CN102665750B

CN102665750B - The alimentation composition beneficial to small intestine

Info

Publication number: CN102665750B
Application number: CN201080048765.2A
Authority: CN
Inventors: 粂久枝; 山地健人
Original assignee: Meiji Co Ltd
Current assignee: Meiji Co Ltd
Priority date: 2009-11-30
Filing date: 2010-11-30
Publication date: 2018-01-02
Anticipated expiration: 2030-11-30
Also published as: TWI612902B; HK1246098A1; CN107822150A; JPWO2011065552A1; WO2011065552A1; JP5946642B2; CN102665750A; TW201121430A; JP6158380B2; JP2016172722A

Abstract

Hepatitis model is induced using mouse ConA, the cell factor that be have studied for the composition intake group of the present invention in small intestine and spleen produces and injury of small intestine.As a result find, in the composition intake group of the present invention, not only the generation of cell factor rises and is suppressed in liver and blood plasma, and confirms that the MCP 1 in small intestine, liver and IL 6 generation rises inhibitory action, also show the mitigation of the tissue damage of small intestine.Determine, have rated the small intestine weight and large intestine weight of normal mouse of the composition of the intake present invention after 2 weeks.As a result find, small intestine weight and large intestine weight show significant increase, and the average length of fine hair and the thickness of muscularis propria are significantly higher compared with control group.

Description

The alimentation composition beneficial to small intestine

Technical field

The present invention relates to the composition useful to improving gut function, and it includes milk protein hydrolysate, the egg from acidified milk White matter, lipid and carbohydrate.

Background technology

Ever-increasing disease of life-style has important relationship with eating habit in recent years., must in order to maintain and improve health The intake for the nutrient wanted is important, in order to efficiently digest and assimilate these nutrients, it is desirable to maintain normal gut function.But It is in reality, chaotic, irregular eating habit, the phrenoblabia of life style are such as frightened, grieved, terrified, cause just The gut functions such as secret, diarrhoea are abnormal.In addition, there is the generation for causing the diseases such as enteropathy and cancer in the lasting of these gut functions exception. So far, using the lactic acid bacteria of display gut function improvement result, such as newborn bacillus (Lactobacillus) and bifid bar The yogurt and fermented beverage of (probiotics) such as bacterium (bifidobacteria) are widely used as food.In addition, it can help in enteron aisle The oligosaccharides of useful microbial growth, the food with gut function regulatory function such as dietary fiber is also widely applied.Though Right known such food has the function that individually to repair enteral environment, but they are unlikely with promotion intestinal villi life The function of length/reparation, it is desirable to develop the food with such function.

In terms of clinical point, the pathological condition for reducing Small Intestine surface area can be enterectomy, radiation, Intestinal ischemia Or wound, Crohn's disease, ulcerative colitis etc..For these pathological states, the reparation to the mucous membrane of small intestine of damage And the treatment of raising compensation is necessary.For this purpose it is known that specific nutrient such as glutamine, n-3 types are more not Saturated fatty acid and zinc etc. are important.By enteron aisle chamber nutrient is supplemented/applied for promoting the metabolism response of intestines such as Propagation/repair ability of metabolism/endocrine compliability and mucous membrane of small intestine is necessary, and physiology intestines such as bile/pancreatic secretion Content by being premise.Nutrition can be provided by intravenous hyperalimentation, high heat infusion or total parenteral nutrition, But these measures frequently result in mucous membrane of small intestine atrophy, so as to further reduce gut function.Accordingly it is desirable to develop has to enteron aisle The medicament or food of benefit.A variety of enteral nutrition food have been developed, and has developed containing dietary fiber and there are intestines The food of the Function Regulation.However, not yet develop available for maintain/improve gut function, such as promote intestinal villi growth and Increase the medicament or comprehensive nutritional food of muscularis propria thickness.

Prior art literature

[patent document]

[patent document 1] WO 2004/047556

[patent document 2] Japanese Unexamined Patent Publication (JP-A) 2004-99563 (the co-pending Japanese patent application looked into)

The content of the invention

[problems to be solved by the invention]

It is an object of the present invention to provide available for the composition for maintaining/improving gut function.Or of the invention one Purpose is to provide the composition for promoting intestinal villi to grow, and for increasing the composition of small intestine muscularis propria thickness, is used for Improve the composition of gut function, for the composition for preventing small intestine from damaging, and anti-inflammatory composition.

[means for solving problem]

The mouse model that the present inventor induces hepatitis using ConA is prepared for common liq diet and the present invention's The tissue sample of the intake group of alimentation composition, and checked the cell factor production in small intestine's damage and small intestine and spleen It is raw.For cell factor, in addition to producing TNF-α and IL-6, chemotactic factor (CF) MCP-1 generation has also been investigated.As a result, taking the photograph In the group for taking the alimentation composition of the present invention, it is thus identified that suppress the generation increase of MCP-1 and IL-6 in small intestine and spleen, and suppress Increased effect caused by cell factor in blood plasma and liver.It moreover has been found that the damage of small intestine reduces (Examples 1 and 2).

According to these results, the present inventor guesses that the intake of the alimentation composition of the present invention brings certain to enteron aisle Kind changes, and then measures normal rat weight of small intestine and large intestine after absorbing 2 weeks.In addition, prepare and have rated small intestine group The sample knitted.As a result, the weight of small intestine and large intestine shows obvious increase.In addition, compared with control group, to small intestine Evaluation does not show the difference of fine hair number, but the average length of fine hair and the thickness of muscularis propria show it is more considerably higher than control group Value.There is the protective effect for injury of small intestine in the display of these results, and promote muscle layer and mucous membrane of small intestine epithelial growth Effect (embodiment 3).

In addition, the present inventor uses the injury of small intestine rat model that Indomethacin induces, drunk for common liq The intake group of food or the alimentation composition of the present invention has investigated the homaluria speed of enteron aisle permeability indicant phenolsulfonphthalein.In addition, Except general blood test, displacement of the bacterium to liver and lymphonodi mesenterici has also been investigated.As a result, in the nutrient combination of the present invention In the intake group of thing, show that the displacement of the enhancing and bacterium of small goldbeater's skin permeability to liver and lymphonodi mesenterici is suppressed. In addition, general hematological results are shown, in alimentation composition intake group, along with small intestine caused by being applied as Indomethacin Neutrophil cell number and the increase of monocyte number are suppressed in the blood of damage.From the above results, the alimentation composition Intake can protect enteron aisle, and with the effect for such as non-steroid antiinflammatory medicament suppression injury of small intestine.It can also have Bacterial translocation caused by effect ground prevention intestinal disorder and infection such as septicemia and pneumonia for inducing etc., and immune system is maintained in just Normal state (embodiment 4).

In addition, the present inventor used ConA induce hepatitis mouse model come investigate gained alimentation composition Hepatitis inhibitory action and gut function maintain be related to which component, and its protective effect to injury of small intestine.As a result show, Serum protein hydrolysate, isomaltoketose and quark (quark) are related to the maintenance (embodiment 5) of gut function.In addition, display breast Albumin matter hydrolysate and quark relate generally to hepatitis inhibitory action (embodiment 6).

Based on these discoveries, the application provides following inventions：

[1] a kind of composition for being used to promote intestinal villi to grow, it includes milk protein hydrolysate and from acidified milk Protein is as protein, grease as lipid and isomaltoketose as carbohydrate；

[2] composition of [1], wherein the lactoprotein is selected from the group：Casein, milk protein concentrate (MPC), whey egg White matter, whey protein concentrate (WPC), whey protein sepd (WPI), α-lactalbumin, beta lactoglobulin and newborn iron Albumen；

[3] composition of [1] or [2], wherein the protein source from acidified milk is in fresh cheese；

[4] a kind of composition for being used to increase small intestine muscularis propria thickness, it includes milk protein hydrolysate and from fermentation The protein of breast is as protein, grease as lipid and isomaltoketose as carbohydrate；

[5] composition of [4], wherein the lactoprotein is selected from the group：Casein, milk protein concentrate (MPC), whey egg White matter, whey protein concentrate (WPC), whey protein sepd (WPI), α-lactalbumin, beta lactoglobulin and newborn iron Albumen；

[6] composition of [4] or [5], wherein the protein source from acidified milk is in fresh cheese；

[7] a kind of composition for being used to improve gut function, it includes milk protein hydrolysate and the protein from acidified milk As protein, grease as lipid and isomaltoketose as carbohydrate；

[8] composition of [7], wherein the lactoprotein is selected from the group：Casein, milk protein concentrate (MPC), whey egg White matter, whey protein concentrate (WPC), whey protein sepd (WPI), α-lactalbumin, beta lactoglobulin and newborn iron Albumen；

[9] composition of [7] or [8], wherein the protein source from acidified milk is in fresh cheese；

[10] a kind of composition for being used to prevent that small intestine from damaging, it includes milk protein hydrolysate and from acidified milk Protein is as protein, grease as lipid and isomaltoketose as carbohydrate；

[11] composition of [10], wherein the lactoprotein is selected from the group：Casein, milk protein concentrate (MPC), whey Protein, whey protein concentrate (WPC), whey protein sepd (WPI), α-lactalbumin, beta lactoglobulin and breast Ferritin；

[12] composition of [10] or [11], wherein the protein source from acidified milk is in fresh cheese；

[13] a kind of anti-inflammatory composition, its include milk protein hydrolysate and protein from acidified milk as protein, Grease is as lipid and isomaltoketose as carbohydrate；

[14] composition of [13], wherein the lactoprotein is selected from the group：Casein, milk protein concentrate (MPC), whey Protein, whey protein concentrate (WPC), whey protein sepd (WPI), α-lactalbumin, beta lactoglobulin and breast Ferritin；

[15] composition of [13] or [14], wherein the protein source from acidified milk is in fresh cheese；

[16] a kind of method for being used to promote intestinal villi to grow, it is included using comprising milk protein hydrolysate and from hair The protein of kefir milk as protein, grease as composition as carbohydrate of lipid and isomaltoketose the step of；

[17] it is a kind of be used for increase small intestine muscularis propria thickness method, it include using comprising milk protein hydrolysate with Protein from acidified milk is as protein, grease as the step of lipid and isomaltoketose as the composition of carbohydrate Suddenly；

[18] a kind of method for being used to improve gut function, it is included using comprising milk protein hydrolysate and from acidified milk Protein as protein, grease as composition as carbohydrate of lipid and isomaltoketose the step of；

[19] a kind of method for being used to prevent that small intestine from damaging, it is included using comprising milk protein hydrolysate and from hair The protein of kefir milk as protein, grease as composition as carbohydrate of lipid and isomaltoketose the step of；

[20] a kind of method for being used to suppress inflammation, it is included using the egg comprising milk protein hydrolysate and from acidified milk White matter as protein, grease as composition as carbohydrate of lipid and isomaltoketose the step of；

[21] comprising milk protein hydrolysate and protein from acidified milk as protein, grease as lipid and Isomaltoketose is used to promote the purposes in the composition of intestinal villi growth as the composition of carbohydrate in preparation；

[22] comprising milk protein hydrolysate and protein from acidified milk as protein, grease as lipid and Isomaltoketose is being prepared for the purposes in the composition for the thickness for increasing small intestine muscularis propria as the composition of carbohydrate；

[23] comprising milk protein hydrolysate and protein from acidified milk as protein, grease as lipid and Isomaltoketose is preparing the purposes in being used to improve the composition of gut function as the composition of carbohydrate；

[24] comprising milk protein hydrolysate and protein from acidified milk as protein, grease as lipid and Isomaltoketose is used to prevent the purposes in the composition of small intestine's damage as the composition of carbohydrate in preparation；

[25] comprising milk protein hydrolysate and protein from acidified milk as protein, grease as lipid and Composition purposes during preparing anti-inflammatory composition of the isomaltoketose as carbohydrate；

[26] comprising milk protein hydrolysate and protein from acidified milk as protein, grease as lipid and Composition of the isomaltoketose as carbohydrate, for for promoting to use in the method for intestinal villi growth；

[27] comprising milk protein hydrolysate and protein from acidified milk as protein, grease as lipid and Composition of the isomaltoketose as carbohydrate, for being used in the method for the thickness for increasing small intestine muscularis propria；

[28] comprising milk protein hydrolysate and protein from acidified milk as protein, grease as lipid and Composition of the isomaltoketose as carbohydrate, for being used in the method for improving gut function；

[29] comprising milk protein hydrolysate and protein from acidified milk as protein, grease as lipid and Composition of the isomaltoketose as carbohydrate, for for preventing from using in the method for small intestine's damage；

[30] comprising milk protein hydrolysate and protein from acidified milk as protein, grease as lipid and Composition of the isomaltoketose as carbohydrate, for being used in the method for suppressing inflammation；

[31] a kind of composition for being used to improve gut function, it includes the protein from acidified milk；

[32] a kind of composition for being used to improve gut function, it includes milk protein hydrolysate and the protein from acidified milk As protein, and isomaltoketose is as carbohydrate；

[33] composition of [32], wherein the lactoprotein is selected from the group：Casein, milk protein concentrate (MPC), whey Protein, whey protein concentrate (WPC), whey protein sepd (WPI), α-lactalbumin, beta lactoglobulin and breast Ferritin；

[34] composition of [31] to any one of [33], wherein the protein source from acidified milk is in new fresh milk Junket；

[35] a kind of composition for being used to prevent that small intestine from damaging, it includes the protein from acidified milk；

[36] a kind of composition for being used to prevent that small intestine from damaging, it includes milk protein hydrolysate and from acidified milk Protein is as protein, and isomaltoketose is as carbohydrate；

[37] composition of [36], wherein the lactoprotein is selected from the group：Casein, milk protein concentrate (MPC), whey Protein, whey protein concentrate (WPC), whey protein sepd (WPI), α-lactalbumin, beta lactoglobulin and breast Ferritin；

