Oral hair growth promoter

Abstract

To provide a food composition, a feed composition, and a pharmaceutical composition which exhibit a hair growth effect even with a small amount of intake and serve as a hair growth promoter with safety and supply stability.SOLUTION: A hair growth promoter according to the present invention comprises one selected from a microalga containing n-6DPA (n-6 docosapentaenoic acid), a fatty acid composition containing n-6DPA, and n-6DPA, and is intended for oral ingestion.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a hair-growth composition that contains n-6DPA (docosapentaenoic acid) and is expected to have a hair-growth effect when orally ingested, and to a food, feed, or medicine that contains said composition. [Background technology]

[0002] Since hair has a great influence on the impression of a person, its changes and abnormalities are of great concern. From birth to adolescence, the head hair gradually develops, and in a healthy state, there are about 100,000 hairs. However, thereafter, although there are gender and individual differences, changes such as loss of hair luster, loss of hair volume, thinning of hair, and increase in gray hair are observed with aging. Approximately 60% of women in their 20s to 60s have problems with their hair and scalp (Non-Patent Document 1), and there is concern that the deterioration of the appearance of hair can lead to loss of confidence and energy, a decrease in concentration at work or housework due to stress, and a decrease in opportunities for interpersonal interaction, leading to a decrease in quality of life.

[0003] On the other hand, the fur of animals plays a role in protecting the body from external stimuli such as enemies, ultraviolet rays, and pathogens, and in regulating body temperature. The condition of the fur is not only an important indicator for estimating the health condition, but also the appearance and texture have a large impact on the impression of the animal, so there is an increasing desire among owners to keep the fur of pet animals in good condition, especially for pet animals.

[0004] To date, collagen peptides (Patent Document 1) have been proposed as orally ingested hair care products, in particular processed collagen gel for the purpose of improving hair shine (Patent Document 2) and lactic acid bacteria (Patent Document 3). However, there is a need to further explore new materials that are excellent in productivity, safety, and stable supply.

[0005] 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.

[0006] 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 (Patent Document 4), Aurantiochytrium limacinum SR21 strain, etc. (Patent Documents 5 to 8, Non-Patent Document 2), Thraustochytrium sp. LFF1 strain (Patent Document 9), Thraustochytrium microorganisms (Patent Documents 10 and 11), etc. have been proposed.

[0007] 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 3). n-6DPA (docosapentaenoic acid), a (n-6) PUFA, has been reported to have an antithrombotic effect (Non-Patent Document 4) and an effect of promoting vascular endothelial cell migration (Non-Patent Document 5). However, no hair care composition containing these PUFAs and the microalga Thraustochytrid has been reported so far. [Prior art documents] [Patent documents]

[0008] [Patent Document 1] Patent No. 4204503 [Patent Document 2] Patent No. 6301479 [Patent Document 3] JP 2020-202759 A [Patent Document 4] Patent No. 3127161 [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]

[0009] [Non-Patent Document 1] Mochida Healthcare Co., Ltd., “Survey on the Actual Condition of Hair and Scalp among Women in Their 20s to 60s”, [online], October 6, 2021, [Retrieved October 23, 2023], Internet < URL: https: / / cdn.kyodonewsprwire.jp / prwfile / release / M000406 / 202110051167 / _prw_OR1fl_fUHJ7Ki4.pdf> [Non-Patent Document 2] Journal of Bioengineering, The Society of Biotechnology, Japan, 2015, Vol. 93, No. 7, pp. 426-429 [Non-Patent Document 3] Lipid in Health and Disease(2017), 16:118 [Non-Patent Document 4] blood advances (2020), 4, p.4522-4537 [Non-Patent Document 5] 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]

[0010] Conventional topical hair care products have raised concerns about skin irritation and side effects, as well as limitations to percutaneous absorption of ingredients, and there are still very few internal hair care products on the market.

[0011] An object of the present invention is to provide a food composition, feed and pharmaceutical composition that can be used as a hair growth agent, which is safe, can be stably supplied, and has a sufficient hair growth effect even when taken in a small amount. [Means for solving the problem]

[0012] As a result of intensive research to solve the above problems, it was found that the fur gloss of rats that were fed microalgae containing n-6DPA was improved, leading to the completion of the present invention.

[0013] That is, the first aspect of the present invention is a hair care product that is characterized by being orally ingested and that comprises any one of microalgae containing n-6DPA (n-6 docosapentaenoic acid), a fatty acid composition containing n-6DPA, or n-6DPA. A second aspect of the present invention is a hair care product characterized in that the microalgae in the first aspect of the present invention is Thraustochytrid. The third aspect of the present invention is a food composition or feed composition for hair growth, which contains the hair growth agent according to any one of the first and second aspects of the present invention. The fourth aspect of the present invention is a pharmaceutical composition for hair care, comprising the hair care agent according to any one of the first and second aspects of the present invention. Effect of the Invention

[0014] According to the present invention, it is possible to provide a hair growth agent in the form of a food composition, feed, pharmaceutical composition, etc., which has a hair growth effect even when taken in a low dose and can be used as a safe and stable hair growth agent. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0015] The configuration of the present invention will be described in detail below, however, the present invention is not limited to the following embodiments.

[0016] 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.

[0017] 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.

[0018] The n-6DPA contained in the agent of the present invention may be obtained from any organism such as fish, or may be synthesized, but from the viewpoint of production efficiency, it is preferable to obtain it from microalgae.

