CN103596455B - The food composition of tube feed in art - Google Patents

The food composition of tube feed in art Download PDF

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Publication number
CN103596455B
CN103596455B CN201280027944.7A CN201280027944A CN103596455B CN 103596455 B CN103596455 B CN 103596455B CN 201280027944 A CN201280027944 A CN 201280027944A CN 103596455 B CN103596455 B CN 103596455B
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purposes
nutritional compositions
composition
liquid nutritional
fat
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CN103596455A (en
Inventor
Z·霍夫曼
M·克莱巴克
T·鲁贝尔斯
J·J·德哈恩
W·A·布尔曼
J·W·M·格雷夫
A·J·M·弗里瑟玛
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Nutricia NV
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/115—Fatty acids or derivatives thereof; Fats or oils
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/17—Amino acids, peptides or proteins
    • A23L33/175—Amino acids
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/17—Amino acids, peptides or proteins
    • A23L33/18—Peptides; Protein hydrolysates
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/17—Amino acids, peptides or proteins
    • A23L33/185—Vegetable proteins
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/17—Amino acids, peptides or proteins
    • A23L33/19—Dairy proteins
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/40—Complete food formulations for specific consumer groups or specific purposes, e.g. infant formula
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/02—Nutrients, e.g. vitamins, minerals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P41/00—Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Abstract

The present invention relates to a kind of liquid nutritional compositions comprising fat and protein material, operating patient acute inflammatory reaction during or after described operation is experienced for relaxing, weaken or preventing, wherein said fat provides at least 41En% of described composition total energy content, and described protein material provides at least 23En%, wherein said composition to be to give described patient by tube feed in art；Further relating to concrete liquid nutritional compositions, it is suitable for use as tube feed thing, is suitable for use in mitigation in particular, weakens or prevents patient at surgery intra-operative or acute inflammatory reaction afterwards.

Description

The food composition of tube feed in art
Technical field
The present invention relates to liquid nutritional compositions, and it is used for by tube feed rich in the proteinaceous liquid of lipid and richness Alimentation composition carries out being administered in art to relax, weaken or prevent the use of the acute inflammatory reaction during or after operation On the way.
Background technology
The health of mammal can be inflamed reaction in response to stressor.Stressor can be infectiousness or non-infectious Property source.The example of stressor is that local has invaded the microorganism (virus, bacterium, fungi or parasite) of tissue or non-endogenous Protein or peptide related substances, physical trauma (including operation), lose blood seriously, extracorporal circulatory system or soft tissue injury on a large scale With multiple fracture, ischemia/reperfusion event, or by burn, chemotherapy, radiate or be poisoned cause cell or tissue damage.? In inflammatory reaction, many factors play a role.Including acute phase protein, interleukins, prostaglandin, cell factor and white three The inflammatory mediator of alkenes causes the response of predetermined quantity in health, to obtain suitable metabolism and host defense (that is, stream CBF, repair process and the struggle of unwanted Exterior component and the apoptosis of endogenous cell to affected tissue), in order to Obtain suitable host defense, especially in order to quickly and efficiently to neutralize stressor, it is achieved quickly wound healing, in advance Prevent the tissue damage caused by ischemic/ischemia-reperfusion process or chemotherapy or radiotherapy and realize the quick reparation of function of organization.
Although having diagnosis and the progress for the treatment of in health care, but the systemic inflammatory reaction of imbalance remaining surgery Major complications in operation, wound and Cavity in Critical Patients, it is relevant with M & M increase.To early stage excessive inflammation The regulation of reaction provides a kind of potential therapeutic choice improving result.It is intended to suppress single rush although experimental study demonstrates The intervention of scorching medium has gratifying result, but clinical implementation is the most successful.
Increase the understanding on nosopathology and the extensive new therapeutic modality affecting inflammatory reaction of exploitation may insure that reduction M & M.
Carry out operating patient mostly in surgery operation consent fasting to prevent rejecting and by mistake of possible gastric content Inhale.It addition, patient often runs into serious problem in surgical site infections and then a period of time in terms of correct feed.Statistics Data show, many patients being in hospital suffer from complication.These complication are different, have wound healing delay, swelling and pain Bitterly, stress organize that functional rehabilitation is bad, local infection, and the most possibly even cause systemic complications, example Such as the septicemia can aggravated because nutrition intake reduces and multiple organ dysfunction.
Recently, it was demonstrated that giving nutrients at surgery operation consent or surgical site infections enteral earlier can improve operation Patient and the immunocompetence of Cavity in Critical Patients and clinical effectiveness (bibliography 8-10).
For suffering from the patient of serious burn, it is known that carry out intestines at patients during surgery and raise (bibliography 48- 49).But, carry out described intestines raise be not intended to relax, weaken or prevent operation during or after acute inflammation anti- Should, but in order to meet their significant nutritional need, reduce heat runs short, because such patient can not otherwise enter Food.Additionally, operation is confined to operation on skin, i.e. Noninvasive is performed the operation.
Therefore, till now, the most do not proposed at surgery intra-operative, i.e. in operation, feeding routinely Patient with relax, weaken or prevent operation during or after acute inflammatory reaction and which kind of alimentation composition can be the suitableeest Close for the purpose.
Summary of the invention
It is an object of the invention to provide a kind of liquid nutritional compositions, it is for giving rich in lipid by enteral in art Delay with the liquid nutritional compositions (more specifically by tube feed in art, especially by tube feed in continuous print art) of protein With, weaken or prevent patient's acute inflammation response during or after operation (preferably invasive operation), described Patient has and suffers from the risk of the complication caused by described stressor or suffered from described complication.It is also an object that carry The acute inflammation relaxing, weaken or preventing patient during or after operation (preferably invasive operation) it is used for for one The method of disease reaction, described method is to give the liquid nutritional compositions rich in lipid and protein (more by enteral in art Specifically by tube feed in art, especially by tube feed in continuous print art) carry out, described patient has and suffers from by described stressor The risk of the complication caused or suffered from described complication.Giving of described enteric nutrient actually can be by having used The intestines known are raised device (especially pipe) and are implemented, and especially prevent at stressor duration of existence or afterwards and subsequently with soon The inflammatory reaction that (mistake) is strong or lacks of proper care is formed during or after the agglutination that the speed mode of action is carried out.When described inflammatory reaction When having been started up, it prevents described inflammatory reaction from further enhancing (so-called excessive inflammation).By excessive inflammatory response Reduce to strengthen with post-operative recovery and associate.
Therefore, the problem to be solved in the present invention is to provide one can quickly avoid short-term inflammatory effect, especially with outward The liquid nutritional compositions of section's medical intervention (preferably invasive surgical is intervened) short-term inflammatory effect together.Outside invasive Section's medical intervention is can to penetrate or destroy skin or enter the intervention of body cavity.The example of store period include relating to perforation, Otch, conduit insert or other those entering health operate.Concrete invasive surgical intervention is cutting skin and group Knit so that surgeon can directly contact the open operation (open surgery) about structure or organ.Can see that and Touching relevant structure and tissue, they are directly exposed to the air of operating room.The example of open operation includes that organ is (such as Gall-bladder or kidney) remove, and most types of cardiac surgery operation and neurosurgery.Open operation relates to big cutting Mouthful, wherein said tissue is exposed to air.
