Composition for prevention or treatment of renal disorder

Abstract

To provide a composition for preventing or treating renal disorder, which has potential effectiveness against renal ischemia-reperfusion injury and related conditions.SOLUTION: The composition for prevention or treatment of renal disorder comprises microalgae.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a composition for preventing or treating renal damage. [Background technology]

[0002] For example, 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 (hereinafter also referred to as "GABA"), etc. Recently, the nutritional components contained in microalgae (such as chlorella and euglena) have attracted attention, and efforts are underway to use them in health foods, food ingredients, etc. [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] Among acute kidney injuries, renal ischemia-reperfusion injury is thought to cause inflammation and necrosis of kidney tissue due to oxidative stress caused by the resumption of blood flow. The microalgae disclosed in Patent Document 1 are said to contain high concentrations of fucoxanthin, eicosapentaenoic acid, GABA, etc., which have been reported to have antioxidant and anti-inflammatory effects, but there is no mention of whether they have any effect on kidney injury.

[0005] In view of the above circumstances, an object of the present invention is to provide a composition for preventing or treating renal disorders, which may be effective against renal ischemia-reperfusion injury and the like. [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 were effective against renal ischemia-reperfusion injury and the like. As a result, they found that oral ingestion of the microalgae reduces the amount of urea nitrogen in the blood and the amount of protein excreted in urine, leading to the completion of the present invention. Based on these findings, the present invention may be effective against renal ischemia-reperfusion injury and the like. That is, the present invention relates to a composition for preventing or treating renal damage, as described below.

[0007] [1] A composition for preventing or treating kidney damage, comprising microalgae. [2] The composition for preventing or treating kidney damage according to [1], wherein the microalgae are classified into the genus Pavlova. [3] The composition for preventing or treating nephropathy according to [1] or [2], which is an agent for reducing urinary protein excretion. [4] The composition for preventing or treating nephropathy according to any one of [1] to [3], which is a blood urea nitrogen lowering agent. [5] The composition for preventing or treating renal damage according to any one of [1] to [4], which is used to reduce the amount of protein excreted in urine or the amount of urea nitrogen in blood. [6] The composition for preventing or treating kidney damage according to any one of [1] to [5], wherein the microalgae is administered orally to a living body at a daily dose of 1 mg / kg to 100 g / kg. [7] A food or beverage material comprising the composition for preventing or treating nephropathy according to any one of [1] to [6]. [8] The food and beverage material according to [7], 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, a composition for preventing or treating renal damage, which may be effective against renal ischemia-reperfusion injury and the like, is provided. DETAILED DESCRIPTION OF THE INVENTION

[0009] 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.

[0010] As used herein, "urinary protein excretion" refers to the amount of protein excreted in urine without being reabsorbed by the kidney, specifically the amount of albumin excreted in urine. The unit of urinary protein excretion is mg / day. As used herein, "blood urea nitrogen" refers to the amount of nitrogen in urea contained in blood. Hereinafter, blood urea nitrogen is also referred to as "blood BUN amount." The unit of blood urea nitrogen is mg / dL.

[0011] [Composition for preventing or treating kidney damage] The composition for preventing or treating nephropathy according to this embodiment contains microalgae. The composition for preventing or treating nephropathy preferably contains microalgae as an active ingredient. As described below, a composition for preventing or treating nephropathy having these characteristics can prevent or treat nephropathy by reducing urinary protein excretion and / or blood urea nitrogen levels, as described below. Alternatively, when used in combination with an existing nephropathy treatment drug, the composition for preventing or treating nephropathy may be able to reduce the dosage of the nephropathy treatment drug, thereby suppressing side effects, etc. As used herein, "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.

[0012] 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.

[0013] The microalgae are preferably classified into 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, and the NBRC accession number for P. granifera is 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.

[0014] As used herein, the term "biological activity" refers to various functions (e.g., reducing urinary protein excretion, reducing blood urea nitrogen, etc.) that can be exhibited by organisms, including microalgae, in a certain environment. 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 given exposure or stimulus. For example, the biological activity of the microalgae can be evaluated by an increase or decrease in the amount of upstream or downstream proteins, or an improvement or decrease in other functions, after some stimulus or event.

