JP2011201842A - Proliferation promoter for intestine-derived cell - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a proliferation promoter for intestine-derived cells, easy to produce, comprising, as an active ingredient, an ingredient found in colostrum which is safe in making an oral administration, to provide a nutrient or medicament absorption promoter with the promoter as an active ingredient, and to provide pharmaceutical compositions or food compositions each containing the promoter as an active ingredient.SOLUTION: The proliferation promoter for intestine-derived cells comprises, as an active ingredient, a casein composition obtained by extraction of colostrum with an acid. The nutrient or medicament absorption promoter with the promoter as an active ingredient is also provided. Besides, pharmaceutical compositions or food compositions each containing the proliferation promoter as an active ingredient are provided.

Description

  The present invention relates to a casein composition derived from colostrum.

  Mammalian milk is known to have a function of providing various benefits to a living body. Therefore, in consideration of the safety of milk itself, there are many foods, pharmaceuticals, and the like in which various components derived from milk are formulated as oral compositions.

  Milk collected from mammals can be fractionated into an acid-soluble fraction (so-called whey fraction) and an acid-insoluble fraction (so-called casein fraction). The casein fraction contains several types of casein proteins in which a large number of serine residues are phosphorylated, and these casein proteins occupy most of the protein contained in milk. Generally, as the casein protein contained in the casein fraction, for example, α-casein, β-casein, κ-casein and the like are known, and since these various casein proteins have high nutritional value, there are various It is used as a nutritional supplement for simple foods (Patent Document 1).

  Mammal milk can also be broadly divided into colostrum that is milked in a relatively short period of time, such as about 10 days after parturition, and normal milk after about 10 days. It is known to play. Examples of such an effect include an effect of increasing the thickness of the intestine and intestinal mucosa, the surface area of the intestine, and the like, and the effects include EGF (epidermal growth factor), IGF contained in the whey fraction of colostrum. It is said that growth hormone stimulating factors such as (insulin-like growth factor), various peptides, lactoferrin, α-lactalbumin, glutamine (Patent Documents 2 to 6) and the like are carried.

  Furthermore, the present inventors compared bovine colostrum and bovine normal milk and found that colostrum has a superior effect on the intestine, and that the whey fraction of colostrum stimulated growth hormone. It has been confirmed that it contains a lot of factors, various peptides, lactoferrin and the like (Non-patent Document 1).

  On the other hand, there is no report that the casein fraction has an effect on the intestine, and it has only been reported that κ-casein glycomacropeptide, which decomposes a part of casein, has an effect of suppressing gastric acid secretion. (Patent Documents 7 to 9). Patent Document 10 discloses that the acid-soluble fraction in micellar casein has an effect on the intestine. The acid-soluble fraction of this document is a fraction containing glucagon-like peptide, lactoferrin, and the like. Minutes and does not contain casein proteins such as α-casein.

JP 2006-534683 A JP-A-11-505528 JP-A-6-510066 JP 2003-033160 A JP 2004-231643 A JP 2010-006764 A JP-A-4-210647 JP-A-5-065295 Japanese Patent Laid-Open No. 5-262793 JP2007-525404A Yoshitaka Kanemaru et al., “Effects of bovine late colostrum on rat cultured intestinal cells and mouse small intestinal epithelial tissue”, Abstracts of the 2009 Annual Meeting of the Japanese Society of Agricultural Chemistry, p. 220 3P035A

  The main object of the present invention is an intestinal cell growth promoter, nutritional or drug absorption enhancer, pharmaceutical composition, comprising as an active ingredient an ingredient contained in colostrum that is easy to manufacture and safe for oral consumption A food composition is provided.

  As a result of intensive studies in view of the above problems, the present inventors have found an intestinal-derived cell growth promoter containing a casein composition obtained by acid extraction of colostrum as an active ingredient. That is, this invention is completed based on this knowledge, and includes the aspect shown below.

