Enteral nutrition composition for improving intestinal intolerance of postoperative patient and application of enteral nutrition composition

Abstract

The invention belongs to the technical field of medical nutritional food, and particularly relates to an enteral nutritional composition for improving intestinal intolerance of postoperative patients and application of the enteral nutritional composition. The invention provides an enteral nutrition composition for improving intestinal intolerance of postoperative patients, the enteral nutrition composition is composed of carbohydrates, proteins and composite minerals, the carbohydrates and the proteins are taken as the basis, the composite minerals are strengthened, the requirement of enteral nutrition support is met, the normal secretion function of intestinal mucosa is ensured, and the intestinal intolerance of the postoperative patients is improved. According to the present invention, the intestinal tract barrier function can be maintained, the nutrition state can be improved, the nitrogen balance of the body can be promoted, the immune regulation can be maintained, the polysaccharide-protein composite gel system can be formed in vivo, the free water of the intestinal tract can be cured, the postoperative enteric cavity water sample diarrhea can be significantly reduced, and the dehydration and electrolyte disorder caused by diarrhea can be rapidly corrected;

Description

Technical Field

[0001] This invention belongs to the technical field of medical nutritional foods, and specifically relates to an enteral nutrition composition for improving intestinal intolerance in postoperative patients and its application. Background Technology

[0002] With the advancement of modern medicine, enteral nutrition support has received increasing attention from the medical community. Enteral nutrition support helps ensure that the intestinal mucosa maintains normal secretory function, maintains intestinal barrier function, improves nutritional status, promotes nitrogen balance, and maintains immune regulation, thus becoming the preferred nutritional intervention method for critically ill patients.

[0003] However, due to the severity and complexity of the disease, 30–70% of patients undergoing general anesthesia for abdominal, gastrointestinal, hepatobiliary, and pancreatic surgeries experience early intestinal intolerance, manifested as mixed osmotic / secretive diarrhea, decreased bowel sounds, interruption of enteral nutrition (EN), and prolonged hospitalization for 3–7 days. The main reasons include: (1) sympathetic nerve excitation during surgery leads to ischemia-reperfusion of the intestinal mucosa, causing degradation of epithelial tight junctions (ZO-1, occludin); (2) anesthetics and antibiotics cause dysbiosis, resulting in a decrease in short-chain fatty acid (SCFA) levels and causing water and sodium absorption disorders; (3) early postoperative EN formulas often use whole protein + maltodextrin, with high osmotic pressure (≥450 mOsmol / kg) leading to "backflow" of water in the intestinal lumen. Therefore, it is impossible to achieve the target feeding dose as originally planned to achieve the purpose of nutritional therapy. If enteral nutrition intolerance persists for a long time, it will directly affect the normal physiological structure and function of the intestine, damage the intestinal mucosal barrier function, lead to intestinal flora translocation, and thus cause enterogenic endotoxemia, ultimately leading to multiple organ dysfunction syndrome (MODS).

[0004] Enteral nutrition preparations, when used in conjunction with medication or surgery, play a positive role in promoting disease progression and improving the nutritional status of patients. Enteral nutrition suspensions are common enteral nutrition preparations in special medical purpose formula foods. Their main components are water, carbohydrates, proteins, fats, vitamins, minerals, and trace elements—essential nutrients for the human body. They are suitable for patients with gastrointestinal function or partial gastrointestinal function who cannot or do not wish to consume sufficient amounts of regular food to meet their nutritional needs and require enteral nutrition therapy. CN111194912A discloses a stable medical liquid enteral nutrition composition and its preparation method, as an enteral nutrition preparation. Other related products are also on the market, such as Nengliquan and Jiaviti.

[0005] According to GB29922, "General Rules for Foods for Special Medical Purposes," non-complete nutritional foods for special medical purposes are classified into nutrient components, electrolyte formulas, thickening components, liquid formulas, and amino acid metabolism disorder formulas, based on their product composition characteristics. Among them, liquid formulas are non-complete nutritional foods for special medical purposes based on carbohydrates and proteins, and may contain various vitamins, minerals, and appropriate amounts of dietary fiber. Because they do not contain fat, they are suitable for patients who need to restrict their fat intake.

[0006] Existing enteral nutrition preparations, including enteral nutrition suspensions or liquid formulations, usually have the following technical problems: (1) Oral rehydration salts (ORS): only correct electrolyte imbalances and cannot repair the intestinal barrier; (2) Monoglutamine (Gln) or zinc preparations: effective only at doses ≥0.3 g / kg / d, poor compliance; (3) Prebiotics / probiotics: pose a risk of bacteremia in patients with weakened immune systems after surgery; (4) Hydrolyzed whey protein: Contains β-lactoglobulin, still causing 5–8% allergic reactions; (5) Ordinary glutinous rice flour or resistant starch: retains water but has high viscosity, which can easily clog tubes when fed via tube feeding.

[0007] In addition, to maintain the stability of the main components such as proteins and fats in the formulation, the amount of vitamins and / or minerals added to the formulation often does not meet the specified requirements; the product is prone to protein flocculation and precipitation, which affects its clinical application and safety; the product is mostly a liquid product, which presents difficulties in transportation and storage.

[0008] Therefore, there is an urgent need for an isotonic enteral nutrition composition that can repair the intestinal barrier, quickly alleviate intestinal intolerance, and can be fed via tube. This composition can rapidly correct negative nitrogen balance, reduce infection rate, reduce gastrointestinal adverse reactions, improve the quality of life of postoperative patients, and shorten hospital stay. Summary of the Invention

[0009] The purpose of this invention is to provide an enteral nutrition composition for improving postoperative intestinal intolerance in patients and its application, which can rapidly relieve postoperative intestinal intolerance (diarrhea, low electrolyte absorption, mucosal inflammation) and can be used for medical purposes such as oral and tube feeding.

[0010] The objective of this invention is achieved through the following technical solution: In a first aspect, the present invention provides an enteral nutrition composition for improving intestinal intolerance in postoperative patients, comprising carbohydrates, proteins and complex minerals, wherein, by weight, the carbohydrates are 10-80 parts, the protein is 5-40 parts, and the minerals are 1-10 parts.

