Composition for improving intestinal environment

Abstract

To provide a composition for improving intestinal environment that can improve intestinal environment through adjustment of intestinal bacterial flora balance.SOLUTION: The composition for improving intestinal environment comprises microalgae.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a composition for improving the intestinal environment. [Background technology]

[0002] Recently, the nutritional components contained in microalgae (such as chlorella and euglena) have been attracting attention, and efforts are underway to use them in health foods and food ingredients. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Patent Publication No. 2021-013313 Summary of the Invention [Problem to be solved by the invention]

[0004] Japanese Patent Application Laid-Open Publication No. 2021-013313 (Patent Document 1) discloses microalgae of the Pavlovaceae family that contain high concentrations of fucoxanthin, dietary fiber, eicosapentaenoic acid, gamma (γ)-aminobutyric acid, etc. However, there have been few reports to date of the health-promoting effects of oral ingestion of the microalgae pavlova, and there is a strong desire to develop such health-promoting effects.

[0005] In view of the above circumstances, an object of the present invention is to provide a composition for improving the intestinal environment, which contains microalgae of the genus Pavlova and can improve the intestinal environment by adjusting the balance of the intestinal bacterial flora as one of its health-promoting effects. [Means for solving the problem]

[0006] The present inventors conducted extensive research to solve the above-mentioned problems and arrived at the present invention. The inventors focused on microalgae of the Pavlovaceae family, particularly microalgae of the genus Pavlova, and investigated whether they possess any health-promoting effects. As a result, they discovered that the microalgae have the effect of increasing the production of short-chain fatty acids in the intestine, particularly at least one selected from the group consisting of acetic acid, propionic acid, and butyric acid, by regulating the intestinal microflora, thereby potentially improving the intestinal environment, leading to the completion of the present invention. Since the short-chain fatty acids in the present invention have immunostimulatory effects, they may also contribute to biological defense. Specifically, the present invention relates to a composition for improving the intestinal environment, as described below.

[0007] [1] A composition for improving the intestinal environment, comprising microalgae. [2] The composition for improving intestinal environment according to [1], wherein the microalgae are classified into the genus Pavlova. [3] The composition for improving the intestinal environment according to [1] or [2], which is an agent for promoting intestinal short-chain fatty acid production. [4] The composition for improving intestinal environment according to any one of [1] to [3], which is an intestinal regulator. [5] The composition for improving the intestinal environment according to any one of [1] to [4], which is used to increase the amount of production in the intestine of at least one short-chain fatty acid selected from the group consisting of acetic acid, propionic acid, and butyric acid. [6] The composition for improving the intestinal environment according to any one of [1] to [5], which increases the amount of production in the intestine of at least one short-chain fatty acid selected from the group consisting of acetic acid, propionic acid, and butyric acid within one month after administration. [7] The composition for improving the intestinal environment according to any one of [1] to [6], which is used to increase the amount of production in the intestine of at least one short-chain fatty acid selected from the group consisting of acetic acid, propionic acid, and butyric acid within one month after administration. [8] The composition for improving the intestinal environment according to any one of [1] to [7], wherein the dosage of the microalgae per day to a living body is 0.01 mg / kg or more and 10 g / kg or less, and the composition is used for oral administration. [9] A food or beverage ingredient comprising the composition for improving the intestinal environment according to any one of [1] to [8].

[10] The food and beverage material according to [9], which is applied to at least one selected from the group consisting of food and beverage products, oral medicines, and animal feed. [Effects of the Invention]

[0008] According to the present invention, there is provided a composition for improving the intestinal environment, which can improve the intestinal environment by adjusting the balance of the intestinal bacterial flora. [Brief explanation of the drawings]

[0009] [Figure 1] Figure 1 is a graph illustrating the positive correlation between the occupancy rate of intestinal bacteria belonging to the Clostridiaceae family (Clostridiaceae X.12) obtained from an analysis of the rat cecal microbiota and the butyric acid content in the cecum. DETAILED DESCRIPTION OF THE INVENTION

[0010] Hereinafter, embodiments of the present invention (hereinafter also referred to as "present embodiments") will be described, but the present invention is not limited thereto. Herein, in this specification, an expression in the form of "A to B" means the upper and lower limits of a range (i.e., A or more and B or less), and when no unit is specified for A and a unit is specified only for B, the unit of A and the unit of B are the same.

[0011] As used herein, the term "short-chain fatty acid" refers to a fatty acid having seven or fewer carbon atoms, in which one carboxyl group is bonded to a hydrocarbon group, and specifically refers to formic acid, acetic acid, propionic acid, isobutyric acid, butyric acid, isovaleric acid, valeric acid, methylbutyric acid, caproic acid, etc.