I. Growth accelerating agent (I-1) An intestinal cell-derived cell growth accelerating agent comprising a casein composition obtained by acid extraction of colostrum as an active ingredient.
(I-2) The growth promoter according to (I-1), wherein the casein composition contains κ-casein having N-acetyllactosamine as part of a sugar chain.
(I-3) The casein composition contains three casein proteins, α-casein, β-casein, and κ-casein, and the total amount of the three casein proteins is 60 to 99% by weight in the casein composition. (I-1) or (I-2).
(I-4) The casein composition contains α-casein: β-casein: κ-casein in a weight ratio of 1: 0.5 to 0.8: 0.1 to 0.4 (I-1 ) To (I-3).
(I-5) The growth promoter according to any one of (I-1) to (I-4), wherein the colostrum is milked within 10 days after delivery.
(I-6) The growth promoter according to any one of (I-1) to (I-5), wherein the colostrum is milked within 10 days from 1 day after delivery.
(I-7) The growth promoter according to any one of (I-1) to (I-6), wherein the intestinal cell is an intestinal epithelial cell.
(I-8) The growth promoter according to any one of (I-1) to (I-7), wherein the intestinal cell is a small intestinal epithelial cell.

II. Nutrition or drug absorption enhancer (II-1) A nutrition or drug absorption enhancer comprising as an active ingredient a casein composition obtained by acid extraction of colostrum.
(II-2) The nutrition or drug absorption enhancer according to (II-1), wherein the casein composition contains κ-casein having N-acetyllactosamine as part of a sugar chain.
(II-3) The casein composition contains three casein proteins, α-casein, β-casein, and κ-casein, and the total amount of the three casein proteins is 60 to 99% by weight in the casein composition. (II-1) or (II-2).
(II-4) The casein composition contains α-casein: β-casein: κ-casein in a weight ratio of 1: 0.5 to 0.8: 0.1 to 0.4 (II-1 ) To (II-3) The nutrition or drug absorption enhancer according to any one of the above.
(II-5) The nutrition or drug absorption enhancer according to any one of (II-1) to (II-4), wherein the colostrum is milked within 10 days after delivery.
(II-6) The nutrition or drug absorption enhancer according to any one of (II-1) to (II-5), wherein the colostrum is milked within 10 days from 1 day after delivery.

III. Pharmaceutical compositions (III-1) a pharmaceutical composition comprising, as an active ingredient, casein composition obtained by extracting the acid colostrum.
(III-2) The pharmaceutical composition according to (III-1), wherein the casein composition contains κ-casein having N-acetyllactosamine as part of a sugar chain.
(III-3) The casein composition contains three casein proteins, α-casein, β-casein, and κ-casein, and the total amount of the three casein proteins is 60 to 99% by weight in the casein composition. (III-1) or (III-2).
(III-4) The casein composition contains α-casein: β-casein: κ-casein in a weight ratio of 1: 0.5 to 0.8: 0.1 to 0.4 (III-1 )-(III-3) The pharmaceutical composition according to any one of the above.
(III-5) The pharmaceutical composition according to any one of (III-1) to (III-4), wherein the colostrum is milked within 10 days after delivery.
(III-6) The pharmaceutical composition according to any one of (III-1) to (III-5), wherein the colostrum is milked within 10 days from 1 day after parturition.
(III-7) The pharmaceutical composition according to any one of (III-1) to (III-6), which is a preventive or therapeutic agent for intestinal diseases.
(III-8) The pharmaceutical composition according to (III-7), wherein the intestinal disease is a disease accompanied by inflammation.
(III-9) The pharmaceutical composition according to (III-7) or (III-8), wherein the intestinal disease is a disease that develops in the small intestine.

IV. Food composition (IV-1) A food composition comprising a casein composition obtained by acid extraction of colostrum as an active ingredient.
(IV-2) The food composition according to (IV-1), wherein the casein composition contains κ-casein having N-acetyllactosamine as part of a sugar chain.
(IV-3) The casein composition contains three casein proteins, α-casein, β-casein, and κ-casein, and the total amount of the three casein proteins is 60 to 99% by weight in the casein composition. The food composition according to (IV-1) or (IV-2).
(IV-4) The casein composition contains α-casein: β-casein: κ-casein in a weight ratio of 1: 0.5 to 0.8: 0.1 to 0.4 (I-1 The food composition according to any one of (I-3).
(IV-5) The food composition according to any one of (IV-1) to (IV-4), wherein the colostrum is milked within 10 days after delivery.
(IV-6) The food composition according to any one of (IV-1) to (IV-5), wherein the colostrum is milked within 10 days from 1 day after parturition.
(IV-7) The food composition according to any one of (IV-1) to (IV-5), which is a food additive.

