TWI612902B - Use of a composition for manufacturing an improved intestinal functional composition and preparation method thereof - Google Patents

Abstract

The mouse model of hepatitis induced by ConA was used to evaluate the production of cytokines in the small intestine or spleen and the damage to the small intestine by the group ingesting the composition of the present invention. The results show that the group ingesting the composition of the present invention, in addition to suppressing the production of liver and plasma cytokines, also inhibits the production of MCP-1 or IL-6 in the small intestine and spleen, and the tissue damage of the small intestine is also reduced. Normal mice 2 weeks after ingesting the composition of the present invention, the small intestine weight and large intestine weight were measured and evaluated. The results showed that both the weight of the small intestine and the weight of the large intestine increased significantly, and the average length of the villi and the thickness of the muscle layer showed significantly higher values than the control group.

Description

Use of composition for manufacturing composition for improving intestinal function and preparation method thereof

The present invention is a composition containing a milk protein hydrolysate, a protein derived from fermented milk, lipids, and saccharides to improve intestinal function.

The increase in lifestyle-related diseases in recent years has a significant relationship with diet. Ingesting necessary nutrients is very important for maintaining and improving health. In order to effectively digest and absorb this nutrient, normal intestinal function must be maintained. However, in reality, disordered habits, abnormal diet, mental disorders such as sadness and fear often cause intestinal dysfunction such as constipation or chin. If this intestinal function continues to be abnormal, it can be a cause of diseases such as bowel disease or cancer. Currently, Bifidobacterium or Lactobacillus lactic acid bacteria (probiotics), yoghurt or fermented beverages, which can improve intestinal function, are widely used as food. Foods having an intestinal rectifying function such as oligosaccharides or dietary fiber that can promote the proliferation of useful microorganisms in the intestine are also widely used. However, these foods can only improve the intestinal environment, but it is difficult to promote the proliferation of the intestinal mucosa and the repair of functions. Therefore, the development of such foods is urgently needed.

From a clinical point of view, lesions that cause a decrease in the functional surface area of the small intestine include intestinal resection, radiation irradiation, intestinal ischemia or trauma, Crohn's disease, or ulcerative colitis. For these lesions, there is a need for a treatment that improves the repair or compensatory function of the damaged small intestinal mucosa. It is currently known that specific nutrients such as glutamic acid, n-3 polyunsaturated fatty acids, or zinc are very important for this treatment. As an intestinal metabolic response ability to promote metabolism, endocrine adaptability, intestinal mucosal proliferation, and repair ability, nutrients must be supplied through the intestine and nutrients should be administered, provided that the nutrients pass through physiological intestinal contents such as bile and pancreatic juice. Although nutrition can be supplemented by central venous nutrition or high-calorie infusion or complete intravenous nutrition infusion, it can easily lead to atrophy of the small intestinal mucosa and intestinal dysfunction. Therefore, there is an urgent need for the industry to develop pharmaceuticals or foods that are beneficial to the gut. Although various enteral nutritional foods and dietary fiber-containing foods have been developed, so far, no pharmaceutical or comprehensive nutritional food that can promote the growth of the small intestine villi and increase the thickness of muscle layers has been developed. .

[Previous Technical Literature] [Patent Literature]

[Patent Document 1] WO2004 / 047556

[Patent Document 2] JP 2004-99563

An object of the present invention is to provide a composition capable of maintaining and improving intestinal function. Alternatively, the present invention provides a composition that promotes growth of the small intestine villi, a composition that increases the thickness of the small intestine muscle layer, a composition that improves intestinal function, a composition that prevents damage to the small intestine tissue, or an anti-inflammatory composition.

The present inventors used a mouse model of hepatitis induced by ConA to prepare tissue samples for ingesting the composition group of the present invention and ingesting general fluid food groups to evaluate the production of cytokines in the small intestine or the spleen and damage to the small intestine. The investigation promotes the production of cytokines TNF-α or IL-6 and the production of chemokine MCP-1. The results showed that the production of cytokines in the liver and plasma was inhibited, and the production of MCP-1 or IL-6 in the small intestine and spleen was also suppressed. In addition, damage to the small intestine tissue was reduced (Examples 1 and 2).

From this result, it is impossible to know what kind of changes the intestinal tract caused by ingestion of the nutritional composition of the present invention, and the weight of the small intestine and the large intestine was measured 2 weeks after ingestion by normal mice. Preparation and evaluation of small intestine tissue specimens. The results showed a significant increase in the weight of the small and large intestines. The evaluation of the small intestine showed that there was no difference in the number of villi, but the average length of villi and the thickness of the muscle layer had significantly higher values compared to the control group. From these results, it was shown that it has a protective effect on the small intestine damage and promotes the proliferation of the small intestinal mucosa epithelium or muscle layer (Example 3).

The present inventors even used a model of intestinal damage induced by indomethacin to investigate the urine of phenolsulfonphthalein, which is an indicator of intestinal permeability, for ingesting the nutritional composition group of the present invention and ingesting general fluid food groups. Medium excretion rate. Bacterial translocation of liver and intestinal membrane lymph nodes was examined by a general blood test. The results showed that ingestion of the nutritional composition group of the present invention inhibited the hyperpermeability of the intestinal membrane, and inhibited the bacterial translocation of phosphorous nodes in the liver or intestinal membrane. In addition, from the results of general blood tests, an increase in the number of neutrophils or monocytes in the blood accompanying the damage to the small intestine of indomethacin was suppressed in the nutrient composition group. From the above results, it can be seen that ingestion of nutritional composition can protect the intestine, inhibit non-sterol anti-inflammatory drugs and other drugs from causing damage to the small intestine, effectively prevent bacterial displacement caused by intestinal damage, and induce sepsis or pneumonia. Effect of waiting for infectious diseases and maintaining normal immune system (Example 4).

The present inventors analyzed what kind of ingredients in the nutritional composition is related to the hepatitis inhibitory effect and small intestinal damage protection effect or maintenance of intestinal function that are known in the ConA-induced mouse hepatitis model. The results showed that the maintenance of intestinal function was related to whey protein hydrolysate, isomaltulose, and Quark (Example 5). Hepatitis inhibitory effect is mainly related to whey protein hydrolysate and Quark (Example 6).

Based on the above findings, the present invention provides the following inventions.

[1] Compositions that promote the growth of small intestinal villi, including milk protein hydrolysates as protein and protein derived from fermented milk, fats and oils as lipids, and isomaltulose as sugars.

[2] The composition according to [1], the milk protein is selected from the group consisting of casein, milk protein concentrate (MPC), whey protein, whey protein concentrate (WPC), milk Whey protein isolate (WPI), α-lactoprotein, β-lactoglobulin and lactoferrin.

[3] The composition according to [1] or [2], wherein the protein derived from fermented milk is derived from fresh cheese.

[4] A composition for increasing the thickness of the small intestine muscle layer, including milk protein hydrolysate as protein and protein derived from fermented milk, oil and fat as lipid, and isomaltulose as sugar.

[5] The composition according to [4], the milk protein is selected from the group consisting of casein, milk protein concentrate (MPC), whey protein, whey protein concentrate (WPC), milk Whey protein isolate (WPI), α-lactoprotein, β-lactoglobulin and lactoferrin.

[6] The composition according to [4] or [5], wherein the protein derived from fermented milk is derived from fresh cheese.

[7] Compositions for improving intestinal function, including milk protein hydrolysate as protein and protein derived from fermented milk, oil and fat as lipid, and isomaltulose as sugar.

[8] The composition according to [7], the milk protein is selected from the group consisting of casein, milk protein concentrate (MPC), whey protein, whey protein concentrate (WPC), milk Whey protein isolate (WPI), α-lactoprotein, β-lactoglobulin and lactoferrin.

[9] The composition according to [7] or [8], wherein the protein derived from fermented milk is derived from fresh cheese.

[10] A composition for preventing damage to small intestine tissue, including milk protein hydrolysate as protein and protein derived from fermented milk, oil and fat as lipid, and isomaltulose as sugar.

[11] The composition according to [10], the milk protein is selected from the group consisting of casein, milk protein concentrate (MPC), whey protein, whey protein concentrate (WPC), milk Whey protein isolate (WPI), α-lactoprotein, β-lactoglobulin and lactoferrin.

[12] The composition according to [10] or [11], wherein the protein derived from fermented milk is derived from fresh cheese.

[13] Anti-inflammatory composition, including milk protein hydrolysate as protein and protein derived from fermented milk, oil and fat as lipid, and isomaltulose as sugar.

[14] The composition according to [13], the milk protein is selected from the group consisting of casein, milk protein concentrate (MPC), whey protein, whey protein concentrate (WPC), milk Whey protein isolate (WPI), α-lactoprotein, β-lactoglobulin and lactoferrin.

[15] The composition according to [13] or [14], wherein the protein derived from fermented milk is derived from fresh cheese.

[16] A method for promoting the growth of the small intestine villi, comprising the step of administering a composition containing a milk protein hydrolysate as a protein and a protein derived from fermented milk, a fat and oil as a lipid, and an isomaltulose as a sugar.

[17] A method for increasing the thickness of the small intestine muscle layer, comprising the step of administering a composition containing a milk protein hydrolysate as a protein and a protein derived from fermented milk, a fat as a lipid, and an isomaltulose as a sugar.

[18] A method for improving intestinal function, comprising the step of administering a composition containing milk protein hydrolysate as protein and protein derived from fermented milk, fats and oils as lipids, and isomaltulose as sugars.

[19] A method for preventing damage to small intestine tissue, comprising the step of administering a composition containing milk protein hydrolysate as protein and protein derived from fermented milk, fats and oils as lipids, and isomaltulose as sugars.

[20] A method for suppressing inflammation, comprising the step of administering a composition containing milk protein hydrolysate as protein and protein derived from fermented milk, fats and oils as lipids, and isomaltulose as sugars.

[21] Use of a composition containing milk protein hydrolysate as protein and protein derived from fermented milk, fat and oil as lipid, and isomaltulose as sugar in manufacturing composition for promoting intestinal villus growth .

[22] Use of a composition containing a milk protein hydrolysate as a protein and a protein derived from fermented milk, a fat and oil as a lipid, and an isomaltulose as a sugar for producing a composition that increases the thickness of the small intestinal muscle layer Its use.

[23] Use of a composition containing a milk protein hydrolysate as a protein and a protein derived from fermented milk, a fat and oil as a lipid, and an isomaltulose as a carbohydrate for producing a composition that improves intestinal function. .

[24] Use of a composition containing milk protein hydrolysate as protein and protein derived from fermented milk, fat and oil as lipid, and isomaltulose as carbohydrate in a composition for preventing intestinal tissue damage .

[25] Use of a composition containing a milk protein hydrolysate as a protein and a protein derived from fermented milk, a fat and oil as a lipid, and an isomaltulose as a carbohydrate in an anti-inflammatory composition.

[26] A composition for promoting the growth of small intestinal villi, including milk protein hydrolysate as protein and protein derived from fermented milk, oil and fat as lipid, and isomaltulose as sugar.

[27] The composition for increasing the thickness of the small intestinal muscle layer includes milk protein hydrolysate as protein and protein derived from fermented milk, oil and fat as lipid, and isomaltulose as sugar.

[28] A composition for a method for improving intestinal function, including milk protein hydrolysate of protein and protein derived from fermented milk, oil and fat as lipid, and isomaltulose as sugar.

[29] A composition for a method for preventing damage to small intestine tissue, including milk protein hydrolysate as protein and protein derived from fermented milk, oil and fat as lipid, and isomaltulose as sugar.

[30] A composition for a method for suppressing inflammation, including a milk protein hydrolysate of protein and protein derived from fermented milk, oils and fats as lipids, and isomaltulose as a sugar.

[31] Compositions for improving intestinal function, including protein derived from fermented milk.

[32] Compositions for improving intestinal function, including milk protein hydrolysate as protein and protein derived from fermented milk, and isomaltulose as sugar.

[33] The composition according to [32], the milk protein is selected from the group consisting of casein, milk protein concentrate (MPC), whey protein, whey protein concentrate (WPC), milk Whey protein isolate (WPI), α-lactoprotein, β-lactoglobulin and lactoferrin.

[34] The composition according to any one of [31] to [33], wherein the protein derived from fermented milk is derived from fresh cheese.

[35] Composition for preventing damage to small intestine tissue, including protein derived from fermented milk.

[36] A composition for preventing damage to small intestine tissue, including milk protein hydrolysate as protein and protein derived from fermented milk, and isomaltulose as sugar.

[37] The composition according to [36], the milk protein is selected from the group consisting of casein, milk protein concentrate (MPC), whey protein, whey protein concentrate (WPC), milk Whey protein isolate (WPI), α-lactoprotein, β-lactoglobulin and lactoferrin.

[38] The composition according to any one of [35] to [37], wherein the protein derived from fermented milk is derived from fresh cheese.

[39] An anti-inflammatory composition comprising a milk protein hydrolysate as a protein and a protein derived from fermented milk.

[40] The composition according to [39], further including isomaltulose as a sugar.

[41] The composition according to [39] or [40], the milk protein is selected from the group consisting of casein, milk protein concentrate (MPC), whey protein, whey protein concentrate (WPC), whey protein isolate (WPI), alpha-lactoprotein, beta-lactoglobulin, and lactoferrin.

[42] The composition according to any one of [39] to [41], wherein the protein derived from fermented milk is derived from fresh cheese.

[43] A method for improving intestinal function, comprising the step of administering a composition containing protein derived from fermented milk.

[44] A method for improving intestinal function, comprising the step of administering a composition containing milk protein hydrolysate as protein, protein derived from fermented milk, and isomaltulose as sugar.

