JP2003313138A - Medicament or functional food for suppressing pruritus, and method for evaluating the effect - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a medicament or functional food effective for not only ordinary pruritus but also intractable pruritus, and to provide a method for evaluating pruritus-suppressive effect even more objectively. <P>SOLUTION: The medicament (antipruritic) or functional food contains fruit polyphenols. The method for evaluating the effectiveness of the medicament or functional food is based on the cumulative scratching action time within a specified period of time for small-size experimental animals intracutaneously administered with an itch-causing substance. <P>COPYRIGHT: (C)2004,JPO

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a drug or functional food for suppressing itch and a method for evaluating the effect thereof.

[0002]

BACKGROUND OF THE INVENTION Most skin diseases are generally accompanied by itching. The pruritus includes pruritus (general pruritus) that can be suppressed by commercially available antipruritic agents represented by antihistamines, such as eczema and urticaria, and pruritus cutaneus of hemodialysis patients,
There is pruritus (intractable pruritus) that cannot be suppressed by antihistamines and steroid preparations, such as senile pruritus dermatitis and atopic dermatitis. Especially, the latter which is difficult to suppress with currently known antipruritic agents. With regard to (1), it is one of the major problems in today's medical field.

Antipruritics, which are mainly antihistamines, are not only ineffective against intractable pruritus, but when used as an internal medicine, they have side effects of causing central depression such as drowsiness.

On the other hand, in evaluating the drug efficacy, a method is known in which small animals such as mice, rats, and guinea pigs are used, and the behavioral patterns when the pruritic substance is intradermally administered to these animals are observed (Japanese Patent Laid-Open No. Hei 10 (1999) -242945). 3-287536). However, this conventional evaluation method makes objective evaluation difficult because the subjectivity of the observer intervenes, and in order to make it as objective as possible, the average value of the scores of multiple observers is taken. It was very troublesome to do so.

[0005]

SUMMARY OF THE INVENTION The present invention has been devised to solve the above-mentioned problems of the prior art.
The first purpose thereof is to provide a drug or functional food effective not only for general pruritus but also for intractable pruritus. A second object of the present invention is to provide an evaluation method capable of more objectively and relatively easily evaluating the effect of suppressing itch.

[0006]

In order to achieve such an object, in the present invention, a fruit polyphenol is contained in an antipruritic agent for suppressing itch.

In particular, the fruit polyphenols shall be derived from apples, pears or peaches belonging to the family Rosaceae, squeezed and / or extracted from these immature fruits and then purified from this squeezed and / or extracted liquor. I decided. In addition, the above-mentioned drug is included in the functional food.

The effectiveness of the above-mentioned drug or functional food was decided to be evaluated based on the cumulative value of the pruritic behavior time within a predetermined time of a small experimental animal to which the pruritic substance was intradermally administered.

[0009]

DETAILED DESCRIPTION OF THE INVENTION The present invention will be described in detail below with reference to the accompanying drawings.

The drug having an inhibitory effect on general pruritus and intractable pruritus of the present invention contains a fruit polyphenol. This fruit polyphenol is generally a compound widely distributed in the plant kingdom, and can be extracted relatively easily from fruits such as apples, pears, or peaches belonging to the family Rosaceae, and can be extracted from mature fruit juice, of course. , The content of polyphenol compound is relatively high,
It is most advantageous to use immature apples.

North of the Kanto region of Japan, especially Aomori prefecture, produces about 50% of the total apple production in Japan.
It has been found that apples in this region contain relatively high amounts of fruit polyphenols. By pressing or centrifuging the unripe fruit, a fruit juice containing the fruit polyphenol can be easily obtained. The polyphenol fraction can be purified by treating the squeezed fruit juice and the extract with an adsorbent, but since a known method can be applied to the purification method, detailed description thereof is omitted here (necessary). Then, 1994 issue "food and development" VOL.29 N
See O.7 "Development and Utilization of Apple Polyphenols").

A liquid preparation can be obtained by concentrating the purified polyphenol fraction. Furthermore, a powder formulation can be obtained by spray-drying or freeze-drying this concentrated solution.

Next, the verification result of the antipruritic effect of the drug containing the fruit polyphenol according to the present invention will be described.

First, a pruritic animal model for inducing general pruritus and intractable pruritus was prepared in mice, rats, and small animals such as guinea pigs. In particular, guinea pigs were most suitable for observing pruritic behavior and scratches on the skin.