[0015] The present inventors focused on the above-mentioned Pavlova microalgae and investigated whether they are effective against renal ischemia-reperfusion injury, etc. As a result, as will be described in the Examples below, it was found that the microalgae exhibited an unknown attribute of reducing at least the amount of blood urea nitrogen and the amount of urinary protein excretion, making the microalgae suitable for use in a new application, namely, the prevention or treatment of renal damage. Here, the microalgae contained as an active ingredient in the composition for preventing or treating renal damage may typically be the algae bodies of the microalgae, or a dried product containing some of the components contained in the algae bodies, or may be a product further processed from the dried product.

[0016] When the microalgae contained as an active ingredient in the composition for preventing or treating kidney damage 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 composition for preventing or treating kidney damage 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 such an embodiment, the composition for preventing or treating kidney damage can be stabilized.

[0017] The composition for preventing or treating kidney damage may contain the microalgae in any amount, but may contain 0.01 to 100% by mass. The composition for preventing or treating kidney damage 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 composition for preventing or treating kidney damage 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 composition for preventing or treating kidney damage can contain any combination of flavoring agents, odorants, masking agents, etc. to adjust the taste or flavor of the microalgae when ingested. The composition for preventing or treating kidney damage can also adjust the taste or flavor of the microalgae when ingested by means of coating or encapsulation.

[0018] <Urinary protein excretion reducing agent> The composition for preventing or treating renal damage according to this embodiment is preferably a urinary protein excretion reducer. The urinary protein excretion reducer can reduce urinary protein excretion after ingestion into the body. Urinary protein excretion is known as an indicator for assessing the presence or absence of renal dysfunction and, if present, the degree of renal dysfunction. The lower the urinary protein excretion, or if it is below a certain value, the healthier the renal function. Furthermore, if renal dysfunction is present, a decrease in urinary protein excretion indicates that the degree of renal dysfunction is alleviated. Therefore, the urinary protein excretion reducer may be capable of preventing or treating renal damage that may occur due to renal ischemia-reperfusion injury, etc.

[0019] The agent for reducing urinary protein excretion can reduce the amount of protein excreted in urine, specifically the amount of albumin in urine. In particular, the agent for reducing urinary protein excretion can exhibit the effect of reducing the amount of albumin in urine by ingesting the microalgae at a dose of 500 mg / kg or more (preferably 600 mg / kg or more) for about 7 days (preferably 7 days or more).

[0020] <Blood urea nitrogen lowering agent> The composition for preventing or treating renal damage according to this embodiment is preferably a blood urea nitrogen lowering agent. After ingestion, the blood urea nitrogen lowering agent can reduce the amount of urea nitrogen in the blood. The amount of urea nitrogen in the blood is known as an indicator for assessing the presence or absence of renal dysfunction and, if present, the degree of renal dysfunction. The lower the amount of urea nitrogen in the blood, or if it is below a certain value, the healthier the renal function. Furthermore, in the presence of renal dysfunction, a decrease in the amount of urea nitrogen in the blood indicates a reduction in the degree of renal dysfunction. Therefore, the blood urea nitrogen lowering agent may be capable of preventing or treating renal damage that may result from renal ischemia-reperfusion injury, etc. In particular, the blood urea nitrogen lowering agent's effect of reducing the amount of urea nitrogen in the blood can be achieved by ingesting the microalgae at a dose of 500 mg / kg or more (preferably 600 mg / kg or more) for approximately 7 days (preferably 7 days or more).