[45] The method according to [44], the milk protein is selected from the group consisting of casein, milk protein concentrate (MPC), whey protein, whey protein concentrate (WPC), whey Isolate protein (WPI), alpha-lactoprotein, beta-lactoglobulin and lactoferrin.

[46] The method according to any one of [43] to [45], wherein the protein derived from fermented milk is derived from fresh cheese.

[47] A method for preventing damage to small intestine tissue, comprising the step of administering a composition containing protein derived from fermented milk.

[48] A method for preventing damage to small intestine tissue, comprising the step of administering a composition containing a milk protein hydrolysate as a protein, a protein derived from fermented milk, and isomaltulose as a sugar.

[49] The method according to [48], the milk protein is selected from the group consisting of casein, milk protein concentrate (MPC), whey protein, whey protein concentrate (WPC), whey Isolate protein (WPI), alpha-lactoprotein, beta-lactoglobulin and lactoferrin.

[50] The method according to any one of [47] to [49], wherein the protein derived from fermented milk is derived from fresh cheese.

[51] A method for suppressing inflammation, comprising the step of administering a composition containing a milk protein hydrolysate as a protein and a protein derived from fermented milk.

[52] The method according to [51], wherein the composition contains isomaltulose as a sugar.

[53] The method according to any one of [51] or [52], the milk protein is selected from the group consisting of casein, milk protein concentrate (MPC), whey protein, and whey protein concentrate (WPC), whey protein isolate (WPI), alpha-lactoprotein, beta-lactoglobulin and lactoferrin.

[54] The method according to any one of [51] to [53], wherein the protein derived from fermented milk is derived from fresh cheese.

[55] The use of fermented milk-derived protein for the production of a composition that improves intestinal function.

[56] Use of a milk protein hydrolysate, a protein derived from fermented milk, and an isomaltulose saccharide for producing a composition that improves intestinal function.

[57] Use as described in [56], milk protein is selected from the group consisting of casein, milk protein concentrate (MPC), whey protein, whey protein concentrate (WPC), whey Isolate protein (WPI), alpha-lactoprotein, beta-lactoglobulin and lactoferrin.

[58] The use according to any one of [55] to [57], the protein derived from fermented milk is derived from fresh cheese.

[59] Use of a protein derived from fermented milk for producing a composition for preventing damage to small intestine tissue.

[60] Use of a composition containing a milk protein hydrolysate as a protein, a protein derived from fermented milk, and isomaltulose as a saccharide, for producing a composition for preventing damage to small intestine tissue.

[61] Use as described in [60], milk protein is selected from the group consisting of casein, milk protein concentrate (MPC), whey protein, whey protein concentrate (WPC), whey Isolate protein (WPI), alpha-lactoprotein, beta-lactoglobulin and lactoferrin.

[62] The use according to any one of [59] to [61], wherein the protein derived from fermented milk is derived from fresh cheese.

[63] Use of a composition containing a milk protein hydrolysate and a protein derived from fermented milk to produce an anti-inflammatory composition.

[64] The use according to [63], the composition further includes isomaltulose as a sugar.

[65] Use as described in [63] or [64], milk protein is selected from the group consisting of casein, milk protein concentrate (MPC), whey protein, whey protein concentrate (WPC) ), Whey Protein Isolate (WPI), α-lactoprotein, β-lactoglobulin and lactoferrin.

[66] The use according to any one of [63] to [65], the protein derived from fermented milk is derived from fresh cheese.

[67] A composition containing fermented milk-derived protein, used to improve intestinal function.

[68] A composition containing a milk protein hydrolysate, a protein derived from fermented milk, and an isomaltulose saccharide, which is used for a method for improving intestinal function.

[69] Use as described in [68], the milk protein is selected from the group consisting of casein, milk protein concentrate (MPC), whey protein, whey protein concentrate (WPC), whey Isolate protein (WPI), alpha-lactoprotein, beta-lactoglobulin and lactoferrin.

[70] The composition according to any one of [67] to [69], wherein the protein derived from fermented milk is derived from fresh cheese.

[71] A composition containing protein derived from fermented milk, used in a method for preventing damage to small intestine tissue.

[72] A composition containing a milk protein hydrolysate, a protein derived from fermented milk, and a sugar of isomaltulose for use in a method for preventing damage to small intestine tissue.

[73] The composition according to [72], the milk protein is selected from the group consisting of casein, milk protein concentrate (MPC), whey protein, whey protein concentrate (WPC), milk Whey protein isolate (WPI), α-lactoprotein, β-lactoglobulin and lactoferrin.

[74] The composition according to any one of [71] to [73], wherein the protein derived from fermented milk is derived from fresh cheese.

[75] A composition containing a milk protein hydrolysate and a protein derived from fermented milk, and used to suppress inflammation.

[76] The composition according to [75], further including isomaltulose as a sugar.

[77] The composition milk according to [75] or [76], the milk protein is selected from the group consisting of casein, milk protein concentrate (MPC), whey protein, whey protein concentrate (WPC), whey protein isolate (WPI), alpha-lactoprotein, beta-lactoglobulin, and lactoferrin.

[78] The composition according to any one of [75] to [77], wherein the protein derived from fermented milk is derived from fresh cheese.

The present invention provides a composition for promoting villus growth in the small intestine, which contains a milk protein hydrolysate as a protein, a protein derived from fermented milk, a fat and oil as a lipid, and isomaltulose as a saccharide.

The growth of the small intestine villi is to promote the proliferation of small intestinal epithelial cells. Small intestinal villi growth judgment can promote the absorption of nutrients, or promote the repair of small intestine damage. Therefore, the composition of the present invention can be used, for example, as a "small intestinal villus growth agent", a "small intestinal epithelial cell proliferation agent", a "nutritional absorption enhancer", and a "small intestine damage repair enhancer". The composition of the present invention can be used to improve the small intestine function of normal people, improve the nutritional status of elderly people who are malnourished, maintain the intestinal function of patients with severe insufficiency such as breathing, circulation and metabolism (ICU patients) and maintain brain / nerve Nutritional supplement and intestinal function in patients with dysphagia and dysphagia, improvement of intestinal function and nutritional status in patients with chronic bowel disease such as ulcerative colitis or Crohn's disease, and improvement of intestinal function and nutrition in chronic obstructive pulmonary disease (COPD) Condition, or improve intestinal function and nutritional status of intestinal damage caused by antibiotics or anticancer drugs, such as cancer patients.

The present invention provides a composition capable of increasing the thickness of the small intestine muscle, comprising a milk protein hydrolysate as a protein, a protein derived from fermented milk, a fat and oil as a lipid, and isomaltulose as a sugar.

It is judged that the thickness of the small intestine muscle layer can promote the peristalsis of the small and large intestines. The increase in the thickness of the small intestine muscle layer is judged to promote intestinal remodeling. Therefore, the composition of the present invention can be used, for example, as an "intestinal muscle layer thickness increasing agent", an "intestinal peristaltic motion promoting agent", and an "intestine regulating agent". The composition of the present invention can be used to improve the small intestine function of normal people, improve the nutritional status of elderly people who are malnourished, maintain the intestinal function of patients with severe dysfunction such as breathing, circulation and metabolism (ICU patients) and maintain brain / nerve Nutritional supplement and intestinal function in patients with dysphagia and dysphagia, improvement of intestinal function and nutritional status in patients with chronic bowel disease such as ulcerative colitis or Crohn's disease, and improvement of intestinal function and nutrition in chronic obstructive pulmonary disease (COPD) Condition, or improve intestinal function and nutritional status of intestinal damage caused by antibiotics or anticancer drugs, such as cancer patients.

The present invention provides a composition for improving intestinal function, which contains protein derived from fermented milk. The present invention provides a composition for improving intestinal function, comprising a milk protein hydrolysate as a protein, a protein derived from fermented milk, a fat and oil as a lipid, and isomaltulose as a sugar.

The present invention provides a composition for improving intestinal function, comprising a milk protein hydrolysate which is a protein, a protein derived from fermented milk, and isomaltulose as a sugar.

The improvement of intestinal function refers to the promotion of digestion and absorption of nutrients ingested, and the excretion of waste through the peristalsis of the intestine. Intestinal dysfunction often results in the destruction of the barrier, including bacterial fragility of the intestinal lymphatic tissue (GALT), bacterial translocation (BT), or sepsis, etc., and reduces the defense ability of the organism. Decreased intestinal function leads to malnutrition and poor production / secretion of gastrointestinal hormones (hormones) or neurotransmitters that regulate biological functions. The "intestine" in the present invention includes a "small intestine" and a "large intestine".

Therefore, the composition for improving intestinal function of the present invention can promote digestion and digestion, and can be used as, for example, "intestinal function improving agent", "digestion and absorption promoting agent", "intestinal regulating agent", "waste excretion promoting agent" "Intestinal immune improver".

Intestinal immunity refers to the immune response that occurs in the intestine. Immune response is also called immunological response. When an antigen (other than itself) enters an organism, it triggers various biological reactions to produce antibodies or white blood cells (sensitized lymphocytes) with specific immunity to this antigen. It can be called a series of biological immune response to the invading antigen.

Because the digestive tract is an organ that is easy to contact with foreign bodies, the lymph ball surrounds the small intestine as the center of the intestine, engulfing the virus in the intestinal tract, or the foreign protein broken down by digestive enzymes. Because the absorption of these substances is prevented, the intestine is an important immune tissue that the organism originally evolved. For example, one of the functions of the digestive tract is reduced intestinal immunity. Decreased intestinal immunity refers to the reduction of immune response of abnormal cells (i.e., antigens) or waste (i.e., antigens) that occur in the body such as foreign viruses (i.e. antigens), cancer cells, etc. Increased disease leads to delayed healing. Improved intestinal immunity is to improve these symptoms caused by decreased intestinal immunity.

The composition of the present invention can be used to improve the small intestine function of normal people, improve the nutritional status of elderly people who are malnourished, maintain the intestinal function of patients with severe insufficiency such as breathing, circulation and metabolism (ICU patients) and maintain brain / nerve Nutritional supplement and intestinal function in patients with dysphagia and dysphagia, improvement of intestinal function and nutritional status in patients with chronic bowel disease such as ulcerative colitis or Crohn's disease, and improvement of intestinal function and nutrition in chronic obstructive pulmonary disease (COPD) Condition, or improve intestinal function and nutritional status of intestinal damage caused by antibiotics or anticancer drugs, such as cancer patients.

The present invention provides a composition for preventing damage to small intestine tissue, which contains protein derived from fermented milk. The present invention provides a composition capable of preventing damage to small intestine tissue, comprising a milk protein hydrolysate as a protein, a protein derived from fermented milk, a fat and oil as a lipid, and a composition of isomaltulose as a saccharide.

The present invention provides a composition capable of preventing damage to small intestine tissue, comprising a milk protein hydrolysate as a protein, a protein derived from fermented milk, and a composition of isomaltulose as a sugar.

Small intestinal tissue damage can be caused by cancer or ulcers in the intestine, or damage caused by villi or mucosal muscle layers caused by cancer patients and other antibiotics or anticancer agents. The composition of the present invention described above can be used to prevent such small intestinal tissue damage. The "damage" in the present invention includes a broad interpretation such as "inability to fully function", "external damage", "injury" and the like.

The above-mentioned composition of the present invention has a function to promote villus repair or a mucosal muscle layer repair, and can be used, for example, as a "preventive agent for small intestinal tissue damage", "vill repair repair agent", and "mucosal muscle layer repair promoter".

The composition of the present invention can improve the intestinal function and nutritional status of patients with chronic bowel disease such as ulcerative colitis or Crohn's disease, and improve the intestinal function and nutrition of intestinal damage caused by antibiotics or anticancer drugs, such as cancer patients. status.

The present invention provides an anti-inflammatory composition comprising a milk protein hydrolysate as a protein, a protein derived from fermented milk, oils and fats as lipids, and isomaltulose as a sugar.

The present invention provides an anti-inflammatory composition comprising a milk protein hydrolysate as a protein and a protein derived from fermented milk.

The anti-inflammatory composition of the present invention has the effect of inhibiting the inflammation of patients with chronic intestinal diseases such as ulcerative colitis or Crohn's disease. The anti-inflammatory effect is to inhibit the production of inflammatory cytokines, and at the same time to suppress the persistence or progress of inflammation by inhibiting the production of MCP-1 related to the infiltration of monocytes or T cell tissues. MCP-1, also known as MCAF (monocyte chemotactic and activating factor), is considered as a chemokine for mononuclear spheres. The effect on mononuclear spheres not only strengthens chemotacticity, but also promotes the release of lysosomal enzymes or reactive oxygen species, enhances anti-tumor activity, and induces the production of IL-1 and IL-6. It is now very clear that mononuclear spheres The role of active factors. In addition to mononuclear spheres, it also promotes the release of basophilic chemically conductive substances and the chemotactic activity of T cells. The production and secretion of MCP-1 are thought to stimulate various cells in the organism by LPS or inflammatory cytokines, including monocytes / macrophages, fibroblasts, or vascular endothelial cells. It has been observed that certain tumor cells can continuously produce MCP-1 (without the need for other stimulating factors). Today's research results show that MCP-1 is associated with tissue infiltration of monocytes and T cells in various inflammatory diseases such as arteriosclerosis, delayed allergies, rheumatoid arthritis, or lung disease.

The anti-inflammatory composition of the present invention has an effect of anti-inflammatory or reducing tissue damage, and can be used as, for example, "anti-inflammatory agent" or "tissue damage reducing agent".

