , phobias, and obsessive-compulsive disorders. Anxiety disorders are associated with a relatively high prevalence, tendency to become chronic, and the occurrence of serious disabilities due to comorbidities, and 10.4% of Disability Adjusted Life Years (DALYs) due to neurological disorders, psychiatric disorders, and substance abuse. It was found to account for 1.1% of the global disease burden.

Subjects with anxiety disorder also have high sensitivity to negative situations, which can lead to stress responses easily. Excessive sympathetic nervous system activity due to stress response affects body metabolism, growth, gastrointestinal function, cardiovascular function, immune system, etc. Chronic activation of the sympathetic nervous system can lead to metabolic syndrome. As such, since anxiety disorder reduces the quality of life in various areas including social and economic aspects, efforts to prevent and manage it are necessary.

Currently, a representative drug for treating anxiety disorders is a benzodiazepine class of drugs. Benzodiazepine-based drugs are most commonly prescribed worldwide and have a sedative-hypnotic effect to quickly relieve symptoms such as anxiety and insomnia, but there is a problem that may cause side effects. For example, benzodiazepines may cause side effects such as drowsiness, confusion, ataxia, orthostatic hypotension, decreased work capacity, and decreased liver function. Therefore, it is necessary to develop a new anti-anxiety drug that has few side effects and overcomes the limitations of efficacy and tolerability of existing anti-anxiety drugs.

In response to these demands, efforts have been made in recent years to use natural products with few side effects to the human body. For example, as a result of inhaling Bitter orange extract for 3 days before bedtime in a type 2 diabetic patient, a study has reported that anxiety levels after inhalation significantly decreased compared to before inhalation. As a result of ingesting Ashwagandha extract for 12 weeks in patients with schizophrenia, a study result has been reported that significantly reduced anxiety scores compared to the control group. As such, the anti-anxiety effect through natural products has the advantage that it can be used safely because there are few side effects.

Materials derived from natural products developed so far have the advantage of fewer side effects in the body compared to conventional anti-anxiety drugs, but have a problem of insufficient anti-anxiety efficacy.

On the other hand, linalyl acetate is a colorless, clear liquid and has a unique fragrance, so it is widely used as a fragrance ingredient in cosmetics, shampoos, soaps, and detergents. there is a bar Regarding the useful function of linalyl acetate, Korean Patent No. 10-1737046 discloses the antidiabetic effect of linaryl acetate, and Korean Patent No. 10-1970280 discloses that linyl acetate prevents tachycardia induced by olmesartan. and therapeutic efficacy, and Korean Patent No. 10-1970281 discloses the preventive or therapeutic efficacy of linalyl acetate for intestinal hypermotility.

However, it is not known whether linalyl acetate alone is effective in preventing or treating anxiety disorders.

Accordingly, the present inventors inhaled the fragrance of linyl acetate in solid cancer patients before chemotherapy as a new drug that can be safely used without side effects for preventing or improving anxiety disorders. As a result, the subject's anxiety scale score was significant after inhalation of fragrance compared to before inhalation of fragrance. As it was confirmed that it decreases, the present invention was completed by first identifying the anti-anxiety effect of linalyl acetate alone.

1. Republic of Korea Patent No. 10-1737046 2. Republic of Korea Patent No. 10-1970280 3. Republic of Korea Patent No. 10-1970281

Therefore, it is an object of the present invention to provide a pharmaceutical composition for preventing or treating anxiety disorders, comprising linaryl acetate as an active ingredient.

Another object of the present invention is to provide a health functional food composition for preventing or improving anxiety disorders, comprising linaryl acetate as an active ingredient.

In order to achieve the above object, the present invention provides a pharmaceutical composition for preventing or treating anxiety disorders, comprising linyl acetate as an active ingredient.

In one embodiment of the present invention, the linalyl acetate may be included in 4 to 6% by weight based on the total weight of the composition.

In one embodiment of the present invention, it may further include a carrier, excipient or diluent in addition to the active ingredient.

