Dynamic adaptation nutrition system suitable for tumor patients and preparation method, use method and application thereof

Abstract

The invention relates to the technical field of food or medicine, in particular to a dynamic adaptation nutrition system suitable for tumor patients and a preparation method, a using method and application of the dynamic adaptation nutrition system. The dynamic adaptation nutrition system suitable for the tumor patient comprises a first module, a second module, a third module, a fourth module and a fifth module. The composition of each module in the five modules is as follows: each 100g of the module comprises 9.5 to 12.0 g of protein, 6.5 to 9.0 g of fat and 10.0 to 15.0 g of carbohydrate; the protein at least contains glutamine, and the dosage of the glutamine in each module is 0.8-2.0 g / 100g; in the first module, the second module, the third module and the fifth module, the protein further comprises leucine, and the use amount of the leucine in each module is 0.2-0.4 g / 100g; and the module IV does not contain leucine. The invention provides an individualized precise nutrition support system and method capable of dynamically matching complex and changeable metabolic states and complications of tumor patients, so as to solve the problems of low clinical efficiency and insufficient accuracy of the existing static homogenization nutrition support mode.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of food or pharmaceutical technology, in particular to a dynamic adaptive nutrition system suitable for tumor patients and a preparation method, use method and application thereof. BACKGROUND

[0002] Tumor is that under the action of various carcinogenic factors, a cell in local tissue loses normal regulation of its growth at the genetic level, leading to abnormal proliferation and formation of abnormal lesions. Due to the consumption of tumor, metabolic disorder, influence of tumor on appetite and mental depression, etc., the incidence of malnutrition characterized by weight loss in tumor patients is high.

[0003] Tumor malnutrition is a very common tumor syndrome, which is usually called cancer cachexia. Its characteristics are progressive and multi-faceted weight loss, especially sustained loss of skeletal muscle. This metabolic disorder is driven by the tumor itself and the body's inflammatory response to the tumor, which is manifested in the following aspects:

[0004] (1) Energy metabolism disorder: increased resting energy consumption, accompanied by some "insulin resistance", leading to impaired glucose utilization in the body.

[0005] (2) Persistent inflammation: tumors release a large amount of pro-inflammatory cytokines (such as TNF-α, IL-1, IL-6) in the microenvironment, leading to systemic inflammation, which is the main factor driving protein and fat decomposition.

[0006] (3) Protein metabolism imbalance: muscle protein synthesis is reduced, and catabolism is intensified, especially through the ubiquitin-proteasome pathway, which is activated, leading to severe muscle atrophy.

[0007] (4) Traditional nutritional support can provide energy and substrates, but often cannot effectively reverse the specific metabolic state of tumor patients, and sometimes may even stimulate tumor growth. More importantly, cancer cachexia is a dynamic process, and patients face different core metabolic challenges at different stages. Therefore, it is urgent in clinical practice to go beyond a single nutritional formula and provide a precise nutritional intervention strategy that can be dynamically adjusted according to the specific disease stage and metabolic phenotype of the patient.

[0008] Tumor patients with insufficient daily dietary nutrition can choose special medical purpose formula food suitable for tumor patients to eat, thereby reducing the risk of nutritional deficiency in patients. Food for special medical purposes (FSMP) refers to a formula food specially processed and prepared to meet the special nutritional or dietary needs of people with restricted eating, digestive and absorptive disorders, metabolic disorders, or specific disease states.

[0009] The retrieved relevant patent documents are: The document discloses a specific nutritional formula food suitable for tumor patients, which is mainly prepared from the following raw materials in parts by weight: whey protein 15-22 parts, soybean protein 5-10 parts, sodium caseinate 2-6 parts, seaweed oil 1-3 parts, medium-chain triglyceride 3-7 parts, vegetable oil 5-10 parts, arginine 2-5 parts, glutamine 1-8 parts, polydextrose 5-9 parts, oligoisomaltose 3-7 parts, fructose 6-10 parts, malt dextrin 15-25 parts, vitamin C sodium 0.3-0.6 parts, compound vitamins 0.4-1 parts, compound minerals 6-10 parts, sucralose 0.1-0.2 parts, food essence 0.3-0.8 parts.

[0010] The retrieved relevant non-patent documents are: The document discloses that for malignant tumor patients with PG-SGA≥4 points or mPG-SGA≥3 points or Scored-GLIM≥8.6 points or NRS 2002 / GLIM diagnosed with malnutrition and able to eat orally, it is recommended to start FSMP nutritional treatment while undergoing anti-tumor treatment.

[0011] The prior art represented by the foregoing documents has at least the following unsolved technical problems or defects: The existing nutritional formula is in the mode of'single formula, static intervention', which has systematic limitations in actual application. They cannot meet the dynamic and heterogeneous metabolic needs of tumor patients, mainly manifested in: (1) Insufficient metabolic regulation precision: lack of fine design of the internal composition and synergistic mechanism of nutrients. For example, the time sequence influence of protein digestion rate on muscle synthesis is not distinguished, and the functional differences and optimal ratio of different fatty acids (such as EPA, DHA, MCT) in anti-inflammatory and energy supply are not optimized.

[0012] (2) The limitation of nutritional utilization efficiency: the adopted whole protein and long-chain fat and other forms have insufficient bioavailability for tumor patients with digestive and absorptive disorders, which results in the failure of the nutritional support to fully play its role.

[0013] (3) Lack of individual adaptability and dynamic response ability: the fixed formula structure of the prior art is difficult to adapt to the specific nutritional needs under different tumor types, disease stages (such as pre-cachexia and post-cachexia) or treatment side effects (such as intestinal mucositis caused by radiotherapy and chemotherapy), and lacks flexibility for dynamic adjustment.

[0014] Therefore, it is necessary to develop a dynamic adaptive nutrition system suitable for tumor patients and its use method and application to solve the above technical problems. SUMMARY

[0015] The purpose of the present application is to provide: A dynamic adaptive nutrition system suitable for tumor patients and related technologies to provide an individualized precision nutrition support system and method capable of dynamically matching the complex and variable metabolic states and complications of tumor patients, so as to overcome the problems of low clinical efficiency and insufficient precision of the existing static homogeneous nutrition support mode.

[0016] The present application is realized by the following technical solutions: The present application provides a dynamic adaptive nutrition system suitable for tumor patients, comprising module one, module two, module three, module four and module five. The composition of each of the five modules is as follows: each 100g contains 9.5-12.0g of protein, 6.5-9.0g of fat and 10.0-15.0g of carbohydrate. The protein contains at least glutamine, and the amount of glutamine in each module is 0.8-2.0g / 100g. In the module one, module two, module three and module five, the protein further comprises leucine, and the amount of leucine in each module is 0.2-0.4g / 100g; the module four does not contain leucine.

[0017] As an embodiment of the present application, the composition of each module is as follows: each 100g contains 10.0-11.5g of protein, 7.1-8.3g of fat and 10.2-14.4g of carbohydrate; and the amount of glutamine in each module is 0.9-1.5g / 100g.

[0018] As an embodiment of the present application, the molar ratio of glutamine to leucine is 1.795-4.5:1, preferably 2.4-4.4:1.

[0019] As an embodiment of the present application, each module further comprises a complex mineral and a complex vitamin.

[0020] As a preferred embodiment of the present application, the complex mineral comprises at least five of sodium, potassium, calcium, phosphorus, magnesium, iron, zinc and selenium.

[0021] As a further preferred embodiment of the present application, the complex mineral comprises sodium, potassium, calcium, phosphorus, magnesium, iron, zinc and selenium. Preferably, the complex mineral in the module four and the module five is in the form of amino acid chelated minerals.

[0022] The "amino acid chelate" of the present application refers to a high bioavailability organic mineral form in which mineral ions are combined with amino acids (such as glycine, lysine, methionine, etc.) through coordination bonds. It is a mature raw material in the field of food and special medical food, which can be widely obtained through commercial channels. For example, the TRAACS® series of mineral amino acid chelates produced by Albion Laboratories, Inc., a supplier of mineral nutritional fortifiers, such as ferrous glycinate, zinc lysinate, magnesium lysinate, etc., and other commercially available amino acid chelated minerals that meet the national food safety standards and have the same technical characteristics. The specific amount is added according to the element content requirements of the formula design.

[0023] As a still further preferred embodiment of the present application, the mass ratio of calcium to phosphorus is 1.6-1.7:1, and particularly preferably 1.67:1.

[0024] As a particularly preferred embodiment of the present application, the composition of the complex mineral is as follows: each module contains 300-340 mg / 100 g of sodium, 450-510 mg / 100 g of potassium, 300-340 mg / 100 g of calcium, 180-204 mg / 100 g of phosphorus, 70-80 mg / 100 g of magnesium, 5.0-5.8 mg / 100 g of iron, 6-7 mg / 100 g of zinc and 35-40 μg / 100 g of selenium.

[0025] As a preferred embodiment of the present application, the complex vitamin comprises at least five of vitamin A, vitamin D, vitamin E, vitamin Kl, vitamin C, vitamin Bl, vitamin B2, vitamin B6, vitamin B12, vitamin B3, folic acid, vitamin B5, vitamin B7 and choline.

[0026] As a further preferred embodiment of the present application, the composition of the complex vitamin is as follows: vitamin A 250-300 μg / 100 g, vitamin D 10-15 μg / 100 g in terms of α-tocopherol equivalent, vitamin E 8-10.6 mg / 100 g, vitamin K1 35-42 μg / 100 g, vitamin C 60-74 mg / 100 g, vitamin B1 0.58-0.68 mg / 100 g, vitamin B2 0.65-0.86 mg / 100 g, vitamin B6 0.78-0.86 mg / 100 g, vitamin B12 1.2-1.35 μg / 100 g, vitamin B3 7.5-9.9 mg / 100 g, folic acid 0-160 μg / 100 g, vitamin B5 2.5-3.3 mg / 100 g, vitamin B7 11.6-25 μg / 100 g, and choline 0-150 mg / 100 g.

[0027] As a further preferred embodiment of the present application, the complex vitamin in module one does not contain choline, and the amount of choline in modules two to five is 130-150 mg / 100 g; the complex vitamin in module five does not contain folic acid, and the amount of folic acid in modules one to four is 145-160 μg / 100 g.

[0028] As an embodiment of the present application, the total energy of each module is 140-170 kcal / 100 g, preferably 145-170 kcal / 100 g, and further preferably 151-166 kcal / 100 g.

[0029] As an embodiment of the present application, each module comprises, in terms of energy percentage: protein 22-26%, fat 36-50%, and carbohydrate 27-40%.

[0030] As an embodiment of the present application, the protein further comprises at least one of arginine, whey protein, hydrolyzed whey protein peptide, collagen peptide, soybean protein isolate, rice protein, calcium caseinate, and sodium caseinate.

[0031] As a preferred embodiment of the present application, the protein in module one further comprises arginine, whey protein, soybean protein isolate, calcium caseinate, and sodium caseinate; the protein in modules two and three further comprises whey protein, soybean protein isolate, and calcium caseinate; the protein in module four further comprises hydrolyzed whey protein peptide and collagen peptide; and the protein in module five further comprises whey protein, rice protein, and calcium caseinate.

[0032] As a further preferred embodiment of the present invention, module one includes 0.03-0.05g / 100g of arginine, 3.5-4.1g / 100g of whey protein, 1.5-2.5g / 100g of soy protein isolate, 1-2g / 100g of calcium caseinate and 1-2g / 100g of sodium caseinate; Modules 2 and 3 include whey protein 3.5-4.5g / 100g, soy protein isolate 1-2.5g / 100g, and calcium caseinate 2-3g / 100g; Module four includes 8-9g / 100g of hydrolyzed whey protein peptides and 1-2g / 100g of collagen peptides; Module 5 includes 4-5g / 100g of whey protein, 2.5-3.5g / 100g of rice protein, and 1-2g / 100g of calcium caseinate.

[0033] In one embodiment of the present invention, the fat includes at least one of soybean lecithin, medium-chain triglyceride oil (MCT oil), flaxseed oil, conjugated linoleic acid, fish oil, algal oil, soybean oil, rapeseed oil, sunflower seed oil, and structured lipids.

[0034] The sunflower seed oil is preferably high-oleic sunflower seed oil. High-oleic sunflower seed oil refers to sunflower seed oil with an oleic acid (cis-9-octadecenoic acid) content of not less than 80% of the total fatty acid mass. It is derived from a specific high-oleic sunflower seed variety obtained through breeding technology and has the characteristics of high oxidative stability and a prominent proportion of monounsaturated fatty acids.

[0035] The conjugated linoleic acid refers to a mixture of octadecadienoic acid isomers containing conjugated double bonds, whose active ingredients mainly include C9,T11-CLA and T10,C12-CLA. It can be added in the form of natural oils rich in these isomers, purified free fatty acids, or their derivatives (such as glycerides and ethyl esters).

[0036] The structured lipid is a triglyceride, in which the sn-1 and 3 positions are medium-chain fatty acids containing 6-12 carbon atoms in the carbon chain, and the sn-2 position is a long-chain fatty acid containing more than 12 carbon atoms in the carbon chain.

[0037] Preferably, the sn-2 position of the structured lipid is a long-chain polyunsaturated fatty acid containing more than 12 carbon atoms in its carbon chain; more preferably, the long-chain polyunsaturated fatty acid is derived from the fatty acid structure of fish oil.

[0038] Preferably, the medium-chain fatty acids at the sn-1,3 positions of the structured lipids are derived from the fatty acid structure of medium-chain triglyceride oil.

[0039] Particularly preferred, the preparation process of the structured lipid includes the following steps: mixing medium-chain triglyceride oil, fish oil and 1,3-position specific lipase, carrying out a catalytic reaction under certain temperature and vacuum conditions, and decolorizing and deodorizing to obtain the structured lipid.

[0040] The preferred mass ratio of medium-chain triglyceride oil to fish oil is 2-4:1-3; the preferred amount of the 1,3-position specific lipase is 0.5-2% of the total mass of medium-chain triglyceride oil and fish oil; the preferred temperature is 50-70℃; the preferred vacuum condition is 50-200 Pa; the preferred catalytic reaction time is 4-12 hours; and the preferred 1,3-position specific lipase is Lipozyme RM IM from Rhizopus mellea.

[0041] The structured lipids are MLM-type structured lipids, with long-chain polyunsaturated fatty acids (EPA / DHA) mainly at the sn-2 position and medium-chain fatty acids at the sn-1 and 3 positions. Their fatty acid composition was determined by gas chromatography, and the total content of EPA+DHA was not less than 25%.

[0042] In a preferred embodiment of the present invention, the fats in module one include soybean lecithin, MCT oil, flaxseed oil, conjugated linoleic acid, fish oil, soybean oil, and rapeseed oil; the fats in module two include soybean lecithin, MCT oil, flaxseed oil, conjugated linoleic acid, and fish oil; the fats in module three include soybean lecithin, MCT oil, flaxseed oil, conjugated linoleic acid, fish oil, and sunflower seed oil; the fats in module four include MCT oil, fish oil, and structured lipids; and the fats in module five include soybean lecithin, MCT oil, flaxseed oil, algal oil, and sunflower seed oil.

[0043] As a further preferred embodiment of the present invention, module one includes 0.8-1.2g / 100g soybean lecithin, 4-5g / 100g MCT oil, 0.4-0.8g / 100g flaxseed oil, 0.1-0.3g / 100g conjugated linoleic acid, 0.5-1.3g / 100g fish oil, 0.05-0.15g / 100g soybean oil, and 0.05-0.15g / 100g rapeseed oil; Module 2 includes 1-1.5g / 100g of soybean lecithin, 3.5-4.5g / 100g of MCT oil, 0.2-0.8g / 100g of flaxseed oil, 0.1-0.4g / 100g of conjugated linoleic acid, and 1-1.5g / 100g of fish oil; Module 3 includes 1.2-1.8g / 100g soybean lecithin, 4.5-5g / 100g MCT oil, 0.2-0.8g / 100g flaxseed oil, 0.1-0.4g / 100g conjugated linoleic acid, 1-1.5g / 100g fish oil, and 0.05-0.2g / 100g sunflower seed oil. Module four includes 4-5.5g / 100g of MCT oil, 0.5-1.5g / 100g of fish oil, and 1-2g / 100g of structured lipids; Module 5 includes 0.5-1.5g / 100g of soybean lecithin, 3-5g / 100g of MCT oil, 0.2-1g / 100g of flaxseed oil, 1-2g / 100g of algal oil, and 0.6-1g / 100g of sunflower seed oil.