The composition of the present invention can maintain the intestinal function of patients with severe insufficiency (ICU patients) such as breathing, circulation and metabolism, maintain the nutritional supply and intestinal function of patients with brain / nerve damage and difficulty swallowing, and improve ulcerative large intestine Intestinal function and nutritional status in patients with chronic bowel disease such as inflammation or Crohn's disease, improve intestinal function and nutritional status of chronic obstructive pulmonary disease (COPD), or improve intestinal tract caused by antibiotics or anticancer drugs, such as cancer patients Impaired gut function and nutritional status.

Hereinafter, the active ingredients contained in the above-mentioned compositions of the present invention will be described.

The composition of the present invention contains a milk protein hydrolysate as a protein and a protein derived from fermented milk.

The milk protein hydrolysate of the present invention is selected from casein, milk protein concentrate (MPC), total milk protein (TMP), whey, whey protein, whey protein concentrate (Whey Protein Concentrate: WPC), Whey Protein Isolate (WPI), α-lactoprotein (α-La), β-lactoglobulin (β-Lg), and lactoferrin hydrolysate.

For the definition, classification and manufacturing method of milk protein, please refer to Japanese Food Science, July 1989, p42 ～ 48, or the Milk Comprehensive Dictionary, January 20, 1992. Editor: Yamanouchi, edited by Kenji Yokoyama, Asakura Bookstore issued.

Casein is a type of phosphoprotein in which the main protein such as milk is covalently bonded to phosphate. Casein accounts for approximately 3% of cow's milk, approximately 0.9% of human milk, and approximately 80% of protein in cow's milk.

Whey is a water-soluble component remaining after removing fat, casein, fat-soluble vitamins and the like from cow's milk. Whey is generally a by-product of cheese whey or rennet casein (also known as sweet (sweet) whey) by-products made from natural milk cheese or rennet casein, which produces acidity from skim milk sources Casein or quark (casein whey, skimmed whey) (also known as acidic (acid) whey). The main components of whey are protein (β-lactoglobulin, α-whey protein, etc.), lactose, water-soluble vitamins, and salts (mineral components). Their respective characteristics have been clearly defined for whey components and for milk components. Research.

Whey protein includes, for example, a general term for protein that has been removed from casein in cow's milk. Whey protein is composed of multiple components such as β-lactoglobulin, α-lactoprotein, and lactoferrin, but does not contain lactose, vitamins, minerals, and the like. When the milk ingredients such as milk are adjusted to be acidic, the protein of Shen Dian is casein, and the protein of Shen Dian is whey protein.

"Whey-related products" means concentrated whey after whey has been concentrated, whey powder after whey has been dried, and main proteins of whey after being subjected to concentration treatment such as ultrafiltration (UF). The dried whey protein concentrate (Whey Protein Concentrate: hereinafter referred to as "WPC"), whey is removed by microfiltration (MF) method or centrifugal separation method, etc., and then concentrated by UF method. Whey Protein Isolate (Whey Protein Isolate) : Hereinafter referred to as "WPI"), after desalting treatment such as nanofiltration (NF) or electrodialysis, the desalted whey obtained by drying treatment, and the mineral components derived from whey are treated by Shen Dian and centrifuged Mineral concentrate whey, etc. obtained by concentration processing such as separation method. Among these, WPC containing 15% to 80% of dry weight of milk protein (solid content) as protein concentrated whey powder is defined as dairy products (concentrated whey according to provincial ordinances such as milk as amended on March 30, 2010). , Whey powder, WPC, Whey protein concentrated powder, are obtained through the process specified in the dairy regulations, regardless of whether there is a desalination step).

After the skim milk is concentrated by the MF method or the UF method and dried, the milk protein concentrate (Milk Protein Concentrate: hereinafter referred to as "MPC") is the same as WPC or WPI. If the content of lactose or salts is reduced, The casein or whey protein content will increase relatively.

Concentration processing can be performed using a common device or method, for example, using a vacuum evaporator, vacuum kettle, thin film vertical upward tube type thickener, thin film vertical downward tube type thickener, plate type thickener, etc. Depressed heating method. The drying process can also be performed using a general device or method. For example, a spray drying method, a drum drying method, a freeze-drying method, a vacuum (decompression) drying method, or the like can be used.

The standard manufacturing method of milk protein concentrate (MPC) is shown below.

(1) after the skim milk is separated through the membrane, the stage of concentration; or

(2) After the skim milk is separated through the membrane, it is concentrated and dried.

The whey protein concentrate (WPC) is obtained by subjecting the main protein of whey and the like to an ultrafiltration (UF) method, followed by a drying treatment. Generally, about 25% of the solids are collectively referred to as those with whey protein. If lactose or salt in whey is reduced, the content of whey protein is relatively increased, and a solid component of about 25% to about 80% can be obtained. In particular, according to provincial regulations such as milk, WPC containing 15% to 80% of the dry weight of milk protein is defined as protein concentrated whey powder.

The standard manufacturing method of whey protein concentrate (WPC) is shown below.

(1) the stage of concentration after whey separation through the membrane; or

(2) After the whey is separated through the membrane, it is concentrated and dried.

The concentration process can be performed using a general device or method. For example, a vacuum evaporator, a vacuum kettle, a thin film vertical rising tube type thickener, a thin film vertical falling tube type thickener, a plate type thickener, etc. can be used. Heating method under reduced pressure. The drying process can also be performed using a general device or method. For example, a spray drying method, a drum drying method, a freeze-drying method, a vacuum (decompression) drying method, or the like can be used.

Whey protein isolate (WPI) is obtained by concentrating a main protein of whey and the like through an ion exchange resin or an electrodialysis method and then subjecting it to a drying treatment. Generally speaking, about 85% to 95% of the solid content is the general name of those who have whey protein. If lactose or salt in whey is reduced, the content of whey protein will be relatively increased, and a solid content of about 90% (85% to 95%) can be obtained.

The standard manufacturing method of whey protein concentrate (WPI) is shown below.

(1) the stage where the whey is concentrated after membrane separation, ion exchange resin treatment or electrodialysis treatment; or

(2) After the whey is separated by membrane separation, ion exchange resin treatment, or electrodialysis, it is concentrated and dried.

Concentration processing can be performed using a common device or method. For example, a vacuum evaporator, a vacuum kettle, a thin film vertical upward tube type thickener, a thin film vertical downward tube type thickener, a plate type thickener, etc. can be used. Press the heating method. The drying process can also be performed using a general device or method. For example, a spray drying method, a drum drying method, a freeze-drying method, a vacuum (decompression) drying method, or the like can be used.

Regarding the milk protein hydrolysate of the present invention, taking whey protein hydrolysate as an example, the enzymes usually used for this protein hydrolysis may be pepsin, trypsin, and chymotrypsin. There are also reports of using plant-derived papain, bacteria, or Fungal-derived proteases (Food Technol., 48: 68-71, 1994; Trends Food Sci. Technol., 7: 120-125, 1996; Food Proteins and Their Applications, pp. 443-472, 1997). The enzyme activity of hydrolyzed whey protein varies greatly. Pepsin can hydrolyze α-La and denatured α-La, but cannot hydrolyze native β-Lg (Neth. Milk dairy J., 47: 15-22, 1993). Trypsin can slowly hydrolyze α-La, but can hardly break down β-Lg (Neth. Milk dairy J., 45: 225-240, 1991). Chymotrypsin can rapidly degrade α-La, but only slowly degrade β-Lg. Papain hydrolyzes bovine serum albumin (BSA) and β-Lg, but α-La is resistant (Int. Dairy Journal 6: 13-31, 1996a). Therefore, α-La not bound to Ca is completely decomposed by papain in an acidic environment (J. Dairy Sci., 76: 311-320, 1993).

By modifying the protein to control the enzymatic degradation of milk protein, the functional properties of this protein can be changed through a wide range of pH and processing conditions (Enzyme and Chemical Modification of proteins in Food proteins and their Applications, pp. 393-423, 1997, Marcel Dekker, Inc., New York, 1997; Food Technol., 48: 68-71, 1994).

Hydrolysis of the peptide chain results in an increase in charge number and hydrophobicity, a decrease in molecular weight, and a change in the molecular stereostructure (J. Dairy Sci., 76: 311-320, 1993). The change of functional characteristics is highly correlated with the degree of hydrolysis. As functional as whey protein, the biggest changes seen are increased solubility and decreased viscosity. When the degree of hydrolysis is high, the hydrolysate usually does not precipitate when heated, and its solubility is high at pH 3.5 to 4.0. Most hydrolysates have lower viscosity than intact proteins. This difference is particularly significant at high protein concentrations. Other effects include changes in gum properties, increased thermal stability, increased emulsification and foaming properties, and decreased emulsification and foam stability (Int. Dairy journal, 6: 13-31, 1996a; Dairy Chemistry 4, pp. 347-376, 1989; J. Dairy Sci., 79: 782-790, 1996).

Oligo-peptides of various physiological activities known from milk proteins (edited by Masaaki Yoshikawa, "Advanced Functions of Milk" edited by Masaaki Yoshikawa, etc., p 188-195, Hongxue Publishing, 1998; Masaaki Otani, "Advanced Functions of Milk" Yoshikawa Editor, p 97-99, Hongxue Publishing, 1998; Otani, Milk Science 47: 183, 1998; Trends in Food Science and Technology, 9: 307-319, 1998). Peptides with angiotensin-converting enzyme (ACE) inhibitory activity (with antihypertensive effect) are also among them.

The majority of peptides that may have ACE-inhibitory activity have been reported from in vitro activity tests (e.g., J. Dairy Res., 67: 53-64, 2000; Br. J. Nutr., 84: S33-S37, 2000). Numerous literatures have revealed the use of various chromatography techniques to refine and identify peptides that inhibit ACE from hydrolysates. (E.g. Maruyama, S., & Suzuki, H., Agricultural and Biological Chemistry, 46: 1393-1394, 1982; Miyoshi S. et al., Agri. Biol. Chem., 55: 1313-1318, 1991; Food Science and Biotechnology, 8: 172-178, 1999; Biosci. Biotech. Biochem., 57: 922-925, 1993).

From these documents, it can be seen that ACE inhibitory activity exists in many liquid-separated fractions obtained by column operation with various separation principles, and these show many aspects of the molecular characteristics of ACE inhibitory substances. The fact that ACE inhibition is found in hydrolysates produced by various proteins, proteases, and hydrolysis conditions indicates the possibility that various peptides containing various amino acid sequences have ACE inhibitory activity. Due to the chemical diversity of the above peptides, purification of the hydrolysate by chromatography is often accompanied by a loss of some active peptides. During hydrolysis, ACE inhibitory activity is continuously formed, but on the other hand, it is continuously decomposed. The maximum activity of the hydrolysate is the result of the optimization of the two steps described. The entire peptide composition of the hydrolysate determines the ACE inhibitory activity, and has the specificity of the hydrolase and the step-condition dependence.

Regarding the optimization of whey protein hydrolysis, the literature has pointed out the use of response surface methodology to minimize the required hydrolysis to obtain the maximum ACE inhibitory activity (International Dairy Journal 12: 813-820, 2002 ).

The milk protein hydrolysate used in the present invention can inhibit the production of TNF-α and IL-6 induced by LPS in vivo. Here, taking the inhibitory effect of LPS-induced TNF-α and / or IL-6 as an indicator, the optimal conditions for the hydrolysis of milk proteins (denaturation temperature, pH, temperature, hydrolysis time, and enzyme / matrix ratio) can be referred to. The aforementioned literature (International Dairy Journal 12: 813-820, 2002).

On the other hand, in addition to the above literatures, there are also many patents (published patents and patents) that disclose the content of milk protein hydrolysates. For example, a casein and a whey protein are hydrolyzed separately, and a hydrophobic portion is absorbed / removed, and then the two are mixed in a specific ratio (Japanese Patent No. 2,986,764) to hydrolyze by a protease of the genus Bacillus and a protease of an actinomycete Patent for removing enzymes and insoluble hydrolysates after whey protein (Japanese Patent No. 3,222,638), to decompose β-lactoglobulin by enzymes to obtain a branched chain amino acid / aromatic amino acid with a molar ratio of 10 weight % Or more, aromatic amino acid less than 2.0% by weight, peptide mixture with an average molecular weight of hundreds to thousands (Japanese Patent No. 3,183,945), a patent that selectively degrades β-lactoglobulin in whey protein by enzymes (Japanese Patent No. 2,794,305), or using a protease from B. licheniformis and / or a protease from B. subtilis to hydrolyze whey protein to 15-30% by non-pH-stat method Degree of hydrolysis (DE), a patent (Japanese Patent No. 3167723) for obtaining a filtrate of an ultrafiltration membrane with a cut off of more than 10,000.

Whether the hydrolysates of the above-mentioned documents or patents have the effect of inhibiting the production of LPS-induced TNF-α and IL-6, can use a conventional analysis system (for example, a separate volume of experimental medicine, "biological handbook UP experiment series", cytokine experiment method , Atsushi Miyajima, Masahiro Yamamoto, Yangtusha Co., Ltd., 1997).

5 parameters for milk protein hydrolysis optimization, such as preheating, enzyme / matrix ratio (E / S), pH, hydrolysis temperature, and hydrolysis time.

Preheating: 65 ～ 90 ℃

E / S: 0.01 ～ 0.2

pH: 2 ～ 10

Hydrolysis temperature: 30 ～ 65 ℃

Hydrolysis time: 3 to less than 20 hours

The enzyme used is, for example, selected from the products of Novo Nordisk, which is described below.