[0011] In some specific embodiments of the present invention, the carbohydrate is one or more of puffed rice flour, puffed corn starch, puffed tapioca starch, and puffed glutinous rice flour; further, the water absorption index (WAI) of the carbohydrate is 3.0–8.0 g / g; further, the amylose content of the carbohydrate is 5–30%; further, the degree of puffing of the carbohydrate is 12–18; further, the cold water solubility index (CWSI) of the carbohydrate is ≥75%.

[0012] In some specific embodiments of the present invention, the protein is a non-animal source protein, further, the protein has an amino acid score ≥1 and the proportion of high-quality protein ≥50%, further, the protein is yeast protein and wheat hydrolysate protein in a weight ratio of (1-2):1.

[0013] In some specific embodiments of the present invention, the yeast protein has ≥1% (w / w) β-glucan, ≥1% (w / w) nucleotides, and ≥1% (w / w) arginine. Further, the yeast protein is Saccharomyces cerevisiae protein, and the β-glucan is β-1,3 / 1,6-glucan. Further, the wheat hydrolysate has ≥22% (w / w) Gln peptides, ≥30% (w / w) peptides with a molecular weight <1kDa, and <5% (w / w) free amino acids.

[0014] In some specific embodiments of the present invention, the composite minerals, by weight, comprise one or more of the following: 0-10 parts sodium salt, 0-10 parts potassium salt, 0.01-2 parts iron salt, 0.01-2 parts zinc salt, 0.1-10 parts calcium salt, and 0-10 parts magnesium salt; further, the sodium salt is one or more of sodium chloride, sodium citrate, disodium hydrogen phosphate, sodium bicarbonate, and sodium dihydrogen phosphate; further, the potassium salt is one or more of potassium chloride, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, potassium bicarbonate, potassium citrate, and potassium acetate; further, the iron salt is ferric sodium ethylenediaminetetraacetate, ... The zinc salt is one or more of the following: ferrous pyrophosphate, ferrous fumarate, ferrous gluconate, ferric citrate, ferrous glycinate, and ferrous sulfate; further, the zinc salt is one or more of the following: zinc gluconate, zinc sulfate, zinc glycinate, zinc oxide, zinc lactate, zinc citrate, zinc chloride, and zinc acetate; further, the calcium salt is one or more of the following: calcium carbonate, calcium gluconate, calcium citrate, L-calcium lactate, calcium hydrogen phosphate, calcium chloride, tricalcium phosphate, calcium oxide, calcium sulfate, and glycerophosphate; further, the magnesium salt is one or more of the following: magnesium carbonate, magnesium sulfate, magnesium chloride, magnesium oxide, magnesium hydrogen phosphate, and magnesium gluconate.

[0015] In a second aspect, the present invention provides the use of the aforementioned enteral nutrition composition in the preparation of a food for special medical purposes (FSMP) for improving intestinal intolerance in postoperative patients, wherein the FSMP is a nutritional food for early enteral nutritional support for patients with incomplete or poor gastrointestinal function after surgery.

[0016] In a third aspect, the present invention provides an FSMP for improving intestinal intolerance in postoperative patients, wherein, by weight, the special medical purpose formula food contains 20-90 parts of the enteral nutrition composition as described in any one of claims 1-5, 5-80 parts of maltodextrin, 0.1-2 parts of compound vitamins, and 0-2 parts of edible flavoring.

[0017] In some specific embodiments of the present invention, the maltodextrin is MD10 maltodextrin, MD15 maltodextrin, or MD20 maltodextrin.

[0018] In some embodiments of the present invention, the compound vitamins, by weight, comprise: 0.2-0.7 parts of vitamin A derivatives, 0.1-0.4 parts of vitamin D derivatives, 1-4 parts of dl-α-tocopherol acetate, 0.04-0.09 parts of thiamine salt derivatives, 0.04-0.09 parts of riboflavin, 0.1-0.5 parts of pyridoxine hydrochloride, 0.1-0.5 parts of cyanocobalamin, 0.1-0.9 parts of nicotinamide, and leaf extract. The vitamin A derivative comprises 0.01-0.09 parts of acid, 0.1-0.9 parts of D-calcium pantothenate, 8-16 parts of sodium L-ascorbate, and 1-9 parts of taurine, or one or more thereof; furthermore, the vitamin A derivative comprises retinyl acetate, retinyl palmitate, and β-carotene, the vitamin D derivative comprises cholecalciferol and ergocalciferol, or one or more thereof, and the thiamine salt derivative comprises thiamine hydrochloride and / or thiamine nitrate.

[0019] In some embodiments of the present invention, the FSMP has an osmotic pressure of 200–340 mOsmol / kg, a pH of 6.0–7.8, and an energy density of 0.5–1.5 kcal / mL; furthermore, the FSMP can be formulated into ready-to-drink oral rehydration suspensions, semi-solid tube feeding gels, or oral nutritional supplements by adjusting the amount of water added.

[0020] The technical solution provided by this invention has the following technical contributions: (1) The present invention provides an enteral nutrition composition for improving intestinal intolerance in postoperative patients, which is composed of carbohydrates, proteins and complex minerals. Based on carbohydrates and proteins, it meets the needs of enteral nutrition support, helps to ensure that the intestinal mucosa maintains normal secretory function, maintains intestinal barrier function, improves nutritional status, promotes nitrogen balance and maintains immune regulation. In addition, it can form a complex gel system composed of polysaccharides and proteins in vivo, "solidifying" the free water in the intestine and significantly reducing "watery diarrhea" in the postoperative intestinal lumen.

[0021] (2) The enteral nutrition composition of the present invention uses carbohydrates obtained by a "twin-screw extruder-high pressure explosion-vacuum flash steaming" process or other processes. The carbohydrates have an expansion degree of 12-18, an amylose content of 5-30%, a water absorption index (WAI) of 3.0-8.0 g / g, and a cold water solubility index (CWSI) ≥75%. The carbohydrates of the present invention can absorb 3-5 times their own weight in water and have a viscosity of <80 mPa·s at 37°C and 100 s⁻¹ shear. They can be continuously fed through tubes for 24 hours without clogging the tube and will not increase the workload of clinical nursing.

