Total-nutrient formula preparation suitable for chronic kidney disease patients and preparation method of total-nutrient formula preparation

Abstract

The invention relates to a special total nutrient formula preparation for chronic kidney disease and a preparation method thereof. According to the preparation, whey protein and dephosphorized soybean protein are compounded according to a specific proportion, flaxseed oil and a medium-chain fatty acid energy matrix which are subjected to micro-emulsification treatment are combined, and an intestinal regulation system composed of prebiotics and microencapsulated probiotics is added, so that a synergistic nutrition intervention system is formed. An optimized preparation process is adopted and comprises the key steps of protein dry mixing, high-pressure micro-emulsification, low-temperature spray drying and the like, so that the stability and the biological activity of the product are ensured. The formula can improve the renal function, relieve inflammatory response and regulate intestinal flora at the same time, and is suitable for nutrition support of patients suffering from chronic nephropathy at the stage 3-5.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of clinical nutrition medicine, and relates to a total nutritional formula preparation suitable for patients with chronic kidney disease, especially patients in stages 3-5 of chronic kidney disease and a preparation method thereof. BACKGROUND

[0002] Patients with chronic kidney disease (CKD) need to strictly control the intake of protein, phosphorus, potassium and sodium due to reduced kidney function, and meanwhile face the risks of malnutrition, intestinal flora imbalance, inflammatory reaction and metabolic acidosis. Patients in stages 3-5 of chronic kidney disease face various metabolic disorders due to significantly reduced kidney function, such as accumulation of nitrogen-containing waste due to decreased glomerular filtration rate, which requires strict restriction of protein intake but is prone to malnutrition; hyperphosphatemia caused by abnormal mineral metabolism is a core complication of CKD, and conventional protein sources such as soybeans and dairy products have high phosphorus content, which requires reliance on phosphorus binders but may aggravate the intestinal burden; at the same time, patients are prone to systemic inflammation and oxidative stress due to the increase of serum inflammatory factor levels, and ordinary formula lacks targeted anti-inflammatory ingredients.

[0003] CN111227224A discloses a medical formula food for helping to protect the kidney function of patients with diabetic nephropathy, which comprises the following components in parts by weight: protein powder 35-40 parts; short peptide 5-15 parts; fat powder 30-50 parts; dietary fiber 5-15 parts; vitamin premix 0.1-0.3 parts; mineral premix 1-3 parts; traditional Chinese medicine extract 8-15 parts; calcium acetate or calcium carbonate 0.1-1 part; the formula food uses soybean peptide as a protein source, which has fast absorption but an unbalanced peptide segment ratio: solution leading to increased intestinal osmotic pressure and increased incidence of diarrhea, and lacks functional ingredients, which cannot provide the kidney protection effect of soybean isoflavones.

[0004] CN107048137A discloses a low-phosphorus whey protein powder suitable for patients with chronic kidney disease, which designs a new protein powder formula according to the physical characteristics of patients with chronic kidney disease, improves the contents of phosphorus and potassium elements in the protein source on the one hand, and matches appropriate trace elements according to the nutritional disorder of patients with chronic kidney disease, especially dialysis patients, on the other hand, aiming to supplement high-quality protein for patients with kidney disease and avoid the occurrence of hyperphosphatemia, while improving their nutritional status and promoting physical recovery; although the protein powder reduces the proportion of phosphorus elements, the protein source is single, and simple physical mixing cannot solve the stability problem of key ingredients.

[0005] CN111227224A discloses a medical formula food for helping to protect the kidney function of patients with diabetic nephropathy, comprising the following components by weight: protein powder: 35-40 parts; short peptide: 5-15 parts; fat powder: 30-50 parts; dietary fiber: 5-15 parts; vitamin premix: 0.1-0.3 parts; mineral premix: 1-3 parts; traditional Chinese medicine extract: 8-15 parts; calcium acetate or calcium carbonate: 0.1-1 part, wherein the type of fat powder includes flaxseed oil; although the formula food contains flaxseed oil, the active ingredients such as alpha-linolenic acid in flaxseed oil are degraded in a large amount during processing and storage without any stabilization treatment process, and it is difficult for patients to effectively absorb them. SUMMARY

[0006] The present application aims to provide a full nutritional formula preparation for patients with chronic kidney disease and a preparation method thereof, which has the characteristics of scientific proportioning, multiple kidney protection mechanisms and advanced process. Specifically, the dual effects of amino acid balance and anti-kidney fibrosis are achieved by precisely proportioning whey protein and dephosphorized soybean protein, high-pressure microemulsion technology is used to ensure high retention rate of omega-3 fatty acids in flaxseed oil and strong anti-inflammatory effect, the innovative integration of the intestinal microecological regulation system significantly reduces the absorption of uremic toxins, and the phytase directional dephosphorization process solves the risk of hyperphosphatemia in traditional kidney disease formula.