  The casein composition obtained by acid extraction of the colostrum of the present invention can be used as an active ingredient of an intestinal cell growth promoter, food or drug absorption enhancer, pharmaceutical composition or food composition.

The cell growth-promoting effect which the casein composition derived from colostrum exerts on IEC-6 cells. Analysis of villi length of the small intestine of mice that were orally ingested with casein composition derived from colostrum. The ratio of the number of proliferating cells in the small intestine crypt of the mouse | mouth which orally ingested the casein composition derived from colostrum.

Regarding the casein composition, the colostrum of the present invention is milk that can be milked within 10 days immediately after delivery of a mammal. In particular, milk that is milked within one day after parturition is initial colostrum, and milk that is milked within ten days after parturition is termed late colostrum. As the colostrum of the present invention, late colostrum is preferable.

  The origin of the colostrum is not particularly limited as long as it is colostrum derived from an animal that can grow by breastfeeding, but in view of the casein composition of the present invention used in combination with a pharmaceutical or functional food, Colostrum derived from an animal whose safety has already been confirmed for the human body is preferred. Specific examples include colostrum derived from cows, goats, sheep, horses, humans and the like. Preferably, it is bovine-derived colostrum.

  The cattle may be wild cattle including buffalo, bison, buffalo and the like, and may be cattle of various varieties that are adapted and raised as livestock. Specific cattle breeds include Angler, Welsh Black, Ayrshire, Groningen, Kelly, South Devon, Jersey, Simmental, Swedish Red and White, Dexter, Daily Shorthorn, Norway Red species, Norman species, Pyrrouge Flanders species, Finnish species, Brown Swiss species, Holstein species, Museline Issel species, Montbelière species, Lincoln red species, Red Danish species, Red Paul species, and the like. A preferred variety is the Holstein variety.

  The colostrum contains special casein protein in addition to the casein protein contained in regular milk. Specifically, only colostrum is characterized by having two κ-caseins having N-acetyllactosamine as part of the sugar chain.

  The method for confirming the above-mentioned two kappa-caseins with N-acetyllactosamine is described in “T. Saito et al., Biochinica et Biophysica Acta, 678 (1981) 257-267 The Chemical Structure of Neutral Candace of Nature of Science. Bovine Colostrum κ-Casein. As described in the above, a sugar chain cut out from κ-casein and methylated can be confirmed by using a known mass spectrometry technique.

  The acid extraction of the present invention refers to a raw material obtained by defatting powdered raw milk (colostrum) within 10 days after delivery, after adding acid to fractionate into an acid-soluble fraction and an acid-insoluble fraction, followed by solid-liquid separation. The casein composition of the present invention can be obtained as an acid-insoluble fraction (solid component after the solid-liquid separation step) after acid extraction of the colostrum.

  When emulsifying raw milk defatted powder in the above-described method, it can usually be prepared by subjecting it to steps such as lipid separation, sterilization, protein concentration, and drying according to methods known in the art.

  Examples of the lipid separation step include a method using a three-way separator. In this case, the separation step is usually about 5000 to 7000G, preferably about 5200 to 6500G, more preferably about 5300 to 6200G, and usually about 45 to 120 ° C, preferably about 46 to 100 ° C, more preferably 47 to 80. It is performed under the condition of about ° C. For example, raw milk milked within 7 days after delivery usually contains about 5 to 10% by weight of lipid, but it is possible to separate 99% or more of lipid by the above conditions.

  Said sterilization process can be suitably performed, for example within the range of about 10 second-about 30 minutes on the conditions of about 62-85 degreeC normally.

