JP2003048827A - Composition for oral cavity - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a composition for the oral cavity, which improves sleep quality by use before sleep and activates awakening by use on rising. SOLUTION: This composition for the oral cavity comprises (A) menthol and (B) a sesquiterpene alcohol having a cedrene skeleton in the content ratio of the component A to the component B [(A):(B)] of 1:0.01-10 by weight.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an oral composition having a sleep onset promoting action, a sleep improving action or a wakefulness action.

[0002]

2. Description of the Related Art Since the production of dental plaque, which is the cause of dental caries and periodontal disease, is accelerated during the sleep period when salivary secretion is decreased, brushing the teeth before going to bed is recommended from the viewpoint of oral hygiene. Very important. Menthol is often added to oral compositions such as toothpaste and mouthwash in order to impart a refreshing and refreshing feeling after brushing teeth. However, since menthol has a strong awakening effect, this is 0.2 to 0.
When a dentifrice containing 8% by weight is used before bed, there is a tendency that sleep onset is disturbed or sleep becomes light. Such a sleep disorder is caused by a state of hyperactivity when the arousal action of menthol enhances the sympathetic nerve, and the parasympathetic and sympathetic nerves are unbalanced and the autonomic nervous system suffers from ataxia. It is thought that it is derived from that.
Therefore, attempts have been made to obtain effective sleep by making the function of the parasympathetic nerve relatively dominant over the function of the sympathetic nerve. Other than the oral composition, it has been proposed to perform aromatherapy using low boiling point components of bitter orange essential oil, jasmine lactone, and cedar wood oil. However, all of these have a unique scent, and when added to an oral composition, there is a dislike due to a peculiar taste and the like, which may cause a state of mental excitement.

[0003]

DISCLOSURE OF THE INVENTION The present invention provides a menthol-containing oral composition which regulates the wakefulness effect of menthol and enables effective sleep without inhibiting sleep onset even when used before bed. The purpose is to provide things.

[0004]

Therefore, the present inventor has conducted various studies on the combined effect of menthol and various components, and found that sesquiterpene alcohol having a sedrene skeleton has an action of strongly suppressing the arousal action of menthol, Furthermore, when the parasympathetic nerve is increased immediately after waking up, it does not interfere with the wakefulness of menthol, and if these are contained in a certain ratio, a composition for oral administration in which a sleep-promoting action, a sleep-improving action and a wake-up action are well balanced is obtained. It was found that it can be obtained.

That is, the present invention contains the following components (A) and (B): (A) menthol (B) sesquiterpene alcohol having a sedrene skeleton, and the content ratio of the components (A) and (B). [(A):
(B)] provides an oral composition having a weight ratio of 1: 0.01-10.

[0006]

BEST MODE FOR CARRYING OUT THE INVENTION As the menthol [component (A)] used in the present invention, synthetic 1-menthol or dl-menthol, or a menthol-containing natural essential oil such as peppermint oil, spearmint oil or peppermint oil is used. 1-menthol purified from Further, the essential oil containing menthol can be used as it is.

The component (A) is contained in the oral composition in an amount of 0.2 to 0. 0 in terms of menthol, from the viewpoints of arousal action, feeling of use such as taste and lather, and irritation to oral mucosa. It is preferable to contain 8% by weight, particularly 0.3 to 0.6% by weight.

Examples of the sesquiterpene alcohol having a sedrene skeleton [component (B)] used in the present invention include cedrol and cedrenol, with cedrol being particularly preferred.

The component (B) can also be used as an essential oil obtained by extraction from plants or steam distillation, for example, using essential oils such as hay oil, cedar oil, cedar wood oil, cage oil, granberry oil, and lemon oil. Alternatively, these fermented products may be used.
Examples of the fermented product here include those obtained by allowing a microorganism belonging to the genus Rhodococcus to act on α-cedrene (JP-A-4-365488).

