Composition containing <i>Perilla frutescens </i>fermented extract for prevention, alleviation, or treatment of sleep disorder

Abstract

A pharmaceutical composition, dietary supplement, or food containing a Perilla frutescens fermented extract is disclosed. The composition is useful for prevention or treatment of a sleep disorder. A composition or a fiber or fragrance composition containing a Perilla frutescens fermented extract is also disclosed. A method for treating sleep disorder employing the pharmaceutical composition, dietary supplement, food, or the fiber or fragrance composition is disclosed.

Claims

1. A method for treatment of a sleep disorder, the method comprising a step of administering an effective amount of Perilla frutescens fermented extract to a patient with a sleep disorder, wherein the Perilla frutescens fermented extract is obtained by (a) extracting Perilla frutescens with water, a C.sub.1 to C.sub.4 alcohol, or a mixture thereof as an extraction solvent in an extraction solution, (b) fermenting the extraction solution with a microorganism comprising any one or more microorganisms selected from the group consisting of Bacillus subtilis, Lactobacillus rhamnosus, and Saccharomyces cerevisiae.

2. The method of claim 1, wherein the extract of Perilla frutescens is obtained from any one or more selected from the group consisting of leaves, stems, flowers, fruit, and seeds of Perilla frutescens.

3. The method of claim 1, wherein the fermentation is performed at 5° C. to 80° C. for 30 minutes to 10 days.

4. The method of claim 1, wherein the sleep disorder is any one or more selected from the group consisting of disturbance of sleep induction, deep sleep disorder, halfway awakening, early awakening, insomnia, nightmares, somnambulism, narcolepsy, abnormal behavior during sleep, hypersomnia, sleep seizures, breathing-related sleep disorder, apnea syndrome, circadian rhythm sleep disorders, parasomnia, restless leg syndrome, and periodic limb movement disorder.

Description

DESCRIPTION OF DRAWINGS

(1) FIG. 1 illustrates the measurement results of sleep latency after inducing sleep by administering pentobarbital to rats to which a Perilla frutescens extract (Perilla-W) or a Perilla frutescens fermented extract (Perilla-B) was administered. Physiological saline was administered to a control, and diazepam was administered to Dia (positive control). It could be confirmed that when the Perilla frutescens extract was administered, sleep latency was the shortest, which was a value significantly decreased compared to the Perilla frutescens extract or the positive control group.

(2) FIG. 2 illustrates the measurement results of total sleeping time after inducing sleep by administering pentobarbital to rats to which a Perilla frutescens extract (Perilla-W) or a Perilla frutescens fermented extract (Perilla-B) was administered. Physiological saline was administered to a control, and diazepam was administered to Dia (positive control). It could be confirmed that when the Perilla frutescens fermented extract was administered, total sleeping time was significantly increased compared to the Perilla frutescens extract.

(3) FIG. 3 illustrates the measurement results of sleep latency after inducing sleep by administering pentobarbital to rats to which a Perilla frutescens extract (Perilla-W) or a Perilla frutescens fermented extract (Perilla-B, Perilla-L, and Perilla-S) was administered. Physiological saline was administered to a control. It could be confirmed that when the Perilla frutescens extracts were each administered, sleep latency was significantly decreased compared to the Perilla frutescens extract.

(4) FIG. 4 illustrates the measurement results of total sleeping time after inducing sleep by administering pentobarbital to rats to which a Perilla frutescens extract (Perilla-W) or a Perilla frutescens fermented extract (Perilla-B, Perilla-L, and Perilla-S) was administered. Physiological saline was administered to a control. It could be confirmed that when the Perilla frutescens extracts were each administered, total sleeping time was significantly increased compared to the Perilla frutescens extract.

MODES OF THE INVENTION

(5) Hereinafter, the present invention will be described in more detail through Examples. These Examples are only for exemplifying the present invention, and it should be obvious to a person with ordinary skill in the art that the scope of the present invention is not to be interpreted as being limited by these Examples.

Example 1

Preparation of Perilla frutescens Extract and Fermented Product Thereof

(6) Perilla frutescens leaves were subjected to hot water extraction at 80° C. and sterilized at 121° C. for 20 minutes (Perilla-W). A Perilla frutescens fermented extract was prepared by fermenting the sterilized Perilla frutescens hot water extract with a bacillus, lactobacillus, or yeast.

(7) Specifically, after Bacillus subtilis as one species of Bacillus, Lactobacillus rhamnosus as one species of Lactobacillus, or Saccharomyces cerevisiae as the yeast was each inoculated into the Perilla frutescens extract, fermented extracts of a Perilla frutescens Bacillus subtilis fermented product (Perilla-B), a Perilla frutescens Lactobacillus rhamnosus fermented product (Perilla-L), and a Saccharomyces cerevisiae fermented product (Perilla-S) were prepared by fermenting the one species for 5 days while being subjected to shaking culture at 140 rpm in an environment of a temperature of 25° C. and a humidity of 80%.

Example 2

Sleep Improvement Effects of Perilla frutescens Fermented Extract

(8) <2-1> Comparison of sleep improvement effects with existing sedatives

(9) The sleep improvement effects of the Perilla frutescens fermented extract and conventionally sold sedatives were intended to be confirmed from comparison of sleep latency and total sleeping time.

(10) Specifically, 0.9% physiological saline, 10 mg/kg of the Perilla frutescens extract (Perilla-W) or fermented extract thereof (Perilla-B) prepared in [Example 1], and 1 mg/kg of diazepam (Myung In Pharm. Co., Ltd.) were each orally administered to ICR mice (OrientBio). 30 minutes after the administration of the test materials, 45 mg/kg of a nerve stabilizer pentobarbital (HANLIM PHARM. Co., Ltd.) was intraperitoneally administered to induce sleep. After the administration of pentobarbital, the time required to go into deep sleep (sleep latency) and the total sleep maintenance time (total sleeping time) were measured for each test material administration group. Physiological saline and diazepam were used as a control and a positive control, respectively.