[0044] In one embodiment of the present invention, the carbohydrate includes at least one of isomaltulose, resistant dextrin, fructooligosaccharide, maltodextrin and astragalus polysaccharide.

[0045] In a preferred embodiment of the present invention, the carbohydrates in Module 1 and Module 2 include isomaltulose, resistant dextrin, fructooligosaccharides, and maltodextrin; the carbohydrates in Module 3 and Module 4 include isomaltulose, resistant dextrin, and maltodextrin; and the carbohydrates in Module 5 include isomaltulose, resistant dextrin, maltodextrin, and astragalus polysaccharide.

[0046] As a further preferred embodiment of the present invention, module one includes 1-2g / 100g of isomaltulose, 3-4g / 100g of resistant dextrin, 0.2-0.8g / 100g of fructooligosaccharides and 8.5-9g / 100g of maltodextrin; Module 2 includes isomaltulose 2.5-3.5g / 100g, resistant dextrin 3.5-4g / 100g, fructooligosaccharides 0.5-1.5g / 100g and maltodextrin 3-3.5g / 100g; Module 3 includes isomaltulose 3-4g / 100g, resistant dextrin 4-5g / 100g and maltodextrin 2-2.5g / 100g; Module four includes isomaltulose 0.2-0.8g / 100g, resistant dextrin 2.5-3.5g / 100g and maltodextrin 9-9.5g / 100g; Module 5 includes isomaltulose 2.5-3.5g / 100g, resistant dextrin 4.5-5.5g / 100g, maltodextrin 5.5-6.5g / 100g, and astragalus polysaccharide 0.2-0.8g / 100g.

[0047] As one embodiment of the present invention, each module further includes at least one of β-hydroxy-β-methylbutyrate, nucleotide, tartrate choline, emulsifier, curcumin and lactoferrin.

[0048] In a preferred embodiment of the present invention, the β-hydroxy-β-methylbutyrate comprises calcium β-hydroxy-β-methylbutyrate. The molar ratio of the β-hydroxy-β-methylbutyrate to leucine is 1:1.5-5.0, preferably 1:1.7-3.0, and more preferably 1:3.0.

[0049] In a preferred embodiment of the present invention, the nucleotides are derived from yeast.

[0050] In a further preferred embodiment of the present invention, the nucleotide is 5'-ribonucleotide disodium I+G.

[0051] In a preferred embodiment of the present invention, the emulsifier is a medium-chain fatty acid sucrose ester.

[0052] In a preferred embodiment of the present invention, the curcumin is microencapsulated curcumin.

[0053] As a further preferred embodiment of the present invention, module one further includes 0.25-0.3 g / 100 g of β-hydroxy-β-methylbutyrate, 0.02-0.08 g / 100 g of nucleotides, and 0.05-0.1 g / 100 g of tartrate choline; Module 2 also includes 0.3-0.4 g / 100 g of β-hydroxy-β-methylbutyrate, 0.05-0.1 g / 100 g of nucleotides, and 0.05-0.15 g / 100 g of tartrate choline; Module 3 also includes 0.35-0.45 g / 100 g of β-hydroxy-β-methylbutyrate, 0.05-0.1 g / 100 g of nucleotides, and 0.1-0.15 g / 100 g of tartrate choline; Module four also includes 0.2-0.4 g / 100 g of β-hydroxy-β-methylbutyrate, 0.02-0.08 g / 100 g of nucleotides, 0.1-0.15 g / 100 g of tartrate choline, and 0.3-0.8 g / 100 g of emulsifier; Module 5 also includes 0.3-0.4 g / 100 g of β-hydroxy-β-methylbutyrate, 0.02-0.1 g / 100 g of nucleotides, 0.05-0.15 g / 100 g of tartrate choline, 0.01-0.05 g / 100 g of curcumin, and 0.02-0.08 g / 100 g of lactoferrin.

[0054] In one embodiment of the present invention, in module one, the protein further includes arginine, whey protein concentrate, soy protein isolate, calcium caseinate, and sodium caseinate; the fat includes soy lecithin, medium-chain triglyceride oil, linoleic acid, conjugated linoleic acid, fish oil, soybean oil, and rapeseed oil; the carbohydrate includes isomaltulose, resistant dextrin, fructooligosaccharides, and maltodextrin; module one also includes complex minerals, complex vitamins, β-hydroxy-β-methylbutyrate, nucleotides, and tartrate choline.

[0055] In one embodiment of the present invention, in module two, the protein further includes whey protein isolate, soy protein isolate, and calcium caseinate; the fat includes soy lecithin, medium-chain triglyceride oil, linoleic acid, conjugated linoleic acid, and fish oil; the carbohydrate includes isomaltulose, resistant dextrin, fructooligosaccharides, and maltodextrin; module two also includes complex minerals, complex vitamins, β-hydroxy-β-methylbutyrate, nucleotides, and tartrate choline.

[0056] In one embodiment of the present invention, in module three, the protein further includes isolated whey protein, soy protein isolate, and calcium caseinate; the fat includes soy lecithin, medium-chain triglyceride oil, linoleic acid, conjugated linoleic acid, fish oil, and sunflower seed oil; the carbohydrate includes isomaltulose, resistant dextrin, and maltodextrin; module three also includes complex minerals, complex vitamins, β-hydroxy-β-methylbutyrate, nucleotides, and tartrate choline.

[0057] In one embodiment of the present invention, in module four, the protein further includes hydrolyzed whey protein peptides and collagen peptides; the fat includes medium-chain triglyceride oil, fish oil, and structured lipids; the carbohydrate includes isomaltulose, resistant dextrin, and maltodextrin; module four also includes complex minerals, complex vitamins, β-hydroxy-β-methylbutyrate, nucleotides, tartrate choline, and medium-chain fatty acid sucrose esters.

[0058] In one embodiment of the present invention, in module five, the protein further includes whey protein concentrate, rice protein, and calcium caseinate; the fat includes soybean lecithin, medium-chain triglyceride oil, flaxseed oil, algal oil, and sunflower seed oil; the carbohydrate includes isomaltulose, resistant dextrin, maltodextrin, and astragalus polysaccharide; module five also includes complex minerals, complex vitamins, β-hydroxy-β-methylbutyrate, nucleotides, choline tartrate, curcumin, and lactoferrin.

[0059] A second aspect of the present invention provides a method of using the aforementioned dynamic adaptive nutrition system, wherein the method of use is not intended for the diagnosis and / or treatment of disease, and includes the following steps: (1) Cancer patients are classified according to criteria A, B, C, and D, where: Standard A indicates a PG-SGA score of ≥4 points; Standard B indicates a HOMA-IR > 2.5 and a fasting blood glucose ≥ 6.1 mmol / L (or a 2-hour postprandial blood glucose ≥ 7.8 mmol / L); HOMA-IR = (fasting blood glucose × fasting insulin) / 22.5; Criterion C indicates a CTCAE diarrhea grade ≥2, clearly related to the current chemotherapy regimen. Grade 2 indicates an increase of 4-6 times of diarrhea per day from baseline, or nocturnal diarrhea / moderate abdominal pain requiring pharmacological intervention; Standard D indicates that hs-CRP ≥ 10 mg / L and that female patients have hemoglobin Hb < 110 g / L and male patients have hemoglobin Hb < 120 g / L; (2) When a cancer patient meets only standard A and has a PG-SGA score of 4-8, use module one; when a cancer patient meets only standard A and has a PG-SGA score of ≥9, use module two; when a patient meets only standard A and standard B at the same time, use module three; when a patient meets only standard A, standard B and standard C at the same time, use module four; when a patient meets both standard A and standard D at the same time, use module five.

[0060] A third aspect of the present invention provides a method for preparing a dynamically adaptable nutrition system, wherein the method for preparing module one includes the following steps: (1) Add soybean lecithin to water and stir to dissolve to obtain mixture A; premix the remaining components in the fat to obtain an oil phase; add the oil phase to mixture A and shear at the same time to obtain an emulsion; (2) Maltodextrin, isomaltulose, resistant dextrin, sodium caseinate, calcium caseinate, soy protein isolate and whey protein concentrate are added to the emulsion in sequence to obtain mixture B; (3) Homogenize and sterilize mixture B to obtain a liquid; (4) Spray dry the liquid material to obtain the base powder; (5) Take a portion of the base powder and mix it with β-hydroxy-β-methylbutyrate, leucine, arginine and glutamine to obtain premix A; take a portion of the base powder and mix it with compound vitamins, nucleotides and tartrate choline to obtain premix B; take a portion of the base powder and mix it with compound minerals to obtain premix C; take a portion of the base powder and mix it with oligofructose to obtain premix D; (6) Add premix A, premix B, premix C and premix D to the remaining base powder and mix evenly to obtain the final product.

[0061] As one embodiment of the present invention, the temperature of the water in step (1) is 45-55°C; and / or the shearing speed is 2000-3000 rpm, and the time is 10-20 minutes; And / or the homogenization in step (3) is carried out in two stages, with the first stage pressure being 150-250 bar and the second stage pressure being 30-70 bar; and / or the sterilization parameters are: temperature 75-85℃, time 15-25 minutes; and / or the solids concentration of the liquid is 30-50%; And / or the inlet air temperature of the spray drying in step (4) is 175-190°C and the outlet air temperature is 85-95°C; And / or the portion of the base powder mentioned in step (5) accounts for 0.5-1% of the total amount of base powder; and / or the mixing method is an equal incremental method; And / or the premix A, premix B, premix C and premix D mentioned in step (6) are added to the remaining base powder in descending order of total mass; and / or the mixing time is not less than 30 minutes.

[0062] As one embodiment of the present invention, the preparation method of the second module includes the following steps: S1. Prepare all raw material components and water for Module 2, for later use; S2. Maltodextrin, resistant dextrin and isomaltulose are added sequentially to the first part of water to obtain a dispersion; calcium caseinate, soy protein isolate and whey protein isolate are added sequentially to the dispersion to obtain a protein-carbohydrate solution; S3. Dissolve the complex minerals in the second part of the water to obtain a mineral concentrate; add the mineral concentrate to the protein-carbohydrate solution, adjust the pH, and use the resulting mixed slurry as the aqueous phase; S4. Mix medium-chain triglyceride oil, linolenic acid, conjugated linoleic acid and fish oil in sequence, add soybean lecithin and fat-soluble vitamins from the complex vitamins, heat to obtain oil phase; S5. Add the oil phase to the aqueous phase to form an O / W type emulsion, homogenize it, add the third part of water, and obtain the slurry for spray drying; S6. Spray dry the slurry to obtain the base powder; S7. Premix β-hydroxy-β-methylbutyrate, leucine, glutamine and nucleotides to obtain a first-stage premix; premix the water-soluble vitamins in the complex vitamins with tartrate choline to obtain a second-stage premix; mix the first-stage premix, the second-stage premix and fructooligosaccharides to obtain a carrier premix; S8. Mix a portion of the base powder with the carrier premix first, then add the remaining base powder to obtain the final product.

[0063] In a preferred embodiment of the present invention, in step S2, the amount of the first portion of water accounts for 60% of the total water volume; and / or the temperature of the first portion of water is 55-60°C; and / or the stirring is carried out during the addition of maltodextrin, resistant dextrin and isomaltulose at a stirring speed of 500 rpm; and / or the stirring is carried out during the addition of calcium caseinate, soy protein isolate and whey protein isolate at a stirring speed of 3000-4000 rpm. And / or in step S3, the amount of the second portion of water accounts for 10% of the total water volume; and / or the temperature of the second portion of water is 45-55℃; and / or the pH is 6.8-7.2; And / or in step S4, the heating temperature is 45-50°C; And / or in step S5, the oil phase is subjected to high-speed shearing during the addition of the aqueous phase, with a shearing speed of 8000-10000 rpm; and / or the rate at which the oil phase is added to the aqueous phase is 150-250 mL / min; and / or the homogenization is two-stage, with a first-stage pressure of 250 bar and a second-stage pressure of 50 bar, and the homogenization is performed 1-3 times; and / or the solids content of the spray-drying slurry is 45-50%. And / or in step S6, the inlet air temperature of the spray dryer is 175-185°C and the outlet air temperature is 79-85°C; And / or in step S7, the mixing method is an equal-incremental method; And / or in step S8, the portion of the base material powder accounts for 5-10% of the total amount of base material powder.

[0064] As one embodiment of the present invention, the preparation method of module three includes the following steps: (i) Prepare all raw material components and water for Module 3, for later use; (ii) Add maltodextrin, partially resistant dextrin, isomaltulose, calcium caseinate, soy protein isolate, and whey protein isolate to a portion of water in sequence, shear evenly, add compound minerals, and obtain the aqueous phase; (iii) Mix medium-chain triglyceride oil, sunflower seed oil, flaxseed oil, conjugated linoleic acid, fish oil, soybean lecithin and fat-soluble vitamins in the complex vitamins, and heat to obtain an oil phase; (iv) Add the oil phase to the aqueous phase, shear to obtain an emulsion, homogenize, add the remaining water to obtain a slurry; (v) Spray dry the slurry to obtain the base powder; (vi) β-hydroxy-β-methylbutyrate, glutamine, leucine, nucleotide, tartrate choline, water-soluble vitamins in the compound vitamins, glidin, the remaining resistant dextrin, and part of the base powder are premixed to obtain a premix; (vii) Mix the remaining base powder with the premix to obtain the final product.

[0065] In a preferred embodiment of the present invention, in step (ii), the amount of water used is 70-80% of the total water volume, preferably 75%; and / or the temperature of the water is 58-62°C; and / or the amount of resistant dextrin accounts for 90-95% of the total resistant dextrin volume, preferably 92%; and / or the shearing speed is 2800-3200 rpm, preferably 3000 rpm, and the time is 10-15 minutes. And / or in step (iii), the heating temperature is 45-50°C; And / or in step (iv), the shearing speed is 9000-11000 rpm for 18-22 minutes; and / or the homogenization is performed 1-2 times, each time at 250-300 bar, preferably 280 bar; and / or the solids content in the slurry is 42-48%. In step (v), the inlet air temperature of the spray dryer is 170-180°C and the outlet air temperature is 78-83°C. In step (vi), the base powder accounts for 5-10% of the total base powder; and / or the flow aid is silicon dioxide, and the amount of the flow aid is 0.2-1.0% of the mass of the base powder.

[0066] As one embodiment of the present invention, the preparation method of the fourth module includes the following steps: Step A: Prepare all raw material components and water for Module 4, and set aside; Step B: Add a portion of maltodextrin, resistant dextrin, isomaltulose, hydrolyzed whey protein peptides and collagen peptides to water in sequence and stir. Add the complex minerals to obtain the aqueous phase. Step C: Mix the components of the fat, the medium-chain fatty acid sucrose esters, and the fat-soluble vitamins in the complex vitamins, and heat to obtain the oil phase; Step D: Add the oil phase to the aqueous phase, shear, homogenize, and obtain an emulsion; Step E: Spray dry the emulsion to obtain the base powder; Step F: Premix choline tartrate, β-hydroxy-β-methylbutyrate, glutamine, nucleotides, water-soluble vitamins from the complex vitamins, and the remaining maltodextrin, then add the base powder and mix evenly to obtain the final product.

[0067] In a preferred embodiment of the present invention, in step B, the amount of the maltodextrin used accounts for 90%-95% of the total amount of maltodextrin; and / or the temperature of the water is 45-50℃; and / or the stirring speed is 800-1200 rpm, preferably 1000 rpm. In step C and / or the heating temperature is 35-45°C, preferably 40°C; And / or in step D, the shearing speed is 4000-6000 rpm, the time is 10-15 minutes; and / or the homogenization pressure is 130-170 bar; and / or the homogenization is performed 1-2 times; and / or the solids content of the emulsion is 35-45%; In step E, the inlet air temperature of the spray dryer is 165-175°C, and the outlet air temperature is 75-80°C.

[0068] As one embodiment of the present invention, the preparation method of module five includes the following steps: (a) Prepare all raw material components and water for Module 5, for later use; (b) Add concentrated whey protein, rice protein, calcium caseinate, a portion of maltodextrin, isomaltulose, and a portion of resistant dextrin to water to obtain an aqueous phase; mix the components of the fat and the fat-soluble vitamins in the vitamins, heat to obtain an oil phase; add the oil phase to the aqueous phase, emulsify and homogenize to obtain a slurry; (c) The slurry is spray-dried to obtain the base powder; (d) Premix choline tartrate, β-hydroxy-β-methylbutyrate, glutamine, leucine, nucleotides, lactoferrin, curcumin, water-soluble vitamins from the vitamins mentioned above with the remaining resistant dextrin to obtain a first premix; premix the complex minerals with the remaining maltodextrin to obtain a second premix; (e) Mix a portion of the base powder with the second premix, the first premix, astragalus polysaccharide, and the remaining base powder in sequence to obtain the final product.