[0022] (3) The enteral nutrition composition of the present invention uses non-animal-derived proteins, which are plant and / or yeast-derived and free of milk allergens. Among them, wheat hydrolyzed protein (WHP) is cleaved by alkaline protease to enrich Gln (≥22% w / w) and <1 kDa small peptides by more than 30%, which can activate mTOR signaling on the intestinal epithelial basement membrane side, upregulate claudin-4, inhibit NF-κB inflammatory cascade, and can be directly absorbed by the brush border without trypsin cleavage; yeast protein (YP) is rich in β-1,3 / 1,6-glucan (≥1%), nucleotides (RNA ≥1%) and arginine, which can activate the Syk and NO pathways through Dectin-1 to increase Na+. + - Glucose cotransporter (SGLT1).

[0023] (4) The enteral nutrition composition of the present invention promotes the absorption of water in the intestine through compound minerals, which can quickly prevent and correct dehydration and electrolyte imbalance caused by diarrhea, and promote the absorption of nutrients in the intestine to a certain extent.

[0024] (5) The present invention provides a special medical purpose formula food (FSMP) for improving intestinal intolerance in postoperative patients. This FSMP is based on the concept of "structural water retention - mucosal repair - immune anti-inflammatory - absorption complementarity" for the first time. It has five major clinical pain point solutions: "fast diarrhea relief, good absorption, strong immunity, low cost and no tube blockage". It is significantly better than existing whole protein or single short peptide FSMP.

[0025] (6) The advantages of the FSMP provided by the present invention are: ① Reduce the frequency of diarrhea. The FSMP provided by the present invention has an osmotic pressure of 200–340 mOsmol / kg, which is significantly lower than that of whole protein formula (≥450 mOsm kg-1), thus reducing the risk of osmotic diarrhea; ② Accelerate postoperative intestinal mucosal repair and reduce inflammatory response; ③ Reduce the incidence of postoperative infection; ④ Reduce the leakage of bacterial metabolites and intracellular enzymes; ⑤ Improve the EN target achievement rate and shorten the average hospital stay.

[0026] (7) The main raw materials of the FSMP provided by this invention are all domestic bulk food-grade by-products (such as broken rice, gluten powder, and brewing yeast), and the overall cost is 35-40% lower than that of imported short peptide FSMP, which is conducive to large-scale promotion.

[0027] (8) This invention provides multiple dosage forms based on the same formula by adjusting the amount of water added: ready-to-drink oral rehydration suspension (0.5 kcal / mL); semi-solid tube feeding gel (1.5 kcal / mL, suitable for slow infusion in ICU); oral nutritional supplement (30g-50g strip), 1.0 kcal / mL, achieving "three uses in one bag" and covering the entire nutritional transition period from 0 to 7 days after surgery. Attached Figure Description

[0028] Figure 1 These are HE-stained sections, with the left side representing the sham-operated group, the middle side representing the model group, and the right side representing the experimental group. Detailed Implementation

[0029] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0030] Unless otherwise indicated, the practice of this disclosure will employ conventional techniques within the scope of the art, including molecular biology (including recombinant techniques), microbiology, cell biology, biochemistry, and immunology.

[0031] In the following embodiments, unless otherwise specified, the terms used are explained as follows: In this disclosure, unless otherwise specified, the terms “comprising” or “including” are open-ended expressions used to refer to the phrase “including but not limited to” and are used interchangeably with it, meaning that they include the contents specified in this disclosure but do not exclude other contents.

[0032] In this disclosure, unless otherwise specified, the term "amino acid score" is a key indicator for measuring the nutritional value of protein. Its principle is to calculate the ratio of the content of each essential amino acid in the protein being tested to the content of the corresponding amino acid in a reference protein (usually egg protein or breast milk protein, representing the ideal amino acid pattern for the human body), and take the lowest ratio as the amino acid score of the protein. AAS = (content of a specific essential amino acid in the protein being tested (mg / g nitrogen)) / (content of that amino acid in the reference protein (mg / g nitrogen)) × 100%. When the amino acid score (AAS) of a protein is ≥1, it indicates that the essential amino acid composition of the protein perfectly matches or exceeds the human body's requirements, classifying it as a high-quality protein that can efficiently meet the body's protein synthesis needs in nutritional support.

[0033] In this disclosure, unless otherwise specified, the term "degree of expansion" refers to the ratio of the volume of the expanded material to the volume of the unexpanded material; it can also be indirectly calculated through the density ratio (volume is inversely proportional to density), and the results of both methods are consistent. The degree of expansion is determined by both the characteristics of the raw materials and the processing parameters.

[0034] Unless otherwise specified in this disclosure, the term "Food for Special Medical Purposes (FSMP)" refers to a type of formulated food designed for people with impaired intestinal function and insufficient nutrient intake after surgery. It should be used under the guidance of a doctor or clinical nutritionist. Its core objectives are to quickly replenish nutrients, promote intestinal mucosal repair, reduce the risk of intolerance, and accelerate postoperative recovery.

[0035] In this disclosure, unless otherwise specified, the term "enteral nutrition tolerance" (EN tolerance) refers to a patient's gastrointestinal tract's ability to accept and process nutritional solutions ingested through tubes (nasogastric tubes, nasojejunal tubes, etc.) or orally without serious adverse reactions. It is typically assessed using rating scales, most commonly the I-FEED score or INTUITION score. Assessment indicators include: gastric residual volume (GRV): the gastric tube is aspirated every few hours to check how much nutritional solution remains. Too much remaining indicates indigestion; intra-abdominal pressure (IAP): measuring the pressure within the abdomen; bowel sounds: listening for peristalsis; and the presence of diarrhea or vomiting.

