JP2024060269A - Composition for suppressing nasal secretion - Google Patents

Abstract

[Problem] The object is to provide a composition for suppressing nasal secretion that can suppress nasal secretion. [Solution] The composition for suppressing nasal secretion is characterized by containing hesperidin with a daily intake of 200 mg or more and narirutin with a daily intake of 50 mg or less. [Selected Figure] None

Description

Application for application of Article 30, Paragraph 2 of the Patent Act has been filed (1) Disclosure Takahiro Deguchi, Yumiko Tokunaga, Takeshi Zeniya, Masao Enomoto, Kazuya Murata, Yuichi Endo Publication name Pharmacology and Treatment, Vol. 49, No. 11, pp. 1877-1887, Life Science Publishing Co., Ltd. Publication date November 20, 2021 (2) Disclosure Consumer Affairs Agency Website address https://www. fld. caa. go. jp/caaks/cssc02/? recordSeq=42210040230301 and 13 other items Posting date December 28, 2021 (3) Disclosure Consumer Affairs Agency Website address https://www. fld. caa. go. jp/caaks/cssc02/? recordSeq=42205301190201 and 13 others Date of publication January 26, 2022 (4) Publisher Nikkei BP Co., Ltd. Website address https://bio.nikkeibp.co.jp/atcl/news/p1/22/01/20/09051/ Date of publication January 25, 2022 (5) Publisher A-Pharma Kindai Co., Ltd. Website address https://a-pharma-kindai.co.jp/atcl/news/p1/22/01/20/09051/ jp/ and 2 others Date of publication: October 4, 2022 (6) Distributor: A-Pharma Kindai Co., Ltd. Website address: https://a-pharma-kindai.com/ and 2 others Date of launch: October 4, 2022 (7) Distributor: Kindai University Educational Corporation Website address: https://newscast.jp/news/8057185 Date of publication: October 4, 2022 (8) Distributor: A-Pharma Kindai Co., Ltd. Distribution: Kirindo Co., Ltd. Date of distribution: December 2, 2021

Application for application of Article 30, Paragraph 2 of the Patent Act filed (9) Discloser: A-Pharma Kindai Co., Ltd. Distribution location: ICT Co., Ltd. Distribution date: December 24, 2021 (10) Discloser: A-Pharma Kindai Co., Ltd. Distribution destination: Kirindo Co., Ltd. Distribution date: January 26, 2022 (11) Discloser: A-Pharma Kindai Co., Ltd. Distribution location: Oki Co., Ltd. Distribution date: April 15, 2022 (12) Discloser: A-Pharma Kindai Co., Ltd. Distribution location: ICT Co., Ltd. Distribution date: June 29, 2022 (13) Discloser: A-Pharma Kindai Co., Ltd. Distribution destination: Oki Co., Ltd. Distribution date: December 3, 2021 (14) Discloser: A-Pharma Kindai Co., Ltd. Distribution destination: Oki Co., Ltd. Distribution date: January 27, 2022 (15) Discloser: A-Pharma Kindai Co., Ltd. Distribution location: Kinki University Nara Hospital Distribution date: October 17, 2022 (16) Distributor: A-Pharma Kindai Co., Ltd. Distribution destination: Toseiban Printing Co., Ltd. Distribution date: January 5, 2022 (17) Distributor: Toseiban Printing Co., Ltd. Distribution destination: Nikko Gravure Printing Co., Ltd. Distribution date: March 11, 2022 (18) Distributor: A-Pharma Kindai Co., Ltd. Distribution location: A-Pharma Kindai Co., Ltd. General Meeting of Shareholders Distribution date: June 24, 2022

The present invention relates to a composition for suppressing nasal secretion that can suppress nasal secretion.

Rhinitis is inflammation of the mucous membrane of the nasal cavity, and allergic rhinitis is known as rhinitis caused by allergies. Allergic rhinitis can be broadly divided into two types: perennial allergic rhinitis, caused by allergens that are present regardless of the season, such as house dust, and seasonal allergic rhinitis, caused by allergens that are present in a specific season, such as cedar pollen. The main symptoms of both perennial and seasonal allergic rhinitis are nasal discharge (rhinorrhea), sneezing, and nasal congestion. These symptoms significantly reduce the quality of life (QOL) in daily life.

