JP7705791B2 - Composition for improving allergic rhinitis symptoms, composition for improving reduced QOL caused by allergic rhinitis symptoms, and composition for suppressing sneezing caused by allergic rhinitis symptoms - Google Patents

Description

The present invention relates to a composition for improving allergic rhinitis symptoms, a composition for improving a decline in QOL caused by allergic rhinitis symptoms, and a composition for suppressing sneezing caused by allergic rhinitis symptoms.

Allergic rhinitis is a type of allergic symptom affecting the nasal mucosa, and is characterized by symptoms such as sneezing, runny nose, and nasal congestion. Allergic rhinitis not only reduces quality of life (QOL) but also affects social activities such as learning and work, making it a serious social problem. Perennial allergic rhinitis is a type of allergic rhinitis caused by mites and house dust, and presents symptoms such as sneezing, runny nose, nasal congestion, and itchy eyes throughout the year.

The symptoms of allergic rhinitis are known to be sneezing, runny nose, swelling of the nasal mucosa, and nasal congestion, which are triggered by the release of histamine and leukotrienes from mast cells and eosinophils, following the production of antigen-specific IgE antibodies when antigens such as house dust, mites, and pollen invade the body (Non-Patent Document 1). In recent years, with a focus on these mechanisms, there has been progress in the search for food ingredients and the development of foods that suppress the symptoms of allergic rhinitis.

Patent Document 1 describes a food product for preventing the onset of allergic rhinitis and/or improving symptoms, which contains collagen hydrolysate. Patent Document 2 describes a composition for inhibiting degranulation of mast cells, which contains a serotonin derivative, and describes that the serotonin derivative is believed to improve the symptoms of allergic rhinitis, which is included in type I allergy (immediate-type allergy), by inhibiting the reaction between an antigen and a specific IgE antibody on the cell membrane of mast cells and the like, as well as the reaction related to the release of chemical mediators due to degranulation of mast cells. Patent Document 3 describes an allergic rhinitis inhibitor characterized by containing as an active ingredient one or more plant extracts selected from the group consisting of oleander, oleander, and palo santo.

Beta-carotene, which is found in various vegetables including carrots, has been suggested to have cancer preventive effects in epidemiological studies and is a representative functional ingredient found mainly in plant-based foods. Regarding the relationship between beta-carotene and allergic symptoms, it has been reported that administration of beta-carotene suppresses increases in antigen-specific IgE concentrations in the blood and the infiltration of inflammatory cells (Non-Patent Document 2), and that beta-carotene suppresses the degranulation of mast cells (Non-Patent Document 3).

Drug therapy is widely used for allergic rhinitis. However, it is merely a symptomatic treatment, and if administration is discontinued, the condition may recur within a short period of time, or drowsiness may be induced as a side effect, raising concerns about reduced productivity and quality of life. For this reason, there has been a demand for a new composition that is safe, easy to continue, and provides effects in a relatively short period of time.

Patent No. 6671671 JP 2011-93857 A JP 2011-26267 A

Okubo K, Kurono Y, Ichimura K, Enomoto T, Okamoto Y, Kawauchi H. et al. Japanese guidelines for allergic rhinitis 2017. Allergol Int. 2017;66(2):205-219. Sato Y, Akiyama H, Suganuma H, Watanabe T, Nagaoka MH, Inakuma T. et al. The feeding of beta-carotene down-regulates serum IgE levels and inhibits the type I allergic response in mice. Biol Pharm Bull. 2004; 27(7): 978-84. Sakai S, Sugawara T, Matsubara K, Hirata T. Inhibitory effect of carotenoids on the degranulation of mast cells via suppression of antigen-induced aggregation of high affinity IgE receptors. J Biol Chem. 2009; 284(41): 28172-9.

The problem that the present invention aims to solve is to provide a new composition for improving allergic rhinitis symptoms.

In light of the above, the present inventors have conducted intensive research and discovered that β-carotene has the effect of improving allergic rhinitis symptoms. In other words, the use of a composition containing β-carotene as a contributing component can improve allergic rhinitis symptoms. From this perspective, the present invention is defined as follows.

