Capillary shape improver

Abstract

To provide a food composition and a pharmaceutical composition suitable for use as a capillary shape improver that can effectively improve a capillary shape even when consumed at low dosages, while ensuring safety and stable supply.SOLUTION: The present invention provides a capillary shape improver for oral administration that comprises any one of microalgae containing n-6 docosapentaenoic acid (n-6DPA), a fatty acid composition containing n-6DPA, and n-6DPA.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to an agent, food, or medicine used to improve the shape of capillaries. More specifically, the present invention relates to an agent, food, or medicine that contains n-6 DPA (n-6 docosapentaenoic acid), is orally administered, and has an excellent effect of improving the shape of capillaries. [Background technology]

[0002] Blood plays an important role in maintaining homeostasis in the body, transporting oxygen, nutrients, signaling substances such as hormones, immune cells, and waste products, and also maintaining body temperature by circulating blood at a constant temperature.

[0003] Blood flows to every corner of the body through capillaries that are spread all over the body, even to peripheral areas. However, deterioration of the structure and function of capillaries due to aging, poor diet, lack of exercise, lack of sleep, stress, etc., causes blood components to leak out of the blood vessels, leading not only to chills and swelling, but also to a decline in the function of tissues and organs such as the bones and brain (Non-Patent Document 1).

[0004] Capillaries in good condition are thin, straight, and hairpin-shaped, and are arranged in a uniform, regular pattern, but capillaries with poor blood flow are seen to have a large diameter, short loop lengths, twisted structures, and unclear shapes due to the cloudiness of the extracellular fluid around the vessels (Non-Patent Document 2).

[0005] As a method for improving the function of capillaries, moderate exercise such as walking and heel raising and lowering, massage, bathing, etc. are said to be effective (Non-Patent Document 3). In addition, Angelica sinensis extract (Patent Document 1) has been proposed as an agent for improving abnormal blood vessels, and lipopolysaccharide derived from Pantoea agglomerans is used as an active ingredient to increase the number of capillaries (Patent Document 2). However, further exploration of materials with excellent productivity, safety, and stable supply is required.

[0006] In recent years, n-3 PUFAs (polyunsaturated fatty acids), such as DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid) derived from fish oil, and n-3DPA (n-3 docosapentaenoic acid) derived from the subcutaneous fat of harp seals and sunfish, have become increasingly popular for use in health foods, supplements, and infant formulas due to their ability to improve brain function and neutral fat levels.

[0007] Microalgae Thraustochytrids have been attracting attention as a new source of PUFAs other than fish oil and subcutaneous fat of harp seals and sunfish. Thraustochytrids belong to the Labyrinthulae, are heterotrophic algae that do not have chlorophyll, and can be cultured on a large scale in a fermenter, so they have been attracting attention from the perspective of stable supply, safety, and SDGs (Sustainable Development Goals). As sources of PUFAs, Schizochytrium sp. ATCC20888 strain and its derivatives (Patent Documents 3 and 4), Aurantiochytrium limacinum SR21 strain, etc. (Patent Documents 5 to 8, Non-Patent Document 4), Thraustochytrium sp. LFF1 strain (Patent Document 9), Thraustochytrium microorganisms (Patent Documents 10 and 11), etc. have been proposed.

[0008] EPA, one of the (n-3) PUFAs, has been proposed as a peripheral blood flow disorder treatment agent by acting on the deformability of red blood cells when taken at 1.2 to 3.6 g per day (Patent Document 12), and DHA has been reported to have an effect of improving vascular endothelial function (Non-Patent Document 5). n-6DPA (docosapentaenoic acid), a (n-6) PUFA, has been reported to have an antithrombotic effect (Non-Patent Document 6) and an effect of promoting vascular endothelial cell migration (10 times that of EPA, Non-Patent Document 7). However, it has not been proposed that these PUFAs have an effect of improving the shape of capillaries, or that PUFAs have an effect of improving the shape of capillaries. [Prior art documents] [Patent documents]

[0009] [Patent Document 1] Patent Publication No. 2021-187802 [Patent Document 2] Patent No. 6851819 [Patent Document 3] Patent No. 3127161 [Patent Document 4] Patent No. 3669372 [Patent Document 5] Patent No. 2764572 [Patent Document 6] Patent No. 3985035 [Patent Document 7] Patent No. 6055469 [Patent Document 8] JP 2020-054391 A [Patent Document 9] Patent No. 4280158 [Patent Document 10] Patent No. 5762393 [Patent Document 11] JP 2018-108096 A [Patent Document 12] Japanese Patent Publication No. 58-180423 [Non-patent literature]

