WO2020256017A1 - Milky plasma improving agent - Google Patents

Milky plasma improving agent Download PDF

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Publication number
WO2020256017A1
WO2020256017A1 PCT/JP2020/023776 JP2020023776W WO2020256017A1 WO 2020256017 A1 WO2020256017 A1 WO 2020256017A1 JP 2020023776 W JP2020023776 W JP 2020023776W WO 2020256017 A1 WO2020256017 A1 WO 2020256017A1
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plasma
red yeast
yeast rice
cholesterol
chylothorax
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PCT/JP2020/023776
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French (fr)
Japanese (ja)
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浅野　幸一
悠貴 比嘉
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小林製薬株式会社
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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/06—Fungi, e.g. yeasts
    • A61K36/062—Ascomycota
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid

Definitions

  • the present invention relates to a chylothorax plasma improving agent.
  • the present invention also relates to an agent for suppressing or ameliorating chylomicronemia.
  • lipids such as triglyceride, cholesterol, phospholipids, and free fatty acids are usually present.
  • the phenomenon that serum and plasma become cloudy white occurs as if milk was mixed. Such a state is called “chylothorax”.
  • the causes of "milk” are an increase in triglycerides and cholesterol (exogenous lipids) in the blood due to ingestion of a high-fat diet and a high-cholesterol diet, and a deficiency and function of lipoprotein lipase that decomposes lipids in the blood.
  • Various causes such as a decrease can be considered.
  • red yeast rice and its processed products have been conventionally used as functional foods having a cholesterol lowering action (for example).
  • Patent Document 1 Monascus is a bright red yeast rice in which red yeast rice is propagated on grains such as rice. In China and Taiwan, it is used as a brewing ingredient for red sake, old sake, red roasted milk, etc., and also helps digestion and improves blood circulation. It has long been known as a Chinese herbal medicine.
  • red yeast rice contains a plurality of functional substances such as GABA and coenzyme Q10.
  • GABA GABA
  • coenzyme Q10 In addition to the cholesterol-lowering action, blood pressure lowering action, blood sugar level lowering action, carcinogenesis-preventing action, etc. Has also been reported.
  • An object of the present invention is to provide a new functional composition based on the action newly found for red yeast rice. Specifically, it is an object of the present invention to provide a use as a chylothorax plasma improving agent and a use as a chylomicronemia suppressing or improving agent based on the chylothorax improving action of plasma and serum of red yeast rice. ..
  • the present inventors have been diligently studying to find a new effect on red koji, and found that plasma collected from rabbits fed with red koji together with a high-fat, high-cholesterol-loaded diet is a high-fat, high-cholesterol-loaded diet. It was found that the white turbidity phenomenon (milkiness) was significantly reduced compared to the plasma collected from rabbits fed only with red koji, and the red koji was eaten with a high-fat diet and a high-cholesterol diet. It was found that it has an effect of improving "milkiness" caused by the lipid (exogenous lipid) contained in.
  • red koji is not lactated due to a temporary diet, but is continuously high. It was confirmed that it has the effect of reducing and improving the milk loss caused by ingesting a fat diet or a high cholesterol diet, that is, the milk loss caused by eating habits and eating habits.
  • plasma turbidity phenomenon chylothorax
  • red yeast rice has an effect of suppressing or ameliorating chylomicronsemia.
  • the present invention has been completed based on these findings, and includes the following embodiments.
  • Chylothorax plasma improving agent and its production method (I-1) Chylothorax plasma improving agent containing red yeast rice or a processed product thereof.
  • the chylothorax plasma improving agent of the present invention can also be referred to as a chylothorax improving agent.
  • Oral Monascus-containing oral composition having a function of improving milky plasma which comprises a step of preparing an oral composition using Monascus purpureus or blending Monascus or a processed product thereof into the oral composition. Method for producing the composition.
  • (I-5) By preparing an oral composition using Monascus purpureus, or by blending Monascus or a processed product thereof in the oral composition, the oral composition is imparted with a function of improving milk plasma. How to use Monascus purpureus or Monascus, characterized by
  • An agent for suppressing or ameliorating chylomicronemia (II-1) An agent for suppressing or ameliorating chylomicronemia containing red yeast rice or a processed product thereof. (II-2) The agent for suppressing or ameliorating chylomicronemia according to (II-1), wherein the chylomicronemia is caused by a deficiency or functional deterioration of a lipolytic enzyme. (II-3) The agent for suppressing or ameliorating chylomicronemia according to (II-1) or (II-2), wherein the producing bacterium of Monascus pilosus is Monascus pilosus.
  • (II-4) The chylomicron according to any one of (II-1) to (II-3), wherein the chylomicronemia is caused by ingesting a high-fat diet and / or a high-cholesterol diet.
  • (II-5) A red yeast rice having a function of suppressing or ameliorating chylomicronemia, which comprises a step of preparing an oral composition using Monascus purpureus or blending red yeast rice or a processed product thereof into the oral composition.
  • a method for producing an oral composition containing koji A method for producing an oral composition containing koji.
  • lipids (exogenous lipids) contained in a diet such as ingestion of a high-fat diet or a high-cholesterol diet (hereinafter, these are also collectively referred to as "high-fat diet") )
  • high-fat diet lipids contained in a diet
  • a milky lotion plasma improving agent of the present invention a milky lotion produced by continuously ingesting a high-fat diet or the like, that is, a high-fat diet or the like is preferred rather than a milky lotion caused by a temporary diet. It is possible to reduce and improve lactation caused by eating habits and eating habits such as ingestion.
  • Chylothorax found in serum and plasma affects the values of biochemical tests performed using blood as a sample, especially those measured by the colorimetric method and the turbidimetric method. Is also useful for obtaining accurate test values.
  • red yeast rice is also useful for suppressing or ameliorating chylomicronsemia.
  • chylomicrons due to lipids (exogenous lipids) contained in the diet such as ingestion of a high-fat diet or a high-cholesterol diet, especially a high-fat diet. It is possible to suppress and improve chylomicronemia caused by eating habits and eating habits such as preferential intake of high-cholesterol diet.
  • the cause of chylomicrons increasing or accumulating in blood is a deficiency of neutral lipolytic enzyme or a decrease in its function, particularly a decrease in lipoprotein lipase activity. Therefore, the agent for suppressing or ameliorating chylomicrons of the present invention may be able to suppress or ameliorate chylomicronsemia caused by a deficiency of such a neutral lipolytic enzyme or a decrease in its function.
  • the time course of the blood cholesterol concentration of the rabbits (control group, red yeast rice group) ingesting the high-fat, high-cholesterol-loaded diet performed in the experimental example is shown.
  • T-Cho Total cholesterol
  • LDL-cholesterol (LDL-C) concentration in plasma are shown.
  • the blood cholesterol concentration of the high-fat, high-cholesterol-loaded diet-ingested rabbits (control group, red yeast rice group) performed in the experimental example and the time course of triglyceride are shown.
  • B) neutral fat (triglyceride) (TG) concentration in plasma are shown.
  • the light transmission rate (%) of plasma after ingesting a high-fat, high-cholesterol-loaded diet and red koji for 2 weeks after ingesting a cholesterol-loaded diet is shown.
  • the light transmission rate (%) of plasma after ingesting red koji for 3 weeks is shown. In each case, the value is the average value of each group.
  • the chylothorax plasma improving agent of the present invention is characterized by containing red yeast rice as an active ingredient.
  • Monascus is a koji obtained by breeding Monascus purpureus belonging to the genus Monascus using cereals as a raw material.
  • Monascus purpureus may belong to the genus Monascus, for example, Monascus pilosus, Monascus purpureus, Monascus pubigerus, Monascus anka, these. Variants or mutants can be mentioned.
  • Monascus purpureus having the ability to produce Monascus K Preference is given to Monascus purpureus having the ability to produce Monascus K, and examples thereof include Monascus pilosus, Monascus purpureus, and Monascus pubigerus. More preferably, it is Monascus pilosus.
  • the cereals used as a raw material for jiuqu are not limited, and examples thereof include rice such as white rice and brown rice, wheat, and beans such as soybean.
  • rice various kinds such as white soybean, black soybean, and green soybean can be used without limitation.
  • any of defatted soybean, soybean hypocotyl, and whole soybean may be used.
  • the cereals used as a raw material for jiuqu are preferably rice, and more preferably white rice.
  • the shape of these cereals is not particularly limited, and may be granular, or may be in a crushed or crushed state. Further, these cereals may be heat-treated in advance, and may be cooked rice or barley rice cooked with water, steamed cooked rice or barley rice, boiled beans or the like.
  • the method for producing Monascus purpureus using the above-mentioned Monascus purpureus and the raw material for Jiuqu is not particularly limited and can be carried out according to a conventional method.
  • Monascus can be produced and obtained by inoculating a koji raw material such as steamed white rice, soybeans or wheat flour with Monascus purpureus and statically culturing it under aerobic conditions of 20 ° C to 40 ° C.
  • the red yeast rice used in the present invention is preferably rice red yeast rice produced by using Monascus pyrosus as a red yeast rice, and cooked or steamed polished rice as a raw material for the yeast rice.
  • the red yeast rice prepared in this way can be used as it is, but it can also be further processed.
  • the red yeast rice produced by the above method may be dried after inactivating bacteria and enzymes by heat treatment to obtain dried red yeast rice. It can also be prepared as a fine granule or powder by crushing or pulverizing after drying. It is also possible to grind red yeast rice to prepare a paste.
  • dried red yeast rice can be extracted with an arbitrary solvent to be used as an extract, and it can be further concentrated to make a concentrated extract, or dried and used as an extract powder. It is preferably dried red yeast rice, and more preferably a powdered product thereof.
