JP2008133292A - Medicine for suppressing itching - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a medicine effective for common itches and intractable itches of dermatosis. <P>SOLUTION: The medicine for suppressing itching comprises fruit polyphenol. The fruit polyphenol is obtained by juicing and/or extracting from immature fruits of apple, pear or peach belonging to Rosaceae family and then refined from the juices or the extracts, and, by external application or internal use of a medicine or functional food containing the fruit polyphenol, not only itching caused by eczema, hives or the like of common dermatosis (common itch), but also itching of pruritus cutaneous of hemodialysis patient, senile pruritus cutaneous, atopic dermatitis and the like, hardly suppressed with conventional antipruritic agent (antihistamine or antiallergic agent) (intractable itch), are safely suppressed without causing side effects such as drowsiness, and much effects on effective prevention, improvement and treatment of cutaneous symptoms are expressed. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a drug for suppressing itch.

  Most skin diseases are usually accompanied by itching. The pruritus includes pruritus (general pruritus) that can be suppressed with commercially available antipruritic agents such as antihistamines, such as eczema and urticaria, and pruritus, senile pruritus, and atopy in hemodialysis patients. There are itchiness (refractory pruritus) that cannot be suppressed by antihistamines and steroids, such as atopic dermatitis. Is also one of the big problems.

  In addition, antipruritic agents mainly composed of antihistamines are not only ineffective for intractable pruritus, but also have the side effect of causing central depression such as sleepiness when used as an internal medicine.

  On the other hand, in order to evaluate the drug efficacy, a method is known in which small animals such as mice, rats, and guinea pigs are used, and behavioral patterns are observed when an irritant is administered intradermally (Japanese Patent Laid-Open No. Hei 3-287536). No. publication). However, this conventional evaluation method is difficult to objectively evaluate 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 necessary to do so, and it was very troublesome.

  The present invention has been devised to solve such problems of the prior art, and the first object thereof is a drug or functional food effective not only for general pruritus but also for intractable pruritus. Is to provide.

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

  In particular, fruit polyphenols shall be derived from apples, pears, or peaches belonging to the family Rosaceae, extracted and / or extracted from these immature fruits, and then purified from the juice and / or extract. did. Moreover, the said chemical | medical agent shall be included in a functional food.

  As described in detail above, according to the present invention, by applying or internally applying a drug or functional food containing fruit polyphenols, itching only with general skin diseases such as eczema and urticaria (genital pruritus) First, itching and other side effects such as drowsiness, such as skin pruritus, senile pruritus, and atopic dermatitis in hemodialysis patients that are difficult to suppress with conventional antipruritic agents (antihistamines and antiallergic agents) It can be safely suppressed without causing any problems, and can have a great effect in effectively preventing, improving or treating skin symptoms.

  Hereinafter, the present invention will be described in detail with reference to the accompanying drawings.

  The chemical | medical agent which shows the inhibitory effect with respect to the general pruritus and refractory pruritus of this invention contains fruit polyphenol. This fruit polyphenol is generally a compound widely distributed in the plant kingdom. For example, it can be extracted relatively easily from fruits such as apples, pears, or peaches belonging to the family Rosaceae, but of course can also be extracted from mature fruit juice. It is most advantageous to use immature apples in that the content of the polyphenol compound is relatively high.

  In the Kanto region north of Japan, especially Aomori Prefecture, it produces about 50% of the total apple production in Japan. It turns out that apples in this region contain a relatively large amount of fruit polyphenols. Yes. By squeezing or centrifuging the immature fruit, fruit juice containing fruit polyphenol can be easily obtained. The polyphenol fraction can be purified by treating the juice juice and extract with an adsorbent. However, since a known method can be applied to the purification method, detailed description is omitted here (necessary) (See “Development and Use of Apple Polyphenols” published in 1994, “Food and Development”, VOL. 29 No. 7).

  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 chemical | medical agent containing the fruit polyphenol by this invention is demonstrated.

First, a puppy animal model that induces general pruritus and refractory pruritus was made with mice, rats, and small animals such as guinea pigs. In particular, guinea pigs were optimal for observing pruritic behavior and skin scratch marks.
The hair on the right flank of a healthy Hartley male guinea pig (8 laps old) was shaved on the day before the experiment with a clipper and a shaver, and 0.05 ml of a pruritus (general pruritus is histamine hydrochloride, intractable pruritus is porcine spleen-derived kallikrein) Was intradermally administered to the site to cause wrinkling, which was used as a wrinkled animal model.

  As a result, it is possible to obtain a carrot animal model that can similarly determine the effect of pruritus against general pruritus that can be suppressed with commercially available antipruritic drugs and refractory pruritus that cannot be suppressed with commercially available antipruritic drugs.