[0010] [Non-Patent Document 1] Atto Corporation, Supervised by Professor Nobuyuki Takakura of the Institute for Microbial Diseases, Osaka University, "Learn about Capillaries," [online], [Retrieved June 19, 2023], Internet<URL:http: / / lab.kekkan-bijin.jp / know.html#know2> [Non-Patent Document 2] Atto Corporation, Supervised by Professor Nobuyuki Takakura, Research Institute for Microbial Diseases, Osaka University, "Let's Observe Capillaries," [online], [Retrieved June 19, 2023], Internet<URL:http: / / lab.kekkan-bijin.jp / observ.html> [Non-Patent Document 3] NHK, "Asaichi: Farewell! A Great Plan to Improve Blood Flow Against Winter Fatigue," January 11, 2023, [online], [searched June 19, 2023], Internet <URL:https: / / www.nhk.jp / p / asaichi / ts / KV93JMQRY8 / episode / te / PW7WMYLN4L / ?fbclid=IwAR3EQ8NEzJgYpjixOE5lu5bv52ZWznj56hiGFZx76hZpGixBgZ0EfIBxi_0> [Non-Patent Document 4] Journal of Bioengineering, The Society of Biotechnology, Japan, 2015, Vol. 93, No. 7, pp. 426-429 [Non-Patent Document 5] Lipid in Health and Disease(2017), 16:118 [Non-Patent Document 6] blood advances (2020), 4, p.4522-4537 [Non-Patent Document 7] Lipid Nutrition, Society of Lipid Nutrition, 1996, Vol. 5, No. 1, pp. 17-22 Summary of the Invention [Problem to be solved by the invention]

[0011] No effect of improving capillary shape has been found for the (n-3) PUFAs DHA and EPA derived from fish oil and microalgae, and no suggestion has been made about the effect of the (n-6) PUFA n-6DPA on improving capillary shape.

[0012] An object of the present invention is to provide a food composition and a pharmaceutical composition that can be used as a capillary shape improving agent that has the effect of improving the shape of capillaries when ingested in low doses, is safe, and can be supplied stably. [Means for solving the problem]

[0013] As a result of intensive research to solve the above problems, it was discovered that the effect of improving capillary shape can be achieved by ingesting a low dose of microalgae containing n-6DPA, which led to the completion of the present invention.

[0014] That is, the first aspect of the present invention is a capillary shape improving agent that is characterized by being composed of one of microalgae containing n-6DPA (n-6 docosapentaenoic acid), a fatty acid composition containing n-6DPA, or n-6DPA, and is administered orally. A second aspect of the present invention is a capillary shape improving agent, characterized in that the microalgae in the first aspect of the present invention are Thraustochytrids. A third aspect of the present invention is a food composition for improving a capillary vessel shape, which contains the capillary vessel shape-improving agent according to any one of the first and second aspects of the present invention. A fourth aspect of the present invention is a pharmaceutical composition for improving a capillary blood vessel shape, comprising the capillary blood vessel shape-improving agent according to any one of the first to third aspects of the present invention. Effect of the Invention

[0015] INDUSTRIAL APPLICABILITY The present invention makes it possible to provide a food composition and a pharmaceutical composition that have a capillary shape improving effect even when ingested in a low dose, and can be used as a capillary shape improving agent that is safe and can be supplied stably. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0016] The configuration of the present invention will be described in detail below, however, the present invention is not limited to the following embodiments.

[0017] First, the microalgae contained in the agent of the present invention will be described. The microalgae contained in the agent of the present invention are algae bodies of microalgae that can be used as food. "Usable as food" refers to algae that have been eaten or that have been shown to have no problems in safety tests on animals and humans. Microalgae is a general term for algae that require a microscope to identify individuals, and taxonomically they range from prokaryotic cyanobacteria belonging to bacteria in the broad sense, green algae closely related to higher plants, and flagellates that are also classified in the phylum Protozoa. Examples of microalgae that can be used as food in the present invention include Chlorella (green algae), Spirulina (cyanophyte), Euglena (Japanese name: Midorimushi, protozoa / green algae), Dunaliella (green algae), Nannochloropsis (true eyespot algae), and Labyrinthulea Thraustochytrids (Labyrinthula is considered to be a type of microalgae in this specification). Of these, preferred are Spirulina, Euglena, Nannochloropsis, and Labyrinthulea Thraustochytrids which inherently contain PUFAs, or Chlorella which can be cultured with the addition of fatty acids to contain PUFAs in its algae, more preferably Nannochloropsis and Labyrinthulea Thraustochytrids which have a high PUFA content, and even more preferably Labyrinthulea Thraustochytrids which can be cultured in a closed tank system and are therefore highly safe.

