JP2008239620A - Antiallergic agent containing cranberry fruit juice as active ingredient - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To ameliorate diseases caused by I-type allergy in relating to an antiallergic agent containing Vaccinium macrocarpon fruit juice as an active ingredient. <P>SOLUTION: The antiallergic agent for ameliorating diseases caused by I-type allergy is constituted by using the cranberry fruit juice as a raw material. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to an antiallergic agent comprising cranberry juice as an active ingredient.

  In recent years, the number of patients suffering from allergic diseases due to changes in eating habits and the environment has increased rapidly, which is a serious problem. Allergies are classified into four types, from type I to type IV, depending on the mechanism of their onset. Of these, type I is caused by the activation of IgE-sensitized mast cells by reaction with antigen, causing degranulation and releasing chemical mediators such as histamine, and includes atopic dermatitis, hay fever, etc. To do.

  Atopic dermatitis is defined as “a disease with repeated pruritus and exacerbation, with itchy eczema as the main lesion”, but the details of the pathological condition remain unclear, and established treatments and diets are still unclear. There is no actual situation. In addition, hay fever often has serious symptoms that hinder daily life, and more than 20% of Japanese people are said to suffer from some form of hay fever.

  In order to prevent and treat such diseases caused by type I allergy, it is necessary to suppress any stage of the above reaction. From this viewpoint, various antiallergic agents have been developed. These may be accompanied by side effects such as worsening of symptoms due to long-term administration, drowsiness by acting on the central nervous system, and effects on the endocrine system by percutaneous absorption.

  On the other hand, cranberries are a plant belonging to the genus Turberry, which bears fruit. In fact, it can be eaten as it is, and has a high content of dietary fiber, vitamins, and organic acids, so it is effective in adjusting urine pH and urinary tract infections, and preventing periodontal disease gingivitis It is known to have an effect. However, it is not known that the cranberry juice used in the present invention has an antiallergic action, and therefore, it has not been considered at all to use the cranberry juice for improvement and treatment of allergic diseases.

  The present invention has been made in view of such circumstances, and an object thereof is to provide an antiallergic agent having an excellent antiallergic action that is easy to be taken without suffering from side effects.

  In order to achieve the above object, the antiallergic agent of the present invention comprises cranberry juice as an active ingredient. Here, the cranberry juice refers to raw fruit juice obtained by squeezing from cranberry fruit, or concentrated fruit juice obtained by concentrating it.

  That is, the present inventor has conducted experiments and studies on the efficacy of various plants on leaves and fruits for allergic diseases, and found that cranberry juice is effective against allergic diseases, and has reached the present invention.

  Thus, since the antiallergic agent of the present invention uses cranberry juice as the main ingredient, it can be taken for a long time without suffering from side effects, and it is taken in place of tea that is usually drunk. Ingestion is also easy.

  Furthermore, if the antiallergic agent is a powder, it is not only possible to store for a long period of time, but it is also convenient to carry, so it is easier to take. In the present invention, the above-mentioned powder is meant to include granules, powders and powders.

  Next, embodiments of the present invention will be described in detail.

  As described above, the antiallergic agent of the present invention takes the form of a raw fruit juice of cranberry (Vaccinium macrocarpon) or a concentrated fruit juice thereof, or a solid preparation containing a solid content in the cranberry juice. The antiallergic agent herein can improve and treat diseases caused by allergic reactions, and can improve and treat diseases caused by type I allergic reactions.

  The antiallergic agent of the present invention can be produced, for example, by squeezing juice from cranberry fruit. In this case, the squeezed residue is usually removed by filtration or the like, but may be left as it is. Moreover, the juice (raw fruit juice, concentration of 100% by weight) which is the above juice may be concentrated, and the concentration of the juice may be further increased, or conversely diluted. Usually, such a liquid preparation that is used for drinking as it is is diluted and adjusted to contain cranberry juice so as to contain a concentration of 10 to 80% by weight (hereinafter referred to as “%”), more preferably 15 to 70%. If the concentration is less than 10%, the effect of drinking is small, and if it exceeds 80%, it becomes difficult to drink. However, when concentrated, the cranberry juice concentration within the range of 700% at the maximum is also provided for drinking.