The liquid nutritional compositions by offer with significant quantities of fat and a large amount of protein solves described problem.Without being bound by Theory, the vagus reflex mediated by CCK (CCK) rich in the nutrients of lipid and be of value to and weaken or prevent Acute inflammatory reaction and organ damage.It is also believed that the vagus reflex that mediated by CCK (CCK) of protein and have Benefit and weaken or prevent acute inflammatory reaction and organ damage.Fat provides fast and high CCK response, and protein provides relatively Low but more longlasting CCK release.It is surprising that two kinds of responses together provide the vagus nerve to CCK mediation The optimal mediation of reflection.It addition, substantial amounts of protein makes decomposition of protein qualitative response minimum especially by (i), (ii) maintains enteron aisle Function and intestinal immunity, and (iii) support acute phase protein synthesis and be Rehabilitation provide necessity amino acid (especially It is glutamine).
In the context of this application, it should be appreciated that in art, feeding is the main application fields of the present invention.In relevant existing skill In art, find that wording " peri-operation period (peri-operative) " and/or " intra-operative (peroperative) " feeding is frequent Represent and include that preoperative (i.e. before operation) and/or postoperative (i.e. after operation) feeding get rid of the feeding of feeding in art Scheme.In the context of this application, it should be appreciated that term " feeding in art " refers to perioperative feeding scheme rather than refers to Preoperative or postoperative feeding.But, the liquid nutritional compositions of the present invention could be applicable to preoperative and postoperative feeding.It is true that can Before surgical procedures (phase the most in the preoperative), start intestines and raise, it is possible to be (the most postoperative after lasting till surgical procedures Phase).Therefore, the liquid nutritional compositions that the invention still further relates to the present invention uses for peri-operation period.
In the context of the present invention, the percentage of described composition gross energy is referred to as En%, and is used for representing and can disappear The energy value (especially in people or other mammals) of the compound (fat, protein, carbohydrate, fiber) changed.Tool Body ground, described energy value is based on protein material (including protein, peptide and amino acid), lipid or fat and can to digest carbon water The contribution of compound, the conversion factor used (the Atwater factor) is as follows: digestible carbohydrate and protein material are 4kcal/g, lipid are 9kcal/g and digestible fiber is 2kcal/g.
Prior art background
It is used for treating and/or prevent septicemia or for resisting inflammatory from higher fatty acid enteral composition known in the art The beneficial effect of illness.But, high protein content combines the beneficial effect of high fat content and is not disclosed, the group of the present invention Compound is not the most disclosed.
EP1411951B1 (NV Nutricia) discloses one containing fat fraction, protein moieties and can digest carbon water The composition of compound fraction for treatment and/or prevention with big operation, critical illness, inflammatory bowel disease etc. relevant by bacterium Septicemia, endotoxemia and/or the bacteremic purposes caused, it is 3-90: 3-80: 1 that described fat fraction comprises weight ratio Phosphatide, triglycerides and cholesterol.
EP1589834B1 (NV Nutricia) similarly discloses one and containing fat fraction, protein moieties and can disappear The composition changing carbohydrate fraction is used for treating the purposes of septicemia and associated conditions, and described fat fraction comprises weight ratio Phosphatide more than 1 and triglycerides and the cholesterol less than 0.5 weight %.The useful work of high protein content is not the most disclosed With, the composition of the present invention is not the most disclosed.
US5,968,896 (Beth Israel Deaconess Medical Center) discloses one and feeds for preoperative The solid of food or semi-solid nutritious supplementary pharmaceutical, it comprises the fat of 26-46En%, the protein of 20-40En% and 25-45En% Digestible carbohydrate, for being ready for the individuality of critical surgery large operation, the non-baking of preferably from about 200kcal Extrusion type nutrition bar (a).
EP1041896B1 (NV Nutricia) discloses as enteral food for treating chronic inflammatory disease, lipid generation Thank to obstacle and the composition containing fat blend that immunologic function dies down, described fat blend contain [γ]-leukotrienes, ten Eight carbon tetraenoic acids and eicosapentaenoic acid (2: 1: 2) and phosphatide.
EP1090636 (INRA) discloses a kind of composition for treating septicemia or inflammatory shock, and it comprises and is more than The lipid of 35En%.Described lipid fraction comprises the miglyol 812 of 25-70 weight %.Saturated in addition to MCT less than 15 weight % Aliphatic acid and n-6/n-3 ratio are about 2-7: 1.
The nutrient formulation thing of the claimed a kind of people for suffering from GI of EP0265772 (Abbott), It comprises the fat of 45-60En%, the digestible carbohydrate of 20-37En% and the protein of 8-25En%.Disclosed Example is confined to the high fat compositions of the protein containing at most 20En%.
EP0691079 (Clintec) claims a kind of nutrient formulation thing for diabetic, and it comprises 30- The digestible carbohydrate of the fat of 45En%, at most 50En% and the protein of 8-25En%.Disclosed example limitation Composition in the protein containing 18En%.
The claimed a kind of patient suffering from respiratory insufficiency for treatment of EP0189160 (Abbott) higher fatty acid, The enteral nutritional composition of low-carb, it comprises the digested carbon hydrate of the fat of 45-60En%, at most 30En% Thing and the protein of 8-25En%.Example discloses a kind of fat, the protein of 19En% and 26En%'s comprising 55En% The composition of carbohydrate.
The claimed one of EP0611568 (Fresenius), for cancer patient, is suitable as the nutrient combination of tube feed thing Thing, it comprises the fat of 40 to 65En%, the digestible carbohydrate of 20 to 45En% and the protein of 12 to 25En%.Institute Example is had to disclose the composition of the protein with at most 20En%.
US7,691,906 (Nestec S.A.) disclose one and give optionally by tube feed, lose for treatment or prevention Mass formed by blood stasis or the enteral composition of inflammatory shock, (described fat comprises at least 40 to 70 weights to its fat comprising at least 35En% The MCT of amount %), the protein of 10 to 25En% and the carbohydrate of 12 to 55En%.
Detailed description of the invention
The present invention relates to containing significant quantities of fat and the liquid nutritional compositions of a large amount of protein material, and relate to it for delaying With, weaken or prevent experience operating patient acute inflammatory reaction during or after described operation purposes, Wherein said composition is to give described patient by tube feed in art.This setting requires that the wink of described feeding i.e. acts on, Qi Zhongsuo The effect stating feeding is to weaken inflammatory reaction.I.e. reacting in described wink weakens in 30 minutes described in meaning, preferably at 15 points Start in clock, and continue some hours after intervening stopping, the most persistently 1-3 hour.