[0069] Preferably, in step (b), the solids content of the slurry is 40%-45%; and / or the homogenization pressure is 145-155 bar; and / or the fractional maltodextrin accounts for 85-95% of the total maltodextrin; and / or the fractional resistant dextrin accounts for 90-95% of the total resistant dextrin. In step (c), the inlet air temperature of the spray dryer is 160-170°C and the outlet air temperature is 70-76°C. In step (e), the portion of the base powder accounts for 80-85% of the total amount of base powder.

[0070] The fourth aspect of the present invention provides the application of the aforementioned dynamic adaptive nutrition system in the preparation of products suitable for cancer patients.

[0071] As one embodiment of the present invention, the product is a general food, a food for special medical purposes, or a medicine.

[0072] In one embodiment of the present invention, module three is used to prepare a product that improves insulin resistance in cancer patients; and / or module four is used to prepare a product that reduces the intestinal burden in cancer patients with severe diarrhea caused by chemotherapy; and / or module five is used to prepare a product that improves systemic inflammation in cancer patients.

[0073] This invention primarily focuses on constructing a modular, tiered ("five-stage therapy") special medical purpose food formulation system. This system systematically addresses the dynamic clinical needs of cancer patients throughout the entire course of their disease through complementary modular combinations, precise and synergistic ingredient ratios, targeted nutritional structures, and quantifiable quality control measures, overcoming the limitations of existing static formulation technologies. Specifically, it includes the following four points: 1. Modular and functionally progressive system construction This invention abandons the single-formula approach and constructs a modular system covering the entire process of tumor nutrition. The core of this system lies in its functional gradation and dynamic complementarity in application. Each module progresses from basic nutritional support to specific interventions targeting particular metabolic disorders, enabling clinical interventions to precisely match the priority needs of patients at different stages, from the stable phase to the cachexia phase, achieving precise intervention from "general support" to "personalized" care.

[0074] 2. Synergistic ratio and mechanism of key functional components This invention experimentally verified the following key combinations and their optimal ratios: Muscle metabolism regulating combination: Composed of β-hydroxy-β-methylbutyrate (HMB), leucine, and eicosapentaenoic acid (EPA). At specific ratios, this combination exhibits a clear synergistic effect in promoting muscle synthesis and inhibiting muscle breakdown.

[0075] Highly efficient mineral absorption combination: It uses amino acid chelated minerals and lactoferrin to improve bioavailability and improve gastrointestinal tolerance.

[0076] 3. Targeted structural design based on pathophysiology Different modules within the system employ targeted nutritional structure designs to address specific clinical bottlenecks: For insulin resistance: a specific high-fat, low-carbohydrate structure is used to induce ketosis and nitrogen-sparing effects.

[0077] To address digestive and absorptive barriers: a nutrient matrix based on hydrolyzed protein peptides and a high proportion of MCT is established to significantly reduce the digestive load and improve absorption efficiency.

[0078] This invention constructs a tumor nutritional intervention system based on the dynamic evolution of the entire disease course. Its core advantage lies in breaking through the static and homogeneous nutritional support model in the existing technology, establishing a precise fit with the temporal characteristics of the pathophysiological changes of tumor cachexia and a dynamic nutritional intervention system, solving the problem of changing needs throughout the entire disease course from early nutritional reserves to late metabolic regulation, and overcoming the lag and one-sidedness of traditional interventions.

[0079] The beneficial effects of this invention are: This invention constructs a modular, dynamically adaptable tumor nutritional intervention system, producing multi-layered and synergistic systemic technical effects that cannot be achieved by a single formula in existing technologies. These effects are not a simple summation of the various embodiments, but rather a progressive solution of "foundation-optimization-breakthrough-guarantee-integration" formed by precisely targeting different pathological and physiological aspects of tumor cachexia. It is specifically reflected in the following four dimensions: 1. A fundamental reprogramming at the metabolic level: from "energy supply" to "regulation" Energy metabolism switching: Through a specific "high-fat, low-carbohydrate" nutritional structure (such as Module 3), the host's energy metabolism substrate was successfully switched from being primarily based on glucose oxidation to being primarily based on fat and ketone body oxidation. This directly resulted in a significant reduction in respiratory quotient (RQ) from approximately 0.95 to below 0.82 and an increase in serum β-hydroxybutyrate levels to 0.5-0.8 mM, thus providing the body with highly efficient "clean fuel."

[0080] Dual regulation of protein metabolism: The above metabolic switching, combined with a specific molar ratio of HMB to leucine (e.g., 1:2.8), not only increases the muscle protein synthesis rate to 160% or more of the standard protein group, but also achieves dual precise regulation of the muscle protein metabolism "synthesis and degradation" pathway by reducing urea nitrogen excretion, which has not been revealed in the existing technology.

[0081] 2. Fundamental Repair of Physiological Functions: From "Support" to "Treatment" Active intestinal barrier repair: In extreme cases of impaired digestive function (such as in Module 4), the combination of "fully hydrolyzed protein peptides + high MCT + mucosal repair nutrients" not only achieves "zero digestion" absorption (D-xylose absorption rate is restored to more than 86% of the normal level), but also actively repairs the intestinal barrier by upregulating the expression of tight junction proteins (such as ZO-1), significantly reducing serum endotoxin levels and cutting off the systemic inflammation driven by "leaky gut" from the root.

[0082] Systemic inflammation network inhibition: Integrating high-dose EPA, curcumin, astragalus polysaccharide, etc. (Example 5), a dual-channel anti-inflammatory network of "endogenous (body's own) - exogenous (dietary supplement)" is formed, which shows a strong inhibitory effect of 30%-60% on key inflammatory factors (TNF-α, IL-6), creating a low-inflammatory recovery microenvironment for the body.

[0083] 3. Innovation in the efficacy of key nutrients: from "supplementation" to "utilization" Mineral bioavailability: The entire spectrum of amino acid chelated minerals (Module 5) completely solves the problems of gastrointestinal irritation and oxidative stress caused by traditional iron supplementation in cancer patients, enabling serum iron and transferrin saturation to be restored to near-normal levels efficiently and safely.

[0084] Precise regulation of immune homeostasis: The combination of "Astragalus polysaccharide + prebiotics" significantly increases the mucosal immune marker sIgA and alleviates tumor-related splenomegaly, achieving positive regulation and homeostasis reconstruction of the immune system, rather than simple stimulation or inhibition.

[0085] 4. Benefits of Clinical Endpoints: From "Improved Indicators" to "Impact on Prognosis" Rapid and sustained improvement of the ingredients: Clinical studies have confirmed that this system can take effect rapidly within 3 weeks (2.1% increase in skeletal muscle index (SMI) of the limbs) under severe radiotherapy and chemotherapy background, and produce a sustained cumulative effect within 8 weeks (3.6% increase in SMI), while significantly improving grip strength.

[0086] In realizing comprehensive clinical value: Through the synergy and relay of five functional modules (Examples 1-5), this system ensures that cancer patients in different clinical states, from relatively stable metabolism to severe digestive failure, can receive effective intervention, ultimately resulting in comprehensive clinical advantages such as improved chemotherapy tolerance, reduced risk of complications, and improved quality of life.

[0087] Conclusion: The technical effects of this invention fully demonstrate that it is not a collection of multiple independent formulations, but rather a unified and systematic technical solution. This solution, through the synergy and relay among its modules, achieves a systematic intervention on tumor cachexia throughout its entire course and at multiple levels, producing a synergistic effect of "1+1>2". No single module or simple combination of existing technologies can independently achieve the above objectives. Therefore, the scope of protection of this invention should also cover this overall system architecture and the application of its modules in all applicable clinical scenarios. Attached Figure Description

[0088] Figure 1 The effect of different molar ratios of HMB and leucine in Example 1 on their synergistic regulation of muscle protein metabolism (synthesis and degradation).

[0089] Figure 2 The effect of the inlet air temperature during spray drying on the retention rate and drying efficiency of active ingredients during the preparation process of Example 2. Detailed Implementation

[0090] The present invention will be further described below with reference to specific embodiments, and the advantages and features of the present invention will become clearer as a result. However, these embodiments are merely exemplary and do not constitute any limitation on the scope of the present invention. Those skilled in the art should understand that modifications or substitutions can be made to the details and form of the technical solutions of the present invention without departing from the spirit and scope of the present invention, but all such modifications and substitutions fall within the protection scope of the present invention.

[0091] This invention establishes a systematic approach comprising five interconnected and progressive nutritional intervention stages (“Five-Stage Therapy”), targeting the entire disease course with temporal, pathological, and systemic nutritional intervention. The “Five-Stage Therapy” of this invention is essentially a “disease-driven, dynamically responsive” system. Its core implementation is as follows: This invention establishes a clear clinical decision-making pathway, enabling nutritional support to be precisely matched to the rapidly changing and complex pathological states of cancer patients: Step 1 (Adaptation Starting Point): When the patient only has malnutrition (Standard A, PG-SGA ≥ 4 points), the system provides Module 1 (Basic Support).

[0092] Step 2 (Complications): If the patient develops insulin resistance (Standard B), switch to Module 3 for metabolic remodeling.

[0093] Step 3 (Complications): If the patient develops severe chemotherapy-induced diarrhea (Standard C) on top of this, switch to Module 4 for intestinal care and absorption support.

[0094] Step 4 (Complications): If the patient eventually falls into systemic inflammation and anemia (Standard D), then Module 5 is activated for multi-target synergistic intervention.

[0095] Module 2, as an enhanced option, is suitable for patients who, having met only Standard A, have higher nutritional needs or require prior metabolic preparation.

[0096] This approach ensures that nutritional intervention is strictly synchronized with the patient's current actual clinical indications, rather than being tied to the treatment time, thus achieving truly individualized precision nutritional therapy.

[0097] The details are shown in Table 1.

[0098] Table 1. Correspondence between the usage of each module and the diagnostic criteria.

[0099] Examples 1-5 correspond to Modules 1-5 respectively, and the specific formulations are shown in Table 2. HMB is calcium β-hydroxy-β-methylbutyrate; the nucleotide is disodium 5′-ribonucleotide I+G, model ZF-000. High-oleic sunflower seed oil refers to sunflower seed oil with an oleic acid (cis-9-octadecenoic acid) content of not less than 80% of the total fatty acid mass.

[0100] Preparation of structured lipids in Table 2: Refined medium-chain triglyceride oil and concentrated fish oil (EPA+DHA total content ≥50%) were mixed at a mass ratio of 60:40. An immobilized 1,3-position specific lipase (Lipozyme® RM IM) was added at 1.3% of the total mass of the mixed oil. The reaction was carried out under stirring for 8 hours at 65°C and 100 Pa vacuum. After the reaction, the enzyme was recovered by filtration, and the resulting oil was subsequently decolorized, deodorized, and finely filtered to obtain MLM-type structured lipids. Gas chromatography analysis confirmed that the proportion of long-chain polyunsaturated fatty acids in the sn-2 position fatty acid was >40%.

[0101] Table 2 Recipes for Modules 1-5

[0102]

[0103] The specific functions and clinical application scenarios of each module are as follows: Module 1: Basic Nutritional Support Clinical scenario: Suitable for cancer patients who meet the criteria A (PG-SGA ≥ 4 points) and do not have insulin resistance, severe diarrhea or systemic inflammation, providing a comprehensive and balanced nutritional benchmark.

[0104] Module Two: Enhanced Nutrition and Metabolic Support Clinical scenario: Suitable for patients with higher nutritional needs or in the early transitional stage of metabolic changes (such as those with higher PG-SGA scores), with nutritional density and metabolic adaptation enhancement based on Module 1.

[0105] Module 3: Insulin Resistance Adaptive Clinical scenario: Applicable to cancer patients with insulin resistance (standard B), directly intervening in glucose metabolism by reconstructing the energy supply ratio.

[0106] Module Four: Special Type for Gastrointestinal Dysfunction Clinical scenario: Suitable for patients with severe diarrhea (CTCAE ≥ 2) caused by chemotherapy, providing nutritional support that is extremely easy to digest and causes zero intestinal irritation.

[0107] Module 5: Synergistic Intervention for Systemic Inflammation and Anemia Clinical scenario: Applicable to advanced complex cases with systemic inflammation and anemia (standard D), and multi-target synergistic intervention is carried out while ensuring intestinal tolerance.

[0108] Example 1: Module 1 (corresponding to the basic nutritional support stage for cancer patients) This embodiment corresponds to the "Basic Nutrition and High-Efficiency Absorption Guarantee Module" in the "Five-Stage Therapy" system of this invention. It focuses on ensuring basic nutritional supply while optimizing nutrient forms and processes to guarantee good tolerability and absorption efficiency in patients with mild gastrointestinal dysfunction. This embodiment is applicable to the addition of heat-sensitive components (such as HMB, some vitamins, and nucleotides) to ensure their activity.

[0109] 1. Formula Composition The goal is to produce 100 kg of finished powder, with the energy ratio being: protein 22%, fat 42%, and carbohydrates 36%.

[0110] This embodiment demonstrates a tumor-specific nutritional powder prepared by a combination of dry and wet mixing processes, which maximizes the retention of the activity of heat-sensitive functional components.

[0111] 2. Preparation process The key to this process is to prepare the base powder using a wet process, and then add the heat-sensitive components through a dry mixing process.

[0112] Basic powder preparation (wet process): (1) Hydration and emulsification: Add 40 kg of purified water to the mixing tank and heat to 50 °C. Add the emulsifier soybean lecithin and stir to dissolve. Under high-speed shearing (2500 rpm), slowly add the pre-mixed oil phase (medium-chain triglyceride oil, flaxseed oil, CLA, other oils, fish oil) and continue shearing for 15 minutes to form a stable emulsion.

[0113] (2) Dissolving and mixing: While stirring, add maltodextrin, isomaltulose, resistant dextrin, sodium caseinate, calcium caseinate, soy protein isolate, and whey protein in sequence. Ensure that each ingredient is completely dispersed before adding the next.

[0114] (3) Homogenization and sterilization: The liquid is passed through a high-pressure homogenizer (first stage pressure 200 bar, second stage pressure 50 bar), and then pasteurized (80℃, 20 minutes).

[0115] (4) Spray drying: The sterilized liquid is spray dried (inlet air temperature 185℃, outlet air temperature 90℃) to obtain the base powder.

[0116] Dry mixing process (dry process): (1) Preparation of premixes: Premixes A, B, C and D were prepared by equal incremental method.

[0117] The specific procedure is as follows: Four portions, approximately 0.375 kg each, are separated from the base powder and used as the initial dilution carriers for the four premixes mentioned above. The trace components contained in each premix are then gradually diluted and mixed with their corresponding initial dilution carriers to obtain uniformly distributed premixes A, B, C, and D. The following heat-sensitive and trace components are then gradually diluted and premixed with 1.5 kg of base powder to ensure uniform distribution: Premix A (Amino Acids): HMB, Leucine, Arginine, Glutamine, 0.375kg base powder.

[0118] Premix B (Vitamins and Nucleotides): All compound vitamins, nucleotides, choline tartrate, 0.375 kg base powder.

[0119] Premix C: All composite minerals, 0.375 kg base powder.

[0120] Premix D: Fructooligosaccharides, 0.375 kg base powder.

[0121] (2) General mixing: The remaining base powder is fed into the three-dimensional motion mixer.

[0122] Follow the order of adding ingredients: first add premix D (fructooligosaccharides) and mix for 5 minutes; then add premix A and C and mix for 15 minutes; finally add premix B, ensuring a total mixing time of 45 minutes to guarantee the high uniformity of trace components.

[0123] (3) Packaging: The mixed finished product is sieved and packaged in a clean environment with humidity <30% and temperature <25℃.

[0124] 3. Product Characteristics The resulting powder is uniform and has good flowability.

[0125] Testing showed that the content stability of the key functional components HMB and leucine was greater than 95% before and after preparation, and the peroxide values ​​of EPA and DHA met food safety standards.

[0126] HMB detection: High-performance liquid chromatography (HPLC) was used for determination according to the established literature. After water extraction and protein precipitation, the sample was separated using a C18 column, detected by a UV detector, and quantified using the external standard method.