[0018] The PUFAs contained in the agent of the present invention may be obtained from any microalgae that contains n-6DPA, regardless of whether it can be used as a food product, but it is preferable to obtain them from microalgae that can be used as a food product.

[0019] The n-6DPA contained in the agent of the present invention may be obtained from any organism, such as fish oil, or may be synthesized, but from the viewpoint of production efficiency, it is preferable to obtain it from microalgae.

[0020] Labyrinthulae are classified into the kingdom Chromista, the phylum Heterokonta, the class Labyrinthulacea, and the order Labyrinthulales. They are further classified into the Labyrinthulids, which belong to the family Labyrinthulidae, and the Thraustochytrids, which belong to the family Thraustochytrididae. Thraustochytrids include the genera Schizochytrium, Aurantiochytrium, Oblongichytrium, Thraustochytrium, Parietychytrium, Ulkenia, and Botryochytrium, which have been frequently studied in terms of application from the viewpoints of cell proliferation and PUFAs productivity, but are not particularly limited in the present invention.

[0021] The algae cells of microalgae can be commercially available products, OEM manufactured products, or homemade products. Examples of commercially available products include dried algae cells of Chlorella, Spirulina, and Euglena, and dried algae cells of Schizochytrium and Aurantiochytrium. There are no particular limitations on OEM manufacturing or homemade products, but algae cells obtained by culturing under optimized conditions using a food-grade culture medium can be used.

[0022] Next, the microalgae, fatty acid composition, and n-6DPA contained in the agent of the present invention will be described with a focus on the cultivation of microalgae, collection of algae bodies, drying, and powderization. The solid medium and liquid medium used in the cultivation of microalgae can be any known medium base material containing natural or artificial seawater, carbon source, nitrogen source, inorganic salt, etc. For example, examples of carbon sources include carbohydrates such as glucose, fructose, and galactose, as well as oils and fats such as oleic acid and soybean oil, glycerol, acetic acid, and sodium acetate, but are not limited thereto. The carbon source can be used at a concentration of, for example, 20 to 300 g per 1 L of medium. In a particularly preferred embodiment, after the initial carbon source is consumed, the carbon source can be fed to continue the cultivation. By culturing under such conditions, it is possible to increase the amount of carbon source consumed, and the production amount of the fatty acid composition obtained from the microalgae can be increased. For example, the nitrogen source may be organic nitrogen such as yeast extract, corn steep liquor, peptone, polypeptone, sodium glutamate, urea, etc., or inorganic nitrogen such as ammonium acetate, ammonium sulfate, ammonium chloride, sodium nitrate, ammonium nitrate, ammonia, etc., but is not limited thereto. As the inorganic salt, potassium phosphate, etc. may be used in appropriate combination.

[0023] The medium containing each of the medium bases is preferably adjusted to pH 4.0 to 9.5 with an appropriate acid or base, and then sterilized by autoclaving before use. The pH during culture is generally 3.5 to 10.0, and preferably 4.0 to 9.5. Liquid culture can be carried out for 2 to 10 days under aeration and stirring. The culture temperature is generally 10 to 45°C, and preferably 15 to 35°C. The culture temperature is preferably controlled to a culture temperature at which a fatty acid composition can be produced. The scale of liquid culture is not particularly limited, and commercially available closed culture equipment can be used. The algae can be collected from the obtained culture liquid by a known conventional method such as centrifugation or filtration.