In one embodiment of the present invention, the composition may be administered prior to anticancer treatment of a cancer patient, thereby reducing the patient's anxiety disorder.

In one embodiment of the present invention, the cancer may be a solid cancer.

In one embodiment of the present invention, the administration may be by inhaling the composition through the nose of the patient.

The present invention also provides a health functional food composition for preventing or improving anxiety disorders, comprising linyl acetate as an active ingredient.

In one embodiment of the present invention, the linalyl acetate may be included in 4 to 6% by weight based on the total weight of the composition.

In one embodiment of the present invention, in addition to the active ingredients, nutrients, vitamins, electrolytes, flavoring agents, colorants, enhancers, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusters, stability It may further contain one or more selected from the group consisting of an agent, a preservative, glycerin, alcohol, and a carbonation agent used in carbonated beverages.

As it was confirmed that the subject's anxiety scale score significantly decreased after inhalation of fragrance compared to before inhalation of fragrance in the group administered to the subject through inhalation of the linaryl acetate of the present invention, by confirming, There is an effect that can be usefully used in the pharmaceutical and health functional food industries for the purpose of preventing, improving or treating disorders.

1 shows the results of confirming the effect of reducing anxiety scale scores in solid cancer patients before chemotherapy according to inhalation of linalyl acetate incense in an embodiment of the present invention ( ^* P < 0.05 vs before inhalation of incense).

The present invention has identified a novel use of linyl acetate, and it is characterized in that it provides for the first time that it has an effect to improve or treat anxiety disorders.

Specifically, the present invention provides a pharmaceutical composition for preventing or treating anxiety disorders, comprising linaryl acetate as an active ingredient.

In the present invention, the linalyl acetate may be used isolated and purified from nature, or commercially available ones may be used.

The linaryl acetate contained in the composition of the present invention may be used in the form of a pharmaceutically acceptable salt, and as the salt, an acid addition salt formed by a pharmaceutically acceptable free acid is useful. Acid addition salts include inorganic acids such as hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, nitrous acid or phosphorous acid and aliphatic mono and dicarboxylates, phenyl-substituted alkanoates, hydroxy alkanoates and alkanes. It is obtained from non-toxic organic acids such as dioates, aromatic acids, aliphatic and aromatic sulfonic acids. Such pharmaceutically non-toxic salts include sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, nitrate, phosphate, monohydrogen phosphate, dihydrogen phosphate, metaphosphate, pyrophosphate chloride, bromide, ioda. Id, fluoride, acetate, propionate, decanoate, caprylate, acrylate, formate, isobutyrate, caprate, heptanoate, propiolate, oxalate, malonate, succinate, suberate , sebacate, fumarate, maleate, butyne-1,4-dioate, hexane-1,6-dioate, benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, hydroxybenzoate, Toxybenzoate, phthalate, terephthalate, benzenesulfonate, toluenesulfonate, chlorobenzenesulfonate, xylenesulfonate, phenylacetate, phenylpropionate, phenylbutyrate, citrate, lactate, β-hydroxybutyrate, glycol lactate, malate, tartrate, methanesulfonate, propanesulfonate, naphthalene-1-sulfonate, naphthalene-2-sulfonate or mandelate.

In addition, the linyl acetate of the present invention may be used for extracting, separating and purifying useful components from natural products containing the same, and the method can be used any extraction and separation method known in the art. . Extraction as defined in the present invention is extracted from the corresponding natural product using an appropriate solvent, and includes, for example, all crude extracts, polar solvent-soluble extracts, or non-polar solvent-soluble extracts.

As a suitable solvent for obtaining the extract, 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, propanol, isopropanol, alcohols having 1 to 4 carbon atoms, including butanol, acetone, ether, benzene, chloroform Various solvents such as , ethyl acetate, methylene chloride, hexane and cyclohexane may be used alone or in combination.

