KR102590559B1 - Composition comprising slugs extract as an active ingredient for preventing, improving or treating insomnia - Google Patents

Abstract

The composition containing the snail extract according to the present invention reduces the sleep induction time required to enter sleep, improves sleep duration, enables quality sleep, and further induces sleep again after waking up after inducing sleep. It is highly effective in preventing, alleviating, improving, or treating insomnia and sleep disorders, making it of great value as a pharmaceutical composition or health food composition.

Description

Composition comprising slugs extract as an active ingredient for preventing, improving or treating insomnia}

The present invention relates to a composition useful for insomnia and lifespan disorders, and more specifically, to a pharmaceutical composition or health food composition that serves as an effective means of preventing, improving, or treating insomnia and sleep disorders.

In modern society, many people suffer from sleep disorders due to stress, anxiety, and nervousness. However, when the period is short and mild, drug treatment is not necessary, but when it interferes with daily life such as work, drug treatment is necessary.

Defining the cause in individuals suffering from insomnia is complex. Transient or acute insomnia usually lasts for several days or weeks and is often associated with sudden changes in the life cycle, sleep schedule, or sleep environment. In this case, the symptoms may be resolved or alleviated once the initial trigger disappears.

The common cause of insomnia is often incorrect lifestyle habits. It often occurs in people who have irregular sleeping times or habits, and symptoms often worsen due to environmental changes, excessive worry, tension, fear, and psychological stress.

Insomnia refers to a condition in which one cannot sleep well at night due to mental excitement, nervous breakdown, or mental and physical exhaustion, or a disease having these conditions, and can be expressed as a sleep disorder.

Insomnia is a condition of dissatisfaction with the quantity and quality of sleep that lasts for a considerable period of time. Insomnia is a clinically common and frequently occurring disease, and its clinical symptoms include difficulty falling asleep, waking up easily, not being able to fall back to sleep after waking up, waking up too early in the morning, napping, and not being able to sleep all night. It indicates not being able to sleep deeply or feeling sleepy, and may be accompanied by many dreams. Additionally, insomnia can cause discomfort after waking up, fatigue, decreased mental efficiency, or interference with social functioning.

If you lack sleep, you may feel drowsy, irritable, or lack energy, which will result in loss of quality of life. In some cases, it may cause serious disruption to life support. Sleep is a function to prevent the above-mentioned conditions from occurring, and getting a good night's sleep is not simply a matter of quality of life, but is also a very important factor in terms of life maintenance and economic productivity.

For some patients suffering from insomnia, the severity of the condition causes them to make extreme choices, and most patients experience personal pain that makes it difficult to carry out their daily lives. Problems such as reduced social productivity and increased social costs arise due to reduced work efficiency due to insomnia and safety accidents.

1. Republic of Korea Patent Publication No. 10-2010-0022974 2. Republic of Korea Patent Publication No. 10-2013-0062347

Therefore, the problem to be solved by the present invention is to provide a pharmaceutical composition or health food composition that is an effective means of solving insomnia.

In order to achieve the above technical problem, the present invention provides a composition for preventing, alleviating, improving or treating insomnia containing snail extract as an active ingredient.

As described above, the composition according to the present invention may be a pharmaceutical composition, and the dosage form may be an oral dosage form such as tablets or syrups, a transdermal dosage form such as a patch or ointment, or an injection, known in the art to which the present invention pertains. There are no special restrictions.

As described above, the composition according to the present invention may be a health food composition, and there is no particular limitation as to the form of food that can be manufactured using the health food composition of the present invention as long as it is known in the technical field to which the present invention pertains.

In the composition according to the present invention as described above, the snail extract is

Slugs fed with a single feed selected from the group consisting of bellflower shell powder, lettuce powder, seaweed powder, and mixtures thereof,

More preferably

Lactobacillus Casei was added in an amount of 5 parts by weight to a feed selected from the group consisting of bellflower shell powder, lettuce powder, seaweed powder, and mixtures thereof, and fermented at 37°C for 7 days. It is characterized in that the solid-state fermented product is steam-sterilized again at 100°C for 30 minutes and extracted from slugs fed with feed that inhibits fermentation.