  This model is divided into groups with an appropriate number of heads (for example, 12), 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. The time during which the behavior (the scratched area was scratched with the mouth or hind limb) was accumulated (seconds / 120 minutes). At this time, it is possible to easily collect data by editing the video camera image so as to extract only the part where the pruritus is seen.

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

  As a result, as shown in FIG. 1, when DPH was applied to the first group in which the cumulative pruritus behavior time immediately after the histamine generation was 22.2 ± 6.3 (seconds / 120 minutes), The pruritus behavior time was 13.6 ± 4.6 (seconds / 120 minutes), indicating a suppression rate of 38.7%.

  On the other hand, when AP was applied to the second group whose cumulative pruritus behavior time immediately after histamine development was 18.8 ± 5.5 (seconds / 120 minutes), the cumulative pruritus behavior time was 11 It was found that the drug of the present invention had an antipruritic effect equivalent to that of an antihistamine agent against histamine germination.

  In addition, 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 was sprouted, the cumulative pruritus was obtained. The action time was 51.3 ± 8.1 (seconds / 120 minutes), a suppression rate of −4.3%, and it was found that DPH did not provide any antipruritic effect against kallikrein generation.

  On the other hand, when AP of 0.3% concentration was applied to the fourth group which had a cumulative pruritus behavior time of 36.8 ± 7.5 (seconds / 120 minutes) immediately after the kallikrein was spawned. The cumulative pruritus behavior time was 36.2 ± 6.1 (seconds / 120 minutes), a decrease rate of 1.6%. Similarly, when a 1.0% concentration of AP was applied to the fifth group, which had a cumulative pruritus behavior time of 46.8 ± 4.2 (seconds / 120 minutes) immediately after the kallikrein was sprouted, the cumulative pruritus was applied. The action time was 32.0 ± 9.0 (seconds / 120 minutes), indicating a suppression rate of 31.6%. Similarly, when a 3.0% concentration of AP was applied to the sixth group, which had a cumulative pruritus behavior time of 39.8 ± 5.6 (seconds / 120 minutes) immediately after the occurrence of kallikrein, The pruritus behavior time was 28.0 ± 4.8 (seconds / 120 minutes), indicating a suppression rate of 29.6%.

  From the above, it was proved that an antipruritic effect that was not able to be suppressed at all with an antihistamine was obtained by the AP at a concentration of at least 1%, which is almost the same as that for histamine pruritus.

  This test method is based on Shelley and Arthur, mainly organized by humans, “Histamine germination can be suppressed with antihistamines (commercial antipruritic agents, but kallikrein germination cannot be suppressed with antihistamines” (Shelley WB, Arthur BP, Arch. Dermatol, 76, 296-323 (1957)) is applied to an animal model. By this test method, it is possible to determine whether or not there is an antipruritic effect on intractable pruritus caused by kallikrein occurrence as well as general occurrence due to histamine occurrence.

  When the agent according to the present invention is used as a pharmaceutical, an amount of fruit polyphenol effective for prevention or treatment is preferably formulated together with a pharmaceutically acceptable carrier or diluent. In addition, a binder, an absorption accelerator, a lubricant, an emulsifier, a surfactant, an antioxidant, an antiseptic, a colorant, a fragrance, a sweetener, and the like may be added.

  In such a pharmaceutical preparation, the blending 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, and particularly preferably in the range of 0.5 to 5.0% by weight.

  The dosage forms of pharmaceutical preparations include sprays, sprays, solutions, suspensions, ointments, gels, pastes, creams, granules, fine granules, tablets, pills, capsules, etc. Examples of the administration route include various administration routes such as patching, coating, oral, intravenous, intramuscular, subcutaneous, and joint cavity, and an external preparation is particularly preferable. When the substance of the present invention is used as an external preparation for skin, usual components to be added to general external preparations for skin may be appropriately added as necessary. Further, the dose and frequency of administration of the active ingredient can be appropriately changed according to the disease state, age, sex, administration route and the like.

  You may add the chemical | medical agent containing the fruit polyphenol by this invention to a functional foodstuff. This functional food refers to a natural product containing one or more nutrients and a processed product thereof, and can be applied to all foods and drinks such as confectionery and soft drinks.

  The present invention can also be applied to pharmaceuticals, quasi-drugs, and cosmetics as external preparations, injections, and internal medicines as disclosed in JP-A-3-287536. In that case, the substance of the present invention may be used in place of the zinc picolinate proposed in the publication.

Graph showing the effect on general occurrence Graph showing the effect on intractable development

Claims (3)

A drug for suppressing itching characterized by containing fruit polyphenols. The agent for suppressing itch according to claim 1, wherein the fruit polyphenol is derived from apples, pears, or peaches belonging to the family Rosaceae. The fruit polyphenol is extracted and / or extracted from an immature fruit of apple, pear or peach belonging to the Rosaceae family, and then purified from the juice and / or extract. Item 3. A drug for suppressing itch according to Item 2.

Images