As the extraction method, any one of methods such as hot water extraction, cold extraction, reflux cooling extraction, solvent extraction, steam distillation, ultrasonic extraction, elution, and compression may be selected and used. In addition, the desired extract may be additionally subjected to a conventional fractionation process, or a desired useful component may be purified using a conventional purification method.

Linaryl acetate according to the present invention can be obtained from an extract of a natural product containing it through a conventional purification method.

On the other hand, the composition comprising linaryl acetate of the present invention as an active ingredient has an effect of preventing, improving or treating anxiety disorders.

According to an embodiment of the present invention, it was confirmed that the anxiety scale score was significantly reduced after inhalation of incense compared to before inhalation of incense in the experimental group administered with linalyl acetate. As a result of performing an anxiety scale test on the patients in the experimental group who inhaled the composition containing linyl acetate in the nose and the control patient who did not inhale the composition, the anxiety after inhalation of the fragrance in the group inhaling the linalyl acetate composition compared to before inhalation of the fragrance It was found that the scale score was significantly decreased.

Therefore, the present inventors found that the linaryl acetate of the present invention can improve or treat anxiety disorders through these results.

In the present invention, "anxiety disorder" is also referred to as anxiety, and includes diseases characterized by extreme fear, anxiety, and related behavioral disorders. Anxiety is a widespread, very unpleasant and vaguely anxious feeling that arises from the prediction of a future threat, whereas fear is an emotional response to an immediate actual or perceived threat. Anxiety disorder can be diagnosed when physical symptoms such as headache, heart rate increase, respiratory rate increase, gastrointestinal abnormality, etc. appear due to anxiety and fear beyond the normal range, which makes it difficult to perform daily activities. Anxiety disorders include generalized anxiety disorder, social anxiety disorder, post-traumatic stress disorder, panic disorder, and phobia-compulsive disorder.

In the present invention, the term "improvement" is meant to include the prevention, improvement, treatment, or delay of the expression of anxiety disorder by administration of the pharmaceutical composition according to the present invention.

As used herein, the term “prevention” is meant to include suppression or delay of anxiety disorders by administration of the pharmaceutical composition according to the present invention.

In the present invention, the term "treatment" is meant to include all actions in which anxiety disorders are improved or beneficially changed by administration of the pharmaceutical composition according to the present invention.

The pharmaceutical composition of the present invention may include a pharmaceutically acceptable carrier. The composition comprising a pharmaceutically acceptable carrier may be in various oral or parenteral formulations. In the case of formulation, it is prepared using diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, and surfactants that are usually used.

Solid preparations for oral administration include tablet pills, powders, granules, capsules, etc., and such solid preparations include at least one excipient in one or more compounds, for example, starch, calcium carbonate, sucrose or lactose. ), gelatin, etc. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid formulations for oral administration include suspensions, internal solutions, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included. have.

Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin, and the like can be used.

The pharmaceutical composition is any selected from the group consisting of tablets, pills, powders, granules, capsules, suspensions, internal solutions, emulsions, syrups, sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations and suppositories It may have one formulation.

In an embodiment of the present invention, a parenteral administration method through inhalation of fragrance was performed.

In the present invention, the "pharmaceutically effective amount" refers to an amount sufficient to treat a disease at a reasonable benefit/risk ratio applicable to medical treatment, and the effective dose level refers to the type and severity of the subject, age, sex, and drug activity. , sensitivity to drug, administration time, administration route and excretion rate, duration of treatment, factors including concomitant drugs, and other factors well known in the medical field.

The composition 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 single or multiple. Taking all of the above factors into consideration, it is important to administer an amount that can obtain the maximum effect with a minimum amount without side effects. A typical dosage of the pharmaceutical composition of the present invention is within the range of 0.001-100 mg/kg for adults.

The administration route of the pharmaceutical composition may be administered through any general route as long as it can reach the target tissue. The composition of the present invention may include intraperitoneal administration, intravenous administration, intramuscular administration, subcutaneous administration, intradermal administration, oral administration, intranasal administration, intrapulmonary administration, rectal administration, fragrance inhalation through the nose, etc. , but not limited thereto. In addition, the composition may be administered by any device capable of transporting the active substance to the target site.

