CN1555729A - Intestine nutritire preparation used for nutrition supply or/and inmune enforcement - Google Patents

Abstract

A nutritive intestinal preparation for providing nutrients and improving immunity is prepared from basic raw materials, the raw materials for preventing tumor and diabetes, the raw materials for preventing tumor and nephrosis, and the raw materials for improving immunity through emulsifying by the emulsifier prepared from monoglyceride, lecithin and tween-60, homogenizing and sterilizing.

Description

A kind ofly be used for nutrition supply or/and the enteral nutrition preparation that immunity strengthens

Technical field

The present invention relates to a kind of nutrition supply or/and enteral nutrition preparation that immunity strengthens and preparation method thereof, this enteral nutrition preparation is applicable to that malnutrition, immunity degradation are or/and the abominable people of life condition, the patient who is particularly useful for the concurrent diabetes of tumor patient and tumour, ephrosis, immunity degradation, occupation mode is suitable in the stomach and intestine and directly gives, also can be oral.

Background technology

Tumour, AIDS, various virus infections, operation and wound, radioactive ray, chemical substance and poor environment cause a series of pathophysiological change of body, it is hyperfunction to show as catabolism, energy consumption increases, be obvious negative nitrogen balance, Hypoproteinemia and hyperglycemia, the patient is because energy consumption increase and nutrition substrate insufficiency of intake, and the function of immune system that often occurs due to the malnutrition descends.Tumour itself also can produce some immunosuppressive factors and increase the weight of immunologic function decline.After the operation, the catabolism increase can increase the weight of malnutrition, and operation wound also makes body be in immunosuppressive condition.Tumor patient is because these several factors interweave, and immunologic function is in low state after operation.Immunologic hypofunction can increase the danger of infection and tumor recurrence.Therefore, improve the perioperative nutritional status of tumor patient and to recover body's immunological function very important.

In recent years, along with being that surgery stress the center organ and the raising of enteric infection understanding to enteron aisle, EA (enteral nutritionen) especially postoperative EEN (EEN) causes clinician's attention day by day, the clinical discovery postoperative gave instillation Nutrison Fibre in the intestines in 1～2 day, there is not obvious severe complication, generally only slight abdominal distension is felt sick or diarrhoea.EA can directly stimulate intestinal mucosa to make its propagation again, and the protection barrier prevents the intestinal bacterium transposition, and Chinese scholars is emphasized the important function of EA, as long as function of intestinal canal exists, will use EA as far as possible.

All tumor patients are many to be suppressed with immunologic function, shows as the NK cytoactive and descends, and peripheral blood CD3 and CD4 quantity reduce, CD8 quantity increase and/ratio descends.Art is hit to minimum because of fasting, anesthesia surgery one day after, and it is fast that early nutrition recovers, even before being higher than operation.Cerra etc. think that conventional EEN can not correct the immunosupress of tumor patient, and the domestic report that this respect is also arranged adds arginine and then can significantly improve immunologic function.There is report EEN group obviously to improve patient's albumin, transferrins and body weight, thus improve immunologic function, reduce various complication.

Total parenteral nutrition (TPN) and EA (EN) are the nutritional supplementation approach of using always.The available nutritional amt of total parenteral nutrition is higher than the intestines and stomach approach, and in making, the correction of severe malnutrition becomes possibility, but complication is many, expense is high.Compare with parenteral nutrition, EA economy, safety more meet body physiological state, help the recovery of gastrointestinal function.The EA support has the following advantages: 1. nutriment can absorb through portalsystem, helps alimentary canal particularly liver synthetic protein and adjusting metabolism, to hepatic and renal function tool significant protective effect; 2. keep intestinal mucosa eucaryotic cell structure and functional integrity, help preventing bacterial translocation from intestine and the endotoxin enterogenic infection due to absorbing; 3. metabolic nutrition material energy consumption is low than parenteral nutrition.There are some researches prove that the tumor patient power of stomach and colon after surgery weakens to some extent, but small bowel peristalsis and absorption function usually after surgery a few hours promptly recover, postoperative 6～12h small intestine just can be accepted the input of nutriment.There are some researches show that it is safety, feasible that postoperative 48h begins EA.The postoperative body is in the high de-agglomeration metabolism state, needs to increase heat, and body obtains energy with muscle in the decomposer and fat.Have result of study to show that the Infusion in Patients with Digestive postoperative is in stress situation in early days, body loses weight and protein decomposes and EA or parenteral nutrition support all can not reverse.No matter in the intestines group still intestines organize outward, the body weight of postoperative patient all obviously descends, triceps muscle of arm skinfold and arm muscle circumference obviously reduce before than art, the plasma albumin level also obviously descends, but intestines are organized patient's postoperative plasma albumin level outward and descended more obvious.As seen support plasma albumin horizontal aspect, EA is better than parenteral nutrition,, rectifier body protein malnutritive for improving lacks more effective.Nitrogen balance studies show that, though two groups of postoperatives through the nutrition support, still are negative nitrogen balance in early days, show body underwent operative wound after visceral protein consumption very big.Two groups of nitrogen balances there is no significant difference, show that suitable EA can reach the effect of similarly keeping nitrogen balance with parenteral nutrition.Petersson etc. studies show that, just can recover behind the nitrogen 18d that the postoperative accumulation consumes, and the albumen synthesis still are in low state in 30d.The overnutrition that surpasses the organism metabolism ability instead can increase the weight of the internal organs burden, influences body function and recovers.Nutritional support also exerts an influence to body's immunity when improving the postoperative nutrition condition.The long-term TPN that implements, alimentary canal lacks the food effective stimulus, can cause intestinal mucosa atrophy, gut barrier function impaired, the bacterium displacement occurs.The immunosupress that TPN causes also may be relevant with aliphatic acid in the nutrient raw material proportioning etc.For example fat emulsion may damage the function of monocyte, lymphocyte and neutrophil leucocyte.Normal configuration, iuntercellular that EA can be kept the intestinal mucosa cell connect and height of naps; Keep the normal growth of the resident flora of enteron aisle; Help intestinal cell normally to secrete IgA, stimulate hydrochloric acid in gastric juice and pepsic secretion, the secretion of stimulate digestion liquid and gastrointestinal hormone promotes gall-bladder to shrink and gastrointestinal peristalsis, increases visceral bloodflow, makes metabolism more meet physiology course.

There is research also to find, EEN and parenteral nutrition all can improve the nutrition condition of patients with gastric cancer, but parenteral nutrition but can not be corrected the t lymphocyte subset group disorder of patient's postoperative, show that EA is not due to the improvement of nutrition condition to the improvement effect of immunologic function, may have reason in addition.In recent years, gut mucosal immune function comes into one's own, and enteron aisle is considered to the immune organ of body maximum, and the quality of its function not only is related to the intestinal mucosal barrier function, and relevant with the general immunity function.Wound, stress the time its function be subjected to obvious inhibition, when EA, can offer the enough nutrient matrixes of intestinal mucosa immunocyte, activate enteron aisle neuroendocrine immunity axle, thereby help to keep gut mucosal immune function and general immunity function.Therefore have scientist to infer, the mechanism that EEN improves postoperative gastric cancer T lymphocyte immunologic function may realize by the promotion gut mucosal immune function.But its precise mechanism awaits further further investigation.Discover that EA group CD3, CD4 level obviously increased in the 8th day after surgery, and parenteral nutrition group NK cellular level obviously descended in the 8th day after surgery.CD3 participates in constituting T cell antigen receptor (TCR) complex, antigenic information can be transmitted in the T cell, makes it activation.CD4 and CD8 are present in Ti/Th (inducing-helper cell) and TS/TC (inhibition-killer T cell) surface respectively.The Th cell function strengthens, and can strengthen immune response.NK cell (NK) but direct killing target cell and have immunoregulation effect.Originally studies show that EA can improve the Th function, and keep the NK cellular level; On the contrary, parenteral nutrition might suppress the body cell immunologic function.This is to anti-infective, antitumor and to keep body homeostasis most important.This research also finds, and compares before the art, and group CRP and IgM level obviously raise in the 8th day intestines of postoperative.CRP is a kind of acute phase reactive protein, can combine with bacteria cell wall, plays antibody sample opsonic action; But and activating complement classical pathway and promotion phagocytic function.IgM is the main immunoglobulin that first humoral immune reaction commitment produces.As seen EA to protection body major operation after defense mechanism under the stress situation may be more useful.

