Composition for improving bowel movements

Abstract

The present invention addresses the problem of providing a means for improving bowel movements. The present invention provides a composition for improving bowel movements, the composition containing apple polyphenol.

Description

Composition for improving bowel movements

[0001] The present invention relates to a composition for improving bowel movements.

[0002] Constipation is a condition in which feces remain in the large intestine, resulting in infrequent bowel movements or the inability to comfortably excrete feces in the rectum, and is accompanied by symptoms such as rabbit-like or hard stools, excessive straining, a feeling of incomplete evacuation, a feeling of blockage in the rectum and anus, and difficulty in defecation. Constipation is broadly divided into organic and functional constipation. Organic constipation is caused by endocrine disorders, collagen diseases, neurological diseases, etc., whereas functional constipation has no underlying cause and is characterized by symptoms of difficulty in defecation, decreased frequency of defecation, or incomplete evacuation, and is thought to be caused by lifestyle, psychological, or behavioral factors.

[0003] Constipation is a common symptom among adults, affecting approximately 2-10% of the Japanese population, with a particularly high prevalence among women and the elderly. Poor nutrition, lack of sleep, lack of exercise, and psychological stress are suggested causes of constipation. Furthermore, constipation has been reported to increase the risk of more serious complications, such as cardiovascular disease and kidney disease, and to be associated with increased mortality. Therefore, in Japan, where the population is rapidly aging, the appropriate prevention and treatment of constipation is an urgent issue.

[0004] Lifestyle improvements and dietary therapy are thought to be effective methods for relieving constipation, and specific examples include the intake of dietary fiber, oligosaccharides, disaccharides, monosaccharides or polyols, and polyphenols. Water-soluble dietary fiber and oligosaccharides, disaccharides, monosaccharides or polyols are utilized by the intestinal flora to produce short-chain fatty acids, which in turn promote the production of serotonin, which stimulates intestinal motility. It is thought that constipation is relieved by regulating intestinal motility via serotonin. On the other hand, polyphenols are thought to alleviate constipation through the action of the enteric nervous system and bile acids. In a study using a constipation model animal, naringenin, a type of polyphenol, was shown to increase Cl levels in the colonic epithelium via a signaling pathway involving an increase in intracellular cyclic adenosine monophosphate and activation of protein kinase A. -It has been suggested that it contributes to increased secretion and exerts a laxative effect by providing osmotic pressure to the subsequent secretion of large intestinal fluid.

[0005] Furthermore, regarding the effect of apples in improving constipation, it has been reported that when a constipation model rat ingested apple juice, the amount of bile acids in the feces increased (Non-Patent Document 1). Since a lack of bile acids in the intestinal tract can cause constipation, it has been suggested that ingesting apple juice may improve constipation. However, the ingested components in this study were apple juice, which contains a large amount of water-soluble components such as carbohydrates, and the effects of ingesting apple polyphenols were not evaluated.

[0006] Furthermore, in a clinical trial evaluating the effects of ingesting foods containing apple polyphenols and oleanolic acid on weight loss and waist circumference reduction, it was reported that bowel movements (questionnaire survey) in the intake group were significantly improved compared to the placebo group (Non-Patent Document 2), but there have been no reports on the bowel movement-improving function of apple polyphenols alone. Regarding the bowel movement-improving function of oleanolic acid, mouse studies have reported that it promotes intestinal peristalsis (Non-Patent Document 3) and optimizes the intestinal bacterial flora (Non-Patent Document 4). In other words, no research has been reported that actually investigated the effect of apple polyphenols alone on bowel movements.

[0007] Food Funct. 2023;14(10):4836-46. Clinical Practice and New Drugs 2016;53(3):237-244. Gastroenterology 2013 jan;144(1):145-154. J Sci Food Agric. 2022 Jan 30;102(2):764-773.

[0008] In view of the above circumstances, an object of the present invention is to provide a new means for improving bowel movements.

[0009] As a result of extensive research aimed at solving the above problems, the present inventors have found that ingestion of apple polyphenols improves bowel movements. Based on this finding, the present invention has been completed.

[0010] That is, the gist of the present invention relates to the following. [1] A composition for improving bowel movements, comprising apple polyphenols. [2] The composition, wherein the apple polyphenols are derived from unripe apples. [3] The composition, wherein the apple polyphenols comprise procyanidins. [4] The composition, wherein the procyanidins are procyanidin B2. [5] The composition, wherein the improvement in bowel movements is an improvement in one or more of bowel movements frequency and number of days with bowel movements. [6] The composition, wherein the content of apple polyphenols in the composition is 1% by weight or more. [7] The composition, wherein the composition is prepared so that apple polyphenols are ingested at a dose of 30 mg to 900 mg per day. [8] The composition, wherein the composition is an oral composition. [9] The composition, wherein the composition is a food or beverage.

[10] The composition, wherein the composition is a food or beverage additive.

[0011] The present invention can also be embodied in the following aspects.

[11] Apple polyphenols for use in improving bowel movements.

[12] Use of apple polyphenols for improving bowel movements.

[13] Use of apple polyphenols for the manufacture of a composition for improving bowel movements.

[14] A method for improving bowel movements, comprising administering apple polyphenols to a subject.

[15] A method for preventing, improving, and / or treating bowel movement disorders, comprising administering apple polyphenols to a subject.

[0012] The present invention provides a new means for improving bowel movements.