[0012] [Composition for improving intestinal environment] The intestinal environment-improving composition according to this embodiment contains microalgae. The intestinal environment-improving composition preferably contains microalgae as an active ingredient. As explained below, an intestinal environment-improving composition having these characteristics may be able to improve the intestinal environment through, for example, the effect of the microalgae in increasing the production of short-chain fatty acids in the intestine. In particular, the intestinal environment-improving composition may be able to exert the above-mentioned effects in vivo when ingested at a low dose (e.g., a low dose of several tens of mg per 1 kg of rat) for a short period of time (e.g., within one month, preferably within two to three weeks, more preferably within one to two weeks, and even more preferably within five days). As used herein, the term "microalgae" refers to microorganisms containing chloroplasts and having a microscopic size of, for example, 0.1 μm to 1 mm, and generally refers to algae of this size that live in water. Microalgae include organisms belonging to the prokaryotic phylum Cyanobacteria and the eukaryotic phylum Glaucophyta, Rhodophyta (red algae), Chlorophyta, Cryptophyta (cryptophytes), Haptophyta (haptophytes), Heterokontophyta, Dinophyta (dinoflagellates), Euglena, and Chlorarachniophyta.

[0013] Of these, the phylum Haptophyta (haptophytes) includes the class Haptophyceae. Haptophytes are phytoplankton with cell diameters of approximately 5 to 50 μm, and are autotrophic organisms that perform photosynthesis. The class Haptophyceae includes the subclass Pavloviales and the subclass Prymnesiophyceae. The subclass Pavloviales includes the order Pavlovales. The order Pavlovales includes the family Pavlovaceae. The family Pavlovaceae includes the genus Pavlova. The genus Pavlova includes P. calceolate, P. granifera, P. gyrans, P. lutheri, P. pinguis, and P. salina.

[0014] The microalgae are preferably, but not limited to, classified in the genus Pavlova. In this preferred embodiment, the microalgae are more preferably P. granifera or P. gyrans. The P. granifera and P. gyrans have been deposited, with the NBRC accession number for P. granifera being NBRC 114066. The NBRC accession number for P. gyrans is NBRC 102809. Specifically, the microalgae may be the Pavlova OPM S30543 strain (the algae strain identified by the accession number NBRC 114066, the P. granifera), or the Pavlova OPM S30543X strain (the algae strain identified by the accession number NBRC 102809, the P. gyrans), or a derivative thereof. As used herein, the term "derivative" refers to a strain containing a gene that contains a region substantially homologous to the DNA of the microalgae of interest. When such a strain is aligned using a computer homology program known in the art and compared with the whole genome sequence of the original strain, it has a whole genome sequence that is at least 30% identical, preferably 60% identical, more preferably 90% identical, and most preferably 95% identical or 99% identical. However, as used herein, the term "a strain derived from Pavlova OPM S30543 or the like" does not necessarily mean that the strain was derived from Pavlova OPM S30543 or the like, but rather means a microalga that contains a gene containing a region substantially homologous to the DNA of the target microalgae and that exhibits at least some of its biological activity.

[0015] As used herein, the term "biological activity" refers to various functions that organisms, including microalgae, can exhibit in a certain environment (e.g., improving the intestinal environment (specifically, promoting intestinal short-chain fatty acid production, regulating the intestines, etc.)). Such biological activity can be measured by techniques well known in the art. For example, the biological activity can be measured qualitatively and quantitatively by evaluating the response of the organism to a specific exposure or stimulus. For example, the biological activity of the microalgae can be evaluated by analyzing the intestinal microflora after certain stimuli or events, analyzing the content of short-chain fatty acids in the intestine, or improving or decreasing other functions.

[0016] The present inventors focused on the microalgae of the genus Pavlova described above and investigated whether they possess any health-promoting effects. As a result, as will be described in the Examples below, it was discovered that an unknown attribute of the microalgae is at least the effect of increasing the production of short-chain fatty acids in the intestine by regulating the intestinal bacterial flora, and therefore the microalgae can contribute to a new use of improving the intestinal environment. Here, the microalgae contained as an active ingredient in the composition for improving the intestinal environment may typically be the algae bodies of the microalgae, or a dried product containing some of the components contained in the algae bodies, or a product further processed from the dried product.

[0017] When the microalgae contained as an active ingredient in the intestinal environment-improving composition is a dried product, the moisture content of the microalgae may be 50% by mass or less, 10% by mass or less, 5% by mass or less, 3% by mass or less, 1% by mass or less, 0.5% by mass or less, 0.2% by mass or less, 0.1% by mass or less, or 0.05% by mass or less. The intestinal environment-improving composition may be provided by immersing the dried microalgae or a purified product thereof in oil or encapsulating it in a capsule (e.g., a soft capsule). In this manner, the intestinal environment-improving composition can be stabilized.