The body hair of the right flank of a healthy Hartley male guinea pig (8 weeks old) was clipped with a clipper and a shaver the day before the experiment, and 0.05 ml of pruritic substance (general pruritus histamine hydrochloride, refractory pruritus porcine spleen). Origin kallikrein) was intradermally administered to the site to cause itching, which was used as an animal model for itching.

As a result, a pruritic animal model can be obtained in which the antipruritic effect on general pruritus which can be suppressed by a commercially available antipruritic agent and intractable pruritus which cannot be suppressed by the commercially available antipruritic agent can be similarly determined.

This model has an appropriate number of heads (eg, 12 heads)
It is divided into groups, and the pruritic behavior of each group is observed from directly above for a predetermined time (2 hours) immediately after administration with a video camera with a time display, and pruritic behavior (scratching the pruritic site with the mouth or hind limbs) ) Was accumulated (second / 12
0 minutes). At this time, if the editing is performed so that only the part in which the pruritus behavior can be seen is extracted from the image of the video camera, the data can be easily collected.

Next, in the first group, 0.1 ml of 3% concentration of diphenhydramine hydrochloride (hereinafter abbreviated as DPH) dissolved in physiological saline as an antihistamine was uniformly applied to the itch site, and the second group was applied. Is similarly applied with 1% concentration of apple phenone (hereinafter abbreviated as AP), which is a drug of the present invention dissolved in physiological saline, and the pruritic behavior of the pruritic site is observed and timed in the same manner as above, The presence or absence of antipruritic effect was judged by a significant difference test of pruritic behavior.

As a result, as shown in FIG. 1, the cumulative pruritus action time immediately after the histamine was itched was 22.2 ± 6.3.
When the DPH was applied to the first group, which had been (second / 120 minutes), the cumulative pruritus action time was 13.6 ± 4.6 (second / 120 minutes), and the inhibition rate was 38.7%. It was

On the other hand, the cumulative pruritus action time immediately after the histamine was pruritus was 18.8 ± 5.5 (second / 120 minutes).
When AP was applied to the second group, the cumulative pruritus behavior time was 11.9 ± 4.3 (second / 120 minutes) and 3
The inhibitory rate was 6.7%, and it was found that the drug of the present invention has an antipruritic effect equivalent to that of an antihistamine against histamine pruritus.

Further, as shown in FIG. 2, when DPH was applied to the third group, which had a cumulative pruritus action time of 49.2 ± 9.1 (seconds / 120 minutes) immediately after the kallikrein itch was itched. , Cumulative pruritus behavior time 51.3 ± 8.1 (sec / 1
It was 20 minutes) and the inhibition rate was -4.3%, and it was found that the antipruritic effect was not obtained at all by DPH against pruritus kallikrein.

On the other hand, the cumulative pruritus action time immediately after the kallikrein was also pruritus was 36.8 ± 7.5 (seconds / 1).
When the 0.3% concentration of AP was applied to the 4th group, which had been for 20 minutes), the cumulative pruritus behavior time was 36.2 ± 6.1.
(Second / 120 minutes), a decrease rate of 1.6%. Similarly, when a cumulative pruritus behavior time of 46.8 ± 4.2 (seconds / 120 minutes) immediately after the elicitation of kallikrein was applied to the fifth group, AP at a concentration of 1.0% was applied. Action time 32.0 ± 9.0 (second / 120 minutes) and 3
The inhibition rate was 1.6%. Similarly, the cumulative pruritus behavior time immediately after the kallikrein was pruritus was 39.8 ± 5.6.
When the AP of 3.0% concentration was applied to the 6th group, which had been (second / 120 minutes), the cumulative pruritus behavior time was 28.0.
The inhibition rate was ± 4.8 (second / 120 minutes), which was 29.6%.

From the above, it was demonstrated that even with regard to pruritus kallikrein which could not be suppressed at all by antihistamines, an antipruritic effect approximately equal to that against histamine pruritus can be obtained with AP at a concentration of at least 1% or more. .

This test method is based on Shelly and Arthur, who systematizes mainly in humans, "Histamine pruritus can be suppressed by antihistamines (commercially available antipruritics), but kallikrein pruritus cannot be suppressed by antihistamines" ( Shelley
WB, Arthur BP, Arch. Dermatol, 76, 296-323 (1957)) was applied to an animal model. By this test method,
It is possible to determine whether or not there is an antipruritic effect against intractable pruritus due to kallikrein itch as well as general itch due to histamine itch.