The contributing component of the composition for improving allergic rhinitis symptoms according to the present invention is β-carotene. The allergic rhinitis symptoms are at least one of eye symptoms and nasal symptoms, preferably at least one of watery eyes, sneezing, itchy nose, and stuffy nose, and more preferably sneezing.

The contributing component of the composition for improving the decline in QOL caused by allergic rhinitis symptoms according to the present invention is β-carotene. The allergic rhinitis symptoms are at least one of eye symptoms and nasal symptoms, preferably at least one of watery eyes, sneezing, itchy nose and stuffy nose, more preferably sneezing. The QOL is at least one of daily life, social life and sleep.

The contributing component of the composition for suppressing sneezing caused by allergic rhinitis symptoms according to the present invention is beta-carotene.

The present invention makes it possible to provide a new composition for improving allergic rhinitis symptoms. Furthermore, the present invention also makes it possible to provide a composition for improving the decline in QOL caused by allergic rhinitis and a composition for suppressing sneezing caused by allergic rhinitis.

Figure showing the number of sneezes in an OVA-sensitized allergy model mouse Figure showing the amount of OVA-specific IgE ((a) day 41 and (b) day 50) FIG. 1 shows the actual measured scores of severity classification of eyes and nose in Example 2 and the changes from week 0 of intake of the test food FIG. 1 shows the actual measured values of JRQLQ eye and nose symptoms in Example 2 and the changes from week 0 of test food intake. FIG. 1 shows the actual measured values of the JRQLQ QOL score in Example 2 and the change from week 0 of the intake of the test food. FIG. 1 shows the actual measured scores of severity classification in Example 3 and the changes from week 0 of intake of the test food FIG. 1 shows the actual measured values of JRQLQ eye and nose symptoms in Example 3 and the changes from week 0 of test food intake. FIG. 1 shows the actual measured values of QOL of JRQLQ in Example 3 and the change from week 0 of ingestion of the test food.

<Allergic rhinitis> The "allergic rhinitis" of the present invention is a disease in which a type I allergic reaction, i.e. an IgE-dependent reaction, occurs in the nasal mucosa. Symptoms of allergic rhinitis include repeated sneezing, watery nasal discharge, and nasal congestion. Allergic rhinitis is an allergy that is purely IgE-dependent, and symptoms appear only in areas where allergens are attached (near the nose and eyes). Allergic rhinitis is divided into perennial allergic rhinitis and seasonal allergic rhinitis. Seasonal allergic rhinitis includes hay fever.

<Composition for improving allergic rhinitis symptoms> The composition for improving allergic rhinitis symptoms according to the present invention contains β-carotene as a contributing component, and has an excellent effect of suppressing allergic rhinitis symptoms. The allergic rhinitis symptoms are at least one of eye symptoms and nasal symptoms. The allergic rhinitis symptoms are preferably at least one of watery eyes, sneezing, nasal itching, and nasal congestion, and more preferably sneezing.

<Composition for improving QOL decline caused by allergic rhinitis symptoms> The composition for improving QOL decline caused by allergic rhinitis symptoms according to the present invention contains β-carotene as a contributing component, and has the effect of improving QOL decline caused by allergic rhinitis symptoms. The allergic rhinitis symptoms are at least one of eye symptoms and nasal symptoms. The allergic rhinitis symptoms are preferably at least one of watery eyes, sneezing, nasal itching, and nasal congestion, and more preferably sneezing. The details of the QOL are at least one of daily life, social life, and sleep. The composition for improving QOL decline caused by allergic rhinitis symptoms according to the present invention is one embodiment of the composition for improving allergic rhinitis symptoms described above.

<Composition for suppressing sneezing caused by allergic rhinitis symptoms> The composition for suppressing sneezing caused by allergic rhinitis symptoms according to the present invention contains β-carotene as a contributing component, and has the effect of suppressing sneezing caused by allergic rhinitis symptoms. The composition for suppressing sneezing caused by allergic rhinitis symptoms according to the present invention is one embodiment of the composition for improving allergic rhinitis symptoms described above.