All there is malnutrition in various degree in late tumor patient, and underfed criterion is: ABW is lower than 90% of ideal body weight; Triceps rhicnosis thickness is lower than normal value 50%; Upper arm middle part muscle girth is lower than normal value 50%; UCr/height index is less than 80%; Prealbumin is less than 200mg/L; Transferrins is less than 2.0g/L.Late tumor patient causes underfed reason to have four: one: feed difficulty, indigestion or malabsorption that protopathy or operation, radiotherapy, chemotherapy etc. cause; Its two: Cori circulation is active, and 1M glucose only produces 2MATP through the anerobic glycolysis approach, on the contrary, then need consume 6MATP from lactic acid regeneration glucose, so forms the power consumption process, and makes the glucose recirculation rate be higher than 2 times of normal persons; Its three: employ body fat; Its four: reduce because skeletal muscle protein is synthetic.The muscle protein that decomposes is except that part is absorbed by tumour, and all the other are used as the gluconeogenesis precursor or supply liver synthesized acute phase protein, thereby whole protein turnover rate is increased, and power consumption increases.Malnutrition often shows as N K cytoactive and descends all with immunologic hypofunction, and the interleukin-22 that lymphocyte produces reduces, and t helper cell (CD4) descends, and T inhibition cell (CD8) increases.Degradation changes under the CD4/CD8 ratio.The reason that causes immunologic hypofunction mainly is malnutritive, and some immunosuppressive factors that next some tumour itself is produced also can cause the low of immunologic function.TPN mainly is to utilize exogenous glucose and fat emulsion energy supply for late tumor patient, reduces the decomposition of body protein, corrects malnutrition and improves immunologic function.

According to investigations, in the existing inpatient of China, have 40%～50% to have malnutrition in various degree, need nutritional support, but reality can obtain this curer's less than 20%, reason wherein be on the one hand because the technical merit that China clinical nutrition is supported is advanced inadequately, between the area development unbalanced, another major reason is owing to do not have high-quality and price is suitable, can be fit to the enteral nutrition preparation of different needs of patients.

The home and abroad analysis for similar products be comparison shows that the research of China's enteral nutrition preparation is also relatively backward, and be badly in need of the research and development of liquid enteral nutritional preparation.About ten kinds of enteral nutrition preparations such as the peace element that present China uses always clinically, elental, Nutrison Fibre, the pure element of knob, be all external product, and cost an arm and a leg, the nutrition cost of every day with minimum near 100 yuan, the highest does not wait near 300 yuan, and general patient is difficult to bear; And because the difficulty of liquid preparation transportation, storage, imported product mostly is pulvis, needs the water allotment when clinical practice, causes microbial contamination easily.Domestic like product seldom, wherein representative have several prods such as Rui Kang, upright suitable health, three nine-day periods after the winter solstice homogenate meals, rehabilitation be fast.Three nine-day periods after the winter solstice homogenate meals, rehabilitation are fast etc. mostly is the mixing powdery, poorly soluble, can not carry out clinical nasal feeding perfusion, and application is restricted; And Rui Kang, upright suitable health be owing to reasons such as quality, curative effect, mouthfeels, and the competitiveness in market is very poor, is difficult to widely at clinical application.

Traditional Chinese medicine is with a long history in China, and is of long standing and well established.In the process that long-term and tumour are struggled, people filter out much the Chinese herbal medicine for preventing of good curative effect compound and simple, and development theoretical along with modern medicine and pharmaceutical technology, contained active component in clear and definite these Chinese herbal medicines, extract and isolation and purification method, clinical effective, toxic and side effect, this uses and enters the international market for it and has laid a good basis in food.

The oral medicinal herb prescription that is applied to tumor patient was at present both stopped up the characteristics of containing at wet poison in the enteron aisle, and bitter-cold herbs easing dampness is with eliminating evil, and is basic at this morbidity of deficiency-weakness of spleen-QI again, air making-up and spleen enlivening is to set upright, at the important pathology link of the stagnation of the circulation of vital energy, blood stasis etc. in the course of disease, take into account the promoting flow of qi and blood circulation, relieving spasm to stop pain simultaneously.Full side's compatibility is attacked heresy and is not just hindered, and qi-restoratives and do not hold back heresy is played tonifying spleen antidiarrheal, the effect of regulating qi-flowing for relieving pain altogether.

The Chinese medicine and the mechanism of action thereof that enteral nutrition preparation is commonly used are as follows: the main Chinese medicine anticancer active constituent of generally acknowledging has at present: matrine, elemene, coix seed oil, green tea element, perilla herb oil, LBP-X, GL-B, astragalus polyose, Chinese caterpillar fungus polysaccharide, various algal polysaccharides etc.

Elemene (elemene) is the anticancer effective component that extracts from the zingiberaceous plant curcuma zedoary, and motherland's medical science is thought: curcuma zedoary has that blood is broken in promoting the circulation of qi, the long-pending pain relieving that disappears, antineoplastic effect.Coix seed is the seed of grass family Coix plant Coix lachrymajobi, and Compendium of Material Medica is carried coix seed strengthening QI of middle-JIAO, the effect of disease eliminating powder junction.Coix seed oil is its fat oil, and to the mouse EC, U-14 (U-14) all has the obvious suppression effect with the HCA solid tumor.Astragalus polyose: from the Radix Astragali, extract, in vivo studies has antitumaous effect, proved by immunologic function and worked, can improve cyclic adenosine monophosphate level in the blood plasma, make CAMP/cyclic guanosine monophosphate keep stable, thereby prevent the uncontrolled propagation of mutant, play the effect that pre-preventing tumor continues diffusion, shifts.Chinese caterpillar fungus polysaccharide: the proteoglycan C909 that obtains from the Cordyceps sinensis of cultivating has anticancer and immune promotion activity.Pharmacological evaluation confirms that Chinese caterpillar fungus polysaccharide can obviously suppress tumor growth.Chinese caterpillar fungus polysaccharide can be by activated T cell etc., directly or indirectly discharges cytotoxic factor, and killing tumor cell suppresses tumor growth.With Cordyceps sinensis is the zhiling capsules adjuvant therapy of malignant tumor of main component, and effect is more obvious.The green tea element: the active component that from green tea, extracts, be green tea element (TP-91) crystallization, contain the compound of trace elements such as flavanol compound and selenium, germanium, anti-oxidant, anti-sudden change that anticancer mechanism is mainly.Tumour to tumor-bearing mice has certain inhibitory action, and can improve total number of peripheral blood and T lymphocyte positive rate increases.The green tea element can be eliminated host's high blood coagulation shape, improves microcirculation disorder, increases the phagocyte activity.Perilla herb oil: foreign studies such as Japan find, perilla herb oil can obviously suppress the incidence of disease of breast cancer due to chemical carcinogens (DMBA) or the strain of subcutaneous transplantation knurl, reduce the weight of tumour, dwindle gross tumor volume, prolong the time of occurrence of tumour; Suppress the transfer of ascites tumor in lung, colon cancer, tumor of kidney etc. is all had the obvious suppression effect.(Lycium barbarum Polysaccharides LBP) is the active component that extracts to LBP-X from matrimony vine.Matrimony vine is the ripening fruits of plant of Solanaceae lycium barbarum.Have another name called matrimony vine, FRUCTUS LYCII, day smart, celestial being etc.Nature and flavor are sweet flat, go into liver, kidney two warps.Be longer than filling liver kidney, benefiting essence-blood can nourish the liver to improve visual acuity again, is flat tonic product simply, so no matter the deficiency of Yin, the deficiency of yang can be used, and is successive dynasties health care good medicine.Modern study shows that LBP-X all has nospecific immunity, cellular immunity and the humoral immune function of normal and animal pattern and promotes widely and the improvement effect.As improving the phagocytic function of macrophage, stimulate B, T lymphopoiesis, obviously improve cytotoxic T lymphocyte function and NK cell killing activity, make the T cell produce the obvious enhancing of IL-2 ability etc.Clinical research finds that LBP has obvious enhanced sensitivity and protective action to radiotherapy, and LBP-X can also obviously promote the propagation of pluripotential hemopoietic stem cell, improves the hematopoiesis function of normal mouse.This has very good restitution undoubtedly to owing to disease or acceptance is put, chemotherapy causes the immunity and the tumor patient of the dual disorder of hematopoiesis function.

The hit rate of number of research projects proof screening antineoplastic from natural animal and plant medicine is more much higher than synthetic drug.In addition,, make people produce the idea of " going back to nature " because the toxic and side effect of natural medicine is little, thus the extremely people's attention of screening natural antitumor medicine, but do not see the report that any antitumor active ingredient of Chinese herbs is used so far yet in enteral nutrition preparation.

Therefore, or/and the crowd of the immunity degradation that wound causes, adopt to give nutrients in the intestines or immune reinforce strengthens its physique, promote it and return to form for tumor patient, AIDS patient, other virus infectionses person, operation.Research and develop the enteral nutrition preparation that high in technological content, product good effect, steady quality, price are low, can be fit to different needs of patients, have very important realistic meaning.

Goal of the invention

The purpose of this invention is to provide a kind of enteral nutrition preparation that contains nutritional factors and immunopotentiator and preparation method thereof, be used for malnutrition, immunity degradation or/and the abominable crowd of living environment is particularly useful for patient with operation, AIDS patient, tumor patient, the harmful radioactive ray of acceptance or/and the abominable crowds' of living environment such as poisonous chemical raw material nutrition supply and immunity enhancing.