[0036] In this disclosure, unless otherwise specified, the term "water absorption index (WAI)" is a key indicator used in food science and materials science to measure the ability of macromolecules (such as starch, protein, and cellulose) to absorb and retain water in excess water. It is not merely about "dissolving" in water, but rather refers to the ability of a substance to swell after absorbing water, forming a gel or viscous paste and "locking" water within its network structure. The WAI of carbohydrates typically ranges from 1.0 to 15.0 g / g, or even higher. The WAI value depends on the carbohydrate's chemical structure (linear vs. branched), particle size, temperature, and processing method (such as the degree of gelatinization).

[0037] The selection and quantity of these reagents fall within the scope of professional competence and routine techniques of those skilled in this art. The following is an explanation using specific examples.

[0038] Example 1: Preparation of Enteral Nutrition Composition Weigh 70 parts of puffed rice flour, 10 parts of hydrolyzed wheat protein, 15 parts of yeast protein, and 5 parts of compound minerals, and put them into a three-dimensional motion mixer. Set the mixing speed to 10 r / min and the mixing time to 5 min.

[0039] The compound minerals contain, by weight, 0.8 parts sodium chloride, 0.3 parts ferric pyrophosphate, 0.5 parts zinc gluconate, 2 parts calcium carbonate, and 2 parts magnesium carbonate.

[0040] Example 2 Preparation of Foods for Special Medical Purposes (FSMP) Take 60 parts of the enteral nutrition composition prepared in Example 1, add 0.6 parts of compound vitamins, 0.4 parts of edible flavoring, and 39 parts of maltodextrin, put them into a three-dimensional motion mixer, set the mixing speed to 14 r / min, the mixing time to 10 min, and package them in nitrogen-filled aluminum foil bags, each bag weighing 50g.

[0041] The compound vitamin contains, by weight, 0.2 parts retinyl acetate, 0.3 parts cholecalciferol, 1 part dl-α-tocopherol acetate, 0.05 parts thiamine hydrochloride, 0.05 parts riboflavin, 0.2 parts pyridoxine hydrochloride, 0.3 parts cyanocobalamin, 0.1 parts nicotinamide, 0.09 parts folic acid, 0.1 parts D-calcium pantothenate, 8 parts sodium L-ascorbate, and 2 parts taurine.

[0042] Example 3: Performance Testing of FSMP The FSMP prepared in Example 2 was used for performance testing. The methods were as follows: ① Referring to the freezing point method in GB 5009.301 National Food Safety Standard - Determination of Osmolarity in Food, the osmolarity was indirectly determined by measuring the freezing point depression of the solution; ② Referring to GB 5009.124 National Food Safety Standard - Determination of Amino Acids in Food, the amino acid composition was determined and the amino acid score was calculated; ③ Referring to GB 5009.5 National Food Safety Standard - Determination of Protein in Food, GB 5009.6 National Food Safety Standard - Determination of Fat in Food, GB 5009.3 National Food Safety Standard - Determination of Moisture in Food, and GB 5009.4 National Food Safety Standard - Determination of Ash in Food, the protein, fat, moisture, and ash content were determined, and the carbohydrate content was calculated according to GB 28050 National Food Safety Standard - General Rules for Nutrition Labelling of Prepackaged Foods, and the energy was calculated accordingly.

[0043] The results are as follows: (1) The osmotic pressure of FSMP is 252 mOsmol / kg; (2) The FSMP amino acid score results are shown in Table 1. The scores of each essential amino acid are greater than 1, indicating that the protein is a high-quality protein.

[0044] Table 1: Amino acid test values ​​and amino acid scores of FSMP products (3) The energy of FSMP is 1747kJ. When 50g of sample is added to 180ml of water and stirred thoroughly to prepare a solution of about 210ml, its energy density is about 1kcal / ml.

[0045] Example 4 In vitro water retention / sodium retention experiment Take 50g of FSMP prepared in Example 2, add 180ml of water and stir thoroughly to prepare the test solution, with an energy density of approximately 1kcal / ml; the control group is a commercially available similar whole protein formula, Lizcon. ® The homogenized diet, manufactured by Anhui Kaisixinda Technology Co., Ltd., consists mainly of rice flour, corn flour, soy protein isolate, vegetable fat powder, and whole milk powder. 50g of the mixture is added to 180ml of water and stirred thoroughly to prepare a control solution of the same concentration. The energy density is approximately 1kcal / ml. An in vitro water retention / sodium retention experiment was conducted using the dialysis bag method (MWCO 3.5kDa).

[0046] I. Preparations before the experiment 1. Dialysis bag pretreatment New dialysis bags need to be cleaned of heavy metals, sulfides, and other impurities, and the membrane structure needs to be activated. The standard treatment method is as follows: cut the dialysis bag into 10-20cm segments and soak them in distilled water to moisten them; boil them in 500mL of 2% (w / v) sodium bicarbonate + 1mM EDTA·2Na (pH 8.0) solution for 10 minutes; rinse them thoroughly with distilled water, and then boil them in 1mM EDTA solution for 10 minutes; after cooling, soak them in 30-50% ethanol or a storage solution containing preservatives and store them at 4°C; before use, they must be thoroughly cleaned inside and out with distilled water.

[0047] 2. Selection of Molecular Weight Cutoff (MWCO) Water retention test: The molecular weight of the target macromolecule was selected to be much smaller than the molecular weight of the target macromolecule (MWCO 3.5kDa).

[0048] Sodium-locking experiment: Sodium ions are very small, so it is necessary to ensure that the "sodium-locking substance" to be tested (such as protein, polysaccharide) can be retained. + Passage is permitted.

[0049] II. Procedure for In Vitro Water Retention Experiment Step 1: Sample loading and sealing After sealing one end with a dialysis clip, inject the sample solution (FSMP solution and control solution) into the bag, leaving 30-50% space (because water will enter the bag during dialysis, causing volume expansion). After removing the air, seal the other end to ensure no leakage.

[0050] Step 2: Set up the dialysis environment Immerse the sealed dialysis bag in dialysis solution (usually distilled water or physiological saline) containing 100-200 times the volume of the sample solution to be tested. Use a magnetic stirrer to stir continuously at low speed to maintain a low concentration outside the bag. Dialyze at 4°C (to prevent sample degradation; increasing the temperature can speed up the dialysis process).