[0013] Figure 1 is a flowchart showing the follow-up of participants in the study. Figure 2 shows the results of the study (changes in number of days with bowel movements, number of bowel movements, and amount of stool). The results of the bowel movement diary during the study period are shown as the mean and standard deviation. *P < 0.05 (placebo group). In Figure 2, A indicates the number of days with bowel movements, B indicates the number of bowel movements, and C indicates the amount of stool. The number of days with bowel movements, number of bowel movements, and amount of stool were total values ​​over 7 days. The amount of stool was calculated based on the size of a film case-type container (volume 20 mL, dimensions 26 mm, bottle height 54.5 mm, total height 57.0 mm) and expressed as the number of containers the stool amount was equivalent to. Period 1 (P1), 7 days before the start of ingestion; Period 2 (P2), from the start of ingestion to the 7th day of ingestion; Period 3 (P3), from the 8th day of ingestion to the 14th day of ingestion; Period 4 (P4), from the 15th day of ingestion to the 21st day of ingestion; Period 5 (P5), from the 22nd day of ingestion to the 28th day of ingestion; Period 6 (P6), from the 29th day of ingestion to the 35th day of ingestion; Period 7 (P7), from the 36th day of ingestion to the 42nd day of ingestion; Period 8 (P8), from the 43rd day of ingestion to the 49th day of ingestion; Period 9 (P9), from the 50th day of ingestion to the 56th day of ingestion; Period 10 (P10), from the 57th day of ingestion to the 63rd day of ingestion; Period 11 (P11), from the 64th day of ingestion to the 70th day of ingestion; Period 12 (P12), from the 71st day of ingestion to the 77th day of ingestion; Period 13 (P13), 7 days before the test date after 12 weeks of ingestion. Figure 3 shows the test results of the example (proportion of stool shape). The proportion of subjects with different stool shapes during the study period for each group is shown in Figure 3. A in the apple polyphenol group (n = 12) and B in the placebo group (n = 11).Period 1 (P1), 7 days before the start of ingestion; Period 2 (P2), from the start of ingestion to the 7th day of ingestion; Period 3 (P3), from the 8th day of ingestion to the 14th day of ingestion; Period 4 (P4), from the 15th day of ingestion to the 21st day of ingestion; Period 5 (P5), from the 22nd day of ingestion to the 28th day of ingestion; Period 6 (P6), from the 29th day of ingestion to the 35th day of ingestion; Period 7 (P7), from the 36th day of ingestion to the 42nd day of ingestion; Period 8 (P8), from the 43rd day of ingestion to the 49th day of ingestion; Period 9 (P9), from the 50th day of ingestion to the 56th day of ingestion; Period 10 (P10), from the 57th day of ingestion to the 63rd day of ingestion; Period 11 (P11), from the 64th day of ingestion to the 70th day of ingestion; Period 12 (P12), from the 71st day of ingestion to the 77th day of ingestion; Period 13 (P13), 7 days before the test date after 12 weeks of ingestion. Figure 4 shows the test results (percentage of stool odor) of the example. The proportion of subjects with stool odor during the test period for each group is shown in Figure 4. A in Figure 4 shows the apple polyphenol group (n = 12), and B in Figure 4 shows the placebo group (n = 11). Period 1 (P1), 7 days before the start of ingestion; Period 2 (P2), from the start of ingestion to the 7th day of ingestion; Period 3 (P3), from the 8th day of ingestion to the 14th day of ingestion; Period 4 (P4), from the 15th day of ingestion to the 21st day of ingestion; Period 5 (P5), from the 22nd day of ingestion to the 28th day of ingestion; Period 6 (P6), from the 29th day of ingestion to the 35th day of ingestion; Period 7 (P7), from the 36th day of ingestion to the 42nd day of ingestion; Period 8 (P8), from the 43rd day of ingestion to the 49th day of ingestion; Period 9 (P9), from the 50th day of ingestion to the 56th day of ingestion; Period 10 (P10), from the 57th day of ingestion to the 63rd day of ingestion; Period 11 (P11), from the 64th day of ingestion to the 70th day of ingestion; Period 12 (P12), from the 71st day of ingestion to the 77th day of ingestion; Period 13 (P13), 7 days before the test date after 12 weeks of ingestion. Figure 5 shows the test results of the example (percentage of feeling refreshed when defecate). The percentage of subjects who felt refreshed during bowel movements during the test period for each group is shown in Figure 5. A in Figure 5 shows the apple polyphenol group (n = 12), and B in Figure 5 shows the placebo group (n = 11).Period 1 (P1), 7 days before the start of intake; Period 2 (P2), from the start of intake to day 7 of intake; Period 3 (P3), from day 8 of intake to day 14 of intake; Period 4 (P4), from day 15 of intake to day 21 of intake; Period 5 (P5), from day 22 of intake to day 28 of intake; Period 6 (P6), from day 29 of intake to day 35 of intake; Period 7 (P7), from day 36 of intake to day 42 of intake; Period 8 (P8), from day 43 of intake to day 49 of intake; Period 9 (P9), from day 50 of intake to day 56 of intake; Period 10 (P10), from day 57 of intake to day 63 of intake; Period 11 (P11), from day 64 of intake to day 70 of intake; Period 12 (P12), from day 71 of intake to day 77 of intake; Period 13 (P13), 7 days before the test date 12 weeks after intake.

[0014] The present invention will be described below. However, the present invention is not limited to the following preferred embodiments, and can be freely modified within the scope of the present invention.

[0015] In the present invention, "apple polyphenols" refers to polyphenols originally contained in apples, and does not refer to the source of extraction. In other words, polyphenols with the same structure as polyphenols contained in apples are included in the apple polyphenols of the present invention. Furthermore, "apple polyphenols" not only refers to polyphenols with the same structure as polyphenols contained in apples, but also includes derivatives with partially different structures, as long as they maintain the effects required for the present invention.

[0016] <Composition for Improving Bowel Movements> One aspect of the present invention relates to a composition for improving bowel movements (hereinafter, sometimes referred to as "the composition of the present invention") containing apple polyphenols.

[0017] <Apple Polyphenol> The composition of the present invention contains apple polyphenol as an active ingredient. The composition of the present invention may contain only apple polyphenol as an active ingredient, or may contain ingredients other than apple polyphenol. Preferably, the composition of the present invention does not contain oleanolic acid.

[0018] The content of apple polyphenols in the composition is not limited, but may be, for example, 1% by weight or more, 3% by weight or more, 5% by weight or more, 7% by weight or more, 8% by weight or more, 9% by weight or more, 10% by weight or more, or 11% by weight or more, or 100% by weight or less, 90% by weight or less, 80% by weight or less, 70% by weight or less, 60% by weight or less, 50% by weight or less, 40% by weight or less, 30% by weight or less, 20% by weight or less, or 15% by weight or less, or any combination thereof that is compatible with these. The content may be, for example, 1 to 100% by weight. The content of apple polyphenols can be analyzed, for example, by high-performance liquid chromatography. More specifically, it can be analyzed by the method described in the Examples below.

[0019] Apple polyphenols, the active ingredient of the composition of the present invention, can be obtained, for example, by extraction from apples (fruit, peel, pulp, etc.). In the present invention, apple polyphenols may be derived from either ripe or unripe apples, but are particularly preferably derived from unripe apples. Apple polyphenols may be in the form of an extract containing apple polyphenols, or may be pure apple polyphenols purified by known purification methods. The extract may be dried and powdered.