  Further, the fruit juice may be dried to form a powder (solid content), and the anti-allergic agent of the present invention may be used as a powder. In this case, the fruit juice is subjected to an evaporator, a spray dryer, a freeze dryer or the like. Such pulverization is carried out, for example, by adding a sweetener such as sugar or dextrin to cranberry juice, so that the solid content of the cranberry juice is 20% to 80% of the powder, Insertion processing is performed. However, sweeteners such as sugar may not be added, and the entire powder may be composed of only the solid content of cranberry juice. Ingestion of such a powder is usually carried out with reference to the solid content of cranberry juice obtained by drying the liquid.

  The antiallergic agent of this invention can be drunk as a liquid agent (liquid medicine) which consists of fruit juice in the state of said juice. In addition, when using fruit juice as a dried product, it can be ingested in the form of tablets, pills and powders, and in that case, it can be taken using water or the like, as with normal drugs. It is. Further, the fruit juice may be concentrated and used for drinking as a syrupy liquid, or may be packed in a capsule and used for drinking as a capsule or the like. In particular, when it is a powder, it may be taken together with dairy products such as yogurt and ice cream (for example, sprinkle on the surface of yogurt or ice cream). In this case, a powder having a flavor derived from cranberry juice is used. It becomes the flavor of the dairy product, and the intake becomes even easier.

  Next, examples will be described together with comparative examples. However, the present invention is not limited to these examples.

  First, prior to Examples and Comparative Examples, cranberry juice was prepared and mice with atopic dermatitis were prepared as described below.

[Preparation of cranberry juice]
Cranberry juice is concentrated 7 times (concentration 700%), 2% aqueous potassium bicarbonate (KHCO3) is added to adjust to pH 7, and then a large amount of water is added to adjust the cranberry juice concentration to 105%. did.

[Dermatitis-onset mouse]
12 NC / Nga mice (hereinafter referred to as “mouse”), which are widely used as atopic dermatitis model animals, are commercially available for 119.0 ± 33.0 days in a normal environment where airborne microorganisms are not controlled. Feed: Breeded with Nippon Claire CE-2 (hereinafter referred to as “commercial feed”) to develop dermatitis similar to human atopic dermatitis.

  After that, we observed skin inflammation in mice and based on clinical evaluation method for atopic dermatitis, pruritus, crust, epidermis peeling (ear defect + ear bleeding), facial bleeding (facial bleeding + erythema), edema, scales, Eight items of palpation and hair loss were scored on the basis of the following evaluation criteria, with 0 indicating no symptom and 6 indicating severe symptoms, and were evaluated in 7 stages from 0 to 6. The score of the above 8 items evaluated in this way was summed to obtain the [skin inflammation degree] of the mouse. The pruritus, scab, and epidermis detachment are caused by the mouse rubbing the affected area because of itching based on skin inflammation.

[1: Evaluation criteria for pruritus]
The behavior of the mouse was observed twice from the outside of the cage once for 30 seconds.
1 ... Vigorous grooming is seen.
2 ... The act of scratching with the front foot around the top of the head is seen.
3 ... There is an act of relentlessly scratching the forefoot around the top of the head.
4 ... The act of scratching the entire body using the hind legs is also seen.
5 ... The act of scratching the whole body using the hind legs is seen.
6 ... The act of scratching the whole body without interruption is seen.

[2: Evaluation standard for crusts]
The skin condition of the head, neck, and back (excluding the face and auricle) was observed.
1 ... 1-2 small crusts are seen.
2 ... 1-2 medium scabs are seen.
3 ... Many small crusts are seen.
4 ... Many moderate crusts are seen.
5 ... Many scabs are conspicuous and there are several with bleeding.
6 ... Many crusts are conspicuous, and there are countless cases with bleeding.

[3-1: Evaluation criteria for ear defects]
1 ... One minimal laceration can be seen on either the left or right auricle margin.
2 ... Minimal lacerations are seen on the edge of the auricle.
3 ... Rears or deformations were observed at the edge of the auricle, and the ears were shrunken to about 70% of the original size.
4 ... Rears or deformations were observed at the edge of the auricle, and the ears were shrunken to about half the original size.
5 ... Rears or deformations were observed at the edge of the auricle, and the ears were shrunken to about 30% of the original size.
6: The degree of laceration or deformation at the edge of the auricle is severe, and the ears are shrunk to less than 20% of the original size.