[38] composition of [35] to any one of [37], wherein the protein source from acidified milk is in new fresh milk Junket；

[39] a kind of anti-inflammatory composition, its protein comprising milk protein hydrolysate and from acidified milk is as protein；

[40] composition of [39], it is also comprising isomaltoketose as carbohydrate；

[41] composition of [39] or [40], wherein the lactoprotein is selected from the group：Casein, milk protein concentrate (MPC), whey protein, whey protein concentrate (WPC), whey protein sepd (WPI), α-lactalbumin, β-breast Globulin and lactoferrin；

[42] composition of [39] to any one of [41], wherein the protein source from acidified milk is in new fresh milk Junket；

[43] a kind of method for being used to improve gut function, it includes the composition applied and include the protein from acidified milk The step of；

[44] a kind of method for being used to improve gut function, it is included using comprising milk protein hydrolysate and from acidified milk The step of protein is as composition as carbohydrate of protein and isomaltoketose；

[45] method of [44], wherein the lactoprotein is selected from the group：Casein, milk protein concentrate (MPC), whey egg White matter, whey protein concentrate (WPC), whey protein sepd (WPI), α-lactalbumin, beta lactoglobulin and newborn iron Albumen；

[46] method of [43] to any one of [45], wherein the protein source from acidified milk is in new fresh milk Junket；

[47] a kind of method for being used to prevent that small intestine from damaging, it, which includes to apply, includes the protein from acidified milk The step of composition；

[48] a kind of method for being used to prevent that small intestine from damaging, it is included using comprising milk protein hydrolysate and from hair The step of protein of kefir milk is as composition as carbohydrate of protein and isomaltoketose；

[49] method of [48], wherein the lactoprotein is selected from the group：Casein, milk protein concentrate (MPC), whey egg White matter, whey protein concentrate (WPC), whey protein sepd (WPI), α-lactalbumin, beta lactoglobulin and newborn iron Albumen；

[50] method of [47] to any one of [49], wherein the protein source from acidified milk is in new fresh milk Junket；

[51] a kind of method for being used to suppress inflammation, it is included using the egg comprising milk protein hydrolysate and from acidified milk The step of composition of the white matter as protein；

[52] method of [51], wherein the composition also includes isomaltoketose as carbohydrate；

[53] method of [51] or [52], wherein the lactoprotein is selected from the group：Casein, milk protein concentrate (MPC), Whey protein, whey protein concentrate (WPC), whey protein sepd (WPI), α-lactalbumin, beta lactoglobulin, And lactoferrin；

[54] method of [51] to any one of [53], wherein the protein source from acidified milk is in new fresh milk Junket；

[55] protein from acidified milk is preparing the purposes in being used to improve the composition of gut function；

[56] milk protein hydrolysate and protein from acidified milk as protein and isomaltoketose as carbohydrate Preparing the purposes in being used to improve the composition of gut function；

[57] purposes of [56], wherein the lactoprotein is selected from the group：Casein, milk protein concentrate (MPC), whey egg White matter, whey protein concentrate (WPC), whey protein sepd (WPI), α-lactalbumin, beta lactoglobulin and newborn iron Albumen；

[58] purposes of [55] to any one of [57], wherein the protein source from acidified milk is in new fresh milk Junket；

[59] purposes of the protein from acidified milk in the composition for preventing small intestine's damage is prepared；

[60] milk protein hydrolysate and protein from acidified milk as protein and isomaltoketose as carbohydrate Purposes in the composition for preventing small intestine's damage is prepared；

[61] purposes of [60], wherein the lactoprotein is selected from the group：Casein, milk protein concentrate (MPC), whey egg White matter, whey protein concentrate (WPC), whey protein sepd (WPI), α-lactalbumin, beta lactoglobulin and newborn iron Albumen；

[62] purposes of [59] to any one of [61], wherein the protein source from acidified milk is in new fresh milk Junket；

[63] anti-inflammatory is being prepared as the composition of protein comprising milk protein hydrolysate and the protein from acidified milk Purposes in composition；

[64] purposes of [63], wherein the composition also includes isomaltoketose as carbohydrate；

[65] purposes of [63] or [64], wherein the lactoprotein is selected from the group：Casein, milk protein concentrate (MPC), Whey protein, whey protein concentrate (WPC), whey protein sepd (WPI), α-lactalbumin, beta lactoglobulin, And lactoferrin；

[66] purposes of [63] to any one of [65], wherein the protein source from acidified milk is in new fresh milk Junket；

[67] a kind of composition for including the protein from acidified milk, for being used in the method for improving gut function；

[68] protein comprising milk protein hydrolysate and from acidified milk is as protein and isomaltoketose conduct The composition of carbohydrate, for being used in the method for improving gut function；

[69] composition of [68], wherein the lactoprotein is selected from the group：Casein, milk protein concentrate (MPC), whey Protein, whey protein concentrate (WPC), whey protein sepd (WPI), α-lactalbumin, beta lactoglobulin and breast Ferritin；

[70] composition of [67] to any one of [69], wherein the protein source from acidified milk is in new fresh milk Junket；

[71] composition of the protein from acidified milk is included, for for preventing from making in the method for small intestine's damage With；

[72] protein comprising milk protein hydrolysate and from acidified milk is as protein and isomaltoketose conduct The composition of carbohydrate, for for preventing from using in the method for small intestine's damage；

[73] composition of [72], wherein the lactoprotein is selected from the group：Casein, milk protein concentrate (MPC), whey Protein, whey protein concentrate (WPC), whey protein sepd (WPI), α-lactalbumin, beta lactoglobulin and breast Ferritin；

[74] composition of [71] to any one of [73], wherein the protein source from acidified milk is in new fresh milk Junket；

[75] milk protein hydrolysate and composition of the protein as protein from acidified milk are included, for for suppressing Used in the method for inflammation；

[76] composition of [75], it is also comprising isomaltoketose as carbohydrate；

[77] composition of [75] or [76], wherein the lactoprotein is selected from the group：Casein, milk protein concentrate (MPC), whey protein, whey protein concentrate (WPC), whey protein sepd (WPI), α-lactalbumin, β-breast Globulin and lactoferrin；With

[78] composition of [75] to any one of [77], wherein the protein source from acidified milk is in fresh cheese.

Brief Description Of Drawings

Fig. 1 presents the figure of smaller intestinal surface product.

Fig. 2 shows the photo (stained with Hematoxylin-Eosin) of small intestine's pathological image.

Fig. 3 shows the photo of normal small intestine tissue (H-E is dyed, x150 amplifications).

The figure for showing PSP urine ejection speed is presented in Fig. 4.Average value ± SE, student T-test (the 0th day：N=9；2nd My god：N=9-10, the 4th day：N=9-10, the 8th day：N=8).

Fig. 5, which is presented, to be shown in using being detected in liver (above) and lymphonodi mesenterici (figure below) after Indomethacin Count of bacteria.Average value ± SE, student T-test；*：P ＜ 0.05 (the 0th day：N=6, the 4th day：N=8-9, the 8th day：n =8).

The figure for being shown in the change using blood neutrophils after Indomethacin and monocyte count is presented in Fig. 6. Average value ± SE, student T-test；*：P ＜ 0.05 (the 8th day：N=7-8).

Fig. 7, which is presented, to be shown in using the weight of small intestine (above) and fine hair (figure below) after con A 24 hours Figure.Average value ± SD, Scheffe inspection；*：P ＜ 0.05 (n=8-10).SF：Common liq diet；ND：Alimentation composition；- P：Alimentation composition-serum protein hydrolysate；-P-I：Alimentation composition-serum protein hydrolysate-isomaltoketose；With And-P-I-Q：Alimentation composition-serum protein hydrolysate-isomaltoketose-quark.

The figure being shown in using AST and ALT activity in blood plasma after con A 8 hours is presented in Fig. 8.Average value ± SE, Mann-Whitney are examined；*：P ＜ 0.05 (n=5-9).

The embodiment of invention

The present invention is provided to promote the composition that intestinal villi grows, it includes milk protein hydrolysate and from acidified milk Protein as protein, grease is as lipid, and isomaltoketose is as carbohydrate.

The growth of intestinal villi promotes the propagation of intestinal epithelial cell.In addition, the growth of intestinal villi is considered as promoting The reparation of absorption or the injury of small intestine of nutrient.Therefore, composition of the invention can be used as, for example, " intestinal villi growth stimulator ", " intestinal epithelial cell growth stimulator ", " Nutrients Absorption accelerator ", and " injury of small intestine restoration accelerator ".In addition, above-mentioned sheet The composition of invention can be used for the Small Intestine of healthy individuals to improve, the nutrition improvement of underfed People, breathing, circulation Maintained with the gut function of the patient (ICU patient) of the severe dysfunction such as metabolic system, there is the dysphagia of brain/neurological disorder The nutrient and gut function of patient maintains, and the gut function for the chronic intestines illness such as ulcerative colitis and Crohn's disease changes Kind and nutritional status improves, and improves for chronic obstructive pulmonary disease (COPD) and underfed gut function and nutritional status changes It is kind, or because the nutritional status of intestines impaired patients such as cancer patient caused by antibiotic and anticancer improves.

The present invention is provided to increase the composition of small intestine muscularis propria thickness, it includes milk protein hydrolysate and from hair The protein of kefir milk is as protein, grease as lipid and isomaltoketose as carbohydrate.

The increase of small intestine muscularis propria thickness can promote the vermicular movement of small intestine and large intestine.In addition, small intestine muscularis propria is thick The increase of degree can promote intestines regulating effect.Therefore, composition of the invention can be used as, for example, " small intestine muscularis propria thickness increase Agent ", " enterocinesia campaign accelerator " and " intestines conditioning agent ".In addition, above-mentioned composition of the invention can be used for healthy individuals Small Intestine improves, the nutrition improvement of underfed People, the trouble of the severe dysfunction such as breathing, circulation and metabolic system The gut function of person (ICU patient) maintains, and the nutrient and gut function with the dysphagia patients of brain/neurological disorder maintain, Gut function for the chronic intestines illness such as ulcerative colitis and Crohn's disease improves and nutritional status improves, for chronic resistance Plug property tuberculosis (COPD) and underfed gut function improve and nutritional status improves, and because antibiotic and anticancer cause Intestines impaired patients such as cancer patient nutritional status improve.

The present invention is provided to improve the composition of gut function, it includes the protein from acidified milk.It is in addition, of the invention Composition for improving gut function is provided, its include milk protein hydrolysate and protein from acidified milk as protein, Grease is as lipid and isomaltoketose as carbohydrate.

In addition, the present invention is provided to improve the composition of gut function, it includes milk protein hydrolysate and from acidified milk Protein as protein and isomaltoketose as carbohydrate.

Improve gut function and refer to the digestion and absorption of the nutrient that promotion is ingested, and promote to realize by intestines peristalsis Waste discharge.Function of intestinal canal lowly causes barrier breakdown, and (including gut associated lymphoid tissue (GALT) is fragile, bacterial translocation (BT), septicemia etc., biophylaxis underactivity is caused.Function of intestinal canal lowly causes malnutrition, and induces control biology The gastrointestinal hormone of function and generation/secretion of neurotransmitter are bad.In addition, in the present invention, " intestines " include " small intestine " and " big Intestines ".

Therefore, the composition for being used to improve gut function of the invention, which has, promotes digestion and the function of absorbing or intestines regulation Function, it can be used as, for example, " gut function improver ", " digestion and sorbefacient ", " antiflatulent ", " waste discharge promotes Agent ", and " improver is immunized in intestines ".

So-called intestines are immunized, and refer to the immune response occurred in enteron aisle.Immune response is also referred to as immunological response.Work as antigen (non-self) when entering live body, live body is produced with the antibody of antigentic specificity reaction or with specific immune function Lymphocyte (sensitized lymphocyte), and induce diversified biologically.Occur in response to the intrusion of antigen A series of biologicallies are referred to as immune response.

Because alimentary canal is the position of easy contact alien material, lymphocyte surrounds the enteron aisle centered on small intestine, And the virus of pathogen can be turned into food and be digested the foreign protein that enzyme is degraded and be ingested in alimentary canal.Enteron aisle is biology Body evolves come to suppress the important immuning tissue of these material absorbings at first.A low example of digestive tract function is intestines Dysimmunity.Intestines dysimmunity, which is meant, removes foreign matter (virus such as entered from the external world) (i.e. antigen), and caused by body Abnormal cell (such as cancer cell) (i.e. antigen), and the reduction of the immune response function of waste (i.e. antigen), it can increase enteron aisle The morbidity of the various diseases of middle generation, and postpone to cure.Improve the referred to as improvement intestines of these diseases as caused by intestines dysimmunity to exempt from Epidemic disease.

In addition, above-mentioned composition of the invention can be used for the Small Intestine of healthy individuals to improve, underfed advanced age The gut function of the patient (ICU patient) of severe dysfunction such as the nutrition improvement of person, breathing, circulation and metabolic system maintains, tool The nutrient and gut function for having the dysphagia patients of brain/neurological disorder maintain, for ulcerative colitis and Chron The gut function of the chronic intestines illness such as disease improves and nutritional status improves, for chronic obstructive pulmonary disease (COPD) and underfed Gut function improves and nutritional status improves, or the battalion due to intestines impaired patients such as cancer patient caused by antibiotic and anticancer Support condition improvement.

The present invention is provided to prevent the composition of small intestine's damage, it includes the protein from acidified milk.In addition, The present invention provides a kind of composition for being used to prevent that small intestine from damaging, and it includes milk protein hydrolysate and the egg from acidified milk White matter is as protein, grease as lipid and isomaltoketose as carbohydrate.

In addition, the present invention provides a kind of composition for being used to prevent that small intestine from damaging, it is hydrolyzed comprising lactoprotein Thing and protein from acidified milk are as protein and isomaltoketose as carbohydrate.