[0020] The method for extracting apple polyphenols is not particularly limited, and any appropriate method may be selected, including those commonly used by those skilled in the art. For example, extraction can be performed on plants by procedures such as solvent suspension, drying, mechanical crushing, squeezing, and solvent extraction. These extraction procedures can be performed alone or in combination. Solvents used for extraction include water and organic solvents such as chloroform, hexane, acetone, methanol, and ethanol, and can be selected appropriately. Drying can be performed using conventional methods such as tray drying, fluidized bed drying, flash drying, and spray drying. Mechanical pulverization can be performed using either a wet or dry method, such as a bead mill, roll mill, hammer mill, jet mill, or pin mill. Compression can be performed using conventional methods.

[0021] Apple polyphenols can be prepared by known methods such as those described above, but commercially available products such as ApplePhenon (registered trademark) available from BGG Japan Co., Ltd. can also be used.

[0022] The apple polyphenol may contain procyanidins, and is preferably procyanidins. Procyanidins belong to the flavan-3-ol group of flavonoids and are oligomers or polymers (2-15 mers) formed by condensation of epicatechin or catechin. The procyanidins are not limited to, but may be, for example, procyanidin B, which is a dimer, or procyanidin B2, which is a polymer of (-)-epigallocatechin.

[0023] Procyanidins are contained in apple polyphenols at, but not limited to, 1% by weight or more, 5% by weight or more, or 10% by weight or more, and 70% by weight or less, 50% by weight or less, or 30% by weight or less. Procyanidins are contained in apple polyphenols at, but not limited to, 10 to 30% by weight. In addition to procyanidins, apple-derived polyphenols may also contain catechins, phenolic carboxylic acids, phloretin glycosides, and the like.

[0024] The content of procyanidins in the composition of the present invention is not limited, and may be, for example, 1% by weight or more, 5% by weight or more, 10% by weight or more, or 11% by weight or more, or 100% by weight or less, 30% by weight or less, 20% by weight or less, or 15% by weight or less, or any compatible combination thereof. The content may also be, for example, 1 to 100% by weight.

[0025] As shown in the Examples below, the composition of the present invention contains apple polyphenols as an active ingredient, and administration of the composition of the present invention to a subject produces an excellent effect of improving bowel movements in the subject. That is, the composition of the present invention can be used for improving bowel movements. Here, "improvement of bowel movements" may particularly refer to improvement of constipation, and may also refer to improvement in the number of bowel movements and / or the number of days with bowel movements over a predetermined period of time. The "predetermined period" is not limited, and may be, for example, one week, one month, or three months.

[0026] Furthermore, "improving bowel movements" also means improving bowel movements to a more favorable state compared to when the composition of the present invention is not taken, or conversely, preventing bowel movements from becoming unfavorable, and particularly means increasing the number of bowel movements and / or the number of days with bowel movements that have decreased, or suppressing a decrease in the number of bowel movements and / or the number of days with bowel movements. That is, the composition of the present invention may be used by people who are experiencing poor bowel movements, or may be used prophylactically by people who are experiencing poor bowel movements.

[0027] The composition of the present invention exerts the above-mentioned effects when administered to humans or non-human target animals. The target of administration may be not only humans but also non-human mammals, for example, livestock such as pigs, and pets such as dogs and cats. There are no particular limitations on the administration method, but oral administration is preferred, for example. Here, "administration" may be substituted with "ingestion."

[0028] Subjects for whom the composition of the present invention is used include, but are not limited to, subjects with constipation (e.g., fewer than three bowel movements per week), subjects prone to constipation (e.g., three to five bowel movements per week), subjects desiring to prevent constipation, etc. More preferred subjects include, but are not limited to, subjects with constipation, those prone to constipation, or subjects desiring to prevent constipation, and those with a high BMI (e.g., 25 kg / m ２ More than 30kg / m ２ (less than 18 years old) are included.

[0029] Furthermore, although not limited thereto, the present invention is preferably applied to healthy individuals. In the present invention, a "healthy individual" refers to an individual who has not been diagnosed with a disease that affects bowel movements. The "healthy individual" also refers to an individual who is not a hospitalized patient or undergoing medical treatment, but is living a normal life.

[0030] The daily intake of the composition of the present invention can be adjusted depending on the subject's gender, age, weight, symptoms, or the level of effect desired. It is not limited, but may be, for example, 30 mg or more, 50 mg or more, 60 mg or more, 70 mg or more, 80 mg or more, 90 mg or more, or 100 mg or more of apple polyphenols, or 900 mg or less, 800 mg or less, 700 mg or less, 600 mg or less, 500 mg or less, 400 mg or less, 300 mg or less, 200 mg or less, or 110 mg or less, or any compatible combination thereof. Furthermore, the daily intake of the composition of the present invention may be, for example, 30 to 900 mg of apple polyphenols. The composition of the present invention may be taken once a day or in divided doses. In this specification, the daily intake refers to the amount consumed by an adult per day.

[0031] The composition may be, but is not limited to, a food or beverage, a food or beverage additive (which may also be referred to as a "food or beverage additive" or "material for food or beverage additives"), a pharmaceutical product, or the like.

[0032] <Foods, Drinks, etc. of the Present Invention> The composition of the present invention may be provided as a food or drink. That is, the active ingredient apple polyphenols may be made into a food or drink either as is or in combination with other food and drink ingredients. Examples of food and drink ingredients to be combined with apple polyphenols include known food and drink ingredients, sweeteners, flavorings, excipients, coloring agents, etc. The food and drink of the present invention can be produced by referring to known production techniques commonly used in this field.

[0033] The form of the food or drink is not particularly limited, and can be any form such as liquid, paste, gel, solid, etc. The form of use of the composition is also not particularly limited as long as the effects of the present invention can be obtained, and can be any form such as drink, syrup, cream, jelly, powder, granules, tablets, soft capsules, hard capsules, etc. In particular, the present invention is preferably used in the form of capsules.

[0034] The forms of the food and beverages of the present invention include ordinary foods, beverages, health foods, health supplements, foods for the sick, nutritional supplements, supplements, and health functional foods (functional food, nutritional functional food, specified health food), etc., and include all those in a form that is taken orally, but functional food is particularly preferred.

[0035] When the food or drink of the present invention is used as a composition for improving bowel movements, the food or drink may be labeled with information about its usefulness and functionality when it is commercialized. Specifically, such information may be attached to the packaging container of the functional food.

[0036] Such "indication" acts include all acts for informing consumers of the above-mentioned uses, and any expression that can evoke or infer uses such as "regulating stomach condition" or "improving bowel movements" falls under the category of "indication" acts of the present invention, regardless of the purpose of the indication, the content of the indication, the object or medium on which it is displayed, etc.