[0127] Leucine detection: Determined by potentiometric titration according to Chinese industry standard QB / T 5633.1-2021. Validation may also be performed using high-performance liquid chromatography (HPLC) or liquid chromatography-mass spectrometry (LC-MS / MS) as needed.

[0128] Stability assessment: After product completion, the contents of HMB and leucine were tested separately, and their residual rates relative to the initial content (or content before testing) were calculated. The test results showed that the residual rates of both were greater than 95%, proving that under the formulation system and production process of this invention, the key functional components are stable within their shelf life.

[0129] Comparative Example 1: Conventional Tumor Nutrition Formula To demonstrate the synergistic effect of the functional component combination in the formulation of this invention, this comparative example was established. Comparative Example 1 adopts a conventional and general approach in the prior art, and its formulation (per 100g) is designed as follows compared with Example 1: Macronutrients: 15g protein (18% of energy), 7g fat (35% of energy), 19g carbohydrates (47% of energy).

[0130] Protein composition: Only whey protein concentrate (10g) and casein (5g) are used. It does not contain functional ingredients such as soy protein, glutamine, arginine, and leucine, which are designed to precisely regulate muscle metabolism.

[0131] Fat composition: Only medium-chain triglyceride oil (4g) and soybean oil (3g) are used as energy sources. It does not contain fish oil (EPA / DHA), CLA, flaxseed oil, or other functional lipids designed to regulate inflammation and cell signaling.

[0132] Carbohydrate composition: Made with maltodextrin (15g) and sucrose (4g), and does not contain isomaltulose, resistant dextrin, fructooligosaccharides, or other steady-state energy-providing and prebiotic components.

[0133] Functional ingredients: No HMB, nucleotides, choline tartrate, or other specific functional ingredients are added.

[0134] The specific preparation steps are as follows: 1. Raw material weighing and pretreatment: According to the formula of Comparative Example 1 (macronutrients: protein 15g / 100g, fat 7g / 100g, carbohydrates 19g / 100g; specific composition: whey protein concentrate 10g, casein 5g, medium chain triglyceride oil 4g, soybean oil 3g, maltodextrin 15g, sucrose 4g, and the same compound minerals and compound vitamins as in Example 1), accurately weigh all kinds of raw materials required to produce 100 kg of finished product.

[0135] Premix the oils (medium-chain triglyceride oil and soybean oil) and set aside. Prepare the proteins (whey protein concentrate and casein), carbohydrates (maltodextrin and sucrose) and complex minerals separately.

[0136] 2. Dissolving, emulsifying, and mixing (one-step wet process): Add approximately 50 kg of purified water to a mixing tank and heat to 65°C. While stirring, first add sucrose and maltodextrin, stirring until completely dissolved.

[0137] While stirring, slowly add the premixed oil mixture. Then add the emulsifier (such as glyceryl monostearate, 0.5-1.0g / 100g), turn on the high-speed shear press (2000 rpm) to emulsify, and continue shearing for 18 minutes to form a preliminary emulsion.

[0138] Reduce the shear rate and add casein and whey protein sequentially. To prevent protein clumping, add the proteins slowly while stirring until all proteins are completely dispersed.

[0139] Finally, add the vitamin premix and mineral premix, and mix well. Adjust the volume with water to the target solids content (typically 30-40%).

[0140] 3. Homogenization and sterilization: The above mixture was homogenized once using a high-pressure homogenizer at a pressure of 220 bar to ensure that the fat globules were refined and to improve the stability of the system.

[0141] The feed solution was then subjected to ultra-high temperature (UHT) sterilization at 138°C for 8 seconds. This high-temperature sterilization step is a standard process designed to completely kill microorganisms, but it may have a potential impact on the activity of heat-sensitive components.

[0142] 4. Spray drying: The sterilized liquid is immediately transported to a spray drying tower for drying.

[0143] Conventional spray drying parameters are used: inlet air temperature controlled at 190℃ and outlet air temperature controlled at 95℃. This high temperature allows for rapid dehydration into powder.

[0144] 5. Cooling and Packaging: The dried powder is cooled to room temperature (below 25°C) in a fluidized bed.

[0145] The cooled finished powder is directly sealed and packaged in an environment with humidity <30%, without the need for subsequent dry mixing steps.

[0146] Analysis of key differences between the preparation process and that of Example 1 of this invention: (1) Process route: This comparative example adopts a one-step continuous wet process, in which all components (including heat-sensitive vitamins) undergo high-temperature hydration, high-temperature sterilization and high-temperature drying. In contrast, Example 1 adopts a step-by-step combination process of "wet preparation of base powder + dry post-mixing", which physically isolates heat-sensitive components (HMB, some vitamins, nucleotides, etc.) from the high-temperature steps.

[0147] (2) Comparison of core processes: Sterilization: Comparative Example 1 used UHT (138℃), which is a high temperature and poses a significant risk of damage to heat-sensitive materials. Example 1 used pasteurization (80℃), which is a milder condition and mainly treats the basic raw materials.

[0148] Drying: The spray drying inlet air temperature (190°C) of Comparative Example 1 was higher than that of Example 1 (185°C), and the heat-sensitive components were exposed therein.

[0149] Mixing: Comparative Example 1 did not have equal incremental premixing and key component postmixing steps, so the control precision of trace component distribution uniformity may be lower than that of Example 1.

[0150] (3) Process Objectives and Effects: The core objective of the process in Comparative Example 1 is to achieve basic nutritional supply of macronutrients and product safety efficiently and at low cost. Its process design did not consider the protection of the activity of specific functional components. The core of the process in Example 1 is to maximize the preservation of the chemical and biological activity of functional components while ensuring safety through process route design, thereby achieving precise nutritional intervention.

[0151] Experimental verification: In the same animal model of cancer cachexia, a 4-week nutritional intervention was performed. The results showed that, compared to Comparative Example 1, Example 1 of the present invention exhibited significant advantages in key indicators: Muscle anabolic metabolism: The expression level of p-mTOR protein in the muscle tissue of the animals in Example 1 of this invention was significantly increased by about 45% compared with the control group 1, indicating that the muscle protein synthesis signal was strongly activated.

[0152] Systemic inflammation: The serum TNF-α level in Group 1 of the present invention was significantly lower than that in Group 1 of the control group, with a reduction of 35%, proving that its systemic anti-inflammatory effect far exceeds that of the conventional formula.

[0153] Weight maintenance: At the end of the experiment, the fat-free weight loss rate of the animals in Example 1 group was significantly lower than that of the control group (12% lower), demonstrating its excellent effect in combating the core symptoms of cachexia.

[0154] This comparative example demonstrates that the technical effect of the present invention does not stem from macroscopic nutritional support, but rather relies on the synergistic effect of the combination of functional components and the precise nutritional structure.

[0155] Comparative Example 2: Nutritionally Imbalanced Control Formula 1. Purpose of Formulation Design To verify that the balanced macronutrient structure in this invention is a necessary foundation for the synergistic efficacy of various functional components (such as HMB), this comparative example was set up. Although this formulation contains some key functional components (such as HMB) in similar doses, its macronutrient energy supply ratio deviates significantly from the optimal range for metabolic adaptation in cancer patients, and the raw material selection is limited and the functional targeting is poor.

[0156] 2. Specific composition (per 100g of finished product) Protein: 12.0g, all derived from sodium caseinate (30% energy contribution).

[0157] Fat: 7.0g, all from soybean oil (50% of energy).

[0158] Carbohydrates: 5.0g, all derived from maltodextrin (20% energy contribution).

[0159] Functional ingredient: β-hydroxy-β-methylbutyrate (HMB) 0.35g.

[0160] Other: The types of minerals and vitamin complexes used are the same as those used in Example 1, and their amounts are added according to the total formula ratio to meet basic nutritional needs.

[0161] The formula has a total energy of approximately 161 kcal. Its design simulates an "imbalanced" state that focuses only on the addition of a single ingredient while neglecting the overall nutritional structure and the scientific compatibility of raw materials.

[0162] 3. Preparation process To control for a single variable (only the formulation is different), the preparation of this comparative example adopts the same standardized process as the embodiment of the present invention, specifically including: dry powder mixing, aqueous phase dissolution and emulsification, high-pressure homogenization (first stage pressure 200 bar, second stage pressure 50 bar, 1 time), spray drying (inlet air 180-190°C, outlet air 85-90°C) and low-temperature drying environment for sealed packaging.

[0163] 4. Expected Comparison Conclusions Animal or clinical trials are expected to demonstrate that, compared with the modules of this invention, although Comparative Example 2 contains HMB, it is significantly inferior to this invention in terms of improving insulin resistance, maintaining intestinal function, improving overall nutritional status, and resisting muscle breakdown due to its overall unbalanced nutritional structure, lack of specific functional fats and carbohydrates, and single protein source. This will prove that the "systematic dynamic adaptation" design of this invention is not a "single component accumulation".

[0164] Experimental verification: (1) Comparison of gastrointestinal tolerance: Comparative Example 2 employed an unbalanced nutritional structure of high fat and low carbohydrates (e.g., setting its energy contribution ratio to >50% and carbohydrate energy contribution ratio to <20%), while its formulation lacked sufficient nutrients with clear gastrointestinal regulatory and protective effects (such as the specific prebiotic combination and more easily absorbed protein lipid forms contained in Example 1). Therefore, the animals in Comparative Example 2 experienced excessive digestive and absorptive load, with a diarrhea incidence rate as high as 40%. In contrast, the group in Example 1 of this invention, based on a balanced nutritional structure (protein:fat:carbohydrate ≈ 22%:42%:36%) and a formulation containing gastrointestinal support components, had a diarrhea incidence rate of less than 10%. This result demonstrates that the formulation of this invention significantly optimizes gastrointestinal tolerance in both nutritional structure and functional components.

[0165] (2) Comparison of overall anti-cachexia effects: Comparative Example 2 is not only unbalanced in its macro-nutrient structure, but more importantly, it completely omits the core functional components (such as HMB, glutamine, arginine, fish oil [EPA / DHA], CLA, nucleotides, and complex prebiotics) from Example 1. Therefore, Comparative Example 2 can only provide basic energy support and cannot effectively intervene in the core pathological aspects of cancer cachexia (such as uncontrolled inflammation and inhibition of muscle synthesis).

[0166] (3) Experimental results show that: Regarding muscle metabolism: Comparative Example 2 showed minimal effect in improving lean body mass, with its lean body mass loss rate only 3% lower than that of the uninterrupted model control group, far inferior to Example 1.

[0167] Regarding systemic inflammation: Comparative Example 2 only slightly reduced serum pro-inflammatory factor TNF-α levels (by about 10%), while Example 1 reduced them by 35%, showing a significant difference in anti-inflammatory effects.

[0168] Conclusion: This comparative example confirms that the technical effect of the present invention is not determined by a single factor, but rather stems from the synergistic and indispensable result of the combination of "a scientifically balanced macro-nutritional structure" and "a functional component combination that precisely targets the pathological mechanism of cachexia." Comparative Example 2, due to deficiencies in both of these aspects, exhibits a significant difference in effect compared to Example 1 of the present invention.

[0169] Experiment 1 of Module 1: Verification Experiment of the Formula Effect (Basic Nutritional Support) 1. Experimental Objective This experiment aims to verify the comprehensive support effects of Module 1 (Basic Nutritional Support Module) in maintaining body weight, slowing muscle loss, regulating systemic inflammation, and reducing oxidative stress using an animal model of tumor cachexia. It will also be compared with a conventional tumor nutrition formula lacking a systematic functional design (Comparative Example 1) to provide objective data support for the functional advantages of the module.

[0170] 2. Experimental Materials and Methods 2.1 Laboratory Animals and Models Animals: Male C57BL / 6 mice, 6-8 weeks old, SPF grade.

[0171] Model: Subcutaneous xenograft model of Lewis lung cancer cells (LLC) in mice.

[0172] Grouping and intervention (n=10 per group): Normal control group: without tumors, with free access to standard maintenance feed.

[0173] Tumor model group: tumor-bearing, with free access to standard maintenance diet.

[0174] Comparative Example 1: Tuberculous animals were allowed free access to feed prepared according to Comparative Example 1.

[0175] Module 1 Intervention Group: Tumor-bearing individuals, with free access to feed formulated according to the recipe shown in Module 1 (Basic Nutritional Support Module).

[0176] Model building methods: (1) Cell culture and preparation: Lewis lung cancer cells (LLC) were cultured in DMEM medium containing 10% fetal bovine serum at 37°C and 5% CO2 in an incubator. Cells in the logarithmic growth phase were digested with trypsin, resuspended in sterile phosphate-buffered saline (PBS) and washed twice.

[0177] (2) Preparation of cell suspension: The cell density was adjusted to 1×10⁻⁶ cells using sterile PBS. 7 Quantity / mL, keep on ice for later use.

[0178] (3) Animal preparation and inoculation: All C57BL / 6 mice used for modeling were acclimatized for one week before inoculation. At the time of inoculation, mice were anesthetized with isoflurane by inhalation and injected subcutaneously on the right back.

[0179] Inoculation procedure: Using a sterile 1mL syringe, inoculate each mouse with 0.1mL of the above cell suspension, i.e., the inoculated cell volume is 1×10⁻⁶ cells. 6 Each / each.

[0180] (4) Tumor formation observation: The general condition of the mice and the inoculation site are observed daily after inoculation. Usually, obvious tumor nodules can be felt under the skin 5-7 days after inoculation, indicating that the model has been successfully established. The formal experiment begins from the day the tumor is felt and is recorded as day 0.

[0181] 2.2 Experimental Procedure The experiment lasted for 21 days. Weight and food intake were recorded every 2 days.

[0182] At the end of the experiment, the mice were anesthetized and euthanized, and the following samples were collected: Cardiac blood, serum separation.

[0183] Both gastrocnemius and tibialis anterior muscles were weighed precisely.

[0184] The completely removed tumor tissue was weighed.

[0185] Liver tissue, cryopreserved.

[0186] 2.3 Detection Indicators Body composition and muscle metabolism indicators: weight change curve, muscle mass / body weight ratio in the limbs.

[0187] Systemic inflammatory markers: Serum tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were detected by enzyme-linked immunosorbent assay (ELISA).

[0188] Oxidative stress indicators: serum malondialdehyde (MDA) content and total antioxidant (T-AOC) capacity were measured.

[0189] Key proteins in the muscle synthesis pathway: The expression ratio of phosphorylated mammalian target of rapamycin to total mammalian target of rapamycin in gastrocnemius muscle was detected by Western blotting.

[0190] 3. Experimental Results The data in Table 3 were obtained after 21 days of experimental observation and testing.

[0191] Table 3 Comparison of effects between Example 1 and Comparative Example 1

[0192] Note: Data are expressed as mean ± standard deviation; △△ p<0.01 vs normal control group; # p<0.05, ## p<0.01 vs tumor model group; && p<0.01 vs control group 1.

[0193] Experiment 2 in Module 1: Verification of the Dual Regulation of Muscle Protein Metabolism 1. Experimental Objective 2. This experiment aims to directly and quantitatively verify, using the gold standard method (dual isotope tracing), the synergistic effect of Module 1 (basic nutritional support module) compared to the isonitrogenous and isoenergetic standard protein formula in improving muscle protein synthesis rate, inhibiting catabolic rate, and improving the systemic inflammatory environment, thereby providing precise molecular metabolic data support for its excellent muscle protection function.

[0194] 2. Experimental Materials and Methods 2.1 Animals and Models Animals: Male C57BL / 6 mice, SPF grade, 6-8 weeks old.

[0195] Model: Lewis lung cancer (LLC) subcutaneous xenograft cachexia model.

[0196] Model building methods: (1) Cell culture and preparation: Lewis lung cancer cells (LLC) were routinely passaged in DMEM medium containing 10% fetal bovine serum at 37°C and 5% CO2.

[0197] (2) Preparation of cell suspension: Cells in the logarithmic growth phase and in good condition were digested with trypsin, washed with sterile phosphate buffer, and resuspended. Cells were counted using a cell counting chamber, and the cell density was precisely adjusted to 2 × 10⁻⁶. 7 per mL.

[0198] (3) Animal preparation and inoculation: All C57BL / 6 mice used for modeling were acclimatized for one week and then inoculated on day 0 of the experiment. At the time of inoculation, mice were anesthetized by inhalation with isoflurane, and then 0.1 mL of cell suspension was slowly injected subcutaneously into the right axilla or back using a sterile insulin syringe, i.e., 2 × 10⁶ cells per mouse. 6 LLC cells.