<β-carotene> There are no particular limitations on the β-carotene, and it may be a natural ingredient or a synthetic ingredient. When β-carotene is added as a natural ingredient, it may be added in the form of carrots containing β-carotene, their juice, algae, etc., or β-carotene extracted and purified from these raw materials may be added.

<Contributing ingredients> A contributing ingredient is a substance that affects the physiological functionality of the body. In foods for specified health uses and foods with functional claims, the equivalent of contributing ingredients are so-called "contributing ingredients" and "functional contributing ingredients." In the case of pharmaceuticals and quasi-drugs, they are so-called "active ingredients."

<Administration/ingestion form of the composition according to the present invention> The above-mentioned composition for improving allergic rhinitis symptoms, composition for improving a decrease in QOL caused by allergic rhinitis symptoms, and composition for suppressing sneezing caused by allergic rhinitis symptoms will be explained as compositions according to the present invention. The compositions according to the present invention include pharmaceutical compositions and food compositions. Details will be described later.

In the composition of the present invention, β-carotene is administered or ingested in an amount of 4.0 mg or more per day, preferably 4.2 mg or more, more preferably 4.4 mg or more, and even more preferably 4.7 mg or more. This daily amount can be administered or ingested all at once or in several divided doses, and may be administered or ingested before, after, or between meals.

As described later in the Examples, it has been confirmed that administering or ingesting a composition containing 4.0 mg or more of beta-carotene per day to a subject improves the symptoms of allergic rhinitis.

There is no particular upper limit to the daily dosage or intake of beta-carotene, but excessive intake may cause health problems. Therefore, the upper limit to the dosage or intake of beta-carotene is 15 mg per day, preferably 10 mg per day, and more preferably 6 mg per day.

The administration or intake period of the composition of this embodiment may be 4 weeks or more, preferably 6 weeks or more, and more preferably 8 weeks or more. As described later in the Examples, by continuously administering or ingesting the composition of the present invention for 4 weeks or more, the effect of improving allergic rhinitis tends to become more pronounced.

<Pharmaceutical composition> The composition according to the present invention may be a pharmaceutical composition containing β-carotene and a pharma- ceutical acceptable carrier. The pharmaceutical composition is preferably administered orally, and is preferably formulated in a dosage form for oral use. Examples of dosage forms for oral use include tablets, capsules, elixirs, microcapsules, and the like. Examples of pharma-ceutical acceptable carriers include binders such as gelatin, corn starch, gum tragacanth, and gum arabic; excipients such as starch and crystalline cellulose; and leavening agents such as alginic acid.

The pharmaceutical composition of this embodiment may contain additives. Examples of additives include lubricants such as calcium stearate and magnesium stearate; sweeteners such as sucrose, lactose, saccharin, and maltitol; flavorings such as peppermint and saffron oil; stabilizers such as benzyl alcohol and phenol; buffers such as phosphates and sodium acetate; solubilizers such as benzyl benzoate and benzyl alcohol; antioxidants; preservatives, etc.

The pharmaceutical composition of this embodiment can be formulated by appropriately combining the above carriers and additives and mixing them in a unit dose form required for generally accepted pharmaceutical practice. The pharmaceutical composition of this embodiment may be formulated, for example, to be administered orally once per day.

<Food composition> The composition of the present invention provides a food composition containing β-carotene as a contributing ingredient. As described later in the Examples, by ingesting the food composition of this embodiment, allergic rhinitis symptoms can be improved in humans or animals.

The shape and properties of the food, drink, feed, etc. containing the food composition of this embodiment are not particularly limited, and examples include solid, semi-solid, gel, liquid, powder, etc.

The food composition of this embodiment may be in the form of, for example, a supplement, a beverage, a gel food, any cooked food, or the like. The shape of the supplement is not important, but examples include capsules. When it is made into a beverage, vegetable beverages and vegetable and fruit beverages can be suitably selected.