  • Red yeast rice can also be obtained commercially.
  • dry powder of rice red yeast rice can be obtained from Kobayashi Pharmaceutical Co., Ltd. as "3P-D" or "3P-D20".
  • the milky plasma improving agent of the present invention is composed of, for example, the above-mentioned red yeast rice or a processed product thereof (hereinafter, these are also collectively referred to as "red yeast rice"), or other edible components are added to the red yeast rice.
  • red yeast rice a processed product thereof
  • It is an oral composition prepared by blending.
  • the oral composition includes foods and drinks, oral or oral medicines, and oral or oral quasi-drugs.
  • the foods and drinks, pharmaceuticals, and quasi-drugs targeted by the present invention are products having an effect of improving chylothorax.
  • Chylothorax is a state or finding in which blood samples such as serum and plasma collected from warm-blooded animals including humans are milky white.
  • the causative substance is mainly chylomicrons containing triglycerides, and when a large amount of it is suspended in the blood, serum and plasma, which are liquid components after removing blood cell components such as red blood cells and white blood cells from the blood, are released. Observed in a milky state. Chylothorax is often caused by triglycerides (exogenous lipids) ingested from the diet, so even healthy humans may develop chylothorax if a certain amount of time has not passed since the diet before collecting blood.
  • the chylothorax plasma improving agent of the present invention can be used to improve chylothorax observed in blood samples collected on an empty stomach 12 hours or more after a meal, rather than chylothorax that occurs transiently after a meal.
  • the causes include secondary dyslipidemia caused by continuous intake of a high-fat diet and / and a high-cholesterol diet, deficiency of lipid-degrading enzymes in blood, and functional deterioration.
  • the chylothorax improving agent of the present invention improves chylothorax in a blood sample by suppressing or improving the blood retention of chylomicrons caused by dietary triglyceride (exogenous lipid). Can be suitably used for.
  • Chylothorax plasma improvement means to reduce chylothorax (whitening / turbidity of plasma) observed in plasma.
  • the presence or absence of chylothorax in plasma can be evaluated by measuring the light transmittance to plasma.
  • the light transmittance can be measured by measuring the absorbance (OD660) of plasma at a wavelength of 660 nm using an absorptiometer (colorimeter).
  • the absorbance (OD660) of the collected plasma was compared between the case where the milk plasma improving agent was taken orally and the case where it was not taken (or before it was taken), and the milk plasma was compared.
  • the foods and drinks targeted by the present invention are foods and drinks having an effect of improving milky plasma, for example, functional foods (foods for specified health use [including conditional foods for specified health use], and functional claims. Includes foods), health foods, general foods and drinks, nutritional supplements (including nutritional drinks), and foods and drinks for the sick.
  • functional foods and health foods include supplements having orally administered preparation forms such as tablets, capsules (hard capsules, soft capsules), powders (powder), granules, pills, and liquids.
  • the food or drink can be prepared as a food or drink having a chylothorax plasma improving effect by combining the above-mentioned red yeast rice with ingredients, materials and the like conventionally known in the field of food and drink.
  • the types of foods and drinks are not particularly limited, and for example, beverages (dairy beverages, lactic acid bacteria beverages, soft drinks containing fruit juice, carbonated beverages, fruit juice beverages, vegetable beverages, vegetable / fruit beverages, alcoholic beverages, coffee beverages, sports beverage powders.
  • beverages airy beverages, lactic acid bacteria beverages, soft drinks containing fruit juice, carbonated beverages, fruit juice beverages, vegetable beverages, vegetable / fruit beverages, alcoholic beverages, coffee beverages, sports beverage powders.
  • Beverages, tea beverages confectionery (chewing gum, bubble gum and other gums [including plate gum and sugar-coated granular gum]
  • coated chocolate such as marble chocolate, chocolates with flavors such as strawberry chocolate and bullberry chocolate
  • hard Candy including bonbons, butterballs, marbles, etc.]
  • soft candies including caramel, nougat, gummy candies, marshmallows, etc.]
  • film-like candies film-like candies [edible film]
  • baked sweets such as hard biscuits, cookies, okaki, and rice cakes.
  • the daily intake of the food and drink of the present invention may be any amount as long as the effect of the present invention can be obtained, and is not limited.
  • the total amount of red yeast rice is per daily intake (for an adult weighing about 60 kg). It can be appropriately set from a range of about 100 to 60,000 mg / day, preferably about 200 to 30,000 mg / day.
  • the proportion of red yeast rice to be blended in the food and drink of the present invention can be appropriately set based on the above daily intake so as to achieve the effect of the present application, and the total amount of red yeast rice is, for example, 5 to 100% by mass. It can be selected and set as appropriate from the range of.
  • the drugs or quasi-drugs covered by the present invention are drugs or quasi-drugs that have the effect of improving milk plasma when administered orally or applied orally. is there.
  • the drug or quasi-drug is produced by blending the above-mentioned red yeast rice with a pharmaceutically acceptable carrier and / or additive and molding it into a desired shape.
  • the formulation form may be an oral administration form, for example, a liquid formulation such as a liquid preparation (including syrup), tablets (including troche tablets and chewable tablets), pills, powders, granules, etc.
  • Oral preparations in the form of solid preparations such as capsules (including soft capsules) can be mentioned. It is preferably in the form of a solid preparation.
  • the carriers and / or additives described above may be selected according to a conventional method according to the dosage form, as long as they do not impair the effects of the present invention.
  • the dose of the drug or quasi-drug of the present invention is not particularly limited as long as the effect of the present invention is exhibited, and can be appropriately set depending on the age, weight, degree of symptoms, etc. of the patient.
  • the total amount of red yeast rice is appropriately set as a daily dose (for an adult weighing about 60 kg) from about 100 to 60,000 mg / day, preferably about 200 to 30,000 mg / day. can do.
  • the dose can also be administered once or in multiple divided doses per day.
  • the proportion of red yeast rice to be blended in the pharmaceutical product or quasi-drug of the present invention can be appropriately set based on the above daily intake so as to achieve the effect of the present application, and the total amount of red yeast rice is, for example, 5. It can be appropriately selected and set from the range of about 100% by mass.
  • red yeast rice itself has the effect of improving chylothorax. Therefore, by blending red yeast rice or its processed product in an oral composition (including foods and drinks, pharmaceuticals, quasi-drugs), the oral composition is given a function of improving plasma chylothorax. Can be done. In other words, by blending red yeast rice or a processed product thereof into the oral composition, a red yeast rice-containing oral composition having a function of improving chylothorax can be produced and obtained. As described above, even when an oral composition containing Monascus purpureus is prepared using Monascus purpureus, the oral composition can be imparted with a function of improving plasma chylothorax. That is, even in that case, an oral composition containing red yeast rice having a function of improving chylothorax can be produced and obtained.
  • the suppressing or ameliorating agent for chylomicronemia of the present invention is characterized by containing red yeast rice or a processed product thereof as an active ingredient.
  • the red yeast rice used as an active ingredient, its processed product, and the method for obtaining the production thereof are as described in (I), and the above description can be incorporated herein by reference.
  • the agent for suppressing or ameliorating chylomicronemia of the present invention is prepared as an oral composition (food and drink, pharmaceuticals, quasi-drugs) in the same manner as the above-mentioned chylothorax improving agent, and is used for chylomicronemia.
  • Chylomicron is a lipoprotein in which neutral fat in the blood is bound to a protein, and when the amount of suspension in the blood is large, a phenomenon (chylothorax) in which plasma and serum become milky white is observed. That is, chylomicronemia means a state in which the blood has a large amount of chylomicrons, in other words, a state in which the amount of triglycerides is large.
  • the cause is not particularly limited, but secondary dyslipidemia caused by continuous intake (dietary habits / eating habits) of a high-fat diet and / or a high-cholesterol diet, and lipid-degrading enzymes in the blood Insufficient or functional deterioration is included.
  • the inhibitor or ameliorating agent for chylomicrons of the present invention increases or stores chylomicrons in blood caused by triglyceride (exogenous lipid) derived from diet, especially blood caused by eating habits and eating habits. It is possible to suppress or improve the increase and storage of chylomicrons in the blood.
  • the inhibitory or ameliorating effect of chylomicrons can be evaluated from the decrease in the amount of chylomicrons in plasma.
  • the amount of chylomicrons in plasma can be evaluated by measuring the light transmittance to plasma in the same manner as the above-mentioned chylothorax effect.
  • the evaluation method is as described in (I) as in the evaluation method of the chylothorax improving effect, and the above description can be incorporated herein by reference.
  • a loaded diet (0.25% cholesterol loaded) (Oriental Yeast Co., Ltd.) was ingested 100 g daily. Each rabbit was kept individually in a cage, water was freely ingested, and food was restricted.
  • T-Cho Total cholesterol
  • LDL-C LDL-cholesterol
  • HDL-C HDL-cholesterol
  • FIG. 3 (A) shows the plasma light transmittance (%) of the rabbits (control group) that did not ingest the red yeast rice and the plasma light transmittance (%) of the plasma of the rabbits (monascus group) that received the red yeast rice.
  • FIG. 3 (B) shows changes in plasma light transmittance due to administration of red koji (weeks 2 and 3) (light transmittance of plasma in the red koji group (mean value) -light transmittance of plasma in the control group.