Technical scheme

A kind of enteral nutrition preparation of the present invention, be by comprising that following materials of weight proportions makes: Tea Polyphenols 30-1500mg, bean powder 0-40g, milk powder 13-80g, salt 1-2g, maltodextrin 18-150g, maize germ oil 2-10g, fresh milk 300-1450ml, emulsifying agent 0.5-4g, vitamin, mineral matter.

A kind of enteral nutrition preparation of the present invention, used bean powder are the sugar-free bean powderes, and milk powder is full-cream or/and skimmed milk power.

A kind of enteral nutrition preparation of the present invention, vitamin and mineral matter are selected from: vitamin C 120mg, niacinamide 14mg, vitamin E 8mg, pantothenic acid 4mg, Cobastab ₆2mg, Cobastab ₁1.4mg, Cobastab ₂1.4mg, vitamin A 563 μ g, folic acid 400 μ g, biotin 100 μ g, the plain D of vitamin ₂5 μ g are or/and Cobastab ₁₂3 μ g, and calcium 100mg, phosphorus 77mg, magnesium 30mg, iron 10mg, zinc 10mg, potassium 4mg, manganese 3mg, copper 2mg, molybdenum 100 μ g, chromium 100 μ g are or/and selenium 30 μ g.

A kind of enteral nutrition preparation of the present invention is by comprising that following materials of weight proportions makes: sugar-free bean powder 40g, skimmed milk power 48g, whole milk powder 13g.

A kind of enteral nutrition preparation of the present invention is by comprising that following materials of weight proportions makes: sugar-free bean powder 30g, skimmed milk power 0g, whole milk powder 80g.

A kind of enteral nutrition preparation of the present invention is by comprising that following materials of weight proportions makes: sugar-free bean powder 0g, skimmed milk power 40g, whole milk powder 0g.

A kind of enteral nutrition preparation of the present invention is by comprising that following materials of weight proportions makes: glutamine 25g, arginine 7.5g, LBP-X 500mg.

A kind of enteral nutrition preparation of the present invention is made emulsion and/or electuary.

The preparation method of a kind of enteral nutrition preparation of the present invention, described raw material is divided into water material, oil phase material and emulsifying agent, dissolved emulsifier and oil phase material and add the water emulsification pretreatment in the time of 60-70 ℃, water dissolving water material and in the time of 60-70 ℃ with its rehydration, two kinds of liquid are mixed 20MPa homogeneous, can, sealing, 115 ℃ of sterilizations.10 fens kinds, 37 ℃ of insulations check in 7 days, refrigeration.

The preparation method of a kind of enteral nutrition preparation of the present invention, wherein the adding method of Tea Polyphenols is after various raw materials all fully mix, and with a small amount of hot water dissolving's Tea Polyphenols, joins in the system, through emulsification pretreatment, high pressure, homogeneous, can.

The preparation method of a kind of enteral nutrition preparation of the present invention, described LBP-X is pressed the method for water extract-alcohol precipitation and is extracted, convection drying after repeatedly washing, or after water dissolves again, concentrate drying.

The preparation method of a kind of enteral nutrition preparation of the present invention, HLB value are 9-10, and the compound emulsifying agent proportioning is a monoglyceride: lecithin: Tween60=4: 1: 5; Emulsifying agent addition is 0.4%; Homogenization pressure is 20MPa; Sterilising conditions keeps 10min for being heated to 115 ℃.

The purposes of a kind of enteral nutrition preparation of the present invention is used to prepare suitable tumor patient nutrition supply agent.

The purposes of a kind of enteral nutrition preparation of the present invention is used to prepare the nutrition supply agent of fitting the concurrent diabetic of tumour.

The purposes of a kind of enteral nutrition preparation of the present invention is used to prepare the patient's of the concurrent ephrosis of tumour immunopotentiator.

The purposes of a kind of enteral nutrition preparation of the present invention is used to prepare tumor patient, AIDS patient, various virus infections person, the person that accepts the radiation therapy, accepts chemotherapy person, the person of undergoing surgery or/and person's in poor health immunopotentiator.

The purposes of a kind of enteral nutrition preparation of the present invention is used for preparing the people of the staff of dept. of radiology, diver, astronaut, pilot, duplicating person, the people who contacts harmful radiation exposure, contact harmful chemical or/and other are in the people's of poor environment nutrition supply agent and/or immunopotentiator.

The using method of a kind of enteral nutrition preparation of the present invention, directly from stomach and intestine or/and orally give.

Preparation technology

1 raw material screening

1.1 experiment content

Mainly be the screening of beans and milk protein raw materials: the vegetable oil in the prescription is selected maize germ oil, because it is easy to be absorbed by human body, absorptivity is up to 97%; Itself does not contain cholesterol, and its fatty acid ester composition is the unrighted acid based on oleic acid and linoleic acid; It contains abundant vitamin E etc. in addition.Carbohydrate is mainly provided by maltodextrin, because tumor patient is because sugar tolerance appears in metabolic disorder to be reduced, and the monose sugariness is too high, should not directly add.Vitamin and mineral matter are provided by the Fu Shifu capsule.These raw materials all are easier to select, and are less to the processing stability influence of product.And the beans and the milk raw material of albumen are provided, because it is wide in variety, quality and price difference are big, and be bigger to the processing stability influence of product, therefore answers contrived experiment to screen.

1.1.1 experiment material and method

1.1.1.1 experiment material

1. peas protein is for selecting raw material: in order to reduce the influence of raw material to product sweetness, select the higher bean products of all kinds of sugar-frees common on the market and protein content as supplying the examination raw material.Be specially analysis for soybean powder (A), instant soybean milk powder (B), sugar-free bean powder (C), soybean protein isolate (D) and sugar-free soybean milk powder (E).2. the albuminoid of suckling is for selecting raw material: in order to explore the utilization of new lactoprotein in food, strengthen the function of product, select concentrated whey protein powder-80 (U.S. Proliant Inc), casein sodium (New Zealand), whole milk powder, skimmed milk power (Erie) are as supplying the examination raw material.

1.1.1.2 experimental technique

1. peas protein raw material screening:, can produce bigger influence to the sense organ and the stability of product, so selection sensory properties and centrifugal stability are as judge index because the soybean protein processing stability is relatively poor, and contains dietary fiber and other insoluble matter.According to Protein content in the requirement of vegetable protein and the raw material in the prescription, determine the addition of each raw material, other raw material is only a little once adjusted, so that the amount of protein, fat, carbohydrate is consistent.All raw materials are mixed respectively → dissolve → emulsification → homogeneous → bottling → sealing → sterilization by water, oil phase, take the dish out of the pot and cool off the sensory properties that product is observed in the back, respectively get the conical centrifuge tube that 10ml puts into 10ml band scale in addition, in the centrifugal 10min of 3000r/min (700g), observe the bottom precipitation situation with TDL-40B type supercentrifuge.

2. milk protein raw materials screening: the thermally-stabilised difference of milk albuminoid is bigger, and product needs autoclave sterilization in order to reach the purpose of long preservation, therefore main heat endurance and the sensory properties of investigating product.At first determine the addition of each raw material, the amount of protein, fat, carbohydrate is consistent.Raw material by above-mentioned processes, is taken the dish out of the pot and cools off the sensory properties that product is observed in the back, thermally-stabilised situation.

1.1.2 experimental result and discussion

1.1.2.1 peas protein raw material screening

Each peas protein raw material stable as shown in the table:

The stability of table 1 peas protein raw material

The peas protein raw material

Observation item

A B C D E

There is scum silica frost on the state upper strata of reconstituting, and there is scum silica frost on the upper strata, and supernatant liquor leaves standstill the back deposition down and dissolves more even

Lower floor has precipitation lower floor not have the tiny bottom that is deposited in of obviously heavy layer

Form sediment

The sterilization proterties has wall cling phenomenon, no wall built-up, and the bottle end, do not have wall built-up, bottle end albuminous degeneration, no wall built-up, the bottle end

Bottle has at the end and heavyly precipitation to be arranged at the bottom of having precipitation to have precipitation to condense in bottle in a large number

Form sediment

Centrifugal stable precipitation capacity ≈ 10% precipitation capacity ≈ 10% precipitation capacity ≈ 5% precipitation capacity ≈ 3% precipitation capacity ≈ 1%

According to above result as can be seen, only through corase grind (A, B) or the bean powder that grinds after expanded (C), its impurity is more, and is bigger to the homogeneous operating influence, the product precipitation is more, influences clinical nasal feeding and irritates and feed, and should not adopt; Soybean protein isolate (D) can not be miscible with other composition well, and poor heat resistance, is not suitable for the autoclave sterilization of this product; And through soaking defibrination, and the soymilk powder (E) that obtains of spraying lecithin spray-drying, brew is good, and the centrifugation amount is little, and the processing stability height is adapted at adding in this product.

1.1.2.2 the screening of milk protein raw materials

Sensory properties after the heat endurance of the sterilization of each milk protein raw materials and the sterilization is as shown in table 6.