<Food with functional claims> The food composition of this embodiment may be a food with functional claims. "Food with functional claims" refers to a food that has been notified to the Consumer Affairs Agency as a food that displays functionality on the product package based on scientific evidence. Examples of such claims include, but are not limited to, "relieves nasal discomfort caused by pollen, dust, house dust, etc.," "relieves eye and nasal discomfort caused by house dust and dirt," and "for people with nasal allergic reactions." In addition, even if a food does not have a functional claim, it is possible to manufacture and sell the food by advertising these functions in leaflets, emails, or verbally. As will be described later in the Examples, it has been confirmed that allergic rhinitis symptoms are improved by ingesting the food composition of this embodiment.

<Special purpose food> The food composition of this embodiment may be a special purpose food. Special purpose food means a food that, with government permission, is labeled with a special purpose such as being suitable for the development and maintenance/recovery of health of infants, young children, pregnant women, sick people, etc.

The food composition of this embodiment may be a food for medical patients, which is a special-purpose food. As described later in the Examples, the food composition of this embodiment has been confirmed to have an effect of improving allergic rhinitis.

The food composition of this embodiment may be a food for specified health uses, which is a type of food for special dietary uses. A food for specified health uses is a food that has been recognized based on scientific evidence to be useful in maintaining and promoting health, and is permitted to display that effect. The effects and safety of the foods displayed are examined by the government, and approval is given for each food by the Commissioner of the Consumer Affairs Agency. As described later in the Examples, the food composition of this embodiment has been confirmed to have an effect of improving allergic rhinitis symptoms.

The present invention will now be described in more detail with reference to examples, but the present invention is not limited to the following examples.

Allergic rhinitis symptoms were evaluated using a pollen allergy model mouse.

<Test foods> β-carotene (Sigma-Aldrich: C9750) was prepared in corn oil (Wako Pure Chemical Industries: WDL0579) as a medium at concentrations of 0.48 mg/mL and 4.8 mg/mL, and carrot concentrate (RD2 International) containing 0.48 mg/mL of β-carotene was also used.

<Test method> Forty 6-week-old BALB/c (female) mice (Japan SLC) were used to create a mouse model of allergic rhinitis caused by OVA antigen, and the efficacy of β-carotene was evaluated. After one week of acclimation, the 40 mice were randomly divided into five groups of eight mice each (unsensitized group, sensitized group, high-dose β-carotene group, low-dose β-carotene group, carrot juice group) as shown in Table 1. The categories are Control 1, Control 2, and Categories 1-3, respectively.

Other than the test food, the animals were given commercially available solid feed (Funabashi Farm: FR-2) and tap water, both of which were given ad libitum.

The day of grouping was designated as day 0. Primary and secondary sensitization was performed for the sensitized control 2 and categories 1 to 3 in Table 1 above. Primary sensitization was performed using an OVA antigen suspension. The OVA antigen suspension was prepared by mixing 100 μg/mL ovalbumin (Sigma-Aldrich: SLBD2313V) and 20 mg/mL Imject Alum (Thermo Fisher Scientific: SLBD2313V) in PBS (Wako Pure Chemical Industries: DSH7009). 200 μL of the OVA antigen suspension was administered subcutaneously per mouse near the base of the tail under anesthesia after 15, 22, and 29 days. The unsensitized group of control 1 received the same amount of PBS alone subcutaneously.

Secondary sensitization was performed using NAC solution and OVA antigen solution for the four sections after primary sensitization. NAC solution was prepared by dissolving N-acetyl-L-cysteine (WEF3303, Wako Pure Chemical Industries, Ltd.) in distilled water to a concentration of 15 mg/mL. OVA antigen solution was prepared by dissolving ovalbumin in PBS to a concentration of 2 mg/mL. After 31, 33, 35, 38, 41, 44, and 48 days, 10 μL of NAC solution was instilled into both nostrils, and approximately 5 minutes later, each nostril was washed twice with PBS (10 μL), and 10 μL of OVA antigen solution was instilled into both nostrils. For the unsensitized control group (Control 1), only PBS was instilled into both nostrils at 10 μL each.

Beta-carotene was orally administered using a disposable oral probe and syringe between 8:00 and 11:00 am every day from grouping until the 49th day, except for blood sampling days and the day of primary sensitization. Control 1 and Control 2 were orally administered corn oil alone.