As a method for improving the symptoms of allergic rhinitis, drug therapy using drugs such as antihistamines and steroids is known, but in recent years, techniques using natural products have been developed. For example, Non-Patent Document 1 describes a technique that uses dried powder of Unshu mandarin fruit to improve the symptoms of allergic rhinitis.

Megumi Futamura (Masuda) et al., "Effect of foods containing unripe Unshu mandarin fruit on alleviating symptoms of perennial nasal hypersensitivity," Allergy and Immunology, 2016, Vol. 23, No. 7, pp. 106-116

In Non-Patent Document 1, to confirm whether symptoms of runny nose have improved, subjects are given a dried powder of Unshu mandarin fruit (hereinafter also referred to as "CUP") containing hesperidin and narirutin, so that the daily intake of hesperidin is 177 mg and the daily intake of narirutin is 53 mg, and the number of times the subjects blew their nose during the intake period is scored. According to this score, the score (number of times the subjects blew their nose) was significantly lower in the CUP-administered group compared to before CUP administration.

However, according to the score for the number of times nose-blowing described in Non-Patent Document 1, the CUP-administered group did not show a significant decrease in the score (number of times nose-blowing) compared with the placebo group. Since nasal discharge symptoms can become stronger or weaker depending on the observation period, even if the score (number of times nose-blowing) is significantly lower compared with before CUP administration, if there is no significant decrease in the score (number of times nose-blowing) compared with the placebo group taken at the same time, it cannot be said that nasal discharge has been suppressed by the administration of CUP. In other words, Non-Patent Document 1 does not provide a technology that can suppress nasal discharge.

The present invention aims to provide a composition for suppressing nasal secretion that can suppress nasal secretion.

The gist of the present invention is as follows.
[1] A composition for suppressing nasal secretion, comprising hesperidin in an amount of 200 mg or more per day and narirutin in an amount of 50 mg or less per day.
[2] The composition for suppressing nasal secretion according to [1], wherein the daily intake amount of the narirutin is 30 to 50 mg.
[3] The composition for suppressing nasal secretion according to [1], wherein the daily intake amount of the hesperidin is 200 to 300 mg.
[4] A composition for suppressing nasal secretion described in any one of [1] to [3], characterized in that it contains a dried powder of unripe Unshu mandarin fruit, and the hesperidin and narirutin are the hesperidin and narirutin contained in the dried powder.

The present invention provides a composition for suppressing nasal secretion that can suppress nasal secretion.

FIG. 1 shows the change in score over a period of 8 weeks after the start of tablet intake.

One embodiment of the present invention is described below.

This embodiment relates to a composition for suppressing nasal secretion that can suppress nasal secretion. In this specification, being able to suppress nasal secretion refers to a suppression of nasal secretion that is significantly different when compared with a placebo group (a group that took a placebo) taken at the same time. Furthermore, being significantly different refers to a significance probability of less than 5% (P<0.05). As a method for comparing groups, an appropriate significance test can be selected depending on the type of data, and for example, the Mann-Whitney U test can be used.

The composition for suppressing nasal secretion in this embodiment contains hesperidin and narirutin.

Hesperidin is a compound represented by the following formula (1) and is contained in citrus fruits such as Unshu mandarin, lemon, and Valencia orange.

Although chemically synthesized hesperidin may be used, from a safety standpoint it is preferable to use hesperidin derived from natural sources such as citrus fruits.

In the composition for suppressing nasal secretion of this embodiment, the amount of hesperidin ingested per day is 200 mg or more. In other words, hesperidin is contained in the composition for suppressing nasal secretion at a content such that the total amount of hesperidin contained in the composition for suppressing nasal secretion ingested per day is 200 mg or more. For example, if the composition for suppressing nasal secretion is in the form of a tablet and nine tablets are ingested per day, the content of hesperidin may be such that a total of 200 mg or more of hesperidin is ingested when nine tablets are ingested.

The daily intake of hesperidin should be 200 mg or more, and there is no upper limit, but from the viewpoint of further suppressing nasal secretion, it is preferable that the intake be 300 mg or less, and more preferably 250 mg or less.

Narirutin is a compound represented by the following formula (2) and is contained in citrus fruits such as satsuma mandarin, hassaku, sudachi, and grapefruit.

Although chemically synthesized narirutin may be used, from a safety standpoint, it is preferable to use narirutin derived from natural products such as citrus fruits.