The composition containing the snail extract according to the present invention reduces the sleep induction time required to enter sleep, improves sleep duration, enables quality sleep, and further induces sleep again after waking up after inducing sleep. It is highly effective in preventing, relieving, improving, or treating insomnia, making it of great value as a pharmaceutical composition or health food composition for insomnia.

The present invention provides a composition useful for preventing, alleviating, improving, or treating insomnia containing a snail extract.

The slug is a larva of Protaetia brevitarsis, which is used in Donguibogam to treat adult diseases such as liver cancer, cirrhosis, hepatitis, and relieving accumulated fatigue, as well as decreased vision, cataracts, malignant boils, stomatitis, tetanus, and stroke. It is a traditional herbal medicine that is said to be effective.

Regarding the extract obtained by extracting the slugs, Republic of Korea Patent Publication No. 10-1852840 discloses a composition showing a liver protection effect by containing enzyme treatment of slugs, enzyme treatment of brown mealworm larvae, mugwort extract, dandelion extract, and thistle extract. It is disclosed in Republic of Korea Patent Publication No. 10-0377252, which discloses an anti-cancer food containing a hot-water leached extract from slugs (cicadas, beetles, stag beetles, mulberry or room larvae) and a hot-water leached extract of reishi mushrooms. .

Looking at the above prior art, extracts are obtained by treating slugs with enzymes selected from Flavozyme, Alcalase, or Protease or by hot water leaching, through which liver protection and anticancer effects are obtained. there is.

Separately from this, it is widely known in the public that snails have diabetes-related effects, and reports are being made about their blood sugar-lowering effects (Research on isolation and purification of insect proteoglycans and pharmaceutical materials, National Institute of Agricultural Sciences, 2013). In addition, in Republic of Korea Patent Publication No. 10-1888549, a mixed extract of aged pumpkin extract, goji berry extract, Baekbokryeong extract, psyllium extract, angelica root extract, and kudzu extract was combined in certain amounts according to the composition ratio using slugs as the main ingredient, and was surfaced with chitosan. A diet drink that is coated and integrated and has excellent blood cholesterol and neutral lipid lowering effects is being disclosed.

However, there is no disclosure at all about insomnia relief and treatment effects.

The snail extract can be prepared by a method comprising the following steps, but is not limited to this:

(1) Extracting slugs by adding an extraction solvent;

(2) filtering the extract of step (1); and

(3) Concentrating the filtered extract of step (2) under reduced pressure and drying it to prepare an extract.

In step (1), the extraction solvent is preferably selected from water, C1 to C4 lower alcohol, or a mixture thereof, more preferably C1 to C4 lower alcohol, and even more preferably 70% (v/v). ) Ethanol, but is not limited to this.

In the above manufacturing method, all conventional methods known in the art can be used as the extraction method, such as filtration, hot water extraction, immersion extraction, reflux cooling extraction, and ultrasonic extraction. The extraction solvent is preferably added 1 to 20 times the weight of the dried slugs for extraction, and more preferably 5 to 15 times the weight of the dried slugs. The extraction temperature is preferably 4 to 50°C, but is not limited thereto. In addition, the extraction time is preferably 0.5 to 10 hours, and more preferably 0.5 to 5 hours, but is not limited thereto.

In the above method, the vacuum concentration in step (3) is preferably performed using a vacuum vacuum concentrator or a vacuum rotary evaporator, but is not limited thereto. In addition, drying is preferably performed by reduced pressure drying, vacuum drying, boiling drying, spray drying, or freeze drying, but is not limited thereto.

The composition according to the present invention is administered in a pharmaceutically effective amount. In the present invention, “pharmaceutically effective amount” means an amount sufficient to treat the disease with a reasonable benefit/risk ratio applicable to medical treatment, and the effective dose level is determined by the type, severity, and activity of the patient's disease. , can be determined based on factors including sensitivity to the drug, time of administration, route of administration and excretion rate, duration of treatment, drugs used simultaneously, and other factors well known in the field of medicine. 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 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 composition of the present invention can vary depending on the patient's weight, age, gender, health condition, diet, administration time, administration method, degree of disease, etc.