  The protein concentration step can be performed, for example, by a method using an ultrafiltration membrane. In this case, the process uses a pore-size ultrafiltration membrane that can fractionate a protein having a molecular weight of usually about 5000 to 200000 daltons, preferably about 10000 to 100000 daltons, more preferably about 12000 to 50000 daltons. Done.

  The drying step can be performed by any method such as freeze-drying or spray-drying, but according to spray-drying, a powder or granule that is granulated with protein and other milk-derived components Therefore, it is preferable. The drying process in the spray drying is performed under conditions where the air blowing temperature is usually about 100 to 260 ° C, preferably about 140 to 240 ° C, more preferably about 180 to 230 ° C.

  When fractionating colostrum by adding an acid in the above-described method, it can be carried out usually at a pH of about 4 to 5, more preferably 4.5 to 4.6. By fractionating in such a range of pH, a casein casein composition that does not contain components that adversely affect the living body can be produced. For example, acetic acid or hydrochloric acid can be used as the acid used to adjust the pH to the above range.

  The centrifugation step in the above-described method can be performed based on a conventional method, usually with a force of about 1000 to 1500 G, and the time for centrifugation is usually about 15 to 20 minutes, and the temperature is usually 20 to 20 minutes. It can carry out on 25 degreeC conditions.

  The casein composition obtained by the above-described method may be used without washing, or may be used after washing using a known method.

  The casein composition of the present invention contains three kinds of casein proteins, α-casein, β-casein, and κ-casein, and the content thereof is usually the total amount of the three kinds of casein proteins relative to the casein composition. It is about 60 to 99% by weight. More preferably, it is about 80 to 90% by weight.

  In addition, the weight ratio of the three types of casein proteins contained in the casein composition varies greatly depending on the origin. For example, in the case of bovine origin, α-casein: β-casein: κ-casein = 1: 0.5 It is about -0.8: 0.1-0.4, More preferably, it is 1: 0.4-0.7: 0.2-0.3.

The content of the three kinds of casein proteins contained in the casein composition and the weight ratio of the three kinds of casein proteins can be confirmed by using a known method such as mass spectrometry, for example.
Intestinal-derived cell growth promoter The intestinal-derived cell growth promoter of the present invention (hereinafter referred to as a growth promoter) contains the casein composition described above as an active ingredient and promotes the growth of intestinal cell. The intestine-derived cells are not particularly limited, and specific examples include cells derived from any part of the intestine such as duodenum-derived cells, small intestine-derived cells, large intestine-derived cells, colon-derived cells, rectal-derived cells, and the like. Preferably it is a small intestine-derived cell.

  The promotion of the proliferation of intestinal cells may be the promotion of proliferation of cells forming the intestinal tissue in the intestinal tissue or the promotion of proliferation of cultured cells that are collected from the living body and cultured. . The cultured cells may be primary cultured cells or subcultured cells established by immortalization after being collected from the living body.

  Intestinal cells are not particularly limited, and specific examples include intestinal epithelial cells, mesenteric cells, lamina propria cells, mucosal muscle cells, submucosal cells, circular muscle cells, striated muscle cells, serosa cells and the like. Can be mentioned. Intestinal epithelial cells are preferred.

  The subcultured cells are not particularly limited, and specific examples include IEC-6 cells, CaCo-2 cells, WiDr cells, SW837 cells, RCN-9 cells, ACL-15 cells, ECC4 cells and the like. IEC-6 cells are preferred.

  The growth promoter of the present invention contains the casein composition described above as an active ingredient. In addition, a known drug that does not diminish the growth promoting effect on intestinal cells may be included, and specific examples thereof include antiseptics, bactericides, and stabilizers.

  The casein composition contained as an active ingredient in the growth promoter of the present invention can usually be contained in a proportion of about 1 to 95% by weight, more preferably 10 to 80%.