The stability of table 2 milk protein raw materials

The milk raw material

Observation item

PURE WHEY casein sodium milk powder

The heat endurance thermally labile, product heat of solidification steady heat is stable

Viscosity heightens, and the large-tonnage product good stability is arranged, and is regardless of

The sex change of organoleptic properties's product is solidified

Whiteness come-up layer, the no abnormal variation of viscosity,

Find out that by above result PURE WHEY can not tolerate autoclaving, can not use; Casein sodium has tangible viscosifying action, and this can influence clinical nasal feeding operation, and in mixing the process that stirs, easily fills a lot of gases, forms very fine and closely woven bubble, also can influence the stability of product; And the product Heat stability is good of producing with skimmed milk power, sensory properties meets the requirements.

The screening of 2 emulsifying agents and determining of the suitableeest addition

Concrete experimental technique is: at first calculate the fat content of raw material proportioning, make the simulation mixed system that equates with raw material proportioning fat content with an amount of grease and water.Select two or three kind of emulsifying agent to mix, press HLB6～12 scopes design series raw material proportioning, blended emulsifier with various HLB values is added to respectively in the above-mentioned simulation oil-water system by finite concentration then, with high speed homogenizer in 10000r/min emulsifying 5min, this emulsion is at room temperature left standstill 6h, draw its middle level emulsion and under ultraviolet specrophotometer 550nm wavelength, survey light transmittance, represent the HLB value with abscissa, on behalf of light transmittance, ordinate draw, and the HLB value of trying to achieve the light transmittance minimum is the required HLB value of this emulsion.According to this HLB value, design possible two kinds and three kinds of recovery material proportionings that emulsifier forms then, measure the light transmittance that makes emulsion according to last method, the raw material proportioning of light transmittance minimum is the best blended emulsifier of this emulsion.Optimum emulsification agent with top gained, (percentage that accounts for grease weight is added in the above-mentioned oil-water system design variable concentrations, the same method emulsification is also measured light transmittance, try to achieve light transmittance and begin that emulsifier concentration is critical micelle concentration (CMC) when constant substantially, promptly surpass this concentration and just can play emulsification.

The emulsifier concentration that records according to last method is drawn by simulated system, actual mixture of raw materials is more complex, the emulsifying agent consumption is also much bigger, therefore also mentioned emulsifier to be joined in the raw material by various dose, go out product by promptly deciding processes, wait comprehensively according to the sensory properties after the product sterilization, emulsion stability, storage-stable after centrifugal and judge.

Sensory properties after the sterilization is observed: mainly see to have or not oil film to occur in the process of cooling.

Emulsion stability after centrifugal: get the conical centrifuge tube that the 10ml sample is put into 10ml band scale, in the centrifugal 10min of 3000r/min (700g), separate out situation with top layer, centrifugal back grease and judge with TDL-40B type supercentrifuge.

Storage-stable: product was placed three months under room temperature, and observation has or not layering to separate out situation.

2.1 the selection of sterilising conditions

For the sterilising conditions of selecting to suit, promptly under microbiological indicator meets the requirements of prerequisite, selection is to the minimum processing of product colour influence, experimental design following several groups handle and study suitable sterilising conditions: sterilising temp is 110 ℃, retention time is respectively 10min, 15min, 20min, 25min, 30min; Sterilising temp is 115 ℃, and the retention time is respectively 10min, 15min, 20min, 25min, 30min; 120 ℃ of sterilising temps, the retention time is respectively 10min, 15min, 20min, 25min, 30min.

The inspection of sterilization effect: the product through different temperature, time combination are made, in 37 ℃ ± 1 ℃ cultivation 7 days, carry out the mensuration of total number of bacteria and coliform approximation respectively.

The mensuration of browning degree: measure Δ L, Δ a, Δ b value and the total color difference Δ E that each is handled with the full-automatic colour examining colour-difference-metre of TC-P2, Δ L is the difference of sample whiteness and standard white plate, is negative value, and it is worth, and the clear degree of novel is high more more; Δ E is the total color difference of sample and standard white plate, and its its browning degree of more little explanation of value is more little.

2.2 result and discussion

2.2.1 the screening of emulsifying agent and determining of the suitableeest addition

2.2.1.1 mixture of raw materials is the mensuration of HLB value

Experiment designs the standard emulsifying agent raw material proportioning of serial HLB value from glycerin monostearate, Span80, Tween60.Then the concentration of these emulsifying agents with 2% (accounting for the percentage of grease weight) is added to respectively in the simulation mixed system of being made up of 3% corn oil and water, in shearing homogenizer,, gets white emulsion with 10000r/min emulsification 5min.Same preparation does not add emulsifying agent but the same blank of other operation leaves standstill 6h, gets beaker middle part emulsion 5～10ml with pipette, surveys its light transmittance with UV-2101PC type ultraviolet-uisible spectrophotometer down in the 550nm wavelength.The HLB value of light transmittance minimum is the suitableeest HLB value of this simulated system.Discovery HLB value is that the light transmittance of 9.4 o'clock simulated systems is minimum, and the HLB value is (Tween6050%～55%) in 9～10 scope, and lower light transmittance is all arranged, and promptly all can reach emulsifying effectiveness preferably.

Table 3 mixture of raw materials is the mensuration of HLB value

The mixing ratio of emulsifying agent

The HLB value of standard emulsifying agent

Monoglyceride Span80 Tween60

60 20 20 6.1

60 15 25 6.7

60 10 30 7.2

50 15 35 7.8

50 10 40 8.3

40 15 45 8.9

40 10 50 9.4

30 15 55 10.0

30 10 60 10.5

20 15 65 11.1

2.2.1.2 the screening of best complex emulsifying agent

Keep this optimum HLB value constant, select emulsifying agent monoglyceride, lecithin, Tween60 commonly used in the Dairy Processing to be made into different compound emulsifying agents, make emulsion as stated above, and measure its light transmittance at the 550nm place, the compound emulsifying agent of light transmittance minimum i.e. the optimum emulsification agent raw material proportioning of emulsion for this reason.

The screening of table 4 best complex emulsifying agent

Monoglyceride lecithin tween60

(%) (%) (%) HLB value light transmittance (%)

50 0 50 9.35 41.5

0 50 50 9.45 72.2

40 10 50 9.37 40.7

10 40 50 9.43 53.7

30 20 50 9.39 42.6

20 30 50 9.41 44.4

25 25 50 9.4 42.6

By above result as can be seen, cooperate the compound emulsifying agent that forms best by monoglyceride, lecithin, Tween60 in 4: 1: 5 ratio to the emulsifying effectiveness of this product.

2.2.1.3 the critical micelle concentration of emulsifying agent (CMC) is measured

With the preferable emulsifying agent of top gained, the design variable concentrations is added in the 3% profit mixed system, and the same method emulsification is also measured light transmittance, records light transmittance and begins emulsifier concentration when constant substantially, is to reach the required critical emulsifier concentration of better emulsifying effectiveness.

The critical micelle concentration of table 6 emulsifying agent (CMC) is measured

Emulsifier concentration (accounting for weight of oil %) light transmittance (%)

1.0 67.4

1.5 60.0

2.0 52.1

2.5 45.8

3.0 43.8

3.5 43.8

4.0 43.5

4.5 41.7

5.0 40.4

As seen from the above table, to reach oil heavy 3.0% the time when emulsifier concentration, and the light transmittance of emulsion begins constant substantially, and promptly the concentration of this emulsifying agent reaches 0.1% when above of raw material gross weight, just can reach emulsifying effectiveness preferably.

2.2.1.4 the emulsifying agent addition determines in the actual product

Because actual product is far beyond the simulated system complexity, therefore critical micelle concentration can not satisfy product emulsification requirement, the addition of emulsifying agent generally accounts for 0.1%～0.6% (m/m) of raw material gross mass in the production, and therefore the suitableeest addition of emulsifying agent is determined in the following experiment of design.This blended emulsifier is joined in the raw material by after 0.2%, 0.4%, 0.6% (m/m) of raw material quality and the suitable quantity of water emulsification, after mixing, homogeneous, can, sealing, sterilize, check the emulsion stability of product, each stability indicator is as shown in table 7.

The product emulsion stability of table 7 different emulsifiers addition

Emulsifier concentration (accounting for raw material gross mass %)

Inspection item

0.2 0.4 0.6

Uniformly the uniform emulsus bottle of emulsus wall has cured shape

Sense organ liquid after the sterilization, but leave standstill cold liquid, cool off no elaioleucite, mouthfeel is sent out puckery

Character has yellow chromatography to go out mouthfeel in the surface but the time

The look oil reservoir is separated out, better

Mouthfeel is good

Centrifugal stability has yellow grease to analyse no yellow grease to analyse no yellow grease and analyse

Go out out to go out

(three bottles of walls have the yellow maintenance of a circle stable to storage properties, do not have to keep stable, nothing

Individual month) look grease adhesion layering layering

As seen from the above table, the addition of blended emulsifier is advisable with 0.4% (m/m) in the actual product.