So-called small intestine's damage, refers to due to cancer, ulcer etc., or the antibiosis due to cancer patient occurring in enteron aisle The disorganization such as fine hair, mucous membrane muscularis propria caused by the intake of element, anticancer etc. and caused damage.This above-mentioned hair Bright composition is used to prevent such small intestine's damage.In this application, term " damage " (damage) is used broadly to Refer to " function plays insufficient ", " exterior injury ", and " being hurt ".

Above-mentioned composition of the invention has the effect of fine hair repairing accelerant and the effect of mucous membrane muscularis propria repairing accelerant, can For use as example, " the damage preventing agent of small intestine " " restoration accelerator of fine hair " and " the reparation rush of mucous membrane muscularis propria Enter agent ".

In addition, above-mentioned composition of the invention can be used for the chronic intestines illness such as ulcerative colitis and Crohn's disease Gut function improves and nutritional status improves, and the battalion due to intestines impaired patients such as cancer patient caused by antibiotic and anticancer Support condition improvement.

The present invention provides anti-inflammatory composition, and its protein comprising milk protein hydrolysate and from acidified milk is as albumen Matter, grease are as lipid and isomaltoketose as carbohydrate.

In addition, the present invention provides anti-inflammatory composition, it includes milk protein hydrolysate and the protein conduct from acidified milk Protein.

Present anti-inflammatory composition has antiinflammatory action for chronic gut diseases such as ulcerative colitis and Crohn's disease. So-called antiinflammatory action, refer to suppress inflammatory cytokine and produce and be related to monocyte and T cell is impregnated into tissue MCP-1 generation, so as to suppress the effect for continuing and being in progress of inflammation.MCP-1 is also known as monocyte chemotactic and activation factor (MCAF), it is found as a kind of monocyte chemotactic factor.For the activity for monocyte, it has been illustrated Chemotaxis can not only be strengthened, but also play the part of the role of the monocyte activation factor, such as enhancing antitumor activity and lyase The release of body enzyme and reactive oxygen species, and induction IL-1 and IL-6 generation.Except the activity of monocyte, MCP1 also has There are the activity of induction basophilic granulocyte release chemical mediator, and T cell chemotactic activity.In various kinds of cell in organism Find MCP-1 generation and secretion in the case where cellular inflammation cell factor and LPS are stimulated, these cells be typically monocyte/ Macrophage, fibroblast or vascular endothelial cell, in addition, observing MCP-1 composition in specific tumour cell Generation (be not other stimulating factors caused by).Based on achievement in research so far, MCP-1 is considered as take part in a variety of inflammatory diseases The tissue infiltration of monocyte and T cell in disease, such as artery sclerosis, delayed allergy, rheumatoid arthritis and tuberculosis Deng.

The anti-inflammatory composition of the present invention has the function that antiinflammatory action or mitigates tissue damage, can be used as, such as " anti-inflammatory Agent " and " tissue damage palliative ".

In addition, above-mentioned composition of the invention can be used for breathing, circulate and the trouble of the severe dysfunction such as metabolic system The gut function of person (ICU patient) maintains, and the nutrient and gut function with the dysphagia patients of brain/neurological disorder maintain, Gut function for the chronic intestines illness such as ulcerative colitis and Crohn's disease improves and nutritional status improves, for chronic resistance Plug property tuberculosis (COPD) and underfed gut function improve and nutritional status improves, or because antibiotic and anticancer cause Intestines impaired patients such as cancer patient nutritional status improve.

Active component contained in the above-mentioned various present compositions is summarized below.

Protein of the composition of the present invention comprising milk protein hydrolysate and from acidified milk is as protein.

The example of the milk protein hydrolysate of the present invention includes casein, milk protein concentrate (MPC, also known as total milk proteins =TMP), whey, whey protein, whey protein concentrate (WPC), whey protein sepd (WPI), α-lactalbumin (α-La), beta lactoglobulin (β-Lg) and hydrolysates of lactoferrin.

On the definition, classification and production method of lactoprotein, referring to Japan Food Science, in July, 1989, Pp.42-48 etc., or " Miruku Sogo Jiten (newborn class synthesis dictionary) ", on January 20th, 1992, Yamauchi K. and Yokoyama K. are compiled, and Asakura Shoten are published.

Casein is the main protein in cow's milk etc., is the phosphoprotein that a kind of covalent bond phosphoric acid.Contain junket in cow's milk Albumen about 3%, it is about 0.9% in human milk, and accounts for about 80% of protein in cow's milk.

Meanwhile whey is remaining water-soluble group afterwards such as removing fat, casein liposoluble vitamin from cow's milk Point.Whey refers generally to can conduct when producing natural cheese (natural cheese) or curd cheese (rennet casein) The whey (cheese whey) and curdling whey (rennet whey) (also known as sweet whey) that accessory substance obtains, or refer to from degreasing Newborn (skim milk) produces the casein whey obtained when acid casein (acid casein) or quark (quark) (casein whey) or quark whey (quark whey) (also known as yogurt is clear).The main component of whey is protein (α-milky white Albumen, beta lactoglobulin etc.), lactose, water soluble vitamin and salt (mineral component), respective feature be used as ox Illustrated in the research of the composition of composition of milk rather than whey.

Whey protein is the general name to the protein in such as cow's milk in addition to casein.Whey protein is by a variety of groups Divide and form, such as α-lactalbumin, beta lactoglobulin, lactoferrin, without including lactose, vitamin, mineral matter etc..When newborn source When being adjusted to acidity such as cow's milk, the protein being settled out is casein, and non-setting protein is whey protein.

The example of " whey association product " includes passing through condensed whey caused by condensed whey；By caused by drying whey Whey powder；By using the main protein of the condensed wheies such as ultrafiltration (UF) method, then it is dried and handles and caused whey Protein concentrates (hereinafter also referred to as " WPC ")；Fat is removed from whey by using micro-filtration (MF) method or centrifugal process, then The degreasing WPC (low fat, high protein) for being concentrated and being produced using UF methods and drying process；Pass through the major protein to whey Matter carries out ion-exchange-resin process or the processing of gel filtration selectively grading, then drying process and caused lactalbumin point (hereafter it is also known as " WPI ") from thing；Carry out desalting processing by using nanofiltration (NF) method and electroosmose process, then drying process and produce Raw desalted whey；With by the way that the mineral component from whey is carried out into precipitation process, then carried out by centrifugal process etc. dense Contracting is handled and caused mineral matter condensed whey.Among them, the breast containing the 15%-80% in terms of dry weight (solid content) The WPC of albumen changes the whey for being defined as protein compression on March 30th, 1998 according to the part of province's order on dairy products Powder, and it is categorized as dairy products (condensed whey, whey powder, WPC and whey protein concentration powder, as long as it have passed through on dairy products Province order specified in production stage, and it is unrelated with whetheing there is desalting steps)

In addition, as WPC is as WPI, it is caused by using MF methods or UF methods condensed skim milk and then drying process The content of lactose, salt contained by milk protein concentrate (being also abbreviated by below " MPC ") etc. reduces, and casein and whey protein Content relative raise.

Concentration can use common apparatus and method, such as such method can be used：Using cold boiler, Vacuum kettle, ascending manner film tubulose inspissator, descending manner film tubulose inspissator, plate inspissator etc. add under reduced pressure Heat.In addition, drying process can also use common apparatus and method, for example, can use spray drying process, drum dried method, Freeze-drying, vacuum (decompression) seasoning.

The standard method of production milk protein concentrate (MPC) is described as follows：

(1) the step of skimmed milk being subjected to UF membrane and then condensed skim milk；Or

(2) the step of skimmed milk being carried out UF membrane and then is concentrated and dried skimmed milk.

By using the main protein of the condensed wheies such as ultrafiltration (UF) method, then whey protein concentrate (WPC) is The material that processing is dried and obtains.Usually, it is the general name of such material：In wherein about 25% or more solid Tolerant is whey protein.They can be brought up to relative whey protein content by reducing the lactose plus salts in whey The about 25%-80% of solid content is obtained.Specifically, according to province's order on dairy products, by the 15%- containing dry weight The WPC of 80% lactoprotein is defined as the whey powder of protein compression.

The standard method of production whey protein concentrate (WPC) is described as follows：

(1) the step of whey being carried out UF membrane and then concentrated；Or

(2) whey is subjected to UF membrane and then the step for being concentrated and being dried.

Whey protein sepd (WPI) is that one kind can be by using ion-exchange-resin process or electroosmose process concentrated milk Clear main protein, the material for being then dried and obtaining.Usually, WPI is the general name of such material：Wherein solid About the 85% to 95% of content is whey protein.They can be by reducing the lactose in whey, salt etc. with will be relative Whey protein content brings up to about 90% (85%-95%) of solid content to obtain.

The standard method of production whey protein sepd (WPC) is described as follows：

(1) whey is subjected to UF membrane, ion exchange resin treatment or electrodialysis process, the step of then concentration； Or

(2) whey is subjected to UF membrane, ion exchange resin treatment or electrodialysis process, is then concentrated and dried The step of.

For the milk protein hydrolysate of the present invention, the enzyme for being normally used for hydrolyzed whey protein is such as stomach cardia Enzyme, trypsase and chymotrypsin.But also there is the albumen by the papain of plant origin and bacterium and originated from fungus Report that enzyme is used to studying (Food Technol., 48：68-71,1994；Trends Food Sci.Technol., 7：120- 125,1996；Food Proteins and Their Applications：Pp.443-472,1997).Whey protein hydrolyzes Enzymatic activity is widely different.α-the La and α-La that Pepsin degradation has been denatured, but the β-Lg (Neth.Milk that can not degrade natural Dairy J., 47：15-22,1993).Slow hydrolyzing alpha-the La of trypsase but it is difficult to degraded β-Lg (Neth.Milk dairy J., 45：225-240,1991).Chymotrypsin fast degradation α-La, but the β-Lg that degrade are slow.Papain hydrolysis ox blood Pure albumen (BSA) and β-Lg, but α-La show resistance (Int.Dairy Journal 6 to it：13-31,1996a).However, Under condition of acidic pH, be not associated with Ca α-La by papain it is degradable (J.Dairy Sci., 76：311-320, 1993)。

The albumen is modified by controlling the enzymatic degradation of lactoprotein, can be changed under wider pH range and treatment conditions Functional characteristic (the Enzyme and Chemical Modification of proteins in Food of the albumen Proteins and their Applications pp.393-423,1997 Marcel Dekker, Inc., New York, 1997；Food Technol., 48：68-71,1994).

The number and hydrophobicity of the hydrolysis increase charged group of peptide chain, reduce molecular weight, and change molecular configuration (J.Dairy Sci., 76：311-320,1993).The change of functional characteristic is largely dependent upon hydrolysis degree.Generally The maximum change of observed whey protein function is that dissolubility increase and viscosity reduce.Generally, it is higher in hydrolysis degree When, hydrolysate does not precipitate, under heating state and in this way, under 3.5-4.0 pH value condition high soluble.Water Solution thing also has the viscosity more much lower than whole protein.When protein concentration is high, this species diversity is especially apparent.Others effect Gelling characteristic change, heat endurance increase, emulsification and foaming abilities enhancing, emulsion and foam stability, which should be included, to be reduced (Int.Dairy journal, 6：13-31,1996a；Dairy Chemistry 4, pp.347-376,1989；J.Dairy Sci., 79：782-790,1996).

A variety of bioactive oligopeptides ((Yoshikawa, M, " New Horizon in for coming from lactoprotein are known Milk Science ", Yoshikawa, M.ed., pp.188-195, Kougaku Shuppan, 1998；Otani, H., " New Horizon in Milk Science ", Yoshikawa, M.ed., pp.97-99, Kougaku Shuppan, 1998；Otani, H., Milk Science, 47：183,1998；Trends in Food Science and Technology, 9：307-319, 1998).One such example is the peptide for having angiotensin converting enzyme (ACE) inhibitor activity (hypertension effect).

Have some on it is a variety of may have ACE inhibitory activity peptide report, these report be by vitro detection come Speculate (for example, J.Dairy Res., 67：53-64,2000；Br.J.Nutr., 84：S33-S37,2000).Also some adopt Purified with different chromatographic techniques and identify the ACE inhibitory peptides for coming from hydrolysate research report (for example, Maruyama, S., ＆ Suzuki, H., Agricultural and Biological Chemistry, 46：1393-1394, 1982；Miyoshi S.etal., Agri.Biol.Chem., 55：1313-1318,1991；Food Science and Biotechnology, 8：172-178,1999；Biosci.Biotech.Biochem., 57：922-925,1993).

According to these reports, it is believed that ACE inhibitory activity is present in be classified into using many obtained based on the separation of post In point.Therefore, the characterization of molecules of ACE inhibitory substances is diversified.In fact, find that ACE suppresses to be found in more hatching eggs White matter, protease and the caused hydrolysate under hydrolysising condition.The fact that prompt, have different aminoacids sequence it is a variety of Peptide may all have ACE inhibitory activity.Due to the Chemical Diversity of these peptides, it is often accompanied with using purification by chromatography hydrolysate The loss of a part of active peptide.In hydrolytic process, ACE inhibitory activity is constantly be generated and degraded.When both processes reach During optimization, the hydrolysate activity of maximum is obtained.ACE inhibitory activity is obtained by determining all hydrolysate peptide combinations, It depends on the specificity and treatment conditions of hydrolase.

There is a report to be related to serum protein hydrolysate optimization and (use surface respond methodology, response Surface methodology) so that ACE inhibitory activity maximizes and required hydrolysis is maintained at minimum degree (International Dairy Journal 12：813-820,2002).

The milk protein hydrolysate used in the present invention has caused work inside the TNF-α and IL-6 for suppressing LPS inductions With.Therefore, using depression effect caused by the TNF-α and/or IL-6 induced LPS as instruction, it may be referred to above-mentioned document Optimize condition (denaturation temperature, pH, temperature, hydrolysis time and enzyme/substrate ratio) (International of lactoprotein hydrolysis Dairy Journal 12：813-820,2002).