[0018] The intestinal environment-improving composition may contain the microalgae in any amount, but may contain 0.01 to 100% by mass. The intestinal environment-improving composition may contain the microalgae in an amount of 0.01% or more, 0.1% or more, 1% or more, 5% or more, 10% or more, 20%, 50%, 80% or more, or 100% by mass. The intestinal environment-improving composition may contain the microalgae in an amount of 100% or less, 90% or less, 80% or less, 70% or less, 60% or less, 50% or less, 40% or less, 30% or less, 20% or less, 10% or less, or 1% or less by mass. The intestinal environment-improving composition can contain any combination of flavoring agents, odorants, masking agents, etc. to adjust the taste or flavor of the microalgae when ingested. The intestinal environment-improving composition can also adjust the taste or flavor of the microalgae when ingested by means of coating or encapsulation.

[0019] <Intestinal short-chain fatty acid production promoter> The composition for improving the intestinal environment according to this embodiment is preferably an intestinal short-chain fatty acid production promoter. After being ingested into a living body, the intestinal short-chain fatty acid production promoter can adjust the intestinal bacterial flora of the living body, thereby increasing the proportion (occupancy) of intestinal bacteria that produce short-chain fatty acids, thereby increasing the amount of short-chain fatty acids produced in the intestine. This potentially allows the intestinal short-chain fatty acid production promoter to improve the intestinal environment. Furthermore, since short-chain fatty acids have been reported to have immunostimulatory effects, they may also contribute to biological defense.

[0020] The intestinal short-chain fatty acid production promoter may be able to increase the intestinal production of at least one short-chain fatty acid selected from the group consisting of acetic acid, propionic acid, and butyric acid. In particular, the intestinal short-chain fatty acid production promoter can exert its effect of increasing the intestinal production of short-chain fatty acids when taken in a low dose (e.g., a low dose of several tens of mg per kg of rat) for a short period of time (e.g., within one month, preferably within two to three weeks, more preferably within one to two weeks, and even more preferably within five days).

[0021] <Intestinal regulator> The composition for improving the intestinal environment according to this embodiment is preferably an intestinal regulator. The intestinal regulator improves bowel disorders such as diarrhea or constipation and maintains regular bowel movements daily through the effect of increasing the production of short-chain fatty acids in the intestines by adjusting the intestinal flora, which is a property of the microalgae described above. In particular, the intestinal regulator can exert the effect of increasing the production of short-chain fatty acids in the intestines by taking the low dose and for a short period of time described above, which may result in an early intestinal regulation effect.

[0022] <Uses, directions for use, and dosage> The intestinal environment-improving composition according to this embodiment is preferably administered orally, which may allow the intestinal environment-improving composition to increase the production of short-chain fatty acids in the intestine in a suitable manner (i.e., in a short period of time). The daily dose of the microalgae to a living organism is not particularly limited, but is preferably 0.01 mg / kg or more, 0.05 mg / kg or more, 0.1 mg / kg or more, 0.5 mg / kg or more, 1 mg / kg or more, 2 mg / kg or more, 3 mg / kg or more, 4 mg / kg or more, 5 mg / kg or more, 6 mg / kg or more, 7 mg / kg or more, 8 mg / kg or more, 9 mg / kg or more, 10 mg / kg or more, 20 mg / kg or more, or 25 mg / kg or more, and may be 10 g / kg or less, 1 g / kg or less, 0.5 g / kg or less, 100 mg / kg or less, 90 mg / kg or less, 80 mg / kg or less, 70 mg / kg or less, 60 mg / kg or less, 50 mg / kg or less, 40 mg / kg or less, 30 mg / kg or less, 25 mg / kg or less, 20 mg / kg or less, 15 mg / kg or less, 10 mg / kg or less, 5 mg / kg or less, or the like. Therefore, the daily dose of the microalgae to a living organism may be 0.1 to 100 mg / kg, 0.2 to 90 mg / kg, 0.3 to 80 mg / kg, 0.4 to 70 mg / kg, 0.5 to 50 mg / kg, 0.6 to 40 mg / kg, 0.7 to 30 mg / kg, 1 to 100 mg / kg, 5 to 70 mg / kg, 10 to 50 mg / kg, 0.5 to 20 mg / kg, 1 to 10 mg / kg, etc.