[0021] <Uses, directions for use, and dosage> The composition for preventing or treating kidney damage according to this embodiment is preferably orally administered, with the microalgae being administered to a living body at a daily dose of 1 mg / kg or more and 100 g / kg or less. This may allow the composition for preventing or treating kidney damage to be effectively prevented or treated. The daily dose of the microalgae administered to a living body is not particularly limited, but may be 1 mg / kg or more, 10 mg / kg or more, 25 mg / kg or more, 50 mg / kg or more, 75 mg / kg or more, 100 mg / kg or more, 150 mg / kg or more, 200 mg / kg or more, 250 mg / kg or more, 300 mg / kg or more, 400 mg / kg or more, 500 mg / kg or more, 600 mg / kg or more, 700 mg / kg or more, 800 mg / kg or more, 900 mg / kg or more, or Preferably, the dose is 1000 mg / kg or more, and may be 100 g / kg or less, 50 g / kg or less, 10 g / kg or less, 5 g / kg or less, 2.5 g / kg or less, 1.5 g / kg or less, 1200 mg / kg or less, 1000 mg / kg or less, 900 mg / kg or less, 800 mg / kg or less, 700 mg / kg or less, 600 mg / kg or less, 500 mg / kg or less, 400 mg / kg or less, 300 mg / kg or less, or 200 mg / kg or less. Therefore, the daily dose of the microalgae to a living organism is typically 1 mg to 100 g / kg, and may be administered orally. The daily dose of the microalgae to a living organism may be 1 mg / kg to 100 g / kg, 10 mg / kg to 10 g / kg, 25 mg / kg to 5 g / kg, 50 mg / kg to 1 g / kg, 75 mg / kg to 750 mg / kg, 100 mg / kg to 700 mg / kg, etc. The daily dose of the microalgae to a living organism may be 500 mg / kg to 1.5 g / kg body weight or 600 mg / kg to 1200 mg / kg body weight.

[0022] The desired dosage of the composition for preventing or treating nephropathy can be increased or decreased as appropriate, taking into consideration the method of administration, the patient's age and sex, the severity of symptoms, etc. For example, the dosage of the composition for preventing or treating nephropathy is preferably, but not limited to, 10 mg or more, 50 mg or more, 100 mg or more, 500 mg or more, 1000 mg or more, 1.5 g / kg or more, 2 g / kg or more, 3 g / kg, 4 g / kg, or 5 g / kg per day for an adult, and preferably 100 g or less, 50 g or less, 40 g or less, 30 g or less, 20 g or less, 10 g or less, 7.5 g or less, 5 g or less, 1 g or less, or 500 mg or less. The daily dose of the composition for preventing or treating nephropathy for an adult may be 1 to 100,000 mg, 1 to 75,000 mg, 10 to 50,000 mg, 20 to 30,000 mg, 50 to 30,000 mg, 100 to 20,000 mg, 200 to 15,000 mg, 500 to 10,000 mg, 750 to 7,500 mg, 1,000 to 7,000 mg, 2,000 to 6,000 mg, 3,000 to 5,000 mg, etc.

[0023] The preventive or therapeutic composition for kidney damage is preferably used to reduce the amount of urinary protein excretion or the amount of urea nitrogen in the blood. In particular, the preventive or therapeutic composition for kidney damage may exert its effect of reducing the amount of urinary protein excretion or the amount of urea nitrogen in the blood by ingesting at least the microalgae at a dose of 50 mg / kg or more (preferably 100 mg / kg or more, more preferably 500 mg / kg or more) for about 7 days (preferably 7 days or more).

[0024] The above-mentioned "living organism" includes not only humans as mammals but also animals, particularly pets or companion animals, etc. The dose of the above-mentioned composition for preventing or treating nephropathy can be determined appropriately for ingestion by these living organisms. When the composition for preventing or treating kidney damage is used as feed, pet food, or the like, the target organism is not particularly limited, but is preferably a mammal, reptile, amphibian, bird, or fish, and more preferably a mammal other than human, such as a 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, or horned owl, and more preferably a dog or cat.

[0025] When the above-mentioned composition for preventing or treating kidney damage is used as feed, pet food, etc., it may be given in divided doses several times a day by adding it to staple food, or it may be given at any time as a snack.

[0026] Here, the concept of the dosage (dosage) of the composition for preventing or treating nephropathy to an animal (living body) will be explained using rats as an example as follows: That is, when converting the dosage (dosage) to a rat to the dosage (dosage) to 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

[0027] The biological equivalent dose is calculated using the formula above. For example, for a rat weighing 200 g and dosed at 600 mg / kg, the HED is calculated as 91.3 mg / kg. For a 60 kg human, the HED is calculated as approximately 5500 mg / human, and for a 10 kg dog, it is calculated as approximately 1650 mg / dog.