Except the document of above-mentioned reference, many patent (patent applications announced about milk protein hydrolysate also be present And patent).Example includes：It is related to casein and the hydrolysis respectively of whey protein, then Adsorption hydrophobic ingredient and then general The patent (JP 2,986,764) that casein and whey protein are mixed with designated ratio；With from bacillus and actinomyces Protease hydrolytic whey protein, then go to dezymotize and the patent of insoluble hydrolysate (JP 3,222,638)；On by The mol ratio of branched-chain amino acid/ArAA is 10% or higher, wherein ArAA caused by beta-Lactalbumin degraded Less than 2.0%, the mean molecule quantity of mixture is hundreds of patents (JP 3,183,945) for arriving thousands of peptide mixers；Relevant breast The patent (JP 2,794,305) of the selective enzymatic degraded of beta-Lactalbumin in albumin matter；Using from bacillus licheniformis (B.licheniformis) and/or bacillus subtilis (B.subtilis) protease, using non-constant pH (non-pH- Stat) technology hydrolyzed whey protein is to 15%~30% (glucose equivalent；DE), molecular cut off value is then obtained to be more than The patent (JP 3,167,723) of 10,000 milipore filter filtered solution.

Whether the hydrolysate described in above-mentioned document, patents and patent applicationss suppresses the life of the TNF-α and IL-6 of LPS inductions Production can determine (e.g., Experimental Medicine Supplementary Vol. " using known detecting system Bio Manual UP Experiment Series ", Cytokine Experiment Methods, Miyajima, A., Yamamoto, M.ed., Yodosha, (1997)).

Select five ginsengs of such as preheating, zymolyte ratio (E/S), pH, hydrolysis temperature and hydrolysis time as condition optimizing Number.

Preheating：65-90℃

E/S：0.01-0.2

pH：2-10

Hydrolysis temperature：30-65℃

Hydrolysis time：3 hours to less than 20 hours

The example of used enzyme includes following enzymes from Nova Nordisk：

1) endo protease

The protease in bacillus licheniformis source：Alcalase (registration mark)

The protease in bacillus lentus source：Esperase (registration mark)

The protease in bacillus subtilis source：Neutrase (registration mark)

The protease of bacterial origin：Protamex (registration mark)

Pig Pancreatic trypsin：PTN (registration mark)

2) exoproteinase

The protease in aspergillus oryzae source：Flavorzyme (registration mark)

Pig or the carboxypeptidase in ox internal organ source

The example of enzyme in addition to above-mentioned enzyme includes the pancreatinum (pancreastin), pepsin, plant of animal origin The papain in thing source, bromelain (bromeline), microorganism (e.g., lactobacillus, yeast, mould and branch bar Bacterium) source endo protease and exoproteinase and their crude purified thing and bacterial homogenates.In addition, combining With the Alcalase and the PTN (trypsase) in pig pancreas source enzyme group that bacillus licheniformis source is also commonly used during enzyme Close.

The method of reference example 1 described later is for preparing the method for serum protein hydrolysate example.

The milk protein hydrolysate used in the present invention includes：Itself suppresses caused by the TNF-α and/or IL-6 of LPS inductions Protease hydrolysate；Reservation liquid or permeate after ultrafiltration；And the commercialization milk protein hydrolysate of the similar activity of display.

The serum protein hydrolysate that can be used in the present invention includes following Examples.No. 3,183,945 public affairs of Japanese Patent Publication No. A kind of serum protein hydrolysate (mixture of the peptide of molecular weight 200~3,000) is opened, it is by using endopeptidase and outer Peptase hydrolyzes the whey protein sepd (WPI) of thermal denaturation, then utilizes the fragrance in ion exchange resin adsorption of hydrolyzation thing Amino acid and prepare.The Fischer ratios of the serum protein hydrolysate be 10 or more, branched-amino acid content be 15% or More, and fragrant amido acid content is less than 2%.

Japanese patent application discloses JP-A 6-50756 (corresponding to the unexamined Japan of the International Publication of non-Japanese Family's stage discloses) disclose the serum protein hydrolysate of odorlessness, slightly bitter taste a kind of.The hydrolysate is produced by below. 12% aqueous solution of the whey protein concentrate (WPC) that protein content is at least 65% is added in 60 DEG C or higher of temperature Heat, then using the Alcalase from bacillus licheniformis and the hydrolysis of the Neutrase from bacillus subtilis to 15%~ 35%DH.By the hydrolysate by ultrafiltration (UF) film of cutoff value higher than 10,000, and concentrated by nanofiltration (NF), then should NF retains solution spray drying.

It is not limited except as, the commercialization milk protein hydrolysate used in the present invention includes, for example, Peptigen IF- 3080th, Peptigen IF-3090, Peptigen IF-3091 and Lacprodan DI-3065 (Arla Foods), WE80BG (DMV)、Hyprol 3301、Hyprol 8361、Hyprol 8034(Kerry)、Tatua2016、HMP406(Tatua)、Whey Hydrolysate 7050 (Fonterra) and Biozate3 (Davisco).Prepare one of the method for protein hydrolysate Example is the serum protein hydrolysate preparation method for comprising the following steps (1)~(5)：

(1) will calculate to mix with water containing at least whey protein of 65% protein with dried object has up to produce The slurries of 20% protein content；

(2) it is heated to above 60 DEG C of temperature；

(3) using the protease that can be given birth to from bacillus licheniformis and/or producing bacillus subtilis, non-constant pH is passed through (non-pH-stat) method carries out proteolysis to the mixture from step (2) to 15%~35%DH；

(4) mixture point of step (3) will be come from ultrafiltration/microfiltration equipment with 10,000 or higher cutoff value From so that permeate forms protein hydrolysate；With

(5) stop hydrolyzing by the way that above-mentioned enzyme is deactivated.

Preferably, the slurries in above-mentioned steps (1) have 7%~12% protein content.

Preferably, the heat treatment in above-mentioned steps (2) is carried out between 70 DEG C~90 DEG C.

Preferably, untill the hydrolysis in above-mentioned steps (3) proceeds to 20%~30%DH.

Preferably, the cutoff value of above-mentioned ultrafiltration/microfiltration equipment is 50,000 or higher.

Preferably, it is the mixture obtained after above-mentioned step (3) or step (5) is (relative with relative quantity 1%~5% Calculated in dry-matter content) Temperature Treatment more than 5 minute of the activated carbon preferably between 50 DEG C~70 DEG C, then remove and live Property charcoal.

Preferably, after above-mentioned steps (5), product is passed through into nanofiltration/hyperfiltration (hyperfiltration)/reverse osmosis Thoroughly, and/or evaporate temperature preferably between 50 DEG C~70 DEG C and concentrated, then collect the material of reservation as protein water Solve thing solution.

Preferably, the protein hydrolysate solution from above-mentioned steps (5) is spray-dried to moisture and be less than 6.5%.

Therefore, the feature of the method for the generation serum protein hydrolysate is as follows：

(1) will calculate to mix with water containing at least whey protein of 65% protein with dried object has up to produce About 20%, or the slurries of preferably 12% protein content；

(2) it is heated to above 60 DEG C of temperature；

(3) using the protease that can be prepared from bacillus licheniformis, preferably Alcalase (registration mark), and/or can be from The protease of bacillus subtilis, preferably Neutrase (registration mark) are by non-constant pH methods to the mixing from step (2) Thing carries out proteolysis to 15%~35%DH；

(5) stop hydrolyzing by the way that above-mentioned enzyme is deactivated.

The amino acid composition of the serum protein hydrolysate (IF-3090) is as shown in table 1.

[table 1]

Milk protein hydrolysate can with the 0.1%~22% of whole composition, usually 4.1%~14.0%, be preferably 5.5%~10.0% amount mixture.Or 0.9g~3g, preferably 1.2g~2g can be mixed into 100mL compositions.

The composition of the protein from acidified milk used in the present invention includes, for example, by subtracting from acidified milk (yogurt) Few moisture and caused material (whey) (such as Japanese Patent 3,179,555).The ammonia of protein from acidified milk (yogurt) Base acid score (amino acid score) is 100, due to improving digestion and the absorbent properties of protein by fermentation, is had High nutritive value.

Or the example of the protein from acidified milk used in the present invention is including (uncooked from fresh cheese Cheese) protein.From the protein of fresh cheese be characterized in containing：As the casein of major protein component, bag Whey protein containing α-lactalbumin and beta lactoglobulin, and a part for wherein lactoprotein are degraded to amino acid or peptide Component.Have a many kinds of fresh cheeses, including cottage cheese (cottage cheese), quark cheese (quark cheese), Fibril cheese (string cheese), knob Chartres cheese (neuchatel cheese), buttercream (cream Cheese), horse Soviet Union's lira cheese (mozzarella cheese), Italian whey cheese (ricotta cheese), Yi Jiyi The big sharp soft cheese of milk (mascarpone cheese), in the present invention, it is preferred to use quark.The method for producing quark is ripe (e.g., Japanese Unexamined Patent Publication 6-228013).Quark has low-fat content, and characterized by its pure and fresh fragrance and tart flavour.

The general manufacture method of uncooked cheese is as described below.First, curdled milk (curd) is prepared from raw milk.By bottle opener (starter) it is inoculated into raw milk, after culture, further adds renin (rennet) to produce curdled milk.Producing Before curdled milk, it is necessary to when raw milk can be pre-processed.For example, in order to reduce the mass discrepancy between production batch, can be by mixed A variety of newborn sources are closed to adjust quality.Such processing is referred to as standardization (standardization).In addition, homogenization can be applied Handle mechanically to destroy the fatty globules in breast.Or can be by centrifuging and heat treatment is sterilized and is mixed into breast to remove Microorganism in source.

Uncooked cheese (fresh cheese) is referred to as by the solid constituent separated whey with the curdled milk of gained to obtain.It is logical It is known by the method that whey and curdled milk separate that centrifugation, which is crossed, with UF membrane.For example, the separation of whey uses centrifugation point From device, such as quark separator.Or it is initially switched off and heats in advance curdled milk when needed and can improve the efficiency of separation process.

More specifically, the milk fermentation component of the present invention can be used as by the fresh cheese that following sources and step obtain It is preferable.In following step, fermentation can mainly use lactobacillus bulgaricus (Lactobacillus ) and/or streptococcus thermophilus (Streptococcus thermophilus) bulgaricus：

Ox skimmed milk heat sterilization；

It is inoculated with 0.5%~5% into lactic acid bacteria bottle opener to start to ferment；

Whey is separated with the curdled milk formed when pH reaches 4.6；

Uncooked cheese will be obtained by curdled milk cooling obtained from sepg whey.

The uncooked cheese that can be produced by this mode is alternatively referred to as quark.One example of the composition of uncooked cheese It is as follows：

17%~19% total solid content,

11%~13% protein,

1% or less fat,

2%~8% carbohydrate,

2% or more lactose.

Protein from acidified milk can with such as the 0.1%~30% of total composition, generally 8.0%~ 23.0%th, preferably 10.0%~18.0% ratio mixing, or, 2g~6g can be mixed into 100mL compositions, preferably 2.5g~4.5g.Or the protein from acidified milk included in composition entirety of the invention could be arranged to composition About the 0.1%~90% of protein content, preferably approximately 1%~80%, more preferably from about 30%~70% in entirety.

The composition of the present invention includes grease as lipid.

The composition of the present invention preferably comprises n-3- type aliphatic acid as lipid.The n-3- included in the composition of the present invention The example of type aliphatic acid includes EPA, DHA, alpha-linolenic acid and DPA, preferably EPA, DHA and/or alpha-linolenic acid, more preferably EPA And/or DHA.The example of grease includes the grease containing n-3- type aliphatic acid, including perilla herb oil, linseed oil, weak seed oil (perilla oil), fish oil, rapeseed oil, soybean oil, salad oil and linseed oil (flax oil).In the present invention, these n-3- Type aliphatic acid can directly contain, or they can be contained in the form of grease such as fish oil.

In addition, the present invention composition preferably include medium chain triglyceride (medium-chain triglyceride, MCT) it is used as lipid.MCT is rapidly absorbed and is easily converted to energy in vivo, and using be not easy to be stored as in vivo fat as Feature.The example of grease containing MCT includes palm oil, palm-kernel oil and the grease containing medium chain fatty acid.In the present invention In, MCT can directly contain, or can be contained in the form of grease such as palm-kernel oil.

Therefore, composition of the invention includes protein comprising milk protein hydrolysate and from acidified milk as albumen Matter, medium chain triglyceride, EPA, and/or DHA are as lipid, and composition of the isomaltoketose as carbohydrate.

In addition, the composition of the present invention can contain aliphatic acid such as oleic acid, palmitic acid, palmitoleic acid, linoleic acid (linolic acid), stearic acid, leukotrienes or arachidonic acid, preferably oleic acid is as lipid.Oil containing these aliphatic acid The example of fat includes high oleic sunflower oil (high-oleic sunflower oil), rapeseed oil, olive oil, high oleic acid safflower Oily (high-oleic safflower oil), soybean oil, corn oil and palm oil, they are high oleic acid oil (which are high-oleic-acid oils).They can make as the mixture with sunflower oil, rapeseed oil, olive oil and olive oil With.Leukotrienes, arachidonic acid, gamma-Linolenic acid etc. are n-6- type aliphatic acid.The example of the grease of the aliphatic acid of type containing n-6- includes Safflower oil, sunflower oil, soybean oil, linseed oil, corn oil and peanut oil.

Ratio between n-3- types aliphatic acid and n-6- type aliphatic acid is, for example, for each n-3- type aliphatic acid, to have 5 or less, usually 0.5~4.0, preferably 1.0~4.0 n-6- type aliphatic acid, the more preferably ratio are n-3- type fat Fat acid: n-6- types aliphatic acid=1: 2.