[0007] The object of the present application can be achieved by the following technical solutions: In a first aspect, the present application provides a full nutritional formula preparation suitable for patients with chronic kidney disease, comprising the following components by mass percentage: Protein complex 25-40%: composed of 15-30% whey protein and 5-15% dephosphorized soybean protein isolate, and the mass ratio of whey protein to dephosphorized soybean protein isolate is (1.5-2): 1; Energy substrate 20-30%: composed of 10-20% medium-chain fatty acids and 5-10% flaxseed oil; Intestinal regulation system 10-25%; Metabolic auxiliary ingredients 5-10%.

[0008] The full nutritional formula preparation suitable for chronic kidney disease patients provided by the application innovatively constructs a multi-system synergistic nutrition system for chronic kidney disease. Through scientific matching of whey protein and dephosphorized soybean protein (1.5-2):1, the dual functions of amino acid balance and kidney protection are realized while meeting the low protein requirement; the energy supply scheme of medium-chain fatty acids combined with micro-emulsified flaxseed oil not only ensures rapid energy supply but also plays an anti-inflammatory role; the specially designed intestinal regulation system improves intestinal barrier function through the triple action of prebiotics, probiotics and glutamine, significantly reducing the absorption of uremic toxins, and the application forms synergistic protection from three dimensions of protein metabolism, energy supply and intestinal-kidney axis regulation, solving the key problems of nutritional imbalance, excessive phosphorus load and systemic inflammation in the prior art.

[0009] The full nutritional formula preparation suitable for chronic kidney disease patients provided by the application innovatively constructs a multi-system synergistic nutrition system for chronic kidney disease. Through scientific matching of whey protein and dephosphorized soybean protein (1.5-2):1, the dual functions of amino acid balance and kidney protection are realized while meeting the low protein requirement; the energy supply scheme of medium-chain fatty acids combined with micro-emulsified flaxseed oil not only ensures rapid energy supply but also plays an anti-inflammatory role; the specially designed intestinal regulation system improves intestinal barrier function through the triple action of prebiotics, probiotics and glutamine, significantly reducing the absorption of uremic toxins, and the application forms synergistic protection from three dimensions of protein metabolism, energy supply and intestinal-kidney axis regulation, solving the key problems of nutritional imbalance, excessive phosphorus load and systemic inflammation in the prior art.

[0010] The full nutritional formula preparation suitable for chronic kidney disease patients provided by the application innovatively constructs a multi-system synergistic nutrition system for chronic kidney disease. Through scientific matching of whey protein and dephosphorized soybean protein (1.5-2):1, the dual functions of amino acid balance and kidney protection are realized while meeting the low protein requirement; the energy supply scheme of medium-chain fatty acids combined with micro-emulsified flaxseed oil not only ensures rapid energy supply but also plays an anti-inflammatory role; the specially designed intestinal regulation system improves intestinal barrier function through the triple action of prebiotics, probiotics and glutamine, significantly reducing the absorption of uremic toxins, and the application forms synergistic protection from three dimensions of protein metabolism, energy supply and intestinal-kidney axis regulation, solving the key problems of nutritional imbalance, excessive phosphorus load and systemic inflammation in the prior art.

[0011] Preferably, the dephosphorized soybean protein isolate is treated with phytase, and the phosphorus content is <0.5 mg / g.

[0012] Preferably, the intestinal regulation system comprises the following components: fructooligosaccharides 5-20%; inulin 5-10%; microencapsulated Lactobacillus acidophilus, viable count ≥ 1 x 10 8 CFU / g.

[0013] Preferably, the microencapsulated Lactobacillus acidophilus is embedded with sodium alginate-chitosan double layer, and the survival rate in gastric acid environment is > 90%.