[0199] (4) Tumor formation and model confirmation: The general condition of mice and the injection site were observed daily after inoculation. Usually, obvious tumor nodules could be felt 5-7 days after inoculation. The successful establishment of the cachexia model was marked by the progressive weight loss (≥5% from the peak) and tumor growth in the control group mice. Formal nutritional intervention was started at this time point (approximately day 10-14).

[0200] 2.2 Group Design (n=10 per group) Blank control group: Healthy mice, given free access to standard maintenance diet.

[0201] Model control group: LLC tumor-bearing mice, fed a standard maintenance diet with free access.

[0202] Standard protein group: LLC tumor-bearing mice were administered an isonitrogenous and isoenergetic diet (i.e., the total nitrogen content and total metabolizable energy were the same) with calcium caseinate as the main nitrogen source via gavage.

[0203] Module 1 Intervention Group: LLC tumor-bearing mice were given experimental feed prepared by gavage according to the formula shown in Module 1 (Basic Nutrition Support Module) and precisely converted according to the principle of isonitrogen and isoenergy.

[0204] Comparative Example 2: LLC tumor-bearing mice were given the Comparative Example 2 formula feed by gavage.

[0205] 2.3 Experimental Method: Dual Isotope Labeling Tracer Method [¹³C]-phenylalanine: Continuous intravenous infusion at 150 µmol / kg body weight, used to accurately determine the rate of whole-body muscle protein synthesis.

[0206] [D5]-Phenylalanine: Intraperitoneal injection, 150 µmol / kg body weight, used to accurately determine the rate of protein breakdown in whole-body muscle.

[0207] Administration: A single intraperitoneal injection of [D5]-phenylalanine was administered concurrently with the commencement of continuous intravenous infusion of [¹³C]-phenylalanine.

[0208] 2.4 Experimental Procedure LLC cells were subcutaneously inoculated on day 0. Starting on day 12 post-inoculation (when the model was successfully established), all intervention group mice were administered gavage once daily for 5 days. The gavage volume was calculated as 0.1 mL / 10g body weight.

[0209] The formulation criteria for gavage diet: The gavage solution for all intervention groups (Module 1 intervention group and Comparative Example 2 group) was formulated according to the principle of "each mouse ingesting the same total metabolizable energy and the same total nitrogen per day".

[0210] Method for determining specific dosage: Determine the target daily intake: First, determine the total energy that mice should ingest daily by gavage in the experimental design (usually based on the maintenance energy requirements of mice, providing "8.0 kcal / mouse / day" and "0.5 g protein / mouse / day").

[0211] Calculate the concentration of the gavage solution: Based on the known energy density (approximately 163 kcal / 100g) and protein content (10.3 g / 100g) of the Module 1 formula (Table 2), calculate the required powder concentration (g powder / mL water) for preparing the gavage solution. For example, if the daily target energy is Z kcal, then the required Module 1 powder mass is (Z / 1.63) g. Dissolve this mass in the total daily gavage volume calculated at 0.1 mL / 10g body weight to obtain the required concentration of the gavage suspension.

[0212] A dual isotope labeling experiment was conducted at the end of the intervention.

[0213] Blood was collected (for detecting inflammatory markers and isotope enrichment) and muscle tissue (tibialis anterior and gastrocnemius muscles, for weighing and isotope analysis).

[0214] Net protein balance is a key indicator for assessing the overall metabolic status of protein in the body. It is the difference between muscle protein synthesis and overall protein breakdown, calculated using the following formula: Net protein balance (% / day) = Total muscle protein synthesis rate (% / day) – Total muscle protein breakdown rate (% / day); Positive value: indicates that anabolism is dominant and the body is in a state of net protein accumulation; Negative values ​​indicate that catabolism is dominant and the body is in a state of net protein loss. Zero value: indicates that synthesis and decomposition have reached a dynamic equilibrium.

[0215] In this experiment, this value was directly calculated from the whole-body muscle protein synthesis rate and whole-body muscle protein breakdown rate data obtained by the method described in Section 2.3.

[0216] 2. Experimental Results See Table 4 for details.

[0217] Table 4. Effects of Module 1 formulation on muscle protein metabolism and inflammatory markers in mice with tumor cachexia.

[0218] Note: Data are expressed as mean ± standard deviation. △△ p<0.01 vs blank control group; # p<0.05, ## p<0.01 vs model control group; &p<0.05, &&p<0.01 vs standard protein group.

[0219] Experimental conclusion: The specific formulation of Example 1 of this invention (whose protein matrix is ​​whey protein: soy protein: casein ≈ 43:23:34, and is used in combination with a specific dose of leucine, HMB and high dose of EPA / DHA and other components) can produce a significant synergistic effect in the LLC tumor cachexia model.

[0220] The complete formulation produces a significantly superior overall effect compared to conventional or imbalanced formulations. Specifically, this complete formulation simultaneously and significantly improves net protein balance (-0.3), powerfully reduces systemic inflammation (IL-6: 48±5 pg / mL), and increases muscle mass (tibialis anterior: 45±4 mg). These indicators are significantly better than the model control group and the standard protein group, and the overall effect is far superior to Comparative Example 2, which lacks the key design concept. This demonstrates that the specific component combination claimed in this invention is an indivisible holistic technical solution, and its effect stems from the combined contribution of each component in the stated specific ratio.

[0221] The effect of different molar ratios of HMB to leucine on its synergistic regulation of muscle protein metabolism (synthesis and breakdown) is shown in [reference needed]. Figure 1 .

[0222] To investigate the optimal synergistic ratio of HMB and leucine, this invention established a series of intervention groups with different molar ratios in a Lewis lung cancer (LLC) cachexia mouse model in Module 1, Experiment 2. Muscle protein synthesis rate (FSR) was measured using stable isotope tracing (D2O method), and the excretion of the muscle-specific degradation marker 3-methylhistidine (3-MH) in urine was determined by high-performance liquid chromatography (HPLC) to comprehensively evaluate the bidirectional regulatory effect on muscle protein metabolism. The core results are as follows: Confirmation of dose-effect relationship and optimal molar ratio: like Figure 1 As shown, the vertical axis "relative change rate" refers to the relative change rate of each different ratio group compared to the model control group (the model control group is denoted as baseline 100%). When the molar ratio of HMB to leucine was adjusted from 1:1 to 1:3, the two exhibited a significant synergistic enhancement effect in promoting synthesis and inhibiting degradation. At a molar ratio of 1:3, the synergistic effect reached its peak: the FSR increase rate reached 160%, while the 3-MH level decreased by 52%. This effect was significantly better than other ratio groups (p<0.01) and the single-component group, clarifying that 1:3 is the optimal molar ratio in this invention.

[0223] Evidence for dual regulation of synthesis and degradation pathways: Synthetic pathway: At a 1:3 molar ratio, the phosphorylation level of the key protein (p-p70S6K) in the mTORC1 signaling pathway in muscle was approximately 4.2 times higher than that in the tumor model group, confirming that this ratio has the strongest activating effect on the synthetic signaling pathway.

[0224] Catabolism pathway: Simultaneous detection showed that the mRNA expression levels of muscle atrophy-related E3 ubiquitin ligases (Atrogin-1 and MuRF-1) were maximally inhibited, with decreases of 65% and 58%, respectively, confirming their potent anti-catabolism effects at the molecular level.

[0225] Comprehensive phenotypic validation: Consistent with the above molecular mechanism results, mice receiving the 1:3 molar ratio intervention had the highest retention rates of tumor-free body weight and gastrocnemius muscle wet weight among all ratio groups, which were 31% and 38% higher than the tumor model group, respectively, and significantly better than the 1:1 ratio group (p<0.05).

[0226] Conclusion: This study, through precise dosage combination research, not only demonstrated the synergistic effect of HMB and leucine in regulating muscle protein metabolism, but more importantly, it discovered and determined the specific optimal molar ratio of 1:3. At this ratio, the two produce the strongest dual effect of "synthesis promotion" and "catabolism inhibition." This discovery constitutes one of the core mechanisms and key design bases for the excellent anti-muscle loss efficacy of the embodiments of this invention.

[0227] Experiment 3 of Module 1: A multicenter randomized controlled trial (RCT) on the rapid improvement of muscle function in cancer patients undergoing mid-term intervention (3-5 weeks) after radiotherapy and chemotherapy. 1. Research Title: A multicenter, randomized, double-blind, controlled clinical study evaluating the effects of a precision nutrition formula on nutritional status, muscle mass, and quality of life in cancer patients undergoing radiotherapy and chemotherapy.

[0228] 2. Study Design: A multicenter, randomized, double-blind, parallel-controlled design was adopted.

[0229] Experimental group: Implemented the formulation of Example 1.

[0230] Control group: Received a complete nutritional formula for cancer patients that meets clinical practice (approximately 30% protein, 50% fat, and 20% carbohydrates), Su Yi Su Special Medical Purpose Cancer Complete Nutritional Formula Food (Registration Certificate No.: TY20220004, Manufacturer: Nestlé Health Science (China) Co., Ltd.).

[0231] 3. Study subjects and grouping: Population: Patients with gastrointestinal or head and neck tumors who have been pathologically diagnosed and are scheduled to receive radiotherapy and chemotherapy (these types of patients are at high risk of malnutrition).

[0232] Sample size: 50 cases per group (total sample size N=100).

[0233] Inclusion criteria: age 18-75 years; PG-SGA score ≥4 (i.e. malnutrition or risk); able to receive enteral nutrition orally or via tube feeding.

[0234] Randomization and blinding: Random sequences are generated by computer, and patients, researchers, and outcome assessors are unaware of the group assignments.

[0235] 4. Intervention plan: Patients in the experimental group received oral nutritional supplements with the exact same nutritional formula as in Example 1 of the present invention (which has an energy ratio of protein: about 22%, fat: about 42%, and carbohydrates: about 36%).

[0236] In addition to routine radiotherapy, chemotherapy and diet, the designated research product is supplemented daily via oral or tube feeding at a fixed amount of 250g / day (providing approximately 400 kcal of energy).

[0237] Research period: 8 weeks.

[0238] 5. Core observation indicators and data collection points: Data will be collected at the start of the study (baseline), week 3, week 5, and week 8 of the intervention (study endpoint).

[0239] In the experiment, the formulation of this invention was effective during week 3 of intervention: (1) Muscle mass index: The skeletal muscle index of the limbs increased significantly by 2.8% (95% CI: 2.5-3.1%). Measurement method: In this study, the skeletal muscle mass of the extremities was measured using a bioelectrical impedance analysis (BIA) instrument (e.g., brand: InBody; model: S10), and the skeletal muscle mass index (SMI) of the extremities was calculated.

[0240] Definition and calculation of the index: Limb skeletal muscle index = Limb skeletal muscle mass (kg) ÷ [Height (m)] 2 Unit: kg / m 2 .

[0241] (2) Muscle function indicators: grip strength improved by 2.9 kg (95% CI: 2.6-3.2 kg); Measurement method: This study used a calibrated electronic hand grip dynamometer (e.g., brand: JAMAR; model: EH101). Subjects sat with their arms hanging naturally and elbows extended, gripping with maximum force using their dominant hand. The test was performed three times and the maximum value was recorded. The unit is kilograms (kg).

[0242] (3) Protein synthesis marker: serum prealbumin level reached 265 mg / L (95% CI: 255-275 mg / L); (4) Muscle protection effect: Serum creatine kinase level was maintained within the normal range of 125 U / L.

[0243] The specifics are shown in Table 5.

[0244] Table 5. Experimental Results (Mean ± Standard Deviation)

[0245] The results of this experiment are summarized as follows: 1. Significantly enhanced muscle anabolic metabolism: In the animal model described above, this formula, through the specific HMB / leucine molar ratio, was shown to efficiently activate the mTOR synthesis pathway, resulting in a muscle protein synthesis rate increase of up to 160% compared to the control.

[0246] 2. Effective suppression of systemic inflammation: This formula has shown excellent anti-inflammatory ability in clinical observations, and can reduce the serum TNF-α level of patients by more than 35%.

[0247] 3. Objective improvement in body composition: Patients who follow this formula intervention achieve an objective target of ≥3% improvement in skeletal muscle mass index (SMI) within the preset period.

[0248] 4. High industrial feasibility: The process parameters are clearly defined and suitable for large-scale production, ensuring the consistency and stability of product efficacy.

[0249] Experiment 4 in Module 1: Stability and Security Testing 1. To verify the feasibility of industrial production of this composition and its stability over the shelf life, the present invention conducted accelerated testing in accordance with the "Guidelines for Stability Testing of Health Foods".

[0250] Method: The finished composition of Example 1 was placed in a constant temperature and humidity chamber at a temperature of 40℃±2℃ and a relative humidity of 75%±5%, and samples were taken for testing at the end of the 0th, 1st, 2nd, 3rd and 6th months.

[0251] Results: As shown in Table 6 below, the content of key active ingredients decreased by less than 5% within 6 months, and the microbiological indicators always met the requirements of the national standard GB 29921, indicating that the product has good stability and can meet the requirements of commercial production, storage and distribution.

[0252] Table 6 Stability Test Results

[0253] 2. Safety evaluation of long-term feeding (1) Method: SD rats were administered the composition by gavage for 26 weeks at doses of 5, 10, and 20 times the recommended human dose. The general condition, blood biochemical indicators and histopathological changes of the animals were observed.

[0254] (2) Results: No poisoning symptoms or deaths were observed in any of the dose groups during the entire experiment. Compared with the control group, the weight gain, food consumption, hematological and serum biochemical indicators of the rats in the experimental group fluctuated within the normal historical background data range, and no pathological changes related to the test substance were observed in the major organs. These results indicate that the composition has a high degree of safety under long-term consumption.

[0255] Experiment 5 of Module 1: An exploratory clinical study in patients with advanced colorectal cancer 1. Research Topic To evaluate the impact of the nutritional composition of the present invention on chemotherapy tolerance and survival prognosis in patients with advanced colorectal cancer receiving FOLFOX chemotherapy regimen.

[0256] 2. Research Design An exploratory study design with multiple centers, randomization, open labels, and parallel controls was adopted.

[0257] 3. Study subjects and grouping Population: Patients with advanced (stage IV) colorectal cancer diagnosed by histopathology who are scheduled to receive at least 4 cycles of first-line chemotherapy with the FOLFOX regimen.

[0258] Sample size: Total sample size N=60, randomly allocated in a 1:1 ratio.

[0259] Experimental group (n=30): conventional treatment + the formula of Example 1 of this invention.

[0260] Control group (n=30): Conventional treatment + Su Yi Su Special Medical Purpose Tumor Complete Nutrition Formula Food (Registration Certificate No.: TY20220004, Manufacturer: Nestlé Health Science (China) Co., Ltd.).

[0261] Key inclusion criteria: Age 18-75; ECOG score: 0-2 points; Expected survival ≥ 3 months; The participants had not received systematic nutritional support therapy within one month prior to enrollment.

[0262] Main exclusion criteria: There is severe liver and kidney dysfunction; The presence of gastrointestinal diseases that affect enteral nutrient absorption; Allergic to any of the ingredients in the product studied.

[0263] 4. Intervention Plan Both groups of patients received enteral nutritional support in addition to FOLFOX chemotherapy: Experimental group: The formulation of Example 1 of this invention was administered orally twice daily, providing 230 kcal of energy each time, for at least 4 weeks (or until disease progression or intolerable toxicity).

[0264] Control group: The control group formula was administered orally twice daily, providing equal energy (230 kcal) nutritional support each time, for the same duration as the experimental group.

[0265] All patients received standard dietary guidance.

[0266] 5. Observation Indicators and Evaluation Time Points Primary endpoint (safety / tolerability): Incidence of grade III-IV chemotherapy-related diarrhea: assessed according to CTCAE 5.0 criteria.

[0267] Relative chemotherapy dose intensity: the percentage of the actual dose completed relative to the planned dose.

[0268] Secondary endpoint (survival outcome): Progression-free survival: the time from randomization to disease progression or death from any cause.

[0269] Overall survival: the time from randomization to death from any cause.

[0270] Assessment timing: Adverse events are assessed every cycle; PFS and OS are followed up regularly (e.g., every 2 months), with a follow-up period of at least 6 months.

[0271] 6. Statistical Methods The sample size for this exploratory study is based on feasibility settings.

[0272] Categorical variables were tested using the chi-square test, while continuous variables were tested using the t-test or non-parametric test.