In addition, the slugs for producing the slug extract are

Slugs fed with a single feed selected from the group consisting of bellflower shell powder, lettuce powder, seaweed powder, and mixtures thereof,

More preferably

Lactobacillus Casei was added in an amount of 5 parts by weight to a feed selected from the group consisting of bellflower shell powder, lettuce powder, seaweed powder, and mixtures thereof, and fermented at 37°C for 7 days. It is characterized in that the solid-state fermented product is steam-sterilized again at 100°C for 30 minutes and extracted from slugs fed with feed that inhibits fermentation.

This type of feed is mixed with sawdust feed for slugs and ingested by slugs. At this time, it is preferable to include 1/25 by weight of the feed prepared in the present invention in the sawdust feed for slugs.

In addition, in the present invention, the effect can be further increased by stopping the supply of sawdust feed to the slugs 7 to 14 days before shipping to the slugs and allowing the slugs to consume only the feed prepared in the present invention.

The composition according to the present invention may be a pharmaceutical composition, in which case it may further include commonly used appropriate carriers, excipients, and diluents, and may be used in oral dosage forms such as powders, granules, tablets, capsules, syrups, ointments, patches, and suppositories. It can be used in formulations such as transdermal administration formulations and injections. However, it is not limited to this, and any preparation technology known in the technical field to which the present invention pertains can be used without particular limitation.

In addition, the composition according to the present invention may be a health food composition, in which case it can be manufactured into various types of food by containing commonly used food additives, and there is no particular limitation as it is known in the art to which the present invention pertains.

Hereinafter, the present invention will be described in more detail through specific examples and comparative examples. However, the following examples are only for a clearer understanding of the present invention, and the scope of protection of the present invention is not limited to the examples. The scope of protection of the present invention should be interpreted in accordance with the scope of the patent claims, and equivalents thereof. All technical ideas within the scope should be construed as being included in the scope of rights of the present invention.

<Example 1>

1. Preparation of experimental animals

A total of 60 male ICR mice with an average weight of 20 g were purchased from Orient Bio, 5 for each test group, and were allowed to freely consume food and drinking water for general laboratory animals until the experiment. The mice were kept at a temperature of 22 to 24°C. An environment of 60 to 70% relative humidity was maintained.

One week before the experiment, the day and night cycle was set to 12-hour intervals, and preparation for the experiment was completed by fasting for 24 hours before the experiment.

2. Experimental method

Using experimental animals prepared in the above-described manner, the time taken to fall asleep, i.e., sleep induction time (Sleep latency), and the time to fall asleep, i.e., sleep duration, were measured.

The sleep induction time was set as the time elapsed until the righting reflex was lost for more than 1 minute after intraperitoneal administration of the experimental drug, and the sleep duration was set as the time until the animal regained the righting reflex. set. Animals that did not sleep within 15 minutes were excluded from measuring experimental results.

The test group for measuring sleep induction time and sleep duration was set as follows, the negative control group used physiological saline, the positive control group used sodium pentobarbital, and the test group according to the present invention used snail extract, and the extraction was frozen. Dried slugs were extracted with ethanol.

The slug extract was used in Examples 1 to 3 using general feed, in Examples 4 to 6, dried bellflower gum powder feed, in Examples 7 to 9, lettuce powder feed, and in Examples 10 to 12, slugs fed with seaweed powder feed. Manufactured.

* Negative control group: 5 animals

Administer 30 mg/kg of physiological saline intraperitoneally

* Positive control group 1: 5 animals

Sodium pentobarbital 45 mg/kg administered intraperitoneally

* Test groups 1, 4, 7, 10 of the present invention: 5 animals

Intraperitoneal administration of 100 mg/kg of slug extract

* Test groups 2, 5, 8, 11 of the present invention: 5 animals

Intraperitoneal administration of 200 mg/kg of slug extract

* Test group 3, 6, 9, 12 of the present invention: 5 animals

Intraperitoneal administration of 300 mg/kg of slug extract

3. Experimental results

According to the experimental method described above, the sleep induction time and sleep maintenance time were measured for each test group, and the average values are shown in Tables 1 and 2.