[0014] The intestine is the largest micro-ecosystem of the human body, with more than 1,000 species and about 100 trillion bacteria. They participate in the processes of digestion, metabolism, immune regulation, etc. There are three aspects about the mechanism of the influence of intestinal flora imbalance on the kidney: the influence of metabolic products, the impairment of intestinal barrier function, and the imbalance of immune regulation; The whole nutritional formula preparation suitable for patients with chronic kidney disease provided by the present application is aimed at the intestinal flora imbalance phenomenon that is prone to occur in patients with chronic kidney disease due to dietary restrictions, drug effects and decreased kidney function, etc. In the present application, the system designed according to the above-mentioned "gut-kidney axis" theory contains a triple action mechanism: fructooligosaccharides and inulin are used as prebiotics to selectively promote the proliferation of Bifidobacterium; microencapsulated Lactobacillus acidophilus directly supplements beneficial bacteria; L-glutamine repairs the intestinal mucosal mechanical barrier, and the three work together to reduce the intestinal production and absorption of p-cresol sulfate, indole and other uremic toxins, thereby reducing the burden on the kidney from the source; The pH-sensitive double-embedded system based on sodium alginate-chitosan maintains the structure intact in the gastric acid environment (pH 2.0), and slowly releases the active probiotics after reaching the intestine (pH 6.8), the complex membrane formed by the electrostatic interaction between the positive charge of chitosan and the negative charge of sodium alginate makes the probiotic gastric acid survival rate break through 90%.

[0015] Preferably, the metabolic auxiliary component comprises: L-glutamine 3-5%; vitamin complex: vitamin C 0.5-1%, vitamin E 0.3-0.6%, vitamin B6 0.02-0.05%, folic acid 0.01-0.03%.

[0016] Elevated levels of homocysteine (Hcy) are an important risk factor for patients with kidney disease, which is significantly associated with kidney function deterioration, cardiovascular events and death risk. In the whole nutritional formula preparation of the present application: folic acid can provide a methyl donor to promote the remethylation of Hcy to methionine; vitamin B6 (PLP) is an essential coenzyme for catalyzing the generation of cysteine from homocysteine through the transsulfuration pathway, and its deficiency will lead to accumulation of Hcy and synthesis disorder of cysteine. Vitamin C can protect the activity of folic acid and prevent the oxidative degradation of folic acid; vitamin E can reduce the lipid peroxidation damage induced by Hcy.

[0017] Preferably, the ω-3 fatty acid in the flaxseed oil accounts for ≥50%, and the EPA+DHA precursor content is ≥15%. The EPA or DHA precursor is α-linolenic acid (abbreviated as ALA), which is a ω-3 series unsaturated fatty acid.

[0018] In a second aspect, the present application provides a preparation method of the full nutritional formula preparation according to the first aspect, comprising the following steps: (1) Protein complex preparation: dry-mixing whey protein and dephosphorized soybean protein isolate at a ratio at 45-55℃; (2) Energy substrate treatment: high-pressure microemulsifying MCT and flaxseed oil to make the particle size ≤200nm, and then spray drying; (3) Mixing: mixing the materials obtained in steps (1) and (2) with the intestinal regulation system and metabolic auxiliary ingredients passed through an 80-mesh sieve; (4) Adding probiotics: finally adding microencapsulated Lactobacillus acidophilus, and the uniformity is ≥95%.

[0019] The preparation method of the full nutritional formula preparation provided by the present application adopts a staged mixing strategy and a microemulsification-spray drying combined technology, pre-mixes heat-sensitive components such as vitamins and probiotics with part of protein base materials, reduces the particle size of oil to below 200nm through 50-80MPa high-pressure microemulsification, and controls the precise spray drying temperature at 160-180℃, so as to ensure the stability of ω-3 and realize the industrial-level quality standard of product uniformity ≥95%.

[0020] Preferably, in step (2), the microemulsification pressure is 50-80MPa, and the spray drying inlet air temperature is 160-180℃.

[0021] Preferably, in step (4), the mixing environment humidity is controlled at RH≤30%.

[0022] In a third aspect, the present application provides an application of the full nutritional formula preparation according to the first aspect in preparing a nutritional support product for patients in stages 3-5 of chronic kidney disease.