[0037] The composition of the present invention may also be provided as a food and drink additive for improving bowel movements, which is used as an additive to be added to the above-mentioned foods and drinks.

[0038] When the composition of the present invention is used as a food or beverage additive, the active ingredient, apple polyphenols, may be used as is or combined with other ingredients for food or beverage additives to form the food or beverage additive. There are no particular restrictions on the other ingredients for food or beverage additives that can be combined with the active ingredient, apple polyphenols. If necessary, a base material or carrier acceptable for foods or beverages may be added, and the composition may be formulated into tablets, granules, capsules, pills, powders, liquids, powders, jellies, candies, or other forms using known formulation methods, and used as a food or beverage additive.

[0039] The composition of the present invention may be provided as a pharmaceutical for improving bowel movements. That is, the active ingredient, apple polyphenols, may be used alone or in combination with other pharmaceutical ingredients to form a pharmaceutical composition. There are no particular restrictions on the other pharmaceutical ingredients to be combined with the active ingredient, apple polyphenols. If necessary, pharmaceutically acceptable bases or carriers may be added, and the composition may be formulated into tablets, granules, capsules, pills, powders, liquids, powders, jellies, candies, and other forms by known formulation methods, and used as an oral preparation.

[0040] The composition of the present invention may be used alone, but can also be used in combination with a known composition for improving bowel movements. By using them in combination, it is expected that the improving effect will be enhanced. The composition for improving bowel movements to be used in combination may be contained as a component of the composition of the present invention, or may be formulated separately from the composition of the present invention and used together at the time of use, as long as it does not weaken or eliminate the effect of the composition of the present invention.

[0041] <Use of the Present Invention> Another aspect of the present invention relates to the use of apple polyphenols for improving bowel movements. Furthermore, yet another aspect of the present invention relates to the use of apple polyphenols for the manufacture of a composition for improving bowel movements.

[0042] The present invention also relates to apple polyphenols for use in improving bowel movements.

[0043] <Method of the Present Invention> One aspect of the present invention relates to a method for improving bowel movements, which comprises administering apple polyphenols to a subject. Another aspect of the present invention relates to a method for preventing, ameliorating, and / or treating bowel movement disorders, which comprises administering apple polyphenols to a subject. Here, bowel movement disorders may particularly include, but are not limited to, constipation.

[0044] According to the method of the present invention, by administering the active ingredient apple polyphenols to a subject, bowel movements can be improved in the subject, that is, a bowel movement improving effect can be obtained.

[0045] Furthermore, by administering the active ingredient, apple polyphenols, to a subject according to the method of the present invention, it is possible to prevent, improve, and / or treat bowel movement disorders in the subject, i.e., the effects of preventing, improving, and / or treating bowel movement disorders can be obtained.

[0046] It should be noted that "administering an active ingredient to a subject" may be synonymous with "allowing a subject to ingest the active ingredient." Intake may be voluntary (free intake) or forced (forced intake). That is, the administration step may specifically be, for example, a step of incorporating the active ingredient into a food or drink and supplying it to the subject, thereby allowing the subject to ingest the active ingredient freely. Administration may be oral administration or parenteral administration. Administration may usually be oral administration. Examples of parenteral administration include tube administration and rectal administration.

[0047] The mode of administration of the active ingredient (e.g., the subject, the timing of administration, the duration of administration, the number of administrations, the dosage, and other conditions related to administration) is not particularly limited as long as the desired effects of the active ingredient, such as the effects described above, can be obtained. The mode of administration of the active ingredient can be appropriately determined depending on various conditions, such as the type of active ingredient, the type, age, and health condition of the subject.

[0048] The subject to which the active ingredient is administered is not particularly limited, as long as the desired effects of the active ingredient, such as the effects described above, can be obtained. The description of the subject to which the "composition of the present invention" is administered can be applied mutatis mutandis to the subject to which the active ingredient is administered.

[0049] The dosage of the active ingredient is not particularly limited as long as the desired effects, such as the effects described above, of the active ingredient can be obtained. The dosage of the active ingredient can be the same as that of the "composition of the present invention."

[0050] The administration period of the active ingredient may be, for example, 1 week or more, 4 weeks or more, 8 weeks or more, or 12 weeks or more. The active ingredient may be administered, for example, once a day, or in divided doses per day. The active ingredient may also be administered, for example, every day, or once every few days. The active ingredient may particularly be administered every day. The dosage of the active ingredient at each administration may or may not be constant.

[0051] For example, the active ingredient may be administered to a subject as is, or may be prepared as a composition, such as a food or beverage or pharmaceutical containing the active ingredient, and then administered to a subject. The description of the composition of the present invention applies mutatis mutandis to compositions containing the active ingredient. The active ingredient may also be administered alone or in combination with other ingredients. Examples of other ingredients include foods or beverages, pharmaceuticals, and ingredients contained therein. These other ingredients may or may not be intended for use in the above-mentioned applications based on the effects of the active ingredient (such as for improving bowel movements, preventing, improving, and / or treating bowel movement disorders).

[0052] The active ingredient can also be administered to a subject, for example, using the composition of the present invention (i.e., by administering the composition of the present invention). That is, the method of the present invention may be a method comprising a step of administering the composition of the present invention to a subject. That is, "administration of an active ingredient" also encompasses administration of the composition of the present invention. The administration mode of the composition of the present invention (e.g., the subject, administration time, administration period, number of administrations, dosage, and other administration conditions) is not particularly limited as long as the desired effects, such as the above-mentioned effects of the active ingredient, are obtained. The administration mode of the composition of the present invention can be appropriately determined depending on various conditions, such as the type and content of the active ingredient, the type and content of other ingredients, the type and form (dosage form) of the composition, the type, age, and health condition of the subject. The above-mentioned description of the administration mode of the active ingredient also applies mutatis mutandis to the administration of the composition of the present invention to a subject. That is, the composition of the present invention can be administered to, for example, subjects such as those exemplified above. Furthermore, the dosage of the composition of the present invention can be determined so as to obtain, for example, the dosage of the active ingredient as exemplified above. Furthermore, the composition of the present invention may be administered alone or in combination with other ingredients, such as foods and beverages, pharmaceuticals, and ingredients contained therein.