Sleep induction time (seconds) negative control 510±5 Positive control 1 370±5 Test group 1 401±4 Test group 2 375±4 Test group 3 354±5 Test group 4 372±5 Test group 5 348±4 Test group 6 321±5 Test group 7 367±3 Test group 8 344±5 Test group 9 320±4 Test group 10 365±4 Test group 11 351±3 Test group 12 330±5

Sleep duration (seconds) negative control 1198±5 Positive control 1 1498±4 Test group 1 1412±4 Test group 2 1478±4 Test group 3 1554±5 Test group 4 1508±5 Test group 5 1574±5 Test group 6 1605±5 Test group 7 1512±4 Test group 8 1561±5 Test group 9 1605±5 Test group 10 1501±4 Test group 11 1571±5 Test group 12 1605±5

First, looking at Table 1 showing the sleep induction time, compared to the negative control group administered saline solution, the positive control group 1 administered sodium pentobarbital showed a sleep induction time reduction effect of approximately 27%.

In comparison, among the test groups according to the present invention, test groups 1, 2, and 3 fed with regular feed showed that test group 1, which had a low dose, did not have a better reduction effect than the positive control group, but showed a significant effect compared to the negative control group. , Test groups 2 and 3 showed almost equivalent effects to the positive control group, confirming the superiority of the composition according to the present invention.

In addition, looking at test groups 4 to 12 of the slug extract fed with bellflower bark, lettuce, and columbine feed, all showed better effects than the positive control group 1, confirming the effect of the change in feed.

Next, looking at Table 2 showing the sleep duration, compared to the negative control group administered saline solution, the positive control group 1 administered sodium pentobarbital showed an increase in sleep duration of approximately 25%.

In comparison, among the test groups according to the present invention, test groups 1, 2, and 3 fed with regular feed showed that test group 1, which had a low dose, did not have a better reduction effect than the positive control group, but showed a significant effect compared to the negative control group. , Test groups 2 and 3 showed almost equivalent effects to the positive control group, confirming the superiority of the composition according to the present invention.

In addition, looking at test groups 4 to 12 of the slug extract fed with bellflower bark, lettuce, and columbine feed, all showed better effects than the positive control group 1, confirming the effect of the change in feed.

4. Experiment conclusion

The composition according to the present invention using snail extract as an active ingredient has the effect of shortening sleep induction time and maintaining sleep only when 100 mg/kg of general feed slug extract (test group 1) is administered compared to sodium pentobarbital, which is prescribed as an insomnia treatment drug. Although it was only slightly less effective in increasing time, it showed comparable or superior effects at higher doses, and even when administered at 100 mg/kg, the effect was smaller than that of sodium pentobarbital, but had the effect of shortening sleep induction time and increasing sleep duration. is significant.

<Example 2>

If carried out in the same manner as Example 1, however, the snail extract was

5 parts by weight of Lactobacillus Casei was added to each 100 parts by weight of dried radish bark powder, lettuce powder, and columbine powder, fermented at a temperature of 36°C for 7 days, and then steam heated at 100°C for 30 minutes. There is a difference between slugs fed with sterilized feed and slugs fed with regular sawdust feed.

Specifically, in Example 2, test group 13 was a fermented bellflower bark feed, test group 14 was a lettuce fermented feed, and test group 15 was an extract of snails fed a fermented seaweed feed, and 100 mg/kg of this extract was administered intraperitoneally.

The sleep induction time and sleep maintenance time for each test group were measured, and the average values are shown in Tables 3 and 4.

Sleep induction time (seconds) Test group 13 342±5 Test group 14 341±5 Test group 15 339±3

Sleep duration (seconds) Test group 13 1597±5 Test group 14 1598±4 Test group 15 1592±4

Looking at the results in Tables 3 and 4, test groups 13 to 15 fed fermented feed were similar to test groups 6, 9, and 12 fed unfermented feed and 300 mg/kg of slug extract even when 100 mg/kg of extract was used. The results showed that the effectiveness of fermented feed was significant.

<Example 3: Measurement of re-sleep induction time>

If you fall asleep after taking a drug to treat insomnia, but wake up due to some stimulus and can easily go back to sleep without taking the drug, the drug is very useful in preventing, alleviating, improving, or treating insomnia.