N-3- types aliphatic acid can be with, for example, composition it is all 0.01%~10%, generally 0.05%~7%, it is excellent 0.1%~5% ratio is selected to mix.Or 0.05g~2.2g, preferably 0.1g~1.0g can be mixed into 100mL compositions.

MCT can be with, for example, composition it is all 0.01%~14.5%, generally 0.01%~8.0%, preferably 2.0%~4.0% ratio is mixed into.Or 0.01g~2.0g, preferably 0.5g~1.0g can be mixed into 100mL compositions.

Grease containing oleic acid can be with, for example, composition it is all 0.1%~14.5%, usually 2.0%~ 10.0%, preferably 4.0%~8.0% ratio is mixed into.Or 0.5g~2.0g can be mixed into 100mL compositions, preferably 1.0g~1.8g.

In addition, the composition of the present invention can contain newborn lecithin and soybean lecithin as lipid.

Newborn lecithin and soybean lecithin may be used singly or in combin.

Newborn lecithin includes sphingomyelins (SM), phosphatidyl choline (PC), phosphatidyl-ethanolamine (PE), phosphatidylinositols (PI), phosphatidylserine (PS) and lysophosphatidyl choline (LPC), and exist only in milk fat ball film (milk fat Globule membranes, MFGM) in.The composition of MFGM phospholipid moieties (Bulletin of Japan Dairy as shown in table 2 Technical Association, Vol.50：Pp.58-91,2000).

[table 2]

Phospholipid fraction	Weight %
		Sphingomyelins	22
Phosphatidyl choline	36
		Phosphatidyl-ethanolamine	27
Phosphatidylinositols	11
		Phosphatidylserine	4
Lysophosphatidyl choline	2

In such as field such as biochemistry, medical science and pharmacology, term " lecithin is only used for phosphatidyl choline.But Business or industrial circle, lecithin be used as phosphatidyl choline, phosphatidyl-ethanolamine, phosphatidylinositols, phosphatidic acid and other The general designation of the mixture of phosphatide.In the 7th edition (Japan ' s Specifications and of japanese food additive official compendium Standards for Food Additives ", 7th edition (1999)) in, lecithin is defined as " from oilseed Or the material that animal origin obtains, its principal component is phosphatide ".In the present invention, the phosphatide from breast is also referred to as " newborn ovum in the lump Phosphatide ".

As shown in table 2, newborn lecithin is characterised by including substantial amounts of SM, and SM is not contained in soybean lecithin.Newborn ovum Phosphatide more increases the DHA content in brain and liver when being applied to rat, than soybean lecithin.Moreover, soybean or ovum Yellow lecithin is compared, and newborn lecithin is more efficient for improving hyperlipidemia and fatty liver.Furthermore it is known that SM and cholesterol metabolic It is relevant, for example, the adjustable HMG-CoA reductase activity for participating in Biosynthesis of cholesterol of SM, and it is related to cholesterol in enteron aisle The regulation of absorption.Therefore, it is believed that SM may further enhance PC and PE improvement lipid-metabolism ability (Sasaki, H., Milk Science 51(2)：93-94,2002).

The example of material with high MFGM contents includes：Pass through ultrafiltration (UF) and the WPI of the combination manufacture of micro-filtration (MF) The freeze-drying thing of accessory substance (MF retains solution), the fraction removed from dilute cream or butter obtained by anhydrous milk fat (AMF) are (yellow It is oily clear, butter serum), and it is (newborn from fraction obtained from whey dilute cream (whey cream) removal anhydrous milk fat Thin cream is clear, whey cream serum).The method that phosphatide concentrate is obtained for using these as raw material is known (for example, Japanese Unexamined Patent Publication 7-173182 is included in the present invention).

Although soybean lecithin is widely used as natural additive for foodstuff in field of food, Polyene Phosphatidylcholine also by As medicine (application：It is used to improve liver function, fatty liver and hyperlipidemia in Chronic Liver illness).The physiology of soybean lecithin Learning the example of function includes the regulation of form and function of biomembrane；PFT, artery sclerosis, lipid-metabolism and liver lipid generation The improvement thanked；And nervous function improves (Food Processing and Ingredients, Vol.29 (3)： 18-21,1994).

" natural " lecithin products sort generally according to their PC contents.There are a variety of ovum upgraded according to its application Phosphatide has been produced.As shown in table 3, for convenience, by soybean lecithin product according to the purifying based on soybean lecithin, The principal component PC of classification difference is come (Fujikawa, T., the Oil Chemistry, Vol.40 (10) of classifying：951-958, 1991).

[table 3]

The composition of the present invention contains isomaltoketose (Palatinose (registration mark)) and is used as carbohydrate.Isomaltoketose It is the material registered with CAS registration numbers 13718-94-0, by chemical formula C₁₂H₂₂O₁₁Represent.

Isomaltoketose includes the isomaltoketose of reduction, Palatinose Syrup (registration mark) and isomaltoketose Starch syrup.Isomaltoketose starch syrup is a kind of liquid substance in starch syrup form, is dehydrated containing isomaltoketose Oligosaccharides caused by condensation such as four ficolls, six ficolls and eight ficolls etc. are used as main component.Isomaltoketose and sucrose Equally it is digested glucose and fructose and then is absorbed (Goda, T.et al., Journal of Japanese Society Of Nutrition and Food Science, Vol.36 (3)：169-173,1983).However, the water due to isomaltoketose It is slow to solve speed, is 1/5th (Tsuji, Y.et al., J.Nutr.Sci.Vitaminol., 32 of sucrose：93-100, 1986), after intake the blood level of glucose and insulin keep in a long time constant level (Kawai, K.et al., Endocrinol, Japan, 32 (6)：933-936,1985).

Isomaltoketose can be with, for example, composition it is all 10%~70%, generally 15%~60%, preferably 20%~35% ratio is mixed into.Or 4g~13g can be mixed into 100mL compositions, or preferably 5g~8g.

In order to promote the growth of intestinal villi, increase small intestine muscularis propria thickness, improve gut function, prevent small intestine from damaging Wound suppresses all kinds of inflammation, and the composition of the present invention is applied to subject, this be using the composition of the present invention purpose it One.

In the present invention, " subject " is not particularly limited, but including animal (such as people, livestock animals species, and wild Animal)." subject " not necessarily needs to be ill individual, for example, Healthy People can be used as apply the present composition by Examination person.

In the present invention, " administration " includes oral or parenteral administration, and the form of administration can be pharmaceuticals or diet product It is any.

That is, the composition of the present invention can be used with arbitrary form, as pharmaceutical composition, nutrient drug combine Thing, pharmaceuticals, medicament, dietary composition, diet product, alimentation composition, particular utility food, trophic function food, health food Any forms such as product, pharmaceuticals additive or food additives.For example, the composition of the present invention is also used as supplying nutrition equal Small Intestine that the healthy individuals of weighing apparatus use improve food, the nutrition improvement food of underfed People, breathing, circulation and The gut function of the patient (ICU patient) of the severe dysfunctions such as metabolic system maintains food, has swallowing for brain/neurological disorder tired The nutrient and gut function of difficult patient maintains food, the intestines for chronic gut diseases such as ulcerative colitis or Crohn's diseases Function improves and nutritional status improves food, the underfed gut function for chronic obstructive pulmonary disease (COPD) improves and battalion Condition improvement food is supported, or because the nutritional status of intestines impaired patients such as cancer patient caused by antibiotic and anticancer improves Food.

In addition, pharmaceutical composition, nutraceutical composition, pharmaceuticals and the medicament of the present invention can be by included in diet It is used in composition, diet product, alimentation composition, particular utility food, trophic function food, healthy food etc..Example Such as, pharmaceutical composition of the invention, nutraceutical composition, pharmaceuticals and medicament can also be included in for the balanced health of nutrition The Small Intestine that individual uses improves food, nutrition improvement food, breathing, circulation and the metabolic system of underfed People Gut function etc. the patient (ICU patient) of severe dysfunction maintains food, has the dysphagia patients of brain/neurological disorder Nutrient and gut function maintain food, the gut function for chronic gut diseases such as ulcerative colitis or Crohn's diseases to improve And nutritional status improves food, the underfed gut function for chronic obstructive pulmonary disease (COPD) improves and nutritional status changes Kind food, or add because the nutritional status of intestines impaired patients such as cancer patient caused by antibiotic and anticancer improve in food To utilize.

For example, subject is administered directly to by being used as pharmaceuticals, or it is for example specific for health care as particular utility food Food etc. or trophic function food directly absorb, it is expected to promote growth, the increase intrinsic flesh of small intestine of intestinal villi in subject Thickness degree, improve gut function, prevent small intestine from damaging or suppressing all kinds of inflammation.

When composition of the invention as pharmaceuticals in use, they can be applied with variform.The example of such form Attached bag is included by oral cavity route, by nasogastric tube or by jejunostomy under Ponsky method, Percutaneous endoscopic etc. Enteric nutrient, liquid preparation etc. are applied by enteral approach；And it may also refer to be processed into preparation such as tablet, capsule using form Agent, granule, pulvis and syrup.Every kind of preparation can conventionally use excipient, adhesive, disintegrant, lubrication The conventional known adjuvant in the pharmaceutical preparations technology such as agent, flavouring, solubilizer, suspending agent, coating agent, solvent, isotonic agent field Come together to be prepared with host.Furthermore, it is possible to include proper amount of calcium.Furthermore, it is possible to add proper amount of vitamin, mineral Matter, organic acid, sugar, amino acid, peptide etc..

When the present invention composition in the form of pharmaceuticals in use, it can be oral or enteral.For example, it may be selected Tablet, capsule, granule, pulvis, syrup etc., or nasogastric tube are orally administered, passes through Ponsky method or percutaneous Jejunostomy is enteral under scope；And age and the suitably selected application process of symptom of patient can be depended on. Effective dose selects from each scope applied per kg body weight 0.1mg to 1,500mg.Or each patient 5mg can be selected ~75g, or preferably 100mg~50g dosage.Preferable dosage and the specific example of application process are that every every dose of kg body weight is applied , to three times, applied before the meal or after the meal with 0.1mg~1,500mg, or preferably 2mg~1,000mg, daily one, last January (4 weeks). According to adjusting administration number of times using the trend of rear situation and the blood test value observed.

When composition of the invention as diet product in use, can be by the way that the composition is added into various drinks Taken in food, but regardless of its form (such as liquid, pasty state, solid-state and powdered).The example of diet product includes cow's milk, soft drink Material, acidified milk, yogurt, cheese, bread, biscuit (biscuits, crackers), pizza shell (pizza crust), modulate milk Powder, liquid food, patient are with food, nutraceutical, frozen food, food compositions, processed food, and other commercially available food. When composition of the invention as diet product quilt in use, they are preferably in the form of it can directly use.Under this form, institute Stating composition can be orally ingested, or be absorbed by pipe by nose into stomach and jejunum.Such composition can be taken more Kind form, for example, juice-type beverage or milk shake type beverage.The composition can also be the solubility that can be restored before use Powder.

The osmotic pressure of the composition may be about 300mOsm/L~1,000mOsm/L, for example, about 300mOsm/L~ 750mOsm/L.When in indoor temperature measurement, the viscosity of the composition is about 5cp~40cp (1cp=0.001Pas), excellent Choosing is less than 20.

The energy content of the composition is about 1kcal/ml~2kcal/ml, preferably 1kcal/ml~1.5kcal/ ml。

In addition, when composition of the invention as diet product in use, can be by being mixed with additional nutrient element to adjust Their trophic component.It is water, protein, carbohydrate, lipid, amino acid, dietary fiber, vitamin, mineral matter, organic acid, organic Alkali, fruit juice, flavouring, sweetener (such as Aspartame) may be used as the additional nutrient element in the present invention.

Furthermore, it is possible to 5mg~500mg (0.005%~0.5%) mushroom extract is added to reduce stool odor, and And in order to fortification can add the μ g (0.00001%~0.0002%) of 10 μ g~200 carotenoid prepared product (for example, α- Carrotene, beta carotene, lycopene (licopine) and lutein).

Further, it is also possible to it is used as antioxidant comprising catechol, polyphenol etc..

Furthermore, it is possible to comprising carnitine to improve lipid-metabolism etc..Carnitine is a kind of biological micro composition, in liver or kidney In produced from lysine and methionine.Its known generation level reduces with the age.Generation of the VBT in nutritional ingredient Thank, as long chain fatty acids to muscle cell delivering in play an important role.

In addition to above-mentioned isomaltoketose, carbohydrate includes other a variety of sugar.As the carbohydrate outside isomaltoketose, Use sucrose, glucose, fructose, honey etc..Other examples have dextrin and indigestible dextrins.

Dietary fiber can be divided into water-soluble dietary fiber and Water insoluble dietary fiber, and either of which person can make With.

As indigestible dietary fiber, indigestible oligosaccharides, lactulose, Lactitol (lactitol) can be used, Or gossypose.Indigestible oligosaccharides by with indigested state reach large intestine, promote the activation and growth of intestinal bifidobacteria, So as to play the function of improving intestines environment.Lactulose is a kind of disaccharide of synthesis, is made up of galactolipin and fructose, is used as high ammonia Essential drugs (Bircher, the J.et al., Lancet of mass formed by blood stasis (hyperammonemia)：890,1965).Chronic liver failure is made Into chronic recurrent hepatic encephalopathy to lactulose apply, hepatic failure with special acid (Fischer liquid) be transfused etc. response Well.Lactitol (beta galactose alcohol-sorbierite), should be regarded as second generation lactulose, have the clinical effect similar to lactulose With (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, O., et al., Dig.Dis.Sci., 34：823,1989), it is currently used as the therapeutic agent of hyperammonemia.