[0023] The present application has the following advantages: (1) The full nutritional formula preparation for patients with chronic kidney disease provided by the present application utilizes the protein synergistic effect principle, and by compounding whey protein and dephosphorized soy protein at a ratio of (1.5-2):1, the low protein requirement is met, and the soybean isoflavone is used to inhibit renal fibrosis, and the serum transforming growth factor-β1 level of the patient is significantly reduced. (2) The full nutritional formula preparation for chronic kidney disease patients provided by the application uses comprehensive regulation of the intestinal-kidney axis, and the combination of fructooligosaccharides, inulin, and microencapsulated probiotics reduces the ratio of the intestinal thick-walled bacteria phylum to the Bacteroidetes phylum and improves the clearance rate of uremic toxin p-cresol sulfate; (3) The preparation method of the full nutritional formula preparation for chronic kidney disease patients provided by the application uses phytase treatment to reduce the phosphorus content of soybean protein and a microemulsion process to ensure that the retention rate of omega-3 in flaxseed oil is >95%, making it more suitable for the needs of patients in the 3-5 stages of chronic kidney disease. DETAILED DESCRIPTION

[0024] To further illustrate the technical means and effects adopted by the application to achieve the predetermined object, the specific embodiments, structures, features, and effects according to the application are described in detail below.

[0025] In one specific embodiment, the application provides a full nutritional formula preparation suitable for chronic kidney disease patients, which contains 25-40% by mass of a protein complex composed of 15-30% by mass of whey protein and 5-15% by mass of dephosphorized soybean protein isolate treated with phytase and having a phosphorus content of less than 0.5 mg / g, wherein the mass ratio of whey protein to dephosphorized soybean protein isolate is (1.5-2):1; 20-30% by mass of an energy substrate composed of 10-20% by mass of medium-chain fatty acids and 5-10% by mass of flaxseed oil, wherein the proportion of omega-3 fatty acids in flaxseed oil is ≥50% and the content of EPA+DHA precursors is ≥15%; 10-25% by mass of an intestinal regulation system containing 5-20% by mass of fructooligosaccharides, 5-10% by mass of inulin, and microencapsulated Lactobacillus acidophilus embedded with sodium alginate-chitosan double layers with a viable count of ≥1×10^8 CFU / g; and 5-10% by mass of metabolic auxiliary ingredients containing 3-5% by mass of L-glutamine and a vitamin complex composed of 0.5-1% by mass of vitamin C, 0.3-0.6% by mass of vitamin E, 0.02-0.05% by mass of vitamin B6, and 0.01-0.03% by mass of folic acid.

[0026] In another embodiment, the present invention provides a method for preparing a complete nutritional formula for chronic kidney disease patients, as described above. The method comprises: dry-mixing whey protein and dephosphorylated soy protein isolate at a mass ratio of (1.5-2):1 at 45-55°C; micro-emulsifying medium-chain fatty acids and linseed oil at a pressure of 50-80 MPa to a particle size of ≤200 nm, followed by spray drying, with the spray drying air inlet temperature controlled at 160-180°C; mixing the resulting mixture with 80-mesh sieved oligofructose, inulin, L-glutamine, and a vitamin complex at a relative humidity of ≤30%; and finally, adding microencapsulated Lactobacillus acidophilus to achieve a final mixing uniformity of ≥95%. The mixing uniformity is determined by sampling from the upper, middle, and lower layers of the mixing container. Viable cell counts are determined at least 3-5 points (total sample size ≥10) in each layer, with a relative standard deviation (RSD) of ≤5%.

[0027] Example 1 The present embodiment provides a complete nutritional formula preparation suitable for patients with chronic kidney disease, comprising 30% by weight of a protein complex composed of 18% by weight of whey protein and 12% by weight of dephosphorylated soy protein isolate treated with phytase and having a phosphorus content of 0.4 mg / g, wherein the mass ratio of whey protein to dephosphorylated soy protein isolate is 1.5:1; 25% by weight of an energy matrix composed of 18% by weight of medium-chain fatty acids and 7% by weight of flaxseed oil, wherein the flaxseed oil contains 55% ω-3 fatty acids and 18% EPA+DHA precursors; and 12% by weight of an intestinal regulatory system comprising 6% by weight of oligofructose, 6% by weight of inulin, and a viable bacterial count of 1.2×10 8 CFU / g of microencapsulated Lactobacillus acidophilus encapsulated in a sodium alginate-chitosan double layer; and 8% by weight of metabolic auxiliary components, including 4% by weight of L-glutamine and a vitamin complex consisting of 0.8% by weight of vitamin C, 0.45% by weight of vitamin E, 0.03% by weight of vitamin B6 and 0.02% by weight of folic acid.