In the composition for suppressing nasal secretion of this embodiment, the amount of narirutin ingested per day is 50 mg or less. In other words, narirutin is contained in the composition for suppressing nasal secretion at a content such that the total amount of narirutin contained in the composition for suppressing nasal secretion ingested per day is 50 mg or less. For example, if the composition for suppressing nasal secretion is in the form of a tablet and nine tablets are ingested per day, the content of narirutin may be such that a total of 50 mg or less of narirutin is ingested when nine tablets are ingested.

The daily intake of narirutin should be 50 mg or less, and there is no particular limit to the lower limit, but from the perspective of further suppressing nasal secretion, it is preferable that it be 30 mg or more, and more preferably 40 mg or more.

In the composition for suppressing nasal secretion of this embodiment, the content ratio of hesperidin to narirutin is not particularly limited as long as it satisfies the intake amount described above, but from the viewpoint of further suppressing nasal secretion, the content ratio of hesperidin to narirutin (hesperidin/narirutin) is preferably 4 or more, more preferably 4 or more and 5 or less, and particularly preferably 4.3 or more and 4.7 or less.

Here, satsuma mandarin fruit (fruit including the peel) contains both hesperidin and naringin. Therefore, by adding dried powder of satsuma mandarin fruit to the composition for suppressing nasal secretion of this embodiment, hesperidin and naringin may be added to the composition for suppressing nasal secretion. From the viewpoint of further suppressing nasal secretion, it is preferable to add dried powder of immature satsuma mandarins among dried powders of satsuma mandarin fruit.

An immature Satsuma mandarin refers to a fruit that is in the immature stage during the growth process after fruit set, before the skin turns yellow. A specific example of an immature Satsuma mandarin is a Satsuma mandarin that is harvested within three months of fruit set. The size of an immature Satsuma mandarin is, for example, a horizontal diameter (diameter perpendicular to the core) of 2.0 cm to 4.5 cm.

Furthermore, the dried powder of unshu mandarin fruit refers to dried powder of unshu mandarin fruit including the peel. The method of producing the dried powder of unshu mandarin fruit is not particularly limited, but for example, it can be obtained by cutting up unshu mandarin fruit including the peel, drying the cut pieces in the sun, in the shade, or using a dryer, and then pulverizing the dried material in a mixer, mill, or the like. The unshu mandarin fruit (including the peel) used for the processing of the dried powder may be frozen unshu mandarin fruit (including the peel). The particle size of the dried powder of unshu mandarin fruit is not particularly limited, but for example, it can be a particle size that passes through 100 mesh (mesh size 154 μm).

The content of narirutin and hesperidin can be quantified by reversed-phase chromatography using a liquid chromatograph ultraviolet spectrophotometer (HPLC-UV, Shimadzu Corporation, LC-20 series-SPD-20A). Quantification can be performed using the absolute calibration curve method, which compares the measured value with that of a standard sample. For example, three samples can be prepared for each measurement, and the average of the quantitative results can be used as the measurement result. Methanol can be added to the prepared measurement sample, ultrasonicated for 30 minutes, and then injected into the HPLC-UV to separate narirutin and hesperidin.

The HPLC-UV analysis conditions are, for example, as follows.
Column: Tosoh Corporation, TSKgel ODS-120T (5 μm, 250 mm × 4.6 mm i.d.)
Column oven temperature: 40°C
Mobile phase: flow rate 1.0 mL/min, mobile phase A:mobile phase B=8:2 (mobile phase A 0.1% phosphoric acid water, mobile phase B acetonitrile)
Detection wavelength: UV 280 nm

The composition for suppressing nasal secretion of this embodiment can be used for any purpose, such as medicines, quasi-drugs, or food and beverages. The method of ingestion (administration) of the composition for suppressing nasal secretion of this embodiment is not particularly limited, but can be, for example, orally ingested (administered).

The composition for suppressing nasal secretion of this embodiment may be composed only of narirutin and hesperidin that satisfy the intake amount described above, but may also contain other ingredients in addition to these. When the composition for suppressing nasal secretion of this embodiment is made into a medicine, a quasi-drug, or a food or drink, the other ingredients may include, for example, excipients such as reduced maltose syrup, binders such as edible oils and fats, stabilizers, disintegrants, lubricants, flavorings, suspending agents, coating agents, food and drink ingredients (for example, food ingredients contained in Satsuma mandarin fruit excluding hesperidin and narirutin), etc.