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Abstract

[Problem] To provide a milky plasma improving agent and a prophylactic or ameliorating agent for chylomicronemia. [Solution] Red yeast rice or a processed product thereof is contained as an active ingredient.

Description

乳び血漿改善剤Chylothorax plasma improver
　本発明は乳び血漿改善剤に関する。また本発明はカイロミクロン血症抑制または改善剤に関する。 The present invention relates to a chylothorax plasma improving agent. The present invention also relates to an agent for suppressing or ameliorating chylomicronemia.
　血液中には、通常、中性脂肪(Triglyceride）、コレステロール、リン脂質、及び遊離脂肪酸などの脂質が存在している。特に中性脂肪の血中濃度が高い状態が続くと、牛乳を混ぜたように、血清や血漿が白く濁るという現象が生じる。このような状態を「乳び」という。「乳び」の原因は、高脂肪食や高コレステロール食を摂取することによる血液中の中性脂肪やコレステロール（外因性脂質）の増加、血液中の脂質を分解するリポ蛋白リパーゼの不足や機能低下など、種々の原因が考えられる。健常者でも、食後あまり時間を置かないで採血すると、血清や血漿が白濁する場合があるものの、１２時間以上何も食べずに採血した血漿が白濁している場合は、「脂質異常症」、特に脂肪を分解する酵素の不足または機能低下の可能性があると言われている。また、血液中の脂質レベルが高い状態が続くと、動脈硬化症の発症リスクが高まると考えられていることから、乳び血漿を改善することは動脈硬化症の発症リスクを抑える上でも重要である。 In blood, lipids such as triglyceride, cholesterol, phospholipids, and free fatty acids are usually present. In particular, if the blood concentration of triglyceride continues to be high, the phenomenon that serum and plasma become cloudy white occurs as if milk was mixed. Such a state is called "chylothorax". The causes of "milk" are an increase in triglycerides and cholesterol (exogenous lipids) in the blood due to ingestion of a high-fat diet and a high-cholesterol diet, and a deficiency and function of lipoprotein lipase that decomposes lipids in the blood. Various causes such as a decrease can be considered. Even in a healthy person, if blood is collected shortly after eating, serum and plasma may become cloudy, but if the plasma collected without eating anything for 12 hours or more becomes cloudy, "dyslipidemia", In particular, it is said that there is a possibility of deficiency or functional deterioration of enzymes that break down fat. In addition, it is thought that the risk of developing arteriosclerosis increases if the lipid level in the blood continues to be high, so improving chylothorax is also important for reducing the risk of developing arteriosclerosis. is there.
　一方、紅麹に含まれるモナコリンＫには、肝臓におけるコレステロール合成を阻害する作用があることから、紅麹及びその加工品は、従来よりコレステロール低下作用を有する機能性食品として用いられている（例えば、特許文献１参照）。紅麹は、米などの穀類に紅麹菌が繁殖した鮮紅色の麹であり、中国や台湾などでは紅酒、老酒、紅腐乳などの醸造原料として利用されるほか、消化を助け、血行を良くする漢方生薬として古くから知られている。紅麹には、前述するモナコリンＫのほか、ＧＡＢＡやコエンザイムＱ１０等の機能性物質が複数含まれており、前記コレステロール低下作用に加えて、血圧低下作用、血糖値低下作用、発ガン予防作用なども報告されている。 On the other hand, since monacolin K contained in red yeast rice has an action of inhibiting cholesterol synthesis in the liver, red yeast rice and its processed products have been conventionally used as functional foods having a cholesterol lowering action (for example). , Patent Document 1). Monascus is a bright red yeast rice in which red yeast rice is propagated on grains such as rice. In China and Taiwan, it is used as a brewing ingredient for red sake, old sake, red roasted milk, etc., and also helps digestion and improves blood circulation. It has long been known as a Chinese herbal medicine. In addition to the above-mentioned monacolin K, red yeast rice contains a plurality of functional substances such as GABA and coenzyme Q10. In addition to the cholesterol-lowering action, blood pressure lowering action, blood sugar level lowering action, carcinogenesis-preventing action, etc. Has also been reported.
特開２００２－２７９９６号公報Japanese Unexamined Patent Publication No. 2002-27996
　本発明は、紅麹について新たに見出した作用に基づいて新しい機能性組成物を提供することを目的とする。具体的には、紅麹が有する血漿や血清の乳び改善作用に基づいて、乳び血漿改善剤としての用途、またカイロミクロン血症抑制または改善剤としての用途を提供することを目的とする。 An object of the present invention is to provide a new functional composition based on the action newly found for red yeast rice. Specifically, it is an object of the present invention to provide a use as a chylothorax plasma improving agent and a use as a chylomicronemia suppressing or improving agent based on the chylothorax improving action of plasma and serum of red yeast rice. ..
　本発明者らは、紅麹について新たな作用を見出すべく、鋭意検討を重ねていたところ、高脂肪高コレステロール負荷食とともに紅麹を摂取させたウサギから採取した血漿が、高脂肪高コレステロール負荷食だけを摂取させたウサギから採取した血漿と比較して、有意に白濁現象（乳び）が低減していることを見出し、紅麹には、高脂肪食や高コレステロール食を摂取するなど、食事に含まれる脂質（外因性脂質）を原因とする「乳び」を改善する作用があることを見出した。また、この乳び改善効果は、絶食から１２時間後に採血（空腹時採血）した血漿で認められることから、紅麹には、一時的な食事を原因とする乳びではなく、継続して高脂肪食や高コレステロール食を摂取することによって生じる乳び、つまり食生活・食習慣を原因とする乳びを低減し改善する効果があることを確認した。また、血漿の白濁現象（乳び）は、血漿中に浮遊するカイロミクロンを原因とすることから、紅麹には、カイロミクロン血症を抑制または改善する効果があることを確認した。 The present inventors have been diligently studying to find a new effect on red koji, and found that plasma collected from rabbits fed with red koji together with a high-fat, high-cholesterol-loaded diet is a high-fat, high-cholesterol-loaded diet. It was found that the white turbidity phenomenon (milkiness) was significantly reduced compared to the plasma collected from rabbits fed only with red koji, and the red koji was eaten with a high-fat diet and a high-cholesterol diet. It was found that it has an effect of improving "milkiness" caused by the lipid (exogenous lipid) contained in. In addition, since this effect of improving lactation is observed in plasma collected 12 hours after fasting (fasting blood collection), red koji is not lactated due to a temporary diet, but is continuously high. It was confirmed that it has the effect of reducing and improving the milk loss caused by ingesting a fat diet or a high cholesterol diet, that is, the milk loss caused by eating habits and eating habits. In addition, since the plasma turbidity phenomenon (chylothorax) is caused by chylomicrons floating in plasma, it was confirmed that red yeast rice has an effect of suppressing or ameliorating chylomicronsemia.
　本発明はこれらの知見に基づいて完成したものであり、下記の実施形態を包含するものである。 The present invention has been completed based on these findings, and includes the following embodiments.
（Ｉ）乳び血漿改善剤、及びその製造方法
（Ｉ－１）紅麹またはその加工物を含有する乳び血漿改善剤。なお、本発明の乳び血漿改善剤は、乳び血清改善剤ということもできる。
（Ｉ－２）前記紅麹の生産菌がモナスカス・ピローサス（Monascus pilosus）である、（Ｉ－１）に記載する乳び血漿改善剤。
（Ｉ－３）前記乳び血漿が、高脂肪食または／および高コレステロール食を摂取することに起因するものである、（Ｉ－１）または（Ｉ－１）に記載する乳び血漿改善剤。
（Ｉ－４）紅麹菌を用いて経口組成物を調製するか、または紅麹若しくはその加工物を経口組成物中に配合する工程を有する、乳び血漿を改善する機能を有する紅麹含有経口組成物の製造方法。
（Ｉ－５）紅麹菌を用いて経口組成物を調製するか、または紅麹若しくはその加工物を経口組成物中に配合することにより、前記経口組成物に乳び血漿を改善する機能を付与することを特徴とする、紅麹菌または紅麹の使用方法。 (I) Chylothorax plasma improving agent and its production method (I-1) Chylothorax plasma improving agent containing red yeast rice or a processed product thereof. The chylothorax plasma improving agent of the present invention can also be referred to as a chylothorax improving agent.
(I-2) The chylothorax plasma improving agent according to (I-1), wherein the producing bacterium of Monascus pilosus is Monascus pilosus.
(I-3) The chylothorax improving agent according to (I-1) or (I-1), wherein the chylothorax is caused by ingesting a high-fat diet and / or a high-cholesterol diet. ..
(I-4) Oral Monascus-containing oral composition having a function of improving milky plasma, which comprises a step of preparing an oral composition using Monascus purpureus or blending Monascus or a processed product thereof into the oral composition. Method for producing the composition.
(I-5) By preparing an oral composition using Monascus purpureus, or by blending Monascus or a processed product thereof in the oral composition, the oral composition is imparted with a function of improving milk plasma. How to use Monascus purpureus or Monascus, characterized by
（ＩＩ）カイロミクロン血症の抑制または改善剤
（ＩＩ－１）紅麹またはその加工物を含有するカイロミクロン血症の抑制または改善剤。（ＩＩ－２）前記カイロミクロン血症が脂肪分解酵素の不足または機能低下に起因するものである、（ＩＩ－１）に記載するカイロミクロン血症の抑制または改善剤。
（ＩＩ－３）前記紅麹の生産菌がモナスカス・ピローサス（Monascus pilosus）である、（ＩＩ－１）または（ＩＩ－２）に記載するカイロミクロン血症の抑制または改善剤。
（ＩＩ－４）前記カイロミクロン血症が高脂肪食または／および高コレステロール食を摂取することに起因するものである、（ＩＩ－１）～（ＩＩ－３）のいずれかに記載するカイロミクロン血症の抑制または改善剤。
（ＩＩ－５）紅麹菌を用いて経口組成物を調製するか、または紅麹もしくはその加工物を経口組成物中に配合する工程を有する、カイロミクロン血症の抑制または改善する機能を有する紅麹含有経口組成物の製造方法。
（ＩＩ－６）紅麹菌を用いて経口組成物を調製するか、または紅麹もしくはその加工物を経口組成物中に配合することにより、前記経口組成物にカイロミクロン血症を抑制または改善する機能を付与することを特徴とする、紅麹菌または紅麹の使用方法。 (II) An agent for suppressing or ameliorating chylomicronemia (II-1) An agent for suppressing or ameliorating chylomicronemia containing red yeast rice or a processed product thereof. (II-2) The agent for suppressing or ameliorating chylomicronemia according to (II-1), wherein the chylomicronemia is caused by a deficiency or functional deterioration of a lipolytic enzyme.
(II-3) The agent for suppressing or ameliorating chylomicronemia according to (II-1) or (II-2), wherein the producing bacterium of Monascus pilosus is Monascus pilosus.
(II-4) The chylomicron according to any one of (II-1) to (II-3), wherein the chylomicronemia is caused by ingesting a high-fat diet and / or a high-cholesterol diet. An agent that suppresses or improves blood flow.