2.2.1.5 determining of suitable homogenization pressure

High-pressure homogeneous fat globule and the further fragmentation under effects such as extruding, bump, shearing of other particulate that makes in the material reaches the effect that prevents that fat floating or particulate from sinking, and makes product obtain the favorable tissue state, and helps digestion and absorption.Homogenization pressure is too small, do not reach broken purpose, and homogenization pressure is excessive, can make the particle overcrushing again, and surface tension is excessive, plays pendulum and coagulative precipitation easily, therefore will select suitable homogenization pressure.

Get the material 10ml that utilizes behind the different pressures homogeneous, be put in the conical centrifuge tube of band scale, after centrifugal, the upper strata oil film separates out situation and the lower sediment amount is as shown in the table.

The material stability that the different homogenization pressures of table 8 are handled

Homogenization pressure

Check a 10MPa 15MPa 20MPa 25MP 30Mpa

Order a

Upper strata oil has obvious yellow to have oil film the no oil film appearance of the no oil film appearance of no oil film appearance to occur

The film oil film occurs

Precipitation ≈ bottom, precipitation＜bottom, precipitation＜bottom, the bottom portion of avaling precipitation＜bottom precipitation ≈

Form sediment 1% 1% 1% 1% 3%

Found through experiments, when homogenization pressure surpassed 20MPa, product subsurface has not had oil film separated out, but along with homogenization pressure increases, the bottom precipitation increases gradually, and the homogenization pressure when therefore producing is advisable to select 20MPa.

2.2.1.6 the selection of sterilising conditions

Enteral nutrition preparation need just can be guaranteed its safe and sanitary through sterilization, and reaches the purpose of long-term preservation, and sterilization has the sterilization of maintenance (bottled sterilization) method and ultra high temperature short time sterilization method, and the standard heating condition that freeze mode is sterilized is: 110～120 ℃, and 10～30min.The raising of sterilising temp or the prolongation of time can improve sterilizing efficiency, but this also can cause nutritive loss to increase, and produces a series of physical-chemical reactions such as brown stain even albumen thermocoagulation.Therefore under the prerequisite that guarantees sterilizing efficiency, should select the combination of lower temperature and short period as far as possible.

2.2.1.7 the detection of microbiological indicator

Material is after each sterilization treatment, and product is pressed GB4789.2-1994 in 37 ℃ of constant temperature culture 7d, GB4789.3-1994, and the method for GB4789.18-1994 is checked its total number of bacteria and coliform approximation, and measurement result is as shown in table 9.

The microbiological indicator of the different sterilization treatment of table 9 detects

Sterilization time

The sterilising temp test item

10min 15min 20min 25min 30min

How many can not the counting of total plate count can not count how can not to count how to count many can not counting

110 ℃ of coliforms are negative negative

Total plate count＜10＜10＜10＜10＜10

115 ℃ of coliforms are negative negative

Total plate count＜10＜10＜10＜10＜10

120 ℃ of coliforms are negative negative

By above result as can be known, adopt 115 ℃～120 ℃, respectively handle microbiological indicator more than 10min～30min and all can reach the GB requirement.

2.2.1.8 color difference measurement

Measure the L of each sample with the full-automatic colour examining colour-difference-metre of TC-P2, a, every difference DELTA L that the b value is compared with standard white plate, Δ a, Δ b, and total color difference Δ E survey respectively three times, ask its mean value.The result is as shown in the table.

The color difference measurement of the different sterilization treatment of table 10

Sterilising temp (℃) time

(min) ΔL Δa Δb ΔE

110 10 -20.29 0.72 16.75 26.32

110 15 -21.56 1.53 17.24 27.41

110 20 -22.59 2.68 17.04 28.42

110 25 -23.46 4.18 16.86 29.30

110 30 -24.32 5.66 17.04 30.28

115 10 -23.62 3.65 16.63 29.12

115 15 -24.46 5.83 17.62 30.70

115 20 -25.78 7.69 17.69 32.20

115 25 -27.12 7.22 17.17 32.90

115 30 -28.46 9.97 20.44 36.43

120 10 -28.04 5.37 19.04 34.32

120 15 -29.43 7.54 20.18 36.47

120 20 -30.75 9.51 21.27 38.58

120 25 -32.08 11.62 22.44 40.84

120 30 -33.46 13.88 23.68 43.28

Annotate: Δ L: brightness value difference; Δ a: red scale value is poor; Δ b: yellow value degree is poor; Δ E: total color difference (comparing) with standard white plate

As seen from the above table, along with the rising of sterilising temp, the prolongation of heat time heating time, brightness, the total color difference of product reduce gradually, show that the browning degree of product is more and more darker, also can be more and more serious to the destruction of nutritional labeling.Take all factors into consideration microbiological indicator and aberration experimental result, adopting sterilising temp is 115 ℃, and the retention time is the sterilising conditions of the combination of 10min as product.

Preparation technology is: raw material weighing, extract immunopotentiator A, B, C according to conventional method, drying is with mineral matter, mixed water material, 60～70 ℃ of hot water dissolving's water materials of getting of vitamin, rehydration 40～50min, standby, emulsifying agent, oil phase material, 60～70 ℃ of water-bath dissolvings, add the water emulsification pretreatment, standby; Two kinds of reserve liquids are mixed, the high speed shear homogeneous, 20MPa is high-pressure homogeneous, can, sealing, 115 ℃ of sterilization 10min, 37 ℃ are incubated 7 days, check, refrigeration.

The specific embodiment

Embodiment 1

The enteral nutrition preparation of basic material proportioning (1000ml): energy density: 1kcal/ml; Protein: 35～40g, energy supply 15%, wherein soybean protein 1/3, casein 2/3; Fat: 25～30g, energy supply 25%, corn oil 6～8g wherein, soybean oil 4～5g, all the other are cream; Carbohydrate: 150g, energy supply 60% mainly is a maltodextrin, and all the other are the carbohydrate that contains in bean powder, milk powder, the milk, and too sweet greasy for anti-mouthfeel, bean powder, milk powder etc. should be selected sugarless products as far as possible; The selenium of selecting 12 kinds of vitamin 11 kinds of mineral matters, particularly tumor patient to special procure.The enteral nutrition preparation of this basic material proportioning is applicable to general tumor patient, the patient who undergos surgery, AIDS patient, infects other viral people, and its concrete raw material proportioning is as follows:

Embodiment 2

Be applicable to the enteral nutrition preparation (1000ml) of the raw material proportioning of the concurrent diabetes of tumor patient: because this type of patient's abnormal carbohydrate metabolism, sugar tolerance reduces, and therefore the ratio of three big materials is adjusted into: carbohydrate is reduced to about 100g, energy supply 10%; Protein rises to 40～50g, energy supply 17%～20%; Fat mass is 50～55g, energy supply 45%～50%.Its concrete raw material proportioning is as follows:

Embodiment 3

Be applicable to the enteral nutrition preparation (1000ml) of the raw material proportioning of the concurrent kidney trouble of tumor patient: clinical think should adopt limit protein raw material proportioning to the kidney patients, but the albumen intake should not be lower than 50g/d, and high-quality protein should account for more than 2/3 of total protein concentration.So protein is 25～30g, and all is casein, not enough energy part is supplied with carbohydrate.Its concrete raw material proportioning is as follows:

Embodiment 4

Be applicable to the enteral nutrition preparation (1000ml) of the raw material proportioning that immunity strengthens: use immunopotentiating agent A:10～15g, B:10～15g, C:500mg.The enteral nutrition preparation of basic material proportioning is applicable to the crowd of various immunity degradation, as in tumor patient, AIDS patient, various virus infections person, the person that accepts the radiation therapy, accept chemotherapy person, the person of undergoing surgery or/and in poor health, and other are in the people in the poor environment, as the people of the staff of dept. of radiology, diver, astronaut, pilot, duplicating person, the harmful radiation exposure of contact, the people of contact harmful chemical.Its concrete raw material proportioning is as follows:

Table 11 product proportioning (1000ml)

The proportioning neoplastic disease concurrent immunity of knurl of swelling in raw material basis strengthens and joins

Diabetes patient's kidney patient ratio

The special-purpose proportioning of special-purpose proportioning

Embodiment 1 embodiment 2 embodiment 3

Embodiment 4

Sugar-free bean powder (g) 40 30 0 40

Skimmed milk power (g) 48 0 40 48

Whole milk powder (g) 13 80 0 13

Salt (g) 2221

Maltodextrin (g) 87 18 100 87

Maize germ oil (g) 10 10 10 10

Fresh milk (ml) 334 600 600 334

Emulsifying agent (g) 4444

Tea Polyphenols (mg) 40 40 40 40

Vitamin (seeing note)

Mineral matter (seeing note)

Glutamine (g) 000 12.5

Arginine (g) 000 5.0

LBP-X (mg) 000 500

Water is supplied 1000ml

1000ml 1000ml 1000ml

Each proportioning product contains

Energy, (kcal) 1,000 1,000 1,000 1000 protein, (g) 37.6 42.50 30.1 37.6 fat, (g) 28.2 51.7 31.0 28.2 carbohydrate g150.6 92.4 151.2 150.6

Note: vitamin C 120mg, niacinamide 14mg, vitamin E 8mg, pantothenic acid 4mg, vitamin B6 2mg, vitamin B1 1.4mg, vitamin B2 1.4mg, vitamin A 536 μ g, folic acid 400 μ g, biotin 100 μ g, calciferol 5 μ g are or/and cobalamin 3 μ g, and calcium 100mg, phosphorus 77mg, magnesium 30mg, iron 10mg, zinc 10mg, potassium 4mg, manganese 3mg, copper 2mg, molybdenum 100 μ g, chromium 100 μ g are or/and selenium 30 μ g.