The candidate of other water-soluble dietary fibers includes improving the production of lipid-metabolism (reducing cholesterol and triglycerides) Product such as pectin (protopectin, pectinic acid, pectic acid), the product and tamarind seed glue (tamarind of the degraded of guar gum enzyme seed gum).Guar gum catabolite suppresses blood sugar level rise, saves insulin (Yamatoya, K.et al., Journal of Japanese Society of Nutrition and Food Science、Vol.46：199、1993).It is in addition, water-soluble The candidate of property dietary fiber includes, as high molecular weight water-soluble dietary fiber：Konjak glucomannan, alginic acid, low point Son amount alginic acid, psyllium (psyllium), Arabic gum, algal polysaccharides (cellulose, lichens sample material, agar, carragheen, Alginic acid, fucoidin (fucodine) and laminarin), glue (welan gum (welan gum), the gel as caused by microorganism Polysaccharide (curdlan), Xanthan gun (xanthan gum), gellan gum (gellan gum), dextran (dextran), side chain form sediment Powder (pullulan) and rhamsan gum (rhamsan gum)), other glue (be derived from the carob gum of seed, tamarind seed gum, he draws Glue (tara gum), karaya gum (karaya gum) and bassora gum (tragacanth gum) from resin)；As low Molecular weight water soluble dietary fiber：Polydextrose, indigestible dextrins, maltitol etc..

Volume of the non-digesting material of insoluble diedairy fiber increase in large intestine simultaneously reduces its passage time.This increase defecation Frequency and feces volume.The example of the candidate of insoluble diedairy fiber includes cellulose, hemicellulose, lignin, chitin, shell Glycan, soybean dietary fiber, wheat bran, pine tree fiber, zein fiber and beet fiber.

The example of vitamin include vitamin A, carrotene, vitamin B complex, vitamin C, vitamin D race, vitamin E, Vitamin K race, citrin, CoenzymeQ10, niacin (niacin), nicotinic acid (nicotinic acid), pantothenic acid, biotin, flesh Alcohol, choline and folic acid.

Known vitamin has 13 kinds.Among these, vitamin A, K and B groups (B₁、B₂, nicotinic acid, B₆, pantothenic acid, folic acid, B12 and biotin) known there is very deep relation with liver.The subject matter related to hepatopathy is the shortage and mistake of vitamin A It is surplus, the shortage of vitamin B complex, and the surplus of vitamin K.

When obstructive jaundice etc. causes bile deficiency in alimentary canal, vitamin A absorption rate declines, and causes vitamin A to lack It is weary.In addition, under the conditions of low nutrient protein, RBP ELISA (RBP) produces reduction.Therefore, vitamin A is not transported to Target organ, show to lack symptom.In the occasion of uncompensated hepatic sclerosis, during vitamin A relatively small amount surplus just occurs Toxication shape.In chronic liver disease, it is seen that the Use barriers of vitamin B complex.Because the vitamin K of enteric bacteria synthesis can also be by Utilize, vitamin K deficiency is not common.But when obstructive jaundice etc. causes bile deficiency in alimentary canal, vitamin K is inhaled Receipts may decline.

The example of mineral matter includes calcium, potassium, magnesium, sodium, copper, iron, manganese, zinc and selenium.The example of organic acid includes malic acid, lemon Lemon acid, lactic acid and tartaric acid.

Electrolyte often problematic is sodium, chlorine, potassium, phosphorus, calcium and magnesium in Humoral immunity.When preparation mineral matter prescription When, consider three factors：(1) whether the mineral matter that absorb in cell is sufficiently fed；(2) the endocrine ring of patient Whether border can fully deal with the amount and species of the nutrient matrix to be applied, and (3) to measure the osmotic load to kidney, with And in order to which whether the water for maintaining suitable osmotic pressure of urine and applying is sufficient.

It can also include the trace element of iron and natural origin, such as mineral yeast (mineral yeasts), such as Copper, zinc, selenium, manganese and chromium yeast.Copper gluconate, ZnG etc. can also be used.

The example of organic acid includes malic acid, citric acid, lactic acid and tartaric acid.

As such additional nutrient element, the material of any chemical synthesis or the component from natural products can be used. Or the food for containing component interested can be mixed into as raw material.These components can be by combining at least one, two Kind or more is planted to mix.The form of composition can be solid-state or liquid.In addition, gel or semi-solid shape can be made in it State.

The composition of the present invention can be produced by method known to liquid food and enteric nutrient field.For example, can be with Using by the sterile method being filled in container after the advance heat sterilization of the composition of liquid (for example, UHT sterilizations are used in combination With the method for aseptic packaging), and after fluid composition is filled into container, together with container heat sterilization method (such as Pressure sterilizer method (retort method) and autoclaving).More specifically, work as composition with liquid in use, will Homogeneous compound (homogeneity sterile solution) based on said composition is optionally again in about 120 DEG C~145 DEG C heat sterilizations 1 second To 10 seconds and cool down, then sterile filling, or be filled to progress pressure sterilizer sterilizing in can or soft bag.In addition, when combination Thing is with powdered in use, homogeneous compound to be for example spray-dried or be freeze-dried.

Below will to the detailed description of the invention, but should not be construed as being limited to hereafter described in individual embodiments.Work as tune During (addition/mixing) whey protein, it is reconciled while heating, for example, temperature (mediation temperature) setting of distiller liquor For 55 DEG C or lower.When reconcile temperature be set to such as 70 DEG C of high temperature when, protein setting (solidification), and ought mediation temperature be set to low temperature During such as 2 DEG C, protein is difficult to dissolve or disperse in water etc..Therefore, it is more excellent for mediation step, preferably 5 DEG C~55 DEG C of temperature Select 40 DEG C~55 DEG C, even more preferably 40 DEG C~53 DEG C, particularly preferred 40 DEG C~50 DEG C.Now, preferably considering that bacterium is (dirty Contaminate bacterium etc.) time is reconciled using suitable under conditions of propagation in distiller liquor.

In addition, in the present invention, by homogeneity after distiller liquor high temperature sterilization.Reason is the albumen under high-temperature sterilization (heating) Matter can variability, viscosity may increase (retrogradation), but by carrying out homogeneity after high-temperature sterilization, can reduce the journey of retrogradation Degree.Herein, homogeneity refers to after high-temperature sterilization after high-temperature sterilization, is filled in container etc. before product is made and carries out Homogeneity, its number carried out are not limited only to once, can be it is multiple, such as twice or more.For example, after distiller liquor sterilizes with When sterilizing again as former state, homogeneity will be carried out again after being sterilized at second.It is furthermore, it is possible to after sterilization that distiller liquor is homogeneous Change, and when further second of sterilizing of progress, homogeneity is carried out again in being taken turns after being sterilized at second second.In addition, Can also after sterilization by distiller liquor homogeneity, and can carry out homogeneity again and without sterilizing.More specifically, at this In invention, after distiller liquor high-temperature sterilization, be filled to product is made in container etc. before at least carry out a homogeneity be weight Want.

On the other hand, even in by the distiller liquor of high-temperature sterilization (sterilized solution) by homogeneity after, can also be by it again Sterilizing, to the degree for not causing sterilized solution retrogradation.For example, homogeneity after can distiller liquor be sterilized, then can be without height Temperature sterilizes and sterilized again.Now, as high-temperature sterilization step, for example, heating resume correspond to temperature 100 DEG C~150 DEG C and keeping temperature 1 second~30 seconds；It is preferred that 115 DEG C~145 DEG C 1 second~20 seconds；More preferably 120 DEG C~145 DEG C 1 second~10 seconds； Even more preferably 125 DEG C~145 DEG C 1 second~5 seconds.When carrying out high-temperature sterilization, protein denaturation, the viscosity of sterilized solution is easy Rise.In other words, sterilized solution will not easy retrogradation if not sterilizing at high temperature.Therefore, the reduction viscosity increase of homogeneity Acting on for degree is especially effective when carrying out high-temperature sterilization.

In addition, when carrying out high-temperature sterilization, the pressure (pressurization or decompression) on distiller liquor can be adjusted.Now, generally go out It is set as about 1kg/cm in prevent distiller liquor from seething with excitement the purpose of, such as by sterilization pressure²~10kg/cm².That is, at this In the high-temperature sterilization of invention, in addition to applying temperature (heating), such pressure can also be applied.Dress for high-temperature sterilization Put and add including plate-type exchanger, tubing heat exchanger, steam jet formula sterilizer, steam impregnated sterilizer, and joule Hot type sterilizer.On the other hand, when carrying out homogeneity, if using homogenizer, and such as temperature be arranged at about 10 DEG C~ 60 DEG C, flow velocity is arranged to about 100L/h~10,000L/h, and pressure is arranged to 10MPa~100MPa, preferably 20MPa~80MPa, More preferably 30MPa~70MPa, more preferably 20Mpa~50Mpa.In addition, if necessary, thus it is possible to vary operation such as high-temperature sterilization or The condition of homogeneity etc., is repeatedly handled.

Embodiment will be quoted below to illustrate the present invention, but the invention is not restricted to these embodiments.Reconciling in step, The warm water of aforementioned temperature is stirred in groove, be added sequentially, mix on the premise of mixing, scattered easiness is considered, stir except Raw material outside vitamin mixtures (vitamin component of mixing), produce distiller liquor.The convenient raw material for mixing, disperseing add Add the difference sequentially according to the amount and property of raw material, be separately added into disposably or in a different order them.For example, there is method It is that they are added with the order of sugar, protein, grease and mineral matter.Another example be with some sugar, protein, other sugar, The order of mineral matter and then grease adds them.In addition, another example is with grease, protein, sugar and then mineral matter Order adds them.The distiller liquor is subjected to steam jet formula heat sterilization, then using homogenizer homogeneity (by the two-stage plus Pressure homogeneity) to produce sterilized solution.Vitamin mixtures (vitamin component of mixing), flavouring are added into the sterilized solution (spices) etc. simultaneously mixes, to produce final sterilized solution.The final sterilized solution is further subjected to steam impregnated heat sterilization (sterilizing of two steps), then using homogenizer homogeneity (being pressurizeed homogeneity by the two-stage) to produce composition.

In order to promote the growth of intestinal villi, increase small intestine muscularis propria thickness, improve gut function, prevent small intestine from damaging Wound or the various inflammation for the treatment of, dosage are different because of symptom, body weight etc..For example, when applying (intake) as food or drink, agent Amount is usually daily about 0.05g~1,000g, preferably approximately 0.05g~250g, more preferably from about 2.5g~50g (solid contents Content).This can be suitably before meals, after meal or between meal, and/or once or is dividually administered to needs before going to bed and applies With the subject of the present composition.Dosage can be according to the age and body weight for applying purpose and the subject to be applied individually Suitable adjustment.In addition, the composition of the present invention can be used as substituting meals or complementary diets.

When the composition of the present invention is made into the form of acid pharmaceuticals or diet product, their pH can be set as pH 2.0~pH 6.0, preferably 3.0~pH of pH 5.0.

The purposes of above-mentioned composition of the invention can also be expressed as following (1)~(30)：

(1) a kind of method for being used to promote the growth of intestinal villi, it includes applying comprising milk protein hydrolysate and being derived from The protein of acidified milk as protein, grease as composition as carbohydrate of lipid and isomaltoketose the step of.

(2) a kind of method for being used to increase small intestine muscularis propria thickness, it is included using comprising milk protein hydrolysate and source From the protein of acidified milk as protein, grease as composition as carbohydrate of lipid and isomaltoketose the step of.

(3) a kind of method for being used to improve gut function, it is included using comprising milk protein hydrolysate and from acidified milk Protein is as protein, grease as lipid, and the step of composition of the isomaltoketose as carbohydrate.

(4) a kind of method for being used to prevent that small intestine from damaging, it is included using comprising milk protein hydrolysate and from hair The protein of kefir milk as protein, grease as composition as carbohydrate of lipid and isomaltoketose the step of.

(5) a kind of method for being used to suppress inflammation, it is included using the egg comprising milk protein hydrolysate and from acidified milk White matter as protein, grease as composition as carbohydrate of lipid and isomaltoketose the step of.

(6) comprising milk protein hydrolysate and protein from acidified milk as protein, grease as lipid and different wheat Bud ketose is used to promote the purposes in the composition of the growth of intestinal villi as the composition of carbohydrate in preparation.

(7) comprising milk protein hydrolysate and protein from acidified milk as protein, grease as lipid and different wheat Bud ketose is preparing the purposes in being used to increase the composition of small intestine muscularis propria thickness as the composition of carbohydrate.

(8) comprising milk protein hydrolysate and protein from acidified milk as protein, grease as lipid and different wheat Bud ketose is preparing the purposes in being used to improve the composition of gut function as the composition of carbohydrate.

(9) comprising milk protein hydrolysate and protein from acidified milk as protein, grease as lipid and different wheat Bud ketose is used to prevent the purposes in the composition of small intestine's damage as the composition of carbohydrate in preparation.

(10) it is used as lipid and different as protein, grease comprising milk protein hydrolysate and protein from acidified milk Composition purposes during preparing anti-inflammatory composition of the maltulose as carbohydrate.

(11) it is used as lipid and different as protein, grease comprising milk protein hydrolysate and protein from acidified milk Composition of the maltulose as carbohydrate, for for promoting to use in the method for the growth of intestinal villi.

(12) it is used as lipid and different as protein, grease comprising milk protein hydrolysate and protein from acidified milk Composition of the maltulose as carbohydrate, for being used in the method for increasing small intestine muscularis propria thickness.

(13) it is used as lipid and different as protein, grease comprising milk protein hydrolysate and protein from acidified milk Composition of the maltulose as carbohydrate, for being used in the method for improving gut function.

(14) it is used as lipid and different as protein, grease comprising milk protein hydrolysate and protein from acidified milk Composition of the maltulose as carbohydrate, for for preventing from using in the method for small intestine's damage.

(15) it is used as lipid and different as protein, grease comprising milk protein hydrolysate and protein from acidified milk Composition of the maltulose as carbohydrate, for being used in the method for suppressing inflammation.