(II-5) A red yeast rice having a function of suppressing or ameliorating chylomicronemia, which comprises a step of preparing an oral composition using Monascus purpureus or blending red yeast rice or a processed product thereof into the oral composition. A method for producing an oral composition containing koji.
(II-6) By preparing an oral composition using Monascus purpureus, or by blending Monascus or a processed product thereof in the oral composition, chylomicronemia is suppressed or ameliorated in the oral composition. A method of using Monascus purpureus or Monascus, which is characterized by imparting a function.
　本発明の乳び血漿改善剤によれば、高脂肪食または高コレステロール食（以下、これらを総称して「高脂肪食等」ともいう）の摂取など、食事中に含まれる脂質（外因性脂質）を原因とする「乳び」を改善することができる。特に本発明の乳び血漿改善剤によれば、一時的な食事を原因とする乳びではなく、継続して高脂肪食等を摂取することによって生じる乳び、つまり高脂肪食等を好んで摂取するなどといった食生活・食習慣を原因とする乳びを低減し改善することができる。なお、血清や血漿に認められる乳びは、血液を検体として行われる生化学検査のうち、特に比色法や比濁法により測定される検査の値に影響を与えることから、乳びの改善は正確な検査値を得るうえでも有用である。 According to the milky plasma improving agent of the present invention, lipids (exogenous lipids) contained in a diet such as ingestion of a high-fat diet or a high-cholesterol diet (hereinafter, these are also collectively referred to as "high-fat diet") ) Caused "milkiness" can be improved. In particular, according to the milky lotion plasma improving agent of the present invention, a milky lotion produced by continuously ingesting a high-fat diet or the like, that is, a high-fat diet or the like is preferred rather than a milky lotion caused by a temporary diet. It is possible to reduce and improve lactation caused by eating habits and eating habits such as ingestion. Chylothorax found in serum and plasma affects the values of biochemical tests performed using blood as a sample, especially those measured by the colorimetric method and the turbidimetric method. Is also useful for obtaining accurate test values.
　また、血漿の白濁現象（乳び）は、血漿中に浮遊するカイロミクロンを原因とすることから、紅麹はカイロミクロン血症を抑制または改善するためにも有用である。本発明のカイロミクロン血症抑制または改善剤によれば、高脂肪食または高コレステロール食の摂取など、食事中に含まれる脂質（外因性脂質）を原因とするカイロミクロン血症、特に高脂肪食や高コレステロール食を好んで摂取するなどといった食生活・食習慣を原因とするカイロミクロン血症を抑制し改善することができる。なお、カイロミクロンが血中に増加または貯留する原因として、中性脂肪分解酵素の不足またはその機能低下、特にリポ蛋白リパーゼ活性の低下と言われている。このため、本発明のカイロミクロン血症抑制または改善剤は、こうした中性脂肪分解酵素の不足またはその機能低下を原因としたカイロミクロン血症を抑制または改善することができる可能性もある。 In addition, since the plasma turbidity phenomenon (chylothorax) is caused by chylomicrons floating in plasma, red yeast rice is also useful for suppressing or ameliorating chylomicronsemia. According to the agent for suppressing or ameliorating chylomicrons of the present invention, chylomicrons due to lipids (exogenous lipids) contained in the diet, such as ingestion of a high-fat diet or a high-cholesterol diet, especially a high-fat diet. It is possible to suppress and improve chylomicronemia caused by eating habits and eating habits such as preferential intake of high-cholesterol diet. It is said that the cause of chylomicrons increasing or accumulating in blood is a deficiency of neutral lipolytic enzyme or a decrease in its function, particularly a decrease in lipoprotein lipase activity. Therefore, the agent for suppressing or ameliorating chylomicrons of the present invention may be able to suppress or ameliorate chylomicronsemia caused by a deficiency of such a neutral lipolytic enzyme or a decrease in its function.
実験例で行った高脂肪高コレステロール負荷食摂取ウサギ（コントロール群、紅麹群）の血中コレステロール濃度の経時的推移を示す。（Ａ）血漿中の総コレステロール（T-Cho）濃度、（Ｂ）血漿中のＬＤＬ－コレステロール（LDL-C）濃度を示す。The time course of the blood cholesterol concentration of the rabbits (control group, red yeast rice group) ingesting the high-fat, high-cholesterol-loaded diet performed in the experimental example is shown. (A) Total cholesterol (T-Cho) concentration in plasma and (B) LDL-cholesterol (LDL-C) concentration in plasma are shown. 実験例で行った高脂肪高コレステロール負荷食摂取ウサギ（コントロール群、紅麹群）の血中コレステロール濃度、及び中性脂肪の経時的推移を示す。（Ａ）血漿中のＨＤＬ－コレステロール（HDL-C）濃度、（Ｂ）血漿中の中性脂肪（トリグリセリド）（TG）濃度を示す。The blood cholesterol concentration of the high-fat, high-cholesterol-loaded diet-ingested rabbits (control group, red yeast rice group) performed in the experimental example and the time course of triglyceride are shown. (A) HDL-cholesterol (HDL-C) concentration in plasma, (B) neutral fat (triglyceride) (TG) concentration in plasma are shown. 実験例で行った高脂肪高コレステロール負荷食摂取ウサギ（コントロール群［紅麹非投与］、紅麹群［紅麹投与］）から採取した血漿の光透過率を示す。（Ａ）左図「血漿透過率（２週目）」：コントロール群［紅麹非投与］は高脂肪高コレステロール負荷食を４週間摂取した後、紅麹群［紅麹投与］は高脂肪高コレステロール負荷食摂取２週間後に高脂肪高コレステロール負荷食と紅麹を２週間摂取した後の血漿の光透過率（％）を示す。右図「血漿透過率（３週目）」：コントロール群は高脂肪高コレステロール負荷食を５週間摂取した後、紅麹群は高脂肪高コレステロール負荷食摂取２週間後に高脂肪高コレステロール負荷食と紅麹を３週間摂取した後の血漿の光透過率（％）を示す。いずれも値は各群の平均値である。（Ｂ）上記（Ａ）で示した血漿透過率（２週目）及び血漿透過率（３週目）について、紅麹群の平均値とコントロール群の平均値との差から、紅麹投与による血漿の光透過率（％）の変化を示したグラフである。The light transmittance of plasma collected from the high-fat, high-cholesterol-loaded diet-fed rabbits (control group [non-administered red yeast rice], red yeast rice group [administered red yeast rice]) performed in the experimental example is shown. (A) Left figure "Plasma permeability (2nd week)": The control group [non-administered red koji] ingested a high-fat, high-cholesterol-loaded diet for 4 weeks, and then the red koji group [administered red koji] had high fat. The light transmission rate (%) of plasma after ingesting a high-fat, high-cholesterol-loaded diet and red koji for 2 weeks after ingesting a cholesterol-loaded diet is shown. Right figure "Plasma permeability (3rd week)": The control group ingested a high-fat, high-cholesterol-loaded diet for 5 weeks, and the red koji group received a high-fat, high-cholesterol-loaded diet 2 weeks after ingesting a high-fat, high-cholesterol-loaded diet. The light transmission rate (%) of plasma after ingesting red koji for 3 weeks is shown. In each case, the value is the average value of each group. (B) Regarding the plasma permeability (2nd week) and plasma permeability (3rd week) shown in (A) above, the difference between the average value of the red yeast rice group and the average value of the control group was determined by administration of red yeast rice. It is a graph which showed the change of the light transmittance (%) of plasma.
（Ｉ）乳び血漿改善剤、及びその製造方法
　本発明の乳び血漿改善剤は、紅麹を有効成分として含有することを特徴とする。
　紅麹は、穀類を原料にモナスカス属に属する紅麹菌を繁殖させた麹である。紅麹菌は、モナスカス属に属するものであればよく、例えば、モナスカス・ピローサス（Monascus pilosus）、モナスカス・パープレウス(Monascus purpureus）、モナスカス・プビゲレス（Monascus pubigerus）、モナスカス・アンカ（Monascus anka）、これらの変種または変異株を挙げることができる。好ましくはモナコリンＫ生産能を有する紅麹菌であり、例えばモナスカス・ピローサス（Monascus pilosus）、モナスカス・プルプレウス（Monascus purpureus）、モナスカス・プビゲレス（Monascus pubigerus）を挙げることができる。より好ましくはモナスカス・ピローサス（Monascus pilosus）である。 (I) Chylothorax plasma improving agent and method for producing the same The chylothorax plasma improving agent of the present invention is characterized by containing red yeast rice as an active ingredient.
Monascus is a koji obtained by breeding Monascus purpureus belonging to the genus Monascus using cereals as a raw material. Monascus purpureus may belong to the genus Monascus, for example, Monascus pilosus, Monascus purpureus, Monascus pubigerus, Monascus anka, these. Variants or mutants can be mentioned. Preference is given to Monascus purpureus having the ability to produce Monascus K, and examples thereof include Monascus pilosus, Monascus purpureus, and Monascus pubigerus. More preferably, it is Monascus pilosus.
　麹原料として用いる穀類としては、制限されることなく、例えば白米や玄米などの米類、麦類、及び大豆などの豆類などを挙げることができる。大豆は、白大豆、黒豆、及び青豆等、制限されることなく、各種のものを用いることができる。また大豆として、脱脂大豆、大豆胚軸、及び丸大豆のいずれを用いてもよい。麹原料として用いる穀類として、好ましくは米類であり、より好ましくは白米である。なお、これらの穀類の形状は特に制限されず、粒状であっても、また破砕や粉砕された状態のものであってもよい。またこれらの穀類は予め加熱処理されていてもよく、例えば、水とともに炊きあげた米飯や麦飯、蒸し上げた米飯や麦飯、煮豆などであってもよい。 The cereals used as a raw material for jiuqu are not limited, and examples thereof include rice such as white rice and brown rice, wheat, and beans such as soybean. As the soybean, various kinds such as white soybean, black soybean, and green soybean can be used without limitation. Further, as the soybean, any of defatted soybean, soybean hypocotyl, and whole soybean may be used. The cereals used as a raw material for jiuqu are preferably rice, and more preferably white rice. The shape of these cereals is not particularly limited, and may be granular, or may be in a crushed or crushed state. Further, these cereals may be heat-treated in advance, and may be cooked rice or barley rice cooked with water, steamed cooked rice or barley rice, boiled beans or the like.
　前述する紅麹菌及び麹原料を用いた紅麹の製造方法は、特に制限されず、慣用の方法に従って実施することができる。例えば、蒸煮した白米、大豆または小麦粉等の麹原料に、紅麹菌を接種し、２０℃から４０℃ の好気的条件で静置培養することで紅麹を製造し取得することができる。本発明で用いる紅麹として、好ましくは、紅麹菌としてモナスカス・ピローサスを、また麹原料として炊飯または蒸煮した精白米を用いて製造される米紅麹である。 The method for producing Monascus purpureus using the above-mentioned Monascus purpureus and the raw material for Jiuqu is not particularly limited and can be carried out according to a conventional method. For example, Monascus can be produced and obtained by inoculating a koji raw material such as steamed white rice, soybeans or wheat flour with Monascus purpureus and statically culturing it under aerobic conditions of 20 ° C to 40 ° C. The red yeast rice used in the present invention is preferably rice red yeast rice produced by using Monascus pyrosus as a red yeast rice, and cooked or steamed polished rice as a raw material for the yeast rice.