In the specific embodiment, Tea Polyphenols mostly is 1500mg most, and maltodextrin mostly is 150g most,, maize germ oil is minimum to be 2g, and fresh milk mostly is 1450ml most, and emulsifying agent is minimum to be 0.5g, and glutamine mostly is 25g most, and arginine mostly is 7.5g most.

Obviously, nutritional factors of the present invention is resulting through arduous creative work, and its nutrition formation meets human body requirements, is suitable for the nutritional support of human body.

The drug effect data

Tumour is a kind of multifactor too many levels disease, though its generation and modulation on immune status do not have inevitable direct causality, the development of tumour is closely related with modulation on immune status.On the one hand, tumour has weak immunogenicity, can cause the immune response of body immune system, but be not enough to excite stronger immune response; On the other hand, tumour cell produces inhibitory action by secretion certain or several immunosuppressive factor to the immune system of body, and the development process of tumour depends on the contrast of this two aspects strength.

Body is mainly cellular immunity to the immunity of tumour, comprises the macrophage of T lymphocyte, NK cell, activation and granulocyte etc.Wherein the T lymphocyte has important function to be proved to be in the reaction of mediation tumor rejection and in to the memory of tumour antigen generation specific immunity, therefore this experiment as experimental index, is carried out studies on immune function to the enteral nutrition preparation of being developed with the killing activity of the phagocytic function of lymphopoiesis ability, macrophage and NK cell.

Because the adding of immunopotentiator can exert an influence to the product taste, and some compositions have dual regulation to body's immunity, be that low concentration promotes, high concentration suppresses, thus experimental design two immunity strengthen the raw material proportionings: the low concentration immunity strengthens raw material proportioning (content of immunopotentiator B is 0.5% in the raw material proportioning) and high concentration immunity enhancing raw material proportioning (B content is 1.25%).

3 materials and methods

3.1 animal used as test and grouping

90 of 18～20g male ICR mouses are available from epidemic research institute of China Preventive Medicial Science Institute animal breeding field.Be divided into 5 groups at random according to body weight, 18 every group, divide three cages to raise.Experiment is divided into five groups: negative control group, and irritate and feed physiological saline; Positive controls is irritated stomach import immunity enhancement type enteral nutrition preparation IMPACT (indenes is abundant); Sample I group is irritated and is fed basic material proportioning nutrient solution; Sample II group is irritated and is fed low concentration immunity enhancing raw material proportioning; Sample III group is irritated and is fed high concentration immunity enhancing raw material proportioning.

Every its mouse oral irritated to feed and organized nutrient solution 1ml every day, divide morning and afternoon respectively once, measure the mouse body weight weekly twice, taking off neck after two weeks puts to death, measuring blood parameters, body weight increase and organ coefficient according to conventional method measures, carry out the experiment of carbon particle clearance rate, spleen lymphocyte proliferation experiment, NK cell killing activity ().

3.2 result and discussion

3.2.1 the mouse body weight increases and blood parameters is measured

Table 11 mouse body weight increases and the blood parameters measurement result

Negative control positive control sample I sample II sample III

9.061± 6.729± 6.939± 6.422± 6.800±

Body weight increases (g)

1.633 1.810 ^** 1.840 ^** 2.367 ^** 2.351 ^**

53.95± 55.10± 55.63± 54.75± 53.68±

Total protein (g/L)

3.54 3.30 1.33 2.44 3.32

33.90± 34.63± 34.56± 34.13± 33.56±

Albumin (g/L)

1.34 1.21 0.41 0.86 1.28

Prealbumin

0.24±0.02 0.23±0.02 0.23±0.01 0.23±0.02 0.22±0.01

(g/L)

Hemoglobin 13.46 ± 13.16 ± 12.87 ± 12.48 ± 12.28 ±

(g/dl) 0.98 0.54 0.52 0.83 0.88

Annotate: each group is compared with blank, ^*P＜0.05, ^*P＜0.01; Each group is compared #P＜0.05, ##P＜0.01 with positive control.n＝12

By above result as can be known, the body weight increase of positive control and each group of experiment is significantly less than negative control, and every blood parameters and negative control do not have difference, slow down though the increase of mouse body weight is described, but still can keep normal physiological function, there is no malnutrition and occur.The increase of mouse body weight slows down may be uncomfortable relevant to nutrient solution with mouse, experiment is observed and is found, irritates the food ration of respectively organizing mouse feed of feeding nutrient solution and obviously reduces, and the increase of body weight significantly is lower than negative control during 4d, during to 8d, each increase of organizing body weight is there was no significant difference.

3.2.2 carbon particle clearance rate experiment

It is as shown in the table that each organizes the carbon particle clearance rate K value of mouse.

Table 12 macrophage in 20 minutes to the removing ability of india ink

Negative control positive control sample I sample II sample III

K(×10 ^- 3.47 ± 3.85±0.45 3.64±0.32 3.75±0.39 3.67±0.37

²) 0.40

Annotate: each group is compared with blank, ^*P＜0.05, ^*P＜0.01; Each group is compared #P＜0.05, ##P＜0.01 with positive control.n＝12

The above results shows that the activate the phagocytic capacity that mouse macrophage is respectively organized in experiment all has trend of rising than negative control group, but there was no significant difference.

3.2.3 spleen lymphocyte proliferation experiment

It is as shown in the table that each organizes the propagation percentage of mouse spleen lymphocyte under ConA stimulates.

The multiplication capacity (%) of table 13 SPL under ConA stimulates

Negative control positive control sample I sample II sample III

38.23±8.01 57.5±12.6 50.9±10.9 101.8±27.1 104.0±22.3

Annotate: each group is compared with blank, ^*P＜0.05, ^*P＜0.01; Each group is compared #P＜0.05, ##P＜0.01 with positive control.n＝12

The above results shows, positive control and sample I, II, III all can promote the breeder reaction of mouse spleen lymphocyte under ConA stimulates, its effect is all strong than negative control group, the short multiplication capacity of sample II, III is higher, the rate of increase is all above 100%, apparently higher than positive control, but because the standard deviation of testing in the cell body is too big, there was no significant difference between each group.

3.2.4NK cell killing activity

After table 11 is SPL and K562 cell co-incubation 4h, remaining K562 cell concentration.

The NK cell is to the kill capability of K562 tumour cell in table 14 spleen

Negative control positive control sample I sample II sample III

0.256±0.032 0.159± 0.232± 0.156± 0.253±0.023#

0.024 ^* 0.040# 0.021 ^*

Annotate: each group is compared with blank, ^*P＜0.05, ^*P＜0.01; Each group is compared #P＜0.05, ##P＜0.01 with positive control.n＝12

The above results shows: in two weeks, the killing activity of positive control and II sample sets mice spleen NK cell is significantly higher than negative control, I, III sample are compared with blank the influence of NK cell killing activity does not have difference, significantly is lower than positive control and II sample.

Sample II, III are the content difference of immunopotentiator B on the raw material proportioning, but the killing activity of NK cell has significant difference, and prompting immunopotentiator B killing activity to the NK cell under high concentration has certain inhibitory action.

3.3 conclusion

Three kinds of nutrient solutions and positive controls mouse body weight increase and slow down than negative control group, but every biochemical indicator still keeps normally, with the control group indifference, illustrate that this nutrient solution can keep the normal Physiology and biochemistry level of mouse.

The immunization experiment results suggest, three kinds of nutrient solutions have certain facilitation to immune function of mice.Wherein the effect of II sample is best, can significantly improve the killing activity (P＜0.05) of NK cell, obviously promotes spleen lymphocyte proliferation, and the activate the phagocytic capacity of macrophage is also had facilitation, and its effect and positive control are suitable.The III sample can obviously promote spleen lymphocyte proliferation, and the phagocytic function of NK cell killing activity and macrophage is not had obvious effect; And the basic indifference of I sample and negative control, this and I sample are the basic material proportioning, and II, III sample meet for the design that immunity strengthens the raw material proportioning.

Because positive control is the immunity enhancement type enteral nutrition preparation of selecting for use that effect is best, clinical practice is the widest of generally acknowledging in the world at present, the II sample can reach the immunoenhancement result suitable with it, has reached certain designing requirement.