[0053] In the present invention, apple polyphenols may be used for therapeutic or non-therapeutic purposes. That is, unless otherwise specified, all of the effects exemplified above may be obtained for therapeutic or non-therapeutic purposes. "Therapeutic purposes" may mean, for example, treatment of the human body, etc. for therapeutic purposes, and may particularly mean that the treatment is carried out as a medical procedure. "Non-therapeutic purposes" may mean, for example, not including treatment of the human body, etc. for therapeutic purposes, and may particularly mean that the treatment is carried out as a non-medical procedure. Non-therapeutic purposes include health promotion, beauty, etc.

[0054] "Preventing a disease" can mean, for example, preventing or delaying the onset of a disease, or reducing the likelihood of developing a disease. "Ameliorating a disease" or "treating a disease" can mean, for example, reversing a disease, preventing or delaying the worsening of a disease, or preventing or delaying the progression of a disease.

[0055] The matters explained above regarding the composition of the present invention are all applicable to the method and use of the present invention.

[0056] The present invention will be specifically described below with reference to examples, but these are merely examples of the present invention and the scope of the present invention is not limited to these examples.

[0057] [Quantitative determination of apple polyphenol content] The active ingredient, apple polyphenol, is qualitatively and quantitatively analyzed using the high-performance liquid chromatography (HPLC) method shown below. The procyanidin content of "apple polyphenol" was measured using procyanidin B2 as a standard reagent.

[0058] 1. Reagents and Equipment 1-1. Reagents used: Urea (special reagent grade), hydrochloric acid (special reagent grade), acetonitrile (HPLC grade), procyanidin B2, 0.2% acetic acid (procyanidin B2 standard) - Manufactured by EXTRASYNTHESE (obtained from Funakoshi Co., Ltd.), product code 0984 - Purity 90% or more (HPLC)

[0059] 1-2. Equipment used: HPLC equipment equipped with a fluorescence detector, pH meter

[0060] 1-3. HPLC conditions Column: TSKgel a-2500 (7.8 x 300 mm) particle size: 7 μm Guard column: TSKgel guard column α (6.0 x 40 mm) particle size: 13 μm Mobile phase: 0.2 mol / L urea (pH 2.0) and acetonitrile (1:1) Flow rate: 0.5 mL / min Injection volume: 10 μL Column temperature: room temperature Fluorescence excitation wavelength: 276 nm Fluorescence measurement wavelength: 316 nm

[0061] 2. Preparation of mobile phase: Weigh 12.0 g of urea into a 2 L or 3 L beaker and add 1 L of miliQ® water to dissolve. While measuring the pH with a pH meter, add 6N HCl dropwise to adjust the pH to 2.0. Transfer this to a 2 L medium bottle, then add 1 L of acetonitrile and mix well. Degas the mixture thoroughly using a sonicator and aspirator.

[0062] 3. Preparation of Apple Polyphenol Extract (AP) Sample Aqueous Solution: After crushing the AP in a mill, weigh out one grain, add 200 ml of milliQ water, and extract (shake) for 10 minutes. Then, in a 250 ml measuring flask, add milliQ water to the measuring solution. Record the sample weight to one decimal place (preferably two decimal places). Dilute the above aqueous solution 10 times using an appropriate measuring flask and volumetric pipette.

[0063] 4. Standard Stock Sample Preparation: Weigh out approximately 6 mg of procyanidin B2 into a 100 ml volumetric flask and dilute to a volume of 0.2% acetic acid (approximately 60 ppm). Measure the weight of procyanidin B2 with the lid on and record to two decimal places. Dispense 500 μL of this into assist tubes and store frozen at -20°C or below. Note: Procyanidin is unstable when stored in solution or in direct sunlight, so store frozen immediately. Also, do not refreeze standard samples that have been thawed and used.

[0064] 5. Preparation of standard dilution series: Thaw the standard stock completely and mix well before use. Using an Eppendorf tube and a micropipette, dilute it two-fold by mixing 200 μL:200 μL of the stock with 0.2% acetic acid. Repeat this process twice more to prepare a four-level standard dilution series.

[0065] 6. Calculation of procyanidin content: Measure the peak area at rt 10-27.5 min (all peak areas eluting before this, including PB2) using fluorescence detection for the AP sample solution and the standard sample. Create a calibration curve from the standard sample measurement results, calculate the slope (A) and intercept (B), and calculate the procyanidin content (%) in the sample according to the following formula:

[0066]

[0067] [Subjects and Methods] <Study Design> This study was a randomized, placebo-controlled, double-blind, parallel-group comparative study. The allocation ratio was 1:1. After receiving approval from the Takara Clinic Ethics Committee of Seishinkai Medical Corporation (approval date: February 15, 2023, approval number: 2302-00607-0034-11-TC), this study was registered with UMIN-CTR (registration number: UMIN000050393). Furthermore, the study was conducted with due consideration for medical ethics, in accordance with the Declaration of Helsinki and the ethical guidelines for life science and medical research involving human subjects.

[0068] <Study Participants> The selection criteria for this study were as follows: (a) Japanese, (b) both men and women, (c) adults, (d) healthy individuals, (e) individuals with a bowel movement frequency of 3 to 5 times per week, and (f) a BMI of 25 kg / m 2 More than 30 kg / m 2Those under 18 years of age. The A. muciniphila values ​​from the screening and pre-intake test (Scr) were taken into consideration. The following conditions were excluded from participation in the study. (a) Subjects currently undergoing treatment for or with a history of malignant tumors, heart failure, or myocardial infarction; (b) Subjects with a pacemaker or implanted cardioverter defibrillator; (c) Subjects currently undergoing treatment for arrhythmia, liver damage, kidney damage, cerebrovascular disease, rheumatism, diabetes, dyslipidemia, hypertension, or other chronic diseases; (d) Subjects who regularly consume foods for specified health uses or foods with functional claims; (e) Subjects who regularly use medicines (including herbal medicines) or supplements; (f) Subjects with allergies (to medicines or test food-related foods), especially to apples, apricots, almonds, plums, peaches, pears, strawberries, birch, etc.; (g) Subjects who are pregnant, breastfeeding, or intend to become pregnant during the study period; (h) Subjects with COVID-19; (i) Subjects who have participated in other clinical trials in the 28 days prior to the date of consent acquisition, or who plan to participate during the study period; (j) (k) Anyone who is judged by the investigator to be inappropriate for this study, (k) Anyone who regularly consumes foods / drinks containing ingredients that are thought to affect the intestinal environment (dietary fiber, indigestible dextrin, isomaltodextrin, inulin, guar gum hydrolysate, fructooligosaccharides, galactooligosaccharides, lactulose, lactic acid bacteria, bifidobacteria, butyric acid bacteria, natto bacteria, maltobionic acid, fucose, cocoa polyphenols, raffinose, kestose, polydextrose, lactose oligosaccharides, xylooligosaccharides, isomaltooligosaccharides, psyllium, resistant starch, galactomannan, glucomannan, etc.).