[0051] Step 3: Dialysis Process Water retention capacity test: The dialysis bag is periodically removed, its surface moisture is blotted dry with filter paper, and then weighed. The weight change is recorded. Polyethylene glycol (PEG) or sucrose can be added to the dialysate to generate osmotic pressure and simulate a real-world environment.

[0052] Dialysis time: usually 2-24 hours, with dialysis fluid changed 2-3 times during the process.

[0053] Step 4: Data Recording Calculate the water retention rate = (remaining water in the bag / initial water volume) × 100% The water retention effect can be quantitatively assessed by measuring the change in solution volume or the amount of water migration inside the bag.

[0054] III. In vitro sodium-locking experiment procedure Steps 1-2: Sample loading and setup for the water retention experiment Step 3: Dialysis and Testing Use Na + The dialysis solution (physiological saline 0.9% NaCl) was used, and the sample solution to be tested (FSMP solution and control solution) was placed in the bag.

[0055] Dialysis time: usually 2-24 hours, with dialysis fluid changed 2-3 times during the process.

[0056] Timed sampling and testing: External dialysis solution: Na+ was determined using a flame photometer or ion chromatography. + concentration.

[0057] Sample inside the bag: Determination of retained Na + content.

[0058] Calculate the sodium ion migration rate and retention rate.

[0059] Step 4: Result Calculation Sodium retention rate = [(Initial total sodium content - Leaked sodium content) / Initial total sodium content] × 100% Plot a sodium ion release curve to evaluate the sodium-locking effect.

[0060] Results: The water retention rate of the FSMP prepared in this invention was 82%, while that of the control group was 48%; the sodium ion loss rate of the FSMP prepared in this invention was 15%, while that of the control group was 38%.

[0061] Example 5. Rat Ischemia-Reperfusion (I / R) Model Following general anesthesia for surgeries involving the abdomen, gastrointestinal tract, liver, gallbladder, and pancreas, sympathetic nerve excitation leads to ischemia-reperfusion of the intestinal mucosa. The rat I / R model is an experimental tool that simulates this pathological process by artificially creating temporary ischemia in specific organs (such as the heart, brain, liver, kidneys, and intestines) in experimental rats and then restoring blood flow to them. Its damage mechanisms (calcium overload, oxidative stress, inflammatory response, and apoptosis / necrosis) are highly consistent with those in humans.

[0062] Male SD rats, n=10 / group, were administered 4g / kg·d⁻¹ by gavage 3 days before and 10 days after surgery. The FSMP solution prepared in Example 2 was used for gavage; 50g of FSMP was added to 180ml of water and stirred thoroughly to prepare the FSMP solution, and the specific gavage volume was calculated based on the mouse's body weight. Ileum was harvested 24 hours after surgery. The model control group was fed routinely. The experimental group and sham-operated group underwent the following procedures: 1. Preoperative preparation Animals: Healthy adult SD or Wistar rats, weighing 220-300g. Fasting for 12 hours before surgery (water allowed) to reduce intestinal contents and surgical interference.

[0063] Anesthesia: Intraperitoneal injection of sodium pentobarbital (40-50 mg / kg) or urethane (1-1.2 g / kg) to achieve a stable anesthetic state.

[0064] Fixation and skin preparation: The rat was fixed in a supine position on a temperature-controlled surgical board, maintaining the rectal temperature at approximately 37°C. The abdominal area was shaved and disinfected.

[0065] 2. Surgical procedure (ischemic phase) Opening the abdomen: Make a longitudinal incision of about 3-4 cm along the midline of the abdomen (linea alba) and open the abdominal cavity layer by layer.

[0066] Expose the superior mesenteric artery: Gently push the intestinal loops towards the right side of the abdominal cavity with a cotton swab moistened with warm saline to expose the aortic region of the retroperitoneum. The origin of the superior mesenteric artery can be found below the left renal vein and on the anterior wall of the abdominal aorta. The SMA usually arises independently, without branches, and is easily identifiable.

[0067] Artery separation: Under a microscope or magnifying glass, carefully separate the tissue and nerve plexus around the SMA with fine micro forceps and a glass dissecting needle, freeing it to about 0.5 cm.

[0068] Inducing ischemia: Non-invasive microvascular clamping (experimental group): The root of the SMA is completely clamped with a non-invasive vascular clamp (such as an aneurysm clamp). The ischemic time is usually 30-90 minutes (45-60 minutes is the most common, the longer the time, the more severe the damage and the higher the mortality rate).

[0069] Confirming ischemia: After clamping, the jejunum, ileum, and part of the colon should be observed to rapidly become pale and peristalsis to weaken. Cover the intestinal loops with warm saline gauze and temporarily return them to the abdominal cavity, or cover them with plastic wrap to prevent drying.

[0070] Sham surgery group: SMA was separated but not clamped.

[0071] 3. Reinfusion period Once the predetermined ischemia time has elapsed, carefully remove the vascular clamp.

[0072] Key observation: The previously pale intestinal segments rapidly become congested, turning dark red or even purplish-red (reactive congestion, which may be followed by ecchymosis), and mesenteric vascular pulsation returns. This marks the start of reperfusion.

[0073] Closure of the abdomen: After rinsing the abdominal cavity with warm saline, the abdominal wall muscles and skin are sutured layer by layer.

[0074] Postoperative care: Place the rats in a warm, quiet recovery environment in individual cages, provide free access to water and the previously prepared FSMP solution (usually a small amount can be given 2-4 hours after surgery).

[0075] Evaluation indicators (1) Macroeconomic and survival rate assessment Survival rate: Record the animal mortality rate at different time points after surgery (e.g., 24h, 72h).

[0076] Gross morphology of the intestines: Observation upon re-opening the abdomen: Color: Whether it is dark purple or black (gangrene).

[0077] Edema: Whether the intestinal wall and mesentery are thickened and edematous.

[0078] Peristalsis: Whether intestinal peristalsis has disappeared.

[0079] Ascites: Whether there is bloody or inflammatory fluid in the abdominal cavity.