[3-2: Evaluation criteria for ear bleeding]
1 ... A slight bleeding trace is seen at one of the left and right auricle margins.
2 ... Slight bleeding traces are observed at 1-2 locations on the edge of the auricle.
3 ... 1-2 bleeding spots are found along the edge of the auricle.
4 ... 1-2 bleeding sites are found along the edge of the auricle.
5 ... Several bleeding areas over a wide area are found on the edge of the auricle.
6 ... Several extensive bleeding sites are found on the edge of the auricle, and the degree of bleeding is severe.

[4-1: Evaluation criteria for facial bleeding]
1 ... Slight bleeding traces are seen on either the left or right face.
2 ... Several small bleeding traces are seen.
3 ... Bleeding scars spread and bloody parts are seen.
4 ... The bleeding part spreads and bleeding on either the left or right side is severe.
5 ... The bleeding part covers a wide area, and bleeding is seen on both sides.
6: The bleeding part covers a wide area, and the degree of bleeding is severe on both sides.

[4-2: Evaluation criteria for erythema]
The lesion on the face was observed.
1 ... One erythema or ulcer is seen.
2 ... Several erythema are seen. Or the ulcer part spreads along the eye.
3 ... The left or right ulcer area extends to the cheek.
4 ... The ulcer area extends to the cheeks on both sides.
5: The left and right ulcers cover a wide area and more than half of the face.
6: The left and right ulcers cover a wide area and more than 70% of the face.

[5: Evaluation criteria for edema]
1 ... swelling is seen around the nose.
2: The swelling around the nose is conspicuous, and either the left or right eyeball looks small.
3 ... It is swollen around the nose, and the left and right eyeballs appear to be depressed.
4 ... The swelling spreads over the face and the eyeball looks small.
5 ... The swelling of the face is conspicuous, and the eyeball looks thin.
6: The face is swollen and the eyeball is almost closed.

[6: Evaluation criteria for scales]
1 to 1 to 2 extremely minute scales are observed.
2 ... Many fine scales are seen.
3 ... Scales are seen locally densely.
4 ... Scales spread sparsely from head to back.
5 ... Scales spread throughout the body, and 1-2 large scales are seen.
6 ... Scales spread throughout the body and many large scales are seen.

[7: Evaluation criteria for palpation]
The skin was pinched with the fingertips around the neck and back, and the eczema, crust forming part and clot were palpated. This method is effective in identifying onset that is covered with hair and difficult to detect.
1 ... One small eczema or scab can be palpated.
2 ... Several small eczema or crust can be palpated.
3 ... A plurality of eczema or crusts can be palpated locally.
4 ... Many eczema or crusts can be palpated over a wide area.
5 ... The eczema or crust spreads throughout the body and the clot is palpable.
6 ... Eczema, crusts, and blood clots spread throughout the body.

[8: Evaluation criteria for hair loss]
1 ... Bad fur.
2. The hair from the head to the neck is thin and sparse.
3 ... The part where the hair is thin is extensive.
4 ... Hair loss from the head to the back is obvious and is extensive.
5 ... The surface of the back can be seen by hair removal.
6 ... By epilation, not only the back but also the epidermis of the abdomen can be seen.

  Next, 12 mice were divided into 2 groups (1 group = 6 mice) so that the degree of skin inflammation was equal, one for Example 1 (cranberry juice administration group) and the other for Comparative Example 1 (control) Group).

[Example 1]
The above 6 mice, which are the cranberry juice administration group, were allowed to freely take the cranberry juice prepared as described above instead of water, and were allowed to freely take the commercial feed, and were bred for 35 days.

[Comparative Example 1]
The six mice as a control group were fed with water freely instead of the cranberry juice of Example 1, and were raised for 35 days in the same manner as in Example 1.

  About Example 1 and Comparative Example 1, the symptom degree was evaluated and compared with the symptom degree at the start of the experiment. The results are shown in Tables 1 and 2. The results are expressed as average values (hereinafter the same in Table 2, Table 3, and Table 4).

  In Table 2 above, the degree of improvement in skin inflammation and the rate of improvement were determined as follows. That is, the difference in symptom degree at the start of the experiment and at the end of the experiment was calculated, and this value was taken as [symptom improvement degree]. Also, the degree of improvement in skin inflammation at the start of the experiment is determined by dividing the degree of improvement in skin inflammation by the degree of inflammation in skin at the start of the experiment and multiplying by 100 to obtain the ratio of improvement in skin inflammation. Is shown.

