Enteral flora improving agent

Abstract

The purpose of the present invention is to provide an intestinal flora improving agent capable of increasing the number of bacteria belonging to the genus Bifidobacterium and / or bacteria belonging to the genus Lactobacillus in the intestine and improving intestinal flora. An enzyme-containing substance derived from a fungus belonging to the genus Penicillium increases the number of bacteria belonging to the genus Bifidobacterium and the number of bacteria belonging to the genus Lactobacillus in the intestine, and can exert an excellent intestinal flora improvement effect.

Description

Technical Field

[0001] The present invention relates to an agent for improving intestinal flora that can improve intestinal flora. More specifically, the present invention relates to an agent for improving intestinal flora that can increase the number of Bifidobacterium and Lactobacillus bacteria in the intestine. Background Art

[0002] In recent years, the causal relationship between the intestinal environment and various diseases has been actively studied, and it has been found that improving the intestinal environment is effective in preventing or improving various diseases. There are beneficial bacteria such as Bifidobacterium and Lactobacillus and harmful bacteria such as Escherichia coli mixed in the intestine, and it is important for the beneficial bacteria to form a dominant flora in order to form a healthy intestinal environment.

[0003] In the past, probiotics, prebiotics, etc. have been developed, and various raw materials for improving intestinal flora with the advantage of beneficial bacteria have been proposed. It has also been reported that the administration of enzymes can also improve intestinal flora.

[0004] For example, non-patent document 1 reports that in mice administered lipase derived from Candida rugose, intestinal flora can be improved. In addition, non-patent document 2 reports that in pigs fed with a specific mixed enzyme consisting of amylase, protease and xylanase at the same time as feed, the number of lactobacilli in the large intestine increased and the number of Escherichia coli decreased. In addition, non-patent document 3 reports that in pigs fed with a specific mixed enzyme consisting of amylase from Bacillus amyloliquefaciens, protease from Bacillus subtilis and xylanase from Trichoderma at the same time as feed, the number of lactobacilli increased and the number of Salmonella or Escherichia coli decreased.

[0005] However, conventionally, there has been no report that an enzyme derived from a Penicillium fungus can increase the bacterial count of Bifidobacterium bacteria and Lactobacillus bacteria in the intestine.

[0006] Prior art literature Non-patent literature Non-patent literature 1: Menden et al., Biomedicine&Pharmacotherapy, 2020,130:110579 Non-patent document 2: Yi et al., Asian Astralas. J. Anim. Sci., 2013, 26: 1181-1188 Non-patent literature 3: Zhang et al., J. Amin. Sci., 2014, 92: 2063-2069 Summary of the invention

[0007] Technical problem to be solved by the invention In recent years, as the interest in improving health has increased, there has been a desire to develop new raw materials that improve intestinal flora by making beneficial bacteria such as Bifidobacterium bacteria and Lactobacillus bacteria dominant.

[0008] Therefore, an object of the present invention is to provide an intestinal flora improving agent that can increase the number of Bifidobacterium bacteria and Lactobacillus bacteria in the intestine and improve the intestinal flora.

[0009] Technical solutions for solving technical problems The present inventors have conducted intensive research to solve the above problems and have found that an enzyme derived from Penicillium has the effect of increasing the number of Bifidobacterium and Lactobacillus in the intestine, and that an enzyme-containing substance derived from Penicillium can be used as an intestinal flora improving agent. The present invention has been completed based on the above findings and further research.

[0010] That is, the present invention provides the following inventions.

[0011] Item 1. An intestinal flora improving agent comprising an enzyme-containing substance derived from a Penicillium fungus as an active ingredient.

[0012] Item 2. The intestinal flora improving agent according to Item 1, wherein the enzyme derived from the genus Penicillium is a lipase and / or a nuclease derived from the genus Penicillium.

[0013] Item 3. The intestinal flora improving agent according to Item 1 or 2, wherein the enzyme derived from a fungus of the genus Penicillium is a lipase derived from Penicillium camemberti and / or a nuclease derived from Penicillium citrinum.

[0014] Item 4. The intestinal flora improving agent according to any one of Items 1 to 3, which is used for increasing the intestinal bacterial count of Bifidobacterium bacteria and / or Lactobacillus bacteria.