[0080] (2) Intestinal histopathological evaluation (gold standard) Sampling: Take the same segment of intestine (usually the ileum about 10-15 cm from the ileocecal junction).

[0081] HE staining: Microscopic observation, with semi-quantitative assessment commonly performed using the Chiu pathology score. 0 points: Normal villous structure.

[0082] 1 point: The subepithelial space at the tip of the villi is enlarged.

[0083] 2 points: The subepithelial space is widened, and the tips of the villi are slightly raised.

[0084] 3 points: The villi are more bulging and some villi tip epithelial cells are shed.

[0085] 4 points: Villi loss, exposure of the lamina propria, and dilated capillaries.

[0086] 5 points: Destruction of the lamina propria, bleeding, ulceration.

[0087] (3) Assessment of intestinal barrier function and permeability D-lactic acid: a metabolic product of intestinal bacteria, which enters the bloodstream more frequently when intestinal permeability is increased.

[0088] Diamine oxidase (DAO): It is mainly found in the villi cells of the intestinal mucosa and is released into the blood when the intestinal mucosa is damaged.

[0089] (4) Inflammatory markers Serum levels of TNF-α, IL-1β, and IL-6 were measured.

[0090] result: The mean ± standard deviation was used, and the statistical analysis was performed using one-way ANOVA, followed by LSD-t test.

[0091] Table 2: Macroeconomic Score and Survival Rate Note: *P<0.05, P<0.01, *P<0.001 vs model group; #P<0.001 vs sham surgery group, the same below.

[0092] Macroscopic scoring: The model group scored significantly higher than the sham surgery group, indicating that the model was successful. The experimental group scored significantly lower than the model group, indicating that the composition could significantly reduce visible damage to the intestinal tract (such as edema, congestion, and necrosis).

[0093] Survival rate: The model group had a high mortality rate 24 hours after reperfusion, consistent with the severity of the model. The experimental group showed a significantly improved survival rate, indicating that the combination therapy improved the overall prognosis of the animals.

[0094] Table 3: Serological Indicators of Intestinal Barrier Function In the model group, both serum levels increased sharply, confirming severe damage to the intestinal mucosal barrier and increased permeability. In the experimental group, both indicators were significantly lower than in the model group, indicating that the composition effectively protects the integrity of the intestinal mucosal barrier and reduces the leakage of bacterial metabolites and intracellular enzymes.

[0095] Table 4: Serum inflammatory factor levels (ELISA detection) Serum levels of TNF-α, IL-1β, and IL-6 were significantly elevated in the model group, indicating that I / R triggered a strong systemic inflammatory response. Levels of all inflammatory factors in the experimental group were significantly lower than those in the model group, suggesting that the composition has a clear systemic anti-inflammatory effect and can inhibit the excessive activation of the inflammatory cascade.

[0096] Table 5: Chiu score in intestinal histopathology HE-stained sections, as shown Figure 1 As shown, in the sham-operated group on the left, the intestinal villi structure was intact and slender, with tightly packed epithelial cells. In the model group in the middle, a large number of villi were broken and detached, the lamina propria was exposed and hemorrhaged, and there was extensive infiltration of inflammatory cells. In the experimental group on the right, the villi structure was better preserved, and although there was edema and partial epithelial detachment, the overall structural damage was significantly less than that in the model group.

[0097] Pathological scores: The model group had the highest Chiu score, corresponding to the most severe mucosal structural damage. The experimental group's score was significantly lower than that of the model group, directly confirming the protective effect of the composition on the intestinal mucosal structure from a histomorphological perspective, which was corroborated by the improvement of barrier function indicators (D-lactic acid, DAO).

[0098] Experimental conclusions The model group showed highly significant differences from the sham surgery group on all indicators, successfully replicating the severe intestinal I / R injury model. Compared with the model group, the experimental group showed statistically significant improvements on all pre-specified assessment indicators: Survival and macroscopic aspects: Improved survival rate and reduced visible intestinal damage.

[0099] Barrier function: It significantly reduced serum D-lactic acid and DAO levels, demonstrating its ability to maintain intestinal barrier function.

[0100] Inflammatory response: Significantly inhibited the release of systemic pro-inflammatory cytokines (TNF-α, IL-1β, IL-6).

[0101] Tissue structure: Significantly improved intestinal histopathological damage scores and protected the integrity of the mucosal structure.

[0102] Based on the above results, it is reasonable to infer that the composition may reduce oxidative stress and inflammatory storm during reperfusion through its multiple pharmacological effects, such as anti-inflammatory, antioxidant, anti-apoptotic, or cell membrane stabilizing effects, thereby protecting intestinal mucosal epithelial cells and ultimately achieving systemic protection against intestinal I / R injury.

[0103] Example 6. Prospective randomized controlled clinical trial A randomized controlled trial investigating the effects of FSMP on postoperative bowel tolerance and recovery in patients undergoing elective gastrointestinal tumor surgery. Background: Postoperative complications such as feeding intolerance and diarrhea are common in patients with gastrointestinal tumors, affecting enteral nutrition target achievement rates and prolonging hospital stays. Traditional postoperative management may neglect systemic bowel function maintenance. Objective: To evaluate the effects of the experimental formulation on postoperative bowel tolerance, EN target achievement rates, length of hospital stay, and adverse events.

[0104] 1. Study Design: Prospective, single-center, parallel-group, randomized controlled trial 2. Research Subjects Inclusion criteria: - Age 18-75 years old -A diagnosis of gastrointestinal tumor requires elective surgery. -ASA classification I-III after anesthesiology evaluation - It is expected that enteral nutrition will be required for ≥3 days post-surgery. -Sign informed consent form Exclusion criteria: -Emergency surgery -Preoperative chronic diarrhea Other intestinal diseases besides tumors - Severe liver and kidney dysfunction -Pregnancy or breastfeeding - Long-term use of other nutritional supplements - Currently involved in other nutritional intervention-related research. - Contraindications for enteral nutrition: Complete intestinal obstruction or paralytic ileus that has not been relieved; active upper / lower gastrointestinal bleeding; intestinal ischemia, necrosis, or perforation; severe hemodynamic instability with peripheral hypoperfusion (uncorrected shock); high-flow small bowel fistula (>500 mL / day). - ¹) Inability to place a distal catheter around the fistula; unresolved mechanical obstruction such as superior mesenteric artery syndrome; severe abdominal compartment syndrome (ACS); severe abdominal distension, intractable vomiting, or gastric retention >500 mL / 6 h; uncorrectable electrolyte disturbances, acidosis, or severe hyperglycemia; altered mental status with persistent loss of swallowing reflex and lack of airway protection (high risk of aspiration). - Gluten allergy / Celiac disease 3. Sample size calculation: With a significance level (α) of 0.05 and a power (1-β) of 0.8, and an expected difference of 30% in the Hart Diarrhea Score and a loss to follow-up rate of 20%, and considering a standard deviation σ of 5, each group needs 60 cases, for a total of 120 cases.