[0028] The embodiment also provides a preparation method of the full-nutrition formula preparation suitable for chronic kidney disease patients, and the preparation method comprises the following steps: dry mixing whey protein and dephosphorized soybean protein isolate at a mass ratio of 1.5:1 at 50 DEG C; performing microemulsion treatment on medium-chain fatty acids and flaxseed oil at a pressure of 65 MPa until the particle size is 180 nm, and then performing spray drying, wherein the inlet temperature of the spray drying is controlled at 170 DEG C; mixing the obtained material, oligofructose, inulin, L-glutamine and a vitamin compound sieved through an 80-mesh screen in an environment with a relative humidity of 25%; and finally adding microencapsulated Lactobacillus acidophilus to make the final mixing uniformity 96%.

[0029] Embodiment 2 The embodiment provides a full-nutrition formula preparation suitable for chronic kidney disease patients, which comprises 25% of a protein compound, 30% of an energy base, 15% of an intestinal regulation system and 10% of metabolic auxiliary ingredients. 8 The protein compound comprises 15% of whey protein and 10% of dephosphorized soybean protein isolate treated by phytase and having a phosphorus content of 0.3 mg / g, and the mass ratio of the whey protein to the dephosphorized soybean protein isolate is 1.5:1.

[0030] The embodiment also provides a preparation method of the full-nutrition formula preparation suitable for chronic kidney disease patients, and the preparation method comprises the following steps: dry mixing whey protein and dephosphorized soybean protein isolate at a mass ratio of 1.5:1 at 50 DEG C; performing microemulsion treatment on medium-chain fatty acids and flaxseed oil at a pressure of 65 MPa until the particle size is 180 nm, and then performing spray drying, wherein the inlet temperature of the spray drying is controlled at 170 DEG C; mixing the obtained material, oligofructose, inulin, L-glutamine and a vitamin compound sieved through an 80-mesh screen in an environment with a relative humidity of 25%; and finally adding microencapsulated Lactobacillus acidophilus to make the final mixing uniformity 96%.

[0031] Embodiment 3 The embodiment provides a full-nutrition formula preparation suitable for chronic kidney disease patients, which comprises 40% of a protein complex, 15% of an energy base, 10% of an intestinal regulation system and 5% of a metabolic auxiliary ingredient; the protein complex is composed of 25% of whey protein and 15% of dephosphorized soybean protein isolate treated by phytase and having a phosphorus content of 0.45 mg / g, and the mass ratio of the whey protein to the dephosphorized soybean protein isolate is 1.67:1; the energy base is composed of 12% of medium-chain fatty acids and 8% of flaxseed oil, and the flaxseed oil contains 50% of omega-3 fatty acids and has an EPA+DHA precursor content of 15%; the intestinal regulation system comprises 5% of fructo-oligosaccharides and 5% of inulin, and the number of live bacteria in the intestinal regulation system is 1 x 10 8 CFU / g of microencapsulated Lactobacillus acidophilus embedded by sodium alginate-chitosan double-layer embedding; and the metabolic auxiliary ingredient comprises 3% of L-glutamine and a vitamin compound composed of 0.5% of vitamin C, 0.3% of vitamin E, 0.02% of vitamin B6 and 0.01% of folic acid.

[0032] The embodiment also provides a preparation method of the full-nutrition formula preparation suitable for chronic kidney disease patients, and the preparation method comprises the following steps: dry mixing whey protein and dephosphorized soybean protein isolate at a mass ratio of 1.67:1 under the condition of 55 DEG C; performing microemulsion treatment on medium-chain fatty acids and flaxseed oil under a pressure of 50 MPa until the particle size is 200 nm, and then performing spray drying, wherein the inlet air temperature of the spray drying is controlled to be 160 DEG C; mixing the obtained material, fructo-oligosaccharides, inulin, L-glutamine and a vitamin compound which pass through an 80-mesh sieve in an environment with a relative humidity of 30%; and finally adding microencapsulated Lactobacillus acidophilus, so that the final mixing uniformity is 95%.

[0033] Embodiment 4 The embodiment is different from the embodiment 1 only in that the energy base is adjusted to be MCT 22% and flaxseed oil 3%.

[0034] Embodiment 5 The embodiment is different from the embodiment 1 only in that the proportion of omega-3 fatty acids in flaxseed oil is only 20%, and the EPA+DHA precursor content is only 10%.

[0035] Embodiment 6 The embodiment is different from the embodiment 1 only in that Lactobacillus acidophilus embedded by chitosan single-layer embedding is added.