　このようにして調製される紅麹は、そのまま使用することもできるが、さらに加工処理したものを用いることもできる。例えば、上記方法で製造される紅麹を、熱処理により菌や酵素を失活させた後に、乾燥させて乾燥紅麹としてもよい。また乾燥後、破砕または粉砕処理により、細粒物または粉末物として調製することもできる。また紅麹をすりつぶしてペースト状に調製することもできる。さらに、乾燥紅麹を任意の溶媒で抽出してエキスの状態にして使用することもできるし、さらにそれを濃縮して濃縮エキスにしたり、乾燥してエキス粉末として使用することもできる。好ましくは乾燥紅麹であり、より好ましくはその粉末物である。なお、紅麹は商業的に入手することもでき、例えば米紅麹の乾燥粉末は「３Ｐ－Ｄ」または「３Ｐ－Ｄ２０」として、小林製薬株式会社から入手することができる。 The red yeast rice prepared in this way can be used as it is, but it can also be further processed. For example, the red yeast rice produced by the above method may be dried after inactivating bacteria and enzymes by heat treatment to obtain dried red yeast rice. It can also be prepared as a fine granule or powder by crushing or pulverizing after drying. It is also possible to grind red yeast rice to prepare a paste. Further, dried red yeast rice can be extracted with an arbitrary solvent to be used as an extract, and it can be further concentrated to make a concentrated extract, or dried and used as an extract powder. It is preferably dried red yeast rice, and more preferably a powdered product thereof. Red yeast rice can also be obtained commercially. For example, dry powder of rice red yeast rice can be obtained from Kobayashi Pharmaceutical Co., Ltd. as "3P-D" or "3P-D20".
　本発明の乳び血漿改善剤は、例えば前述する紅麹またはその加工物（以下、これらを総称して「紅麹類」ともいう）からなるか、または紅麹類に他の可食性成分を配合して調製される経口組成物である。ここで経口組成物には、飲食品、経口または口腔用医薬品、及び経口または口腔用医薬部外品が含まれる。本発明が対象とする飲食品、医薬品、及び医薬部外品は、乳び血漿を改善する効果を有する製品である。 The milky plasma improving agent of the present invention is composed of, for example, the above-mentioned red yeast rice or a processed product thereof (hereinafter, these are also collectively referred to as "red yeast rice"), or other edible components are added to the red yeast rice. It is an oral composition prepared by blending. Here, the oral composition includes foods and drinks, oral or oral medicines, and oral or oral quasi-drugs. The foods and drinks, pharmaceuticals, and quasi-drugs targeted by the present invention are products having an effect of improving chylothorax.
　「乳び」とは、ヒトを含む温血動物から採取した血清や血漿などの血液サンプルが乳白色を呈している状態または所見である。その原因物質は、主として中性脂肪を含むカイロミクロンであり、それが血液中に多く浮遊していると、血液から赤血球や白血球等の血球成分を除去した後の液体成分である血清や血漿が乳濁した状態で観察される。なお、乳びは、食事から摂取する中性脂肪（外因性脂質）が原因であることが多いため、健康なヒトでも、採血する前に、食事からある程度の時間を置かなければ生じる場合がある（食後一過性に生じるカイロミクロンによる乳び現象）。一方、食後かなりの時間を置いた後、例えば食後１２時間以上経過した空腹時に採血した血清や血漿で乳びが認められる場合は、血液中に長時間に亘り脂質が存在する状態が続いていることを意味する。その原因としては、制限されないものの、高脂肪食または／および高コレステロール食を継続的に好んで食べるといった、食生活や食習慣を原因とする脂質異常症（二次性脂質異常症）、血液中の脂質を分解または代謝する酵素の不足、または当該酵素の機能低下などの可能性が考えられる。 "Chylothorax" is a state or finding in which blood samples such as serum and plasma collected from warm-blooded animals including humans are milky white. The causative substance is mainly chylomicrons containing triglycerides, and when a large amount of it is suspended in the blood, serum and plasma, which are liquid components after removing blood cell components such as red blood cells and white blood cells from the blood, are released. Observed in a milky state. Chylothorax is often caused by triglycerides (exogenous lipids) ingested from the diet, so even healthy humans may develop chylothorax if a certain amount of time has not passed since the diet before collecting blood. (Chylomicron-induced chylothorax that occurs transiently after eating). On the other hand, if chylothorax is observed in serum or plasma collected on an empty stomach 12 hours or more after a meal after a considerable time has passed after a meal, the state in which lipids are present in the blood continues for a long time. Means that. Causes include, but are not limited to, dyslipidemia (secondary dyslipidemia) caused by eating habits and eating habits, such as continuous preference for high-fat or / and high-cholesterol diets, in the blood. It is possible that there is a shortage of enzymes that decompose or metabolize the lipids in the body, or that the functions of the enzymes are reduced.
　本発明の乳び血漿改善剤は、食後一過性に生じる乳びではなく、特に、食後１２時間以上経過した空腹時に採取した血液サンプルで認められる乳びを改善するために用いることができる。その原因には、前述するように、高脂肪食または／および高コレステロール食の継続的摂取に起因する二次性脂質異常症、血液中の脂質分解酵素の不足や機能低下などが含まれる。特に本発明の乳び血漿改善剤は、食事に由来する中性脂肪（外因性脂質）を原因とするカイロミクロンの血液貯留を抑制ないし改善することにより、血液サンプル中の乳びを改善するために好適に使用することができる。 The chylothorax plasma improving agent of the present invention can be used to improve chylothorax observed in blood samples collected on an empty stomach 12 hours or more after a meal, rather than chylothorax that occurs transiently after a meal. As described above, the causes include secondary dyslipidemia caused by continuous intake of a high-fat diet and / and a high-cholesterol diet, deficiency of lipid-degrading enzymes in blood, and functional deterioration. In particular, the chylothorax improving agent of the present invention improves chylothorax in a blood sample by suppressing or improving the blood retention of chylomicrons caused by dietary triglyceride (exogenous lipid). Can be suitably used for.
　本発明がいう「乳び血漿改善」とは、血漿に認められる乳び（血漿の白色化・白濁化）を低減することを意味する。血漿における乳び低減の有無は、血漿に対する光の透過率を測定することで評価することができる。光透過率は、吸光度計（比色計）を用いて血漿の波長660nmにおける吸光度（OD660）を測定することで実施することができる。後述する実験例に示すように、乳び血漿改善剤を経口的に摂取した場合と、摂取しない場合（または摂取する前）とで、採取した血漿の吸光度（OD660）を比較し、乳び血漿改善剤を摂取した場合の血漿の吸光度（OD660）が低下していれば（言い換えれば、光透過率が上昇していれば）、乳び血漿改善剤の経口摂取により、血漿の乳びが低減し、乳び血漿が改善していると評価することができる。なお、血漿で認められる乳びが低減（改善）すれば、同じく血液の液体部分である血清における乳びも低減（改善）する。このことから、「乳び血漿改善」（血漿の乳び改善）と「乳び血清改善」（血清の乳び改善）とは軌を一とするものであり、本発明が対象とする「乳び血漿改善剤」には「乳び血清改善剤」が含まれる。 "Chylothorax plasma improvement" as used in the present invention means to reduce chylothorax (whitening / turbidity of plasma) observed in plasma. The presence or absence of chylothorax in plasma can be evaluated by measuring the light transmittance to plasma. The light transmittance can be measured by measuring the absorbance (OD660) of plasma at a wavelength of 660 nm using an absorptiometer (colorimeter). As shown in the experimental examples described later, the absorbance (OD660) of the collected plasma was compared between the case where the milk plasma improving agent was taken orally and the case where it was not taken (or before it was taken), and the milk plasma was compared. If the absorbance (OD660) of plasma after ingestion of the improving agent is decreased (in other words, if the light transmittance is increased), oral ingestion of the plasma improving agent reduces plasma emulsion. However, it can be evaluated that the milk plasma is improved. If the chylothorax observed in plasma is reduced (improved), the chylothorax in serum, which is also a liquid portion of blood, is also reduced (improved). For this reason, "chylothorax improvement" (plasma chylothorax improvement) and "chylothorax serum improvement" (chylothorax improvement) are in line with each other, and the "chylothorax" targeted by the present invention is the same. "Plasma improver" includes "chylothorax serum improver".
　飲食品
　本発明が対象とする飲食品は、乳び血漿を改善する効果を有する飲食品であり、例えば機能性食品（特定保健用食品［条件付き特定保健用食品を含む］、及び機能性表示食品が含まれる）、健康食品、一般飲食品、栄養補助食品（栄養ドリンク等も含まれる）、及び病者用飲食品等が含まれる。また機能性食品や健康食品には、錠剤、カプセル剤（ハードカプセル、ソフトカプセル）、散剤（粉末剤）、顆粒剤、丸剤、液剤などの経口投与製剤形態を有するサプリメント等が含まれる。当該飲食品は、前述する紅麹類に、飲食品分野において従来公知の成分、素材等と組み合わせて、乳び血漿改善作用を有する飲食品として調製することができる。 Foods and drinks The foods and drinks targeted by the present invention are foods and drinks having an effect of improving milky plasma, for example, functional foods (foods for specified health use [including conditional foods for specified health use], and functional claims. Includes foods), health foods, general foods and drinks, nutritional supplements (including nutritional drinks), and foods and drinks for the sick. In addition, functional foods and health foods include supplements having orally administered preparation forms such as tablets, capsules (hard capsules, soft capsules), powders (powder), granules, pills, and liquids. The food or drink can be prepared as a food or drink having a chylothorax plasma improving effect by combining the above-mentioned red yeast rice with ingredients, materials and the like conventionally known in the field of food and drink.