[0024] The algal cells (wet algal cells) obtained by cultivation can be dried by methods including, but not limited to, freeze-drying, air drying, spray drying, tunnel drying, vacuum drying (freeze-drying) or similar processes. Wet algal cells or cells washed with water or the like after collection of wet algal cells may be used directly without a drying process. In the case of Thraustochytrium and Aurantiochytrium, the algal cells are killed by freeze-drying, which reduces the risk of bacterial growth during long-term storage. The method of powdering the dried algal cells is not particularly limited, and examples of the equipment include batch or continuous blenders, mixers, mills, kneaders, pulverizers, crushers, grinders, and other equipment.

[0025] In the present invention, the n-6DPA content in the total fatty acids in the dried algae is generally adjusted to 1% by weight or more depending on the microalgae species and its culture conditions, but is preferably 6% by weight or more, and more preferably 7% by weight or more. This makes it possible to reduce the algae and PUFAs content required to achieve the desired capillary shape improvement effect, and is efficient in terms of production.

[0026] A fatty acid composition containing n-6DPA can be prepared from the algae by a known method. That is, after the cultivation, wet or dried algae can be physically crushed by a mill or ultrasonic wave or chemically dissolved by a solvent, and then a fatty acid composition containing PUFAs can be obtained by solvent extraction using chloroform, hexane, methanol, ethanol, etc. Furthermore, the obtained fatty acid composition may be chemically or physically modified or processed based on the requirements of the composition by any known technique.

[0027] n-6DPA can be prepared, for example, from the fatty acid composition or other fatty acid compositions containing n-6DPA by known methods. That is, it can be separated and purified from mixed fatty acids or fatty acid esters by, for example, the urea addition method, the cooling separation method, the column chromatography method, etc. Alternatively, it may be separated and purified by other methods in the art.

[0028] The fatty acid composition extracted from the microalgae and n-6DPA may be mixed with carbohydrates, emulsifiers, milk proteins, antioxidants, etc. in a conventional manner to prepare an emulsion, and then processed into powdered oils and fats by methods including, but not limited to, a spray-type heat drying method, a spray-type cooling method, a pulverization-type freeze-drying method, a pulverization-type cooling solidification method, a coating-type microencapsulation method, a coating-type spray mixing method, or similar processes.

[0029] The upper limit of the daily n-6DPA equivalent amount ( / kg body weight) when taking the agent of the present invention is 1.2 mg or less, preferably 0.9 mg or less, more preferably 0.6 mg or less, and even more preferably 0.3 mg or less, as confirmed by a simple test.

[0030] The lower limit of the daily n-6DPA equivalent amount ( / kg body weight) may be appropriately selected taking into consideration the required effect of improving capillary shape and costs, etc., and is not particularly limited, but may be, for example, 0.03 mg or more, preferably 0.06 mg or more, more preferably 0.09 mg or more, and even more preferably 0.12 mg or more.

[0031] The food composition of the present invention contains the agent of the present invention and is used to improve the shape of capillaries. Specifically, it may be a functional food (including functional food and food for specified health uses, including food additives) and a nutritional supplement. Its form may be solid, semi-liquid, or liquid.

[0032] Examples of foods include, but are not limited to, agricultural products (bread, noodles, rice, sweets, tofu and processed products thereof, etc.), fermented foods (sake, medicinal sake, mirin, vinegar, soy sauce, miso, etc.), livestock products (yogurt, ham, bacon, sausage, etc.), seafood products (kamaboko, fried tempura, hanpen, etc.), and beverages (fruit juice drinks, soft drinks, sports drinks, alcoholic drinks, tea, etc.).

[0033] Functional foods and nutritional supplements can be produced as food and drink in the form of powders, granules, tablets, capsules, lozenges, liquids for internal use, suspensions, emulsions, syrups, drinks, natural liquid diets, semi-digested nutritional foods, elemental nutritional foods, enteral nutrients, etc. In such cases, other nutritional components or functional components may be blended together with the algae of the present invention. Alternatively, the algae of the present invention may be in the form of a pharmaceutical preparation, for example, a natural liquid diet, semi-digested nutritional foods, elemental nutritional foods, drinks, enteral nutrients, etc., in which the algae of the present invention are blended with proteins, sugars, fats, trace elements, vitamins, emulsifiers, flavors, etc., or the like, but may also be in the form of the above-mentioned food and drink.

[0034] The pharmaceutical composition of the present invention contains the agent of the present invention and is used for improving the shape of capillaries through oral administration. The effect of n-6DPA in improving the shape of capillaries, i.e., the effect of promoting blood flow, is expected to contribute to maintaining health.