[0036] Embodiment 7 The difference between this example and Example 1 is only in the ratio, i.e. Lactobacillus acidophilus is added by gelatin-sodium alginate-chitosan three-layer embedding.

[0037] Example 8 The difference between this example and Example 1 is only in the preparation method, i.e. the phosphorus content of the dephosphorized soybean protein isolate is 0.8 mg / g.

[0038] Example 9 The difference between this example and Example 1 is only in the preparation method, i.e. flaxseed oil is directly added without microemulsification treatment.

[0039] Comparative Example 1 The difference between this comparative example and Example 1 is only in the ratio, i.e. the protein complex only contains 30% of whey protein without soybean protein isolate.

[0040] Comparative Example 2 The difference between this comparative example and Example 1 is only in the ratio, i.e. the protein complex only contains 30% of dephosphorized soybean protein isolate without whey protein.

[0041] Comparative Example 3 The difference between this comparative example and Example 1 is only in the ratio, i.e. the mass ratio of whey protein to dephosphorized soybean protein isolate in the protein complex is adjusted to 2.4:1, i.e. the mass fraction of whey protein in the whole nutritional formula preparation is 21.18% and the mass fraction of dephosphorized soybean protein isolate is 8.82%.

[0042] Comparative Example 4 The difference between this comparative example and Example 1 is only in the ratio, i.e. the mass ratio of whey protein to dephosphorized soybean protein isolate in the protein complex is adjusted to 1.2:1, i.e. the mass fraction of whey protein in the whole nutritional formula preparation is 16.36% and the mass fraction of dephosphorized soybean protein isolate is 13.64%.

[0043] Comparative Example 5 The difference between this comparative example and Example 1 is only in the ratio, i.e. the energy substrate is adjusted to MCT 13% and flaxseed oil 12%.

[0044] Comparative Example 6 The difference between this comparative example and Example 1 is only in the ratio, i.e. the energy substrate is adjusted to MCT 22% and flaxseed oil 3%.

[0045] We used a rat model of nephrotic syndrome to study the nutritional support and improvement of kidney function of the whole nutritional formula preparations of Examples 1-9 and Comparative Examples 1-6 in rats.

[0046] Experimental animals: 160 SPF level SD rats with body weight (180 ± 10) g were selected and provided by the Experimental Animal Center of the School of Pharmacy, Shanghai Jiao Tong University. The animal production and use license numbers were SCXK (Shanghai) 2003-0003 and SYXK (Shanghai) 2007-0025, respectively. The animals were raised in an environment with room temperature of 20-25°C and relative humidity of 40-70%, and were allowed to eat freely.

[0047] Grouping and modeling: 150 rats were selected to construct a rat model of nephrotic syndrome. 4 mg / kg adriamycin was injected into the tail vein of the rats, with an interval of 1 week, and 2.5 mg / kg was injected. The 24-hour urine was collected after 24 hours, and the 24-hour urine protein quantification was detected. The level was ≥100 mg, which was considered as a successful modeling. A total of 120 rats were successfully modeled, and the 120 rats were divided into Examples 1-9 and Comparative Examples 1-6, each with 8 rats. The rats were orally administered with 8 mL / kg of the nutritional products of Examples and Comparative Examples, respectively. After 6 weeks, the corresponding indexes were measured.

[0048] Index observation: Biochemical index detection: The abdominal aortic blood of the rats in each group was taken and placed in a centrifuge tube. The centrifuge tube was centrifuged at 12000 r / min for 10 min. The upper clear liquid was taken and the creatinine, IL-6 and uremic toxin clearance rate (%) were detected by ELISA method.

[0049] Glomerular filtration rate (GFR): High performance liquid chromatography-fluorescence analysis method was used. 1) Preparation of standard solution. Indoxyl sulfate potassium salt control 23.71 mg was dissolved and diluted with methanol to obtain a stock solution with a concentration of 800 μg / mL. Acetonitrile was used to dilute the stock solution to obtain a final mass concentration of 80, 40, 20, 10, 5, 0.5, and 0.1 μg / mL, respectively. 2) Chromatographic conditions. The mobile phase was sodium dihydrogen phosphate buffer (0.1% trifluoroacetic acid, pH 2.5)-acetonitrile (92:8); the flow rate was 1.0 mL / min; the column temperature was 30°C; the sample temperature was 6°C; the detection wavelength was λ ex =280 nm, λ em =390 nm. 3) Sample processing method: The serum was separated by centrifugation at 3000 r / min for 10 min and stored at -20°C. Carefully pipette 100 μL of serum into a clean test tube, add 300 μL of 0.2% trifluoroacetic acid-acetonitrile (10:90) to precipitate the protein, vortex for 30 s, then centrifuge (12000 r / min, 8 min, 4°C), and take 200 μL of the upper clear liquid, filter through a microporous filter, and then analyze.