<Number of sneezes> The number of sneezes was measured by videotaping the mice for 5 minutes after the secondary sensitization on days 35, 41, and 48. The mean ± standard error values of the number of sneezes (days 35, 41, and 48) in OVA-sensitized allergy model mice administered β-carotene and carrot juice for 49 days are plotted in Figure 1. Comparisons between the four groups, excluding control 1, were performed using one-way ANOVA, followed by the Tukey-Kramer test as a post-hoc test (*: P<0.05, **: P<0.01). Comparisons between control 1 and control 2 were performed using the Aspin Welch t-test ($$: P<0.01).

<Results> On all measurement days, the number of sneezes was significantly higher in the sensitized control 2 compared to the unsensitized control 1. On the 35th measurement day, no significant difference was observed between control 2 and categories 1-3, but category 1 had significantly fewer sneezes than category 3. On the 41st measurement day, categories 1-3 had significantly fewer sneezes than control 2. Also, on the 48th measurement day, both categories 1 and 2 had significantly fewer sneezes than control 2. Category 3 tended to have fewer sneezes than control 2 (P=0.087).

<Amount of OVA antigen-specific IgE in blood> Measurement of the amount of OVA antigen-specific IgE in plasma was performed on days 0, 41, and 50. Figure 2 shows the mean value + standard error of the amount of OVA antigen-specific IgE in plasma measured on days (a) 41 and (b) 50 in OVA-sensitized allergy model mice administered β-carotene and carrot juice for 49 days. Comparisons between the four groups excluding control 1 were performed using one-way ANOVA, followed by the Tukey-Kramer test (*: P<0.05) as a post-hoc test. Comparisons between control 1 and control 2 were performed using the Aspin Welch t test ($$: P<0.01).

<Results> The amount of OVA antigen-specific IgE before sensitization (day 0) was 0.00±0.00, 0.00±0.00, 0.37±0.37, 0.20±0.19, and 0.04±0.04 (au) for Control 1, Control 2, Category 1, Category 2, and Category 3, respectively. "au" is an abbreviation for Arbitrary Unit, and is an arbitrary unit. On both measurement days, the amount of OVA antigen-specific IgE was significantly increased in Control 2 compared to Control 1. Furthermore, on both measurement days, no significant differences were observed between Control 2 and Categories 1 to 3, but Category 1 showed significantly lower OVA antigen-specific IgE amounts compared to Category 3.

A randomized, double-blind, placebo-controlled, parallel-group comparative study was conducted as follows.

<Selection of research subjects> Only those who provided written informed consent of their own free will were eligible to be research subjects. A total of 40 research subjects were recruited, with 20 people in each group. The 40 people selected as research subjects were those who met the following selection criteria and were not suitable for the study, excluding those who were judged ineligible to be research subjects by the principal investigator or co-investigator.

<Selection Criteria> The selection criteria were: (1) healthy Japanese men and women not receiving any treatment or medication, (2) individuals aged 20 to 59 years at the time of obtaining consent, (3) individuals with subjective symptoms of perennial allergic rhinitis classified as mild to moderate, (4) individuals who tested positive for specific IgE (mite or house dust) in a blood allergy test, and (5) individuals who were determined to be eligible by the principal investigator or co-investigator.

<Grouping of study subjects> Study subjects were stratified by age, sex, and nasal symptoms. Nasal symptoms were stratified by severity classification score based on the "Guidelines for the Treatment of Nasal Allergies - Perennial Rhinitis and Hay Fever" (Life Sciences: 2020 Edition (Revised 9th Edition)) and the score on the Japanese Standard Quality of Life Questionnaire for Allergic Rhinitis (hereinafter referred to as "JRQLQ"). After that, subjects were randomly divided into two groups, a placebo food intake group (placebo group) and a test food intake group (β-carotene group) using a random number generation method so that there were 20 subjects per group. All subjects involved in the study were blinded, and the allocation table was not opened until the analysis subjects were fixed.