[0023] The desired dosage of the composition for improving intestinal environment can be increased or decreased as appropriate, taking into consideration the method of administration, the age and sex of the patient, the severity of symptoms, and the like. For example, the intestinal environment improving composition is preferably, but not limited to, 0.1 mg or more, 0.5 mg or more, 1 mg or more, 10 mg or more, 20 mg or more, 30 mg or more, 40 mg or more, 50 mg or more, 60 mg or more, 70 mg or more, 80 mg or more, 90 mg or more, 100 mg or more, 300 mg or more, 500 mg or more, 700 mg or more, 1000 mg or more per day for an adult, and may be 1000 g or less, 200 g or less, 100 g or less, 10 g or less, 5000 mg or less, 4000 mg or less, 3000 mg or less, 2000 mg or less, 1000 mg or less, 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, etc. The daily dose of the composition for improving intestinal environment for an adult may be 0.1 to 10,000 mg, 1 to 7,500 mg, 10 to 5,000 mg, 20 to 3,000 mg, 50 to 3,000 mg, 100 to 2,000 mg, 100 to 1,000 mg, 40 to 700 mg, 50 to 500 mg, 60 to 400 mg, 70 to 350 mg, 100 to 300 mg, etc.

[0024] The intestinal short-chain fatty acid production promoter is preferably used to increase the intestinal production of at least one short-chain fatty acid selected from the group consisting of acetic acid, propionic acid, and butyric acid. In particular, the intestinal short-chain fatty acid production promoter may be able to increase the intestinal production of at least one short-chain fatty acid selected from the group consisting of acetic acid, propionic acid, and butyric acid within one month after administration. The effect of increasing the production may be observed preferably within 2 to 3 weeks after administration, more preferably within 1 to 2 weeks, even more preferably within one week, and even more preferably within 5 days.

[0025] The "living body" mentioned above includes not only humans as mammals but also animals, particularly pets, etc. The dosage of the intestinal environment-improving composition can be determined appropriately for ingestion by these living bodies. When the intestinal environment-improving composition is used as feed, pet food, or the like, the target organisms are not particularly limited, but are preferably mammals, reptiles, amphibians, birds, or fish, and more preferably mammals other than humans, such as platypus, echidna, opossum, quoll, kangaroo, aardvark, rock badger, elephant, armadillo, sloth, anteater, tree shrew, flying lemur, chimpanzee, rabbit, degu, dormouse, squirrel, raccoon, mouse, hedgehog, chinchilla, ferret, camel, wild boar, giraffe, deer, cow, goat, hippopotamus, whale, dolphin, horse, rhinoceros, tapir, bat, monkey, tiger, wolf, weasel, bear, seal, dog, cat, parakeet, parrot, finch, owl, and horned owl, and more preferably dog ​​or cat.

[0026] When the intestinal environment-improving composition is used as feed, pet food, or the like, it may be given to the pet several times a day by adding it to the staple food, or it may be given as a snack at any time.

[0027] Here, the concept of the dosage (dosage) of the intestinal environment-improving composition for an animal (living body) will be explained using rats as an example as follows: That is, when converting the dosage (dosage) for a rat to the dosage (dosage) for a living body, the concept of the human equivalent dose can be used, although it is not limited thereto. Bioequivalent dose (HED) = rat dose (mg / kg) × (rat body weight (kg) / animal body weight (kg)) 0.33

[0028] The biological equivalent dose is calculated using the formula above. For example, for a rat weighing 160 g and dosed at 25 mg / kg, the HED is calculated as 3.54 mg / kg. For a 60 kg human, the HED is calculated as approximately 210 mg / human, and for a 10 kg dog, it is calculated as approximately 64 mg / dog.

[0029] The following concept can be used to convert the dose for rats to the dose for other living organisms: For example, if a rat takes about 25 mg / kg of body weight of the intestinal environment improving composition per day, the intake per kg of body weight is calculated as follows: 2 To convert this to an intake per person, the factor listed in Table 1 of the FDA guidance (Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers, July 2005) is used. According to this, the factor for rats is multiplied by 6, resulting in a daily intake of 150 mg / m² for rats. 2 This means that the intestinal environment improving composition is ingested in an amount equivalent to the total body surface area of ​​the subject. 2 When converting the intake amount per kg of body weight for each animal species, for humans it is divided by the factor of 37 specified in the FDA guidance above, which gives approximately 4 mg / kg body weight per day, for dogs it is divided by the factor of 20 specified in the FDA guidance above, which gives 7.5 mg / kg body weight per day, and for rabbits it is divided by the factor of 12 specified in the FDA guidance above, which gives 12.5 mg / kg body weight per day.