Accordingly, in this experiment, the re-sleep induction time was measured based on the previous experiment, and the results are shown in Table 5. The re-sleep induction time was 1 minute after intraperitoneal administration of the experimental drug and the righting reflex. This is the result of measuring the time until sleep is induced without providing sufficient sleep time after the loss of abnormality, restoring the righting reflex again by stimulating it after 500 seconds, and then not administering the experimental drug again.

The test group for measuring the sleep re-induction time was set as follows with reference to the results of measuring the sleep induction time, and the test group according to the present invention had a sleep induction time almost equivalent to that of sodium pentobarbital, the positive control group. It was set at the dose of the test group that showed a shortening effect.

* Negative control group: 5 animals

Administer 30 mg/kg of physiological saline intraperitoneally

* Positive control group: 5 animals

Sodium pentobarbital 45 mg/kg administered intraperitoneally

* Test group 16 of the present invention: 5 animals

Intraperitoneal administration of snail extract 200㎎/㎏

* Test group 17 of the present invention: 5 animals

Intraperitoneal administration of 100 mg/kg of snail (bellflower bark feed) extract

* Test group 18 of the present invention: 5 animals

Intraperitoneal administration of 100 mg/kg of snail (lettuce feed) extract

* Test group 19 of the present invention: 5 animals

Intraperitoneal administration of 100 mg/kg of snail (maesaeng feed) extract

* Test group 20 of the present invention: 5 animals

Intraperitoneal administration of 100 mg/kg of slug (fermented bellflower bark feed) extract

* Test group 21 of the present invention: 5 animals

Intraperitoneal administration of 100 mg/kg of snail (fermented lettuce feed) extract

* Test group 22 of the present invention: 5 animals

Intraperitoneal administration of 100 mg/kg of snail (fermented seaweed feed) extract

Re-sleep induction time (seconds) negative control 705±5 positive control 696±5 Test group 16 602±4 Test group 17 592±5 Test group 18 594±3 Test group 19 589ㅍ5 Test group 20 552±5 Test group 21 547±3 Test group 22 542±5

Looking at Table 5 showing the experimental results, it was confirmed that a longer time was needed to induce sleep again than the sleep induction time in Table 1. In the case of the positive control group, the re-sleep induction time was reduced compared to the negative control group, and the reduction value was It was about 1.4%, showing no significant difference from the negative control group. In other words, sodium pentobarbital, which is used as a positive control, can be seen as not showing any effect in re-sleep induction, which induces people to go back to sleep after waking up without sufficient sleep.

In contrast, all test groups according to the present invention did not get enough sleep and had a high possibility of easily returning to sleep even if they woke up midway, confirming that it is an excellent composition for preventing, alleviating, improving or treating insomnia.

Claims (4)

A pharmaceutical for preventing, alleviating, improving or treating insomnia, comprising as an active ingredient a slug extract extracted from slugs fed any feed selected from the group consisting of bellflower shell powder, lettuce powder, columbine powder and mixtures thereof. enemy composition.
Solid-state fermentation obtained by adding 5 parts by weight of Lactobacillus Casei to any one selected from the group consisting of bellflower peel powder, lettuce powder, seaweed powder, and mixtures thereof and fermenting at 37°C for 7 days. A pharmaceutical composition for preventing, alleviating, improving or treating insomnia, comprising a slug extract extracted from slugs fed feed whose fermentation was suppressed by steam sterilizing water at 100°C for 30 minutes.
A health food composition for preventing, alleviating or improving insomnia, comprising as an active ingredient a slug extract extracted from slugs fed any feed selected from the group consisting of bellflower shell powder, lettuce powder, columbine powder and mixtures thereof. .
Solid-state fermentation obtained by adding 5 parts by weight of Lactobacillus Casei to any one selected from the group consisting of bellflower peel powder, lettuce powder, seaweed powder, and mixtures thereof and fermenting at 37°C for 7 days. A health food composition for preventing, alleviating or improving insomnia, comprising slug extract extracted from slugs fed feed whose fermentation was suppressed by steam sterilizing water at 100°C for 30 minutes.