The basic material proportioning can be used for the clinical nutrition support of general tumor patient, and II raw material proportioning product can be used for needing to strengthen the tumor patient of immunocompetence.

Basic material proportioning clinical nutrition Research on effect

4.1 research object and method

4.1.1 research object

Many studies confirm that (Wang Xiaojia, 1995; Liao Jun, 1995; Zhang Fangxin, 1994) remarkable decline all appears in every nutritive index and immune indexes in tumor patient operation back, the chemicotherapy process, the malnutritive patient situation more serious (Peng Junsheng, 1998) that descends.

The validity and the security of the enteral nutrition preparation clinical nutrition of developing in order to inquire into, we select cancer of the stomach, colorectal cancer, lung cancer be main malignant tumor patient 101 examples as research object, the male sex's 67 examples wherein, women's 34 examples, 57.14 ± 13.56 years old mean age, the range of age 30～83 years old.The primary tumor distribution situation is lung cancer 24 examples, colorectal cancer 24 examples, cancer of the stomach 26 examples, head and neck cancer 23 examples, other 4 example; Press (UICC) international TNM standard by stages, the patients undergoing chemotherapy pathological staging is III～IV phase, and chemotherapy regimen mates substantially.

According to voluntary principle the patient is divided into three groups: EA group, parenteral nutrition group, diet guide group.Three groups of patients are mated substantially at aspects such as sex, age, primary tumor distribution and therapeutic modalities.

4.1.2 research method

The tumor patient of underwent operative or radiotherapy, chemotherapeutic treatment carried out three days dietary survey before nutritional support, " meals design and trophic analysis " groupware with Beijing Research Center for Preventive Medicine and the joint research and development exploitation of development in science and technology Co., Ltd of the prosperous Guoan of Beijing monarch carries out evaluation of nutrition, understands the absorption situation of patient's heat energy and other nutrient.According to this patient's normal nutrition intake, to the insufficient section that energy and nutrient are taken in, our enteral nutrition preparation of developing voluntarily of the oral or tube feed of EA group patient, the scope of application of nutrient solution is 250～1000ml/d, average out to 500ml/d.The parenteral nutrition group is used intravenous nutrition.The diet guide group is carried out diet guide by the nutritionist to the patient, and the patient selects food according to doctor's advice oneself then.All patients are not all used other any nutritional preparation, on anti symptom treatment such as give necessary antibiotic, analgesic drug product, protect the liver, do not have difference.Be 14d observing time.Before nutritional support, behind the nutritional support 14d, carry out physical situation evaluation respectively, body measurement, and routine blood test and biochemistry detection.

The evaluation of nutrition index: ECOG (Zubroid) classification of WHO recommendation and physical situation (Performance Status, KPS) standards of grading of Karnofsky are adopted in physical situation evaluation; The anthropological measuring index adopts body weight, upper-arm circumference, triceps muscle of arm skinfold; Routine blood test and biochemical indicator are mainly used leucocyte, LC, red blood cell, hemoglobin, total protein, albumin etc., are checked according to conventional method by clinical laboratory of tumour hospital.

4.1.3 statistical procedures

All experimental datas all are expressed as mean ± standard deviation (form of x ± s).Adopting SAS 6.12 statistical softwares to carry out data analysis handles.The comparison of baseline value: the compositions before the treatment of two groups of cases are carried out Chi-square Test, and each is organized between the different therapeutic modalities relatively: differences before and after two groups of cases treatments are carried out the t check, all with P＜0.05 for having significant difference, P＜0.01 is a utmost point significant difference.

4.2 result and discussion

4.2.1 the comparison of three groups of patient's basic conditions

Three groups of patients are comparing the equal not statistically significant of result (P＞0.05) aspect the distribution of age, sex, primary lesion, therapeutic modality etc.Illustrate that respectively to organize primary condition suitable, have comparativity.The result shows sex distributional difference not statistically significant (P=0.7633) between (table 20) three groups; Age difference not statistically significant (P=0.6514, table 21) between three groups; Three groups of primary tumor difference in distribution not statistically significants (P=0.4429, table 22); Three groups of therapeutic modality difference in distribution not statistically significants (P=0.1797, table 23); Illustrate that respectively to organize primary condition suitable, have comparativity.

Table 15 each nutritional support mode group sex and case load distribution situation

Sex

The nutritional support mode adds up to (example)

Man's (example) woman (example)

EA group 27 14 41

Diet guide group 20 12 32

Parenteral nutrition group 20 8 28

Add up to 67 34 101

Each nutritional support mode group age age ratio of table 16

The age distribution of nutritional support mode

EA group 56.95 ± 14.81

Diet guide group 55.75 ± 12.41

Parenteral nutrition group 59.00 ± 13.17

Average 57.14 ± 13.56

Each nutritional support mode group primary lesion distribution situation of table 17

Primary tumor

The nutritional support mode adds up to

Lung cancer colorectal cancer cancer of the stomach head and neck cancer other

EA group 97 11 10 4 41

Diet guide group 79970 32

Parenteral nutrition group 88660 28

Add up to 24 24 26 23 4 101

Annotate: other is ^*Liver cancer 1 example, cervical carcinoma 1 example, lymthoma 1 example, thymoma 1 example

Each nutritional support mode group therapeutic modality distribution situation of table 18

Therapeutic modality

The nutritional support mode adds up to

The chemotherapy postoperation radiotherapy

EA group 29 2 10 1

Diet guide group 25 432

Parenteral nutrition group 22 428

Add up to 76 10 15 11

4.2.2 the mensuration and the analysis of three groups of forward and backward nutrition deliberated indexs of patient treatment

The measurement result of three groups of every nutrition deliberated indexs in patient treatment front and back is shown in table 19.

The mensuration of three groups of forward and backward each nutritive indexs of patient treatment of table 19

Diet guide group parenteral nutrition group EA group

The mensuration project

After preceding treatment is treated in the treatment back before treating after the treatment before the treatment

1.34± 2.37± 1.29± 3.0± 1.71± 2.37±

The ECOG classification

0.97 1.07 0.85 0.27 0.93 0.89

74.69± 51.88± 75.36± 63.57± 67.56± 55.49±

The KPS scoring

18.49 18.91 6.03 5.59 18.41 19.49

63.23± 61.75± 64.44± 63.41± 62.09± 61.28±

Body weight (kg)

11.12 10.97 9.23 9.14 11.93 11.82

Upper-arm circumference 26.23 ± 25.28 ± 27.02 ± 27.26 ± 25.13 ± 24.89 ±

(cm) 3.84 4.05 3.63 3.80 4.28 4.27

The triceps muscle of arm

21.59± 18.93± 24.71± 24.57± 19.98± 19.91±

Skinfold

11.96 11.50 12.61 12.11 13.30 12.95

(mm)

Leucocyte meter 5.76 ± 6.61 ± 6.77 ± 7.3 ± 6.98 ± 7.47 ±

Number (109/L) 2.52 6.20 2.97 2.83 4.08 3.68

Lymphocyte

1.45± 1.32± 1.64± 1.49± 1.85± 1.78±

Counting

0.79 1.37 0.56 0.57 3.33 3.66

(10/L)

The red blood cell meter

3.79± 3.23± 4.14± 3.92± 3.83± 3.64±

Number

0.75 1.20 0.76 0.60 0.83 0.66

(1012/L)

Hemoglobin 15.26 ± 11.12 ± 12.72 ± 10.78 ± 13.68 ± 13.76 ±

(g/L) 20.33 1.96 2.58 2.5 14.42 18.04

Total protein 68.18 ± 63.01 ± 78.74 ± 76.1 ± 66.43 ± 62.48 ±

(g/L) 6.57 7.01 5.71 5.91 6.05 11.02

Albumin 39.58 ± 31.91 ± 40.82 ± 36.5 ± 40.15 ± 38.04 ±

(g/L) 4.61 5.10 5.03 4.36 3.72 6.64

Table 20 is the situation of change of each nutritive index before and after three groups of patient treatments.