[0019] 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.

[0020] 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.

[0021] 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.

[0022] 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.

[0023] 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.

[0024] 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 content of the algae and PUFAs required to achieve the desired hair growth effect, and is efficient in terms of production.

[0025] 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.

[0026] 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.

[0027] 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.

[0028] 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.

[0029] The lower limit of the daily n-6DPA equivalent amount ( / kg body weight) may be appropriately selected taking into consideration the required hair growth effect and cost, 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.

[0030] The food composition of the present invention contains the agent of the present invention and is used as a hair care product. Specifically, it may be a functional food (including functional food and food for specified health uses, including food additives) and a dietary supplement. Its form may be solid, semi-liquid, or liquid.

[0031] 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.).

[0032] 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.

[0033] As for the feed or animal supplement, the agent of the present invention can be provided as it is as feed or animal supplement, or the agent of the present invention can be provided by being contained in feed or animal supplement. The feed or animal supplement thus provided is a feed or animal supplement containing an effective amount of the composition of the present invention.

[0034] The form of feed or animal supplement is not particularly limited, and may be, for example, semi-liquid, gel, solid or powder.In addition, animal supplements include, but are not particularly limited to, granules and powders obtained by adding excipients, binders, etc. to the composition of the present invention to granulate, tablets produced by kneading the composition of the present invention with excipients and binders and then tableting, and capsules enclosed in capsules, etc.

[0035] The composition of the present invention can be provided in a unit package form in which the amount to be taken per meal is predetermined. The unit package form per meal can be, for example, a pack, a package, a can, a bottle, etc., which specifies a certain amount. In order to better exert the various effects of the composition of the present invention, the intake amount per meal can be determined according to the intake amount of the composition of the present invention per time. The feed and animal supplement of the present invention may be provided with an explanation about the intake amount on the package, or with a text containing the explanation.

[0036] The pharmaceutical composition of the present invention contains the agent of the present invention and is used as a hair care product through oral administration. The hair gloss improving effect of n-6DPA, i.e., hair care effect, can be expected.

[0037] 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.

[0038] Oral preparations include granules, powders, tablets, pills, capsules, syrups, emulsions, and suspensions. These preparations can be formulated using pharmaceutically acceptable carriers by methods commonly used in the art. Pharmaceutically acceptable carriers include excipients, binders, diluents, additives, flavors, buffers, thickeners, colorants, stabilizers, emulsifiers, dispersants, suspending agents, and preservatives. EXAMPLES

[0039] 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.

[0040] Example: Evaluation test of oral administration of dried algae using rats (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 90 L culture device in liquid medium (glycerol 4%, yeast extract 4%, artificial seawater 0.9%) for 4 days. Approximately 3 kg of wet algae obtained by centrifuging the culture solution was vacuum freeze-dried to prepare approximately 700 g of dry algae.

[0041] (2) Lipid extraction and PUFAs analysis According to the usual method (JP Patent Publication 2020-54391), chloroform and methanol (volume ratio 2:1) were added to the wet algae to extract lipids, which were then concentrated to dryness and re-extracted with n-hexane. The sample was then analyzed by gas chromatography (GC-FID). As a result, fatty acids were extracted as fatty acid methyl esters, and the ratio (%) of the peak area of ​​each fatty acid methyl ester to the previous fatty acid methyl ester was calculated. The ratio of each PUFA contained in the dry algae is shown below. DHA:11.6%, n-6DPA:2.9%, n-3DPA:0.1%, EPA:0.1%

[0042] (3) Preparation of administration samples and oral administration The dried algae were suspended in water for injection (Otsuka Pharmaceutical Factory, Inc.) to give 0.4 and 4 mg / mL samples, and the water for injection (control: comparative example) was continuously orally administered (once a day for 28 days) to Wistar rats (5-week-old males, 8 rats / group) using an oral probe. The daily dose of n-6DPA contained in the dried algae and the dried algae per kg of rat body weight are shown below. Dry algae (n-6DPA): 4mg (0.12mg), 40mg (1.2mg)

[0043] (4) Coat gloss evaluation and results After the intake period, each rat was observed from the back and rated on the following 5-point scale. 1 point: very bad, 2 points: bad, 3 points: average, 4 points: good, 5 points: very good

[0044] The scores for each rat were tallied, and the average score was calculated and evaluated (Table 1, Examples 1 and 2).

[0045] [Table 1]

[0046] As shown in Table 1, rats that ingested dried algae had higher evaluation scores than the control group, demonstrating improved hair gloss, i.e., a hair-growth effect. Effects were observed at intakes of 4mg / kg or more, and no correlation was observed between higher intake amounts and the improvement effect. These results confirmed that ingesting dried Aurantiochytrium algae has a hair-growth effect. Furthermore, no abnormalities, such as changes in weight, were observed in the rats during the administration period of the dried algae.

Claims

1. A hair care product which is orally ingested and which comprises any one of microalgae containing n-6DPA (n-6 docosapentaenoic acid), a fatty acid composition containing n-6DPA, and n-6DPA.

2. The hair care product according to claim 1, characterized in that the microalgae is Thraustochytrid.

3. A hair care food composition or feed composition comprising the hair care agent according to claim 1 or 2.

4. A pharmaceutical composition for hair care, comprising the hair care agent according to claim 1 or 2.

Images