1) Endoprotease

Protease from Bacillus licheniformis: Alcalase (registered trademark)

Protease of B. lentus: Esperase (registered trademark)

Protease from Bacillus subtilis: Neutrase (registered trademark)

Bacterial protease: Protamex (registered trademark)

Porcine trypsin: PTN (registered trademark)

2) Exoprotease

Protease of Aspergillus oryzae: Flavourzyme (registered trademark)

Carboxypeptidase

In addition to the above enzymes, trypsin and pepsin of animal origin, papain and bromelain of plant origin, and endogenous protease and exosome of microbial origin (for example, lactic acid bacteria, yeast, fungi, actinomycetes, etc.) Type protease, the above-mentioned purified product, bacterial cell disruption, etc. The enzyme composition is preferably a combination of Alcalase of Bacillus licheniformis and PTN (trypsin) of porcine pancreas.

As a method for producing a whey protein hydrolysate, a method described in Comparative Example 1 described later can be referred to.

The milk protein hydrolysate used in the present invention comprises an enzyme hydrolysate having an inhibitory effect on the production of LPS-induced TNF-α and / or IL-6, a holding solution or a permeate after being treated with an ultrafiltration membrane, and A commercially available milk protein hydrolysate with the same activity.

The whey protein hydrolysate which can be used in the present invention may be the substances described below. Patent No. 3183945 discloses that after thermally denatured whey protein isolate (WPI) is hydrolyzed with endo-peptidase and exo-peptidase, the aromatic amino acid in this hydrolysate is adsorbed and treated with an ion exchange resin to obtain Fisher's ratio greater than 10, branched amino acids above 15%, and aromatic amino acids below 2% of whey protein hydrolysate (molecular weight 200-3,000 peptide mixture).

Tiberium 6-50756 revealed that a 12% aqueous solution of a protein content of at least 65% whey protein concentrate (WPC), after heat treatment at more than 60 ° C, was obtained with Alcalase from B. licheniformis and from Bacillus subtilis (B.subtilis) neutral protease (neutrase) is hydrolyzed to 15 ~ 35% DH, and the hydrolysate is subjected to ultrafiltration (UF) with a cut-off value exceeding 10,000, and then subjected to nanofiltration (NF) After concentrating and spray-drying this NF concentrated solution, a whey protein hydrolysate having no odor and little bitterness was obtained.

The milk protein hydrolysate used in the present invention may be a general commercial product, for example, Peptigen IF-3080, Peptigen IF-3090, Peptigen IF-3091, Lacprodan DI-3065 (Arla Foods), WE80BG (DMV), Hyprol 3301, Hyprol 8361 and Hyprol 8034 (Kerry), Tatua 2016, HMP406 (Tatua), Whey Protein Hydrolyzed 7050 (Fonterra), Biozate3 (Davisco), but not limited thereto. The method for adjusting a protein hydrolysate may include, for example, a method for producing a whey protein hydrolysate in the following steps 1) to 5).

1) Mixing a dried whey protein containing at least 65% of protein with water to form a mud with a protein content of 20%,

2) heat treatment at a temperature exceeding 60 ° C,

3) The mixture of step 2) is hydrolyzed by a protease from B. licheniformis and / or a protease from B. subtilis to a concentration between 15 and 35% by a non-pH-stat method. Proteolytic properties of DH,

4) separating the mixture of step 3 on an ultrafiltration / microfiltration device with a cut-off value exceeding 10,000, and separating the filtrate into a protein hydrolysate, and

5) This hydrolysis ends when the enzyme is deactivated.

The mud in step 1) above preferably contains a protein content of 7-12%.

The heat treatment in the above step 2) is preferably performed at about 70 to 90 ° C.

The hydrolysis in step 3) is preferably carried out to a DH between 20 and 30%.

The cut-off value of the above-mentioned ultrafiltration / microfiltration device preferably exceeds 50,000.

The mixture at the end of step 3) or step 5) above is calculated with respect to the dry matter content, which is an amount between 1 and 5% relative to carbon, preferably at a temperature between 50 and 70 ° C, with activated carbon. The treatment took longer than 5 minutes before removing this activated carbon.

The concentration after the step 5) is preferably at a temperature between 50 and 70 ° C. After performing nano-filtration / ultrafiltration / reverse osmosis and / or evaporation, the residue is recovered as a protein hydrolysate solution.

The protein hydrolysate solution obtained in step 5) is spray-dried to a water content of less than 6.5%.

Therefore, the manufacturing method of whey protein hydrolysate is:

1) mixing whey protein containing at least 65% protein in dry matter with water to form a slime having a protein content of about 20%, preferably 12%,

2) heat treatment at a temperature exceeding 60 ° C,

3) Use the protease of B. licheniformis, preferably Alcalase (registered trademark), and / or the protease of B. subtilis, preferably Neutrase (registered trademark), for the mixture in step 2). ), Non-pH-stat hydrolysis to 15 to 35% degree of hydrolysis (DE), proteolytic hydrolysis,

4) The mixture of step 3 is separated on an ultrafiltration / microfiltration device with a cut-off value exceeding 10,000, and the filtrate constitutes the protein hydrolysate described above.

5) This hydrolysis step ends with the enzyme inactivation described above.

The amino acid composition of whey protein hydrolysate (IF-3090) is shown in Table 1.

The blending amount of the milk protein hydrolysate with respect to the entire composition is, for example, 0.1 to 22%, usually between 4.1 to 14.0%, and preferably 5.5 to 10.0%. For every 100 ml of the composition, 0.9 to 3 g, preferably 1.2 to 2 g, may be prepared.

The raw material for fermented milk-derived protein used in the present invention may be, for example, a substance that reduces moisture (whey) in fermented milk (yog) (for example, Japanese Patent No. 3,179,555). The protein from fermented milk (yog) has an amino acid score of 100. The fermented protein makes the protein easier to digest and absorb, and has higher nutritional value.

The protein derived from fermented milk used in the present invention is preferably a protein derived from fresh cheese (immature cheese (cheese)). Protein from fresh cheese. The protein contains casein as the main component, whey protein containing α-lactoprotein or β-lactoglobulin, and a part of milk protein that is broken down into amino acids or peptides. Fresh cheese can be Cottage, Quark, String, Neufchatel, Cream Cheese, Mozzarella, Ricotta, There are various types such as Mascarpone. In the present invention, Quark is preferably used. The manufacturing method of Quark is known to the public (for example, Japanese Patent Application Laid-Open No. 6-228013). Quark has a low fat content and has a refreshing flavor and sour taste.

A general method for producing non-aged cheese is described below. First, curd is made from milk ingredients. After inoculating the starting material in the milk raw material, it is cultured, and then rennetase is added to form curd. Before manufacturing the curd, the raw milk may be pretreated as necessary. For example, in order to reduce the quality difference between manufacturing batches, multiple types of milk raw materials can be mixed to control the quality. This process is also called standardization. It is also possible to increase the homogenization of fat globules in mechanically broken milk. Alternatively, microorganisms may be removed from the milk material by centrifugal sterilization or heat treatment.

Whey was separated from the obtained curd, and the solid obtained was unripe cheese (fresh cheese). A method for separating whey from curd by centrifugation or membrane separation is generally known. For example, a centrifuge such as a Quark separator may be used to separate whey. If necessary, the curd can be cut or heated in advance to increase the efficiency of the separation process.

More specifically, the fresh cheese obtained by the following raw materials and steps is preferably the fermented milk ingredient of the present invention. In the following steps, Lactobacillus bulgaricus and / or Streptococcus thermophilus are mainly used for the fermentation.

Heat sterilized skim milk; inoculate 0.5 to 5% lactic acid bacteria starting material and start fermentation; when the pH reaches 4.6, separate whey from the curd formed; cool the whey separated curd to obtain Non-aged cheese.

The non-aged cheese made by this method is generally called Quark. An example of the composition of non-aged cheese is shown below.

Total solids are 17 to 19%, protein is 11 to 13%, fat is more than 1%, carbohydrates are 2 to 8%, and lactose is more than 2%.

The amount of the protein derived from fermented milk relative to the entire composition may be, for example, 0.1 to 30%, usually 8.0 to 23.0%, and preferably 10.0 to 18.0%. For each 100 ml of the composition, 2 to 6 g, preferably 2.5 to 4.5 g, is prepared. Relative to the overall protein quality of the composition, the protein derived from fermented milk contained in the composition of the present invention may be about 0.1 to about 90%, preferably about 1 to about 80%, and more preferably about 30 to about 70%.

The composition of the present invention contains fats and oils as lipids.

The composition of the present invention preferably contains an n-3 fatty acid. The n-3 fatty acids contained in the composition of the present invention may be EPA, DHA, α-linolenic acid, DPA, etc., preferably EPA, DHA, or / and α-linolenic acid, and more preferably EPA or / and DHA . Oils containing n-3 fatty acids include perilla oil, linseed oil, flax oil, fish oil, rapeseed oil, soybean oil, salad oil, linseed oil, and the like. These n-3 fatty acids may be contained directly in the present invention, or may be contained in the form of oils and fats such as fish oil.

The composition of the present invention preferably contains a medium-chain triglyceride (MCT) as a lipid. MCT is quickly absorbed into the body to form energy, and has the feature that it is not easy to form fat in the body. MCT-containing fats include palm oil, palm kernel oil, fats containing medium-chain fatty acids, and the like. In the present invention, MCT may be contained directly, or may be contained in the form of oils and fats such as palm kernel oil.

Therefore, the composition of the present invention includes a milk protein hydrolysate as a protein and a protein derived from fermented milk, a medium-chain triglyceride, EPA, and / or DHA as a lipid, and isomaltulose as a sugar.

On the other hand, the composition of the present invention may contain fatty acids such as oleic acid, palmitic acid, palmitoleic acid, linoleic acid, stearic acid, hypolinolenic acid, and arachidonic acid, and oleic acid is preferably used as the lipid. Fats and oils containing these fatty acids include, for example, high oleic high oleic sunflower oil, rapeseed oil, olive oil, high oleic safflower oil, soybean oil, corn oil, palm oil, and the like. Sunflower oil, rapeseed oil, olive oil, and olive oil mixtures can also be used. Linoleic acid, arachidonic acid, γ-linolenic acid and the like are n-6 fatty acids. Oils containing n-6 fatty acids include safflower oil, sunflower oil, soybean oil, linseed oil, corn oil, peanut oil, etc.

The ratio of n-3 fatty acids to n-6 fatty acids is 1. For n-3 fatty acids, the n-6 fatty acids are, for example, 5 or less, usually 0.5 or more and 4.0 or less, preferably 1.0 or more and 4.0 or less, and more The ratio of n-3 fatty acids: n-6 fatty acids = 1: 2 is preferred.

The compounding amount of the n-3 fatty acid with respect to the entire composition is, for example, 0.01 to 10%, usually 0.05 to 7%, and preferably 0.1 to 5%. For each 100 ml of the composition, 0.05-2.2 g, preferably 0.1-1.0 g, can be prepared.

The compounding amount of MCT is formulated at a ratio of, for example, 0.01 to 14.5%, usually 0.01 to 8.0%, and preferably 2.0 to 4.0% with respect to the entire composition. For each 100 ml of the composition, 0.01 to 2.0 g, preferably 0.5 to 1.0 g, can be prepared.

The blending amount of oleic acid-containing oil and fat with respect to the entire composition is blended at a ratio of, for example, 0.1 to 14.5%, usually 2.0 to 10.0%, and preferably 4.0 to 8.0%. For each 100 ml of the composition, 0.5 to 2.0 g, preferably 1.0 to 1.8 g, can be prepared.

The composition of the present invention may also contain milk lecithin or soybean lecithin as lipids.

Milk egg phosphorus and soybean egg phosphorus can be contained individually or in combination.

Milk lecithin can be sphingomyelin (SM), phospholipids choline (PC), phospholipids ethanolamine (PE), phospholipids inositol (PI), phospholipids serine (PS), lysophospholipids choline (LPC ) And is only partially present in milk fat globule membrane (MFGM). The composition of the MFGM phospholipid fraction is shown in Table 2 (Bulletin of Japan Dairy Technical Association, Vol. 50: pp. 58-91, 2000).

Although the term "lecithin" is only used in the fields of biochemistry, medicine, pharmacy, etc. to indicate phospholipids, choline, but in the commercial or industrial fields, they are phospholipids, choline, phospholipids, ethanolamine, phospholipids, inositol, and phosphatidic acid And other phospholipid mixtures. In the 7th edition (1999) of the Food Additives Public Draft, lecithin is defined as "a substance obtained from grain and oil seeds or animal raw materials, the main component of which is phospholipid". The phospholipids derived from milk in the present invention may also be collectively referred to as "milk lecithin".

The characteristics of milk lecithin are shown in Table 2. It does not contain soy lecithin, but contains a large amount of SM. It is currently known that when milk lecithin is administered to rats compared to soybean lecithin, DHA content in the brain and liver is increased, and compared with soybean lecithin or egg yolk lecithin, it effectively improves hyperlipidemia Or fatty liver. SM is also known to regulate the activity of HMG-CoA reductase, which is related to cholesterol biosynthesis, and is related to the absorption of cholesterol in the intestine. SM is known to be related to cholesterol metabolism. From the above speculation, SM can further enhance the lipid metabolism effect of PC or PE (Sasaki I, Milk Science 51 (2): 93-94, 2002).

Substances containing a large amount of MFGM, for example, freeze-dried products of WPI by-products (MF holding solution) produced by combining ultrafiltration (UF) and microfiltration (MF), and anhydrous milk fat from butter (Butter or Cream) (anhydrous milk fat: AMF), a fraction (Butter Serum), and a whey cream (whey cream serum) obtained by removing AMF from whey cream. A method for obtaining a phospholipid concentrate using these as raw materials is known to the public (for example, it is contained in Japanese Patent Application Laid-Open No. 7-173182).