<Test Food> A vegetable and fruit mixed juice containing β-carotene (ingredients: carrot, apple, citric acid, flavoring, 200 mL/bottle) was used as the test food, and a vegetable and fruit mixed juice not containing β-carotene (ingredients: carrot, apple, lemon, citric acid, flavoring, 200 mL/bottle) was used as the placebo food. The nutritional components per bottle of the test food and placebo food are shown in Table 2. The test food and placebo food were produced in plain white containers so that the tester and the research subjects could not distinguish them by appearance.

<Test Method> All study subjects were required to consume one bottle of the test food per day during the test food intake period. They were required to record their severity classification scores every day from the start of pre-study observation until the end of test food intake. The JRQLQ questionnaire was completed a total of six times: -3, 0, 2, 4, 6, and 8 weeks after test food intake. In addition, the following restrictions were observed during the study period.

<Restrictions> The restrictions are: (1) Record the necessary information in a diary every day during the study period, (2) Maintain the same lifestyle (diet, exercise, sleep) as before the study, and avoid irregular lifestyles (binge drinking/eating, extreme dieting, staying up all night, etc.), (3) Refrain from using any new medicines, oral quasi-drugs, herbal medicines, or health foods (including supplements). However, if they are unavoidably used, record the details in the diary, and (4) Continue using any quasi-drugs, herbal medicines, or health foods (including supplements) without changing the dosage or method. If there are any changes, they must be recorded in the daily diary; (5) they are prohibited from taking health foods that claim to have anti-allergic effects, from using health foods (including supplements) that are high in carotenoids, and from taking vegetable juice or mixed vegetable and fruit juice; (6) they are to refrain from taking foods that are high in beta-carotene; (7) they are prohibited from taking alcohol or strenuous exercise the day before blood collection; (8) they are prohibited from eating or drinking anything, except for water or hot water, from 9 p.m. the night before blood collection until blood collection the following morning; (9) they are prohibited from participating in clinical trials that use other test foods, medicines, quasi-drugs, cosmetics, etc.; (10) they are prohibited from taking more than 200 mL of blood (such as donating blood) during the study period; (11) they are prohibited from leaking any information about the study to third parties other than those involved, and from posting or publishing it on the web, including social media; and (12) they are to follow any other instructions from the study's principal investigator and co-investigator.

<Evaluation method> The main evaluation items were the four nasal items of the severity classification (sneezing, runny nose, nasal congestion, nasal symptoms) and the six nasal items of the JRQLQ (runny nose, sneezing, stuffy nose, itchy nose, nasal symptoms, eye and nose symptoms). The severity classification score was recorded daily on a five-point scale of 0 (no symptoms), 1 (mild), 2 (moderate), 3 (severe), and 4 (very severe), and the recorded daily values were averaged for the three-week pre-observation period and every two weeks during the test food intake period and used for analysis. For the JRQLQ, subjects looked back every two weeks up to the two weeks prior to the recording date, and recorded the condition at the time when the symptoms were the worst on a five-point scale of 0 (no symptoms), 1 (mild), 2 (slightly mild), 3 (severe), and 4 (very severe), and these values were used for analysis.

Secondary evaluation items included three eye severity classification items (itchy eyes, tearing, eye symptoms), three JRQLQ eye items (itchy eyes, watery eyes, eye symptoms), and eight JRQLQ QOL items (daily life, outdoor life, social life, sleep, physical function, mental life, overall, overall condition).

<Statistical analysis> Mann-Whitney U test was used for between-group comparison of measured values and changes at each week, and Wilcoxon signed rank test with Bonferroni correction to account for multiplicity was used for within-group comparison with week 0. Both tests were performed at a significance level of 5%. EZR (EZR Version 1.40, R Commander Version 2.5-1) and SPSS (Ver. 15.0J) were used as statistical analysis software. Each evaluation item was expressed as the mean ± standard deviation. In Figures 3 to 5, values that showed significant differences in comparison between the β-carotene group and the placebo group were marked with *: p<0.05, and values that showed significant differences in comparison with week 0 of test food intake were marked with †: p<0.05, ††: p<0.01.