As described above, in the present invention, the sesquiterpene alcohol having a purified sedrene skeleton may be used, or the essential oil containing them may be used. However, since the essential oil contains many other sesquiterpene compounds having a unique flavor, it is difficult to add an effective amount in a substantially tasteless state. It is desirable to use. Furthermore, due to the aversion that comes from the taste and aroma of impurities,
Purity is 70% because the desired effect may not be obtained.
It is preferable to use the above, and more preferably 90% or more.

In the oral composition of the present invention, the content ratio of the component (A) and the component (B) [from the viewpoint of the balance between the sleep onset promoting action and the sleep improving action in the use before sleep, and the awakening action of menthol []. (A) :( B)] is in a weight ratio of 1:
It is preferably 0.01 to 10, and particularly preferably 1: 0.1 to 5.

The oral composition of the present invention comprises, in addition to the components (A) and (B), the components which are usually added to oral compositions, an ointment, a toothpaste, a liquid dentifrice, a mouthwash, It is preferable to use oral pasta, gum massage cream and the like.
Further, as the other component of the present invention, an appropriate component which is usually used can be blended depending on the kind of the oral composition and the purpose of use.

For example, as a component used in an appropriate amount as a toothpaste, calcium carbonate, aluminum hydroxide, silicic acid anhydride, hydrous silicic acid, dicalcium phosphate dihydrate may be used to enhance the effect of removing plaque. An abrasive such as dicalcium phosphate (anhydrous) or alumina can be used. Furthermore, in order to prevent the formation of plaque, benzethonium chloride, benzalkonium chloride, cetylpyridinium chloride, triclosan, chlorhexidine hydrochloride, chlorhexidine gluconate, isopropylmethylphenol,
A bactericide such as alkyldiaminoethylglycine hydrochloride and decalinium chloride can be used.

From the viewpoint of preventing periodontal disease, allantoin,
Anti-inflammatory agents such as allantoin chlorohydroxyaluminum, glycyrrhizinic acid, β-glycyrrhetinic acid, dihydrocholesterol and lysozyme chloride, vitamin E, and various plant extracts can be used. Further, from the viewpoint of preventing dental caries, fluorides such as sodium fluoride, sodium monofluorophosphate and stannous fluffer can be used.

Since the sesquiterpene alcohols as the component (B) are difficult to dissolve in water, in order to accelerate the dissolution,
Anionic surfactants such as sodium lauryl sulfate and lauroyl glutamic acid, and nonionic surfactants such as sucrose fatty acid ester, monoglycerin fatty acid ester, polyglycerin fatty acid ester, sorbitan fatty acid ester, hydrogenated castor oil, and polyoxyethylene polyoxypropylene glycol. Can be used together.

As an excipient, carboxymethyl cellulose, hydroxyethyl cellulose, carrageenan, xanthan gum, sodium alginate, sodium polyacrylate, polyethylene glycol, polyvinylpyrrolidone, silica gel, gelled hydrocarbon (liquid paraffin gelated with polyethylene resin) ), Petrolatum and the like can be used.

Clove oil, cinnamon oil, orange oil, anise oil, anethole, cassia oil and the like can be used as a flavoring component for masking a unique flavor or enhancing palatability. As the sweetener, saccharin sodium, stevioside, aspartame, acesulfame potassium and the like can be used.

In addition, wetting agents such as glycerin, sorbitol, xylitol, propylene glycol and polyethylene glycol, and preservatives such as parabens and sodium benzoate can be appropriately used in combination.

[0019]

EXAMPLES Examples 1 to 4 and Comparative Examples 1 to 2 Toothpastes shown in Table 1 were produced. The l-menthol contents of the peppermint oil and the spearmint oil used were 45% by weight and 5% by weight, respectively. Therefore, the substantial menthol content in the toothpastes of Examples and Comparative Examples was 0.4% by weight.