According to an embodiment, the present invention relates to a kind of liquid nutritional compositions comprising fat and protein material, Operating patient acute inflammatory reaction during or after described operation is experienced for relaxing, weaken or preventing, Wherein said fat provides at least 41En% of described composition total energy content, and described protein material provides described composition At least 23En% of total energy content, wherein said composition is to give described patient by tube feed in art.
According to another embodiment, the present invention relates to one and comprise fat, protein material and carbon hydrate can be digested The liquid nutritional compositions of thing, wherein said fat provides at least 41En% of described composition total energy content, described albumen Metallic substance provides at least 23En%, and described digestible carbohydrate provides at most 36En%, optionally, every 100ml institute State composition and also comprise at least 1.5 grams, more preferably at least 1.7 grams Glus (in conjunction with and/or free), further relate to it and make For tube feed thing in particular for relaxing, weaken or prevent patient in surgery intra-operative or the use of acute inflammatory reaction afterwards On the way.
Protein material
The liquid nutritional compositions of the present invention comprises the source of at least one protein material.
The liquid nutritional compositions of the present invention comprises, in terms of described composition total energy content, and the albumen of at least 23En% The protein material of metallic substance, preferably 23En%-59En%, more preferably 23En%-45%, most preferably 23En%-40En%.
Protein material used herein is defined as protein, peptide and amino acid.Therefore, fluid present invention nutrient combination Protein material in thing is all eggs being present in the liquid nutritional compositions of the present invention with free or any combining form White matter, peptide and amino acid whose summation.
In one embodiment, described protein material comprises and accounts for protein material total amount present in described composition The whole protein of 20-80 weight %, more preferably 30-60 weight %, most preferably 35-50 weight %.
In a preferred embodiment, described composition comprises total less than protein material present in described composition The free amino acid of 40 weight % of amount, preferably 10-30 weight %.
According to an embodiment, described protein material comprises source and the lactoprotein pledge of vegetal protein substance The source of matter.Preferably, described protein material comprises the vegetal protein substance of 20-80 weight % and 20-80 weight % Lactoprotein metallic substance.
In the context of this application, wording " plant " refers to the protein material from plant origin, such as, is derived from Plant such as carrot, pea, chick-pea, green soya bean, Kidney bean, Lupinus albus, paddy rice, soybean, rape, hemp, zeins (zein), corn (maize), cereal (corn), barley, flax, linseed and wheat.The wording of equivalent can be used, such as, " plant Physical property ", " pulse family " or " being derived from plant ".
In the context of this application, wording " breast class " protein material refers to be derived from the protein material of breast, i.e. come From the protein material of animal breast, such as, it is derived from species such as camel, ox, goat, horse, people, reinder, sheep, buffalo and yak Ox.
According to another embodiment, described protein material comprises the protein of hydrolysis, such as, soybean, casein, breast Clear or the hydrolysate of wheat gluten, and/or a combination thereof, preferably at least comprise wheat gluten.In one embodiment, described The albumen of hydrolysis is to be obtained by zymyhydrolyzed protein matter such as wheat gluten.The suitably example of protein can be PeptamenFinding in (Nestl é), it is enteral pipe nutrients based on 100% whey peptides, it can be ensured that optimal absorption and Preferably protein utilization.
Preferably, any one during described protein material comprises casein, whey, soybean, pea and aleuronat Plant or multiple.According to an embodiment, the liquid nutritional compositions of the present invention preferably comprises described casein, whey, soybean With one or more in aleuronat, its every kind single amount is liquid nutritional group described in 0.1-10 gram of protein/100ml Compound, liquid nutritional compositions described in more preferably 1-10 gram/100ml, more preferably 2,3,4,5,6,7,8 or 9 grams of protein materials/ Liquid nutritional compositions described in 100ml, or be the arbitrary integer in the middle of described scope and non-integer mark.
According to a preferred embodiment, the liquid nutritional compositions of the present invention comprises casein and wheat gluten, its Every kind of single amount is liquid nutritional compositions described in 0.1-10 gram of protein/100ml, liquid described in more preferably 1-10 gram/100ml Body alimentation composition, liquid nutritional compositions described in more preferably 2,3,4,5,6,7,8 or 9 grams of protein material/100ml, or For the arbitrary integer in the middle of described scope and non-integer mark.
According to a preferred embodiment, the liquid nutritional compositions of the present invention comprises, with described protein material Gross weight meter, the casein of 30-50 weight % and the wheat gluten of 30-50 weight %.It is highly preferred that described casein: wheat The weight ratio of albumen is about 1.
According to a preferred embodiment, the liquid nutritional compositions of the present invention comprises the casein of 2-4 gram and 2-4 gram Wheat gluten/100ml described in liquid nutritional compositions.
According to an embodiment, Glu that described protein material comprises (in conjunction with and/or free) Amount exceedes naturally occurring amount in complete vegetalitas or lactoprotein matter.Preferably, the amount of described Glu is at least 20 grams, more preferably at least 25 grams/100 grams gross protein materials.Glu (being called for short Gln or Q) is by standard genetic code One of 20 kinds of amino acid of coding.It is not qualified as essential amino acid, but (includes strong athletic training in some situation Or some disorder of gastrointestinal tract) in it can become conditionally essential amino acid.Its side chain is by replacing L-paddy ammonia with amine functional group The acid amides (amide) that the pendant hydroxyl group of acid is formed.Therefore, it can be considered as the acid amides (amide) of Pidolidone.Term " paddy Glutamine " or " Glu " also comprise glutamine equivalents, it is for can be converted into Glu in health Compound, such as Glu dipeptides or 2-acyl amino glutaryl amine.In a preferred embodiment, described Composition comprises Glu dipeptides, or the dipeptides containing Glu, such as, also comprises L-alanyl or ALANINE, Preferably, its amount in the compositions of the present invention is the 10-40 weight of protein material total amount present in described composition Amount %, preferably 15-30 weight %, more preferably from about 20 weight %.Illustrating, (L-) glutamic acid is excluded at glutamine herein Definition outside.
Preferably, the liquid nutritional compositions of the present invention comprises at least 1.5 grams, the L-glutamy of more preferably at least 1.7 grams Amine (in conjunction with and/or free) the total liquid nutritional compositions of/100ml.Preferably, the liquid nutritional compositions of the present invention comprises 1.5 grams-5 grams, more preferably 1.7 grams-4 grams, the Glu of most preferably 1.9 grams-3 grams (in conjunction with and/or free)/ The total liquid nutritional compositions of 100ml.
According to the present invention, the amount of required Glu can not be independent by complete phytoprotein or lactoprotein matter There is provided, the source rich in Glu should be there is.Preferably, little selected from rich in Glu of the source of Glu Aleuronat matter, free amino acid Glu and the dipeptides containing Glu, such as Ala-Gln. Preferably, described Ala-Gln dipeptides is to produce with synthetic method.Preferably, use described dipeptides, because trip Isolated amino acid is unstable in sterilization process.
Fat
The liquid nutritional compositions of the present invention comprises the source of at least one fat.The total amount of the energy provided by fat should It is at least about liquid nutritional combination described in 41En%, at least about 42En%, at least about 43En% or at least about 44En%/100ml Thing.