When the drug according to the present invention is used as a pharmaceutical, a prophylactically or therapeutically effective amount of the fruit polyphenol may be formulated together with a pharmaceutically acceptable carrier or diluent. In addition, binders, absorption promoters, lubricants,
Emulsifiers, surfactants, antioxidants, preservatives, coloring agents, flavors, sweeteners and the like may be added.

In such a pharmaceutical preparation, the compounding ratio of the fruit polyphenol as an active ingredient to the carrier component is in the range of 0.1 to 30.0% by weight, particularly 0.5.
The range of up to 5.0% by weight is preferred.

The dosage form of the pharmaceutical preparation includes a cloth, a spray, a solution, a suspension, an ointment, a gel, a paste,
Creams, granules, fine granules, tablets, pills, capsules and the like can be mentioned, and the administration route thereof includes application, application, oral, intravenous, intramuscular, subcutaneous, joint cavity, etc.
Although various administration routes can be mentioned, an external preparation is particularly preferable. When the substance of the present invention is used as an external preparation for skin, the usual components to be added to a general external preparation for skin may be appropriately added as necessary. In addition, the dose and frequency of administration of the active ingredient can be appropriately changed depending on the condition, age, sex, administration route and the like.

The drug containing the fruit polyphenol according to the present invention may be added to a functional food. This functional food refers to a natural product containing one or more nutrients and a processed product thereof, and is applicable to all foods and drinks such as confectionery and soft drinks.

The present invention provides an external preparation, an injectable drug and an internal drug as disclosed in JP-A-3-287536.
It is also applicable to medicines, quasi drugs, and cosmetics. In that case, the substance of the present invention may be used in place of the zinc picolinate proposed in the publication.

[0030]

INDUSTRIAL APPLICABILITY As described in detail above, according to the present invention, by externally applying or taking a drug or a functional food containing a fruit polyphenol, itching associated with general skin diseases such as eczema and urticaria ( General pruritus) as well as pruritus skin, senile pruritus in hemodialysis patients, which are difficult to suppress with conventional antipruritic agents (antihistamines and antiallergic agents),
In addition, itching (refractory pruritus) such as atopic dermatitis,
It can be safely suppressed without causing side effects such as drowsiness, and can exert a great effect in effectively preventing, improving or treating skin symptoms.

Further, according to the evaluation method of the present invention, it is possible to eliminate the individual difference of the observer who had no choice but to intervene in the conventional method, so that more objective evaluation can be performed. In particular, if a video camera with time display is used, a large number of groups can be observed at the same time, which is effective in facilitating data collection.

[Brief description of drawings]

FIG. 1 is a graph showing the effect on general pruritus.

FIG. 2 is a graph showing the effect on intractable pruritus.

   ─────────────────────────────────────────────────── ─── Continued front page    (72) Inventor Tetsuyuki Kano             31-16-205 Honmachi, Wako City, Saitama Prefecture (72) Inventor Riki Yamanaka             2-1-17-306 Jiyugaoka, Meguro-ku, Tokyo (72) Inventor Teruhiko Matsumiya             3-41-25 Ogikubo, Suginami-ku, Tokyo F-term (reference) 4B018 MD52 ME14 MF01                 4C088 AB51 AC04 BA07 BA08 BA19                       CA14 MA52 NA14 ZA89

Claims (6)

[Claims] 1. A drug for suppressing itch, which comprises a fruit polyphenol. 2. The agent for suppressing itch according to claim 1, wherein the fruit polyphenol is derived from apple, pear or peach belonging to Rosaceae. 3. The fruit polyphenol is obtained by squeezing and / or extracting from an unripe fruit of apple, pear, or peach belonging to the Rosaceae, and then purifying from the squeezing liquid and / or the extract. The drug for suppressing itch according to claim 2, which is characterized in that. 4. A functional food comprising the drug according to any one of claims 1 to 3. 5. The effect of a drug or a functional food for suppressing pruritus, which is characterized in that it is based on the cumulative value of pruritus behavior time within a predetermined time of a small experimental animal intradermally administered with an pruritic substance. Evaluation methods. 6. The cumulative value is obtained from an image with time display captured by a video camera.
The method for evaluating the effect of a drug or a functional food for suppressing the itching according to [4].