[0020]

[Table 1]

Test Example 1 (Effect on sleep-on time) (Method) Example 1 was conducted on 10 healthy women in their 20s.
-4 or the toothpaste of Comparative Examples 1-2 was investigated for the effect on sleep onset. Immediately before entering the bed, after brushing the teeth by a usual use method, the time from entering the bed to falling asleep was measured. The amount of toothpaste used was about 1 g each time. Toothpaste 1
Each type was used continuously for 1 week, and on the 8th day, it was used again for 1 week in place of the next dentifrice. The order in which the toothpaste used was used was randomly determined. When it was found that the period was before or during the period during the test, the measurement was performed again after the period. Actigram was used as the measuring method, and the subject's non-dominant arm was continuously worn during the test period. As data, the average of the values on the 4th day and the 5th day after the start of use by replacing the toothpaste was used. Statistical analysis of the measurement results was performed by Student's t-test by F-test.

(Results) The results are shown in FIG. When the toothpastes of Examples 1 to 4 were used, the sleep onset time was significantly shortened at a risk rate of less than 5% as compared with Comparative Example 1. In Comparative Example 2, the sleep onset time tended to be shortened, but no significant difference was observed.

From the above results, it was found that by using a dentifrice containing a sesquiterpene alcohol having a sedrene skeleton in a weight ratio of 0.01 or more with respect to menthol, the time until falling asleep can be significantly shortened. .

Test Example 2 (Effects on sleep) (Method) Female in her twenties who had been self-reported to have difficulty sleeping
The toothpaste of Example 3 or the toothpaste of Comparative Example 1 was used in 0 subjects immediately before bed, and the effect on sleep was measured. From entry to wake-up, electrocardiogram (chest V5 lead), EEG (international 10-20 method C3, O1), respiration (impedance method: abdomen and chest), surface EMG (left and right muscular bipolar induction). And eye movements (bipolar guidance with the left and right orbits connected horizontally) were measured. The first two days were used as acclimatization days for accustoming to the measuring instruments and the measurement environment, and the third day was the control day when the toothpaste was not used, and the fourth and fifth days were the toothpaste of Comparative Example 1 or Example 3. The date of use. Then, the change of each measurement item on the control day and the use day of the toothpaste of Comparative Example 1 and Example 3 was examined.
The wakefulness / sleep stage was determined by the international standard for sleep stage determination ("Sleep EEG Atlas", pages 3 to 6, edited by Physic Drug Publishing Co., Ltd.) based on the measurement results of EEG, surface EMG and eye movement. In addition, the frequency analysis of the RR interval fluctuation is performed by fast Fourier transform from the falling asleep to the second hour of the cumulative sleep time.
The amplitude of 0.12-2.00 Hz was integrated and it performed about the high frequency component (Sum of high frequency: Hsum). The statistical analysis of the measurement results was performed in the same manner as in Test Example 1.

(Results) (1) Regarding Hsum, when the non-REM sleep was used, the toothpaste of Comparative Example 1 was significantly reduced at a risk rate of less than 5% on the day of use of the toothpaste of Comparative Example 1, and the toothpaste of Example 3 was used. On a daily basis, the risk factor is 5 compared to the day when the toothpaste of Comparative Example 1 was used.
% Significantly increased. However, when compared with the control, it tended to increase, but was not significant (FIG. 2). (2) Cumulative occurrence rates of sleep stages 3 and 4 (Stage 3, 4) are as follows: during the cumulative sleep time of 2 hours, on the toothpaste use day of Example 3, on the control day and the toothpaste of Comparative Example 1. There was a significant increase at a risk rate of less than 5% compared to the day of use (Fig. 3). (3) Regarding the respiratory rate (RR), the risk factor was significantly less than 5% on the toothpaste use day of Comparative Example 1 during non-REM sleep compared to the control, and on the toothpaste use day of Example 3 Compared to the toothpaste use date of Comparative Example 1, the risk rate was significantly reduced at less than 5%. However, when compared with the control, it tended to decrease but was not significant (Fig. 4).

From the above results, the test subjects used the toothpaste of Comparative Example 1 to reduce the quality of sleep, but the use of the toothpaste of Example 3 restored the sleep quality. I was caught. It can be seen that, immediately after falling asleep, the depth of sleep was significantly deeper than on the day when the toothpaste was not used.