[0015] Item 5. An internal medicine for improving intestinal flora, comprising the intestinal flora improving agent according to any one of Items 1 to 4.

[0016] Item 6. A food additive for improving intestinal flora, comprising the intestinal flora improving agent according to any one of Items 1 to 4.

[0017] Item 7. A food or beverage for improving intestinal flora, comprising the intestinal flora improving agent according to any one of Items 1 to 4.

[0018] Item 8. A method for improving intestinal flora, comprising orally administering a substance containing an enzyme derived from a Penicillium fungus to a person who needs improvement of intestinal flora.

[0019] Item 9. An enzyme-containing material derived from Penicillium fungus, which is used for improving intestinal flora.

[0020] Item 10. Non-therapeutic use of an enzyme-containing substance derived from the genus Penicillium for improving intestinal flora.

[0021] Item 11. Use of an enzyme-containing substance derived from Penicillium fungus for the production of an agent for improving intestinal flora.

[0022] Effects of the Invention According to the present invention, by using an enzyme-containing substance derived from Penicillium fungi, the bacterial count of Bifidobacterium bacteria and / or Lactobacillus bacteria in the intestine can be increased, thereby improving the intestinal flora. This is effective for improving the intestinal environment, maintaining a healthy intestinal environment, and preventing or treating diseases and symptoms caused by an unhealthy intestinal environment. DETAILED DESCRIPTION

[0023] The intestinal flora improving agent of the present invention is characterized in that it contains a novel enzyme-containing substance derived from the genus Penicillium as an active ingredient. The intestinal flora improving agent of the present invention is described in detail below.

[0024] [Active ingredients] The intestinal flora improving agent of the present invention contains an enzyme-containing substance derived from the genus Penicillium as an active ingredient. Thus, by selecting and using an enzyme-containing substance derived from the genus Penicillium, the number of Bifidobacterium and Lactobacillus bacteria in the intestine is increased, and the intestinal flora can be effectively improved.

[0025] In the present invention, "a material containing an enzyme derived from Penicillium" refers to a substance containing an enzyme derived from Penicillium, and includes not only purified products of one or more Penicillium-derived enzymes, but also mixtures of one or more Penicillium-derived enzymes and other proteins, excipients, etc. In addition, in the present invention, "a material containing an enzyme derived from Penicillium" also includes purified products and crude products of cultures produced by culturing Penicillium to produce enzymes.

[0026] The source microorganism of the enzyme used in the present invention can be any Penicillium fungus, and specifically, Penicillium camemberti, Penicillium citrinum, Penicillium islandicum, Penicillium verrucosum, Penicillium glabrum, Penicillium chrysogenum, Penicillium digitatum, Penicillium dodgei, Penicillium expansum, Penicillium multicolor, etc. Among these Penicillium fungi, Penicillium camemberti and Penicillium citrinum are preferred examples.

[0027] In addition, the type of Penicillium-derived enzyme used in the present invention is not particularly limited, and examples thereof include lipase, nuclease, protease, amylase, cellulase, etc. Among these enzymes, lipase and nuclease are preferably used from the viewpoint of further effectively increasing the bacterial count of Bifidobacterium and Lactobacillus in the intestine.

[0028] Among the lipases derived from Penicillium fungi, lipases derived from Penicillium camembergis particularly have a remarkable effect of increasing the bacterial count of Bifidobacterium bacteria or Lactobacillus bacteria in the intestine, and are therefore suitable for use in the present invention.

[0029] In addition, about the nuclease derived from Penicillium, it can be a nuclease that can hydrolyze either RNA or DNA, or it can be a nuclease that can hydrolyze both RNA and DNA. In addition, the nuclease derived from Penicillium can be any one of exonuclease or endonuclease, and preferably exonuclease can be cited. As a preferred example of the nuclease derived from Penicillium, 5'-phosphodiesterase can be cited. 5'-phosphodiesterase refers to 5'-exonuclease (EC.3.1.4.1), which is a nuclease that hydrolyzes 5'-nucleotides in sequence from the 3'-end of nucleic acid (RNA and DNA). Among the lipases derived from Penicillium, the nuclease derived from Penicillium citrinum, especially the 5'-exonuclease derived from Penicillium citrinum, has a significant effect on increasing the number of Bifidobacterium or Lactobacillus in the intestine, and is suitable for use in the present invention.