As shown in the Examples, the growth promoter of the present invention has an effect of increasing the length of the villi of the small intestine, thereby expanding the surface area of the intestine. Therefore, nutrition (vitamins, lipids, proteins, ash, water, etc.) and absorption of drugs absorbed from the intestine can be increased in the small intestine, so that the body can efficiently absorb nutrient sources, and nutrition or drug absorption It can be used as an improver.
About pharmaceutical composition The pharmaceutical composition of this invention contains said growth promoter as an active ingredient. Specifically, the above-mentioned casein composition can be prepared as an active ingredient and can be prepared according to the administration method. Of various preparations, oral preparations are preferred. In other words, the pharmaceutical composition of the present invention is preferably an oral pharmaceutical composition containing a casein composition derived from colostrum as an active ingredient.

  The dosage form of the above oral pharmaceutical composition is not particularly limited as long as it is a preparation for oral administration. For example, powders, tablets, granules, pills, capsules (soft capsules, hard capsules), troches, chewable tablets And dry syrups. Moreover, you may have a formulation form which controlled the release | release property of the medicinal component (for example, immediate release formulation, sustained release formulation, etc.). Also preferred are tablets, granules, pills, and capsules (soft capsules and hard capsules). Formulations having such dosage forms can be prepared according to conventional methods in the art.

  In order to formulate the oral pharmaceutical composition into the above-mentioned oral dosage form and to stabilize it, various carriers and additives that are pharmaceutically acceptable for oral administration can be blended (for example, local administration). And “Pharmaceutical Additives Encyclopedia” (published by Yakuji Nippo).

  Carriers or additives for the above oral administration agents include succinylated gelatin, gelatin, medium chain fatty acid triglycerides, calcium carbonate, carmellose sodium and the like; glycerin fatty acid ester, soybean lecithin, methylcellulose, glyceryl monostearate, etc. Emulsifiers; excipients such as lactose, sucrose, glucose, mannitol, sorbitol, corn starch, partially pregelatinized starch, crystalline cellulose, low-substituted hydroxypropylcellulose, carmellose sodium, talc, macrogol 400; starch, α- Starch, agar, gelatin, gum arabic, dextrin, methylcellulose, ethylcellulose, polyvinylpyrrolidone, hydroxypropylmethylcellulose, hydroxypropylcellulose, carboxymethylcellulose or Are binders such as salts and crystalline cellulose; disintegrators such as calcium carbonate, crospovidone, starch, carboxymethyl cellulose calcium, low-substituted hydroxypropyl cellulose, carboxymethyl starch; magnesium stearate, talc, polyethylene glycol, silicic acid anhydride, etc. Lubricants such as polyoxyethylene hydrogenated castor oil and pluronics; surfactants such as polysorbate 80, lauromacrogol, cholesterol; precipitated calcium carbonate, gum arabic, pullulan, carnauba wax, hydroxypropyl methylphthalate Coating agents such as sucrose, glucose, sodium saccharin, sorbitol, citric acid and aspartame; plasticizers such as concentrated glycerin, triacetin and D-sorbitol; Palau It can be mentioned titanium oxide, medicinal carbon, coloring agents such as sodium copper chlorophyllin; phenoxyethyl benzoate, propyl parahydroxybenzoate, preservatives such as citric acid hydrate.

  In addition to the above components, as long as the effect of the present invention is not diminished, stabilizers, dispersants, fluidizing agents, buffering agents, wetting agents, thickening agents, preservatives, and the like, which are usually acceptable as additives for pharmaceuticals, Optional components such as a pH adjuster, a solvent, a solubilizing agent and the like can be added as desired.

  In addition to the above, other active ingredients such as amino acids, vitamins, and inorganic salts may be included. Other active ingredients include, for example, valine, leucine, isoleucine, threonine, methionine, phenylalanine, tryptophan, lysine, glycine, alanine, asparagine, glutamine, serine, cysteine, cystine, tyrosine, proline, hydroxyproline, aspartic acid, glutamic acid , Amino acids such as hydroxylysine, arginine, ornithine, histidine; vitamins such as vitamin A1, vitamin A2, carotene, lycopene (provitamin A), vitamin B6, vitamin B1, vitamin B2, ascorbic acid, nicotinamide; sodium chloride And alkali metal salts such as potassium chloride, and inorganic salts such as citrate, acetate and phosphate.