[0105] 4. Randomization and Blinding -Block randomization (block size 4 / 6), computer-generated random sequence -Hidden allocation: Use an opaque envelope. - Single-blind design: outcome assessors are unaware of group assignments. 5. Intervention measures Experimental group and control group: (1) Preoperative: Supplement with oral nutrition of about 1000 kcal per day for 5 days (prepared using FSMP prepared in Example 2, take 50g of FSMP, add 180ml of water and stir thoroughly to prepare FSMP solution). (2) Intraoperative: restrictive fluid management to avoid hypothermia (3) Postoperative: - Start oral 10% glucose (20ml / h) 6 hours after surgery. Enteral nutrition (using the previously prepared FSMP solution, 20 ml / h) should be started 24 hours post-surgery. -Increase the daily intake by 20 ml / h until reaching the target amount (25 kcal / kg / day). The experimental group received the experimental FSMP; the control group received the isocalcitonin control formulation. 6. Observation Indicators The Hart Diarrhea Scale was used to assess the severity of diarrhea. Stool characteristics and estimated volume were recorded for each bowel movement. Stool characteristics included three categories: formed, semi-solid, and liquid volume, with volumes of <200 mL, 200–250 mL, and >250 mL, respectively. Nine combinations were obtained, each assigned a score from 1 to 15. The total score for each bowel movement within 24 hours was calculated by summing the scores from each bowel movement. A total score ≥12 points was considered indicative of diarrhea. Higher scores indicated more severe diarrhea. (See Table 6.) Table 6: Hart Diarrhea Scoring Table (1) Primary endpoint: - Number of times diarrhea occurs within 5 days post-surgery (Hart diarrhea score ≥ 12 points) (2) Secondary endpoint: -EN target achievement rate (actual intake / target intake ≥ 70% on postoperative day 5) -Postoperative hospital stay days -Time of first gas / blow - Postoperative complications (infection, anastomotic leakage, etc.) -Incidence of adverse events (fatal, life-threatening, disabling, birth defects, anaphylactic shock, etc.) - Changes in nutritional indicators (albumin, prealbumin) -Intestinal tolerance indicators (vomiting, abdominal pain, abdominal distension, etc.). The enteral nutrition tolerance score includes abdominal distension and / or abdominal pain, nausea and / or vomiting, and diarrhea volume. Abdominal distension and / or abdominal pain symptoms: 0 points for no abdominal distension and pain, 1 point for mild abdominal distension and no abdominal pain, 2 points for significant abdominal distension or abdominal pain that can be relieved spontaneously, and 5 points for severe abdominal distension or abdominal pain that cannot be relieved spontaneously. In this study, intra-abdominal pressure monitoring was not required for the cases based on their condition. Nausea and / or vomiting symptoms: 0 points for no nausea and vomiting, 1 point for nausea but no vomiting, 2 points for nausea and vomiting with 250 mL ≤ gastric residual volume < 500 mL and no need for gastrointestinal decompression, and 5 points for vomiting with gastrointestinal decompression or gastric residual volume ≥ 500 mL. Diarrhea symptoms: 0 points for no diarrhea, 1 point for loose stools ≥ 3 times / day with 250 mL ≤ stool volume < 500 mL, 2 points for loose stools ≥ 3 times / day with 500 mL ≤ stool volume < 1500 mL, and 5 points for loose stools ≥ 3 times / day with stool volume ≥ 1500 mL. The severity of the illness is scored, and the scores are added together to get the total score. Enteral nutrition is adjusted or appropriate treatment is given based on the score. If the score is >5, treatment is required.

[0106] 7. Data collection: Record the number of diarrhea episodes, stool characteristics, EN intake, intestinal tolerance, and adverse events daily after surgery.

[0107] 8. Statistical Analysis - Quantitative data: t-test or Mann-Whitney U test -Count data: χ² test or Fisher's exact test - Multivariate analysis: Logistic regression analysis -P < 0.05 indicates a statistically significant difference. 9. Ethical considerations -Approved by the hospital ethics committee - Clinical trial registration -Patient informed consent 10. Test Results (1) Baseline data The baseline data of the two groups of patients were equal in terms of age, sex, tumor type, surgical procedure, etc. (P>0.05).

[0108] (2) Key outcome indicators Table 7: Comparison of Postoperative Patient Conditions (3) Secondary outcome indicators Table 8: Comparison of Postoperative Recovery Indicators (4) Subgroup analysis - The advantage of the experimental group was more obvious in elderly patients (>65 years old). Patients who undergo colorectal surgery benefit the most. 11. Results Analysis (1) The experimental group was significantly better than the control group in all major outcome measures: - Diarrhea control: In the experimental group, the frequency of diarrhea decreased by 67% and the incidence of severe diarrhea decreased by 72% 3 days after surgery. -EN tolerance: EN target achievement rate increased by 25%, average intake increased by 25%. (2) Confirmation of intestinal tolerance Through multidimensional assessment, the experimental group showed comprehensively improved intestinal tolerance: - Significantly reduced frequency and severity of diarrhea -EN feeding tolerance is improved, and the discontinuation rate is reduced. -Accelerated recovery of intestinal function (earlier gas / defecation) -Postoperative hospital stay shortened by 2.3 days - Total adverse events decreased by 58% - The infection trend is decreasing (although not statistically significant). (3) Clinical significance -Patient benefits: Reduced diarrhea, improved nutritional status -Medical resources: Shorten hospital stays and reduce medical costs - Safety: Adverse events decreased, with no serious intervention-related adverse reactions. 12. Conclusion FSMP can significantly improve postoperative intestinal tolerance in patients undergoing elective gastrointestinal tumor surgery, increase EN target achievement rate, shorten hospital stay, and reduce adverse events, thus having clinical application value.