[0050] The test results are shown in Table 1.

[0051] Table 1 Protein composition (whey:soy) Phosphorous content (mg / g) Omega-3 retention (%) Probiotic survival (%) Serum creatinine reduction (%) GFR improvement (%) IL-6 reduction (%) Gut microbiota improvement (F / B / B) Uremic toxin clearance (%) Example 1 1.5:1 0.4 95 92 18 13 38 7.1→2.3 48 Example 2 1.5:1 0.3 93 90 16 12 35 7.0→2.5 45 Example 3 1.33:1 0.45 94 88 15 10 32 7.2→2.8 42 Example 4 1.5:1 0.4 85 91 14 9 25 7.1→3.1 40 Example 5 1.5:1 0.4 70 90 12 8 18 7.0→3.5 38 Example 6 1.5:1 0.4 94 45 10 7 35 7.1→4.2 30 Example 7 1.5:1 0.4 95 95 17 12 37 7.0→2.0 50 Example 8 1.5:1 0.8 94 90 8 5 30 7.2→3.8 28 Example 9 1.5:1 0.4 55 85 9 6 15 7.1→4.5 25 Comparative Example 1 Pure whey 0.3 95 92 5 3 20 7.3→5.8 15 Comparative Example 2 Pure soy 0.4 94 90 7 4 22 7.2→5.5 18 Comparative Example 3 2.4:1 0.4 94 91 10 6 28 7.1→4.0 32 Comparative Example 4 1.2:1 0.4 93 89 11 7 30 7.0→3.8 35 Comparative Example 5 1.5:1 0.4 98 90 13 9 40 7.1→3.0 42 Comparative Example 6 1.5:1 0.4 82 91 12 8 22 7.0→3.6 36 From the above test data we can draw the following conclusions: (1) The serum creatinine reduction, eGFR improvement, IL-6 reduction and uremic toxin clearance rate of Examples 1-9 are significantly better than those of Comparative Examples 1-6, indicating that the present application significantly improves the renal function improvement effect, anti-inflammatory ability and intestinal microecological regulation function of patients with chronic kidney disease by adopting the precise ratio of 1.5-2:1 of whey protein and dephosphorized soybean protein, high-pressure microemulsified flaxseed oil and sodium alginate-chitosan double-layer embedded probiotic technology; (2) As can be seen from Comparative Example 1 and Examples 4-5, when the MCT proportion in the energy substrate is increased to 22%, the retention rate of omega-3 fatty acids decreases by 10%, resulting in a significant weakening of the anti-inflammatory effect, and after reducing the omega-3 content in flaxseed oil to 20%, the IL-6 reduction is reduced by more than 50%, proving that the technical scheme of 18% MCT and 7% flaxseed oil and 35% omega-3 content is the most reasonable; (3) As can be seen from Comparative Example 1 and Examples 6-7, the survival rate of probiotics embedded with single-layer chitosan is less than 50%, which seriously affects the intestinal flora regulation effect, and after upgrading to three-layer embedding technology, although the survival rate is increased by 3%, the process complexity is greatly increased, confirming that the sodium alginate-chitosan double-layer embedding technology has achieved the best balance between effect and cost; (4) As can be seen from Comparative Example 1 and Examples 8-9, when the phosphorus content of dephosphorized soybean protein is increased to 0.8 mg / g, the eGFR improvement is reduced by 60%, and flaxseed oil without microemulsification reduces the retention rate of omega-3 by 40%, fully demonstrating that strict control of phosphorus content and the use of high-pressure microemulsification process play a decisive role in ensuring product efficacy; (5) As can be seen from Comparative Example 1 and Comparative Examples 1-2, the renal function improvement effect of whey protein or soybean protein alone is only 30-40% of the composite protein scheme of the present application, verifying the synergistic effect of the specific proportion of composite protein; (6) As can be seen from Comparative Example 1 and Comparative Examples 3-4, when the protein ratio deviates from (1.5-2):1 to 2.4:1 or 1.2:1, the uremic toxin clearance rate decreases by 20-30%, proving that the determined protein ratio range of the present application is crucial to maintaining the intestinal-kidney metabolic balance; (7) As can be seen from Comparative Example 1 and Comparative Examples 5-6, excessive increase of the flaxseed oil proportion to 12% can increase the retention rate of omega-3, but the energy supply is imbalanced, and too high MCT proportion of 22% will weaken the anti-inflammatory effect, again verifying the scientificity of the energy substrate ratio of the present application.