[0030] The intestinal environment-improving composition of this embodiment can be used together with other intestinal regulators, gastrointestinal drugs, or foods and beverages known for their intestinal regulating effects. In such applications, the amount of other intestinal regulators, gastrointestinal drugs, or foods and beverages known for their intestinal regulating effects used in the hope of improving the intestinal environment is reduced compared to the amount when used alone. For example, the amount of intestinal regulator used together with the intestinal environment-improving composition can be 50% or less, 25% or less, or 10% or less by mass per day compared to the amount when used alone, preferably 5% or less per day, more preferably 3% or less per day, and even more preferably 2% or less, or 1% or less per day. This may allow the intestinal environment-improving composition to maintain its intestinal environment-improving action or effect (especially the effect of increasing the production of short-chain fatty acids in the intestine) while reducing the dosage of the intestinal regulator and suppressing its side effects.

[0031] The intestinal environment-improving composition is expected to be primarily administered orally as described above, but it is not excluded that it may also be in a dosage form for parenteral administration, such as an injection, suppository, or topical skin preparation. For example, topical skin preparations include patches, tapes, creams, lotions, lotions, emulsions, foundations, packs, foams, plasters, ointments, poultices, and aerosols, and in these cases, effects such as intestinal regulation can also be expected.

[0032] [Materials for food and beverages] The food and beverage material according to this embodiment includes the intestinal environment-improving composition. Food and beverage materials with these characteristics may be able to improve the intestinal environment by, for example, increasing the production of short-chain fatty acids in the intestine through the regulation of the intestinal microflora by the microalgae contained in the intestinal environment-improving composition. In particular, the food and beverage material may exhibit the above-mentioned effects through ingestion of the microalgae at a low dose (e.g., a low dose of several tens of milligrams per kilogram of rat) over a short period of time (e.g., within one month, preferably within two to three weeks, more preferably within one to two weeks, and even more preferably within five days). The food and beverage material is preferably applied to at least one selected from the group consisting of food and beverages, oral pharmaceuticals, and animal feed. The food and beverage material may also be provided by mixing it with ordinary meals or feed. The food and beverage material may be used as a food for specified health uses or a food with functional claims.

[0033] As used herein, "food and beverage products" refers to products intended for ingestion by animals (including humans). Food and beverage products include not only commonly used foods and beverages, but also food additives, functional foods (e.g., foods for specified health uses, foods with functional claims, foods with nutrient functions, etc.), and supplements. Furthermore, as used herein, "animal feed" refers to products intended for ingestion by pet animals or livestock, among others.

[0034] As used herein, "drugs" in "oral medications" refers to drugs administered to humans or animals for the diagnosis, treatment, or prevention of disease. This term includes items listed in the Japanese Pharmacopoeia, items intended for use in the diagnosis, treatment, or prevention of disease in humans or animals that are not mechanical instruments, dental materials, medical supplies, or sanitary products, and items intended to affect the structure or function of the human or animal body that are not mechanical instruments, dental materials, medical supplies, or sanitary products. Furthermore, as used herein, "oral medications" also includes quasi-drugs. "Quasi-drugs" are defined in Japan's "Act on Ensuring Quality, Efficacy, and Safety of Pharmaceuticals, Medical Devices, Gene Therapy Products, and Gene Therapy Products," and are classified as intermediates between pharmaceuticals and cosmetics. These include products with mild effects on the human body, including mechanical instruments with mild effects on the human body. Examples of quasi-drugs include, but are not limited to, designated quasi-drugs (such as supplements and some gastrointestinal medications). As used herein, "oral" in "oral medications" refers to the above-mentioned medications that are ingested orally by animals (including humans).

[0035] When the food or beverage material is an "oral pharmaceutical," the daily oral intake or dosage may be divided into 1 to 6 capsules, 1 to 4 capsules, 1 to 3 capsules, or 1 to 2 capsules depending on the dosage form.

[0036] When the food or beverage material is an "oral pharmaceutical," the oral pharmaceutical can be taken or administered once to several times a day, typically 1 to 6 times a day, 1 to 3 times a day, 1 to 2 times a day, or for any period, interval, or as needed, but 3 times a day is preferred.

[0037] [Use of composition for improving intestinal environment] The intestinal environment-improving composition according to this embodiment can be added to or mixed with foods, beverages, pharmaceuticals, feed, and pet foods. The intestinal environment-improving composition may also be used as is in foods, beverages, pharmaceuticals, feed, or pet foods. The intestinal environment-improving composition may be used as a food, beverage, pharmaceutical, feed, or pet food, etc., that explicitly or implicitly claims to have the functions of promoting short-chain fatty acid production in the intestines and regulating bowel movements, i.e., health foods, functional foods, foods for patients, and foods for specified health uses. The intestinal environment-improving composition may also be used as so-called doctor's supplements recommended or recommended by doctors in internal medicine and orthopedic departments in hospitals and / or clinics, veterinary clinics, etc., even if the functionalities are not explicitly or implicitly stated. When the functionalities are explicitly stated, they may be stated as improving bowel movements such as diarrhea or constipation in daily life, or as having an intestinal regulating effect that maintains regular bowel movements daily, but are not limited to these. It may also be stated that prior intake of the intestinal environment-improving composition can prevent temporary bowel movements or alleviate chronic bowel movements.