[0035] The pharmaceutical composition may be formulated for oral administration by known dispensing techniques and may be in any form, such as solid, liquid, semisolid, etc. The n-6DPA or mixtures thereof in the pharmaceutical composition may be in a free form or in the form of a medicament acceptable salt, such as a sodium salt, potassium salt, lithium salt, or other alkali metal salt, other metal salt such as zinc salt, calcium salt, magnesium salt, or in various forms such as monoglyceride, diglyceride, triglyceride, ester of lower alcohol, phospholipid, glycolipid, amide, etc. The lower alcohol here refers to a monohydric alcohol having 6 or less carbon atoms, and examples thereof include methanol, ethanol, propanol, isopropanol, butanol, pentanol, hexanol, etc. EXAMPLES

[0036] The present invention will be described in detail below with reference to examples. However, the examples are merely illustrative and the present invention is not limited thereto. In the following, % indicates % by weight unless otherwise specified.

[0037] (1) Production of dried algae The SPA-214 strain, which was created by UV mutagenesis from Aurantiochytrium sp. NBRC111922 (provided by the National Institute of Technology and Evaluation), was cultured in a 600 L culture device in liquid medium (glycerol 4%, yeast extract 4%, artificial seawater 0.9%) for 4 days. Approximately 15 kg of wet algae obtained by centrifuging the culture solution were vacuum freeze-dried to prepare approximately 3200 g of dry algae.

[0038] (2) Manufacturing of microalgae-containing supplements A microalgae-containing supplement was manufactured with 280 mg of dried algae per capsule. The n-6DPA, DHA, and EPA contents per capsule are shown below. n-6DPA: 14mg DHA: 45mg, EPA: 0.42mg

[0039] Example 1: Evaluation of the effect of taking a microalgae-containing supplement on capillaries The effect on capillary shape of a male in his 40s was investigated when he took one tablet of a microalgae-containing supplement per day for 12 weeks. Before and after taking the microalgae-containing supplement, a capillary observation device was used to take microscopic images of the border between the nail and skin of the ring finger of the left hand, and the length of the capillaries was calculated using an analysis system. The results showed that taking the microalgae-containing supplement increased the length of the capillaries (Table 1). After taking the supplement, the subject commented that his complexion had improved and he felt less tired.

[0040] Example 2: Evaluation of the effect of taking a microalgae-containing supplement on capillaries A test similar to that in Example 1 was conducted on a male in his 60s. The results showed that the length of the capillaries increased after taking the microalgae-containing supplement (Table 1). After taking the supplement, the subject commented that his stiff shoulders and tired eyes had improved.

[0041] Example 3: Evaluation of the effect of taking a microalgae-containing supplement on capillaries A test similar to that in Example 1 was conducted on one male subject in his 40s. The results showed that the length of capillaries increased by taking a supplement containing microalgae (Table 1).

[0042] Comparative Example 1: Evaluation of the effect of taking a microalgae-containing supplement on capillaries A placebo containing dextrin instead of microalgae was prepared and a test similar to that in Example 1 was carried out on one woman in her 30s. No elongation of capillaries was observed before or after ingestion (Table 1).

[0043] [Table 1]

[0044] As shown in Examples 1 to 3, the capillary elongation effect was obtained by taking 280 mg of microalgae per day. The (n-3) PUFAs contained in 280 mg of dried algae were very small, with 45 mg of DHA and 0.42 mg of EPA, which is not an amount that can be expected to improve vascular endothelial function. Considering that the second most abundant PUFAs contained in dried algae after DHA is n-6DPA, it is presumed that the capillary elongation effect in the examples is due to n-6DPA. In addition, no abnormalities were found in the physical condition check at the time of data acquisition, and no subjects complained of adverse events due to the intake of supplements during the test period.

Claims

1. A capillary shape improving agent characterized by comprising any one of microalgae containing n-6DPA (n-6 docosapentaenoic acid), a fatty acid composition containing n-6DPA, and n-6DPA, and being orally administered.

2. 2. The capillary shape improving agent according to claim 1, wherein the microalgae is Thraustochytrid.

3. A food composition for improving capillary vessel shape, comprising the capillary vessel shape-improving agent according to claim 1 or 2.

4. A pharmaceutical composition for improving capillary blood vessel shape, comprising the capillary blood vessel shape-improving agent according to any one of claims 1 to 3.

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