<Results> Figure 3 shows the actual measured values of the severity classification scores for the eyes and nose, and the change (Δ value) from week 0 of test food intake. No significant differences were found between the β-carotene group and the placebo group in either the actual measured values or the change in the severity classification scores for the nose. On the other hand, when compared to week 0 of test food intake, only the β-carotene group showed significantly lower values for sneezing (weeks 6 and 8 of intake) and nasal congestion (week 8 of intake). No significant differences were found between the β-carotene group and the placebo group in either the actual measured values or the change in the severity classification scores for the eyes. On the other hand, when compared to week 0 of test food intake, only the β-carotene group showed significantly lower values for itchy eyes and eye symptoms (both at week 8 of intake).

Figure 4 shows the actual measured values of JRQLQ eye and nose symptoms and the change (Δ value) from week 0 of test food intake. In terms of nose scores, the β-carotene group showed significantly lower scores for eye and nose symptoms (week 6 of intake) compared to the placebo group. Furthermore, compared to week 0 of intake, only the β-carotene group showed significantly lower scores for sneezing (weeks 6 and 8 of intake), nasal itching (week 8 of intake), nasal symptoms (week 8 of intake), and eye and nose symptoms (weeks 2, 6, and 8 of intake). In terms of eye scores, the β-carotene group showed significantly lower scores for watery eyes (week 8 of intake) and eye symptoms (weeks 6 and 8 of intake) compared to the placebo group.

Figure 5 shows the actual measured JRQLQ QOL scores and the change (Δ value) from 0 weeks of test food intake. Compared to the placebo group, the β-carotene group showed significantly lower scores in daily life (8 weeks of intake). Furthermore, compared to 0 weeks of intake, only the β-carotene group showed significantly lower scores in mental life (4, 6, and 8 weeks of intake) and overall (6 and 8 weeks of intake).

A randomized, double-blind, placebo-controlled, parallel-group comparative study was conducted as follows.

<Selection of study subjects> A total of 96 study subjects were recruited, with 48 people in each group. The 96 people selected were those who met the following selection criteria and were not suitable for the study, such as those who were judged ineligible to be study subjects by the principal investigator or co-investigator.

<Selection Criteria> The selection criteria were: (1) healthy Japanese men and women not receiving any treatment or medication, (2) individuals aged 20 to 59 years at the time of obtaining consent, (3) individuals with subjective symptoms of perennial allergic rhinitis classified as mild to moderate, (4) individuals with positive or suspected positive serum specific IgE (to either dust mites or house dust) in a pre-examination allergy test, and (5) individuals who were judged to be eligible by the principal investigator or co-investigator.

<Grouping of study subjects> The 96 people selected as study subjects were stratified by age, sex, and nasal symptoms (severity classification score). They were then randomly divided into two groups, a placebo food intake group (placebo group) and a test food intake group (β-carotene group), using a random number generation method so that there were 48 people per group. All people involved in the study were blinded, and the allocation table was not opened until the analysis subjects were determined.

<Test Food> A vegetable and fruit mixed juice containing β-carotene (ingredients: carrot, apple, citric acid, flavoring, 195 mL/bottle) was used as the test food, and a vegetable and fruit mixed juice not containing β-carotene (ingredients: carrot, apple, lemon, citric acid, flavoring, 195 mL/bottle) was used as the placebo food. The nutritional components per bottle of the test food and placebo food are shown in Table 3. The manufacturing and management methods were the same as in Example 2.

<Test Method> All study subjects were required to consume one bottle of the test food per day during the test food intake period. They were required to record their severity classification scores daily from the start of pre-study observation until the end of test food intake. The JRQLQ questionnaire was completed a total of six times: -6, 0, 2, 4, 6, and 8 weeks after test food intake. Additionally, during the study period, subjects were required to adhere to the same restrictions as in Example 2.

<Evaluation method> The main evaluation items were four nasal severity classification items (sneezing, runny nose, nasal congestion, nasal symptoms). The severity classification score was calculated by averaging the values recorded in the daily diary for the two weeks prior to observation and every two weeks during the test food intake period.