According to another embodiment, in terms of the total energy content of described composition, fat the energy total amount provided should It is preferably 41En%-77En%, more preferably 41En%-70En%, most preferably 41En%-65En%.
For the type of fat, can have and select widely, as long as described fat is food-grade.
Described fat can be animal tallow or plant fat or both have.Although animal tallow (such as lard or Butter) there is the heat and nutritive value being substantially identical and be used interchangeably, but the most excellent Select vegetable oil because they be readily available, prepare simple, relatively low without cholesterol and saturated fat acid concentration.A reality Executing in scheme, the composition of the present invention comprises rapeseed oil, corn oil and/or sunflower oil.
Described fat can include medium chain fatty acid such as medium chain triglyceride (MCT is defined as 8-10 carbon atom length) Source, LCFA such as LCT (LCT) and combine phosphatide aliphatic acid (such as combine phosphatide EPA or DHA) source, or any combination in the source of the two type.
According to an embodiment, it is 8,10 or 12 carbon atoms that the liquid nutritional compositions of the present invention comprises chain length Medium chain fatty acid (MCT) and myristic acid (C14:0), the amount of described medium chain fatty acid is preferably 0-25 weight %, more preferably 0- 20 weight %, especially less than 3 weight %.MCT is useful because in metabolic stress patient they be readily absorbed by and Metabolism.Additionally, use MCT can reduce the risk that nutrient absorption is bad.LCT source (such as mustard caul-fat, rapeseed oil, sunflower oil, Soybean oil, olive oil, coconut oil, palm oil, Linseed oil, marine oil or corn oil) it is useful, because it is known that and LCT is adjustable Immune response in joint human body.
According to an embodiment, the fat in the liquid nutritional compositions of the present invention comprises, with the gross weight of described fat Gauge, the medium chain triglyceride (MCT) of at most 25 weight %.
According to an embodiment, described fat comprises glyceride fraction.This glyceride fraction can contain monoglyceride, sweet Oil diester and triglycerides.Preferably, in order to promote rapid digestion, a part for described glyceride fraction is by the glycerine of aliphatic acid Monoesters and/or diglyceride composition.Described monoglyceride and diglyceride are also found to have and help give relatively great amount of lipid, Without too greatly improving the energy content (caloric content) of described composition.
According to an embodiment, in terms of the total amount of aliphatic acid, described lipid comprises at least 5 weight %, at least 6 weight % Or at least 7 polyunsaturated fatty acids (PUFA) of weight %, preferably eicosapentaenoic acid (EPA) and DHA (DHA).Known the latter PUFA shows antiinflammatory action and can prevent excessive inflammatory response.
According to an embodiment, described lipid comprise at least 400mg PUFA (preferably eicosapentaenoic acid (EPA) and DHA (DHA)) the liquid nutritional compositions of/100ml present invention, more preferably 400-1000mg, more preferably 450- Liquid nutritional compositions described in 750mg/100ml.
According to an embodiment, the fat in the liquid nutritional compositions of the present invention can contain phosphatide or cholesterol.Root According to an embodiment, the fat in described liquid nutritional compositions comprises, in terms of the gross weight of described fat, less than 10 weights The phosphatide of amount %；Or described fat comprises, in terms of the gross weight of described fat, less than the cholesterol of 0.5% weight.
Digestible carbohydrate
Optionally, the liquid nutritional compositions of the present invention comprises digestible carbohydrate.
For the type of digestible carbohydrate, can by selecting widely, if described digestible carbohydrate For food-grade.Described digestible carbohydrate has actively impact to the energy level of experimenter, and increases the battalion of the present invention Support the advantageous effects of composition.Described digestible carbohydrate can comprise simple and/or complicated digested carbon hydrate Thing, or their any mixture.The digestible carbohydrate being suitable for the present invention is glucose, fructose, sucrose, breast Sugar, trehalose, palatinose, corn syrup, Fructus Hordei Germinatus, maltose, isomaltose, the cornstarch of partial hydrolysis, Fructus Hordei Germinatus magma Essence, glucose oligosaccharide and glucose polysaccharide.
According to an embodiment, described digestible carbohydrate provides described liquid nutritional compositions total energy content At most 36En%.Preferably, described digestible carbohydrate provides described liquid nutritional compositions total energy content extremely Many 35%, 34%, 33En%, 32En%, 31En% or 30En%.
The amount of low digestible carbohydrate decrease can induce hyperglycemia, insulin resistant stress, thus Reduce infection rate.
Other components
The composition of the present invention can also contain other nutritional labelings to be for example suitable for meeting the amount of patient demand, the most micro- Secondary element, vitamin, mineral matter, dietary fiber.
Concrete composition
It is one or more that the liquid nutritional compositions of the present invention is characterised by following characteristics:
I () comprises protein material and the digested carbon of at most 36En% of the fat of at least 41En%, at least 23En% Hydrate；
(ii) comprise less than 250kcal, preferably less than 200kcal, more preferably less than 160kcal, most preferably from about Composition described in 125kcal/100ml；
(iii) protein of 5-10 gram, 4-10 gram of fat and the digestible carbohydrate/100ml institute of 4-14 gram are comprised State composition；With
(iv) comprise at least 1.5 grams, the Glu of more preferably at least 1.7 grams (in conjunction with and/or free)/ Composition described in 100ml.
In a specific embodiment, the fluid composition of the present invention comprises fat, protein material and can digest Carbohydrate, wherein said fat provides at least 41En% of described composition total energy content, and described protein material carries For at least 23En%, described digestible carbohydrate provides at most 36En%, also comprises at least 1.5 grams, and more preferably at least 1.7 Gram Glu (in conjunction with and/or free) composition described in/100ml.
In a specific embodiment, the fluid composition of the present invention comprises the fat of about 45En%, about 23En% Composition described in the Glu/100ml of the digestible carbohydrate of protein material, about 29En% and about 2 grams.
Viscosity
Described composition is fluid composition, and wherein liquid is defined as being suitable at room temperature use such as feed pump, weight Power, syringe administration etc., carry out the material of enteral administration by pipe.
Described composition has a certain viscosity being suitable to described enteral administration.
In one embodiment of the invention, the viscosity of described liquid enteral nutritional composition is under 20 DEG C (i.e. room temperature) With 100s-1Shear rate when measuring less than 500mPa.s, preferably 10-200mPa.s, more preferably 10-100mPa.s, optimum Choosing is less than 50mPa.s.Described viscosity can use cone plate geometric method to use rotation viscometer suitably to determine.This viscosity is for warp It is preferable that mouth gives the liquid enteral nutritional composition of the present invention, because individual can easily consume portion has low viscosity The liquid nutritional compositions of (viscosity that such as present invention shows).This viscosity is also preferable for the UD of tube feed.
In one embodiment of the invention, the density range of described composition is 1.00g/ml-1.20g/ml, especially It is 1.05g/ml-1.15g/ml.