[0273] PFS and OS analyses were performed using the Kaplan-Meier method, and intergroup comparisons were performed using the Log-rank test. Hazard ratios and their confidence intervals were calculated using the Cox proportional hazards model.

[0274] All statistical analyses used two-tailed tests, and P < 0.05 was considered statistically significant.

[0275] 7. Research Results Chemotherapy tolerance: The incidence of grade III-IV chemotherapy-related diarrhea was 25% lower in the experimental group (P<0.05), and the completion rate of chemotherapy dose intensity was 15% higher.

[0276] Survival outcomes: With a median follow-up of 6 months, the experimental group showed a trend toward prolonged PFS (median PFS: 8.1 months vs. 6.5 months, HR=0.72, 95% CI: 0.49–1.05, P=0.08). At the time of data analysis, a significant number of patients remained alive, and reliable (median) overall survival data could not yet be calculated.

[0277] "Median PFS: 8.1 months vs. 6.5 months" means that half of the patients in the experimental group had a tumor progression-free survival time of 8.1 months, while the control group had a survival time of 6.5 months.

[0278] The statistical analysis result “HR=0.72, 95% CI: 0.49-1.05, P=0.08” indicates that the risk of disease progression or death in the experimental group was 0.72 times that of the control group (i.e., the risk was reduced by 28%). However, this result did not reach the conventional level of statistical significance (P value>0.05), and is therefore described as “showing a prolonging trend”.

[0279] 8. Preliminary Conclusions This exploratory study suggests that supplementing with the compositions of this invention, compared to standard tumor nutrition formulations, may help improve chemotherapy tolerance in patients with advanced colorectal cancer receiving FOLFOX chemotherapy and shows a potential trend toward prolonging progression-free survival, providing preliminary support for its clinical value.

[0280] Experiment 6 in Module 1: Compared to the metabolic advantages of existing standard protocols, this invention designs a randomized, double-blind, double-dummy, crossover controlled clinical trial protocol. This protocol primarily aims to demonstrate the superiority of the formulation in Example 1 in terms of glycemic stability, insulin response, and gastrointestinal tolerability.

[0281] Experimental methods: 1. We recruited 60 patients aged 40-75 years with pathologically confirmed stable cancer (PG-SGA score ≥4, posing nutritional risks). Key inclusion criteria: abnormal glycemic regulation (fasting blood glucose ≥6.1 mmol / L or 2-hour postprandial blood glucose ≥7.8 mmol / L) but not using insulin therapy. Patients with severe hepatic or renal insufficiency, gastrointestinal obstruction, etc., were excluded.

[0282] 2. Refer to the formula Su Yi Su is a special medical purpose tumor complete nutritional formula food. Registration certificate number: TY20220004. Manufacturer: Nestlé Health Science (China) Co., Ltd.

[0283] 3. Experimental Procedure Preparation period (3 days): Standardize the diet and stabilize the baseline.

[0284] First cycle (7 days): Patients were randomly divided into two groups, A and B. Group A took the formulation from Example 1, while group B took the control formulation. The study product provided 1000-1200 kcal of energy daily (approximately 70% of the patient's estimated total energy requirement), orally in two divided doses.

[0285] Washout period (7 days): Resume a standard diet to eliminate the effects of the previous intervention cycle.

[0286] Second cycle (7 days): Two groups were crossovered, with Group A using the control formula and Group B using the formula from Example 1.

[0287] 4. Double-blind and double-dummy To ensure fairness, the formulations in Example 1 and the control formulation were prepared as powders that were indistinguishable in appearance, taste, and smell. Simultaneously, each group of subjects was provided with a placebo (such as a maltodextrin placebo without functional components) to ensure that neither the researchers nor the subjects were aware of their specific group assignments.

[0288] 5. Core Observation Indicators and Data Collection Data collection will focus on three main dimensions: glycemic stability, insulin response, and gastrointestinal tolerance. Specific indicators and evaluation methods are as follows: Glucose stability: Continuous glucose monitoring (CGM) was conducted on subjects wearing CGM devices on days 1 and 7 of each intervention cycle to monitor 72-hour dynamic blood glucose levels.

[0289] Average blood glucose level: Calculated as the arithmetic mean of all blood glucose monitoring readings over a 24-hour period using continuous blood glucose monitoring data, expressed in mmol / L. The formula is: 24-hour average blood glucose = Σ(all blood glucose readings) ÷ total number of readings.

[0290] Standard deviation of blood glucose (SD) and coefficient of variation (CV): assess the magnitude of blood glucose fluctuation. CV = (SD / average blood glucose) × 100%. CV < 36% is a good control target.

[0291] The percentage of time spent above 7.8 mmol / L (TAR) and the percentage of time spent below 3.9 mmol / L (TBR).

[0292] Postprandial blood glucose fluctuation range: the difference between the peak blood glucose level and the baseline within 0-2 hours after drinking the study product.

[0293] Glycemic index (GI) assessment: The GI values ​​of the formulation in Example 1 and the control formulation were directly measured in a specialized metabolic laboratory using the methodological requirements specified in ISO 26642:2010 on healthy subjects.

[0294] Insulin response: On day 7 of each intervention cycle, venous blood samples were collected before (0 minutes) and 30, 60, and 120 minutes after consumption of the study product to measure insulin concentration. The area under the insulin curve (AUC) and insulin secretion index were calculated to assess the metabolic effort the body makes in response to elevated blood glucose.

[0295] Gastrointestinal tolerance: Participants recorded the frequency and severity of gastrointestinal symptoms such as bloating, diarrhea, abdominal pain, nausea, and vomiting daily in an electronic diary (using a 0-3 scoring system). The incidence of diarrhea was specifically recorded (using the Bristol stool typing system; type 6 or 7 with ≥3 occurrences per day was defined as diarrhea). The overall incidence of adverse gastrointestinal events was assessed weekly by the researchers.

[0296] See Table 7 for details.

[0297] Table 7 Comparison of metabolic indicators between the formulation of Example 1 and the commercially available standard formulation.

[0298] Note: Data are expressed as mean ± standard deviation or percentage (n / N); p-value indicates statistical significance of comparisons between groups.

[0299] Example 1 formulation exhibits better gastrointestinal tolerability and improved patient compliance. This demonstrates that Example 1 formulation in this experiment is significantly superior to the control formulation: it significantly reduces the glycemic index, average blood glucose level, and blood glucose fluctuations in cancer patients, and significantly reduces insulin secretion requirements, while also demonstrating superior gastrointestinal tolerability. These effects collectively confirm that Module 1, through its unique macronutrient energy ratio, produces unexpected synergistic technical effects, providing cancer patients with a nutritional support program that is less metabolically burdensome and better tolerated.

[0300] Example 2: Module Two (Focusing on systemic anti-inflammatory and immune modulation) This embodiment corresponds to the "Precision Anti-inflammatory and Immune Regulation Module" in the "Five-Step Therapy" system of this invention, and aims to provide precise nutritional support for cancer patients undergoing radiotherapy and chemotherapy.

[0301] 1. Design Goals Energy density: 160 kcal / 100 g finished product.

[0302] Energy ratio: Protein 25%, Fat 42%, Carbohydrates 33%.

[0303] It primarily inhibits muscle loss (anti-cachexia), regulates systemic inflammation, supports immune and intestinal function, and improves nutrient metabolism efficiency.

[0304] 2. Preparation method This embodiment employs an integrated process of "high-pressure emulsification - low-temperature spray drying - dry mixing of active ingredients". The core design concept of this process route is: (1) Through refined pretreatment and high-pressure homogenization, the ultimate stability and efficient absorption of the nutrient base are achieved; (2) Through precise temperature-controlled spray drying, the activity of heat-sensitive oils and proteins is protected to the maximum extent while forming powder; (3) By using a step-by-step, graded dry mixing strategy, we can ensure the uniform distribution and maximum activity retention of all trace heat-sensitive functional components.

[0305] Step 1: Slurry preparation This embodiment aims to produce 100 kg of finished powder. The total water consumption for slurry preparation is calculated based on "total dry matter ÷ target solids content (48%) - total dry matter" and is added step by step in the following steps.

[0306] 1.1 Aqueous phase fine pretreatment: Add purified water at a temperature of 58°C, which accounts for about 60% of the total water volume, to the chemical tank.

[0307] Turn on the mixer and slowly add maltodextrin, resistant dextrin, and isomaltulose in sequence at a low speed (500 rpm) to prevent dust and clumping.

[0308] After the carbohydrates are completely dispersed, slowly add calcium caseinate, soy protein isolate, and whey protein in batches. During this process, gradually increase the stirring speed to 3500 rpm and maintain it for 18 minutes until a homogeneous protein-carbohydrate solution without visible particles is formed.

[0309] Step 1.1.1 Preparation of the composite mineral concentrate: The compound minerals are pre-dissolved in a portion (approximately 10% of the total water volume) of purified water at 50°C, and stirred until completely dissolved to form a mineral concentrate for later use.

[0310] Step 1.1.2 Mixing and pH Adjustment: While maintaining the protein-carbohydrate solution at 58°C and continuously stirring, the above-mentioned mineral concentrate was slowly added to obtain a mixed slurry.

[0311] Critical control point (pH): Use food-grade sodium hydroxide or citric acid solution to precisely adjust the pH of the mixed slurry to 6.8-7.2. This pH range is most conducive to protein dissolution and subsequent process stability.

[0312] 1.2 Oil phase standardization pretreatment and high-shear emulsification: In another ingredient container, medium-chain triglyceride oil, flaxseed oil, conjugated linoleic acid (CLA), and fish oil are added in the order of "high inertness → low inertness".

[0313] Add the emulsifier soy lecithin and all fat-soluble vitamins (A, D, E, K1). Slowly heat to 48°C and stir at low speed until the soy lecithin is completely dispersed and the fat-soluble components are fully dissolved to form a homogeneous oil phase.

[0314] High-shear emulsification: Under high-speed shear at 9000 rpm, the preheated oil phase is slowly and uniformly pumped into the aqueous phase through a pipeline at a constant and controllable linear flow rate (e.g., 200 mL / min). This process lasts for 22 minutes to ensure that the oil phase is fully sheared and dispersed into micron-sized droplets, forming a preliminarily stable O / W emulsion.

[0315] 1.3 High-pressure homogenization and slurry volume determination: The crude emulsion was transferred to a high-pressure homogenizer and homogenized twice at a pressure of 250 bar (primary) / 50 bar (secondary). This step aims to further break down the oil droplets to the submicron level (target particle size D90 < 1 μm), significantly enhancing the physical stability of the emulsion and preventing oil-water separation during spray drying and the formation of oil rings after the finished product is mixed.

[0316] After homogenization, the remaining 30% of the total water volume is used for pipeline flushing and slurry volume adjustment, and the solid content of the final slurry is precisely adjusted to 48% to meet the process requirements of subsequent spray drying.

[0317] Step 2: Precisely temperature-controlled spray drying and microencapsulation The prepared slurry is transported to the spray drying tower through an insulated pipeline. A centrifugal atomizer (atomizing disc speed of 20,000 rpm) is used to atomize the slurry into uniform tiny droplets. After spray drying, the base powder is obtained.

[0318] Core temperature control for spray drying: Inlet air temperature: 180℃. This temperature is sufficient to evaporate moisture instantly, but overheating is avoided through subsequent control.

[0319] Outlet air temperature: 82℃. This is a key parameter for protecting heat-sensitive components. By adjusting the feed pump speed and stabilizing the outlet air temperature within this low-temperature range, it is possible to ensure that heat-sensitive proteins such as whey protein do not denature, and to minimize the thermal degradation loss of unsaturated fatty acids (EPA, DHA) and vitamins.

[0320] During this process, carbohydrates such as lactose and maltodextrin rapidly crystallize on the surface of the droplets, encapsulating the internal fats, proteins, and fat-soluble components to form a natural "microcapsule" structure. This not only protects the functional ingredients but also improves the product's flowability and reconstitution properties.

[0321] Based on the above preparation process, only the inlet air temperature of the spray dryer is changed. The specific effects of the inlet air temperature on the retention rate of active ingredients and drying efficiency are as follows: Figure 2 As shown, the retention rate curves of HMB and EPA highly overlap, exhibiting a parabolic shape that first rises and then falls. In the 155℃ to 175℃ range, the increased temperature promotes rapid evaporation of moisture, shortens the heating time of droplets within the column, and consequently reduces heat accumulation damage, significantly improving the retention rate. Above 175℃, the thermal degradation effect caused by excessively hot air becomes dominant, and the retention rate declines. The drying efficiency curve continues to rise until 185℃, after which it slows down, consistent with the general rule that higher temperatures increase evaporation rates.

[0322] Quantitative confirmation of the optimal process point: Intersection analysis of the three curves clearly indicated the optimal balance point of the process. At an inlet air temperature of 175℃, the retention rates of both HMB and EPA reached their peak (approximately 95%), with a drying efficiency of 88.6%, which is also high. In contrast, at 185℃, where the drying efficiency is highest, the retention rates of the two active ingredients decreased to approximately 86-88%. Therefore, choosing 175℃ sacrificed approximately 1.6 percentage points of drying efficiency for an approximately 8 percentage point improvement in the retention rate of key active ingredients, demonstrating a significant cost-benefit ratio.

[0323] Drying efficiency was defined in this study as: Drying efficiency = Powder output rate (kg / h) × Retention rate of key active ingredients (%).

[0324] Its core metric is: at a specific inlet air temperature, how quickly (output efficiency) the system can produce the final product with the highest activity retention rate (quality efficiency). It is a comprehensive process efficiency indicator that takes into account both "quantity" and "quality".

[0325] The data marked next to "Optimal process point" clearly shows this composite definition: The system reached its optimal balance at an inlet air temperature of 175°C.

[0326] At this point, the drying efficiency is 88.5% (this value is the comprehensive efficiency index).

[0327] At the same time, two key quality indicators also reached their peak: HMB retention rate and EPA retention rate were both 95%.

[0328] This means that at 175℃, the system can operate at a high efficiency of 88.5% while ensuring a high retention rate of 95% for the core functional components.

[0329] Note: The "drying efficiency" mentioned in this embodiment is a comprehensive process evaluation index. Its value comprehensively reflects the efficiency of producing finished powder that meets quality requirements per unit time. The calculation takes into account both the powder production rate and the retention rate of key heat-sensitive functional components (such as HMB and EPA).

[0330] Step 3: Dry mixing process with stepwise gradation 3.1 Three-stage premixing and incremental dilution: This step aims to solve the industry problem of the difficulty in uniformly dispersing trace amounts of functional ingredients in a large amount of base material.

[0331] First-stage premixing (core functional ingredient premixing): Small doses of trace solid ingredients such as HMB, leucine, glutamine, and nucleotides are initially mixed.

[0332] Second-stage premix (vitamin premix): All water-soluble vitamins (C, B complex) are thoroughly mixed with choline tartrate.

[0333] The third stage of premixing (carrier premix – using an equal-incremental method): To ensure the absolute uniform distribution of the above-mentioned trace premixes during large-scale mixing, an equal-incremental method is used for carrier premixing. The specific operation is as follows: (1) Take sufficient amounts of fructooligosaccharides and a portion of maltodextrin (accounting for approximately 8% of the total dry matter of the formula) as initial carriers.

[0334] (2) Mix the first-stage premix with an equal mass of the initial carrier in a small three-dimensional mixer for 15 minutes to form the first diluted mixture.

[0335] (3) Add the same mass of the initial carrier as the first diluted mixture and continue mixing for 15 minutes to achieve the second dilution. This "equal volume mixing-dilution" process can be repeated 1-2 times as needed.

[0336] (4) Second-stage premix (vitamin premix): Repeat the equal-volume incremental dilution process of steps (2)-(3) above independently.

[0337] This "equal incremental method" can completely eliminate the "caking" and "component enrichment" phenomena caused by differences in particle size and density. It is a key process control point to ensure that every gram of powder in the final product contains the designed dose of functional ingredients.

[0338] 3.2 Ordered mixing: 3.2 Ordered mixing: A portion of the base powder (e.g., 8% of the total amount) obtained by spray drying and used to disperse the premix is ​​fed into a large three-dimensional motion mixer.

[0339] Follow the principle of "large before small, stable before sensitive" for feeding: first add the remaining maltodextrin, then add the carrier premix and mix for 15 minutes; then add all the remaining base powder, and ensure that the total mixing time is not less than 45 minutes until the set mixing uniformity (CV ≤ 5%) is achieved.

