Lipid absorption promoter

Abstract

To provide a lipid absorption promoter.SOLUTION: A lipid absorption promoter composed of 2'-fucosyllactose.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to a lipid absorption enhancer. [Background technology]

[0002] Human milk oligosaccharides (HMOs) are oligosaccharides found in human breast milk. HMOs are nutrients for beneficial bacteria such as bifidobacteria, and their various physiological functions are expected to be utilized.

[0003] For example, Patent Document 1 describes a growth inhibitor for oral pathogenic bacteria containing one or more selected from milk oligosaccharides and lactulose. Known HMOs include sialyllactose and fucosyllactose.

[0004] Lipids are known as important sources of energy and nutrients. For example, triglycerides accumulate in the body and serve as an energy source. Essential fatty acids, phospholipids, and cholesterol are nutrients that make up the body's hormones, cell walls, and cell membranes. Impaired digestion and absorption of lipids, which serve as energy sources and nutrients, can cause symptoms such as malnutrition, diarrhea, weight loss, general fatigue, abdominal distension, edema, and anemia.

[0005] Therefore, lactoferrin (Patent Document 2) and lactic acid bacteria and / or bifidobacteria (Patent Document 3) have been proposed as lipid absorption promoters with the aim of improving lipid absorption function. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] Patent Publication No. 2021-065176 [Patent Document 2] Japanese Patent Application Laid-Open No. 2009-149550 [Patent Document 3] International Publication No. 2016 / 111276 Summary of the Invention [Problem to be solved by the invention]

[0007] The present invention aims to provide a novel lipid absorption enhancer. [Means for solving the problem]

[0008] The present invention relates to, for example, the following [1] and [2].

[0009] [1] A lipid absorption enhancer consisting of 2'-fucosyllactose. [2] A composition for promoting lipid absorption containing 2'-fucosyllactose. [Effects of the Invention]

[0010] According to the present invention, a lipid absorption enhancer can be provided. [Brief explanation of the drawings]

[0011] [Figure 1] FIG. 1 is a graph and a table showing the change in blood triglyceride concentration in mice over time. DETAILED DESCRIPTION OF THE INVENTION

[0012] 2'-Fucosyl lactose is a trisaccharide consisting of L-fucose, D-galactose and D-glucose, and is a compound in which the 2' position of lactose is fucosylated. 2'-Fucosyl lactose can be produced by known methods, for example, by microbial fermentation, enzymatic process, chemical synthesis, or a combination thereof. In addition, 2'-Fucosyl lactose can be used as a commercially available product.

[0013] The lipid absorption enhancer consists of 2'-fucosyllactose.

[0014] As used herein, "promoting lipid absorption" means promoting lipid absorption from the digestive organs (e.g., the small intestine) and increasing the blood lipid concentration. The type of lipid is not particularly limited, but examples include triglycerides.

[0015] The lipid absorption enhancer can be applied to humans and non-human mammals, preferably humans. Humans may be adults, children, infants, and young children. Non-human mammals include mice, rats, guinea pigs, hamsters, rabbits, cats, dogs, sheep, pigs, cows, horses, goats, and monkeys.

[0016] The dosage or intake of the lipid absorption promoter, i.e., the dosage or intake of 2'-fucosyllactose, is 50 mg to 10,000 mg per day for a subject weighing 60 kg, preferably 100 mg to 5,000 mg, more preferably 6 mg to 3,000 mg, and most preferably 1,000 mg to 2,000 mg.

[0017] The lipid absorption enhancer can be administered once a day, twice a day, or three times a day.

[0018] The lipid absorption enhancer may be administered orally, rectally, intraperitoneally, intravenously, subcutaneously, intramuscularly, transdermally or by eye drop, preferably orally or rectally.

[0019] The lipid absorption enhancer may be in the form of, for example, a solid; a liquid (solution or suspension); an emulsion such as a lotion or cream; a paste; a gel; or a mousse.

[0020] The composition for promoting lipid absorption contains 2'-fucosyllactose.

[0021] The content of 2'-fucosyllactose in the composition for promoting lipid absorption is 0.001% by mass to 99.9% by mass, preferably 0.005% by mass to 75% by mass, and more preferably 0.01% by mass to 50% by mass, based on the total mass of the composition for promoting lipid absorption.

[0022] The dosage or intake of the composition for promoting lipid absorption is not particularly limited, as long as the dosage or intake of 2'-fucosyllactose is 50 mg to 10,000 mg per day for a subject weighing 60 kg, preferably 100 mg to 5,000 mg, more preferably 6 mg to 3,000 mg, and most preferably 1,000 mg to 2,000 mg.

[0023] Examples of the lipid absorption-promoting composition include food compositions, feed compositions, and pharmaceutical compositions.