　飲食品の種類としては、特に限定されず、例えば、飲料（乳飲料、乳酸菌飲料、果汁入り清涼飲料、炭酸飲料、果汁飲料、野菜飲料、野菜・果実飲料、アルコール飲料、コーヒー飲料、スポーツ飲料粉末飲料、茶飲料）、菓子類（チューイングガム、風船ガム等のガム類［板ガム、糖衣粒状ガムを含む］；マーブルチョコレート等のコーティングチョコレート、イチゴチョコレート、ブルベリーチョコレート等の風味を付加したチョコレート類；ハードキャンディー［ボンボン、バターボール、マーブル等を含む］、ソフトキャンディー［キャラメル、ヌガー、グミキャンディー、マシュマロ等を含む］、フィルム状キャンディー［可食性フィルム］；ハードビスケット、クッキー、おかき、煎餅等の焼き菓子；ケーキ類；ババロア、ゼリー、プリンなどの冷菓；アイスクリーム、アイスミルク、かき氷などの氷菓等；パン類；スープ類（粉末スープ等を含む）；各種総菜、レトルト食品等の各種の加工飲食品が挙げられる。 The types of foods and drinks are not particularly limited, and for example, beverages (dairy beverages, lactic acid bacteria beverages, soft drinks containing fruit juice, carbonated beverages, fruit juice beverages, vegetable beverages, vegetable / fruit beverages, alcoholic beverages, coffee beverages, sports beverage powders. Beverages, tea beverages), confectionery (chewing gum, bubble gum and other gums [including plate gum and sugar-coated granular gum]; coated chocolate such as marble chocolate, chocolates with flavors such as strawberry chocolate and bullberry chocolate; hard Candy [including bonbons, butterballs, marbles, etc.], soft candies [including caramel, nougat, gummy candies, marshmallows, etc.], film-like candies [edible film]; baked sweets such as hard biscuits, cookies, okaki, and rice cakes. ; Cakes; Frozen desserts such as bavarois, jelly, pudding; Ice cream, ice milk, ice cream such as shaved ice; Breads; Soups (including powdered soup); Various delicatessen, various processed foods such as retort foods Can be mentioned.
　本発明の飲食品の一日摂取量は、本発明の効果が得られる量であればよく、制限されないが、例えば、紅麹の総量として、１日摂取あたり（体重約６０ｋｇの大人の場合）１００～６０，０００ｍｇ／日程度、好ましくは２００～３０，０００ｍｇ／日程度の範囲から適宜設定することができる。また本発明の飲食品中に配合する紅麹類の割合は、本願の効果を奏するように上記１日摂取量に基づいて適宜設定することができ、紅麹の総量で例えば５～１００質量％の範囲から適宜選択設定することができる。 The daily intake of the food and drink of the present invention may be any amount as long as the effect of the present invention can be obtained, and is not limited. For example, the total amount of red yeast rice is per daily intake (for an adult weighing about 60 kg). It can be appropriately set from a range of about 100 to 60,000 mg / day, preferably about 200 to 30,000 mg / day. Further, the proportion of red yeast rice to be blended in the food and drink of the present invention can be appropriately set based on the above daily intake so as to achieve the effect of the present application, and the total amount of red yeast rice is, for example, 5 to 100% by mass. It can be selected and set as appropriate from the range of.
　医薬品または医薬部外品
　本発明が対象とする医薬品または医薬部外品は、経口的に投与または口腔内で適用されることで、乳び血漿を改善する効果を奏する医薬品または医薬部外品である。当該医薬品または医薬部外品は、前述する紅麹類に、薬学的に許容される担体及び／又は添加剤を配合して所望の形状に成形することで製造される。その製剤形態（剤型）は、経口投与形態であればよく、例えば液剤（シロップ等を含む）等の液状製剤や、錠剤（トローチ錠やチュアブル錠を含む）、丸剤、散剤、顆粒剤、カプセル剤（ソフトカプセルを含む）等の固形製剤形態の経口製剤を挙げることができる。好ましくは固形製剤形態である。前述する担体及び／又は添加剤は、本発明の効果を損なうものでなければよく、剤型に応じて、定法に従って選択することができる。 Drugs or quasi-drugs The drugs or quasi-drugs covered by the present invention are drugs or quasi-drugs that have the effect of improving milk plasma when administered orally or applied orally. is there. The drug or quasi-drug is produced by blending the above-mentioned red yeast rice with a pharmaceutically acceptable carrier and / or additive and molding it into a desired shape. The formulation form (dosage form) may be an oral administration form, for example, a liquid formulation such as a liquid preparation (including syrup), tablets (including troche tablets and chewable tablets), pills, powders, granules, etc. Oral preparations in the form of solid preparations such as capsules (including soft capsules) can be mentioned. It is preferably in the form of a solid preparation. The carriers and / or additives described above may be selected according to a conventional method according to the dosage form, as long as they do not impair the effects of the present invention.
　本発明の医薬品または医薬部外品の投与量は、本発明の効果が奏される限り特に限定されず、患者の年齢、体重、症状の程度等によって適宜設定され得る。制限されないが、例えば、紅麹の総量として、１日投与量として（体重約６０ｋｇの大人の場合）１００～６０，０００ｍｇ／日程度、好ましくは２００～３０，０００ｍｇ／日程度の範囲から適宜設定することができる。当該投与量は、１日に１回または複数回に分けて投与することもできる。また本発明の医薬品または医薬部外品中に配合する紅麹類の割合は、本願の効果を奏するように上記１日摂取量に基づいて適宜設定することができ、紅麹の総量で例えば５～１００質量％の範囲から適宜選択設定することができる。 The dose of the drug or quasi-drug of the present invention is not particularly limited as long as the effect of the present invention is exhibited, and can be appropriately set depending on the age, weight, degree of symptoms, etc. of the patient. Although not limited, for example, the total amount of red yeast rice is appropriately set as a daily dose (for an adult weighing about 60 kg) from about 100 to 60,000 mg / day, preferably about 200 to 30,000 mg / day. can do. The dose can also be administered once or in multiple divided doses per day. Further, the proportion of red yeast rice to be blended in the pharmaceutical product or quasi-drug of the present invention can be appropriately set based on the above daily intake so as to achieve the effect of the present application, and the total amount of red yeast rice is, for example, 5. It can be appropriately selected and set from the range of about 100% by mass.
　後述する実験例に示すように、紅麹には、それ自体に乳び血漿を改善する作用がある。そのため、紅麹またはその加工物を経口組成物（飲食品、医薬品、医薬部外品が含まれる）中に配合することで、当該経口組成物に血漿の乳びを改善する機能を付与することができる。言い換えると、紅麹またはその加工物を経口組成物に配合することで、乳び血漿を改善する機能を有する紅麹含有経口組成物を製造し、取得することができる。なお、前述するように、紅麹菌を用いて紅麹を含む経口組成物を調製した場合でも、当該経口組成物に血漿の乳びを改善する機能を付与することができる。つまり、その場合でも乳び血漿を改善する機能を有する紅麹含有経口組成物を製造し、取得することができる。 As shown in the experimental example described later, red yeast rice itself has the effect of improving chylothorax. Therefore, by blending red yeast rice or its processed product in an oral composition (including foods and drinks, pharmaceuticals, quasi-drugs), the oral composition is given a function of improving plasma chylothorax. Can be done. In other words, by blending red yeast rice or a processed product thereof into the oral composition, a red yeast rice-containing oral composition having a function of improving chylothorax can be produced and obtained. As described above, even when an oral composition containing Monascus purpureus is prepared using Monascus purpureus, the oral composition can be imparted with a function of improving plasma chylothorax. That is, even in that case, an oral composition containing red yeast rice having a function of improving chylothorax can be produced and obtained.
（ＩＩ）カイロミクロン血症の抑制または改善剤、及びその製造方法
　本発明のカイロミクロン血症の抑制または改善剤は、紅麹またはその加工物を有効成分として含有することを特徴とする。有効成分として使用する紅麹、その加工物、及びそれらの製造取得方法は（Ｉ）で説明した通りであり、前述の記載はここに援用することができる。また、本発明のカイロミクロン血症の抑制または改善剤は、前述する乳び血漿改善剤と同様に、経口組成物（飲食品、医薬品、医薬部外品）として調製し、カイロミクロン血症の抑制または改善機能を有し、当該機能を享受するために使用される経口組成物として提供することができる。飲食品、医薬品、及び医薬部外品の種類、形状、紅麹の配合量、用量、及び用法なども（Ｉ）で説明した通りであり、前述の記載はここに援用することができる。 (II) Suppressing or ameliorating agent for chylomicronemia and method for producing the same The suppressing or ameliorating agent for chylomicronemia of the present invention is characterized by containing red yeast rice or a processed product thereof as an active ingredient. The red yeast rice used as an active ingredient, its processed product, and the method for obtaining the production thereof are as described in (I), and the above description can be incorporated herein by reference. Further, the agent for suppressing or ameliorating chylomicronemia of the present invention is prepared as an oral composition (food and drink, pharmaceuticals, quasi-drugs) in the same manner as the above-mentioned chylothorax improving agent, and is used for chylomicronemia. It has an inhibitory or ameliorating function and can be provided as an oral composition used to enjoy the function. The types and shapes of foods and drinks, pharmaceuticals, and quasi-drugs, the amount, dose, and usage of red yeast rice are also as described in (I), and the above description can be incorporated herein by reference.
　カイロミクロンは、血液中の中性脂肪がタンパク質と結合したリポタンパクであり、血液中にその浮遊量が多いと、血漿や血清が乳白濁するという現象（乳び）が認められる。つまり、カイロミクロン血症は、血液中のカイロミクロンが多い状態、言い換えると中性脂肪の量が多い状態を意味する。その原因は、特に制限されるものではないが、高脂肪食または／および高コレステロール食の継続的摂取（食生活・食習慣）に起因する二次性脂質異常症、血液中の脂質分解酵素の不足または機能低下などが含まれる。本発明のカイロミクロン血症の抑制または改善剤は、食事に由来する中性脂肪（外因性脂質）を原因とする血中のカイロミクロンの増加や貯留、特に食生活・食習慣に起因する血中のカイロミクロンの増加や貯留を抑制ないし改善することが可能である。 Chylomicron is a lipoprotein in which neutral fat in the blood is bound to a protein, and when the amount of suspension in the blood is large, a phenomenon (chylothorax) in which plasma and serum become milky white is observed. That is, chylomicronemia means a state in which the blood has a large amount of chylomicrons, in other words, a state in which the amount of triglycerides is large. The cause is not particularly limited, but secondary dyslipidemia caused by continuous intake (dietary habits / eating habits) of a high-fat diet and / or a high-cholesterol diet, and lipid-degrading enzymes in the blood Insufficient or functional deterioration is included. The inhibitor or ameliorating agent for chylomicrons of the present invention increases or stores chylomicrons in blood caused by triglyceride (exogenous lipid) derived from diet, especially blood caused by eating habits and eating habits. It is possible to suppress or improve the increase and storage of chylomicrons in the blood.
　カイロミクロン血症の抑制または改善効果は、血漿中のカイロミクロン量の低下から評価することができる。なお、血漿中のカイロミクロン量は、前述する乳び改善効果と同様に、血漿に対する光の透過率を測定することで評価することができる。その評価方法は、乳び改善効果の評価方法と同じく、（Ｉ）で説明した通りであり、前述の記載はここに援用することができる。 The inhibitory or ameliorating effect of chylomicrons can be evaluated from the decrease in the amount of chylomicrons in plasma. The amount of chylomicrons in plasma can be evaluated by measuring the light transmittance to plasma in the same manner as the above-mentioned chylothorax effect. The evaluation method is as described in (I) as in the evaluation method of the chylothorax improving effect, and the above description can be incorporated herein by reference.