[0030] The enzyme derived from the genus Penicillium can be produced by a known production method such as microbial culture or genetic engineering method, but since the enzyme derived from the genus Penicillium is commercially available, a commercially available product can also be used. For example, a lipase preparation derived from Penicillium camemberti and a 5'-exonuclease preparation derived from Penicillium citrinum can be obtained from Amano Enzyme Co., Ltd.

[0031] The Penicillium-derived enzyme-containing material used in the present invention may contain one type of Penicillium-derived enzyme, or may contain two or more types of Penicillium-derived enzymes.

[0032] [Applicable amount] The amount of the intestinal flora improving agent (enzyme-containing material derived from Penicillium fungi) of the present invention may be appropriately set depending on the type of active ingredient used, the type of product using the agent, the intended use, the expected effect, the form of application, and the like.

[0033] For example, the daily intake or dosage of an adult of an enzyme-containing substance derived from Penicillium fungi, in terms of the amount of the enzyme derived from Penicillium fungi, can be 0.01 g to 10 g, preferably 0.05 g to 5 g, and more preferably 0.1 g to 2.5 g. In the present specification, "the amount of the enzyme derived from Penicillium fungi" refers to a value obtained by converting the amount of the enzyme-containing substance derived from Penicillium fungi into the amount of the enzyme derived from Penicillium fungi contained in the enzyme-containing substance derived from Penicillium fungi.

[0034] For example, if a lipase-containing substance derived from the genus Penicillium is used, the daily intake or dosage of the lipase-containing substance derived from the genus Penicillium for an adult can be 10,000 U to 2,000,000 U, preferably 30,000 U to 1,000,000 U, and more preferably 50,000 U to 600,000 U, calculated as the amount of the lipase-containing substance derived from the genus Penicillium. In the present specification, "the amount of the lipase-containing substance derived from the genus Penicillium" refers to the value obtained by converting the amount of the lipase-containing substance derived from the genus Penicillium into the amount of the lipase-derived Penicillium contained in the substance. In addition, in the present specification, the lipase activity (U) is a value obtained by the following method.

[0035] <Method for measuring lipase activity> Add vinyl laurate to a 2 w / v% polyvinyl alcohol aqueous solution to a final concentration of 3%, and emulsify at 14200-14800 rpm for 10 minutes while cooling to below 10°C. Store in a refrigerator and use immediately after leaving for 1 hour.

[0036] First, accurately weigh 4 mL of 0.1 mol / L McIlvaine buffer (pH 5.6) and 5 mL of vinyl laurate emulsion, place them in a flat-bottom test tube (30×120 mm), shake and mix, place them at 40±0.5°C for 10 to 15 minutes, accurately add 1 mL of the sample solution containing the activity measurement object sample, and immediately shake and mix.

[0037] After the liquid was left to stand at 40±0.5°C for 30 minutes, 10 mL of a liquid prepared by mixing ethanol and acetone in a ratio of 1:1 was added and shaken to mix.

[0038] Next, 10 mL of 0.05 mol / L sodium hydroxide aqueous solution was accurately added, and 10 mL of a 1:1 mixture of ethanol and acetone was further added and shaken to mix, and then the excess sodium hydroxide was titrated with 0.05 mol / L hydrochloric acid (T 30 mL) (Indicator: 2 drops of phenolphthalein solution).

[0039] In addition, 4 mL of 0.1 mol / L McIlvaine buffer (pH 5.6) as a blank and 5 mL of vinyl laurate emulsion were accurately weighed, placed in a flat-bottom test tube (30×120 mm), shaken and mixed, and placed at 40±0.5°C for more than 30 minutes. Then, 10 mL of a liquid prepared by mixing ethanol and acetone in a volume ratio of 1:1 was added, and then 1 mL of a sample solution containing the sample to be measured for activity was accurately added and shaken and mixed.

[0040] Next, 10 mL of a 0.05 mol / L sodium hydroxide aqueous solution was accurately added, and titration was performed in the same manner as described below (T0 mL).

[0041] Use a pH meter to titrate, add 0.05 mol / L hydrochloric acid to titrate to pH 10.00. Under this condition, the fatty acid increases by 1 micromole ( μ The amount of enzyme per mole was taken as 1 U. The following formula was used in the calculation.