[0340] Step 4: Finished Product Packaging and Stability Assurance The uniformly mixed final product is passed through an 80-mesh vibrating screen to break up any soft agglomerates that may form.

[0341] Immediately after sieving, the powder is packaged in a clean environment with humidity <30% RH and temperature <25℃ using nitrogen-filled four-side-sealed aluminum foil bags (oxygen concentration <3% inside the packaging). This measure effectively prevents the product from absorbing moisture and oxidizing, ensuring the stability of key active ingredients such as HMB, EPA / DHA, and others during their shelf life.

[0342] Experiment 1 in Module 2: A Study on Synergistic Precision Nutritional Intervention in a Mouse Model of Tumor Cachexia 1. Experimental Objective This experiment aims to verify whether Module 2, compared to Module 1, can be more effective under the synergistic effect of higher doses of functional components (HMB, EPA, leucine) and optimized nutritional structure: (1) Prevent weight loss and muscle atrophy.

[0343] (2) Suppress systemic inflammatory response.

[0344] (3) Improve intestinal barrier function and gut microbiota health.

[0345] (4) Regulate energy metabolism.

[0346] 2. Experimental Materials and Methods 2.1 Laboratory Animals and Grouping Animals: Male C57BL / 6 mice, SPF grade, 6-8 weeks old.

[0347] Model: Establish a Lewis lung cancer cachexia model (Lewis lung cancer subcutaneous xenograft cachexia model).

[0348] Model building methods: Cell preparation: Resuscitate and routinely culture Lewis lung cancer cells. Take cells in logarithmic growth phase, resuspend in sterile PBS buffer, and adjust the cell density to 2 × 10⁻⁶. 7 per mL.

[0349] Animal inoculation: On day 0 of the experiment, mice were anesthetized by isoflurane inhalation. 0.1 mL of cell suspension was inoculated subcutaneously into the right axilla or back of each mouse using a sterile insulin syringe, i.e., 2 × 10⁶ cells per mouse. 6Lewis lung cancer cells.

[0350] Tumor formation and model confirmation: Daily observation after inoculation. Solid tumor nodules are usually palpable on days 5-7. Progressive weight loss in tumor-bearing mice (e.g., a weight loss of ≥5% from peak value for two consecutive days) is used as the marker for the onset of cachexia and is the starting point for nutritional intervention (usually days 10-14 after inoculation).

[0351] Grouping (n=12 per group): Normal control group: without tumors, fed standard diet.

[0352] Example 1 group: tumor-bearing, Example 1 formula feed (as a positive control, used to compare and demonstrate the enhanced effect of Example 2).

[0353] Example 2 group: tumor-bearing, Example 2 formula feed.

[0354] 2.2 Experimental Design The experiment lasted 21 days. Food intake was recorded daily, and body weight was recorded every 3 days. At the end of the experiment, after a glucose tolerance test, samples were collected. Blood: Used to detect inflammatory factors and metabolic indicators.

[0355] Organization: Precisely separate and weigh the gastrocnemius muscle, tibialis anterior muscle, and epididymal fat; collect colon tissue; collect cecal contents.

[0356] Tumor: Weigh.

[0357] 2.3 Detection Indicators (1) Body composition and muscle function: Weight change curve, muscle mass / body weight ratio in the limbs, and fat mass.

[0358] (2) Systemic inflammation and oxidative stress: Serum: TNF-α, IL-6, MDA, GSH.

[0359] (3) Gut health: Serum lipopolysaccharide-binding protein: indirectly reflects intestinal barrier permeability (endotoxemia).

[0360] Colonic histopathology: Observation of mucosal structural integrity.

[0361] Short-chain fatty acids in cecal contents: butyric acid, acetic acid, and propionic acid content (direct products of intestinal flora function).

[0362] (4) Metabolic indicators: Fasting blood glucose and glucose tolerance test.

[0363] Serum insulin levels were measured, and the HOMA-IR index (for assessing insulin resistance) was calculated.

[0364] 3. Experimental Results The details are shown in Table 8.

[0365] Table 8 Comparison of the effects of Example 1 and Example 2

[0366] Note: Data are expressed as mean ± standard deviation. △△ p<0.01 vs normal control group; # p<0.05, ## p<0.01 vs model group; &p<0.05, &&p<0.01 vs Example 1 group.

[0367] 4. Experimental Results Analysis and Conclusions Experimental data confirm that, within the core framework, by increasing EPA to approximately 800 mg / 100g and HMB to 0.35 g / 100g, while maintaining a specific macronutrient structure, an unexpected synergistic enhancement effect was produced. Compared to Example 1, which already showed significantly better results than the conventional formulation, Example 2 demonstrated statistically significant further advantages in muscle protection, anti-inflammatory efficacy, intestinal barrier repair, and improved insulin sensitivity. This demonstrates that the technical effects of the present invention have an optimized "dose window" and "component matrix," rather than a simple linear relationship.

[0368] The results showed that, compared with the formulation of Example 1, the comprehensively optimized specific composition of Example 2 exhibited significantly enhanced overall efficacy in multiple key cachexia pathological aspects, including reversing muscle loss, inhibiting inflammation, repairing the intestinal barrier, and improving metabolism. This confirms that a systematic and integrated design of the nutritional matrix, functional components, and energy supply structure can achieve comprehensive technological improvements beyond what the basic approach could have anticipated, providing a superior nutritional intervention solution for patients with cancer cachexia.

[0369] (1) Synergistic advantages of muscle protection: The formulation in Example 2 is significantly superior to that in Example 1 in terms of weight maintenance and muscle retention, which reflects the better overall effect achieved by its holistic optimized design of protein and amino acid subsystems.

[0370] (2) Significantly enhanced anti-inflammatory efficacy: The formulation in Example 2 showed the best performance in reducing systemic inflammatory markers, indicating that its anti-inflammatory subsystem design is more effective in targeting cachexia pathology.

[0371] (3) Comprehensive improvement of intestinal barrier and flora function: Serum LBP: The LBP level in the Example 2 group was the lowest, indicating that it was effective in repairing the intestinal barrier and reducing endotoxin entry into the blood.

[0372] Butyric acid in the cecum: The butyric acid content in the group of Example 2 was closest to that in the normal group. Butyric acid is the main energy source for colonic epithelial cells and has anti-inflammatory and anti-cancer effects.

[0373] The formulation in Example 2 showed the best effect in improving intestinal barrier function and the production of beneficial metabolites, which verified the overall design advantages of its intestinal microecological regulation subsystem.

[0374] (4) Metabolic regulation: The Example 2 group exhibited the best insulin sensitivity (lowest HOMA-IR index). The Example 2 formulation demonstrated the best insulin sensitivity, confirming the overall effectiveness of its macronutrient energy structure in improving tumor-related metabolic disorders.

[0375] 5. Safety: There was no statistically significant difference in tumor weight among the groups, further confirming that the effectiveness of nutritional intervention does not depend on promoting tumor growth.

[0376] Experiment 2 in Module 2: Whole-body multi-organ metabolic flux analysis based on dual isotope tracing I. Experimental Objective This experiment aims to go beyond traditional phenotypic observation and empirically demonstrate the synergistic advantages of Module 2 over Module 1 from the perspectives of metabolic kinetics and molecular networks, specifically verifying whether it can: 1. Precisely enhances muscle protein synthesis while inhibiting breakdown, directly quantifying its dual effect of "increasing supply and reducing expenditure".

[0377] 2. Optimizes the utilization of energy substrates throughout the body, promoting more efficient metabolic flexibility.

[0378] 3. Systemic metabolic regulation is achieved through multi-organ coordination (gut-liver-muscle axis).

[0379] 4. Obtain accurate, quantitative data to support strong, quantitative patent claims.

[0380] II. Experimental Materials and Methods 1. Animal models and grouping Model: The Lewis lung cancer cachexia C57BL / 6 mouse model, consistent with that in Example 1, was used to ensure the comparability of the experimental baseline.

[0381] Grouping (n=10 per group): Normal control group: without tumors, fed standard diet.

[0382] Example 1 group: tumor-bearing, Example 1 formula feed.

[0383] Example 2 group: tumor-bearing, Example 2 formula feed.

[0384] Intervention period: 21 days.

[0385] 2. Core Technology: Dual Isotope Labeling Tracer Method [U- 13 C6]-Glucose: Continuously infused via the tail vein at a rate of 35 µmol / kg / min for 150 minutes to trace systemic glucose metabolic flux under metabolic homeostasis.

[0386] D9-Phenylalanine: administered via a single intraperitoneal injection at a dose of 150 µmol / kg body weight, used to accurately calculate the synthesis rates of proteins in muscle, liver, and intestines.

[0387] 3. Experimental Procedure and Sample Collection Day 21: Conduct isotope tracing experiments.

[0388] Under tracer steady-state conditions, the final sample is collected: Blood: Separate plasma for the detection of isotope enrichment, hormones (insulin, glucagon), inflammatory factors (IL-6, TNF-α), and metabolites (glucose, fatty acids, ketone bodies).

[0389] Tissue: Rapidly separate and weigh the following tissues, then immediately freeze in liquid nitrogen for subsequent analysis: Skeletal muscle (gastrocnemius): protein synthesis rate, Akt / mTOR phosphorylation level, expression of key proteins in the ubiquitin-proteasome pathway (MuRF-1, MAFbx).

[0390] Liver: activity of key gluconeogenesis enzyme (PEPCK), lipid content, and protein synthesis rate.

[0391] Jejunum: Intestinal protein synthesis rate, expression of tight junction protein (ZO-1, Occludin).

[0392] Tumor tissue: weighed.

[0393] The specific results are shown in Table 9.

[0394] Table 9 Comparison of the effects of Example 1 and Example 2

[0395] Note: Data are expressed as mean ± standard deviation. # p<0.05, ## p<0.01 vs Tumor model group; &p<0.05, &&p<0.01 vs Example 1 group.

[0396] By synergistically combining whey protein and casein in specific proportions with high doses of leucine (0.30 g / 100 g), HMB (0.35 g / 100 g), and high doses of EPA (800 mg / 100 g), a significant metabolic synergistic effect was achieved in a tumor cachexia model. This combination not only increased muscle protein synthesis to over 140% of the standard protein group but also strongly inhibited catabolic pathways and optimized systemic energy metabolism. This quantitative advantage, achieved simultaneously across multiple metabolic indicators, is unattainable with single components or simple combinations.

[0397] Experiment 3 in Module 2: Human Clinical Research Protocol 1. Research Topic A multicenter, randomized, double-blind, controlled study to evaluate the effects of a high-dose functional ingredient nutritional formula on muscle protein metabolism, systemic inflammation, and functional status in patients with cancer cachexia.

[0398] 2. Research Design Design type: multicenter, randomized, double-blind, parallel controlled.

[0399] Experimental group: Formulation of Example 2.

[0400] Control group: Formulation of Example 1.

[0401] 3. Study subjects and grouping Population: Patients with advanced non-small cell lung cancer or pancreatic cancer who are pathologically diagnosed and have a PG-SGA score ≥9 (clear malnutrition) (high risk of cachexia).

[0402] Sample size: 42 cases per group (total N=84). This sample size is calculated based on the estimated effect size and meets statistical requirements.

[0403] Inclusion criteria: age 18-75 years; weight loss of >5% in at least 2 months; able to eat orally.

[0404] Randomization and blinding: Block randomization was used to ensure baseline balance between groups; all study products were kept consistent in appearance and taste.

[0405] 4. Intervention Plan In addition to standard anti-tumor treatment and diet, the research product is supplemented daily to provide 600 kcal of energy.

[0406] Study duration: 6 weeks. This duration is sufficient to observe significant changes in muscle metabolic parameters, while also considering the feasibility of patient follow-up.

[0407] 5. Core Observation Indicators and Data Collection Points Data were collected at baseline, week 3, and week 6 (study endpoint).

[0408] Baseline (Day 0 / Day 1): Collected immediately before the subject formally receives the intervention (medication, treatment, etc.). This is the "starting line" for evaluating changes in effect.

[0409] Week 3 (approximately day 21): Day 21 (±1 day) from baseline.

[0410] Week 6 - Study Endpoint (approximately day 42): Day 42 (±1 day) from baseline.

[0411] This study, through a multicenter, randomized, double-blind, controlled clinical trial, directly validated the superior efficacy of Module 2 (Example 2) compared to Example 1. Study endpoint: Data at week 6 are shown in Table 10.

[0412] Table 10 Comparison of the effects of Example 1 and Example 2

[0413] Example 2 of this invention, by employing higher doses of leucine (0.30g), HMB (0.35g), and EPA (800mg), and synergistically combining them with a specific fast and slow protein matrix, unexpectedly achieved precise dual regulation of muscle protein metabolism in humans. Stable isotope tracing technology (D2O method) directly confirmed that this formulation not only increased muscle protein synthesis rate (FSR) to an extremely high level of 3.1% / day, but also, for the first time, demonstrated through a specific marker (3-methylhistidine) that it simultaneously and significantly inhibited muscle breakdown. This powerful dual intervention in both the "synthesis" and "degradation" pathways produced a significant synergistic effect, with results (e.g., an increase in SMI of 0.41 kg / m²) significantly superior to the control formulation (Module 1) that only provided basic nutritional support.

[0414] This invention designed four control formulations, which differed from the formulation in Example 2 only in the ratio of HMB to leucine and / or the preparation process. The interventions were conducted in the same animal model of cancer cachexia, and the key results are shown in Table 11.

[0415] Table 11 shows the conventional process, which uses a traditional one-step route to complete mixing and drying. The specific steps are as follows: (1) Raw material dissolution and mixing: Add the total amount of purified water (the total amount of water is the same as in Example 2) to the chemical tank and heat it to 72°C.

[0416] While stirring, add all ingredients to the formula, including but not limited to: maltodextrin, calcium caseinate, whey protein isolate, soy protein isolate, fats, complex minerals, complex vitamins, and heat-sensitive functional ingredients such as HMB and leucine. Maintain the temperature and continue stirring until all ingredients are completely dissolved or dispersed to form a homogeneous liquid.

[0417] (2) Homogenization and sterilization: The above liquid material was homogenized once using a high-pressure homogenizer at a pressure of 225 bar.

[0418] The liquid is then subjected to ultra-high temperature instantaneous sterilization, typically at 138°C for 8 seconds.

[0419] (3) Spray drying: The sterilized liquid is immediately pumped into a spray drying tower for drying.

[0420] Standard spray drying parameters are used: inlet air temperature 192℃, outlet air temperature 95℃.

[0421] Rapid dehydration at this high temperature allows for the collection of dried powder.

[0422] (4) Cooling and Packaging: After drying, the powder is cooled and then packaged directly in a humidity-controlled environment.

[0423] Note: This conventional process places all ingredients (including heat-sensitive HMB, some vitamins, etc.) in a high-temperature hydration and high-temperature drying environment, which may cause degradation of active ingredients.

[0424] Table 11 Effects of the molar ratio of HMB to leucine on cancer cachexia in animals

[0425] Experimental conclusion: Only when a specific molar ratio (1:2.8) and a specific low-temperature directional embedding process are simultaneously satisfied can the best effect be achieved in promoting synthesis (de-fat body mass) and inhibiting decomposition (Atrogin-1), and the effect is significantly improved.

[0426] Regarding parameters such as fat energy ratio and homogeneous pressure, this invention verifies its full-range effectiveness through multiple experimental schemes.

[0427] Fat energy ratio gradient experiment: While keeping the absolute content of core components (such as HMB, leucine, EPA / DHA dosage) constant, the fat energy ratio was adjusted, and the ratio of protein to carbohydrates was adjusted accordingly to maintain a constant total energy level, in order to observe the effects on gastrointestinal tolerance (diarrhea rate) and energy density. The results are shown in Table 12.

[0428] Energy density (kcal / g) = (g protein × 4 kcal / g) + (g fat × 9 kcal / g) + (g available carbohydrates × 4 kcal / g).

[0429] Operational basis: Protein: Calculated as total protein content (which can be determined by the Kjeldahl method).

[0430] Fat: Measured as total fat content (by acid hydrolysis or the Rhodes-Gottlieb method).

[0431] Available carbohydrates: Usually calculated as "total carbohydrates minus dietary fiber" (the energy contribution of dietary fiber is usually calculated as 0-2 kcal / g, but the specific calculation needs to be based on the standard).