Soy lecithin is a natural food additive. On the one hand, it is widely used in the food field. Polyenephosphatidylcholine can also be used as a medicine (Indications: Improve liver function in patients with chronic liver disease, fatty liver, hyperlipidemia ). The physiological effects of soy lecithin are, for example: (1) regulation of morphology and function of biofilm, (2) improvement of lung function, (3) improvement of arteriosclerosis, (4) improvement of lipid metabolism, (5) liver Improvement of lipid metabolism and (6) improvement / promotion of neural function (Food and Development, Vol. 29 (3): 18-21, 1994).

A series of so-called "natural" lecithin products are basically arranged according to the PC content in the products. According to the application of lecithin, various kinds of lecithin are produced. Soy lecithin products are simply classified as shown in Table 3 according to the main PC content after soy lecithin purification and fractionation (Fujikawa Takuma, Petrochemicals Vol. 40 (10), pp. 951-p58, 1991).

The composition of the present invention contains isomaltulose (palatinose (registered trademark)) as a sugar. Isomaltulose has a CAS registration number of 13718-94-0 and a chemical formula of C ₁₂ H ₂₂ O ₁₁ .

Isomaltulose includes reduced isomaltulose, Palatinose syrup (registered trademark), isomaltulose syrup, and the like. Isomaltulose syrup is a syrupy liquid substance mainly composed of oligosaccharides such as tetrasaccharide, hexasaccharide, and octose, which is produced by dehydration and condensation of isomaltulose. Isomaltulose is the same as sucrose, and is decomposed into glucose and fructose and absorbed (Hita Minsho et al., Journal of the Japan Institute of Nutrition and Food Science, Vol. 36 (3): 169-173, 1983), but its hydrolysis rate is relatively slow. Slow, 1/5 of sucrose (Tsuji, Y. et al., J. Nutr. Sci. Vitaminol., 32: 93-100, 1986). After ingestion, the blood glucose and insulin concentrations remain constant for a long time. (Kawai, K. et al., Endocrinol, Japan, 32 (6): 933-936, 1985).

The blending amount of isomaltulose relative to the entire composition is, for example, 10 to 70%, usually 15 to 60%, and preferably 20 to 35%. For each 100 ml of the composition, 4 to 13 g, preferably 5 to 8 g, can be prepared.

The composition of the invention is used for the purpose of promoting the growth of small intestine villi, increasing the thickness of the small intestine muscle layer, improving intestinal function, preventing damage to small intestine tissue, or inhibiting various inflammations.

The "target" described in the present invention is not particularly limited and includes animals (for example, humans, livestock animals, and wild animals). The "subject" does not need to be a patient suffering from a disease. For example, the composition of the present invention can also be administered to a healthy human.

The "administration" described in the present invention includes oral or non-oral administration, and the administration form may be a medicine or a diet.

The composition of the present invention can be a pharmaceutical composition, a nutritional pharmaceutical composition, a medicine, a medicament, a dietary composition, a dietary product, a nutritional composition, a special purpose food, a nutritional functional food, a health food, a pharmaceutical additive, and a food additive Wait for any form to use. For example, the composition of the present invention can be used as a small intestine function-improving food for nutritionally balanced healthy people, a nutrition-improving food for elderly people who are malnourished, and intestinal functions of patients with severe insufficiency such as respiration, circulation, and metabolism (ICU patients). Maintenance of food, nutritional supplementation and intestinal function for patients with dysphagia with brain and nerve damage Maintenance of food, improvement of intestinal function and nutritional status for chronic intestinal diseases such as ulcerative colitis or Crohn's disease Foods with improved intestinal function and nutritional status in patients with chronic lung disease (COPD) malnutrition, or foods with improved intestinal function and nutritional status in patients with intestinal damage caused by antibiotics or anticancer drugs, such as cancer patients .

The medicinal composition, nutritional medicinal composition, medicine and medicament of the present invention may be contained in dietary composition, dietary food, nutritional composition, special purpose food, nutritional functional food, health food and the like. For example, the medicinal composition, nutritional medicinal composition, medicine, and medicament of the present invention may also be included in small intestinal function-improving foods used for healthy people with balanced nutrition, and nutrition-improving foods for elderly people with malnutrition, breathing, circulation, and metabolism. Food for maintaining intestinal function in patients with equal severe insufficiency (ICU patients), nutritional supply for patients with dysphagia with brain and nerve damage, and food for maintaining intestinal function, chronic intestinal diseases such as ulcerative colitis or Crohn's disease Foods with improved intestinal function and nutritional status, foods with improved intestinal function and nutritional status for chronic obstructive pulmonary disease (COPD) malnutrition, or patients with bowel damage caused by antibiotics or anticancer drugs, such as cancer patients It is used in foods with improved intestinal function and improved nutritional status.

For example, direct administration of pharmaceuticals or ingestion of special purpose foods such as specific health foods or nutritional functional foods can promote the growth of the small intestine villi, increase the thickness of the small intestinal muscle layer, improve intestinal function, and prevent small intestine tissue. Damage or inhibit various inflammations.

When the composition of the present invention is used as a pharmaceutical, it can be administered in various forms. This form can be, for example, enteral nutrition, liquids, enteral or oral administration through nasal canals, gastrostoma, intestinal fistula, etc., or it can be processed into preparations such as tablets, capsules, granules, powders, syrups The type of administration. The above-mentioned various preparations can be used in accordance with generally known methods, and use of excipients, binding agents, disintegrating agents, lubricants, flavoring agents, solubilizers, suspending agents, coatings, solvents, and other strong pharmaceutical agents. Technical field Conventional adjuvants commonly used in the formulation of the main agent. May also contain appropriate amounts of calcium. You can also add appropriate amounts of vitamins, minerals, organic acids, sugars, amino acids, peptides, etc.

When the composition of the present invention is used in the form of a pharmaceutical, it can be administered orally or enterally. For example, you can choose tablets, capsules, granules, powders, syrups, etc. to be administered orally, or nasal canals, gastrostomas, intestinal fistulas, etc., which should be administered according to the patient's age and symptoms. The effective dosage is in the range of 0.1 mg to 1500 mg per 1 kg of body weight. Alternatively, the dosage of 5 mg to 75 g, preferably 100 mg to 50 g, can be selected for each patient. The preferred dosage and method of administration, specific examples: 0.1 mg to 1500 mg, preferably 2 mg to 1000 mg per 1 kg of body weight, 1 to 3 times daily for 1 month (4 weeks), Before or after meals. The number of administrations can be observed by observing the state of the administration and the movement of the blood test value, and adjusting the number of administrations according to the state.

When the composition of the present invention is used as food, it can be added to various foods in the form of liquid, paste, solid, powder, etc., and ingested as food. Beverages can be, for example, milk, cold drinks, fermented milk, yogurt, cheese, bread, biscuit, cracker, pizza, prepared milk powder, liquid food, food for patients, nutritious food, frozen food, food composition, Processed foods and other commercially available foods. When the composition of the present invention is used as a food, it is preferably in a form that can be used directly. In this form, the composition can be ingested through the tube through the nose-stomach, jejunum, or orally. Such a composition can take various forms, for example, a fruit juice type drink, a milk shake type drink, etc. The composition may be a soluble powder formed before use.

The osmotic pressure of the composition is about 300 to 1000 mOsm / l, for example, about 300 to 750 mOsm / l. When measured at room temperature, the viscosity of the composition is about 5 to 40 cp (1 cp = 0.001 Pa · s), preferably less than 20.

The calorie of the composition is about 1 to 2 kcal / ml, and preferably 1 to 1.5 kcal / ml.

When the composition of the present invention is used as a food, additional nutrients can be adjusted to adjust its nutritional composition. The additional nutrients in the present invention may be water, protein, sugars, lipids, amino acids, dietary fiber, vitamins, minerals, organic acids, organic bases, fruit juices, flavors, artificial sweeteners (e.g., aspartame Sweet etc) etc.

May contain 5 mg to 500 mg (0.005% to 0.5%) of champignon extract with reduced stool taste, 10 μg to 200 μg (0.00001% to 0.0002%) of a carotenoid preparation for nutritional purposes (for example, Contains α-carotene, β-carotene, lycopene, lutein, etc.).

Furthermore, catechin, polyphenols, etc. may be contained as an antioxidant.

Carnitine may be contained for purposes such as lipid metabolism resistance. Carnitine is a trace component of the organism formed by lysine and methionine in the liver or kidneys. It is currently known that the amount of carnitine produced decreases with age. L-carnitine can carry long-chain fatty acids into muscle cells, etc., and is very important for the metabolism of nutrients.

In addition to the isomaltulose mentioned above, the saccharides may also be various other saccharides. For sugars other than isomaltulose, sucrose, glucose, fructose, honey, and the like are used. Others include dextrin and refractory dextrin.

Dietary fiber is divided into water-soluble dietary fiber and insoluble dietary fiber, and either one can be used.

As the water-soluble dietary fiber, lactulose, lactitol, or raffinose which are hardly decomposable oligosaccharides can be used. At present, it is known that the physiological function of the refractory oligosaccharide is that after the undigested matter reaches the large intestine, Bifidobacterium in the intestine is activated and proliferated, and the intestinal environment is improved, that is, it has an intestinal regulating effect. Lactulose is a synthetic disaccharide formed from galactose and fructose, which is the basic drug for hyperammonemia (Bircher, J. et al., Lancet i: 890, 1965). Recurrent chronic hepatic encephalopathy of chronic liver failure has a good response to lactulose administration, special amino acid drip (Fischer solution) for liver dysfunction, and the like. The second-generation lactulose "lactose" (β-galactosyl-sorbitol) has the same clinical effect on chronic hepatic encephalopathy as lactulose (Lanthier, PL. And Morgan, M., Gut, 26: 415, 1985; Uribe, M., et al., Dig. Dis. Sci., 32: 1345, 1987; Heredia, D. et al., J. Hepatol, 7: 106, 1988; Riggio, 0., et al., Dig. Dis Sci., 34: 823, 1989), is now used as a treatment for hyperammonemia.

Other water-soluble dietary fiber candidates, for example, pectin (pro pectin, pectin ester acid, pectin acid), guar gum, enzyme degradation with improved lipid metabolism (lower cholesterol or neutral fat) Objects, tamarind seed gum, etc. Guar gum breakdown products are known to inhibit blood glucose elevation and reduce insulin secretion. (Iwahiko Yamato, et al., Journal of the Japanese Nutrition / Food Association, 46: 199, 1993). Candidates for water-soluble dietary fiber also include high-molecular-weight water-soluble dietary fiber such as glucomannan, alginic acid, low-molecular-weight alginic acid, psyllium seed, acacia, seaweed polysaccharides (cellulose, lignin Substances, agar, carrageenan, alginic acid, algal oligosaccharides, kelp polysaccharides, microbial gums (Brunei gum, thermogels, xanthan gum, gellan gum, dextran, saccharin polysaccharide, rhamnosin ), Other gums (locust bean gum, tamarind gum, tara gum, karaya gum, tragacanth gum produced from sap), etc., low-molecular-weight water-soluble dietary fiber, polydextrose, difficult to decompose Dextrin, maltitol, etc.

Insoluble dietary fiber increases the weight of indigestible substances in the large intestine and shortens the passage time. As a result, the number of defecations and the amount of defecation are increased. Candidates for insoluble dietary fiber, such as cellulose, hemicellulose, lignin, chitin, chitosan, soybean dietary fiber, wheat bran, pine fiber, corn fiber, beet fiber, and the like.

Vitamins include, for example, vitamin A, carotene, vitamin E group, vitamin C, vitamin D group, vitamin B, vitamin K group, vitamin P, vitamin Q, nicotinic acid, nicotinic acid, pantothenic acid, biotin, inositol , Choline, folic acid, etc.

There are currently 13 known vitamins. Vitamins known to be highly related to the liver are vitamins A, B (B1, B2, niacin, B6, pantothenic acid, folic acid, B12, biotin) and K. In relation to liver damage, vitamin A deficiency and excess, vitamin E group deficiency, and vitamin K excess are major problems.

Vitamin A is deficient due to insufficient bile secretion and decreased absorption in the intestinal tract such as occlusive jaundice. In the low-protein nutrition state, the production of retinol-binding protein (RBP) is reduced, so vitamin A cannot be delivered to the target organs, showing symptoms of deficiency. In the case of non-compensated cirrhosis, symptoms of poisoning caused by a relatively small amount of excess vitamin A are found. Disturbances in the utilization of the vitamin B group are known in chronic liver disease. Vitamin K is usually synthesized by bacteria in the intestine, so it usually does not cause deficiency, but when there is insufficient bile in the intestinal tract such as occlusive jaundice, the absorption rate decreases.

Minerals such as calcium, potassium, magnesium, sodium, copper, iron, manganese, zinc, selenium and the like. As the organic acid, for example, malic acid, citric acid, lactic acid, tartaric acid, and the like can be used.

The electrolytes that usually cause problems when managing body fluids are sodium, chlorine, potassium, phosphorus, calcium, and magnesium. When formulating minerals, the following three points should be considered: (1) whether the minerals that enter the cell are fully distributed, (2) whether the type and amount of nutrients to be administered can fully cooperate with the patient's endocrine environment, ( 3) Estimation of the load of the osmotic substance in the kidney and how much water is used to maintain an appropriate osmotic pressure in the urine.

Iron, or other trace elements derived from natural materials, such as copper, zinc, selenium, manganese, chromium, etc., which contain mineral yeast. Copper gluconate, zinc gluconate and the like can also be used.

Organic acids such as malic acid, citric acid, lactic acid, tartaric acid and the like.