The variation of three groups of forward and backward each nutritive indexs of patient treatment of table 20

Index diet guide parenteral nutrition EA P1 P2

Group group group

ECOG classification 1.03 ± 1.03 1.71 ± 0.90 0.66 ± 0.91＜＜0.01

0.01

KPS scoring---＜＞0.05

22.81±9.22 11.79±6.11 12.07±8.06 0.01

Body weight (kg)-1.48 ±-1.03 ±-0.81 ± 2.50＜＞0.05

2.69 2.98 0.01

Upper-arm circumference (cm)-0.95 ±-0.24 ±-0.24 ± 0.81＜＞0.05

1.99 1.99 0.01

Triceps skinfold thickness-2.66 ±-0.14 ±-0.07 ± 1.66＜＞0.05

(mm) 3.96 7.60 0.01

White blood cell count(WBC) 0.85 ± 6.40 0.53 ± 3.79 0.49 ± 2.56＜＞0.05

(10 ⁹/L) 0.05

LC-0.13 ±-0.15 ±-0.07 ± 0.95＜＜0.01

(10 ⁹/L) 1.24 0.73 0.01

Red blood cell count(RBC)-0.56 ±-0.22 ±-0.19 ± 0.63＜＞0.05

(10 ¹²/L) 1.05 0.63 0.01

Hemoglobin (g/L)-2.74 ± 1.63-1.94 ± 2.76-1.49 ± 2.72＜＞0.05

0.01

Total protein-5.17 ±-2.64 ±-2.95 ± 4.71＜＞0.05

(g/L) 3.22 3.80 0.01

Albumin-7.67 ±-4.32 ±-2.11 ± 3.27＜＜0.05

(g/L) 2.99 3.53 0.01

Annotate: P1 is that EA group and diet guide group compare; P2 is that EA group and parenteral nutrition group compare

By The above results as can be seen, three groups of patients because operation or put, the influence of chemotherapy, descending all appears in physical work capacity, showing as the ECOG classification increases, the KPS reduction of marking, but EA group ECOG classification increase all significantly is lower than other two groups (P＜0.01), KPS scoring reduction significantly is lower than diet guide group (P＜0.01), compare there was no significant difference (P＞0.05) with the parenteral nutrition group, illustrate after EA is supported in operation or chemicotherapy and recover the effect that the physical aspect of patient has and the parenteral nutrition support is similar, significantly be better than the diet guide group.

Aspect the body measurement index, body weight and the reduction of triceps muscle of arm skinfold significantly are lower than diet guide group (P＜0.01) and parenteral nutrition group there was no significant difference; The upper-arm circumference reduction significantly is lower than diet guide group (P＜0.01), but is significantly higher than parenteral nutrition group (P＜0.05).Illustrate that this enteral nutrition preparation significantly is better than full diet to the influence of body index.

White blood cell count(WBC) and LC can reflect patient's immunocompetence to a certain extent.By last table result as can be seen enteral nutrition preparation can increase human leukocytes quantity, reduce the reduction (P＜0.01) of lymphocyte quantity, reduce chemicotherapy to the immune damage of patient.

Red blood cell is the maximum immunocyte of quantity in the human body, can and store antigen by identification and remove CIC ELISA.The reduction of EA group red blood cell and hemoglobin significantly is lower than diet guide group (P＜0.01) and parenteral nutrition group there was no significant difference.Point out this enteral nutrition preparation can reach the effect identical aspect anaemia that chemicotherapy causes and the hematid immunity function reduction correcting, significantly be better than full diet with parenteral nutrition.

Albumin is one of the sensitiveest index of reflection health nutrition condition.The albuminous reduction of EA group patients serum significantly is lower than diet guide group (P＜0.01) and parenteral nutrition group (P＜0.05).Illustrate that this enteral nutrition preparation can correct patient's potein deficiency malnutrition better than full diet and parenteral nutrition.

Head and neck neoplasm and cancer of the esophagus tumor patient are underfed people at highest risk, its most of alimentary canal is not involved by tumour or not subject influence, therefore be well suited for EA, in carrying out the nutritional support process, also find, patient's complexion, the state of mind, skin elasticity obviously improve, and it is good that health is recovered.

The nutritional preparation that experiment is this time used is the base stock proportioning that aims at the tumor patient design, can be used as unique nutrient source of patient, and can use for a long time, and it is at the experiment effect that all reaches expection aspect the nutrition condition of improving the patient and the immunologic function.

4.3 conclusion

Clinical trial shows that basic material proportioning product can better be tolerated by the patient, and the diet guide group is compared, and can significantly increase patient's physical work capacity; Alleviate the patient because the reduction of body weight, upper-arm circumference and the every body measurement index of triceps muscle of arm skinfold that operation and chemicotherapy cause; Can significantly reduce the reduction of the every blood parameters of patient, illustrate that this enteral nutrition preparation has good clinical nutritional support effect.Compare with parenteral nutrition, both nutritional support effects are similar, but the expense of EA is starkly lower than parenteral nutrition, illustrate that a kind of really quality safety of this product is reliable, and the nutritional support effect is remarkable, and the higher enteral nutrition preparation of cost performance.

Above-mentioned drug effect and clinical treatment show, various product of the invention process can provide tumor patient, AIDS patient, various virus infections person, the person that accepts the radiation therapy, accept chemotherapy person, the person of undergoing surgery or/and in poor health, and other are in the people in the poor environment, as the required special nutritional support thing of people of the people of the staff of dept. of radiology, diver, astronaut, pilot, duplicating person, the harmful radiation exposure of contact, contact harmful chemical or/and immune reinforce that is to say that various product of the present invention also all is applicable to them.

Claims (17)

1. enteral nutrition preparation, it is characterized in that by comprising that following materials of weight proportions makes: Tea Polyphenols 30-1500mg, bean powder 0-40g, milk powder 13-80g, salt 1-2g, maltodextrin 18-150g, maize germ oil 2-10g, fresh milk 300-1450ml, emulsifying agent 0.5-4g, vitamin, mineral matter.

2. enteral nutrition preparation as claimed in claim 1, it is characterized in that: used bean powder is the sugar-free bean powder, milk powder is full-cream or/and skimmed milk power.

3. one kind as claim 1 or 2 any one described enteral nutrition preparation, it is characterized in that vitamin and mineral matter are selected from: vitamin C 120mg, niacinamide 14mg, vitamin E 8mg, pantothenic acid 4mg, Cobastab ₆2mg, Cobastab ₁1.4mg, Cobastab ₂1.4mg, vitamin A 563 μ g, folic acid 400 μ g, biotin 100 μ g, vitamin D ₂5 μ g are or/and Cobastab ₁₂3 μ g, and calcium 100mg, phosphorus 77mg, magnesium 30mg, iron 10mg, zinc 10mg, potassium 4mg, manganese 3mg, copper 2mg, molybdenum 100 μ g, chromium 100 μ g are or/and selenium 30 μ g.

4. enteral nutrition preparation as claimed in claim 3 is characterized in that by comprising that following materials of weight proportions makes: sugar-free bean powder 40g, skimmed milk power 48g, whole milk powder 13g.

5. enteral nutrition preparation as claimed in claim 3 is characterized in that by comprising that following materials of weight proportions makes: sugar-free bean powder 30g, skimmed milk power 0g, whole milk powder 80g.

6. enteral nutrition preparation as claimed in claim 3 is characterized in that by comprising that following materials of weight proportions makes: sugar-free bean powder 0g, skimmed milk power 40g, whole milk powder 0g.

7. enteral nutrition preparation as claimed in claim 4 is characterized in that by comprising that following materials of weight proportions makes: glutamine 25g, arginine 7.5g, LBP-X 500mg.

8. preparation method as any one described enteral nutrition preparation of claim 4-7, it is characterized in that: the described raw material of claim 4-7 is divided into water material, oil phase material and emulsifying agent, dissolved emulsifier and oil phase material also add the water emulsification pretreatment, water dissolving water material and with its rehydration, two kinds of liquid are mixed homogeneous, can, sealing, sterilization.

9. the preparation method of an enteral nutrition preparation as claimed in claim 7 is characterized in that: described LBP-X is pressed the method for water extract-alcohol precipitation and is extracted, through washing back convection drying repeatedly, or again after the water dissolving, concentrated, drying.

10. preparation method as any one described enteral nutrition preparation of claim 4-7 is characterized in that: the HLB value is 9-10, and the compound emulsifying agent proportioning is a monoglyceride: lecithin: Tween60=4: 1: 5; Emulsifying agent addition is 0.4%; Homogenization pressure is 20MPa; 115 ℃ of sterilization 10min.

11. the purposes of an enteral nutrition preparation as claimed in claim 4 is characterized in that: be used to prepare the agent of tumor patient nutrition supply.

12. the purposes of an enteral nutrition preparation as claimed in claim 5 is characterized in that: the nutrition supply agent that is used to prepare the concurrent diabetic of tumour.

13. the purposes of an enteral nutrition preparation as claimed in claim 6 is characterized in that: the immunopotentiator that is used to prepare the concurrent nephrotic of tumour.

14. the purposes of an enteral nutrition preparation as claimed in claim 7 is characterized in that: be used to prepare tumor patient, AIDS patient, various virus infections person, the person that accepts the radiotherapy, accept chemotherapy person, the person of undergoing surgery or/and person's in poor health immunopotentiator.

15. the purposes of an enteral nutrition preparation as claimed in claim 7 is characterized in that: be used for preparing the people of the staff of dept. of radiology, diver, astronaut, pilot, duplicating person, the people who contacts harmful radiation exposure, contact harmful chemical or/and other are in the people's of poor environment nutrition supply agent and/or immunopotentiator.

16. one kind as any one described enteral nutrition preparation of claim 4-7, it is characterized in that: make directly from stomach and intestine or/and the formulation of orally give.

17. one kind as any one described enteral nutrition preparation of claim 4-7, it is characterized in that: make emulsion and/or electuary.