[0042] [Number 1] Fat digestibility (U / g, U / mL) = 50×(T0-T 30 )×1 / 30×f×n T0: Blank titration value (mL) T 30 : Titration value of reaction solution (mL) 50: Fatty acid equivalent (micromoles) relative to 1 mL of 0.05 mol / L hydrochloric acid (for quantitative analysis) 30: Reaction time (minutes) f: Factor of 0.05mol / L hydrochloric acid (for quantitative use) n: dilution factor per 1g or per 1mL of sample In addition, for example, if a nuclease-containing substance derived from the genus Penicillium is used, the daily intake or dosage of the nuclease-containing substance derived from the genus Penicillium for adults can be 1000U to 100000U, preferably 3000U to 60000U, and more preferably 5000U to 30000U, as converted to the amount of nuclease derived from the genus Penicillium. In the present specification, "converted to the amount of nuclease derived from the genus Penicillium" refers to the value obtained by converting the amount of the nuclease-containing substance derived from the genus Penicillium into the amount of the nuclease derived from the genus Penicillium contained in the substance. It should be noted that in the present specification, 1U of nuclease activity is the amount of enzyme that releases 1 micromole of phosphate within 1 minute when AMP is used as a substrate. For example, if the nuclease is a phosphodiesterase, it can be measured according to the first method of the phosphodiesterase activity test method specified in the 9th edition of the Food Additives Official Book (2018) (Consumer Affairs Agency, Ministry of Health, Labor and Welfare of Japan).

[0043] [use] The intestinal flora improving agent of the present invention increases the number of beneficial bacteria such as bifidobacteria and lactic acid bacteria in the intestine through the action of the enzyme-containing substance derived from the genus Penicillium, so that the beneficial bacteria can form a dominant flora, and therefore, it is used for the purpose of improving the intestinal environment, maintaining a healthy intestinal environment, etc. In particular, the intestinal flora improving agent of the present invention has an excellent effect of increasing the number of bifidobacteria and / or lactobacilli in the intestine, and therefore, it can also be used as an intestinal flora increasing agent for bifidobacteria and / or lactobacilli.

[0044] In addition, the intestinal flora improving agent of the present invention seeks to improve the intestinal environment by making beneficial bacteria form a dominant flora, and therefore, it can also be used for the purpose of preventing or treating diseases or symptoms caused by an unhealthy intestinal environment. Examples of such diseases or symptoms include: reduced immunity, colorectal cancer, allergic diseases, non-alcoholic fatty liver disease, obesity, inflammatory bowel disease, etc.

[0045] [Use form] The intestinal flora improving agent of the present invention is orally applied by oral ingestion or oral administration. If the intestinal flora improving agent of the present invention is orally ingested or orally administered and reaches the intestine, it plays a role in improving the intestinal flora, and therefore, it can be used in combination with various products such as food and beverages, oral medications, feed, and pet food.

[0046] When the intestinal flora improving agent of the present invention is blended into the above-mentioned various products, the product may contain probiotics and / or prebiotics together with the intestinal flora improving agent of the present invention as needed.

[0047] As microorganisms used as probiotics, for example, lactic acid bacteria, bifidobacterium, Bacillus natto, etc. can be cited. As lactic acid bacteria, specifically, lactobacillus lactic acid bacteria such as Lactobacillus casei, Lactobacillus acidophilus, and Lactobacillus plantarum can be cited; Enterococcus lactic acid bacteria such as Enterococcus faecalis, Enterococcus faecium, and Enterococcus hirae; Streptococcus lactic acid bacteria such as Streptococcus bovis and Streptococcus thermophilus can be cited. In addition, as bifidobacterium, specifically, Bifidobacterium adolescentis, Bifidobacterium longum, Bifidobacterium bifidum, Bifidobacterium pseudolongum, Bifidobacterium thermophilus can be cited. These probiotics can be used alone or in combination of two or more.

[0048] In addition, examples of prebiotics include xylo-oligosaccharides, fructo-oligosaccharides, soybean oligosaccharides, isomaltooligosaccharides, lactofructooligosaccharides, galacto-oligosaccharides, lactulose, etc. These prebiotics may be used alone or in combination of two or more.