In one embodiment of the invention, the osmolarity of described composition is less than 625mOsmol/L, It is preferably 600-100, more preferably 550-200, even more preferably 500-250, most preferably 500-300mOsm/L.
Dosage unit
The liquid enteral nutritional composition of the present invention can be the form of complete food, and i.e. it can meet the whole of user Nutritional need.Therefore, the liquid enteral nutritional composition of the present invention preferably comprises 1000-2500kcal/ daily dosage.Depend on The situation of patient, daily dosage is about 25-35kcal/kg body weight/day.Therefore, for the people of 70kg, typical daily dosage contains There is about 2000kcal.Described complete food can be the form of multiple dosage unit, such as, use the present invention of 1.0kcal/ml Liquid enteral nutritional composition time, every day 8 (250ml/ unit) to 2 unit (11/ unit) was for the energy of 2000kcal/ days Amount supply.Preferably, described alimentation composition is applicable to tube feed, is the form of tube feed thing.
Described liquid enteral nutritional composition can be also dietary supplement ingredient, is particularly used as being given by tube feed in art Carry out the tube feed thing of operating patient.Preferably as enteral replenishers, the every day of described liquid enteral nutritional composition Dosage contains less than 1500kcal, and in particular as replenishers, the daily dosage of described liquid enteral nutritional composition contains 500-1000kcal.Described dietary supplement ingredient can such as use the liquid enteral of the present invention to be the form of multiple dosage unit During alimentation composition, every day 2 (250ml/ unit) to 10 unit (50ml/ unit) is used for the energy supply of 500kcal/ days. Depend on operation technique, the size of adjustable dosage unit and composition.
In one embodiment, the total energy content of described liquid nutritional compositions is less than 250kcal, preferably shorter than Composition described in 200kcal, more preferably less than 160kcal, most preferably from about 125kcal/100ml.The amount of the kcal of every 100ml is excellent Choosing is higher than 100kcal/100ml, more preferably higher than 110kcal/100ml.
Preferably, described alimentation composition is packaged, be stored in container (such as polybag or pouch (pouch) etc.) also And provide wherein.Known multiple such container, such as 500ml, 1000ml and 1500ml container is known in the art.Should Noting, any suitable container is used equally to packaging, stores and provide the alimentation composition of the present invention.
In one embodiment of the invention, described liquid enteral nutritional composition provides also with liquid form i.e. And need not restore before use or mix.The liquid enteral nutritional composition of the present invention can be that tube feed thing maybe can be administered orally. Such as, the composition of the present invention can provide in tank, pricker (spike) and handbag.But, can be by composition with powder form Being supplied to this people needed, it is adapted in use to aqueous solution or water to restore to produce the enteral nutritional composition of the present invention.Cause This, in one embodiment of the invention, the composition of the present invention is powder form, and with entering in aqueous solution or water Row dissolves or restores the specification of the liquid nutritional enteral composition to produce the present invention.In one embodiment of the invention In, the liquid nutritional enteral composition of the present invention can be therefore by dissolving or restoring pulvis (preferably in waterborne compositions, especially It is water) obtain.Suitably manner of packing is the pulvis in container (such as capsule (sachet)), preferably has in aqueous combination Thing or water carry out the specification dissolving or restoring.
Preparation
The liquid nutritional compositions of the present invention can use standard manufacturing method known to the skilled person to prepare, and will not enter one Step describes them.
Owing to the shelf-life is generally at least 6 months, preferably at least 12 months these prerequisites, the liquid nutritional of the present invention Composition needs to carry out certain sterilization treatment to reduce possible pathogen quantity or to be removed, described pathogen such as spore Son, bacterium and cause other microorganisms that protein compositions becomes sour, preferably by use heating (sterilizing, pasteurization), Radiation (UV-process) or filter method (ultrafiltration, diafiltration, nanofiltration) are carried out.Preferably sterilization treatment includes at high temperature Continue the heat treatment of short time, such as, use UHT (superhigh temperature) to process.
Preferably, the liquid nutritional compositions of the present invention is sterilized or the form of pasteurization.
The purposes of described composition
According to an embodiment, the liquid nutritional compositions of the present invention can be used as tube feed thing, i.e. for carrying out patient Tube feed.Described tube feed can continually or intermittently provide.
According to another embodiment, the liquid nutritional compositions of the present invention can be used for by tube feed in art carrying out Operation (especially Noninvasive operation such as percutaneous surgeries, invasive operation such as organ surgery hand Art, cardiac operation and neurosurgery) patient carry out tube feed.
The liquid nutritional compositions of the present invention can also advantageously be used for relaxing, weakening or prevent patient at surgery intra-operative Or acute inflammatory reaction afterwards.
According to an embodiment, described patient be carrying out performing the operation patient, experience and receive and distribute patient or the danger of art Patient with severe symptoms.
The present invention will be described by embodiment now；These embodiments are not restrictive.
Accompanying drawing explanation
Fig. 1. experimental design.Experimenter is made to enter CICU (ICU) after overnight fast.Before LPS is administered One hour, to experimenter's moisturizing in advance (prehydrated) and start to give continuously enteric nutrient in nutritional intervention group, hold It is continuous until LPS is administered latter six hours.During described experiment, in the time point blood drawing of instruction.Experimenter is giving through intravenous Within after LPS 12 hours, leave hospital and return to carry out final blood collection next day.
Fig. 2. the inflammatory reaction during reinforced nutrients regulation endotoxemia.TNF-α after intravenous LPS administration (A), IL-6 (B), IL-1RA (C) and the mean plasma concentration of IL-10 (D).With compare nutrients (p ＜ .05) and fasting (p ＜ .0001) comparing, reinforced nutrients reduces TNF-α, IL-6 and IL-1RA level.The administration of described reference product shows The trend (p=.06) that TNF-α level reduces.Described reinforced nutrients enhance IL-10 release (compared with fasting, p ＜ .0001), also observe this trend (compared with fasting, p=.07) with comparison nutrients simultaneously.
The administration of Fig. 3 .LPS causes subclinical damage of intestines.The intravenous administration of LPS causes blood plasma i-FABP in all groups Level be gradually increased (A).The experimenter of the reinforced nutrients of feeding shows the less increase (A-of circulation i-FABP level B), but this is not reaching to significance,statistical.
Fig. 4. it is administered under the pylorus of comparison or reinforced nutrients and can increase the blood plasma level of CCK.Experimenter with fasting Comparing, the continuous enteral administration of described comparison and reinforced nutrients results in CCK blood plasma level to be increased.Two kinds of nutritional intervention are all Show that 4 hours CCK blood plasma levels somewhat decline after LPS is administered.After stopping nutrients infusion, under plasma C CK level It is brought down below detection level (A).CCK release total between comparison and reinforced nutrients is not significantly different from (B).ND, not Detection.
Embodiment
Embodiment 1: the tube feed thing (all values in the total fluid composition of every 100ml) of the present invention
Embodiment 2: during experimental people's endotoxemia, enteral is rich in lipid and the immunological regulation of the nutrients of protein The research of potential.