[0028] The following concept can be used to convert the dose for rats to doses for other living organisms. For example, if a rat takes about 600 mg / kg of body weight of the above-mentioned composition for preventing or treating nephropathy per day, the intake per kg of body weight is calculated as follows: 2 To convert this to a daily intake, 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 3600 mg / m² for rats. 2 This means that the subject has ingested the above-mentioned composition for preventing or treating kidney damage for 1 m of body surface area. 2 When converting the intake amount per kg of body weight for each animal species, for humans it is divided by the factor 37 specified in the FDA guidance above, which gives 97.3 mg / kg body weight per day, for dogs it is divided by the factor 20 specified in the FDA guidance above, which gives 180 mg / kg body weight per day, and for rabbits it is divided by the factor 12 specified in the FDA guidance above, which gives 300 mg / kg body weight per day.

[0029] The above-mentioned composition for preventing or treating nephropathy can be used together with other nephropathy therapeutic agents, nephropathy preventive agents, or foods and beverages known to have nephropathy-improving effects. In such applications, the amount of other nephropathy therapeutic agents, nephropathy preventive agents, foods and beverages, etc. used in the hope of improving nephropathy is reduced compared to the amount when used alone. For example, the amount of nephropathy therapeutic agent used together with the above-mentioned composition for preventing or treating nephropathy can be 50% or less, 25% or less, or 10% or less by mass per day compared to the amount when the nephropathy therapeutic agent is 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 above-mentioned composition for preventing or treating nephropathy to maintain the nephropathy-improving effect or effect (especially the effect of reducing urinary protein excretion and blood urea nitrogen level) while reducing the dosage of the nephropathy therapeutic agent and thereby suppressing its side effects.

[0030] The above-mentioned composition for preventing or treating kidney damage 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, skin lotions, emulsions, foundations, packs, foams, plasters, ointments, poultices, and aerosols, and in these cases, effects of improving kidney damage can also be expected.

[0031] [Materials for food and beverages] The food and beverage material according to this embodiment includes the composition for preventing or treating kidney damage. Food and beverage materials with these characteristics may potentially be able to prevent or treat kidney damage through the urinary protein excretion-reducing effect or blood urea nitrogen-reducing effect of the microalgae contained in the composition for preventing or treating kidney damage. In particular, the food and beverage material can effectively exhibit the above-mentioned effects by habitually ingesting a predetermined amount (e.g., 500 mg / kg) of the microalgae as a food and beverage material (e.g., for 7 days or more, preferably 1 month or more, more preferably 3 months or more, and most preferably 6 months or more). 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 can also be provided by mixing it with ordinary meals or feed. The food and beverage material can be used as a specified health food or a food with a functional claim.

[0032] 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.

[0033] 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).

[0034] 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.

[0035] 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.

[0036] [Use of the composition for preventing or treating kidney damage] The renal disorder prevention or treatment composition according to the present embodiment may be added to or mixed with foods, beverages, pharmaceuticals, feed, or pet foods. The renal disorder prevention or treatment composition may also be used as is in foods, beverages, pharmaceuticals, feed, or pet foods. The renal disorder prevention or treatment composition may also be used as a food or beverage product that explicitly or implicitly claims to prevent or treat renal disorder, improve renal disorder, or improve or enhance renal function, i.e., health foods, functional foods, foods for patients, and foods for specified health uses. The renal disorder prevention or treatment composition may also be used as a so-called doctor's supplement recommended or offered by doctors in internal medicine or orthopedic departments in hospitals and / or clinics, veterinary clinics, etc., even if the functionality is not explicitly or implicitly claimed. When the functionality is explicitly stated, it may be stated, for example, as having the effect of improving renal function based on the effect of reducing urinary protein excretion or blood urea nitrogen in daily life, but is not limited to these. It may also be stated that the pre-ingestion of the composition for preventing or treating kidney damage by a healthy person or animal prevents temporary kidney damage, or that habitual ingestion by a person or animal with kidney damage alleviates chronic kidney damage, etc. The use of the composition for preventing or treating kidney damage according to this embodiment may be use of microalgae for the production of a composition for preventing or treating kidney damage, and the microalgae is preferably classified as being of the genus Pavlova.

[0037] 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 a suitable excipient, and then producing the preparation using conventional means. The dosage form of the composition for preventing or treating kidney damage 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 composition.

[0038] 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.

[0039] 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.

[0040] Capsules can be prepared by filling a capsule (soft or hard capsule) with powder (powder, granules, etc.) by a conventional method.

[0041] 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.

[0042] 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.

[0043] 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.

[0044] 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.

[0045] In addition, the above-mentioned compositions for preventing or treating kidney disorders 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.