[0024] The food composition may be a general food, a food for specified health uses, a food with nutrient function claims, a food with functional claims, a food for hospital patients, a supplement, etc. It may also be a food additive containing 2'-fucosyllactose.

[0025] The food composition is not particularly limited in form or properties as long as it does not impair the effect of the lipid absorption enhancer, and examples thereof include tablet candy, wheat products (bread, macaroni, spaghetti, etc.), instant foods (retort / prepared foods, canned foods, microwave foods, cup noodles, etc.), processed agricultural products (canned agricultural products, canned fruit, jams / marmalades, cereals (processed grain products), etc.), processed seafood products (canned seafood, fish ham / sausage, etc.), processed livestock products (livestock ham / sausage, etc.), milk / dairy products (processed milk, milk drinks, yogurt, lactic acid bacteria drinks, cheese, ice cream, etc.), oils and fats (butter, margarines, vegetable oils, etc.), seasonings (soy sauce, miso, sauces, mirin, vinegars, etc.), cooking mixes, Examples of such products include curry bases, sauces, dressings, noodle soups, spices, etc., frozen foods, semi-cooked frozen foods, cooked frozen foods, confectioneries (caramel, candy, chewing gum, chocolate, cookies, biscuits, cakes, pies, snacks, crackers, Japanese sweets, rice snacks, bean snacks, dessert sweets, jellies, etc.), beverages (natural fruit juice, fruit juice drinks, soft drinks containing fruit juice, fruit pulp drinks, fruit drinks containing fruit particles, vegetable drinks, soy milk, soy milk drinks, coffee drinks, tea drinks, powdered drinks, concentrated drinks, sports drinks, nutritional drinks, alcoholic beverages, etc.), baby food, infant formula (including powdered milk, liquid milk, etc.), liquid diets, nutritional compositions such as supplements, and functional foods (foods for specified health uses, foods with nutrient functions). When the lipid absorption enhancer is a food composition, it is preferably a nutritional composition such as infant formula, liquid diet, or supplement, and more preferably infant formula.

[0026] When the food composition is a nutritional composition such as a supplement, it can be formulated into solid preparations such as powders, granules, tablets, and capsules; liquid preparations such as solutions, syrups, suspensions, and emulsions; etc.

[0027] The food composition may contain ingredients acceptable for use in food products, as long as they are effective in promoting lipid absorption, such as minerals, vitamins, flavonoids, quinones, polyphenols, amino acids, nucleic acids, essential fatty acids, cooling agents, binders, sweeteners, disintegrants, lubricants, colorants, flavorings, stabilizers, preservatives, sustained-release regulators, surfactants, solubilizers, and humectants.

[0028] The food composition may be taken orally. In particular, when the food composition is a nutritional composition, it may be taken by rectal administration in addition to oral intake.

[0029] Examples of the feed composition include pet food, livestock feed, and fish feed.

[0030] The dosage form of the pharmaceutical composition may be solid preparations such as powders, granules, tablets, and capsules; or liquid preparations such as solutions, syrups, suspensions, and emulsions.

[0031] The pharmaceutical composition may contain other ingredients besides 2'-fucosyllactose, as long as the lipid absorption-promoting effect is not impaired. Other ingredients include active ingredients and ingredients used in formulation.

[0032] Medicinal ingredients include vitamins such as water-soluble vitamins (vitamins B1, B2, B3, B5, B6, B12, B13, B15, B17, biotin, choline, folic acid, inositol, PABA, vitamin C, vitamin P) and oil-soluble vitamins (vitamins A, D, E, K); minerals such as calcium, magnesium, phosphorus, and iron; sulfur-containing compounds found in taurine and garlic; polyphenols such as hesperidin and quercetin; proteins such as collagen; peptides; amino acids; animal fats and oils; vegetable fats and oils; crushed or extracted animals and plants; sweeteners such as aspartame, sucralose, and acesulfame K; dietary fiber; and fungi such as lactic acid bacteria and acetic acid bacteria.

[0033] The ingredients used in the formulation include excipients, pH adjusters, colorants, flavoring agents, binders, disintegrants, lubricants, stabilizers, and the like.

[0034] Examples of excipients include sugar derivatives such as lactose, sucrose, glucose, mannitol, and sorbitol; starch derivatives such as corn starch, potato starch, α-starch, dextrin, and carboxymethyl starch; cellulose derivatives such as crystalline cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, carboxymethyl cellulose, and carboxymethyl cellulose calcium; gum arabic; dextran; pullulan; silicate derivatives such as light anhydrous silicic acid, synthetic aluminum silicate, and magnesium aluminometasilicate; phosphate derivatives such as calcium phosphate; carbonate derivatives such as calcium carbonate; and sulfate derivatives such as calcium sulfate.

[0035] Examples of binders include gelatin, polyvinylpyrrolidone, macrogol, and the like, in addition to the components listed above as excipients.