[0049] The dosage form of the product containing the intestinal flora improving agent of the present invention may be any of solid, semisolid, liquid, etc., and may be appropriately set according to the type and use of the product.

[0050] When the intestinal flora improving agent of the present invention is used in food and beverages, the enzyme containing substance derived from the genus Penicillium is directly or combined with other food raw materials and additives to be adjusted to a desired form, and provided as a food and beverage that has an intestinal flora improving effect. As such food and beverages, in addition to ordinary food and beverages, specific health foods, nutritional supplements, functional foods, foods for patients, etc. can also be cited. There are no particular restrictions on the form of these food and beverages, for example, supplements such as tablets, granules, powders, capsules, and soft capsules; beverages such as nutritional drinks, fruit juice drinks, carbonated drinks, and lactic acid drinks, etc. can be illustrated.

[0051] When the intestinal flora improving agent of the present invention is used in food and drink, the amount of the agent added to the food and drink may be appropriately set within the range satisfying the above-mentioned applicable amount depending on the type of active ingredient used, the form of the food and drink, and the like.

[0052] For example, when the intestinal flora improving agent of the present invention is provided in the form of a supplement, the amount of the Penicillium-derived enzyme contained in the supplement can be 0.001 g to 0.9 g, preferably 0.01 g to 0.5 g, and more preferably 0.02 g to 0.2 g per 1 g of the supplement, calculated as the amount of the Penicillium-derived enzyme.

[0053] More specifically, as the intestinal flora improving agent of the present invention, if a lipase-containing substance derived from the genus Penicillium is used and provided in the form of a supplement, the amount of the lipase-containing substance derived from the genus Penicillium in the supplement, calculated as the amount of the lipase derived from the genus Penicillium, can be 3000 U / g to 1000000 U / g, preferably 10000 U / g to 600000 U / g, and more preferably 15000 U / g to 300000 U / g.

[0054] In addition, as the intestinal flora improving agent of the present invention, if a nuclease-containing substance derived from the genus Penicillium is used and provided in the form of a supplement, the amount of the nuclease-containing substance derived from the genus Penicillium in the supplement is calculated as the amount of the nuclease derived from the genus Penicillium, and can be 300 U / g to 50000 U / g, preferably 1000 U / g to 30000 U / g, and more preferably 1500 U / g to 15000 U / g.

[0055] For example, if the intestinal flora improving agent of the present invention is provided in the form of a beverage, the amount of the enzyme content derived from the genus Penicillium in the beverage, calculated as the amount of the enzyme derived from the genus Penicillium, can be 0.00001 g / mL to 0.02 g / mL, preferably 0.0001 g / mL to 0.01 g / mL, and more preferably 0.0002 g / mL to 0.005 g / mL.

[0056] More specifically, as the intestinal flora improving agent of the present invention, if the lipase-containing substance derived from the genus Penicillium is provided in the form of a beverage, the amount of the lipase-containing substance derived from the genus Penicillium in the beverage, calculated as the amount of the lipase derived from the genus Penicillium, can be 300 U / mL to 10000 U / mL, preferably 100 U / mL to 6000 U / mL, and more preferably 150 U / mL to 3000 U / mL.

[0057] In addition, as the intestinal flora improving agent of the present invention, if a nuclease-containing substance derived from the genus Penicillium is used and provided in the form of a beverage, the amount of the nuclease-containing substance derived from the genus Penicillium in the beverage is calculated as the amount of the nuclease derived from the genus Penicillium, and can be 3 U / mL to 500 U / mL, preferably 10 U / mL to 300 U / mL, and more preferably 15 U / mL to 150 U / mL.

[0058] Furthermore, when the intestinal flora improving agent of the present invention is used in the field of food and beverages, the enzyme-containing substance derived from the genus Penicillium can be provided as a food additive for improving intestinal flora alone or in combination with other ingredients.

[0059] In addition, when the intestinal flora improving agent of the present invention is used in an oral medicine, the intestinal flora improving agent of the present invention is adjusted to a desired form alone or in combination with other pharmacologically active ingredients, pharmaceutically acceptable bases or additives, etc., and provided as an oral medicine that produces an intestinal flora improving effect. There is no particular limitation on the form of such medicine, and specifically, oral preparations such as tablets, granules, powders, capsules, soft capsules, syrups, and liquids can be cited.