Secondary evaluation items included six JRQLQ nasal items (runny nose, sneezing, stuffy nose, itchy nose, nasal symptoms, eye and nose symptoms), three JRQLQ eye items (itchy eyes, watery eyes, eye symptoms), three JRQLQ eye items (itchy eyes, watery eyes, eye symptoms), and eight JRQLQ QOL items (daily life, outdoor life, social life, sleep, physical function, mental life, overall, overall state).

<Statistical analysis> Mann-Whitney U test was used for between-group comparison of measured values and changes at each week, and Wilcoxon signed rank test with Bonferroni correction to account for multiplicity was used for within-group comparison with week 0. Both tests were performed at a significance level of 5%. EZR (EZR Version 1.40, R Commander Version 2.5-1) and SPSS (Ver. 15.0J) were used as statistical analysis software. Each evaluation item was expressed as the mean ± standard deviation. In Figures 6 to 8, values that showed significant differences in comparison between the β-carotene group and the placebo group were marked with *: p<0.05, and values that showed significant differences in comparison with week 0 of test food intake were marked with †: p<0.05, ††: p<0.01, and †††: p<0.001.

<Results> Figure 6 shows the actual measured values of the severity classification scores and the changes (Δ values) from 0 weeks of ingestion of the test food. In the nasal severity classification scores, the β-carotene group showed a significant decrease in the changes in nasal discharge and nasal symptoms (both at 2 weeks of ingestion) compared to the placebo group. In the eye severity classification scores, no significant differences were found between the β-carotene group and the placebo group in either the actual measured values or the changes. Meanwhile, when compared to 0 weeks of ingestion, significant improvements were confirmed in all three items - itchy eyes, tearing, and eye symptoms - in both the β-carotene group and the placebo group.

The actual measured values of JRQLQ eye and nose symptoms and the change (Δ value) from week 0 of ingestion of the test food are shown in Figure 7. In terms of nose scores, the beta-carotene group showed a significantly lower change in sneezing (week 8 of ingestion) than the placebo group. In addition, compared to week 0 of ingestion, only the beta-carotene group showed significantly lower values for sneezing (weeks 4, 6, and 8 of ingestion), stuffy nose (week 8 of ingestion), and itchy nose (weeks 6 and 8 of ingestion). In addition, the placebo group also showed significantly lower values, but the beta-carotene group also showed significantly lower values for nasal symptoms and eye and nose symptoms (both at weeks 4, 6, and 8 of ingestion). In terms of eye scores, no significant difference was confirmed between the beta-carotene group and the placebo group in both the actual measured values and the change. On the other hand, the placebo group also showed significantly lower values, but the beta-carotene group also showed significantly lower values for watery eyes (weeks 4, 6, and 8 of ingestion) and eye symptoms (weeks 6 and 8 of ingestion).

Figure 8 shows the actual measured values of JRQLQ QOL and the change (Δ value) from 0 weeks of test food intake. Compared to the placebo group, the β-carotene group showed significantly lower values in social life and sleep (all at 8 weeks of intake). Furthermore, compared to 0 weeks of intake, only the β-carotene group showed significantly lower values in outdoor life, social life, sleep, mental life (all at 8 weeks of intake) and overall (at 8 weeks of intake). On the other hand, while the placebo group also showed significantly lower values, the β-carotene group also showed significantly lower values in daily life (at 6 and 8 weeks of intake) and overall state (at 6 and 8 weeks of intake).

The field in which this invention is useful is the health food field.

Claims (4)

A composition for improving a decrease in QOL caused by allergic rhinitis symptoms, comprising:
The QOL is at least one of social life and sleep,
The contributing component is beta-carotene.
The amount of β-carotene contained in the composition per day is 4.0 mg or more and 15 mg or less. 2. The composition of claim 1 ,
The allergic rhinitis symptoms are at least one of ocular symptoms and nasal symptoms. 3. The composition of claim 1 or 2,
The allergic rhinitis symptoms include at least one of watery eyes, sneezing, itchy nose, and stuffy nose. 4. The composition of claim 1, further comprising:
The allergic rhinitis symptom is sneezing.

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