[0069] Study participants were recruited through Go Toroku (https: / / www.go106.jp / ), a monitor recruitment website operated by Ortho Medico Co., Ltd. (Bunkyo-ku, Tokyo). Those who wished to participate in the study were given a full explanation of the study details via the internet or in person, and their consent was obtained electronically or in writing. Study participants did not include anyone affiliated with the study's organizers or funding companies. The study was conducted by Takara Clinic (Shinagawa-ku, Tokyo), a medical corporation affiliated with Seishinkai Medical Corporation, which evaluated the data obtained and managed the health of study participants, but testing was carried out in collaboration with Minamimachi Clinic (Nerima-ku, Tokyo), a cooperating medical institution.

[0070] <Sample size> The target number of cases will be 20, the maximum number that can be achieved within the study budget. In addition, to take into account dropouts during the study period, two more people will participate in each group, making the total number of cases to be implemented 24.

[0071] Selection, Randomization, and Blinding: Of the 32 participants who agreed to participate in this study, the principal investigator enrolled 24. The test food was provided by the sponsor to the contracted clinical trial organization. The test food shipping staff at the contracted clinical trial organization confirmed the anonymity of the test food and entered and confirmed the data in the Scr. After notifying the identification number to the randomization officer (not directly involved in the study), the randomization list for this study was generated using SPSS Ver. 23.0 for Windows (IBM Japan, Chuo-ku, Tokyo). Block randomization was used, and the randomization officer randomly assigned 12 participants to the apple polyphenol group and 12 to the placebo group according to a computer-generated randomization list. The randomization list was provided only to the test food shipping staff at the contracted clinical trial organization, who then sent the test food to the participants enrolled in the study according to the randomization list. The subjects of blinding were the principal investigator, the principal investigator, the sub-investigator, all staff at the medical institution conducting the trial, including the person in charge of shipping the test food (study manager, implementation management manager, monitor, statistical analysis person / manager, etc.), staff at the trial institution, members of the ethics committee, and the clinical testing institution.The allocation list was sealed and stored by the person in charge of allocation until the cases and statistical analysis method were fixed.

[0072] Intervention: This study used ApplePhenon as the apple polyphenol. ApplePhenon is a food product made by extracting and purifying polyphenols from unripe apples, sold by BGG Japan, Inc., to a high degree of purity. The main component of apple polyphenols is procyanidin, with other components including catechin, phenolcarboxylic acid, and chalcone. Each tablet of the apple polyphenol-containing food contained 150.0 mg of apple polyphenols (27.5 mg of apple-derived procyanidins), 84.5 mg of starch, 5.0 mg of calcium stearate, and 2.5 mg of silicon dioxide. Each tablet of the placebo food contained 242.5 mg of microcrystalline cellulose, 5.0 mg of calcium stearate, and 2.5 mg of silicon dioxide. Participants were instructed to take four tablets of either the apple polyphenol-containing food or the placebo food once daily (600 mg of apple polyphenols / day, 110 mg of apple-derived procyanidins / day) with water or lukewarm water after breakfast for 12 weeks. All test foods were in the form of hard capsules, and during ethical review prior to the start of the study, it was confirmed that the test foods and placebo foods could not be distinguished by color, smell, or flavor.

[0073] <Evaluation items> The test schedule is shown in Table 1. Efficacy evaluation items were recorded daily in diary format from 7 days before the start of intake until the day before the final examination, and other efficacy evaluation items were conducted at Scr and at the examination 12 weeks after intake (12w). Safety evaluation items were measured at Scr and 12w.

[0074]

[0075] (1) Bowel movement diary The bowel movement diary was used to evaluate the number of bowel movements, number of days with bowel movements, amount of stool, shape, odor, and feeling of refreshment during the test period.

[0076] The number of defecations and the number of days of defecation were evaluated based on the number of times recorded in the bowel movement diary. The amount of stool was evaluated by calculating the number of containers equivalent to the size of a film case type container No. 7 (volume 20 mL, dimensions 26 mm, bottle height 54.5 mm, total height 57.0 mm; Kawashige Co., Ltd., Chiyoda-ku, Tokyo).

[0077] Regarding shape, stool shape was classified into eight categories on a stool shape scale, and participants were asked to select the appropriate category ("1. Watery diarrhea, excretion rate is rapid," "2. Porridge-like, flat surface, excretion rate is moderately rapid," "3. Porridge-like, uneven surface," "4. Shape is starting to lose its shape," "5. Cylindrical, smooth surface," "6. Cylindrical, with cracks on the surface," "7. Cylindrical, with deep cracks," "8. Fragmented or rabbit droppings-like (like deer or rabbit droppings)"). Regarding odor, there were five categories: "1. The odor has become much stronger," "2. The odor has become a little stronger," "3. Same as usual," "4. The odor has become a little weaker," and "5. The odor has become much weaker," and regarding refreshing feeling, there were three categories: "1. Feeling refreshed," "2. Normal," and "3. Feeling like there is still stool left."

[0078] The evaluation period and evaluation value were as follows: Period 1 (P1) is the 7 days before the start of intake, Period 2 (P2) is the 7th day from the start of intake, Period 3 (P3) is the 8th to 17th day of intake, Period 4 (P4) is the 15th to 21st day of intake, Period 5 (P5) is the 22nd to 28th day of intake, Period 6 (P6) is the 29th to 35th day of intake, Period 7 (P7) is the 36th to 42nd day of intake, Period 8 (P8) is the 43rd to 49th day of intake, Period 9 (P9) is the 50th to 56th day of intake, Period 10 (P10) is the 57th to 63rd day of intake, Period 11 (P11) is the 64th to 70th day of intake, Period 12 (P12) is the 7 days before 12 weeks of intake, and Period 13 (P13) is the 7 days before 12 weeks of intake. The number of bowel movements, number of days of bowel movements, and amount of stool were calculated as totals for each 7-day period. The average values ​​for each survey item, shape, odor, and feeling of freshness, were calculated for each 7-day period and rounded to the nearest integer.

[0079] In this study, the primary outcome was the number of bowel movements on P13, and other items were secondary outcomes.