[0060] Examples of bases and additives used in the production of oral medicines include aqueous bases such as water and alcohol, oily bases, excipients, binders, extenders, disintegrants, lubricants, cooling agents, pH adjusters, thickeners, antioxidants, metal blocking agents, surfactants, emulsifiers, solubilizers, solubilizing agents, fragrances, preservatives, and the like.

[0061] When the intestinal flora improving agent of the present invention is used as an oral drug, the mixing ratio of the agent to the oral drug can be appropriately set within the range satisfying the above-mentioned applicable amount depending on the type of active ingredient used, the form of the oral drug, etc.

[0062] For example, if the intestinal flora improving agent of the present invention is provided in the form of a solid or semi-solid oral medicine, the amount of the Penicillium-derived enzyme-containing substance contained in the solid or semi-solid oral medicine can be 0.001 g to 0.5 g, preferably 0.01 g to 0.3 g, and more preferably 0.02 g to 0.15 g per 1 g of the oral medicine, calculated as the amount of the Penicillium-derived enzyme.

[0063] More specifically, as the intestinal flora improving agent of the present invention, if the lipase-containing substance derived from the genus Penicillium is provided in the form of a solid or semi-solid oral medicine, the amount of the lipase-containing substance derived from the genus Penicillium in the solid or semi-solid oral medicine is converted into the amount of the lipase derived from the genus Penicillium, and can be 3000 U / g to 1000000 U / g, preferably 10000 U / g to 600000 U / g, and more preferably 15000 U / g to 300000 U / g.

[0064] In addition, as the intestinal flora improving agent of the present invention, if a nuclease-containing substance derived from the genus Penicillium is used and provided in the form of a solid or semi-solid oral medicine, the amount of the nuclease-containing substance derived from the genus Penicillium in the solid or semi-solid oral medicine is 300 U / g to 50000 U / g, preferably 1000 U / g to 30000 U / g, and more preferably 1500 U / g to 15000 U / g, calculated as the amount of nuclease derived from the genus Penicillium.

[0065] More specifically, as the intestinal flora improving agent of the present invention, if a lipase-containing substance derived from the genus Penicillium is used and provided in the form of a liquid oral medicine, the amount of the lipase-containing substance derived from the genus Penicillium in the liquid oral medicine can be 30 U / mL to 10000 U / mL, preferably 100 U / mL to 6000 U / mL, and more preferably 150 U / mL to 3000 U / mL, calculated as the amount of the lipase derived from the genus Penicillium.

[0066] In addition, as the intestinal flora improving agent of the present invention, if a nuclease-containing substance derived from the genus Penicillium is used and provided in the form of a liquid oral medicine, the amount of the nuclease-containing substance derived from the genus Penicillium in the liquid oral medicine is 3 U / mL to 500 U / mL, preferably 10 U / mL to 300 U / mL, and more preferably 15 U / mL to 150 U / mL, calculated as nuclease-derived Penicillium.

[0067] In addition, when the intestinal flora improving agent of the present invention is used in feed or pet food, the intestinal flora improving agent of the present invention is adjusted to a desired form alone or in combination with other feed ingredients, and provided as feed or pet food that produces an intestinal flora improving effect. Examples of feed ingredients used in feed or pet food include: cereals such as corn, wheat, barley, and rye; brans such as wheat bran and rice bran; distiller's grains such as corn gluten meal and corn germ cake meal; animal feeds such as skim milk powder, whey, fish meal, and bone meal; yeasts such as brewer's yeast; calcium such as calcium phosphate and calcium carbonate; vitamins; amino acids; sugars, etc.

[0068] When the intestinal flora improving agent of the present invention is used as feed or pet food, the mixing ratio of the agent to the feed or pet food can be appropriately set according to the form and type of the feed or pet food, the type of animal to which it is applied, and the like.

[0069] For example, the amount of the Penicillium-derived enzyme-containing material in feed or pet food is 0.00001 g to 0.02 g, preferably 0.0001 g to 0.01 g, and more preferably 0.0002 g to 0.005 g per 1 g of feed or pet food in terms of the amount of the Penicillium-derived enzyme.