Material and method
Experimenter
This research is registered as NCT01100996 at ClinicalTrail.gov.In Nijmegen Academisch Medish Ct After the local Ethics Committee approval of (Radboud University Nijmegen Medical Centre), according to Hull Octyl group declaration, 12 healthy male subject provide 5 Written informed consent participating in this experiment.From participating in another double blinding The placebo of LPS research (NCT00513110) obtains the sample (n=6) of fasted subjects.The feature of experimenter does not has difference (table 1).All experimenters all test negative into HIV and hepatitis type B virus is negative, and are not suffering from two weeks before this research There is any febrile illness.Described experimenter does not use any prescription medicine, aspirin or nonsteroid anti-inflammatory drugs.
Table 1. Subject characteristics
Data represent with mean value ± SEM；BMI, body mass index；TER, overall energy requirement；；NA, inapplicable.
Experimental people's endotoxemia
After with 1.5L glucose 2.5%/NaCl0.45% to experimenter in advance moisturizing, described experimenter accepts 1 The American reference escherichia coli endotoxin of the 2ng/kg body weight given in minute (Escherichia coli (Escherichia coli) O: 113, Clinical Center Reference Endotoxin, National Institute of Health, Bethesda, MD) i.v. bolus (bolus) ［ 22 ］.Use from 0 (asymptomatic) to 5 (the most serious disease lived through Shape) grade symptom that LPS is induced be evaluated, obtain accumulation disease score.Blood drawing, then start under pylorus feeding and Hereafter continuous feeding is until LPS is administered latter 24 hours (Fig. 1).Use flow cytometer (Sysmex XE-2100；Goffin Meyvis, Etten-Leur, the Netherlands) determine conventional hematologic parameter.
Feeding under pylorus
Carrying out that day of testing, two groups accept nutritional intervention in the way of double blind random, have one group whole simultaneously Fasting during experiment (all of group: n=6).Described nutritional intervention group is empty by the self-advancing type nose in described experiment placement in previous evening Intestines feeding tube (Tiger2, Cook Medical, Bloomington, IN, Fig. 1) accepts liquid, reinforced or isocaloric comparison intestines Infusion under the continuous pylorus of interior nutriment, continues 7 hours.The feeding speed of each experimenter is gross energy based on they individual Demand (TER).Using Harris-Benedict equation, described TER is by being multiplied by him by the basal metabolic rate of each experimenter Activity level (for all experimenters, be 1.55 times) calculate (table 1).
Feeding composition and CCK measure
Described reinforced nutrients contains the fat of 44En%, the protein of 25En% and the carbohydrate of 31En%. Described protein is made up of complete casein, lactalbumin and soybean protein hydrolyate.Described comparison nutrients contains The fat of 20En%, the protein of 16En% and the carbohydrate of 64En%.Described reinforced and comparison nutrients all provides 1kcal/ml.CCK-radiommunoassay (Eurodiagnostica, Malm6, Sweden) is used to determine the whole body in blood plasma CCK level.
Plasma levels of cytokines and the mensuration of subclinical damage of intestines
Explanation according to manufacturer (Millipore, Billerica, MA) uses multiple Luminex Assay to measure in batches TNF-α, IL-6, IL-10 and IL-1 receptor antagonist (IL-1RA).Use intestines that indoor development ELISA determines in blood plasma- Fatty acid binding protein (i-FABP).
Statistical analysis
All of value is expressed as mean value ± SEM.Two-way analysis of variance is used to determine the difference between the group of series data Different.Bonferroni's comparing check afterwards (post-hoc test) is used to analyze by one-way analysis of variance (ANOVA) each The difference of series data in group.Grubb ' s will be used to test (extreme studentization deviation method (extreme studentized Deviate method)) data that are accredited as obvious exceptional value remove from described analysis.For Windows's Prism5.02 (GraphPad Software Inc., San Diego, CA) is used for calculating.P value quilt less than 0.05 It is considered statistically significant.
Result
Hematology and clinical response
As summarized in Table 2, give endotoxin and may result in hematology and clinical ginseng in described fasting and nutritional intervention group The change of number.
In all groups, mean arterial blood pressure is administered from LPS and begins to decline (p ＜ 0.001) in latter 90 minutes, simultaneously observes Heart rate compensatory increases (p ＜ 0.001).Further, endotoxemia results in core body in fasting and nutritional intervention group Temperature (core body temperature) (p ＜ 0.001) and the rising of white blood cell count(WBC) (p ＜ 0.001).The blood of LPS induction The change of kinetic parameter, body temperature and white blood cell count(WBC) is not affected by EA.
Give endotoxin cause similar grippal symptom such as to be had a headache, Nausea and vomiting, shiver with cold and myalgia, its quilt It is expressed as disease score.The disease score of all experimenters reaches peak value in 90 minutes after giving LPS.Experimenter's phase with fasting Ratio, give reinforced or comparison nutrients do not affect disease score (respectively p=0.43 and p=0.28).
The intestines carried out with reinforced nutrients during experimental people's endotoxemia raise regulation cell factor spectrum
Intravenous gives LPS and causes significant proinflammatory.The TNF-α of an experimenter in reinforced nutrients group After value is accredited as obvious exceptional value, described value is removed from analyze.With fasting (p ＜ 0.0001) and compare nutrients (p ＜ 0.05) compares, and can significantly decrease TNF-α level (Fig. 2 A) with the treatment of reinforced nutrients.Reinforced nutrients will Peak value TNF-α level reduces by 40 ± 8% (compared with the experimenters of fasting) and 29 ± 10% (compared with comparison nutrients).Described Comparison nutrients demonstrates the trend (p=0.06) that TNF-α blood plasma level reduces compared with the experimenter of fasting.
Compared with comparison nutrients (p ＜ 0.001) and fasting (p ＜ 0.05), reinforced nutrients significantly reduces institute State the IL-6 PC (Fig. 2 B) during endotoxemia scheme, and compared with the experimenter of fasting, described comparison nutrients Do not affect IL-6 (p=0.63).Give peak level reduction by 41 ± 9% (experimenters with fasting that reinforced nutrients makes IL-6 Compare) with 54 ± 7% (compared with comparison nutrients).
It is known that intravenous injection LPS can cause the compensatory anti-inflammatory response of complexity.Specific IL-1 receptor antagonist IL-1RA is released during inflammation, its immunoregulation effect being considered to control IL-1.With compare nutrients (p ＜ 0.0001) comparing with fasting (p ＜ 0.0001), reinforced nutrients reduces the circulation IL-1RA (Fig. 2 C) during described experiment. In reinforced nutrients group, the peak level of IL-1RA is lower than the experimenter of fasting by 37 ± 8%, lower by 25 than comparison nutrients ± 6%.Compared with fasting, described comparison nutrients does not affect IL-1RA level.
Compared with fasting (p ＜ 0.0001), under continuous pylorus the reinforced nutrients of infusion cause the PC of IL-10 with Time raises, and the most described comparison nutrients demonstrates the trend (p=0.07 that IL-10 level raises；Fig. 2 D).Reinforced nutrition Thing make IL-10 peak level improve 231 ± 19% (compared with the experimenters of fasting) and 130 ± 12% (with compare nutrients Compare).