[0046] When the above-mentioned composition for preventing or treating kidney damage 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.

[0047] When the composition for preventing or treating kidney damage is prepared as a pharmaceutical composition, it can be prepared as a formulation containing microalgae as an active ingredient 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, vegetable oils, or other solvents or dispersion media.

[0048] 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 composition for preventing or treating nephropathy.

[0049] 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.

[0050] The pharmaceutical composition can be applied in the form of an oral composition, an internal composition, etc. The pharmaceutical composition can be used therapeutically or non-therapeutically. The above-mentioned composition for preventing or treating kidney damage may be further mixed with the above-mentioned food and beverage material in the above-mentioned dosage form. [Example]

[0051] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples.

[0052] [Sample preparation] A composition for preventing or treating kidney damage (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 consisted of 100% by mass of the above microalgae, which is classified as the Pavlova genus.

[0053] [Preparation of animals] The animals used in this example were prepared by obtaining 7-week-old male SD rats (Japan SLC Co., Ltd.). After a 2-week acclimation period, the rats were housed in a controlled environment of 21±2°C, 50±20% relative humidity (RH), and a 12-hour light / dark cycle (light period 8:00-20:00) until surgery, as described below. During the housing period, the rats were provided with free access to food (product name: "Solid Labo MR Stock"; Japan Nosan Corporation) and tap water.

[0054] Blood samples were taken from the rats before the renal ischemia-reperfusion surgery described below, and urine samples were collected for 24 hours from the day before surgery until just before surgery. Furthermore, the rats were weighed, and based on the results, they were divided into two groups: a distilled water-treated group (hereinafter also referred to as the "control group") (Samples 101 to 105) and a Pavlova-treated group (Samples 11 to 15). Two to three rats per group were then housed in a plastic cage. On the day of the renal ischemia-reperfusion surgery described below, the above-mentioned feed was weighed and a portion was placed on the floor of the cage.

[0055] <Creation of a rat model of renal ischemia-reperfusion injury> (Method of renal ischemia-reperfusion surgery) Each rat was anesthetized by intramuscular injection of 0.30 mL of ketamine-xylazine (6:1) into the leg. When the anesthesia wore off, the rat was anesthetized with isoflurane inhalation. The rat's left flank was incised, and the left kidney was exposed. The arteries and veins around the kidney were clamped with clips to block blood flow, and the kidney was then returned to the abdominal cavity. The affected area was then covered with gauze to prevent drying, and the entire body was wrapped in cloth and kept warm on a hot plate to maintain ischemia for 45 minutes. After the 45-minute period, the arterial and venous clips were removed to allow reperfusion. The muscles around the kidney were sutured with silk thread, and the skin was sutured with absorbable sutures. After suturing, an antibiotic (animal procaine penicillin G aqueous suspension) was injected intramuscularly into the rat's leg. Furthermore, the rats were individually placed in clean plastic cages (hereinafter also referred to as "metabolic cages"). All sterilized instruments were used in the renal ischemia-reperfusion surgery.

[0056] (Collection of various test samples (blood, urine, etc.)) After waking up from anesthesia, 0.075 mL of an analgesic (Repetan) was subcutaneously administered to the rats, and then distilled water or Pavlova was orally administered by force using an oral catheter for rats.

[0057] After the surgery, distilled water or Pavlova was orally administered once daily, and body weight was measured immediately before administration. Specifically, the Pavlova group received daily oral administration of Pavlova at a dose of 600 mg / kg body weight. More specifically, the Pavlova group received a suspension of 1.2 g of Pavlova powder dispersed in 7 mL of distilled water at a dose of 0.35 mL / 100 g body weight. Ultrasonication was used to improve dispersion efficiency during suspension preparation, and the suspension was mixed before each administration. The control group received the same volume of distilled water (0.35 mL / 100 g body weight).

[0058] After the surgery, urine was collected from the metabolic cage every 24 hours. Food and water intake were also recorded daily. Seven days after the surgery (144 hours after surgery), blood was collected from the rats' tail veins. The collected blood was centrifuged at 3000 rpm for 15 minutes in 15 mL tubes. This resulted in the isolation of the plasma component from the blood. The plasma component was then dispensed into Eppendorf tubes and stored at -20°C.