These additional nutrients can be chemically synthesized or derived from natural substances. Alternatively, a food containing a target component may be prepared as a raw material. These ingredients can be mixed with at least one kind or a combination of two or more kinds. The composition may be in the form of a solid or a liquid. It may be in a gel or semi-solid state.

The composition of the present invention can be produced by a method generally known in the field of liquid food or enteral nutrition. For example, the liquid composition can be pre-heated and sterilized and filled into a sterile container (for example, a method using UHT sterilization and aseptic packaging), or the liquid composition can be filled into the container and the container can be filled with the container. A method of heat sterilization together (for example, distillation, autoclaving), and the like. In other words, when the composition is used in a liquid form, the homogenate of the composition (the material after homogenization of the sterilization liquid) can be heated and sterilized at about 120 to 145 ° C for about 1 to 10 seconds, and then cooled , Sterile filling, or filling into canned containers or flexible packaging, and distillation and sterilization. Therefore, when the composition is used as a powder, the homogenate is subjected to, for example, spray drying or freeze drying.

Hereinafter, the present invention will be described in detail, but the present invention is not limited to the following embodiments. In the present invention, when whey protein is prepared (added and mixed), the temperature is adjusted by heating. For example, the temperature of the preparation solution (reconciliation temperature) is 55 ° C or lower. When the mixing temperature is at a high temperature, such as 70 ° C, the protein will coagulate (coagulate and emulsify). When the mixing temperature is at a low temperature, such as 2 ° C, the protein will be difficult to dissolve or disperse in water. Therefore, the temperature of the blending program is preferably 5 to 55 ° C, more preferably 40 to 55 ° C, still more preferably 40 to 53 ° C, and most preferably 40 to 50 ° C. At this time, considering the proliferation of bacteria (contaminating bacteria, etc.) in the reconciliation solution, an appropriate reconstitution time is preferably selected.

Furthermore, in the present invention, the blending liquid is homogenized after being sterilized at a high temperature. Although high-temperature sterilization (heating) will denature proteins and increase viscosity (thickening), homogenization after high-temperature sterilization can reduce the degree of viscosity increase. Here, the homogenization performed after the high-temperature sterilization is performed after the high-temperature sterilization and before filling into a product such as a container. The homogenization is not limited to one time, and may be a plurality of times such as two or more times. For example, when the blending solution is directly sterilized and then subjected to the second sterilization step, a homogenization procedure is also performed after the second sterilization step. After the sterilization solution is homogenized, the second homogenization step is performed after the second sterilization step. Therefore, after the sterilizing liquid is homogenized, the second homogenization may be performed without sterilization. In the present invention, it is very important that the blending solution is homogenized only once after being sterilized at a high temperature and before being filled into a container or the like to form a product.

On the other hand, after the homogenization solution (sterilization solution) for high-temperature sterilization is homogenized, the sterilization step can be performed without the sterilization solution thickening. For example, after the sterilization solution is homogenized, the second sterilization can be performed without sterilizing at high temperature. At this time, the high-temperature sterilization step is, for example, a thermal history with a temperature of 100 to 150 ° C and a holding time of 1 to 30 seconds, preferably 115 to 145 ° C, a holding time of 1 to 20 seconds, and more preferably 120 to 145 ° C and a holding time 1 to 10 seconds, preferably 125 to 140 ° C, and a holding time of 1 to 5 seconds. Although high-temperature sterilization can easily denature proteins and increase the viscosity of the sterilization solution, the viscosity is not easily increased without high-temperature sterilization. Therefore, the effect of homogenization to reduce the viscosity is particularly exhibited in high-temperature sterilization.

When performing high-temperature sterilization, the pressure (pressurization or decompression) of the conditioning liquid can also be adjusted. In this case, it is usually for the purpose of preventing boiling of the blending liquid, for example, the sterilization pressure is about 1 to 10 kg / cm ² . That is, in the high-temperature sterilization of the present invention, in addition to the temperature (heating), the pressure as described above can be increased. The high-temperature sterilization device is, for example, a flat plate heat exchanger, a tube heat exchanger, a steam injection sterilizer, a steam injection sterilizer, an electric heating sterilizer, or the like. On the other hand, when a homogenization program is performed using a homogenizer, for example, when the temperature is set to about 10 to 60 ° C. and the flow rate is set to about 100 to 10000 L / h, the pressure may be 10 to 100 MPa, preferably 20 to 80 MPa. It is more preferably 30 to 70 MPa, and most preferably 20 to 50 MPa. If necessary, the operating conditions of high-temperature sterilization or homogenization can be changed, and multiple treatments can be performed.

Hereinafter, the present invention will be described in detail by way of examples, but the present invention is limited thereto. The blending step is to stir warm water at the above temperature in the tank in advance, considering easy mixing / diffusion, and sequentially adding, mixing, and stirring raw materials other than the vitamin mixture (mixed component of vitamins) to form a blending solution. The order in which the raw materials are easily mixed and diffused varies depending on the amount or characteristics of the raw materials, and can be added at once or in various orders, such as a method of adding sugar, protein, oil, and minerals in that order. In another example, a method of adding a part of sugar, protein, other sugars, minerals, and fats in that order. In another example, a method of adding fat, protein, sugar, and minerals in that order. This blending liquid is heated and sterilized by a vapor injection method, and then homogenized (homogenized by two-stage pressure) with a homogenizer to form a sterilization liquid. A vitamin mixture (mixed component of vitamins), seasoning (fragrance), and the like are added and mixed into the sterilizing solution to form a final sterilizing solution. This final sterilization solution was heated and sterilized by a steam injection method (two-stage sterilization), and then homogenized by a homogenizer (homogenized by two-stage pressure) to obtain a composition.

It is used to promote the growth of small intestine villi, increase the thickness of the small intestine muscle layer, improve intestinal function, prevent damage to small intestine tissues, and treat various inflammations. It varies depending on symptoms, weight, etc., for example, when administered as a food or drink The dosage is generally about 0.05g to about 1000g of solid content per day, preferably about 0.05g to about 250g, more preferably about 2.5g to about 50g. The subject who must administer the composition of the present invention can be administered appropriately at one time or before meals, after meals, between meals, and / or before bedtime. The amount of administration is appropriately adjusted depending on the age, weight, and purpose of administration. The composition of the present invention can also be used as a meal replacement or food supplement.

When the composition of the present invention is in the form of an acidic pharmaceutical or food, its pH value is pH 2.0 to pH 6.0, and preferably pH 3.0 to pH 5.0.

The use of the composition of the present invention is as described in the following (1) to (30).

(1) A method for promoting the growth of small intestine villi, comprising administering a composition containing a milk protein hydrolysate as a protein and a protein derived from fermented milk, a fat and oil as a lipid, and an isomaltulose as a sugar.

(2) A method for increasing the thickness of the small intestine muscle layer, comprising administering a composition containing a milk protein hydrolysate as a protein and a protein derived from fermented milk, a fat and oil as a lipid, and an isomaltulose as a sugar.

(3) A method for improving intestinal function, comprising administering a composition containing milk protein hydrolysate as protein and protein derived from fermented milk, lipid as oil and fat, and isomaltulose as sugar.

(4) A method for preventing damage to the small intestine tissue by administering a composition containing milk protein hydrolysate as protein and protein derived from fermented milk, fat and oil as lipid, and isomaltulose as sugar.

(5) A method for suppressing inflammation, comprising administering a composition containing a milk protein hydrolysate as a protein and a protein derived from fermented milk, a fat or oil as a lipid, and an isomaltulose as a sugar.

(6) Use of a composition containing milk protein hydrolysate as protein and protein derived from fermented milk, lipid as oil and fat, and isomaltulose as a saccharide in manufacturing a composition for promoting intestinal villus growth .

(7) In a composition for increasing the thickness of the small intestine muscle layer, a composition containing a milk protein hydrolysate as a protein and a protein derived from fermented milk, a fat and oil as a lipid, and an isomaltulose as a sugar Its use.

(8) Use of a composition containing a milk protein hydrolysate as a protein and a protein derived from fermented milk as a lipid, an oil and fat, and a composition containing isomaltulose as a saccharide in the manufacture of a composition for improving intestinal function. .

(9) Use of a composition containing milk protein hydrolysate as protein and protein derived from fermented milk, lipid as oil and fat, and isomaltulose as carbohydrate in a composition for preventing intestinal tissue damage .

(10) Use of a composition containing a milk protein hydrolysate as a protein and a protein derived from fermented milk, a fat and oil as a lipid, and an isomaltulose as a sugar in an anti-inflammatory composition.

(11) A composition for a method for promoting the growth of small intestinal villi, comprising a milk protein hydrolysate as a protein and a protein derived from fermented milk, a fat as a lipid, and an isomaltulose as a sugar.

(12) A composition for a method for increasing the thickness of the small intestinal muscle layer, comprising a milk protein hydrolysate as a protein and a protein derived from fermented milk, an oil as a lipid, and isomaltulose as a sugar.

(13) A composition for a method for improving intestinal function, including a milk protein hydrolysate of protein and protein derived from fermented milk, a fat and oil as lipid, and isomaltulose as a sugar.

(14) A composition for a method for preventing damage to a small intestine tissue, comprising a milk protein hydrolysate as a protein and a protein derived from fermented milk, a fat as a lipid, and an isomaltulose as a sugar.

(15) A composition for a method for suppressing inflammation, including a milk protein hydrolysate of protein and protein derived from fermented milk, oils and fats as lipids, and isomaltulose as a sugar.

(16) A method for improving intestinal function, comprising the step of administering a composition containing protein derived from fermented milk.

(17) A method for improving intestinal function, comprising the step of administering a composition containing a milk protein hydrolysate as a protein, a protein derived from fermented milk, and isomaltulose as a sugar.

(18) A method for preventing damage to small intestine tissue, comprising the step of administering a composition containing protein derived from fermented milk.

(19) A method for preventing damage to the small intestine tissue, comprising the step of administering a composition containing a milk protein hydrolysate as a protein, a protein derived from fermented milk, and isomaltulose as a sugar.

(20) A method for suppressing inflammation, comprising the step of administering a composition containing a milk protein hydrolysate as a protein and a protein derived from fermented milk.

(21) Use of a protein derived from fermented milk for producing a composition for improving intestinal function.

(22) Use of a milk protein hydrolysate and a protein derived from fermented milk, and isomaltulose sugars for producing a composition that improves intestinal function.

(23) Use of a protein derived from fermented milk for producing a composition for preventing damage to small intestine tissue.

(24) Use of a composition containing a milk protein hydrolysate as a protein, a protein derived from fermented milk, and isomaltulose as a saccharide to prevent damage to small intestine tissue.

(25) Use of a composition containing a milk protein hydrolysate as a protein and a protein derived from fermented milk for producing an anti-inflammatory composition.

(26) A composition containing fermented milk-derived protein, which is used to improve intestinal function.

(27) A composition containing a milk protein hydrolysate as a protein, a protein derived from fermented milk, and isomaltulose as a saccharide, which is used for a method for improving intestinal function.

(28) A composition containing protein derived from fermented milk and used for preventing small intestinal tissue damage.

(29) A composition containing a milk protein hydrolysate as a protein, a protein derived from fermented milk, and isomaltulose as a saccharide, which is used for a method for preventing damage to small intestine tissue.

(30) A composition containing a milk protein hydrolysate and a protein derived from fermented milk, and used for a method for suppressing inflammation.

The composition of the present invention may be, for example, MEIN (Meiji Dairy Co., Ltd.). The composition containing a MEIN component is a composition containing the components described in Table 4.

Table 5 shows the composition of milk phospholipids (also referred to as milk-derived phospholipids and milk lecithin) in the fat in Table 4.

Examples of the fatty acid composition in Table 4 are shown in Table 6.

All prior art references cited in the present specification are incorporated into the present specification.

[Example] [Example 1] Small intestinal tissue damage reduction effect of nutritional composition (1)

The nutritional composition of the present invention and general fluid food (Maibalance: Meiji Dairy Co., Ltd.) and fluid food A (Impact: Ajinomoto Pharmaceutical Co., Ltd.) as a control group were tested, and tested after 24 hours of administration to ConA Degree of damage to small intestine tissue.

C57BL / 6 mice (6 weeks old, male) purchased from Japan SLC Co., Ltd. were used. The breeding environment is 21.0 ± 2.0 ° C, and the humidity is 55.0 ± 15.0%, and the light and dark are switched every 12 hours (lighting period: 7-19 points). During the experiment, feed and water were freely available.

The body weight of the purchased animals after one week of domestication was used as an index and divided into three groups. The experimental groups are: Group 1: General fluid food (Meiji Dairy: Maibalance), Group 2: Nutritional composition (Meiji Dairy: MEIN), Group 3: Fluid Food A (Ajinomoto Pharmaceutical: IMPACT), perform 2 Week of feeding. The composition of general fluid food, nutritional composition, and fluid food A is shown in Table 7 and Table 8. The isomaltulose used in this example is a substance having a CAS registration number of 13718-94-0 and a chemical formula of C ₁₂ H ₂₂ O ₁₁ .

12 mg / kg of ConA (Sigma) was administered through the tail vein, 24 hours after the administration, anesthesia was performed with ether, blood was collected from the large abdominal vein, and the small intestine was removed. The small intestine is 6 cm to 3 cm below the stomach, fixed with 10% formalin solution, and then embedded in general methods to prepare tissue samples and stained with hematoxylin-yin red. Using a digital microscope (Keyence), 100 times photographed tissue specimens to measure the entire area of the villi-containing mucosal layer and muscle layer in the image. Results are shown as mean ± SD (n = 7-9). Statistical analysis After SPSS analysis of single-factor mutations, Scheffe's test showed that p <0.05 represented a significant difference.