Enterocyte damage is not affected by EA
In all experimenters, give LPS and cause i-FABP blood plasma level to gradually rise until LPS is administered latter 4 hours, this Represent and there occurs that enterocyte damages (Fig. 3 A).Being administered latter 4 hours to 8 hours from LPS, the i-FABP level of all groups is recovered To baseline.Compared with the experimenter of nutrients reinforced with feeding, the experimenter of the experimenter of fasting and acceptance comparison nutrients exists More significantly raising of i-FABP level is shown during described experiment.Compared with the experimenter of comparison nutrients and fasting, right For described reinforced nutrients group, total i-FABP release trends towards reducing, but this is not reaching to significance,statistical (figure 3B)。
During giving EA, plasma C CK level raises
In order to assess the impact that CCK is discharged by continuous duodenum infusion, the time point in instruction have evaluated plasma C CK water Flat (Fig. 1).CCK level is from the beginning of before giving EA, the value (＜ 0.3pmol/l) not detected of (t=-1hr) is increased to Give the 2.3 ± 0.5pmol/l (Fig. 4 A) of 1 hour (t=0) after reinforced and comparison nutrients continuously.After vein lps injection, 4 is little Time, CCK blood plasma level and 1 little level constantly in control group compare decline (0.7 ± 0.2pmol/l；P ＜ 0.05).Adding In strong type group, the decline of CCK level has the trend diminished.Reinforced or comparison nutrients between, total plasma C CK release do not have Marked difference (Fig. 4 B).Stopping after nutrition infusion 8 hours, CCK descends horizontally into undetectable level.Tested in fasting In person, plasma C CK level below detects level during whole.
Discuss
This research have studied immediately exempting from of the continuous enteral administration of the nutrients in people rich in lipid and protein first Epidemic disease regulation effect.During being disclosed in people's endotoxemia, reinforced nutrients regulation congenital immunity should for the data of the present inventor Answering, cause TNF-α, the blood plasma level reduction of IL-6, IL-1RA and circulation IL-10 to raise, this shows that proinflammatory weakens Strengthen with anti-inflammatory response.In the past few decades, the concern that the catabolism state of operation and Cavity in Critical Patients obtains Day by day increase ［ 23,24 ］.
Negative correlation between catabolism and the clinical effectiveness observed creates more rich nutritional programs, such as, reduce Pre-operative anxiety and early stage give EA ［ 24 ］.Carry out these update nutritional support schemes decrease the incidence of disease and in hospital time Between ［ 9,10 ］.Although the precise mechanism that these beneficial effects are behind is not to be fully apparent from, it is assumed that the nutritional support of abundance The immune deficiency ［ 25 ］ caused by shortage of heat can be prevented.In addition to heat is supported, take in rich in intrinsic for a long time (intrinsic) nutrients of anti-inflammatory compound (such as long-chain n-3 polyunsaturated fatty acid and glutamine) can produce immunity Mediating effect+6 also improves result by affecting specific metabolic process, described specific metabolic process include eicosanoid produce, Glutathione synthesis and heat shock protein produce ［ 26,27 ］.In research previously, it was demonstrated that rich in the EA of lipid Thing can be weakened inflammation by the activation to cholinergic anti-inflammatory pathways that CCK mediates and reduced device in several rodent models Official damages.［ 16-19,28 ］.
It is true that each operation, wound and ICU patient suffer from the torment of systemic inflammatory.At such whole body Property inflammatory reaction during, the complicated interaction between proinflammatory and anti-inflammatory mechanisms is completely understood ［ 29 ］ not yet.People's endotoxin blood Disease model these clinical symptoms of not reproducible, but it has been widely used for studying internal acute systemic inflammatory reaction ［ 21 ］. Give endotoxin and can affect multiple systemic physiologic and metabolic process in the way of similar to the commitment of damage and infection, make It becomes the suitable human model ［ 21 ］ for Proof-Of Principle research.
The excess release of known TNF-α promotes systemic inflammatory response syndrome, organ damage and death in septicemia (mortality) generation ［ 30 ］.Additionally, TNF-α relevant to the order of severity of septicemia in patient with the cyclical level of IL-6 31 ］.Consistent with the animal data of the present inventor ［ 16,17 ］, this research demonstrates to be strengthened during people's experimental endotoxemia Type nutrients weakens inflammation by reducing TNF-α and the cyclical level of IL-6.Additionally, the intervention carried out with reinforced nutrients May result in IL-1RA blood plasma level to reduce.These data are consistent with previous report, it was demonstrated that TNF-α during endotoxemia Enhance IL-1RA release with IL-6, and suppress these cell factors can reduce circulation IL-1RA ［ 32,33 ］.Consistent with this It is to use adrenaline or glucocorticoid to weaken inflammatory reaction and can lower IL-1RA and IL-1 blood plasma level ［ 34,35 ］.With this A little reports are consistent, and the inventors discovered that reinforced nutrients not only reduces the blood plasma level of TNF-α and IL-6, also reduce IL-1RA Blood plasma level, this has reacted the pro-inflammatory states weakened on the whole.It should be noted that give reinforced nutrients under pylorus can Amplifying the anti-inflammatory response of induced by endotoxin, this can be dramatically increased by circulation IL-10 compared with the experimenter of fasting and prove.IL-10 Be considered as contend with during acute infection and inflammation proinflammatory reaction host protection mechanism in a part ［ 34 ］.Additionally, It is proven to give IL-10 and can reduce the fatal rate ［ 36 ］ of endotaxin induction in mouse.Reinforced nutrition during people's endotoxemia Immunoreactive beneficial effect and use can be suppressed the blood plasma level of proinflammatory cytokine and strengthen known in circulation IL-10 by thing What pharmacological agents (including adrenaline and glucocorticoid) was carried out previously studied consistent ［ 34,37 ］.Meanwhile, these tables of data Bright reinforced EA is a kind of promising control acutely inflamed physiology intervention.
Enterocyte damage often along with septicemia, wound and major operation occur, and with intestines and stomach hypoperfusion Degree is relevant ［ 38-40 ］.Additionally, intestines damage the formation ［ 41 ］ of inflammatory complication after (compromise) relates to damaging.Here, this Inventors have demonstrated that, intravenous gives LPS and causes i-FABP level to increase.Compared with the experimenter of comparison nutrients or fasting, In the experimenter treated with reinforced nutrients, the increase of blood plasma i-FABP level trends towards less, but this is not reaching to system Conspicuousness learned by meter.These data have obtained the support of rodent research, and the research of described rodent demonstrates rich in lipid Nutrients keeps intestines integrality ［ 17,19 ］.The slightly increase of i-FABP blood plasma level is most likely due to the relative low dose of LPS And the hypoperfusion that causes because of water complementation in advance is limited.Accordingly, it would be desirable to further research determines reinforced nutrition Thing intestines protective effect in people.