  The above-mentioned oral pharmaceutical composition can be prepared and administered as the above-mentioned solid or liquid oral preparation (internal preparation), and the dosage depends on the age, sex, degree of symptoms to be treated, and administration method. The daily dose of the above casein composition contained in the oral pharmaceutical composition for an adult is usually about 10 to 10000 mg, preferably about 100 to 1000 mg, more preferably 200 to 500 mg. Degree. If it is this administration range, it can also administer in 1 to several times a day.

  The pharmaceutical composition of the present invention can also be administered directly into the body after gastric fistula treatment for patients suffering from conditions that are difficult to take orally. The gastric fistula treatment is a treatment in which a fistula is formed in a digestive organ such as the stomach or intestine, and water, nutrients, etc. are administered into the body through a tube or the like.

  The pharmaceutical composition of the present invention is preferably used as a preventive or therapeutic agent for intestinal diseases. Here, prevention means preventing the onset of the disease, specifically, preventing the onset of the disease by acting on the onset mechanism of the disease in advance, and preliminarily normal to the lesioned part of the disease. Or it can be understood that the function exceeding the time of remission is acquired and damage to the lesion caused after the onset of the disease is reduced.

  The above bowel disease is not particularly limited as long as it is a disease that develops in the intestine. Specifically, Crohn's disease, inflammatory bowel disease such as ulcerative enteritis, infectious enteritis induced by infection with viruses, bacteria, Intestinal diseases associated with inflammation of the entire intestine such as infectious enteritis caused by food allergies, food poisoning, drugs, alcohol, etc .; irritable bowel syndrome and the like. Preferably, the site of inflammation is an intestinal disease from the duodenum to the rectum, and more preferably an intestinal disease that is the small intestine or the large intestine.

The pharmaceutical composition of the present invention can be used in combination with a pharmaceutical agent for a known disease in order to provide a better preventive or therapeutic effect.
About food composition The food composition of this invention contains said growth promoter as an active ingredient. Specifically, the casein composition described above is contained as an active ingredient, and can be prepared as foods in various food forms together with acceptable carriers and additives.

  The type of such food is not particularly limited. For example, confectionery (such as chewing gum and bubble gum) (including plate gum and sugar-coated granular gum); coated chocolate such as marble chocolate, strawberry chocolate, and berry chocolate Chocolates with flavors such as hard candy (including bonbon, butterball, marble, etc.), soft candy (including caramel, nougat, gummy candy, marshmallow, etc.), film candy (edible film); hard biscuits Baked confectionery such as cookies, rice crackers and rice crackers); breads; various foods such as soups (including powdered soups); various pet foods such as dog foods and cat foods.

  In addition to the above-mentioned foods, the food composition of the present invention includes health foods (nutrient functional foods, foods for specified health use, etc.), supplements, foods for the sick, etc. intended to improve the absorption of nutrients or drugs. The food composition of the present invention can also be prepared as a functional food. When preparing as such foods, it is desirable to prepare them in the form of granules, capsules, tablets (including chewables, etc.), beverages (drinks), etc., so that continuous intake is easy. However, capsules and tablets are preferable from the viewpoint of ease of ingestion, but are not particularly limited thereto.

  The food composition prepared in a capsule or tablet form can be appropriately prepared according to a conventional method using the above-described pharmaceutically acceptable carrier. Moreover, even when preparing in other forms, conventional methods may be followed, and the production method is not particularly limited as long as it does not impair the effects of the present invention, and is used by those skilled in the art for each application. It is sufficient to follow the method.

  In addition, food for specified health use (including conditionally specified food for specified health use) should show the function / effect of the food, such as displaying on its packaging container that it has the effect of improving the absorption of nutrients or drugs. Is a possible food.