[0109] Other embodiments of this application will readily occur to those skilled in the art upon consideration of the specification and practice of the invention disclosed herein. This application is intended to cover any variations, uses, or adaptations of this application that follow the general principles of this application and include common knowledge or customary techniques in the art not disclosed herein. The specification and examples are to be considered exemplary only, and the true scope and spirit of this application are indicated by the claims.

[0110] The above description is merely a preferred embodiment of this application and is not intended to limit this application. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of this application should be included within the scope of protection of this application.

Claims

1. An enteral nutrition composition for improving postoperative intestinal intolerance in patients, comprising carbohydrates, proteins, and complex minerals, characterized in that, By weight, the carbohydrates are 10-80 parts, the protein is 5-40 parts, and the minerals are 1-10 parts.

2. The enteral nutrition composition according to claim 1, characterized in that, The carbohydrate is one or more of puffed rice flour, puffed corn starch, puffed tapioca starch, and puffed glutinous rice flour. Further, the water absorption index (WAI) of the carbohydrate is 3.0–8.0 g / g. Further, the amylose content of the carbohydrate is 5–30%. Further, the degree of puffing of the carbohydrate is 12–18. Further, the cold water solubility index (CWSI) of the carbohydrate is ≥75%.

3. The enteral nutrition composition according to claim 1, characterized in that, The protein is a non-animal source protein, further, the protein has an amino acid score ≥1 and the proportion of high-quality protein ≥50%, further, the protein is yeast protein and wheat hydrolysate protein in a weight ratio of (1-2):

1.

4. The enteral nutrition composition according to claim 3, characterized in that, The yeast protein contains ≥1% (w / w) β-glucan, ≥1% (w / w) nucleotides, and ≥1% (w / w) arginine. Further, the yeast protein is *Saccharomyces cerevisiae* protein, and the β-glucan is β-1,3 / 1,6-glucan. Further, the wheat hydrolysate contains ≥22% (w / w) Gln peptides, ≥30% (w / w) peptides with a molecular weight <1 kDa, and <5% (w / w) free amino acids.

5. The enteral nutrition composition according to claim 1, characterized in that, By weight, the composite mineral contains one or more of the following: sodium salt 0-10 parts, potassium salt 0-10 parts, iron salt 0.01-2 parts, zinc salt 0.01-2 parts, calcium salt 0.1-10 parts, and magnesium salt 0-10 parts; further, the sodium salt is one or more of sodium chloride, sodium citrate, disodium hydrogen phosphate, sodium bicarbonate, and sodium dihydrogen phosphate; further, the potassium salt is one or more of potassium chloride, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, potassium bicarbonate, potassium citrate, and potassium acetate; further, the iron salt is ferric sodium ethylenediaminetetraacetate, ferric pyrophosphate, or fumaric acid. The zinc salt is one or more of zinc gluconate, ferrous citrate, ferrous glycinate, and ferrous sulfate; further, the zinc salt is one or more of zinc gluconate, zinc sulfate, zinc glycinate, zinc oxide, zinc lactate, zinc citrate, zinc chloride, and zinc acetate; further, the calcium salt is one or more of calcium carbonate, calcium gluconate, calcium citrate, L-calcium lactate, calcium hydrogen phosphate, calcium chloride, tricalcium phosphate, calcium oxide, calcium sulfate, and glycerophosphate; further, the magnesium salt is one or more of magnesium carbonate, magnesium sulfate, magnesium chloride, magnesium oxide, magnesium hydrogen phosphate, and magnesium gluconate.

6. The use of the enteral nutrition composition according to any one of claims 1-5 in the preparation of food for special medical purposes (FSMP) for improving intestinal intolerance in postoperative patients, characterized in that, The FSMP is a nutritional food that can provide early enteral nutritional support for patients with incomplete or poor gastrointestinal function after surgery.

7. A FSMP for improving postoperative intestinal intolerance in patients, characterized in that, By weight, the special medical purpose formula food contains 20-90 parts of the enteric nutrition composition as described in any one of claims 1-5, 5-80 parts of maltodextrin, 0.1-2 parts of compound vitamins, and 0-2 parts of edible flavoring.

8. The FSMP according to claim 7, characterized in that, The maltodextrin is MD10 maltodextrin, MD15 maltodextrin, or MD20 maltodextrin.

9. The FSMP according to claim 7, characterized in that, By weight, the compound vitamin comprises one or more of the following: 0.2-0.7 parts of vitamin A, 0.1-0.4 parts of vitamin D, 1-4 parts of dl-α-tocopherol acetate, 0.04-0.09 parts of thiamine salt derivatives, 0.04-0.09 parts of riboflavin, 0.1-0.5 parts of pyridoxine hydrochloride, 0.1-0.5 parts of cyanocobalamin, 0.1-0.9 parts of nicotinamide, 0.01-0.09 parts of folic acid, 0.1-0.9 parts of D-calcium pantothenate, 8-16 parts of sodium L-ascorbate, and 1-9 parts of taurine; furthermore, the vitamin A is one or more of retinyl acetate, retinyl palmitate, and β-carotene, the vitamin D is one or more of cholecalciferol and ergocalciferol, and the thiamine salt derivatives are thiamine hydrochloride and / or thiamine nitrate.

10. The FSMP according to claim 7, characterized in that, The FSMP has an osmotic pressure of 200–340 mOsmol / kg, a pH of 6.0–7.8, and an energy density of 0.5–1.5 kcal / mL. Furthermore, the FSMP can be formulated into ready-to-drink oral rehydration suspensions, semi-solid tube feeding gels, and oral nutritional supplements by adjusting the amount of water added.

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