[0038] Health foods, functional foods, foods for patients, and foods for specified health uses can be used in various dosage forms, such as solid preparations (tablets, orally disintegrating tablets, granules, fine granules, powders, capsules, chewable tablets, candy, etc.), liquid preparations (syrups, suspensions), and liquid diets. Food preparations can be produced in the same manner as known pharmaceutical preparations, by mixing the active ingredient with a food-acceptable carrier, such as an appropriate excipient, and then producing the preparation using conventional means. The dosage form of the intestinal environment-improving composition is not particularly limited, but is preferably an orally disintegrating tablet, chewable tablet, candy, granules, powder, or liquid, from the viewpoint of significantly exhibiting the effects of the intestinal environment-improving composition.

[0039] For example, tablets can be prepared by compressing a mixture of a powdered active ingredient and a pharmaceutically acceptable carrier (such as an excipient). Confectionery tablets such as candies may be prepared by pouring the mixture into a mold. Tablets may also be sugar-coated tablets. Furthermore, tablets may be single-layer tablets or layered tablets such as double-layer tablets.

[0040] Powdered granules such as granules may be prepared by various granulation methods (extrusion granulation, milling granulation, dry compaction granulation, fluidized bed granulation, tumbling granulation, high-speed stirring granulation, etc.), and tablets can be prepared by an appropriate combination of the above-mentioned granulation methods and tableting methods (wet tableting, direct tableting), etc.

[0041] Capsules can be prepared by filling a capsule (soft or hard capsule) with powder (powder, granules, etc.) by a conventional method.

[0042] A liquid preparation can be prepared by dissolving or dispersing each component in an aqueous medium (purified water, purified water containing ethanol, etc.) which is a carrier component, filtering or sterilizing the resulting solution as necessary, filling the resulting solution into a predetermined container, and sterilizing the resulting solution. The preferred dosage form of the solid preparation is a capsule or tablet, and soft capsules (soft capsules) are more preferred.

[0043] Soft capsules are preferred by users because they have a smooth surface and are easy to swallow. Common methods for manufacturing soft capsules include the flat plate method, the rotary method, and the seamless method.

[0044] In the rotary method (punching method), a sheet-like capsule shell is formed into a capsule shape by sandwiching the flowing filling material and following the holes in a rotating cylindrical mold. On the other hand, in the seamless method (dropping method), the capsule shell composition and the filling material are simultaneously ejected from multiple concentric nozzles to form a seamless capsule shape.

[0045] The base material for the soft capsule shell is not particularly limited, but may be starch, pullulan, cellulose, polyvinyl alcohol, gelatin, succinated gelatin, etc., with starch, gelatin, and succinated gelatin being preferred, and gelatin and succinated gelatin being more preferred. These may be used alone or in combination of two or more.

[0046] The intestinal environment-improving composition may also be used in liquid beverages such as soups, juices, fruit juice drinks, milk, dairy drinks, whey drinks, lactic acid bacteria drinks, tea drinks, alcoholic drinks, coffee drinks, carbonated drinks, soft drinks, water drinks, cocoa drinks, jelly drinks, sports drinks, and diet drinks; semi-solid foods such as pudding and yogurt; noodles, confectioneries, spreads, and the like.

[0047] When the intestinal environment-improving composition is prepared as a food composition, various food additives may be blended in. Examples of food additives include antioxidants, colorants, flavorings, seasonings, sweeteners, acidulants, pH adjusters, quality stabilizers, and preservatives.

[0048] When the intestinal environment-improving composition is prepared as a pharmaceutical composition, it can be prepared as a formulation containing the active ingredient, microalgae, and preferably a pharmaceutically acceptable carrier. A pharmaceutically acceptable carrier generally refers to an inert, non-toxic, solid or liquid filler, diluent, or encapsulating material that does not react with the active ingredient, such as water, ethanol, polyols, suitable mixtures thereof, or solvents or dispersion media such as vegetable oils.

[0049] The pharmaceutical composition is administered orally or parenterally, for example, into the oral cavity, the digestive tract, or the nasal cavity. Orally administered formulations include solid formulations (tablets, orally disintegrating tablets, granules, fine granules, powders, capsules, chewable tablets, candy, etc.) and liquid formulations (syrups, suspensions, inhalants). Parenterally administered formulations include eye drops, drip infusions, nasal drops, and injections. The formulation form is not limited, but is preferably an orally disintegrating tablet, chewable tablet, candy, granule, powder, or liquid formulation, from the viewpoint of significantly exhibiting the effects of the intestinal environment-improving composition.