  In preparing the above-mentioned foods, functional foods and the like, it can be added together with commonly used auxiliary ingredients and additives. Specifically, glucose, fructose, sucrose, maltose, sorbitol, stevioside, rubusoside, Corn syrup, lactose, mannitol, dextrin, citric acid, sodium citrate, tartaric acid, malic acid, succinic acid, lactic acid, L-ascorbic acid, dl-α-tocopherol, sodium erythorbate, glycerin, propylene glycol, glycerin fatty acid ester , Polyglycerin fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, gum arabic, carrageenan, casein, gelatin, pectin, agar, vitamin C, vitamin B, vitamin E, nicotinic acid amide, calcium pantothenate, amino acid , Calcium salts, surfactants, dyes, fragrances, preservatives, and the like.

  The food composition of the present invention can be directly administered into the body after the gastric fistula treatment, in the same manner as the use of the pharmaceutical composition described above.

  The blending amount of the casein composition in the food composition of the present invention is not particularly limited as long as the absorption of food or drug is improved, and is usually about 0.01 to 99% by weight, preferably 0.1 to 0.1% by weight. About 80% by weight, more preferably about 0.1-30% by weight.

  The food composition of the present invention can also be used as the food additive, and contains the above-described growth promoter as an active ingredient. Specifically, it contains the casein composition described above as an active ingredient, and has the effect of improving the absorption of food or drugs, etc., as in the case of the food composition described above, by using it as an additive for various foods. It is given.

The amount added when using the food additive is not particularly limited as long as the above-described effects are exhibited. However, in the food after addition, the casein composition is usually about 0.01 to 99% by weight. It can be added so that it is contained, Preferably it is about 0.1 to 80 weight%, More preferably, it is about 0.1 to 30 weight%.
About the nutrition or drug absorption enhancer The nutrition or drug absorption enhancer of the present invention (hereinafter referred to as absorption enhancer) contains the above growth promoter as an active ingredient. Specifically, it contains the casein composition described above as an active ingredient, an auxiliary agent that promotes the prevention or treatment effect of diseases associated with a decrease in nutrient absorption ability, PEM (hypoproteinosis), dwarf disease, It can be used as an auxiliary to promote prevention or recovery against recovery delay due to worsening nutritional status after surgery.

  Since the absorption enhancer of the present invention contains an intestinal-derived cell growth promoter as an active ingredient, the surface area of the intestinal epithelial villous tissue increases, and the effect of absorption of nutrients and drugs is increased. can do.

  The absorption enhancer of the present invention can be prepared according to the above-described method for preparing a pharmaceutical composition or food composition as long as the effects of the present invention are not diminished.

  The absorption enhancer of the present invention can be administered directly into the body after the gastric fistula treatment, in the same manner as the use of the pharmaceutical composition described above.

  The amount of casein composition in the absorption enhancer of the present invention is usually about 0.01 to 99% by weight, preferably about 0.1 to 80% by weight, more preferably about 1 to 50% by weight.

Hereinafter, the present invention will be described in detail. However, it goes without saying that the present invention is not limited to the following examples.
The casein composition used in Examples for the production of various components derived from bovine colostrum was produced by the following method. As the colostrum, 100 L of milk squeezed from cows (Holstein) on the 6th and 7th day after delivery was used as a raw material, and powdered by spray drying in a conventional manner to obtain 11 kg of skim milk powder.
Then, after suspending in distilled water whose pH was adjusted to 4.6 using hydrochloric acid, the mixture was allowed to stand for 15 minutes for acid fractionation. The colostrum subjected to acid fractionation was subjected to a centrifugation step under a condition of 4 ° C. and a force of 1500 G for 25 minutes to perform solid-liquid separation. Using the liquid phase as the whey fraction of the comparative example, 3 kg of solid phase component was obtained. By subjecting the obtained whey fraction and the solid component to freeze-drying, 9 kg of the whey composition used in the comparative example and 2 kg of the casein composition of the present invention could be obtained.

  In addition, the casein fraction and whey fraction derived from normal milk, which serve as control experiments, are obtained from milked cows (Holstein) 8 days after delivery, using the acid fractionation method described above. Produced.