[0080] (2) Safety Items: Safety evaluation items included checking for the occurrence of adverse events during the study period, and physical measurements, physical examinations, urinalysis, and peripheral blood tests were conducted. The number of adverse events was tallied. If symptoms recognized as adverse events occurred, the principal investigator immediately took necessary and appropriate measures and decided whether the participant could continue the study and whether the emergency key could be unlocked. The principal investigator also evaluated the relationship between the adverse events and the test food and reported the results in writing.

[0081] To confirm the health status of the study participants, a medical interview and a dietary survey using the Calorie and Nutrition Diary (CAND) were conducted on each test day. Study participants were also asked to record daily information about their lifestyle, including intake of test foods, changes in their physical condition, and medication use.

[0082] <Statistical analysis> All statistical analyses were performed using two-sided tests, with a significance level set at 5%. The software used was SPSS Ver. 23.0 for Windows (IBM Japan, Chuo-ku, Tokyo) and Microsoft Excel 2013 (Microsoft Japan, Minato-ku, Tokyo). This study focused on the primary outcome, and did not take into account the multiplicity that occurs in secondary outcomes set as multiple hypotheses.

[0083] Regarding participant background, gender is shown as the number of men and women in the group, and other items are shown as means and standard deviations. Comparisons between groups were performed using the chi-square test for gender and Welch's t-test for other items.

[0084] The number of days with defecation, frequency of defecation, and amount of stool were shown as means and standard deviations, and the difference between groups was the difference between the apple polyphenol group and the placebo group (Scr was the difference in means, and after intervention, the difference in estimated marginal means), with its 95% confidence interval (CI) shown. Shape, odor, and refreshing sensation were shown as the number of people affected and the proportion in the group, and the difference between groups was shown as the difference in the proportion affected in the apple polyphenol group from the proportion affected in the placebo group, with its 95% CI shown.

[0085] Comparisons of each item between groups for number of days with bowel movements, frequency of bowel movements, and stool volume were performed using a linear mixed model with time point, group, time point and group interaction, and study participant as factors. Comparisons of shape, odor, and refreshing sensation were performed using the chi-square test.

[0086] For safety evaluation, the number of subjects who experienced adverse events was tallied, and the 95% CI of the incidence rate within the group and the difference in incidence rate between groups (the difference between the apple polyphenol group and the placebo group) was calculated. Additionally, the proportion of subjects whose urinalysis and peripheral blood test values ​​for Scr, which were within the reference range, fell outside the reference range after intervention, was tallied for each study participant. The subjects who experienced changes and their incidence rates were tallied by group, and the 95% CI of the incidence rate by group and the difference in incidence rate between groups (the apple polyphenol group minus the placebo group) was calculated. The incidence rates were compared between groups using the chi-square test. Additionally, the principal investigator checked other safety evaluation items on an individual and group basis to confirm that no medically significant changes occurred due to the intake of the test food.

[0087] The handling of the datasets in this study was defined as follows at the time of study planning: Intention to treat is all cases that provided informed consent and were enrolled in the study. The full analysis set (FAS) is the set obtained by excluding cases that fit one or more of the following conditions from the entire registered population set: (1) cases that did not receive the allocated intervention, (2) cases that do not meet the conditions for the target population (cases with a definitive diagnosis of some disease or cases that meet clearly defined, objectively assessable important inclusion / exclusion criteria), (3) cases that never received the intervention after allocation, and (4) cases with no post-allocation data. The per protocol set is the set obtained by excluding cases that fit one or more of the following conditions from the FAS. (1) Cases with an intake rate of less than 80% of the test food, (2) Cases with significant behavior that undermines the reliability of the study results, such as missing diary records, (3) Cases whose exclusion criteria were found to apply after study enrollment, (4) Cases found to have violated compliance during the study period, (5) Cases who ingested foods or medications during the study period that are expected to significantly affect the study results, (6) Cases who engaged in activities that significantly differed from their lifestyle at the time of study enrollment, and (7) Other cases for which there were clear reasons that made exclusion appropriate. The Safety Analysis Population (SAF) was defined as a group from the entire enrollment population excluding cases that met one or more of the following conditions: (1) Cases who did not receive the allocated intervention, (2) Cases who never received the intervention after allocation, and (3) Cases for which safety evaluation items were never measured after allocation.

[0088] [Results] <Analysis subjects> Figure 1 shows the follow-up flowchart for study participants. Participants were recruited between March 10 and March 22, 2023, and the study period was from May 31 to September 5, 2023. One subject did not return at 12 weeks (i.e., never received the intervention after allocation) and was therefore excluded from analysis. The final analysis subjects were the Full Analysis Set, consisting of a total of 12 subjects in the apple polyphenol group (6 men, 6 women, 49.2 ± 9.0 years old) and 11 subjects in the placebo group (6 men, 5 women, 50.3 ± 12.2 years old). The background of the study participants is shown in Table 2. No significant differences were observed between the groups in any background factors.

[0089]

[0090] In addition, the mean and standard deviation of the intake rate of the test food in this study were 100.6 ± 0.5% for FAS and SAF in the apple polyphenol group and 100.1 ± 1.8% for FAS and SAF in the placebo group.

[0091] <Number of days with defecation, frequency of defecation, and stool volume> No significant differences were observed between the groups in the number of days with defecation, frequency of defecation, or volume of defecation during the non-intervention period, P1. Regarding the frequency of defecation after the intervention, the apple polyphenol group showed a significantly higher value than the placebo group at P13 (apple polyphenol group: 7.0 ± 2.1 times, placebo group: 4.9 ± 1.4 times, between-group difference: 2.1 times [95% CI 0.0 to 4.2], P = 0.048; Figure 2). The number of days with bowel movements was also significantly higher in the apple polyphenol group than in the placebo group at P4, P5, P7, P8, P9, P11, and P13 (P4, apple polyphenol group: 6.0 ± 1.1 days, placebo group: 4.5 ± 0.9 days, difference between groups: 1.5 days [95% CI 0.4 to 2.6], P = 0.006; P5, apple polyphenol group: 5.7 ± 1.6 days, placebo group: 4.1 ± 1.2 days, difference between groups: 1.6 days [95% CI 0.5 to 2.7], P = 0.005; P7, apple polyphenol group: 5.8 ± 1.5 days, placebo group: 4.4 ± 1.1 days, difference between groups: 1.5 days [95% CI 0.4 to 2.6], P = 0.005). 2.6], P = 0.009; P8, apple polyphenol group: 5.6 ± 1.2 days, placebo group: 4.5 ± 1.3 days, difference between groups: 1.1 days [95%CI 0.0 to 2.2], P = 0.044; P9, apple polyphenol group: 5.8 ± 1.1 days, placebo group: 4.7 ± 1.2 days, difference between groups: 1.1 days [95%CI 0.0 to 2.2], P = 0.048; P11, apple polyphenol group: 5.8 ± 1.1 days, placebo group: 4.2 ± 1.8 days, difference between groups: 1.6 days [95%CI 0.5 to 2.7], P = 0.006; P13, apple polyphenol group: 5.8 ± The mean stool volume was 1.0 day in the control group, 4.4 ± 1.3 days in the placebo group, and 1.4 days [95% CI 0.3 to 2.5] in the placebo group (p = 0.014; Figure 2). No significant difference was observed between the apple polyphenols group and the placebo group in stool volume.