  From the results shown in Table 1 above, the degree of skin inflammation at the start of the experiment in both Example 1 and Comparative Example 1 was around 23. However, Comparative Example 1 significantly deteriorated after the start of the experiment, and at the end of the experiment. After 35 days, it is found to be 25.59 ± 4.96. On the other hand, in Example 1, the symptoms were improved, and the degree of skin inflammation at the end of the experiment was 20.26 ± 1.98, showing a significant improvement (p <0.05). In addition, a significant difference was observed in the symptom levels of Example 1 and Comparative Example 1 at the end of the experiment (p <0.05). From the results shown in Table 2, Example 1 has a higher degree of symptom improvement than Comparative Example 1, and in terms of total evaluation (average), Example 1 is + 17.4%, and Comparative Example 1 is -11. .1%, and a significant difference (p <0.05) was recognized between the two. That is, it was shown that the symptoms of atopic dermatitis are remarkably improved by ingesting cranberry juice.

  On the other hand, for Example 1 and Comparative Example 1, the body weight was measured at the start of the experiment and at the end of the experiment, and the organ weight was measured at the end of the experiment. In addition, water intake during the test period was also measured. The measurement results are shown in Tables 3 and 4.

  From Tables 3 and 4 above, no significant difference was found between Example 1 and Comparative Example 1 in mouse body weight, but Example 1 was smaller in Comparative Example 1 than before and after the experiment. . In terms of liver weight, spleen weight, and water intake, Example 1 was less than Comparative Example 1 (p <0.01). This is considered that Example 1 approached the standard value of NC mice in terms of liver weight and spleen weight, and hypertrophy was suppressed. Regarding the water intake, there is no significant difference in the actual water intake, the standard water intake of the mouse is 6 g / day, Comparative Example 1 is 8.8 ± 0.76 g / day, and Example 1 is 7.2 ±. At 0.16 g / day, both exceeded the standard water intake, and it is considered that there is no difference affecting growth. Therefore, it is considered that cranberry juice slightly reduces the organ weight of mice, but does not affect body weight and water intake.

  Next, in order to examine whether the improvement of the skin symptom by ingesting cranberry juice is due to the elimination of the hyper-IgE state, the measurement of the IgE values of Example 1 and Comparative Example 1 ELISA) method. Here, the ELISA method is a kind of quantitative measurement method of antigen-antibody reaction, which is a method of quantifying an antibody (IgE) using a labeled enzyme (antigen), and an enzyme immunoassay (Enzyme Linked immuno-sorbent). assay, ELISA). In the present invention, specifically, the sandwich method was used to measure IgE. As a result, Example 1 was 29.3 μg / ml, Comparative Example 1 was 19.1 μg / ml, and the IgE value was found to be significantly higher in Example 1 than in Comparative Example 1. Although the skin inflammation degree was significantly improved in Example 1 in spite of the higher IgE value compared to the comparative example, the cranberry juice is free from the production and release of various mediators regardless of the suppression of IgE. It is considered that there is a component that improves symptoms of atopic dermatitis by another mechanism such as suppression. IgE is a kind of immune antibody, and when IgE antibody reacts with an antigen, a disorder reaction appears. Atopic allergy (atopy) is an allergic reaction mediated by IgE antibodies. Atopic diseases include atopic dermatitis, allergic rhinitis, and allergic asthma, and the present invention is effective for these.

[Example 2]
A pack of cranberry juice, prepared using chickenpox etc., as shown in Table 5 below, is stored in a pack for several days. 30 college students (female, 18 to 20 years old) who are hay fever and 30 adults A person (9 males, 21 females, average age 48 ± 11 years) was ingested 30 g a day in several divided doses for 10-12 weeks. A questionnaire was given to patients about the improvement of symptoms after the end of intake relative to the symptoms before the start of intake. The results of the questionnaire are shown in Tables 6 and 7.

  From Table 6 above, the majority of the patients who took the solution replied that their symptoms had improved, and from Table 7 they felt that the intake of the solution was effective in improving the symptoms. In this way, the cranberry juice was concentrated seven times (juice concentration 700% (concentrated fresh cranberry juice, and the concentration was increased sevenfold when the fresh fruit juice was 100%)). It was found that ingesting 30 g (equivalent to 94.5 g of cranberry fresh fruit juice) of a liquid preparation containing 45% concentrated fruit juice a day has the effect of improving human hay fever symptoms.