[0050] The pharmaceutical composition may further contain additives commonly used in the pharmaceutical field. Such additives include, for example, excipients, binders, disintegrants, lubricants, antioxidants, coloring agents, flavoring agents, etc. These are used appropriately as needed. These may be coated with known retardants or the like to achieve sustained release so as to act over a long period of time. The pharmaceutical composition may further contain other additives or drugs, such as antacids and gastric mucosa protectants, as needed.

[0051] The pharmaceutical composition can be applied in the form of an oral composition, an oral composition, etc. The pharmaceutical composition may be used therapeutically or non-therapeutically. The intestinal environment-improving composition may be further mixed with the food or beverage material in the above-mentioned dosage form. [Example]

[0052] The present invention will be described in more detail below with reference to several examples, but the present invention is not limited to these examples.

[0053] [First Example] <Sample preparation> A sample (composition for improving intestinal environment, hereinafter also referred to as "Pavlova") used in this example was prepared by obtaining a dried product of microalgae (trade name: "Pavlova", manufactured by Rohto Pharmaceutical Co., Ltd.) This sample was composed of 100% by mass of the above microalgae, which is classified as the Pavlova genus.

[0054] <Preparation of animals> Six-week-old male Wistar / ST rats (Japan SLC Co., Ltd.) were obtained to prepare the animals used in Example 1. After a one-week acclimation period, the rats were housed in a controlled environment at 24±1°C with a 12-hour light / dark cycle for five days before being used in Example 1. The rats were fed Certified Diet MF solids for mice, rats, and hamsters (12 mm diameter pellets, 359 kcal / 100 g, Oriental Yeast Co., Ltd.).

[0055] (Extraction of rat cecum) The rats were divided into two groups: a water-treated group (5 rats each) and a Pavlova-treated group (5 rats each), housed individually in cages. Rats in the water-treated group were orally administered 2.5 mL of ultrapure water per kg of body weight. Rats in the Pavlova-treated group were administered a 10 mg / mL Pavlova suspension in ultrapure water at 2.5 mL per kg of body weight at 11:00 AM for five days. Feces were collected from the water-treated and Pavlova-treated rats on days two through five. Furthermore, rats in the water-treated and Pavlova-treated groups were fasted from 5:00 PM on day four, and the cecum was collected one hour after administration of the ultrapure water or suspension on day five.

[0056] (Quantitative determination of short-chain fatty acids and lactic acid in rat cecum) 50 mg of cecal contents were collected from rats in the water and Pavlova groups. 450 μL of ultrapure water was added to the contents and thoroughly stirred to obtain a suspension. The suspension was then centrifuged at 10,000 G for 10 minutes at 5°C, and the supernatant was collected.

[0057] To 20 μL of the supernatant, 40 μL of ultrapure water, 40 μL of 0.02 M 2-nitrophenylhydrazine solution, and 40 μL of 120 mM 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride in pyridine / methanol (6:94 by volume) were added and incubated at 60°C for 20 minutes. 40 μL of 1 M potassium hydroxide in methanol was added and incubated at 60°C for 15 minutes, followed by ice cooling for 15 minutes. 20 μL of 10% formic acid (volume) was added. The same procedure was repeated for acetic acid, lactic acid, propionic acid, and butyric acid as external standards. Thus, samples for quantifying short-chain fatty acids and lactic acid in the cecum were obtained from the cecal contents of rats treated with water and Pavlova.

[0058] The samples were then filtered using an aqueous filter (trade name: "Cosmonice® Filter," pore size 0.45 μm, manufactured by Nacalai Tesque, Inc.), and 10 μL of the filtrate was injected into an LC / MS / MS (trade name (product number): "LCMS8040," manufactured by Shimadzu Corporation). An Inersil ODS-3 column (2.1 mm × 250 mm, 4 μm, manufactured by GL Sciences) was used as the column for the LC / MS / MS. The short-chain fatty acids and lactic acid in each sample were quantified by positive-mode multireaction monitoring (MRM) analysis in the LC / MS / MS. The LC / MS / MS eluents used were 0.1% by volume formic acid (liquid A) and 80% by mass acetonitrile-0.1% by volume formic acid (liquid B). The flow rate was 0.2 mL / min, and the column temperature was 40°C. Ultrapure water was used as the needle wash solution. The gradient was 0-20 min, 0-40% B; 20-35 min, 40-100% B; 35-40 min, 100% B; 40.1-50 min, 0% B. The LC (HPLC) section consisted of two LC-20ADs, a CBM-20A, a SIL-20AC, an SPD-2 AV, and a CTO-20AC.