(11) As a result, as illustrated in [FIG. 1], it was confirmed that when the Perilla-W was administered, the sleep latency (261 seconds) of the Perilla-W-administered group was reduced by about 20% compared to the sleep latency (325 seconds) of the control, and the sleep latency (180 seconds) of the Perilla-B-administered group was reduced by about 45% compared to the sleep latency of the control, and thus was more significantly reduced compared to the Perilla-W-administered group. In particular, a significant effect was confirmed by confirming that the Perilla frutescens fermented extract exhibited a sleep latency reduced by 10% or more compared to when the positive control diazepam was used (220 seconds).

(12) In addition, as illustrated in [FIG. 2], it was confirmed that compared to the total sleeping time (46 minutes) of the control, the total sleeping time was increased by about 123% (57 minutes) when the Perilla-W was administered, and the total sleeping time was increased by about 138% (68 minutes) when the Perilla-B was administered, and thus was more significantly increased compared to that of the Perilla-W-administered group.

(13) <2-2> Comparison of Sleep Improvement Effects Per Fermentation Strain

(14) It was intended to confirm whether there is a difference in sleep improvement effects between fermentation strains fermenting the Perilla frutescens extract. As the fermentation strain, a bacillus, lactobacillus, or yeast was used.

(15) Specifically, sleep latency and total sleeping time ere measured in the same manner as in Example <2-1> using 0.9% physiological saline and 10 mg/kg of the Perilla frutescens extract (Perilla-W) or fermented extract thereof (Perilla-B, Perilla-L, and Perilla-S) prepared in [Example 1].

(16) As a result, as illustrated in [FIG. 3], compared to the sleep latency (350 seconds) of the control, the sleep latency of the Perilla-W-administered group was reduced by about 25% (261 seconds). It was shown that the sleep latency was reduced by about 49% (180 seconds), about 44% (198 seconds), and about 42% (206 seconds) in the case of administration of Perilla frutescens fermented extracts Perilla-B, Perilla-L, and Perilla-S, respectively. That is, it could be confirmed that when the Perilla frutescens fermented extracts were administered, sleep latency was significantly shortened compared to when the Perilla frutescens extract was administered, and among them, the fermentation case using a bacillus was best in effect.

(17) In addition, as illustrated in [FIG. 4], it was shown that when the Perilla-W was administered, the total sleeping time was increased by about 123% (57 minutes) compared to the total sleeping time (46 minutes) of the control, and it was shown that in the case of administration of Perilla frutescens fermented extracts Perilla-B, Perilla-L, and Perilla-S, the total sleeping time was increased by about 148% (68 minutes), about 139% (64 minutes), and about 141% (65 minutes), respectively compared to the total sleeping time of the control. That is, it could be confirmed that when the Perilla frutescens fermented extracts were administered, total sleeping time was significantly increased compared to when the Perilla frutescens extract was administered, and among them, the fermentation case using a bacillus was best in effect.

Preparation Example

(18) 1. Preparation of Health Functional Beverage

(19) TABLE-US-00001 Vitamins 0.5 wt % Dietary fiber 4.0 wt % Liquid fructose 93.0 wt %  Emulsifier 1.0 wt % Flavor 0.5 wt % Perilla frutescens fermented extract 1.0 wt %

(20) The composition was mixed with purified water such that the total volume became 50 ml. A final mixed solution obtained by allowing the mixed solution to pass through a 2 to 3 μm filter to remove suspended matter was sterilized at 90 to 93° C. for 15 to 20 seconds and filled in a 50 ml bottle and sterilized at 80 to 85° C. for 15 to 20 minutes, thereby completing a health functional beverage product.

(21) 2. Preparation of Lotion

(22) TABLE-US-00002 Hydroxyethylene cellulose (2% aqueous solution) 12.0 wt %  Xanthan gum (2% aqueous solution) 2.0 wt % 1,3-butylene glycol 6.0 wt % Glycerin 4.0 wt % Sodium hyaluronate (1% aqueous solution) 5.0 wt % Ion exchanged water 73.0 wt %  Perilla frutescens fermented extract 3.0 wt %

(23) A lotion was prepared by a typical lotion preparation method.

(24) 3. Preparation of Fragrance

(25) TABLE-US-00003 95% ethanol 65.0 to 75.0 wt % Perilla frutescens fermented extract 25.0 to 35.0 wt %

(26) After the ethanol and the Perilla frutescens fermented extract were mixed, a fragrance was prepared by stirring the resulting mixture at room temperature for 12 to 20 minutes.

(27) 4. Preparation of Bathing Agent

(28) TABLE-US-00004 Sodium hydrogen carbonate 70.0 wt % Anhydrous sodium sulfate 29.0 wt % Perilla frutescens fermented extract  1.0 wt %

(29) After the sodium bicarbonate and anhydrous sodium sulfate were stirred with a V-type mixer until the mixture became uniform, the Perilla frutescens fermented extract was added thereto, and the resulting mixture was sufficiently stirred until the mixture again became uniform, thereby preparing a bathing agent.

INDUSTRIAL APPLICABILITY

(30) Therefore, in the present invention, the Perilla frutescens fermented extract, compared with an unfermented Perilla frutescens extract, significantly shortens sleep latency and significantly increases total sleeping time, and thus the Perilla frutescens fermented extract is effective as a composition for prevention, alleviation, or treatment of a sleep disorder or for sleep improvement, and can be also effectively used in a treatment method for a sleep disorder, so that the present invention is highly industrially applicable.