The results are shown in Figures 1 and 2. As a result of comparing the area of the small intestine, it was found that the nutrient composition intake group showed the highest value, and the rest were the general fluid food intake group and the fluid food A intake group in order (Figure 1). There is a significant difference between the nutrient composition intake group and the fluid food A intake group. From the tissue chart shown in Figure 2, it can be seen that administration of ConA will cause damage to the small intestinal mucosa epithelium, fall off, or decrease in muscle layer thickness. On the other hand, those close to the normal tissue map are the nutrient composition intake group (Figure 2). From this result, it can be seen that the intake of the nutritional composition can reduce the degree of damage to the small intestine.

[Example 2] Small intestinal tissue damage reduction effect of nutritional composition (2)

The nutritional composition of the present invention and Maibalance as a control group were used for testing. Two hours after administration of ConA, the production of cytokines in the small intestine was analyzed, and the degree of tissue damage after 24 hours was evaluated.

C57BL / 6 mice (6 weeks old, male) purchased from Japan SLC Co., Ltd. were used. The breeding environment is 21.0 ± 2.0 ° C, and the humidity is 55.0 ± 15.0%, and the light and dark are switched every 12 hours (lighting period: 7-19 points). During the experiment, feed and water were freely available.

The body weight of the purchased animals after domestication for one week was used as an index and divided into 4 groups. The experimental group is: group 1: general fluid food (dissected 2 hours after ConA administration), group 2: nutritional composition (dissection 2 hours after ConA administration), group 3: general fluid food (ConA administration 24 Dissected after hours), group 4: nutritional composition (dissected 24 hours after ConA administration), and reared for 2 weeks. The general fluid food and nutritional composition used were the same as in Example 1.

12 mg / kg of ConA (Sigma) was administered through the tail vein. After 2 and 24 hours of administration, anesthetized with ether, blood was collected from the abdominal large vein, and the liver, spleen, small intestine, and large intestine were removed. Measure the length of the small intestine, the weight of 11 cm to 10 cm below the stomach, and the weight of the large intestine (5 cm below the cecum). Measure the weight of each organ. The small intestine was cut out from 6 cm to 3 cm below the stomach, fixed with a 10% formalin solution, and then embedded in a general method to prepare a tissue specimen and perform hematoxylin-yin red staining. The cytokines in the organs were adjusted in the following manner, and then detected using a Mouse inflammat ion kit (CBA method: Becton, Dickinson Co., Ltd., Japan). The results were expressed as a concentration per unit weight of the organs. Results are expressed as mean ± SD. The statistical results were analyzed by single factor variation with SPSS, and then Student's t test or Mann-Whitney test.

<Detection method of cytokine concentration in organs>

1. Add 1 ml of lysis buffer to 100 mg of organs and homogenize with a Glass‧Teflon (registered trademark) homogenizer.

Decomposition buffer

20mM Tris‧HCl (pH7.4)

0.25M sucrose

2mM EDTA‧2Na

10mM EGTA

1% Tritonx-100

+1 Complete Mine protease inhibitor cocktail tablets / 10ml

2. The homogenized homogenate was rotated at 100,000 g, centrifuged for 40 minutes, and the supernatant was collected (operating in ice cooling).

3. BCA protein assay was used to detect the protein concentration in the supernatant. The cytokine content per unit of protein is measured in the same way as for cytokines in plasma.

(References: Journal of Neuroinflammation 2008, 5:10, Increased systemic and brain cytokine production and neuroinflammation by endotoxin following ethanol treatment Liya Qin, Jun He, Richard N Hanes, Olivera Pluzarev, Jau-Shyoung Hong and Fulton T Crews)

The results are shown in Tables 9 to 11.

There was no difference in body weight between groups. On the one hand, the weight of the small intestine and large intestine was significantly increased. The length of the intestine was also shown to be significantly longer (Table 9).

The results of cytokine concentrations in plasma and organs are shown next (Table 10). The concentrations of cytokines or chemokines TNF-α, IFN-γ, MCP-1, and IL-6 in the plasma significantly increased in the general fluid food group, but all showed significant low values in the nutrient composition group. The concentrations of IL-12 and IL-10 are below the detection limit. Cytokines in the organs are mainly produced in the spleen, and the concentrations of IFN-γ, MCP-1, and IL-6 in the nutrient composition group show significantly lower values than the concentration of the general fluid food group. Compared with the general fluid food group, TNF-α (p = 0.07), IFN-γ, and MCP-1 in the liver of the nutrient composition group showed significantly lower values. MCP-1 and IL-6 in the small intestine showed significantly low values. It is known that ConA obviously causes liver damage, and the nutrient composition group inhibits liver damage, which has been shown to be related to the inhibition of TNF-α production in the liver. Since the increase in IL-6 concentration in plasma cannot be explained solely by the concentration of IL-6 in the liver, it may be related to the amount produced in the spleen. Compared with other organs, the concentration of inflammatory cytokines in the small intestine is lower. Compared with normal concentrations, the concentrations of MCP-1 and IL-6 are higher. Compared with the general fluid food group, the nutritional composition group shows a significant The low value of is considered to be related to the reduction of damage.

The results of the evaluation of the small intestine pathological tissues to the extent of 0 to 3 24 hours after administration of ConA are shown below. The small intestinal damage of the nutrient composition group is reduced compared to the general fluid food group (Mann-whitney test, p = 0.021) (Table 11).

[Example 3] Proliferation of mucosal epithelium or muscle layer of nutritional composition

Two weeks after free ingestion of the nutritional composition of the present invention and general fluid food, the weight of the small intestine, large intestine, and small intestine tissue were evaluated.

C57BL / 6 mice (6 weeks old, male) purchased from Japan SLC Co., Ltd. were used. The breeding environment is 21.0 ± 2.0 ° C, and the humidity is 55.0 ± 15.0%, and the light and dark are switched every 12 hours (lighting period: 7-19 points). During the experiment, feed and water were freely available.

The body weight of the purchased animals after one week of domestication was used as an index. Five animals in each group were divided into two groups. The experimental group was: Group 1: General fluid food, Group 2: Nutritional composition, and reared for 2 weeks. The general fluid food and nutritional composition are the same as in Example 1.

After anesthesia with ether, blood was collected from the large abdominal vein, and the liver, spleen, small intestine, and large intestine were harvested. The total length of the small intestine, the weight of 11 cm to 10 cm below the stomach, and the large intestine weight of 5 cm below the cecum were measured. Measure the weight of each organ. The small intestine was cut out from 6 cm to 3 cm below the stomach, fixed with a 10% formalin solution, and then embedded in a general method to prepare a tissue specimen and perform hematoxylin-yin red staining. Biochemical examination of ALT, AST, albumin, total protein, triglyceride, cholesterol, glucose and urea nitrogen in tissue samples. Results are expressed as mean ± SD. The statistical results were analyzed by SPSS with single factor variation and then tested by Student's t test.

Table 2 shows the organ weight and blood biochemical examination results of normal mice during the two weeks of ingestion of general fluid food and nutritional composition. There were no significant differences in body weight and liver between normal mouse groups. Compared with the general fluid food group, the relative weight of the spleen, the weight of the small intestine, and the large intestine of the nutritional composition group showed significantly higher values. On the other hand, there was no significant difference in the values of all blood biochemical test results between the groups.

Next, a specimen of a normal small intestine tissue was prepared, and the number of villi, the height of the villi, and the thickness of the muscle layer in a field of view were analyzed at 150 times a photograph (Figure 3 and Table 13). Compared with the general fluid food group, the number of villi and the total length of the villi of the nutritional composition group were not significantly different, but the average length of the villi and the thickness of the muscle layer showed a significant high value. From this result, it is inferred that the increase in the weight of the small intestine of the nutritional composition group is due to the increase in the length of the villi and the thickness of the muscle layer.

[Example 4] Intestinal hyperpermeability of nutritional composition and inhibition of bacterial translocation

A model of intestinal damage in rats induced by indomethacin was used to evaluate the effect of the nutritional composition of the present invention on small intestinal damage.

SD rats (6 weeks old, male) purchased from Japan SLC Co., Ltd. were used. The breeding environment is 21.0 ± 2.0 ° C, and the humidity is 55.0 ± 15.0%, and the light and dark are switched every 12 hours (lighting period: 7-19 points). During the experiment, feed and water were freely available.

The body weight of the purchased animals after domestication for one week was used as an index and divided into 6 groups. Two weeks before the administration of indomethacin, a general fluid food or nutritional composition was fed. The general fluid food and nutritional composition are the same as in Example 1. Thereafter, indomethacin was dissolved in 5% NaHCO ₃ , and a solution of 10 mg / kg was injected subcutaneously once a day for 2 consecutive days to induce damage to the small intestine. Thereafter, they were reared with the same feed, and the first day of administration was set as the 0th day, and the anatomical examination was performed on the 4th and 8th days. In the normal group without administration of indomethacin, half of the rats were dissected and examined on the 4th and 8th days, respectively.

On the 1st, 3rd, and 7th days, 0.6% of phenol sulfophthalate "Daisankyo" (Daisankyo Co., Ltd.) was orally administered in 3 ml of each, and collected within 24 hours. Urine, the amount of PSP excretion in the urine was measured, expressed as the rate of PSP excretion in the urine. PSP is a general index of human renal function. When PSP is administered orally, although the excretion rate in urine is very low, the permeability is increased due to damage to the intestinal membrane, it enters the blood through the interstitial space, and is excreted in the urine through the kidney. In the present embodiment, intestinal membrane permeability is used as an index.

The hunger strike was started at 5 pm the day before the dissection, and the dissection was performed one night after the hunger strike. Anesthetized with ether, blood was collected from the heart, and intestinal lymph nodes (MLN) and liver were removed under aseptic conditions. After measuring the weight of the organs, the homogenized solution of the organs was cultured in a BL ocean containing 5% defibrin blood. The vegetable medium was cultured at 37 ° C for 72 hours under aerobic and anaerobic conditions, and the number of bacteria was counted. Gram staining was performed and the bacteria detected were either Gram-negative or Gram-positive.

Second, measure the full length of the small intestine, the weight of the cecum and large intestine, and the pH of the cecum.

An automatic blood cell analyzer (Sysmex ST-1800i) was used to analyze the general blood tests. In general blood tests, various indicators of pathological changes are investigated. An increase in neutrophils or monocytes is known to cause infections (bacteria).

Result 1

Although intestinal membrane permeability was enhanced by intestinal damage induced by indomethacin, compared with the control group, the nutrient composition ingestion group significantly inhibited the intestinal permeability increase (Figure 4) . From the above results, it was found that the intestinal damage caused by indomethacin was suppressed by ingesting a nutritional composition.

From this result, it is speculated that ingestion of a nutritional composition has the possibility of preventing damage to the small intestine caused by non-steroidal anti-inflammatory drugs and the like.

Result 2

Due to the intestinal damage induced by indomethacin, damage to the intestinal mucosa's defense force and decreased immunity, etc., caused the intestinal bacteria in the original digestive tract to pass through the intestinal mucosal barrier and migrate Liver or intestinal lymph nodes.

On the 4th and 8th days after the administration of indomethacin, all the intestinal membrane lymph nodes and part of the liver were taken out, and the number of bacteria in the homogenized solution was measured by the culture method. The results of this experiment show that in individuals with no bacteria detected in the intestinal membrane lymph nodes on the 4th day after administration of indomethacin, 2 of the 9 fluid food groups and 10 of the nutrient composition group There are only 3 of them. Bacteria were detected in the liver of all individuals. On the 8th day, individuals with no bacteria detected in the intestinal membrane lymph nodes included 1 in 8 of the general fluid food group and 4 of 8 nutritional composition groups. No bacteria were detected in the liver of the general fluid food group and the nutrient composition group. Actually, the number of bacteria detected in each organ is shown in Fig. 5. The number of bacteria detected in the intestinal membrane lymph nodes on the 4th day after the administration of indomethacin was not significantly different between the nutrient composition group and the general fluid food group (not shown). On the other hand, the liver in the nutrient composition group showed less tendency (p = 0.068) (upper graph 5). On the eighth day after indomethacin administration, although no bacterial shift (BT) occurred in the liver, compared with the general fluid food group, the nutritional composition group had significant BT on intestinal lymph nodes. Inhibitory effect (p <0.05) (below Figure 5).

The bacteria detected were aerobic Gram-positive bacteria.

From the above results, it can be seen that ingestion of the nutritional composition inhibits BT to the intestinal membrane lymph nodes or the liver. That is, BT induced by damage to the small intestine caused by the administration of indomethacin is suppressed by ingesting a nutritional composition. It is speculated that ingestion of a nutritional composition may protect the small intestine and prevent the possibility of damage to the small intestine caused by nonsteroidal anti-inflammatory drugs and the like.

Result 3

A general blood test was performed to analyze changes before and after administration of indomethacin. In general blood tests, indicators that analyze various pathological changes are used. The increase in neutrophils and monocytes is known to cause infections (bacteria).

The results of the examination showed that in normal individuals, there was no significant difference between the nutritional composition group and the general fluid food group. On the other hand, the number of white blood cells increased in the indomethacin-administered group compared with normal individuals (Figure 6). The increase in white blood cells was due to an increase in the number of lymphocytes, neutrophils, and monocytes (Figure 6). It was found in the general fluid food group that white blood cells increased on the 4th day and continued to increase on the 7th day. On the other hand, the white blood cell increase of the nutritional composition group showed a peak on the fourth day, and then decreased. Among the white blood cells, those that are considered to be different between the groups, especially the number of neutrophils and mononuclear cells. Although there was no difference between the groups on the fourth day, the number of neutrophils and mononuclear spheres of the nutrient composition group showed a low value compared with the general fluid food group on the seventh day.