[0036] Examples of disintegrants include, in addition to the ingredients listed as the excipients above, chemically modified starch or cellulose derivatives such as croscarmellose sodium, sodium carboxymethyl starch, and cross-linked polyvinylpyrrolidone.

[0037] Examples of lubricants include talc; stearic acid; metal stearates such as calcium stearate and magnesium stearate; colloidal silica; waxes such as veegum and gaelt; boric acid; glycol; carboxylic acids such as fumaric acid and adipic acid; sodium carboxylates such as sodium benzoate; sulfates such as sodium sulfate; leucine; lauryl sulfates such as sodium lauryl sulfate and magnesium lauryl sulfate; silicic acids such as silicic anhydride and silicic acid hydrate; and starch derivatives.

[0038] Examples of stabilizers include paraoxybenzoic acid esters such as methylparaben and propylparaben; alcohols such as chlorobutanol, benzyl alcohol and phenylethyl alcohol; benzalkonium chloride; acetic anhydride; sorbic acid; and the like. [Example]

[0039] The present invention will be described in more detail below using examples, but the present invention is not limited to these examples.

[0040] Eight 4-week-old C57BL / 6J male mice (CLEA Japan, Inc.) were divided into two groups (Group 1 and Group 2) of four mice each so that the average body weight was equal, and the mice were allowed to acclimate for one week before being used in the study from the age of 5 weeks. During the acclimatization period, the mice were allowed to drink water ad libitum and were given solid feed (CLEA Japan, Inc., product name: CE-2) ad libitum.

[0041] After acclimatization, one of the two groups was designated as the 2'-fucosyllactose-administered group (hereinafter also referred to as the "2'FL-administered group") (Example 1). A 2'FL aqueous solution (2'FL concentration: 80 mg / mL) was prepared using physiological saline (0.9% by mass NaCl aqueous solution) as a solvent. The 2'FL aqueous solution was orally administered to the mice of the 2'FL-administered group once daily for 11 days, so that the dose of the 2'FL aqueous solution was 0.1 mL / 20 g body weight based on the mouse's body weight. At this time, the dose of 2'FL per mouse body weight was 400 mg / kg body weight based on the mouse's body weight. During the oral administration period of the 2'FL aqueous solution, the mice were allowed to drink water ad libitum and were given solid feed (manufactured by CLEA Japan, product name: CE-2) ad libitum. They were housed at a temperature of 22°C, humidity of 40%, and a 12-hour light-dark cycle.

[0042] The remaining group was used as a control group (Comparative Example 1). The control group was kept under the same conditions as the 2'FL-administered group, except that the 2'FL aqueous solution administered to the 2'FL-administered group was replaced with physiological saline.

[0043] The human equivalent dose of 2'FL in the 2'FL-treated group corresponds to 28.9-30.7 mg / kg per person weighing 60 kg. The human equivalent dose was calculated based on the "Guidance for Industry Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers" (U.S. Department of Health and Human Services (HHS) / U.S. Food and Drug Administration (FDA) / Center for Drug Evaluation and Research (CDER) (July 2015)).

[0044] Subsequently, a nutrient absorption test was conducted on day 11 of oral administration. In the nutrient absorption test, first, 2'FL aqueous solution or sterile water was administered on day 11 of oral administration, followed by a 5-hour fast. Then, a lipoprotein lipase inhibitor (P407, manufactured by Merck) was dissolved in sterile saline to a concentration of 10 w / w% as a lipid absorption inhibitor, and a solution of 0.2 mL / 20 g body weight per mouse was administered intraperitoneally.

[0045] One hour after the administration of the lipid absorption inhibitor, soybean oil (Fujifilm Wako Pure Chemical Industries, Ltd.) was orally administered to each group of mice at a dose of 0.2 mL / 20 g body weight. The time point at which soybean oil was orally administered was set as 0 minutes, and 0.05 mL of blood was collected from the tail vein of each mouse 0, 15, 30, 60, 120, and 300 minutes after the administration of soybean oil. The blood triglyceride concentration (blood TG concentration) was measured using EnzyChrom. TM Measurement was performed using a Triglyceride Assay Kit (manufactured by BioAssay Systems), and the mean value ± standard deviation of the blood TG concentration for each group was calculated.

[0046] The measurement results are shown in Figure 1.

[0047] The results in Figure 1 show that in the 2'FL-administered group of Example 1, the blood triglyceride concentration over time after soybean oil administration was higher than that of the control group of the comparative example, and 300 minutes after soybean oil administration, the average blood TG concentration in the 2'FL-administered group was more than 2.5 times the average blood TG concentration in the control group.

Claims

1. A lipid absorption promoter consisting of 2'-fucosyllactose.

2. A composition for promoting lipid absorption, comprising 2'-fucosyllactose.

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