(16) a kind of method for being used to improve gut function, it is included using the composition for including the protein from acidified milk The step of.

(17) a kind of method for being used to improve gut function, it is included using comprising milk protein hydrolysate and from acidified milk The step of protein is as composition as carbohydrate of protein and isomaltoketose.

(18) a kind of method for being used to prevent that small intestine from damaging, it is included using comprising the protein from acidified milk The step of composition.

(19) a kind of method for being used to prevent that small intestine from damaging, it is included using comprising milk protein hydrolysate and from hair The step of protein of kefir milk is as composition as carbohydrate of protein and isomaltoketose.

(20) a kind of method for being used to suppress inflammation, it is included using the egg comprising milk protein hydrolysate and from acidified milk The step of composition of the white matter as protein；

(21) protein from acidified milk is preparing the purposes in being used to improve the composition of gut function.

(22) milk protein hydrolysate and protein from acidified milk as protein and isomaltoketose as carbohydrate Preparing the purposes in being used to improve the composition of gut function.

(23) purposes of the protein from acidified milk in the composition for preventing small intestine's damage is prepared.

(24) milk protein hydrolysate and protein from acidified milk as protein and isomaltoketose as carbohydrate Purposes in the composition for preventing small intestine's damage is prepared.

(25) anti-inflammatory is being prepared as the composition of protein comprising milk protein hydrolysate and the protein from acidified milk Purposes in composition.

(26) composition of the protein from acidified milk is included, for for being used in the method for improving gut function.

(27) protein comprising milk protein hydrolysate and from acidified milk is as protein and isomaltoketose conduct The composition of carbohydrate, for being used in the method for improving gut function.

(28) composition of the protein from acidified milk is included, for for preventing from making in the method for small intestine's damage With.

(29) protein comprising milk protein hydrolysate and from acidified milk is as protein and isomaltoketose conduct The composition of carbohydrate, for for preventing from using in the method for small intestine's damage.

(30) milk protein hydrolysate and composition of the protein as protein from acidified milk are included, for for suppressing Used in the method for inflammation.

One example of the composition of the present invention includes MEIN (Meiji Dairies Corporation).Include MEIN The composition of composition can be expressed as including the composition of composition as described in Table 4.

[table 4]

On the lipid in table 4, newborn phosphatide (being also known as derived from the phosphatide of breast or newborn lecithin) is shown in table 5 below One example of composition.

[table 5]

Phosphatide

%

Phosphatidyl choline	24.2
		Phosphatidyl-ethanolamine	20.4
Sphingomyelins	17.1

In addition, on the lipid in table 4, table 6 below shows the example that aliphatic acid forms.

[table 6]

n-6∶n-3≈2∶1

*：Essential fatty acid

This specification states all references for being incorporated herein reference by carrying.

[embodiment 1]

Alimentation composition reduces the effect (1) of small intestine's damage

Using the composition of the present invention, and as the common liquid food (Meibalance for comparing control：Meiji Dairies Corporation), liquid food A (Impact：Ajinomoto Pharma Co.Ltd.) tested.Measure and apply The degree damaged with small intestine after ConA 24 hours.

Use the C57BL/6 mouse (6 week old, male) purchased from Japan SLC Inc..Mouse is raised under following environment： 21.0 ± 2.0 DEG C, 55.0 ± 15.0%, 12 hour (bright phase in bright-dark cycle of humidity：From the morning 7 up to afternoon 7 when).Whole The free feeding of animal and drinking-water are allowed in experimentation.

After the animal of purchase is tamed 1 week, it is divided into three groups according to their body weight.Experimental group is group 1：Common liquid food (Meiji Dairies Corporation：Meibalance)；Group 2：Alimentation composition (Meiji Dairies Corporation：MEIN)；Group 3：Liquid food A (Ajinomoto Pharma：Impact), letting animals feed 2 weeks.The common stream The composition of food, alimentation composition and liquid food A is as shown in table 7 and table 8.The isomaltoketose used in the embodiment is to be registered as CAS registration numbers 13718-94-0 material, with chemical formula C₁₂H₂₂O₁₁Represent.

[table 7]

Nutritional information table

[table 8]

Nutritional information table

ConA (Sigma) is intravenously applied by tail vein with 12mg/kg dosage.Using after 24 hours in etherization Under from abdominal aorta take blood, then extract small intestine.The small intestine of 6cm~3cm under stomach is consolidated in 10% formalin solution It is fixed, then embedded with conventional method.Prepare tissue sample and dyed with hematoxylin-eosin method.Utilize digital microscope (Keyence, Inc.) shoots the picture of tissue sample with 100 times of magnifying powers, and determines full muscularis propria and gluing including fine hair The area of liquid layer.As a result represented with average value ± SD (n=7~9).Statistical analysis is after carrying out unary variance analysis with SPSS, Examined using Scheffe, p ＜ 0.05 are defined as significantly.

As a result as depicted in figs. 1 and 2.The comparison of small intestine area shows the numerical value highest of alimentation composition intake group, and number Value reduces (Fig. 1) according to the order of common liquid food group and liquid food A intake groups.In alimentation composition intake group and liquid food A intake groups Between observe significant difference.In addition, the histology shown in Fig. 2 confirms that ConA administration causes skin lesion on mucous membrane of small intestine Wound or loss or muscle layer thickness decline equivalent damage.On the other hand, alimentation composition intake group shows almost normal histology (Fig. 2), the degree of such injury of small intestine can be reduced by as a result showing the intake of the alimentation composition.

[embodiment 2]

The effect (2) that alimentation composition damages to reducing small intestine

Tested, be have evaluated by using the alimentation composition of the present invention and as the Meibalance for comparing control Cell factor after Con A are applied 2 hours in small intestine produces, and ConA is using the degree of tissue damage after 24 hours.

After mouse is tamed 1 week, four groups are divided into according to its body weight.Experimental group is respectively with following diets 2 weeks：Group 1： Common liquid food (cut open inspection after ConA is applied 2 hours)；Group 2：Alimentation composition (cut open inspection after ConA is applied 2 hours)；Group 3：Common stream Food (cut open inspection after ConA is applied 24 hours)；Group 4：Alimentation composition (cut open inspection after ConA is applied 24 hours).Common liquid food used It is identical with being used in embodiment 1 with alimentation composition.

ConA (Sigma) is intravenously applied by tail vein with 12mg/kg dosage.Using behind 2 hours and 24 hours Blood is taken from abdominal aorta under etherization, then extracts liver, spleen, small intestine and large intestine.Measure small intestine total length, its 11cm~10cm weight and the large intestine 5cm under caecum weight under stomach.Also measure the weight of each organ.By 6cm under stomach ~3cm small intestine is fixed in 10% formalin solution, is then embedded with conventional method.Prepare tissue sample and use bush Essence-eosin method dyeing.The cell factor in the organ is prepared in following methods, and uses mouse anti-inflammatory agent box (Mouse Inflammation kit) (CBA methods：Japan Becton and Dickenson Co.) measurement.As a result with Unit organ weight The concentration of amount represents.As a result it is shown as average value ± SD.After carrying out unary variance analysis with SPSS, using StudentShi examine or Mann-Whitney, which is examined, carries out statistical analysis.

1. 1 milliliter of lysis buffer is added into 100mg organs, will using glass-teflon (registration mark) homogenizer It is homogenized

Lysis buffer

20mM Tris·HCl(pH 7.4)

0.25M sucrose

2mM EDTA·2Na

10mM EGTA

1%Tritonx-100

+ 1 Complete Mine protease inhibitor cocktails piece/10ml

2. by homogeneous homogenate 100,000g is centrifuged 40 minutes, collects supernatant (being operated while cooled on ice).

3. use the protein concentration in BCA Protein Assay Kits measure supernatant.In addition, using with blood plasma Cytokine class as method determine unit-protein matter cell factor amount.

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

As a result as shown in table 9~11.

Weight differences are not observed between each group.On the other hand, the weight of small intestine and large intestine dramatically increases.In addition, display intestines Length significantly longer (table 9).

Then, it is shown that the result (table 10) in measure blood plasma with cytokine concentrations in organ.Cell factor and chemotactic Factor TNF-α, IFN-γ, MCP-1 and IL-6 plasma concentration dramatically increase in common liquid food group, and in alimentation composition It is all significantly low in group.IL-12 and IL-10 concentration is below test limit.Cell factor produces at most in spleen in each organ, and The concentration of IFN-γ, MCP-1 and IL-6 is in notable low-level compared with common liquid food group in alimentation composition group.Seeking Support in composition group compared with common liquid food group, TNF-α (p=0.07), IFN-γ and MCP- show significantly low in liver Value.In small intestine, MCP-1 and IL-6 show significantly low value.Known ConA can cause significant hepatic injury, in alimentation composition The suppression of hepatic injury shows relate to caused by TNF-α to suppress in liver in group.Because the rising of the concentration of plasma IL -6 can not be used only IL-6 concentration illustrates in liver, and the yield in spleen may play contribution to the increase.It is scorching compared with other organs in small intestine The concentration of disease cell factor is low.However, because the MCP-1 in small intestine and IL-6 is compared to normal increase, and in alimentation composition Significantly low value is shown in group compared with common liquid food group, they may relate to the mitigation of damage.

In addition, small intestine's pathological tissue is assessed with following 0-3 ranks after being applied 24 hours as ConA As a result, it is shown in alimentation composition group the injury of small intestine compared with common liquid food group and has reduced (Mann-Whitney inspections, p =0.021) (table 11)

[table 9]

Organ weight and blood biochemistry checking result

Average value ± SD, n=5~7, StudentShi examine *：P ＜ 0.05

[table 10]

Blood plasma

IL-12 and IL-10 is less than test limit

Spleen

Liver

Small intestine

Average value ± SD *：P ＜ 0.1, * *：P ＜ 0.05, * * *：P ＜ 0.01

[table 11]

Mann-Whitney is examined

P=0.021

[embodiment 3]

Alimentation composition promotes the effect of mucodermis and muscle layer growth

Common liquid food or alimentation composition of the invention are freely absorbed after 2 weeks, have evaluated small intestine and large intestine and small intestine The weight of tissue.

After mouse is tamed 1 week, two groups will be divided into according to its body weight, every group of 5 mouse.Experimental group is：Group 1：Common stream Food；Group 2：Alimentation composition；By animal feeding two weeks.Common liquid food and alimentation composition used is as used in embodiment 1 It is identical.

Blood is taken from abdominal aorta under etherization, then extracts liver, spleen, small intestine and large intestine.Measure small intestine Total length, its 11cm~10cm under stomach weight and the large intestine 5cm under caecum weight.Also measure the weight of each organ Amount.The small intestine of 6cm~3cm under stomach is fixed in 10% formalin solution, then embedded with conventional method.Prepare tissue sample Product are simultaneously dyed with hematoxylin-eosin method.Tissue sample is carried out for serum alt, AST, albumin, gross protein, sweet Oily three esters, cholesterol, the biochemical analysis of glucose and urinary nitrogen.As a result represented with average value ± SD.A dimension deviation is carried out with SPSS After analysis, examined using StudentShi and carry out statistical analysis.

Table 12 shows that normal mouse absorbs common liquid food or alimentation composition blood biochemical test and organ weight after 2 weeks Result.In normal mouse, body weight and liver weight have no significant difference between each group.Compared with common liquid food group, nutrition group Compound group spleen relative weight and small intestine and large intestine weight show significantly high value.On the other hand, blood biochemical test result is shown All numerical value is between each group without significant difference.

Then, normal small intestine tissue sample is prepared for, measures fine hair number and height in single 150 times of magnification fields With muscularis propria thickness (Fig. 3 and table 13).Compared with common liquid food group, the number of fine hair and fine hair in alimentation composition group Overall length does not show significant difference, but average fluff length and muscularis propria thickness show significantly high value.In terms of these results, battalion Caused by the increase of small intestine weight seen in foster composition group is probably villus length and muscularis propria thickness.

[table 12]

Organ weight and biochemical analysis result

Average value ± SD, n=5, StudentShi examine *：P ＜ 0.05

[table 13]

Intestinal villi length and muscularis propria thickness (normal)

Average value ± SD, n=5 * *：P ＜ 0.01

[embodiment 4]

Alimentation composition is to improving intestinal permeability and suppressing the effect of bacterial translocation

The injury of small intestine rat model induced using Indomethacin, the alimentation composition of the present invention has been investigated to injury of small intestine Effect.

Use the SD rats (6 week old, male) purchased from Japan SLC Inc..They are raised under following environment： 21.0 ± 2.0 DEG C, 55.0 ± 15.0%, 12 hour (bright phase in bright-dark cycle of humidity：From the morning 7 up to afternoon 7 when).Whole The free feeding of animal and drinking-water are allowed in experimentation.

The animal bought is tamed one week, six groups are then divided into according to their body weight.Use common liquid food or nutrition Composition letting animals feed 2 weeks, then using Indomethacin.The common liquid food and alimentation composition used in embodiment 1 with using It is identical.Afterwards, 5%NaHCO will be dissolved in₃Indomethacin solution applied with 10mg/kg dose subcutaneous, once a day continuously Carry out two days, to induce injury of small intestine.Afterwards, with identical feed letting animals feed, the first day of administration is defined as the 0th, Carry out cut open inspection within 4th day and the 8th day.In the normal group of Indomethacin is not applied, in the time of the 4th day and the 8th day by half Animal cut open inspection.

In addition, at the 1st day, the 3rd day and the 7th day, 0.6% phenolsulfonphthalein parenteral solution is orally administered with 3mL/ bodies " DAIICHISANKYO " (Daiichi Sankyo Co.Ltd.), urine is collected after 24 hours, PSP excretions are horizontal in measure urine, As a result it is expressed as urinating PSP excretion rates.Generally, PSP is used for the indicant of renal function in human body.When orally administering PSP, into urine Excretion it is very low, but when being damaged due to goldbeater's skin when causing permeability to improve, PSP passes through intercellular space, into blood Liquid, then entered by kidney in urine.In the present embodiment, it is used as the indicant of goldbeater's skin permeability.