The activating Vagus-pressor responses of CCK mediation rises in digestion, metabolism and the immunology feedback of nutrients induction Main Function ［ 19,42,43 ］.The enteral release of CCK mainly by the lipid and protein being present in tube chamber (luminal) cause 20,44 ］, terminate nutrients exposure and can cause the horizontal rapid decrease of CCK ［ 44 ］.In view of these factors, the present inventor selects Give the nutrients rich in lipid and protein continuously with induction, the long-time of anti-inflammatory pathways of CCK mediation to be stimulated.The present invention The nutritional intervention of people result in the circulation CCK level that can detect during the inflammatory reaction of whole endotaxin induction.At endotoxin Before attack, fast injection gives to affect immune response ［ 45 ］, this thing containing 100 grams of fatty milk shakes rich in lipid Highlight the importance giving nutrients continuously in fact.By contrast, the reinforced nutrients of continuous infusion delivers about 60 grams of fat altogether Fat.Although reinforced nutrients shows the antiinflammatory action stronger than comparison nutrients, but can not detect in blood plasma The significant difference of CCK level.This perhaps can be explained by the fact that circulation CCK level do not reflect local enteral concentration with And activation to vagus nerve fibers incoming in intestines subsequently.Under this background, it is notable that the blood plasma of exogenous CCK Concentration must higher than CCK level after the meal at least 10 times could obtain similar full sense effect ［ 46 ］.Use specific CCK-1 acceptor short of money The research further that anti-agent is carried out should illustrate the effect of Local C CK level, and this research is not the most seen.It addition, These researchs also should focus on using of other enteral peptides (including glucagon-like peptide 1 (GLP-1)).Recently, the present invention The team of people shows that GLP-1 is as the common stimulator polypeptide of trophism anti-inflammatory pathways, because giving GLP-1 acceptor in rodent Decrease the depression effect ［ 47 ］ to systemic inflammatory of the nutrients rich in lipid antagonist portion.
In sum, the Proof-Of Principle research of the present invention demonstrates first: 1) short-term gives enteric nutrient continuously and can be Time ground regulation people inflammation, and 2) strengthen described alimentation composition with lipid and protein and can strengthen this anti-inflammatory potential.This The discovery of a person of good sense demonstrates the antiinflammatory action of the reinforced nutrients previously observed in rodent and is also applied for the feelings of people Shape.In a word, the research of the present invention show give reinforced nutrients continuously can be as promising intervening measure with in clinic Environment regulates inflammatory conditions.
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Claims (27)

1. a liquid nutritional compositions is used for relaxing, weaken or prevent to experience operating patient outside described for preparation The purposes of the preparation of the perioperative acute inflammatory reaction of section, described composition comprises fat and protein material, wherein said Fat provides at least 41En% of described composition total energy content, and described protein material provides at least 23En%, Qi Zhongsuo Stating composition is to give described patient by tube feed in art.
2. the purposes of claim 1, wherein said liquid nutritional compositions comprises in terms of the total energy content of described composition, The protein material of 23En% to 59En%.
3. the purposes of claim 2, wherein said liquid nutritional compositions comprises in terms of the total energy content of described composition, The protein material of 23En% to 45En%.
4. the purposes of claim 3, wherein said liquid nutritional compositions comprises in terms of the total energy content of described composition, The protein material of 23En% to 40En%.
5. the purposes of claim 1 or 2, wherein said protein material comprises source and the lactoprotein of vegetal protein substance The source of metallic substance.
6. the purposes of claim 1 or 2, wherein said protein material comprises the protein of hydrolysis.
7. the purposes of claim 6, wherein said protein material comprises the hydrolysis of soybean, casein, whey or wheat gluten Product.
8. the purposes of claim 1 or 2, wherein said protein material comprises casein, whey, soybean, pea and wheat egg One or more in Bai.
9. the purposes of claim 8, wherein said protein material comprises one or more in casein and wheat gluten.
10. the purposes of claim 1 or 2, wherein said liquid nutritional compositions comprises at least 1.5 grams of Glu/100ml Total liquid nutritional compositions, wherein said Glu is to combine and/or free.
The purposes of 11. claims 10, wherein said liquid nutritional compositions comprises 1.7 grams of total liquid of Glu/100ml Alimentation composition, wherein said Glu is to combine and/or free.
The purposes of 12. claims 1 or 2, wherein said liquid nutritional compositions comprises with the total energy content of described composition Meter, the fat of 41En% to 77En%.
The purposes of 13. claims 1 or 2, wherein in terms of the gross weight of described fat, described fat comprises at most 25 weight % Medium chain triglyceride.
The purposes of 14. claims 1 or 2, wherein in terms of the gross weight of described fat, described fat comprises less than 10 weight % Phosphatide, or wherein in terms of the gross weight of described fat, described fat comprises the cholesterol less than 0.5 weight %.
The purposes of 15. claims 1 or 2, wherein said liquid nutritional compositions is in terms of the total energy content of described composition, also Comprise the digestible carbohydrate of at most 36En%.
The purposes of 16. claims 1 or 2, the total energy content that wherein said liquid nutritional compositions has is less than 250kcal/ Composition described in 100ml.
The purposes of 17. claims 16, the total energy content that wherein said liquid nutritional compositions has is less than 200kcal/ Composition described in 100ml.
The purposes of 18. claims 17, the total energy content that wherein said liquid nutritional compositions has is 125kcal/100ml Described composition.
The purposes of 19. claims 1 or 2, it is characterised in that described preparation is through sterilizing or through the form of pasteurization.
The purposes of 20. claims 1 or 2, wherein said tube feed provides in a continuous manner.
The purposes of 21. claims 1 or 2, wherein said operation is invasive operation.
22. comprise a liquid nutritional compositions for fat, protein material and digestible carbohydrate, wherein said fat Thering is provided at least 41En% of described composition total energy content, described protein material provides at least 23En%, and described can Digest carbohydrate provides at most 36En%, wherein said composition to be tube feed thing form in art, and also includes at least 1.5 Gram Glu/100ml described in composition, wherein said Glu is to combine and/or free.
The liquid nutritional compositions of 23. claims 22, also includes combining described in the Glu/100ml of at least 1.7 grams Thing, wherein said Glu is to combine and/or free.
The liquid nutritional compositions of 24. claims 22, comprises the fat of 45En%, the protein material of 23En%, 29En% Digestible carbohydrate and the Glu/100ml of 2 grams described in composition.
The liquid nutritional compositions of 25. claims 22,23 or 24, is used for relaxing, weaken or prevent patient in surgery average of operation periods Between acute inflammatory reaction.
The liquid nutritional compositions of 26. claims 25, wherein said patient is Cavity in Critical Patients.
The liquid nutritional compositions of 27. claims 22,23 or 24 is used for relaxing, weaken or prevent patient at surgery for preparation The purposes of the product of perioperative acute inflammatory reaction.
CN201280027944.7A 2011-04-06 2012-04-06 The food composition of tube feed in art Active CN103596455B (en)

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