The composition of the present invention can be used alone or in combination with surgery, hormone therapy, drug therapy, and methods using biological response modifiers for the prevention and treatment of anxiety disorders.

In particular, in one embodiment of the present invention, a treatment for inhaling the composition of the present invention through the nose was performed prior to performing anticancer treatment for a solid cancer patient with significant anxiety and fear, and as a result, the patient's anxiety was effectively improved. Confirmed.

Therefore, the composition of the present invention can be administered prior to anticancer treatment of cancer patients, thereby effectively reducing anxiety disorders in cancer patients.

In addition, it is preferable that the composition of the present invention contains linaryl acetate in an amount of 4 to 6% by weight based on the total weight of the composition.

If linyl acetate is included in an amount of less than 4% by weight, there is a slight problem in the improvement effect of anxiety disorder, whereas when it is included in excess of 6% by weight, the improvement effect of anxiety disorder is not increased in proportion to the added amount, There is a problem with the economic feasibility.

Therefore, it is important to include the amount of linaryl acetate in the range described above.

Furthermore, the present invention may provide a health functional food composition for preventing or improving anxiety disorders, comprising linaryl acetate as an active ingredient.

The food composition of the present invention may further include a food pharmaceutically acceptable carrier, and the food composition includes the form of pills, powders, granules, needles, tablets, capsules or liquids, and the active ingredient of the present invention There is no particular limitation on the type of food that can be added, for example, various beverages, gum, tea, vitamin complexes, health supplements, and the like.

In addition to the active ingredient of the present invention, other ingredients that do not interfere with the prevention and improvement activity of anxiety disorders may be added to the food, and the type thereof is not particularly limited. For example, it may contain various herbal extracts, food-logically acceptable food supplements or natural carbohydrates as additional ingredients, such as conventional food.

The term "health functional food" as used in the present invention refers to food manufactured and processed in the form of tablets, capsules, powders, granules, liquids, pills, etc. using raw materials or ingredients useful for the human body. Here, the term "functionality" refers to obtaining useful effects for health purposes, such as regulating nutrients or physiological effects on the structure and function of the human body. The health functional food of the present invention can be prepared by a method commonly used in the art, and at the time of manufacture, it can be prepared by adding raw materials and components commonly added in the art. In addition, unlike general drugs, it has the advantage that there are no side effects that may occur when taking the drug for a long period of time by using food as a raw material, and it is excellent in portability.

There is no particular limitation on the type of health functional food of the present invention, and specific examples include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, There are beverages, teas, drinks, alcoholic beverages, and vitamin complexes, and may include all health functional foods in a conventional sense.

In addition, the linyl acetate according to the present invention can be added to food as it is or used together with other foods or food ingredients, and can be appropriately used according to a conventional method. The amount of the active ingredient may be appropriately determined depending on the purpose of use (for prevention or improvement). In general, the amount of linaryl acetate in the health food may be added at 0.01 to 15% by weight of the total food weight, and the health beverage composition may be added at a ratio of 0.02 to 5g, preferably 0.3 to 1g, based on 100ml. have. However, in the case of long-term ingestion for health and hygiene purposes or for health control, the above 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.

In addition, the linaryl acetate of the present invention may contain natural fruit juice and pulp for the production of fruit juice beverages and vegetable beverages. These components may be used independently or in combination. The proportion of these additives is not so important, but it is generally added in an amount of 15 parts by weight or less, preferably 10 parts by weight or less, based on 100 parts by weight of the linyl acetate of the present invention.

Hereinafter, the present invention will be described in more detail by way of Examples. These examples are merely for illustrating the present invention in more detail, and it will be apparent to those of ordinary skill in the art that the scope of the present invention is not limited to these examples.