Test Example 3 (Effects on awakening) The toothpaste of Example 3 or the toothpaste of Comparative Example 1 was used immediately after waking up for 10 women in their 20s who had self-reported that they had poor sleep. Then, the effect on the awakening was investigated. The test was conducted continuously for 2 days, and 5 people were in Comparative Example 1 on the first day.
The dentifrice of Example 3 was used for the remaining 5 people. Two
On the day, it was used instead of the dentifrice of Example 3 or Comparative Example 1, respectively. Using an electric brush (Matsushita Electric Works, Dental by One EW188), tooth brushing was performed for 3 minutes so that the dominant arm with the brush had no amplitude as much as possible. To measure the effect on sleepiness, blood pressure (tonometry method) and respiration (instantaneous lung volume was measured by a respiratory rate sensor) were measured after resting for 5 minutes after brushing.

(Results) (1) Systolic blood pressure (SB) before and immediately after brushing
Comparing P), it was recognized that the dentifrices of Comparative Example 1 and Example 3 tended to increase (FIG. 5). (2) Diastolic blood pressure before and after brushing teeth (DB
Comparing P), it was recognized that the dentifrices of Comparative Example 1 and Example 3 tended to increase (FIG. 6). (3) Comparing the respiratory rate (RR) before and after brushing the teeth, it was observed that the dentifrices of Comparative Example 1 and Example 3 tended to increase (FIG. 7).

From the above results, sesquiterpene alcohol having a sedrene skeleton did not reduce the awakening effect of menthol in a state where the parasympathetic nerve was enhanced immediately after waking up.

[0030]

EFFECTS OF THE INVENTION The oral composition of the present invention suppresses the awakening effect of menthol when used before bedtime, thereby shortening the time until falling asleep and improving the quality of sleep, while menthol is used when waking up. It does not interfere with the awakening effect of.

[Brief description of drawings]

FIG. 1 is a diagram showing the time until falling asleep after the use of various dentifrices (* indicates that the risk rate is less than 5%, which is significant as compared with the case of using Comparative Example 1).

[Fig. 2] From sleep onset after use of various dentifrices to cumulative sleep time 2
It is a figure which shows the high frequency component (Hsum) by the time time (* shows that significance is less than 5% of a risk rate).

FIG. 3 is a diagram showing cumulative appearance rates of sleep stages 3 and 4 for each cumulative sleep time after using various dentifrices (* indicates a risk rate of 5%.
Is less than 1%, and ** indicates that the risk rate is less than 1%.

[Fig. 4] Respiratory rate during sleep (R after use of various dentifrices)
It is a figure which shows R) (* shows that significance is less than 5% of a risk rate).

FIG. 5 is a diagram showing systolic blood pressure when various dentifrices are used immediately after waking up.

FIG. 6 is a diagram showing diastolic blood pressure when various dentifrices are used immediately after waking up.

FIG. 7 is a diagram showing respiratory rates when various dentifrices are used immediately after waking up.

   ─────────────────────────────────────────────────── ─── Continued front page    (72) Inventor Yoshinao Nagashima             Kao Stock Association 2-1-3 Bunka, Sumida-ku, Tokyo             Company research institute (72) Inventor Yukihiro Yada             Kao Stock Association 2-1-3 Bunka, Sumida-ku, Tokyo             Company research institute F-term (reference) 4C206 AA01 AA02 CA03 MA02 MA04                       MA72 NA05 ZA05 ZA11

Claims (2)

[Claims] 1. The following components (A) and (B): (A) Menthol (B) A sesquiterpene alcohol having a sedrene skeleton is contained, and the content ratio of the components (A) and (B) [(A)]. :
(B)] is a composition for oral cavity in which the weight ratio is 1: 0.01-10. 2. The composition for oral cavity according to claim 1, wherein the sesquiterpene alcohol having a sedrene skeleton is cedrol or cedrenol.