The dosage form of the composition for suppressing nasal secretion of this embodiment is not particularly limited and can be set appropriately. For example, when the improving agent of this embodiment is a medicine, a quasi-drug, or a food or drink, it can be in the dosage form of tablets, pills, capsules, granules, powders, dust, syrup, etc.

In particular, when the composition for suppressing nasal secretion of this embodiment is used as a food or drink, it may be a normal food or drink, but it may also be a health functional food such as a food for specified health uses, a food with nutritional functions, or a food with functional claims. Specific examples of food or drink include nutritional supplements, milk, processed milk, milk drinks, soft drinks, alcoholic beverages, non-alcoholic beer, fermented milk, yogurt, cheese, bread, biscuits, crackers, pizza crust, ice cream, candy, gummies, chewing gum, infant formula, liquid food, food for the sick, foods such as powdered milk for infants, and foods such as powdered milk for breastfeeding women.

The frequency of ingestion of the composition for suppressing nasal secretion of this embodiment is not particularly limited, but can be, for example, 1 to 3 times a day. The period of ingestion of the composition for suppressing nasal secretion of this embodiment can be, for example, 7 weeks or more.

The composition for suppressing nasal secretion of this embodiment can be produced by a conventional method by appropriately mixing narirutin and hesperidin that satisfy the intake amounts described above, and other ingredients that are included as necessary, and there are no particular limitations on the production method or production conditions.

The composition for suppressing nasal secretion of the present embodiment described above can suppress the secretion of nasal secretion. An example of nasal secretion that can be suppressed is nasal secretion caused by allergies (nasal secretion that is increased due to allergies).

The present invention will be explained in more detail below with reference to examples, but the present invention is not limited to these.

[Dried powder of immature Unshu mandarins]
Immature unshu mandarin fruits (about one month after fruiting) grown in the Arida region of Wakayama Prefecture were harvested. The harvested unshu mandarins were frozen, cut, and dried at a low constant temperature of 50° C. with far-infrared rays. The resulting dried product was sterilized using a sterilizer and then crushed using a flour mill to obtain a dried powder of immature unshu mandarin with a particle size passing through a 100 mesh (hereinafter also referred to as "CUP").

Quantification by reverse phase chromatography using a liquid chromatograph ultraviolet spectrophotometer (HPLC-UV, Shimadzu Corporation, LC-20 series-SPD-20A) revealed that 1.71 g of CUP contained 215 mg of hesperidin and 48 mg of narirutin.

The HPLC-UV analysis conditions were as follows:
Column: Tosoh Corporation, TSKgel ODS-120T (5 μm, 250 mm × 4.6 mm i.d.)
Column oven temperature: 40°C
Mobile phase: flow rate 1.0 mL/min, mobile phase A:mobile phase B=8:2 (mobile phase A 0.1% phosphoric acid water, mobile phase B acetonitrile)
Detection wavelength: UV 280 nm

[CUP Tablets (Example 1)]
1.71 g of CUP, 256.5 mg of reduced maltose syrup (Amalty MR-50 manufactured by Mitsubishi Corporation Foodtech Co., Ltd.), and 103.5 mg of edible oil and fat (TP-9 manufactured by NOF Corp.) were mixed, and the resulting mixture was tableted (compressed) to obtain 9 tablets (hereinafter also referred to as "CUP tablets"). The resulting 9 CUP tablets were used as one day's worth of test food (Example 1).

[Placebo tablet (Comparative Example 1)]
A coloring matter (a mixture of Caramel SF-720 manufactured by Ikeda Tohka Kogyo Co., Ltd. and Saf Yellow SP1000 manufactured by Yaegaki Hakko Giken Co., Ltd.) that would give the same color as the CUP tablets, and a citrus flavoring (Dry Coat Grapefruit #3261 manufactured by Takada Fragrance Co., Ltd.) that would give the same flavor as the CUP tablets were prepared. 12.2 mg of the mixture of the prepared coloring matter and citrus flavoring, 1860.6 mg of reduced maltose syrup, and 197.1 mg of edible oils and fats (TP-9 manufactured by NOF Corp.) were mixed, and the resulting mixture was tableted (compressed) to obtain 9 tablets (hereinafter also referred to as "placebo tablets"). The obtained 9 placebo tablets were used as one day's worth of test food (Comparative Example 1).