　以上、本明細書において、「含む」及び「含有する」の用語には、「からなる」及び「から実質的になる」という意味が含まれる。 As described above, in the present specification, the terms "including" and "containing" include the meanings of "consisting of" and "consisting of substantially".
　以下、本発明の構成及び効果について、その理解を助けるために、実験例を用いて本発明を説明する。但し、本発明はこれらの実験例によって何ら制限を受けるものではない。以下の実験は、特に言及しない限り、室温（２５±５℃）、及び大気圧条件下で実施した。また、下記の動物実験の全手順は、「動物実験の適正な実施のためのガイドライン（日本学術会議、2006年6月1日）」に従って実施した。なお、特に言及する場合を除いて、「％」は「質量％」、「部」は「質量部」を意味する。 Hereinafter, the present invention will be described with reference to experimental examples in order to help understanding the structure and effects of the present invention. However, the present invention is not limited by these experimental examples. The following experiments were performed under room temperature (25 ± 5 ° C.) and atmospheric pressure conditions, unless otherwise noted. In addition, all the procedures for animal experiments below were carried out in accordance with the "Guidelines for Proper Implementation of Animal Experiments (Science Council of Japan, June 1, 2006)". Unless otherwise specified, "%" means "mass%" and "part" means "parts by mass".
　実験例
　被験動物として日本白色ウサギの雄（オリエンタル酵母工業株式会社）に紅麹を経口摂取させて、血中コレステロール（総コレステロール、ＬＤＬ－コレステロール、ＨＤＬ－コレステロール）濃度、血中トリグリセリド濃度、及び乳び血漿に対する紅麹の作用を検証した。 Experimental example A male Japanese white rabbit (Oriental Yeast Industry Co., Ltd.) was orally ingested with red yeast rice as a test animal to obtain blood cholesterol (total cholesterol, LDL-cholesterol, HDL-cholesterol) concentration, blood triglyceride concentration, and milk. The effect of red yeast rice on cholesterol was examined.
（１）被験動物、及び試験方法
　日本白色ウサギ（２週齢）をコントロール群（ｎ＝１０）と紅麹群（ｎ＝１０）の２群にわけ、両群に２週間にわたり高脂肪高コレステロール負荷食（0.25％コレステロール負荷）（オリエンタル酵母工業株式会社）を、毎日１００ｇ摂取させた。なお、各ウサギは、ケージに１匹ずつ個飼いし、水は自由摂取、餌は制限給餌した。 (1) Test animals and test method Japanese white rabbits (2 weeks old) were divided into two groups, a control group (n = 10) and a red yeast rice group (n = 10), and both groups had high fat and high cholesterol for 2 weeks. A loaded diet (0.25% cholesterol loaded) (Oriental Yeast Co., Ltd.) was ingested 100 g daily. Each rabbit was kept individually in a cage, water was freely ingested, and food was restricted.
　高脂肪高コレステロール負荷食摂取開始から２週間後、両群のウサギを１２時間絶食させて、その後、各群のウサギの耳介辺縁静脈から血液を採取した（０週）。さらにそれから３週間にわたり、コントロール群には引き続き高脂肪高コレステロール負荷食（100g／日）を摂取させ、一方、紅麹群には高脂肪高コレステロール負荷食（100g／日）と紅麹（500mg／日）を摂取させた。紅麹群に紅麹を摂取させてから２週間目（２週）と３週間目（３週）に、両群ともに１２時間絶食させた後に血液を採取した。なお、紅麹群のウサギに摂取させる紅麹として、市販の米紅麹粉体（３Ｐ－Ｄ２０；小林製薬株式会社製）を使用した。 Two weeks after the start of the high-fat, high-cholesterol load diet, the rabbits in both groups were fasted for 12 hours, and then blood was collected from the auricular marginal veins of the rabbits in each group (week 0). For the next 3 weeks, the control group continued to receive a high-fat, high-cholesterol-loaded diet (100 g / day), while the red yeast rice group received a high-fat, high-cholesterol-loaded diet (100 g / day) and red yeast rice (500 mg / day). Sun) was ingested. Blood was collected after fasting for 12 hours in both groups at the 2nd week (2nd week) and the 3rd week (3rd week) after the red yeast rice group was fed with red yeast rice. Commercially available rice red yeast rice powder (3P-D20; manufactured by Kobayashi Pharmaceutical Co., Ltd.) was used as the red yeast rice to be ingested by rabbits in the red yeast rice group.
（２）血液サンプルの処理と測定
　上記で両群のウサギから採取した血液サンプル（０週、２週、３週）を遠心分離し、血漿を調製した。調製した血漿の一部は、下記の方法で白色度（白濁度）を評価した。また残りの試料は、下記の測定キットを用いて、各マニュアルに記載されている方法に従って、総コレステロール濃度、ＬＤＬ－コレステロール濃度、ＨＤＬ－コレステロール濃度、及びトリグリセリド濃度を測定した。 (2) Treatment and measurement of blood samples Blood samples (0 week, 2 weeks, 3 weeks) collected from rabbits in both groups were centrifuged to prepare plasma. The whiteness (whiteness) of a part of the prepared plasma was evaluated by the following method. In the remaining samples, the total cholesterol concentration, LDL-cholesterol concentration, HDL-cholesterol concentration, and triglyceride concentration were measured using the following measurement kits according to the methods described in each manual.
（ａ）総コレステロール（T-Cho）：
　コレステロールキット　ＬタイプワコーＣＨＯ・Ｍ（コレステロールオキシダーゼ・ＨＭＭＰＳ法）（富士フィルム和光純薬株式会社製）
（ｂ）ＬＤＬ－コレステロール（LDL-C）：
　コレステロールキット　コレステストＬＤＬ（界面活性剤による分離、酵素発色法）（積水メディカル株式会社製）
（ｃ）ＨＤＬ－コレステロール（HDL-C）：
　コレステロールキット　コレステストＮ　ＨＤＬ（界面活性剤による分離、酵素発色法）（積水メディカル株式会社製）
（ｄ）トリグリセリド（TG）：
　トリグリセライドキット　Ｌタイプワコー　ＴＧ・Ｍ（ＧＰＯ・ＨＭＭＰＳ法）（富士フィルム和光純薬株式会社製） (A) Total cholesterol (T-Cho):
Cholesterol kit L type Wako CHO / M (cholesterol oxidase / HMMPS method) (manufactured by Fuji Film Wako Pure Chemical Industries, Ltd.)
(B) LDL-cholesterol (LDL-C):
Cholesterol kit Cholesterol LDL (separation with surfactant, enzyme coloring method) (manufactured by Sekisui Medical Co., Ltd.)
(C) HDL-cholesterol (HDL-C):
Cholesterol kit Cholesterol N HDL (separation with surfactant, enzyme coloring method) (manufactured by Sekisui Medical Co., Ltd.)
(D) Triglyceride (TG):
Triglyceride kit L type Wako TG / M (GPO / HMMPS method) (manufactured by Fuji Film Wako Pure Chemical Industries, Ltd.)
（ｅ）血漿の白濁度の測定
　得られた血漿約５ｍＬをφ１８ｍｍの試験管に入れ、デジタル比色計簡易モニター（miniphoto518R）（TAITEC社製）を用いて、水をブランク（光透過率100％）として、波長660nmにおける吸光度（OD660）に基づいて光の透過率（％）を測定し、血漿の白濁度を評価した。各群（コントロール群［ｎ＝10］、紅麹群［ｎ＝10］）のウサギから採取調製した血漿をそれぞれ測定して、得られた透過率（％）の平均値を求めた。 (E) Measurement of plasma turbidity Place approximately 5 mL of the obtained plasma in a test tube of φ18 mm, and use a digital colorimetric meter simple monitor (miniphoto518R) (manufactured by TAITEC) to blank water (light transmittance 100%). ), The transmittance (%) of light was measured based on the absorbance (OD660) at a wavelength of 660 nm, and the white turbidity of plasma was evaluated. Plasma collected and prepared from rabbits in each group (control group [n = 10], red yeast rice group [n = 10]) was measured, and the average value of the obtained transmittance (%) was obtained.
（３）測定結果
　各群（コントロール群：―●―、紅麹群：--●--）の血漿中の総コレステロール濃度を図１（Ａ）、ＬＤＬ－コレステロール濃度を図１（Ｂ）、ＨＤＬ－コレステロール濃度を図２（Ａ）、及びトリグリセリド濃度を図２（Ｂ）に、それぞれ示す。 (3) Measurement results The total plasma cholesterol concentration of each group (control group: ― ● ―, red yeast rice group:-●-) is shown in FIG. 1 (A), and the LDL-cholesterol concentration is shown in FIG. 1 (B). The HDL-cholesterol concentration is shown in FIG. 2 (A), and the triglyceride concentration is shown in FIG. 2 (B), respectively.
　図１（Ａ）に示すように、紅麹を摂取していないウサギ（コントロール群）は、高脂肪高コレステロール負荷食を摂取し続けることで、血液サンプル中の総コレステロール濃度が経時的に増加することが確認された。一方、紅麹を摂取させたウサギ（紅麹群）は、紅麹を摂取させる前（０週）と比較して、総コレステロール濃度の低下は認められないものの、高脂肪高コレステロール負荷食の継続摂取にも関わらず、コントロール群で認められた総コレステロール濃度の増加は認められなかった。 As shown in FIG. 1 (A), in rabbits (control group) not ingesting red yeast rice, the total cholesterol concentration in the blood sample increases over time by continuing to ingest a high-fat, high-cholesterol-loaded diet. It was confirmed that. On the other hand, in the rabbits fed with red yeast rice (monascus group), the total cholesterol concentration did not decrease as compared with before ingesting red yeast rice (0 week), but the high-fat, high-cholesterol-loaded diet was continued. Despite ingestion, no increase in total cholesterol levels was observed in the control group.
　図１（Ｂ）及び図２（Ａ）に示すように、紅麹を摂取していないウサギ（コントロール群）は、高脂肪高コレステロール負荷食を摂取し続けることで、血液サンプル中のＬＤＬ－コレステロール濃度はほとんど変化しなかったものの、ＨＤＬ－コレステロール濃度が経時的に増加することが確認された。紅麹を摂取させたウサギ（紅麹群）は、紅麹を摂取させる前（０週）と比較して、ＬＤＬ－コレステロール濃度は低下するものの、ＨＤＬ－コレステロール濃度はコントロール群と同様に増加することが確認された。 As shown in FIGS. 1 (B) and 2 (A), rabbits (control group) who did not ingest red yeast rice had LDL-cholesterol in blood samples by continuing to ingest a high-fat, high-cholesterol-loaded diet. It was confirmed that the HDL-cholesterol concentration increased with time, although the concentration hardly changed. Rabbits fed with red yeast rice (monascus group) had lower LDL-cholesterol levels but increased HDL-cholesterol levels as compared with the control group before ingesting red yeast rice (week 0). It was confirmed that.
　図２（Ｂ）に示すように、紅麹を摂取していないウサギ（コントロール群）及び紅麹を摂取させたウサギ（紅麹群）ともに、トリグリセリド濃度に有意な変化は認められなかった。 As shown in FIG. 2 (B), no significant change was observed in the triglyceride concentration in both the rabbits not ingesting red yeast rice (control group) and the rabbits ingested red yeast rice (monascus group).
　図３（Ａ）に、紅麹を摂取してないウサギ（コントロール群）の血漿の光透過率（％）と紅麹を摂取させたウサギ（紅麹群）の血漿の光透過率（％）を比較したグラフを記載する（左図：紅麹摂取から２週目に採取した血漿サンプル、右図：紅麹摂取から３週目に採取した血漿サンプル）。いずれも結果は、各群のウサギから採取した血漿サンプルについて測定した光透過率の平均値である。図３（Ｂ）に、紅麹投与（２週目と３週目）による血漿の光透過率の変化（紅麹群の血漿の光透過率（平均値）－コントロール群の血漿の光透過率（平均値））を示す。これからわかるように、高脂肪高コレステロール負荷食の継続摂取にも関わらず、紅麹を摂取することで、血漿の白濁が低下すること、つまり血漿の乳びが低減改善し、カイロミクロン血症が改善することが確認された。