[0059] The amounts of short-chain fatty acids (specifically, acetic acid, propionic acid, and butyric acid) and lactic acid in the cecum of rats in the water-administered and Pavlova-administered groups obtained from the above-mentioned LC / MS / MS analysis are shown in Table 1. The values ​​in Table 1 are the average amounts of short-chain fatty acids and lactic acid in the cecum of rats in the water-administered and Pavlova-administered groups (five rats each).

[0060] [Table 1]

[0061] <Consideration> According to Table 1, the Pavlova-administered group had increased levels of short-chain fatty acids and lactic acid in the cecum compared to the water-administered group. In particular, the Pavlova-administered group had significantly increased levels of acetic acid and butyric acid compared to the water-administered group.

[0062] [Second Example] The cecal contents of the water-administered group and the Pavlova-administered group collected in Example 1 were subjected to an intestinal bacteria test by Sheep Medical Co., Ltd. Specifically, the gene sequences of the intestinal microbiota of the contents were analyzed using a next-generation sequencer, and the types of intestinal bacteria and their occupancy rates (%) were calculated. Furthermore, based on the results of the analysis, the types of intestinal bacteria that showed significant differences between the water-administered group and the Pavlova-administered group and their occupancy rates (%) were determined using a Wilcoxon signed-rank test. The results are shown in Table 2. Table 2 particularly shows the occupancy rates of selected intestinal bacteria in the cecum of five animals in the water-administered group (water-administered groups 1-5) and five animals in the Pavlova-administered group (Pavlova-administered groups 1-5).

[0063] [Table 2]

[0064] In Example 2, statistical analysis was performed using Spearman's rank correlation coefficient between the intestinal bacteria and their metabolites (short-chain fatty acids). As a result, as shown in Figure 1, it was determined that there was a positive correlation between the cecal occupancy rate of Clostridiaceae X.12 and the amount of butyric acid in the cecum. Figure 1 is a graph illustrating the positive correlation between the occupancy rate of intestinal bacteria belonging to the Clostridiaceae family (Clostridiaceae X.12) obtained from an analysis of the rat cecal microbiota and the butyric acid content in the cecum.

[0065] <Consideration> Table 2 and Figure 1 suggest that the Pavlova-treated group had a higher proportion of intestinal bacteria that produce short-chain fatty acids in the cecum than the water-treated group, which resulted in increased production of short-chain fatty acids (especially butyric acid) in the intestine.

[0066] [Summary] Examples 1 and 2 suggest that the Pavlova-administered group may have the effect of increasing the production of short-chain fatty acids, particularly butyric acid, in the intestine by adjusting the balance of the intestinal flora, thereby improving the intestinal environment. In particular, because the cecal contents on the fifth day after Pavlova administration were analyzed, it is estimated that the adjustment of the balance of the intestinal flora due to Pavlova occurs within, for example, five days to two weeks. Therefore, it is expected that the intestinal environment may be improved by taking Pavlova for a short period of time (for example, within one to two weeks, preferably within five days).

[0067] Although the embodiments and examples of the present invention have been described above, it is also intended from the beginning that the configurations of the above-described embodiments and examples may be appropriately combined.

[0068] The embodiments and examples disclosed herein should be considered to be illustrative in all respects and not restrictive. The scope of the present invention is defined by the claims, not by the above description, and is intended to include all modifications within the meaning and scope of the claims.

Claims

1. A composition for improving the intestinal environment, comprising microalgae.

2. The composition for improving intestinal environment according to claim 1 , wherein the microalgae is classified into the genus Pavlova.

3. 3. The composition for improving intestinal environment according to claim 1 or claim 2, which is an agent for promoting intestinal short-chain fatty acid production.

4. The composition for improving the intestinal environment according to claim 1 or claim 2, which is an intestinal regulator.

5. A composition for improving the intestinal environment described in claim 1 or claim 2, which is used to increase the production in the intestines of at least one short-chain fatty acid selected from the group consisting of acetic acid, propionic acid, and butyric acid.

6. A composition for improving the intestinal environment described in claim 1 or claim 2, which increases the production of at least one short-chain fatty acid selected from the group consisting of acetic acid, propionic acid, and butyric acid in the intestines within one month after administration.

7. A composition for improving the intestinal environment described in claim 1 or claim 2, which is used to increase the production of at least one short-chain fatty acid selected from the group consisting of acetic acid, propionic acid, and butyric acid in the intestines within one month after administration.

8. The composition for improving the intestinal environment according to claim 1 or claim 2, wherein the microalgae is administered orally to a living body at a daily dose of 0.01 mg / kg or more and 10 g / kg or less.

9. A food or beverage material comprising the composition for improving intestinal environment according to claim 1 or 2.

10. The food and beverage material according to claim 9, which is applied to at least one selected from the group consisting of food and beverage products, oral medicines, and animal feed.

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