[0052] The full-nutrition formula preparation of the application protects renal function effectively while meeting the low protein requirement of patients with chronic kidney disease through the synergistic effect of scientifically proportioned whey protein and dephosphorized soybean protein; the innovative high-pressure microemulsification technology significantly improves the stability and bioavailability of active ingredients in flaxseed oil, providing balanced energy supply and significant anti-inflammatory effect for patients; the unique intestinal regulation system combined with the patented probiotic embedding technology reduces the generation and absorption of uremic toxins from the source, achieving comprehensive nutritional intervention for multiple targets of chronic kidney disease. The technical scheme exhibits significant advantages in improving renal function indicators, regulating inflammation levels and optimizing intestinal microecology.

[0053] The above is only a preferred embodiment of the application, and does not limit the application in any form. Although the application has been disclosed as above with a preferred embodiment, it is not intended to limit the application. Any person skilled in the art can make slight changes or modifications to the above disclosed technical content to obtain equivalent embodiments with equivalent changes, without departing from the scope of the technical scheme of the application. Any simple modification, equivalent change and modification made to the above embodiments according to the technical essence of the application are still within the scope of the technical scheme of the application.

Claims

1. A complete nutritional formula preparation suitable for patients with chronic kidney disease, characterized in that: The following components are included by mass percentage: Protein complex 25-40%: composed of 15-30% whey protein and 5-15% dephosphorylated soy protein isolate, with the mass ratio of whey protein to dephosphorylated soy protein isolate being (1.5-2):1; Energy matrix 20-30%: composed of 10-20% medium-chain fatty acids and 5-10% flaxseed oil; Intestinal regulatory system 10-25%; Metabolic auxiliary ingredients 5-10%.

2. The complete nutritional formula preparation according to claim 1, characterized in that The dephosphorized soybean protein isolate is treated with phytase, and the phosphorus content is less than 0.5 mg / g.

3. The complete nutritional formula according to claim 1 or 2, characterized in that: The intestinal regulation system includes the following components: Fructooligosaccharides 5-20%; Inulin 5-10%; Microencapsulated Lactobacillus acidophilus, viable count ≥ 1×10 8 CFU / g.

4. The complete nutritional formula according to any one of claims 1 to 3, characterized in that The microencapsulated Lactobacillus acidophilus is embedded in a double layer of sodium alginate and chitosan, and has a survival rate in a gastric acid environment of >90%.

5. The complete nutritional formula according to any one of claims 1 to 4, characterized in that: The metabolic auxiliary ingredients include: L-glutamine 3-5%; Vitamin complex: Vitamin C 0.5-1%, Vitamin E 0.3-0.6%, Vitamin B6 0.02-0.05%, Folic acid 0.01-0.03%.

6. The complete nutritional formula according to any one of claims 1 to 5, characterized in that: The flaxseed oil contains ω-3 fatty acids at least 50% and EPA+DHA precursors at least 15%.

7. A method for preparing the complete nutritional formula according to any one of claims 1 to 6, characterized in that: The following steps are involved: (1) Preparation of protein complex: dry mix whey protein and dephosphorylated soy protein isolate in appropriate proportions at 45-55°C; (2) Energy matrix treatment: MCT and linseed oil are microemulsified under high pressure to a particle size of ≤200 nm and then spray-dried; (3) Mixing: Mix the materials obtained in steps (1) and (2) with the intestinal regulating system and metabolic auxiliary components passed through an 80-mesh sieve; (4) Add probiotics: Finally, add microencapsulated Lactobacillus acidophilus and mix uniformly to ≥95%.

8. The preparation method according to claim 7, characterized in that In step (2), the microemulsification pressure is 50-80 MPa, and the spray drying inlet air temperature is 160-180°C.

9. The preparation method according to claim 7 or 8, characterized in that In step (4), the humidity of the mixed environment is controlled at RH≤30%.

10. Use of the complete nutritional formula according to any one of claims 1 to 6 in the preparation of a nutritional support product for patients with chronic kidney disease stages 3 to 5.