[0070] More specifically, when using a material containing a lipase derived from the genus Penicillium as the intestinal flora improving agent of the present invention, the amount of the material containing a lipase derived from the genus Penicillium in the feed or pet food can be 10 U / g to 2000 U / g, preferably 20 U / g to 1000 U / g, and more preferably 50 U / g to 500 U / g, calculated as the amount of the lipase derived from the genus Penicillium.

[0071] In addition, when using a nuclease-containing substance derived from the genus Penicillium as the intestinal flora improving agent of the present invention, the amount of the nuclease-containing substance derived from the genus Penicillium in the feed or pet food can be 1 U / g to 200 U / g, preferably 2 U / g to 150 U / g, and more preferably 5 U / g to 100 U / g, calculated as the amount of nuclease derived from the genus Penicillium.

[0072] Example Hereinafter, the present invention will be specifically described by way of examples, but the present invention is not limited to these examples.

[0073] Test Example 1: Effect of Penicillium-derived enzymes on intestinal flora Using SD rats (male, 4 weeks old, obtained from Hiroshima Experimental Animal Research Institute Co., Ltd.), the effects of ingestion of an enzyme preparation containing lipase from Penicillium camelliae (Amano Enzyme Co., Ltd.) (lipase activity: 50 U / mg) or an enzyme preparation containing nuclease (5'-phosphodiesterase) from Penicillium citrinum (Amano Enzyme Co., Ltd.) (nuclease activity: 7 U / mg) on ​​intestinal flora were investigated. The experiment was divided into two groups: a control group and an implementation group, with 8 rats in each group. Each group freely ingested the feed shown in Table 1 for 14 days.

[0074] [Table 1]

[0075] The unit of content of each component in the table is "weight %".

[0076] # It is composed of AIN-93 (a standard refined diet for mice and rats designed by the National Institute of Nutrition (AIN) of the United States).

[0077] After 14 days of feed intake, the body weight of each group of rats was calculated, and DNA was extracted from the cecal contents and sequenced by 16S rRNA gene analysis (Mishima et al. Am J Physiol Renal Physiol, 2018, 315:F824-F833), and the bacterial counts of Bifidobacterium and Lactobacillus in the cecal contents were quantified.

[0078] The obtained results are shown in Table 2. The bacterial counts of Bifidobacterium and Lactobacillus in the intestines of Examples 1 to 3 were all higher than those of the control. That is, it was found that the growth of Bifidobacterium and Lactobacillus in the intestines was promoted by taking the enzyme derived from the Penicillium fungus, and the intestinal flora was improved.

[0079] [Table 2] Average body weight and 16S rRNA sequencing analysis results

[0080] The results in the table are expressed as mean ± standard error (SE). Indicates the case where p<0.05 in Student's t-test.

Claims

1. An intestinal flora improving agent, characterized in that The active ingredient is an enzyme derived from the fungus Penicillium.

2. The intestinal flora improving agent according to claim 1, wherein The enzyme derived from the genus Penicillium is a lipase and / or a nuclease derived from the genus Penicillium.

3. The intestinal flora improving agent according to claim 1 or 2, wherein The enzyme derived from the genus Penicillium is a lipase derived from Penicillium camemberti and / or a nuclease derived from Penicillium citrinum.

4. The intestinal flora improving agent according to claim 1 or 2, wherein The intestinal flora improving agent is used to increase the intestinal flora count of Bifidobacterium bacteria and / or Lactobacillus bacteria.

5. An internal medicine for improving intestinal flora, characterized in that: Contains the intestinal flora improving agent according to claim 1 or 2.

6. A food additive for improving intestinal flora, characterized in that: Contains the intestinal flora improving agent according to claim 1 or 2.

7. A food or beverage for improving intestinal flora, characterized in that: Contains the intestinal flora improving agent according to claim 1 or 2.

8. A method for improving intestinal flora, characterized in that: The enzyme-containing substance derived from the fungus of the genus Penicillium is orally administered to a person who needs to improve the intestinal flora.

9. An enzyme-containing substance derived from Penicillium fungus, characterized in that: Used to improve intestinal flora.

10. Non-therapeutic use of an enzyme-containing substance derived from Penicillium fungus for improving intestinal flora.

11. Use of an enzyme-containing substance derived from Penicillium fungus in the production of an agent for improving intestinal flora.

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