[0092] <Stool shape, odor, and refreshing feeling> In the item regarding stool shape, the proportion of subjects who answered "it's starting to lose its shape" was significantly lower in the apple polyphenol group than in the placebo group at P7 (apple polyphenol group: 1 subject [8.3%], placebo group: 5 subjects [45.5%], between-group difference: -37.1% [95% CI -73.0 to -1.2], P = 0.04; Table 3), but no significant between-group differences were observed after that period. Furthermore, when the proportion of subjects in each group regarding stool shape during the study period was confirmed, many subjects answered that it was "cylindrical with a smooth surface" (Table 3, Figure 3).

[0093]

[0094]

[0095] No significant differences were observed between groups regarding odor and feeling of freshness during the intervention period, but most participants responded that the odor was "no different from usual" and the feeling of freshness was "normal" (Figures 4 and 5, respectively).

[0096] <Safety> One adverse event was observed in the placebo group (incidence rate 9.1%) during the study period (difference in incidence rate -9.1% [95% CI -25.8, 7.6%]). The adverse event reported by the one subject in the placebo group at their own discretion included headache, dyspepsia, and esophagitis, but the principal investigator determined that none of the symptoms were causally related to the test food. Furthermore, there were no significant differences in the proportion of cases in which the measured values ​​of urine tests and peripheral blood tests, which had Scr data within the reference range, fell outside the reference range after the intervention (data not shown). Furthermore, taking into account the individual data for other safety items, it was deemed that these changes were not medically significant. For the other participants, the principal investigator checked each item on an individual basis and found that no medically problematic changes had occurred due to the intake of the test food.

[0097] [Discussion] In this study, the subjects with a high BMI (25 kg / m 2 More than 30 kg / m 2Subjects who were self-consciously aware of their condition (less than 18 months) and prone to constipation (3-5 bowel movements per week) were asked to take a test food containing apple polyphenols, including apple-derived procyanidins, for 12 weeks to examine the effects on the intestinal environment and blood lipids.

[0098] While no significant difference was observed between the groups in weekly bowel movements at P1 (before the intervention), the number of bowel movements after the intervention at P13 was significantly higher in the apple polyphenol group than in the placebo group. The mean and standard deviation were 7.0 ± 2.1 times in the apple polyphenol group and 4.9 ± 1.4 times in the placebo group, with a difference of 2.1 times (95% CI 0.0 to 4.2). Next, when the number of days with bowel movements per week for each group was examined, no significant difference was observed between the groups at P1, as with the number of bowel movements, but the apple polyphenol group showed significantly higher values ​​than the placebo group at P4, P5, P7, P8, P9, P11, and P13. These results indicate that the bowel movement frequency in the apple polyphenol group after the intervention was higher than that of the placebo group.

[0099] An internet survey of 15,000 general Japanese men and women aged 20 to 79 years reported that the mean and standard deviation of weekly bowel movements among 5,155 respondents (2,542 men and 2,613 women) was 6.9 ± 4.2 times. Furthermore, a cohort study of 45,112 Japanese individuals aged 40 to 79 years (21,669 men and 23,443 women) followed for 13.3 years found that the odds of death from cardiovascular disease in the group with a bowel movement frequency of once per 2 to 3 days (2.3 to 3.5 times per week) was 1.21 (95% CI 1.08 to 1.35) compared with the group with a bowel movement frequency of once per day (7 times per week) or more. Considering these reports, in subjects with low bowel frequency, increasing bowel frequency to more than seven times per week after intervention may bring bowel frequency closer to the general population and may be associated with a reduced risk of death from cardiovascular disease. The change in weekly bowel frequency in each group before and after the 12-week intervention in this study was 5.5 ± 2.8 to 7.0 ± 2.1 times in the apple polyphenol group and 5.8 ± 3.7 to 4.9 ± 1.4 times in the placebo group. While the bowel frequency in the placebo group remained below seven times per week before and after intervention, it exceeded seven times per week in the apple polyphenol group after intervention, suggesting that intake of the test food product resulted in a medically significant improvement in bowel frequency.

[0100] In this study, patients with a high BMI (25 kg / m 2 More than 30 kg / m 2 This study examined the effects of 12 weeks of ingesting a food containing apple polyphenols, including apple-derived procyanidins, on the intestinal environment and blood lipids in subjects with a normal bowel movement rate (less than 180°C) and who perceived themselves as prone to constipation (3-5 bowel movements per week). The results confirmed that the number of bowel movements per week and the number of days with bowel movements, which were the focus of this study, were significantly improved by ingesting a food containing apple polyphenols. Furthermore, the intake of the test food was safe under the conditions of this study.

[0101] The present invention is useful in the fields of foods and beverages, food and beverage additives, pharmaceuticals, and the like.

Claims

1. A composition for improving bowel movements, comprising apple polyphenols.

2. The composition of claim 1, wherein the apple polyphenols are derived from unripe apples.

3. The composition of claim 1, wherein the apple polyphenols include procyanidins.

4. The composition according to claim 3, wherein the procyanidin is procyanidin B2.

5. The composition according to claim 1, wherein the improvement in bowel movements is one or more improvements selected from the frequency of bowel movements and the number of days of bowel movements.

6. The composition according to claim 1, wherein the content of apple polyphenols in the composition is 1% by weight or more.

7. The composition of claim 1, wherein the composition is formulated to be taken at a dose of 30 mg to 900 mg of apple polyphenols per day.

8. The composition of claim 1, wherein the composition is an oral composition.

9. The composition according to claim 7, which is a food or drink.

10. The composition according to claim 1, which is a food or beverage additive.

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