  FIG. 3 (A) shows the plasma light transmittance (%) of the rabbits (control group) that did not ingest the red yeast rice and the plasma light transmittance (%) of the plasma of the rabbits (monascus group) that received the red yeast rice. (Left figure: plasma sample collected 2 weeks after ingestion of Monascus, right figure: plasma sample collected 3 weeks after ingestion of Monascus). In each case, the results are the average values of light transmittance measured for plasma samples taken from rabbits in each group. FIG. 3 (B) shows changes in plasma light transmittance due to administration of red koji (weeks 2 and 3) (light transmittance of plasma in the red koji group (mean value) -light transmittance of plasma in the control group. (Mean value)) is shown. As can be seen, despite continuous intake of a high-fat, high-cholesterol-loaded diet, ingestion of red koji reduces plasma turbidity, that is, reduces and improves plasma chylothorax, resulting in chylomicronemia. It was confirmed that it would improve.

Claims (7)

  1. 　紅麹またはその加工物を含有する乳び血漿改善剤。 Chylothorax plasma improving agent containing red yeast rice or its processed products.
  2. 　前記紅麹の生産菌がモナスカス・ピローサス（Monascus pilosus）である、請求項１に記載する乳び血漿改善剤。 The chylothorax plasma improving agent according to claim 1, wherein the producing bacterium of the red yeast rice is Monascus pyrosus.
  3. 　前記乳び血漿が、高脂肪食または／および高コレステロール食を摂取することに起因するものである、請求項１または２に記載する乳び血漿改善剤。 The chylothorax improving agent according to claim 1 or 2, wherein the chylothorax is caused by ingesting a high-fat diet and / or a high-cholesterol diet.
  4. 　紅麹またはその加工物を含有するカイロミクロン血症の抑制または改善剤。 A suppressor or ameliorating agent for chylomicronemia containing red yeast rice or its processed products.
  5. 　前記カイロミクロン血症が脂肪分解酵素の不足または機能低下に起因するものである、請求項４に記載するカイロミクロン血症の抑制または改善剤。 The agent for suppressing or ameliorating chylomicronemia according to claim 4, wherein the chylomicronemia is caused by a deficiency or functional deterioration of a lipolytic enzyme.
  6. 　前記紅麹の生産菌がモナスカス・ピローサス（Monascus pilosus）である、請求項４または５に記載するカイロミクロン血症の抑制または改善剤。 The agent for suppressing or ameliorating chylomicronemia according to claim 4 or 5, wherein the bacterium that produces the red yeast rice is Monascus pyrosus.
  7. 　前記カイロミクロン血症が高脂肪食または／および高コレステロール食を摂取することに起因するものである、請求項４～６のいずれかに記載するカイロミクロン血症の抑制または改善剤。


          The inhibitor or ameliorating agent for chylomicronemia according to any one of claims 4 to 6, wherein the chylomicronemia is caused by ingesting a high-fat diet and / or a high-cholesterol diet.
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WO2022186042A1 (en) * 2021-03-04 2022-09-09 小林製薬株式会社 Cholesterol-lowering agent

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WO2001006243A1 (en) * 1999-07-16 2001-01-25 Asahi Kasei Kabushiki Kaisha Method for measuring substance and measurement reagent to be used in the method
JP2012158553A (en) * 2011-02-01 2012-08-23 Gunze Ltd Visceral fat accumulation inhibitor
JP2013063925A (en) * 2011-09-16 2013-04-11 Sunway Biotech Co Ltd Mixture capable of reducing blood lipid and raising hdl cholesterol, and method for producing the same
JP2014531418A (en) * 2011-09-06 2014-11-27 アイピー サイエンス リミテッド Products and methods

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Publication number Priority date Publication date Assignee Title
JPH09288111A (en) * 1996-04-23 1997-11-04 Iatron Lab Inc Reagent for removing turbidity of biological sample
WO2001006243A1 (en) * 1999-07-16 2001-01-25 Asahi Kasei Kabushiki Kaisha Method for measuring substance and measurement reagent to be used in the method
JP2012158553A (en) * 2011-02-01 2012-08-23 Gunze Ltd Visceral fat accumulation inhibitor
JP2014531418A (en) * 2011-09-06 2014-11-27 アイピー サイエンス リミテッド Products and methods
JP2013063925A (en) * 2011-09-16 2013-04-11 Sunway Biotech Co Ltd Mixture capable of reducing blood lipid and raising hdl cholesterol, and method for producing the same

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Publication number Priority date Publication date Assignee Title
WO2022186042A1 (en) * 2021-03-04 2022-09-09 小林製薬株式会社 Cholesterol-lowering agent

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