[subject]
Candidates for subjects were adult men and women aged 20 to 64 who regularly suffered from nasal discharge (rhinorrhea) symptoms and did not regularly use medicines to alleviate the symptoms. These candidates were given a one-week observation period for symptoms of nasal discharge (rhinorrhea), and underwent a preliminary test, including a health check. Based on the results of the preliminary test, 80 subjects who were judged by the otolaryngologist who was the responsible physician to have symptoms of nasal discharge caused by allergies (allergies to house dust and mites) were randomly assigned to two groups (the placebo group and the CUP group, described below).

The allocation person created an allocation list using random numbers and assigned an allocation number to the test foods. The allocation list was sealed by the allocation person and kept sealed until it was time to open it. The allocation was kept out of sight of the subjects and doctors.

[test]
A randomized, double-blind, placebo-controlled, parallel-group comparative study was conducted on two groups: a group taking placebo tablets (hereinafter also referred to as the "placebo group") and a group taking CUP tablets (hereinafter also referred to as the "CUP group"). The subjects in the placebo group took nine placebo tablets per day every day during the study period. The subjects in the CUP group took nine CUP tablets per day every day during the study period. The time of tablet intake (study period) was the same for the placebo group and the CUP group.

Subjects in the placebo and CUP groups recorded their nasal discharge symptoms in a diary every day for 8 weeks before and after starting to take the tablets. The items to be recorded in the diary were created in accordance with the nasal allergy diary shown in the Nasal Allergy Treatment Guidelines (Nasal Allergy Treatment Guidelines Creation Committee, Nasal Allergy Treatment Guidelines, Perennial Rhinitis and Hay Fever, Life Sciences, 2016 and 2020), and subjects were asked to evaluate nasal discharge (number of times they blew their nose) on a 5-point scale. The 5-point evaluation criteria were as follows:
<Evaluation criteria>
Score 0: Less than 1 time per day Score 1: 5-1 time per day Score 2: 10-6 times per day Score 3: 20-11 times per day Score 4: 21 or more times per day

For each of the placebo and CUP groups, the average nasal discharge score for the 8 weeks before starting to take the tablets (hereinafter also referred to as the "pre-ingestion score") was calculated, and the average nasal discharge score for each week of the 8 weeks after starting to take the tablets (hereinafter also referred to as the "post-ingestion score") was calculated. For each week of the 8 weeks after starting to take the tablets, the difference between the post-ingestion score and the pre-ingestion score (= "post-ingestion score" - "pre-ingestion score") was calculated, and the amount of change in score before and after taking the tablets (hereinafter also referred to as the "amount of score change") was calculated.

In addition, the change in scores each week over the 8 weeks after starting to take the tablets was compared between the placebo group and the CUP group using the Mann-Whitney U test. Statistical analysis was performed using IBM SPSS Statistics version 26 and Microsoft Excel, and the significance level for both was set at less than 5% (P<0.05) in a two-sided test.

Of the 80 subjects who participated in the study, three subjects were excluded from the evaluation because they were not evaluated during the eighth week of the observation period.

The results are shown in Figure 1. Table 1 shows the specific scores before ingestion, the change in score four weeks after starting to take the tablets, and the change in score eight weeks after starting to take the tablets. In Figure 1 and Table 1, the values show the mean value ± standard error.

As shown in Figure 1, the CUP group taking the CUP tablets showed a significantly larger change in nasal mucus score compared to the placebo group taking the placebo tablets at weeks 7 and 8. From this result, it was understood that the CUP tablets of Example 1 taken at a dose of 9 tablets per day can suppress the secretion of nasal mucus.

Claims (4)

A composition for suppressing nasal secretion, comprising hesperidin in an amount of 200 mg or more per day and narirutin in an amount of 50 mg or less per day. The composition for suppressing nasal secretion according to claim 1, characterized in that the daily intake of narirutin is 30 to 50 mg. The composition for suppressing nasal secretion according to claim 1, characterized in that the daily intake of the hesperidin is 200 to 300 mg. Contains dried powder of immature Unshu mandarin fruit,
4. A composition for suppressing nasal secretion according to claim 1, wherein the hesperidin and narirutin are those contained in the dry powder.