It is fasted at cut open inspection proxima luce (prox. luc) afternoon 5, cut open inspection is carried out after overnight fasting.It is thick that cardiac blood is collected under anaesthesia, Liver and lymphonodi mesenterici (MLN) are extracted under aseptic conditions.After measuring organ weight, solution caused by organ homogenate will be passed through On the BL Agar substrates added with 5% horse beaten blood under aerobic and oxygen free condition 37 DEG C incubate 72 hours, then Determine the number of bacterial cell.In addition, carried out the bacterium that Gram's staining is detected with investigating be gramnegative bacterium or Person is gram-positive bacterium.

Then the weight of the overall length of small intestine, caecum and large intestine, and the pH of caecum are determined.

In addition, general blood test is carried out using automatic hemacytometer (Sysmex ST-1800i).General blood inspection It is instruction for investigating the change of various pathological conditions to look into.The increase of neutrophil cell and monocyte is known to be by infecting Caused by (bacterium).

As a result 1

It was observed that the permeability of the result goldbeater's skin of the injury of small intestine induced as Indomethacin improves, but compared with control group It has been shown that, the intake of alimentation composition significantly suppress the raising (Fig. 4) of intestinal permeability.The above results show, alimentation composition Intake inhibit Indomethacin apply caused by injury of small intestine.

These results prompt the intake of the alimentation composition to prevent the small intestine as caused by non-steroid class antiinflammatory etc. Damage.

As a result 2

It is known that the injury of small intestine that Indomethacin induces causes the defence power of intestinal mucosa to be destroyed, and immunity suppresses etc., cause The enterobacteria for making normally be resident in the gastrointestinal tract is transferred to liver and lymphonodi mesenterici through epithelium of intestinal mucosa barrier.

Applied the 4th day and the 8th day in Indomethacin, take out all lymphonodi mesentericis and liver (part), and pass through training Count of bacteria in the method for supporting measure homogenate.From this experimental result, the 4th day applied in Indomethacin, lymphonodi mesenterici The individual for not detecting bacterium has 2 in common liquid food group in 9 animals, has 3 in 10 animals in alimentation composition group. All individuals have detected bacterium in liver.On 8th, lymphonodi mesenterici did not detected the individual of bacterium in common liquid food There is 1 in 8 animals in group, and there are 4 in 8 animals in alimentation composition group.In addition, common liquid food group and nutrient combination Bacterium is not detected in any animal's liver of both thing groups.Fig. 5 shows the knot of the count of bacteria actually detected in each organ Fruit.The 4th day applied in Indomethacin, the count of bacteria detected in lymphonodi mesenterici is in alimentation composition group and common liquid food It is not significantly different between group (picture is not shown).On the other hand, in liver, lower (p is tended in the counting of alimentation composition group =0.068) (Fig. 5, upper figure).Indomethacin apply the 8th day, do not observe to liver bacterial translocation (BT), but with it is general Through-flow food group is compared, and alimentation composition group significantly suppress the BT (p ＜ 0.05) (Fig. 5, figure below) to lymphonodi mesenterici.

In addition, the bacterium of detection is aerobic gram-positive bacterium.

Visible from the above, the intake of the alimentation composition inhibits the BT to lymphonodi mesenterici and liver.Also It is to say, it is shown that the intake of the alimentation composition inhibits the BT that injury of small intestine caused by Indomethacin administration induces.Prompting The intake of the alimentation composition may protect small intestine and prevent the injury of small intestine as caused by non-steroid antiinflammatory etc..

As a result 3

Carry out general blood test and apply front and rear change to investigate Indomethacin.General blood test is to be used to investigate The instruction of the change of various pathological conditions.The increase of neutrophil cell and monocyte is known to be to be caused by infecting (bacterium) 's.

The result of inspection, in normal individual, significant difference is had no between alimentation composition group and common liquid food group.It is another Aspect, compared with normal individual, find the white blood cell count(WBC) increase (Fig. 6) in Indomethacin administration group.The increase of leucocyte is (Fig. 6) caused by the increase of lymphocyte, neutrophil cell and monocyte.In common liquid food group, observed on 4th The increase of leucocyte, and further increase in leucocyte on the 7th.On the other hand, in alimentation composition group, the increase of leucocyte Reached peak value on 4th, afterwards Neuroleptic Leukocytopenia.In leucocyte, neutrophil count and monocyte count are found It is especially different between the two groups.Do not showed difference between two groups on 4th, but on 7th, in alimentation composition group with it is common Liquid food group is reduced compared to neutrophil count and monocyte count.

From the above, in alimentation composition group, the increase of neutrophil count and monocyte count may It is as bacterial translocation (the bacterial translocation caused by suppressing the injury of small intestine caused by non-steroid antiinflammatory induced by small intestinal damage due to the non-steroidal anti-inflammatory Agent result) and be inhibited.

[embodiment 5]

Serum protein hydrolysate, isomaltoketose, the albumen from acidified milk are removed from the composition of alimentation composition Change 1 during matter

The 6 week old male C57BL/6 mouse purchased from Japan SLC Inc. are used.By the mouse bought tame 1 week, so It is divided into 5 groups according to their body weight afterwards.

Packet is formed：

Group 1：Common liquid food (Meiji Dairies Corporation：Meibalance)；

Group 2：Alimentation composition (Meiji Dairies Corporation：MEIN)；

Group 3：Alimentation composition-serum protein hydrolysate (alimentation composition-P) from alimentation composition (by removing Serum protein hydrolysate and caused material)；

Group 4：Alimentation composition-serum protein hydrolysate-isomaltoketose (alimentation composition-P-I) is (by from nutrition Remove serum protein hydrolysate and isomaltoketose in composition and caused material)；With

Group 5：Alimentation composition-serum protein hydrolysate-isomaltoketose-quark (alimentation composition-P-I-Q) is (logical Cross and serum protein hydrolysate, isomaltoketose and quark and caused material are removed from alimentation composition).

Animal is divided into above-mentioned 5 groups and raised 2 weeks.To alimentation composition addition casein substitution quark and whey in preparation Protein hydrolysate adds dextrin and substitutes isomaltoketose as sugar source as protein source.

ConA (Sigma), next day, under etherization from abdomen are intravenously applied by tail vein with 12mg/kg dosage Sustainer takes blood, then extracts liver, spleen, caecum and small intestine.Measure small intestine center 10cm weight.

(ConA is using the body weight and per weight after 24 hours as shown in Fig. 7 and table 14 for body weight and the result of organ weight Organ weight).

[table 14]

Average value ± SD (n=8~10)

Body weight and relative to the liver of body weight and spleen weight between each group do not observe significant difference.In alimentation composition Caecum weight shows and dramatically increased compared with common liquid food group in group.Due to eliminating whey protein from alimentation composition The group of hydrolysate, isomaltoketose and quark caecum weight compared with alimentation composition group shows significantly lower value, shows These three materials are related to caecum fermentation.In alimentation composition group compared with common liquid food group small intestine weight show it is significantly higher Value.Due to eliminating the group and alimentation composition of serum protein hydrolysate, isomaltoketose and quark from alimentation composition Group shows significantly lower value compared to small intestine weight, shows that these three materials are related to damage and the inflammation of small intestine.

Three kinds of components：Serum protein hydrolysate, isomaltoketose and quark, the intestines that may relate to alimentation composition are protected Shield acts on and antiinflammatory action.

[embodiment 6]

Change when removing serum protein hydrolysate, isomaltoketose, protein from acidified milk from alimentation composition Change 2

The 6 week old male C57BL/6 mouse purchased from Japan SLC Inc. are used.By the mouse bought tame 1 week, so It is divided into 6 groups according to their body weight afterwards.

Group forms (common liquid food and alimentation composition are identical with being used in embodiment 6)：

Group 1：Common liquid food；

Group 2：Alimentation composition；

Group 3：Alimentation composition-serum protein hydrolysate (- P) (removes whey protein hydrolysis from alimentation composition Thing and caused material)；

Group 4：Alimentation composition-isomaltoketose (- I) (removes isomaltoketose and caused thing from alimentation composition Matter)；

Group 5：Alimentation composition-quark (- Q) (from alimentation composition remove quark and caused material)；With

Group 6：Alimentation composition-serum protein hydrolysate-isomaltoketose-quark (- P-I-Q) is (from alimentation composition Middle removal serum protein hydrolysate, isomaltoketose and quark and caused material).

Animal is divided into above-mentioned 6 groups and raised 2 weeks.Casein substitution quark and breast are added in alimentation composition in preparation Albumin matter hydrolysate adds dextrin and substitutes isomaltoketose as sugar source as protein source.

ConA (Sigma) is intravenously applied by tail vein with 12mg/kg dosage, after 2,4 and 8 hours from tail Venous blood collection, and in next day, take blood from abdominal aorta under etherization, then extract liver, spleen, caecum, small intestine and Large intestine.The ALT and AST in blood plasma are measured using Fuji DRI-CHEM.

As a result 1

Body weight and the result of organ weight when table 15 is shown last day.

[table 15]

Average value ± SD, Dunnett t inspection；*：P ＜ 0.05 (n=5~8)

Body weight and relative to body weight organ weight's (liver and spleen) between each group do not observe significant difference.With it is common Liquid food group is compared, and in alimentation composition group, 3 (- serum protein hydrolysates) of group and organizes 4 (- isomaltoketose) Small Intestines and blind The weight of intestines is in significantly high level.

As a result 2

AST and ALT results after ConA is applied 24 hours are shown in Fig. 8.Compared with alimentation composition group, whey remove only The group (group 3) of protein hydrolysate and it remove only the group (organizing 5) of quark and show AST and ALT increase.It is different remove only In the group of maltulose (group 4), AST and ALT are almost identical with alimentation composition group.In addition, removed when from alimentation composition When serum protein hydrolysate, isomaltoketose and quark (group 6), because ALT levels significantly become compared to alimentation composition group Height, the effect for showing to suppress hepatitis relate generally to serum protein hydrolysate and quark.

For the antiinflammatory action of the alimentation composition, serum protein hydrolysate and quark are probably main group Point.Show three kinds of groups including the quark as main component and serum protein hydrolysate and isomaltoketose The gut function that take part in alimentation composition is divided to maintain and enteron aisle protective effect.

The preparation of [reference example 1] serum protein hydrolysate

The whey protein sepd (WPI, Davisco) that will contain about 90% dried albumen is dissolved in distilled water and forms concentration For 8% (w/v) protein solution.85 DEG C of heat treatments of solution are made into protein denaturation in 2 minutes.The pH of solution after the heat treatment Value is about 7.5.Then add and enter water-filling relative to Alcalase (enzyme, Novozymes) 2.4L that concentration of substrate is 2.0% Solution, this mixture react 3 hours in 55 DEG C.Add relative to the pig source trypsase PTN 6.0S that concentration of substrate is 3.0% (Novozymes Japan), by this mixture, 55 DEG C are reacted 3 hours.6 hours complete hydrolysis used times.PH value when reaction is completed It is about 7.0.The serum protein hydrolysate (20,000X g, 10min) is centrifuged, the UF for being then 10,000 with classification molecular weight Film (Millipore, Ultrafree-MC) processing.

Permeate carries out reverse-phase HPLC chromatogram.

Condition

Sample：The UF permeate of serum protein hydrolysate

Pillar：C18 SG120(Shiseido)

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 gradients

Flow velocity：1mL/min

Detection：215nm (UV/ visible detections device)

Industrial applicability

The composition of the present invention shows the raising of gut function, such as promotes the growth of intestinal villi, and the intrinsic flesh of increase The thickness of layer.Therefore, they can be used for promoting the elderly of gut function decline, are caused due to administration of antibiotics or anticancer The patient of enteron aisle obstacle such as cancer patient and the patient due to nutritional support and gut function decline can not be received for a long time, such as The gut function of patient or postoperative patient in ICU.In addition, they can be used for intestinal villi growth and the intestines of Healthy People Function improves.

In addition, the composition of the present invention can be used for preventing small intestine from damaging.In addition, the composition of the present invention can be used as resisting Scorching agent, because they show antiinflammatory action.

Claims

1. the protein comprising milk protein hydrolysate and from acidified milk is as protein, grease as lipid and different malt Ketose is being prepared for the purposes in the composition for the weight for increasing small intestine as the composition of carbohydrate.

2. the purposes of claim 1, wherein the lactoprotein is selected from the group：Casein, milk protein concentrate (MPC), whey egg White matter, whey protein concentrate (WPC), whey protein sepd (WPI), α-lactalbumin, beta lactoglobulin and newborn iron Albumen.

3. the purposes of claim 1 or 2, wherein the protein source from acidified milk is in fresh cheese.

4. the purposes of claim 1 or 2, wherein the composition also promotes the growth of intestinal villi.

5. the purposes of claim 1 or 2, wherein the composition also increases the thickness of tunica muscularis intestini tenuis.

6. purposes of the protein from acidified milk in the composition for preparing the weight for being used for increasing small intestine.

7. milk protein hydrolysate and the protein from acidified milk are being prepared as protein and isomaltoketose as carbohydrate For the purposes in the composition for the weight for increasing small intestine.

8. the purposes of claim 7, wherein the lactoprotein is selected from the group：Casein, milk protein concentrate (MPC), whey egg White matter, whey protein concentrate (WPC), whey protein sepd (WPI), α-lactalbumin, beta lactoglobulin and newborn iron Albumen.

9. the purposes of any one of claim 6~8, wherein the protein source from acidified milk is in fresh cheese.

10. the purposes of claim 6 or 7, wherein the composition also promotes the growth of intestinal villi.

11. the purposes of claim 6 or 7, wherein the composition also increases the thickness of tunica muscularis intestini tenuis.