  In addition, since 94.5 g of fresh fruit juice of cranberry which is said to have the above effect is an absolute amount, when concentrating this fruit juice, the amount is less than 94.5 g, and when diluting, much is required. If it is concentrated too much, the viscosity becomes high and it is difficult to take it. If it is diluted too much, the amount becomes too much to take. When diluting, the concentration is adjusted to 10 to 80% as described above in consideration of ease of drinking. However, when the taste is adjusted by adding sweeteners such as syrup, or when capsules are used, the concentrated cranberry juice is used 5 to 7 times, and the improvement effect can be achieved with a small intake. It will be obtained.

Example 3
Liquid prepared by concentrating cranberry juice seven times (juice concentration 700% (concentrated fresh cranberry fruit juice, and increasing the concentration seven times when the raw fruit juice is 100%)) 15g-60g a day for atopic dermatitis patients (20 women, average age 29.5 years old, 2 men, average age 21.0 years total 22 people) divided into several times for 2-6 weeks Ingested. A questionnaire was given to patients about the improvement of symptoms after the end of intake relative to the symptoms before the start of intake. The results of the questionnaire are shown in Tables 8 and 9.

  From Table 8, 95.2% of the patients who took the above solution answered that their symptoms had improved, and that the intake of the above solution was effective in improving the symptoms (90.9%) and realized that the skin had improved. (86.4%). Thus, it was found that cranberry juice has an effect of improving not only mice but also human atopic dermatitis.

  On the other hand, from Table 9, by taking 20 g of the above solution (equivalent to 140 g of fresh cranberry fruit juice), 5 out of 5 responded “Slightly improved” and ingesting 30 g of the above solution (equivalent to 210 g). As a result, 1 out of 10 responded that “very improved” and 9 answered “improved a little”, and all the subjects felt improvement. Similar results were obtained for 40 g (equivalent to 280 g), 50 g (equivalent to 350 g), and 60 g (equivalent to 420 g) of the liquid. Therefore, it was found that even if the intake of cranberry juice increases, the improvement effect can be obtained.

Example 4
Cranberry juice concentrated 7 times [fruit juice concentration 700% (concentrated fresh fruit juice of cranberry, and increased to 7 times the concentration when raw fruit juice is 100%)] 5 kg of concentrated juice To this, 2.1 kg of dextrin (manufactured by Sanwa Starch Kogyo Co., Ltd .: Sandeck # 100) and 3.15 kg of lactose (Japan Pharmacopoeia: lactose 200M) are added, mixed, and then sprayed and dried with 140 ° C hot air. After drying, the mixture was cooled to obtain 4.3 kg of a powder agent. At this time, 1 g of the powder contained 0.67 g of the concentrated fruit juice (corresponding to 4.69 g of fresh cranberry fruit juice). The powder preparation thus prepared was ingested into 2 to 8 weeks by dividing 10 g to 30 g per day into several times by atopic dermatitis patients (9 women, average age 20.6 years old). The daily intake of the powder at this time is 10 g for 3 people, 20 g for 5 people, and 30 g for 1 person. On average, 17.8 g per person (equivalent to 83.482 g of cranberry fresh fruit juice) Met. A questionnaire was given to patients about the improvement of symptoms after the end of intake relative to the symptoms before the start of intake. Table 10 shows the results of the questionnaire.

  From Table 10, 100% of the patients who took the powder replied that their symptoms had improved, and that the intake of the powder was effective in improving the symptoms (88.9%) and realized that the skin had improved. (66.7%). Thus, it was shown that the effect on the allergy of cranberry juice is sufficiently effective as a powder.

Claims (7)

  An antiallergic agent containing cranberry juice as an active ingredient.   The antiallergic agent according to claim 1, wherein the antiallergic agent is a liquid agent.   The antiallergic agent according to claim 1 or 2, wherein the cranberry juice is contained in one pack for internal use for one day.   The antiallergic agent according to claim 1 or 2, wherein the cranberry juice is contained in one pack for internal use for several days.   The antiallergic agent according to claim 1 or 2, which contains 94.5 g or more of cranberry juice for internal use for one day.   The antiallergic agent according to claim 1, wherein the antiallergic agent is a powder.   The antiallergic agent according to claim 6, wherein the powder is a hot-air dried product of a mixture of cranberry juice, dextrin and lactose.