[0059] <Test Results> (Changes in body weight and food intake) Table 1 shows the body weights of the control group (samples 101-105) and the Pavlova group (samples 11-15) measured immediately before surgery (day 0 after surgery), immediately after surgery (day 1 after surgery), and every 24 hours thereafter (days 2-7 after surgery). Table 2 shows the food intake measured in the same manner. In Tables 1 and 2, "day X (X is 0-7)" means "day X after surgery (X is 0-7)." In Table 1, the unit of body weight is grams (g). In Table 2, the unit of food intake is grams (g / day). In Table 2, the food intake values ​​are shown as the average values ​​of the control group (samples 101-105) and the Pavlova group (samples 11-15).

[0060] [Table 1]

[0061] [Table 2]

[0062] <Consideration> From Tables 1 and 2, it can be seen that there was no difference in body weight and food intake between the control group and the Pavlova group.

[0063] (Blood urea nitrogen (BUN) measurement) Blood samples were collected before surgery (day 0 after surgery) and 7 days after surgery (144 hours after the end of surgery), and blood BUN (unit: mg / dL) was measured for each group (control group (samples 101-105) and Pavlova group (samples 11-15)) by requesting Oriental Yeast Co., Ltd., Nagahama Life Science Laboratory. The results are shown in Table 3. In Table 3, "X day (X is 0 or 7)" means "X days after surgery (X is 0 or 7)."

[0064] (Measurement of urinary protein excretion) The 24-hour urinary protein excretion (unit: mg / day) for each group (control group (samples 101-105) and Pavlova group (samples 11-15)) was calculated using the Bradford method from urine samples taken for the 24 hours immediately before surgery (day 0 after surgery) and the 24 hours from urine samples taken for the 7 days after surgery (144 hours after the end of surgery). The results are shown in Table 4. In Table 4, "day X (X is 0 or 7)" means "day X after surgery (X is 0 or 7)."

[0065] [Table 3]

[0066] [Table 4]

[0067] <Consideration> It can be seen from Tables 3 and 4 that the Pavlova group had a more suppressed increase in blood BUN level and urinary protein excretion level 7 days after surgery than the control group.

[0068] (Changes in water intake) It is known that animals with renal damage, such as renal ischemia-reperfusion injury, increase their water intake. To confirm this phenomenon, the amount of distilled water consumed by rats in each group was measured immediately before surgery (day 0 after surgery), immediately after surgery (day 1 after surgery), and every 24 hours thereafter (days 2 to 7 after surgery). The results are shown in Table 5. In Table 5, "X day (X is 0 to 7)" represents "X days after surgery (X is 0 to 7)." The water intake values ​​in Table 5 are the average values ​​for the control group (samples 101 to 105) and the Pavlova group (samples 11 to 15).

[0069] [Table 5]

[0070] <Consideration> From Table 5, it can be seen that the Pavlova group showed a suppressed increase in water intake compared to the control group.

[0071] [Summary] Based on the above, the Pavlova group had the effect of reducing urinary protein excretion and blood urea nitrogen, suggesting that it may be possible to prevent or treat kidney damage. In particular, the Pavlova group showed a suppressed increase in water intake compared to the control group, suggesting that it may be possible to alleviate the symptoms of kidney damage.

[0072] 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.

[0073] 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 preventing or treating kidney damage, comprising microalgae.

2. The composition for preventing or treating kidney damage according to claim 1 , wherein the microalgae is classified into the genus Pavlova.

3. The composition for preventing or treating nephropathy according to claim 1 or 2, which is an agent for reducing urinary protein excretion.

4. 3. The composition for preventing or treating renal disorders according to claim 1 or 2, which is a blood urea nitrogen lowering agent.

5. 3. The composition for preventing or treating renal disorders according to claim 1 or 2, which is used to reduce the amount of protein excreted in urine or the amount of urea nitrogen in blood.

6. The composition for preventing or treating kidney damage according to claim 1 or claim 2, wherein the microalgae is administered orally at a daily dose of 1 mg / kg or more and 100 g / kg or less to a living body.

7. A material for food or drink, comprising the composition for preventing or treating nephropathy according to claim 1 or 2.

8. The food and drink material according to claim 7, which is applied to at least one selected from the group consisting of food and drink, oral medicines, and animal feed.

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