Example 1
Growth promotion ability of small intestinal epithelial cells of colostrum-derived casein composition Rat small intestine-derived cells (IEC-6) cultured in advance for 24 hours are serum-free Dulbecco's modified eagle (DMEM; 1 × 10 ⁵ cells / well). Inoculated in a Dulbecco's Modified Eagle's Medium) medium, the casein composition derived from colostrum was added to the medium so as to be 1 mg / ml, 5 mg / ml, and 10 mg / ml, respectively, and cultured for 24 hours. After culturing for 24 hours, the number of viable cells contained in the medium was measured using a WST-1 kit by a method using WST-1. As a control experiment, casein derived from normal milk and whey derived from colostrum were added to 5 mg / ml and 10 mg / ml media, respectively, and cultured for 24 hours, and then the number of viable cells was measured by the same method. As a positive control experiment, IEC-6 cells cultured for 24 hours in DMEM medium containing 5% fetal calf serum (FCS) are included as a negative control experiment cultured for 24 hours only in DMEM medium. The number of viable cells was measured in the same manner. The result is shown in FIG.

  It was revealed that casein derived from colostrum has a growth promoting ability for IEC cells in a concentration-dependent manner such as 1 mg / ml, 5 mg / ml, and 10 mg / ml. Moreover, it became clear that it has the growth promotion ability with respect to the IEC cell almost equal to or more than the culture condition in the presence of 5% FCS, which is a general cell growth condition.

Example 2
Usefulness to intestinal tissue after oral administration of colostrum-derived casein composition Three 6-week-old BALB / c mice (female) were prepared and preliminarily raised for 1 week. Thereafter, the above-described casein composition derived from colostrum was administered by freely ingesting 5 mg / ml or 10 mg / ml, respectively, and the small intestine was collected from the mice one week later. As a negative control experiment, water was orally administered by free intake and the small intestine was collected. The collected small intestine was subjected to tissue immunostaining using an anti-PCNA antibody that specifically binds to proliferating cell nuclei by preparing a paraffin section according to a conventional method. At the same time, HE staining was performed.

    As a result, it was revealed that the cells present in the small intestine crypts in the mouse small intestinal mucosal epithelial tissues of the group to which the casein composition derived from colostrum was orally administered were strongly stained for the anti-PCNA antibody. FIG. 2 shows the results of quantifying the number of cells stained with the anti-PCNA antibody in order to compare the effects of normal milk casein, colostrum whey and water. From the results shown in FIG. 2, it is clear that oral administration of the colostrum-derived casein composition has the effect of significantly promoting cell proliferation of small intestinal epithelial cells compared to normal milk casein and colostrum whey. became.

  Moreover, as shown in FIG. 3, the result that the length of the small intestinal villi of the mouse | mouth of the group which orally administered the casein composition derived from colostrum became longer than the negative object group was obtained. Furthermore, the casein composition derived from colostrum significantly extended the length of the intestinal villi both in the whey fraction contained in the colostrum and in the casein fraction derived from normal milk. It was. Therefore, it was clarified that the casein composition derived from colostrum has an effect of promoting the proliferation of cells derived from intestines.

  The above results show that the colostrum-derived casein composition increases the surface area in the small intestinal villous tissue, and the colostrum-derived casein composition enhances the nutrient absorption effect when ingesting normal food. It can be used as an absorption enhancer. It also has the effect of improving absorption of drugs as well as nutrition.

Claims (7)

An intestinal-derived cell growth promoter comprising as an active ingredient a casein composition obtained by acid extraction of colostrum. The growth promoter according to claim 1, wherein the casein composition contains κ-casein having N-acetyllactosamine as part of a sugar chain. The growth promoter according to claim 1 or 2, wherein the intestinal cell is an intestinal epithelial cell. A nutritional or drug absorption enhancer comprising the growth promoter according to any one of claims 1 to 3 as an active ingredient. The food composition which uses the growth promoter of any one of Claims 1-3 as an active ingredient. Pharmaceutical composition which uses the growth promoter of any one of Claims 1-3 as an active ingredient The pharmaceutical composition according to claim 6, which is a preventive or therapeutic agent for intestinal diseases.

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