<Example 1>

Analysis of the effect of improving anxiety disorder following inhalation of linalyl acetate

<1-1> Clinical trial subjects and interventions

For a clinical trial to confirm the efficacy of linalyl acetate for improving anxiety disorders, it was conducted in the following manner based on a randomized control pre-post-experimental design. All experimental procedures were carried out with the approval of the Research Ethics Review Committee of Korea University (IRB NO. ED15338), and patients aged 20 years or older who were diagnosed with stage Ⅲ or higher solid cancer before chemotherapy were recruited as participants. Those who had an olfactory function, those who could not communicate, those who were allergic to linaryl acetate, those who were receiving drug treatment for psychiatric disorders, and those who were receiving essential oil therapy were excluded.

Participants were randomly divided into a control group or a linyl acetate group, and almond oil was administered to the control group and 5% linyl acetate fragrance inhalation to the experimental group was administered once for 20 minutes before chemotherapy. At this time, for the inhalation, 1 ml of almond oil or 5% linalyl acetate was soaked in gauze, and the fragrance was inhaled through natural breathing through the subject's nose.

<1-2> Measurement of anxiety level

In order to evaluate the effect of linalyl acetate on anxiety level, visual analog scale (VAS)-anxiety was performed before inhalation of fragrance and after inhalation of fragrance for 20 minutes for the clinical investigators conducted in <1-1> above. was used to measure anxiety scale scores. On a 10 cm horizontal line, '0' was marked as not at all anxious and '10' as very anxious, and the subject was asked to select a number. Higher scores indicate higher levels of anxiety.

In addition, all experimental results are expressed as mean and standard error. Statistical analysis was performed using SPSS version 24. The difference between the control group and the linalyl acetate group was analyzed by an independent t-test, and the difference before and after inhalation of fragrance in each group was analyzed by a paired t-test. It was judged to be statistically significant at the level of P < 0.05.

As a result of the analysis, as shown in FIG. 1 , it was found that the anxiety scale score was significantly reduced after inhalation of fragrance compared to before inhalation of linalyl acetate fragrance ( ^* P = 0.010). Considering these anxiety scale scores, it was confirmed that linalyl acetate could prevent and improve anxiety disorders in patients with solid cancer before chemotherapy.

Based on the above, it was found that the linaryl acetate of the present invention can effectively prevent or improve anxiety disorders without causing side effects in the body.

So far, with respect to the present invention, the preferred embodiments have been looked at. Those of ordinary skill in the art to which the present invention pertains will understand that the present invention may 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 the scope equivalent thereto should be construed as being included in the present invention.

Claims (9)

A pharmaceutical composition for preventing or treating anxiety disorders, comprising linyl acetate as an active ingredient. According to claim 1,
The linalyl acetate is a pharmaceutical composition for preventing or treating anxiety disorders, characterized in that it is included in 4 to 6% by weight based on the total weight of the composition. According to claim 1,
A pharmaceutical composition for preventing or treating anxiety disorders, characterized in that it further comprises a carrier, excipient or diluent in addition to the active ingredient. According to claim 1,
The composition is administered before anticancer treatment of a cancer patient, characterized in that to reduce the patient's anxiety disorder, Anxiety disorder prevention or treatment pharmaceutical composition. 5. The method of claim 4,
The cancer is a solid cancer, characterized in that, anxiety disorder prevention or treatment pharmaceutical composition. 5. The method of claim 4,
The administration is a pharmaceutical composition for preventing or treating anxiety disorders, characterized in that the composition is inhaled through the nose of the patient. A health functional food composition for preventing or improving anxiety disorders, comprising linyl acetate as an active ingredient. 8. The method of claim 7,
The linalyl acetate is a health functional food composition for preventing or improving anxiety disorders, characterized in that it is included in 4 to 6% by weight based on the total weight of the composition. 8. The method of claim 7,
In addition to the above active ingredients, nutrients, vitamins, electrolytes, flavoring agents, colorants, enhancers, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol and carbonic acid A health functional food composition for preventing or improving anxiety disorders, characterized in that it further contains one or more selected from carbonation agents used in beverages.

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