Judging from the above results, the bacterial shift induced by small intestinal damage caused by non-steroidal anti-inflammatory drugs was inhibited in the nutritional composition group, and the increase in the number of neutrophils and monocytes was suppressed.

[Example 5] Changes in the case of removing whey protein hydrolysate, isomaltulose, and protein derived from fermented milk in nutritional composition 1

C57BL / 6 mice (6 weeks old, male) purchased from Japan SLC Co., Ltd. were used. The weight of the purchased animals after domestication for 1 week was used as an index and divided into 5 groups.

Group:

Group 1: General fluid food (Meiji Dairy: Meibalance)

Group 2: Nutritional composition (Meiji Dairy: MEIN)

Group 3: Nutritional Composition-Whey Protein Hydrolysate (Nutrition Composition-P)

(Removal of whey protein hydrolysate from nutritional composition)

Group 4: Nutrition Composition-Whey Protein Hydrolysate-Isomaltulose (Nutrition Composition-P-I)

(Removes whey protein hydrolysate and isomaltulose from nutritional composition)

Group 5: Nutrition composition-Whey protein hydrolysate-Isomaltulose-Quark (Nutrition composition-P-I-Q)

(Remove whey protein hydrolysate, isomaltulose, Quark in nutrition composition)

The above 5 groups were reared for 2 weeks. Quark and whey protein hydrolysate in the nutritional composition were replaced with casein, and isomaltulose was replaced with dextrin.

12 mg / kg of ConA (Sigma) was administered through the tail vein. The next day, anesthesia with ether was performed. Blood was collected from the large abdominal vein, and then the liver, spleen, cecum, and small intestine were removed. The small intestine measures the weight of the center 10 cm.

The results of body weight and organ weight are shown in Fig. 7 and Table 14 (body weight 24 hours after administration of ConA and organ weight per unit body weight).

Body weight, liver and spleen weight per unit weight did not differ significantly between groups. The weight of the cecum of the nutritional composition group is significantly increased compared to the general fluid food group. Compared with the nutritional composition group, the cecum weight showed a significantly lower value in the group that removed whey protein hydrolysate, isomaltulose, and Quark in the nutritional composition. Related to leaven. The small intestine weight of the nutritional composition group shows a significantly high value compared with a general fluid food group. Compared with the nutrient composition group, the group that removes whey protein hydrolysate, isomaltulose, and Quark in the nutrient composition shows a significantly lower value of the small intestine weight, and therefore shows that these three ingredients and small intestine damage Or inflammation-related possibilities.

Whey protein hydrolysate, isomaltulose, and Quark may be related to the intestinal protective effect or anti-inflammatory effect of nutritional composition.

[Example 6] Changes in the case of removing whey protein hydrolysate, isomaltulose, and protein derived from fermented milk in nutritional composition 2

C57BL / 6 mice (6 weeks old, male) purchased from Japan SLC Co., Ltd. were used. The body weight of the purchased animals after one week of domestication was used as an index and divided into 6 groups.

Group (general fluid food and nutrition composition are the same as in Example 6):

Group 1: General fluid food

Group 2: Nutritional composition

Group 3: Nutritional Composition-Whey Protein Hydrolysate (-P)

(Removal of whey protein hydrolysate from nutritional composition)

Group 4: Nutritional Composition-Isomaltulose (-I)

(Removes isomaltulose from nutritional composition)

Group 5: Nutrition Composition-Quark (-Q)

(Remove Quark in nutrition composition)

Group 6: Nutrition Composition-Whey Protein Hydrolysate-Isomaltulose-Quark (-P-I-Q)

(Remove whey protein hydrolysate, isomaltulose, Quark in nutrition composition)

The above 6 groups were reared for 2 weeks. The protein source Quark and whey protein hydrolysate in the nutritional composition are replaced with casein, and isomaltulose is prepared by replacing with dextrin.

12 mg / kg of ConA (Sigma) was administered from the tail vein, and blood was collected from the tail vein at 2, 4, and 8 hours after the administration. The next day, anesthesia was performed with ether, and blood was collected from the large abdominal vein. Then the liver, spleen, cecum, and small intestine were removed. ,the large intestine. ALT and AST in plasma were detected by Fuji DRI-CHEM.

Result 1

The results of the final daily weight and organ weight are shown in Table 15.

There was no significant difference between body weight and organ weight (liver, spleen) per unit body weight. The weight of the small intestine and cecum of the nutritional composition group, the third group (-whey protein hydrolysate), and the fourth group (-isomaltulose) showed significantly higher values than the general fluid food group.

Result 2

The results of AST and ALT 24 hours after administration of ConA are shown in Fig. 8. Compared with the nutrient composition group, the AST and ALT of the group which removed only the whey protein hydrolysate (group 3) and the group which removed only Quark (group 5) increased. The AST and ALT values of only the isomaltulose (Group 4) were almost the same as those of the nutrient composition group. Compared with the nutrient composition group, when the whey protein hydrolysate, isomaltulose, and Quark were removed from the nutrient composition group (Group 6), the ALT value showed a significantly higher value, indicating a hepatitis inhibitory effect. Mainly related to whey protein hydrolysate and Quark.

The anti-inflammatory effect of the nutritional composition is judged mainly on whey protein hydrolysate and quark. The intestinal function maintenance and intestinal protective effect of the nutritional composition are related to three kinds of raw materials including whey protein hydrolysate, isomaltulose, and skim curd, although Quark is the main ingredient Quark.

[Comparative Example 1] Preparation of whey protein hydrolysate

The dried whey protein isolate (WPI, Davisco) with a protein content of 90% was dissolved in distilled water at 8% (w / v) protein content. This solution was heated at 85 ° C for 2 minutes for heating to denature the protein. The pH of this heated solution was about 7.5. It was hydrolyzed by adding alkaline protease 2.4L (enzyme, Novozymes) to a concentration of 2.0% relative to the substrate and reacted at 55 ° C for 3 hours. Next, pig trypsin PTN 6.0S (Novozymes Japan) was added to a concentration of 3.0% relative to the substrate, and the reaction was performed at 55 ° C for 3 hours. The total hydrolysis time was 6 hours. The pH at the end of the reaction was about 7.0. The whey protein hydrolysate was subjected to centrifugation (20,000 × g, 10 minutes), and then treated with a UF membrane with a molecular weight of 10,000 (Ultrafree-MC from Millipore).

A reverse phase HPLC permeate was provided.

condition

Sample: UF permeate of whey protein hydrolysate

Column: C18 SG120 (Shiseido) 4.6 mmφ × 250 mm

Eluent: A; 0.1% trifluoroacetic acid aqueous solution / acetonitrile 5/95

B; 0.1% trifluoroacetic acid aqueous solution / acetonitrile 32/68

A → B 60-minute linear concentration gradient

Flow rate: 1 mL / min

Detection: 215 nm (ultraviolet / visible light detector)

[Industrial availability]

The composition of the present invention shows hyperintestinal function that promotes intestinal villus proliferation and increases muscle layer thickness. Therefore, it is effective for elderly patients with reduced intestinal function, cancer patients, etc. Patients with intestinal damage caused by administration of antibiotics or anticancer drugs, and patients with intestinal dysfunction caused by postoperative or ICU that cannot provide nutrition for a long time. Improved bowel function. For healthy people, it is also effective for small intestinal villi growth to improve intestinal function.

The composition of the present invention is effective for preventing tissue damage of the small intestine. The composition of the present invention further exhibits an anti-inflammatory effect, and can also be used as an anti-inflammatory agent.

Figure 1 is a comparison chart of the area of the small intestine.

Figure 2 is a photograph of the small intestine pathology (hematoxylin-yin red staining).

Figure 3 is a photograph of normal small intestine tissue (H‧E staining × 150 times).

Figure 4 shows the urine excretion rate of PSP. Mean ± SE, Student's t test (Day 0: n = 9, Day 2: n = 9-10, Day 4: n = 9-10, Day 8: n = 8).

Figure 5 shows the number of bacteria detected in the liver (upper panel) and intestinal lymph nodes (lower panel) after administration of indomethacin. Mean ± SE, Student's t test; *: p <0.05 (Day 0: n = 6, Day 4: n = 8-9, Day 8: n = 8).

Figure 6 shows the change in the number of neutrophils and mononuclear spheres in the blood after administration of indomethacin. Mean ± SD, Student's t test; *: p <0.05 (day 8: n = 7 to 8).

Figure 7 shows the weight of the small intestine (top) and the weight of the cecum (bottom) 24 hours after administration of concanavalin A (ConA). Mean ± SD, Scheffe test; *: p <0.05 (n = 8 ～ 10). SF: general fluid food, ND: nutritional composition, -P: nutritional composition-whey protein hydrolysate, -PI: nutritional composition-whey protein hydrolysate-isomaltulose, -PIQ: nutritional composition -Whey protein hydrolysate-Isomaltulose-Quark.

Figure 8 shows AST and ALT activities in plasma 8 hours after administration of Concanavalin A (ConA). Mean ± SD, Mann-Whitney test; *: p <0.05 (n = 5-9).

Claims (14)

A composition that promotes the growth of small intestine villi, increases the thickness of the small intestine muscle layer, improves intestinal function, or prevents damage to small intestine tissue. The fats and oils and the composition of isomaltulose, which is a sugar, are manufactured by homogenization after high-temperature sterilization. The milk protein is concentrated or concentrated after whey membrane separation or ion exchange resin treatment or electrodialysis treatment. The whey protein isolate (WPI) obtained after drying, or the whey protein concentrate (WPC) obtained after the whey is separated through a membrane, is concentrated or concentrated and dried, and the hydrolysate of milk protein is the following (a ), (B), (c) or (d): (a) by hydrolyzing whey protein isolate (WPI) or whey protein concentrate (WPC) with a protease, This hydrolysate is treated with an ultrafiltration (UF) device having a cut-off value of 10,000 or more, and a whey protein hydrolysate obtained by deactivating the protease with respect to the filtrate containing the hydrolysate; (b) by heating transsexual Whey protein isolate (WPI) is a whey protein hydrolysate obtained by hydrolyzing endo-peptidase and exo-peptidase, and using an ion exchange resin to adsorb and treat the aromatic amino acid in the hydrolysate; (c ) A 12% aqueous solution with a protein content of at least 65% whey protein concentrate (WPC), after a heat treatment in excess of 60 ° C., with Alcalase (registered trademark) from B. licheniformis and from Bacillus subtilis ( Neutrase (registered trademark) of B.subtilis) was hydrolyzed to a DH of 15 to 35%, and the hydrolysate was subjected to a cut-off value exceeding 10,000. After ultrafiltration (UF), the solution was concentrated by nanofiltration (NF), and the NF concentrated solution was spray-dried to obtain a whey protein hydrolysate that was odorless and less bitter; (d) A solution containing whey protein isolate (WPI) with a protein content of 8% was heated at 85 ° C to obtain a solution having a pH of about 7.5. This solution was hydrolyzed by a protease to obtain a hydrolysate having a pH of about 7.0. The product was subjected to ultrafiltration membrane treatment with a fractional molecular weight of 10,000, and the obtained permeate was supplied to a whey protein hydrolysate obtained by reverse-phase HPLC. A method for producing a composition according to item 1 of the scope of patent application, comprising: reconciling a hydrolysate containing milk protein described in item 1 of the scope of patent application as a protein, a protein derived from fermented milk, and a lipid A step of oil and fat and a composition of isomaltulose which is a sugar, a step of sterilizing the blend at high temperature, and a step of homogenizing the blend after sterilization at high temperature. A hydrolysate of milk protein as protein and protein derived from fermented milk, fats and oils as lipid, and isomaltulose as sugar for producing a composition for promoting intestinal villi growth as described in item 1 of the scope of patent application the use of. The use as described in claim 3, wherein the protein derived from fermented milk is derived from fresh cheese. A hydrolysate of milk protein as protein and protein derived from fermented milk, fats and oils as lipid, and isomaltulose as sugar Use for manufacturing a composition for increasing the thickness of the small intestinal muscle layer as described in item 1 of the scope of patent application. The use as described in claim 5 of the application, wherein the protein derived from fermented milk is derived from fresh cheese. A hydrolysate of milk protein as protein and protein derived from fermented milk, oils and fats as lipid, and isomaltulose as sugar for producing a composition for improving intestinal function as described in item 1 of the scope of patent application the use of. The use as described in claim 7 of the application, wherein the protein derived from fermented milk is derived from fresh cheese. A hydrolysate of milk protein as protein and protein derived from fermented milk, oils and fats as lipid, and isomaltulose as sugar for producing a composition for preventing small intestinal tissue damage as described in item 1 of the scope of patent application the use of. The use according to item 9 of the patent application scope, wherein the protein derived from fermented milk is derived from fresh cheese. A protein hydrolysate of milk protein and a protein derived from fermented milk as described in item 1 of the scope of application for protein as a protein, and isomaltulose, which is a sugar, is used for the manufacture of homogenized after high temperature sterilization to improve intestinal function Use of the composition. The use according to item 11 of the patent application scope, wherein the protein derived from fermented milk is derived from fresh cheese. A hydrolysate of milk protein, a protein derived from fermented milk, and a carbohydrate as described in item 1 of the scope of application for protein as a protein Isomaltulose is used to produce a composition that is homogenized after high temperature sterilization to prevent damage to small intestine tissue. The use according to item 13 of the application, wherein the protein derived from fermented milk is derived from fresh cheese.