[0432] Table 12 Effects of changes in energy supply ratio on gastrointestinal tolerance (diarrhea rate) and energy density

[0433] Conclusion: This study demonstrates that 38%-42% is an optimal range that achieves the best balance between "high energy density" and "low gastrointestinal side effects," rather than an arbitrary choice.

[0434] Verification of two-stage homogenization pressure parameters: Homogenization pressure is crucial for ensuring system stability and fat globule size, directly affecting product quality. The effects of different homogenization pressures are shown in Table 13.

[0435] Table 13 Effect of different homogenization pressures on product stability

[0436] Conclusion: Stable emulsions can be formed within the specified pressure range. The preferred combination of 250 / 50 bar achieves the best balance between equipment wear and product stability, and its effect is significantly better than conventional pressure.

[0437] Example 2, the "three-stage premixing + total mixing for 45 minutes" process, has been proven to be efficient and stable on industrial production lines (such as 3000L mixing tanks). See Table 14 for details.

[0438] Table 14 Production Stability Data

[0439] Conclusion: The process achieved the design target of ≥200kg per hour, and the coefficient of variation (CV) of mixing uniformity was much lower than the industry standard (≤10%), proving its high efficiency and reliability in large-scale production.

[0440] Long-term stability: In Example 2, the stability of food for special medical purposes was investigated under normal temperature and light-protected conditions, according to the "National Food Safety Standard GB 29922-2013 Food for Special Medical Purposes". The results are shown in Table 15.

[0441] Table 15 Stability results of Example 2

[0442] Conclusion: Under normal temperature and light-protected conditions, all key indicators of this product remained stable over a 24-month shelf life, meeting national standards and demonstrating that it has sufficient shelf life for commercialization.

[0443] Summarize: Using only the formulation of this case (Comparative Example B) or only the process of this case (Comparative Example C) resulted in improved effects, but only to a limited extent. Only when a specific molar ratio (1:2.8) was combined with a specific process did a significant leap in effect (fat-free body mass +12.3%, Atrogin-1 expression -55%) occur.

[0444] Homogeneous pressure: It is indicated that the combination of 250 / 50 bar achieves the best balance between effect (particle size 0.38 μm) and energy consumption / stability, and its effect is significantly better than that of conventional pressure (200 / 30 bar).

[0445] Fat energy ratio: It is effective in a wide range of 35%-45%, but the tolerance and energy density are better at 38%-42%.

[0446] This invention optimizes process parameters (such as homogenization pressure of 250 / 50 bar). Experimental results show that the process steps and parameters of this invention must be used to significantly reduce fat globule size while improving product stability.

[0447] In Example 2, the specific combination of ingredients (such as HMB, leucine, and high-dose EPA) under specific ratios and processes significantly improved the effect on the complex model of tumor cachexia, achieving the best results in promoting synthesis (lean body mass) and inhibiting breakdown (Atrogin-1).

[0448] Experiment 4 in Module 2: Evaluating the effects of nutritional compositions on muscle protein synthesis and atrophy gene expression 1. Experimental Objective The main purpose of this embodiment is to verify, through standardized animal experiments, the synergistic effect of the nutritional composition (containing HMB, leucine, and high-dose EPA) described in Example 2 in promoting muscle protein synthesis and inhibiting the expression of muscle atrophy genes, and to demonstrate that its effect is significantly better than that of a single component or a binary combination.

[0449] 2. Materials and Methods 2.1 Experimental Animals and Model Construction Animals: Eighty-four 8-week-old SPF-grade male C57BL / 6 mice, weighing 20–22 g, were selected and acclimatized for 7 days in a standard environment (temperature 22–24℃, humidity 50–60%).

[0450] Tumor cachexia model: CT26 colon cancer cells were subcutaneously injected into mice (1 × 10⁶ cells per mouse). 6 A cancer cachexia model was established using individual cells. Mice that lost more than 15% of their body weight 21 days after inoculation were selected for the experiment.

[0451] 2.2 Experimental Grouping and Intervention Eligible mice were randomly divided into 7 groups (n=12). All mice in all groups had free access to a standard maintenance diet during the experiment. The intervention lasted for 14 days. The total functional component dose administered by gavage to all intervention groups was fixed at 1.05 g / kg / day. Maltodextrin and water were added to ensure that the total daily caloric intake was consistent with the gavage volume across all gavage groups. Blank model group: Inoculated with tumor and administered an equal volume of physiological saline by gavage.

[0452] Single-component control group A (HMB): HMB 1.05 g / kg / day + maltodextrin filler with equal calories / volume.

[0453] Single-component control group B (leucine): 1.05 g / kg / day of leucine + maltodextrin of equal calories / volume.

[0454] Single-component control group C (EPA): EPA 1.05 g / kg / day + isocaloric / equal-volume maltodextrin filler.

[0455] Binary combination group A (HMB + Leucine): HMB 0.57 g / kg / day + Leucine 0.48 g / kg / day + maltodextrin filler with equal calories / volume.

[0456] Binary combination group B (HMB+EPA): HMB 0.39 g / kg / day + EPA 0.66 g / kg / day + isothermaltodextrin filler of equal calories / volume.

[0457] The ternary synergistic experimental group (complete formula of Example 2): HMB 0.3 g / kg / day + Leucine 0.25 g / kg / day + EPA 0.5 g / kg / day (this formula itself already contains other macronutrients that make up the total calories, so no additional supplementation is required).

[0458] 2.3 Detection Indicators and Methods Muscle protein synthesis rate (FSR): At the end of the experiment, deuterated phenylalanine (D5-Phe) was injected intraperitoneally, and quadriceps femoris muscle was harvested 2 hours later. The enrichment of D5-Phe in muscle protein was detected by UPLC-mass spectrometry, and the FSR (% / day) was calculated.

[0459] The muscle protein synthesis rate (FSR) is calculated using the following formula:

[0460] Wherein, Ep is the enrichment of D5-Phe in muscle protein 2 hours after injection of D5-Phe; Em is the representative value of plasma D5-Phe enrichment during the labeling period (measured 60 minutes after injection); and t is the labeling time (2 hours, i.e., ≈0.0833 days).

[0461] Muscle atrophy gene expression: Tibial anterior muscle was harvested, and the mRNA expression levels of key muscle atrophy genes (Atrogin-1, MuRF-1) were detected by real-time quantitative PCR, with glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as an internal control.

[0462] Statistical analysis: Data are expressed as mean ± standard deviation. One-way ANOVA and Tukey post-hoc test were used. p < 0.05 was considered statistically significant.

[0463] 3. Experimental Results 3.1 Muscle protein synthesis rate (FSR) As shown in Table 16, the FSR of the complete formulation group in Example 2 was significantly higher than that of all other groups (p<0.01), which was about 125% higher than that of the blank model group, and significantly higher than any single component or binary combination (HMB+leucine group), proving that the three can greatly promote protein synthesis in synergy.

[0464] Table 16 Comparison of muscle protein synthesis rate (FSR) among different groups of mice (mean ± standard deviation, n=12)

[0465] Note: △ indicates a significant difference compared to the blank model group; # indicates a significant difference compared to the complete formulation group of Example 2.

[0466] The above demonstrates that the complete combination of components in Example 2 (containing higher doses of HMB, leucine, EPA, and the fast and slow protein matrix) produced the best synergistic synthesis effect.

[0467] Table 17 shows the comprehensive intervention effects of different nutritional formulations on the multidimensional phenotypes of tumor cachexia mice.

[0468] Table 17. Comprehensive intervention effects of different nutritional formulations on multidimensional phenotypes in mice with tumor cachexia.

[0469] Note: △△ indicates that the tumor model group is p<0.01 compared with the normal control group; ### indicates that the Example 2 group is p<0.001 compared with the tumor model group; and the Example 2 group is p<0.05 and p<0.01 compared with the Example 1 group.

[0470] The above demonstrates that Example 2 is significantly superior to Example 1 in reversing weight loss, muscle wasting, systemic inflammation, and metabolic disorders.

[0471] 3.2 Expression of Muscle Atrophy Genes The complete formulation group in Example 2 showed the most significant effect in inhibiting the expression of muscle atrophy genes (Table 18). The expression levels of Atrogin-1 and MuRF-1 were significantly lower than those in other groups, indicating that Example 2 can most effectively block the protein degradation pathway.

[0472] Table 18 Relative expression levels of muscular atrophy genes (Atrogin-1, MuRF-1) mRNA (mean ± standard deviation, n=12)

[0473] Note: △ p<0.05 vs blank model group, &p<0.05 vs complete formulation group of Example 2.

[0474] Experimental Conclusion: This embodiment, through setting up rigorous controls including single components, binary combinations, and complete formulations, confirms the following facts: 1. Clear synergistic effect: Module 2 (HMB + leucine + EPA) is significantly more effective than any single component or binary combination (HMB + leucine) in both promoting muscle protein synthesis and inhibiting the expression of muscle atrophy genes. This indicates that EPA is not a dispensable auxiliary component, but a key element in the synergistic effect.

[0475] 2. Complete "open source and cost reduction" mechanism: The formulation of module two simultaneously increases the synthesis rate (FSR) to 225% of the model group and inhibits the expression of the core atrophy genes (Atrogin-1, MuRF-1) to 32%-40% of the model group, achieving dual and powerful regulation of the muscle protein metabolism "synthesis" and "decomposition" pathways.

[0476] Example 3: Module 3 (High-fat, high-protein, low-carbohydrate, focusing on the remodeling and regulation of energy metabolism) 1. Design Goals and Concepts Energy ratio: protein 26%, fat 45%, carbohydrates 29%.

[0477] Design concept: Adopting a "high-fat-high-protein-low-carb" strategy, this strategy aims to achieve more effective nitrogen conservation and muscle protection; Metabolic regulation: Significantly reduces carbohydrate load and provides sustained strong anti-inflammatory effects.

[0478] Module Three is designed for cancer patients with insulin resistance (Standard B). The core innovation of this module lies in "reconstructing the macronutrient energy ratio." By significantly increasing the proportion of energy supplied by fat and strictly selecting sustained-release and resistant carbohydrates, a metabolic pattern of "low carbohydrate load, high fat energy supply" is achieved. This design aims to directly reduce postprandial blood glucose fluctuations, provide alternative energy substrates, and thus specifically improve the patient's insulin sensitivity.

[0479] 2. Specific preparation method of Example 3 (powder) Based on the mature process of Example 2, the parameters were optimized to address the characteristics of this formula, which is high in fat and low in carbohydrates (low in maltodextrin).

[0480] Step 1: Preparation of base material slurry (emulsification of aqueous and oil phases) 1.1 Aqueous phase preparation: Add purified water at 60°C, which accounts for about 75% of the total water volume, to the mixing tank (the temperature rises slightly, and the viscosity of the slurry may change slightly due to the reduction of maltodextrin).

[0481] Start stirring and add the following ingredients in sequence: maltodextrin, a portion of resistant dextrin (92% of the total resistant dextrin), isomaltulose, calcium caseinate, soy protein isolate, and whey protein.

[0482] Maintain the temperature and stir at a shear rate of 3000 rpm for 12 minutes to form a homogeneous solution.

[0483] Add the complex minerals and stir until completely dissolved.

[0484] 1.2 Oil phase preparation and emulsification: Mix medium-chain triglyceride oil, high-oleic sunflower seed oil, flaxseed oil, conjugated linoleic acid (CLA), fish oil, soybean lecithin (as an emulsifier), and fat-soluble vitamins (A, D, E, K1).

[0485] Heat to 48°C and mix thoroughly by stirring at low speed to obtain the oil phase.

[0486] The well-mixed oil phase is slowly and uniformly added to the aqueous phase, while the shearing machine speed is increased to 10,000 rpm for high-speed shearing for 20 minutes (due to the higher fat content, stronger shearing force is required to ensure the initial emulsification effect), to obtain the emulsion.

[0487] 1.3 Homogenization and Volume Adjustment: The emulsion was homogenized twice using a high-pressure homogenizer at a pressure of 280 bar (increasing the homogenization pressure ensures small and stable droplets under high fat content).

[0488] Make up the volume with the remaining 25% of the total water volume using purified water at room temperature, and stir thoroughly. Monitor the solids content of the slurry; it should be controlled at 45%.

[0489] Step 2: Spray drying The prepared slurry is pumped to a spray drying tower via a screw pump to obtain a powder base material.

[0490] Key process parameters: Inlet air temperature: 175℃ (Due to the high fat content, the inlet air temperature should be appropriately reduced to decrease the risk of oxidation). Air outlet temperature: 80℃; Atomizer speed: Maintain high speed (20,000 rpm).

[0491] Step 3: Dry mixing (adding heat-sensitive and functional ingredients) 3.1 Premixing: HMB, glutamine, leucine, nucleotides, choline tartrate, water-soluble vitamins (all vitamin components except fat-soluble vitamins), and silica (flow aid, accounting for 0.5% of the base powder mass) are premixed with the remaining resistant dextrin (accounting for 8% of the total resistant dextrin mass) for 18 minutes. Then, a small portion of the powder base material (accounting for 8% of the total mass) is added and mixed evenly to obtain the premixed material.

[0492] 3.2 Overall Mixing: The remaining portion (92% of the total amount) of powder base material obtained from spray drying was fed into a three-dimensional mixer.

[0493] Add the premixed materials mentioned above.

[0494] Mix at room temperature for 40 minutes, or until completely homogeneous.

[0495] Step 4: Sieving and Packaging The uniformly mixed final product is passed through a 70-mesh vibrating screen.

[0496] In a dry environment with humidity <30% RH and temperature <25℃, quickly perform nitrogen filling or vacuum packaging.

[0497] Step 5: Inspection Sampling inspections are conducted on the finished products, with a focus on fat content and oxidation indicators (peroxide value, acid value), content of key functional ingredients (HMB, EPA / DHA, leucine), and reconstitution properties.

[0498] Experiment 1 in Module 3: Study on the metabolic intervention and muscle protection effects in a mouse model of tumor cachexia 1. Experimental Objective This experiment aims to verify whether the "high-fat-high-protein-low-carbohydrate" nutritional strategy adopted in Module 3 can, by regulating the host's energy metabolism pattern, not only more effectively protect muscles but also bring unique advantages such as improved insulin sensitivity and promotion of nitrogen conservation.

[0499] 2. Experimental Materials and Methods 2.1 Laboratory Animals and Grouping Animals: Male C57BL / 6 mice, SPF grade, 6-8 weeks old.

[0500] Model: A Lewis lung cancer (LLC) cachexia model was established, which can well simulate the muscle atrophy and metabolic disorders caused by tumors.

[0501] Model building methods: (1) LLC tumor cell culture and preparation Cell line: Mouse Lewis lung cancer cell line was used.

[0502] Culture conditions: The culture was carried out in DMEM medium containing 10% fetal bovine serum and 1% penicillin-streptomycin at 37°C in an incubator with 5% CO2.

[0503] Cell state: Cells in the logarithmic growth phase, with good morphology and vigorous activity, were seeded.

[0504] Cell suspension preparation: Digest cells with trypsin, collect by centrifugation, and resuspend in sterile phosphate-buffered saline or sterile serum-free medium. Count cells using trypan blue staining to ensure cell viability >95%. Adjust cell concentration to 1×10⁶ cells / mL. 7 per mL.

[0505] (2) Preparation and grouping of experimental animals Six- to eight-week-old male C57BL / 6 mice were randomly divided into the following four groups (n=12 per group) after being acclimatized in an SPF-grade animal facility for at least one week: Normal control group: Tumor-free mice, fed a standard maintenance diet with free access.

[0506] Tumor model group: Tumor-bearing mice, fed a standard maintenance diet with free access. The average daily food intake (and corresponding total calories) of these mice will serve as the feeding baseline for other tumor-bearing groups.

[0507] Example 2 Intervention Group: Tumor-bearing mice received isocaloric paired feeding. That is, they were provided with a special feed formulated according to Example 2, with a total calorie intake equal to the average calorie intake of the tumor model group on that day.

[0508] Example 3 Intervention Group: Tumor-bearing mice received isocaloric paired feeding. That is, they were provided with a special feed formulated according to Example 3, with a total calorie intake equal to the average calorie intake of the tumor model group on that day.

[0509] (3) Tumor cell inoculation (model induction) Operation day: designated as day 0 of the experiment.

[0510] Anesthesia and fixation: All tumor-bearing mice were anesthetized by inhalation or injection of isoflurane. They were then fixed in a lateral recumbent position.

[0511] Inoculation site: The subcutaneous tissue of the right hind limb was chosen as the inoculation site. This site facilitates subsequent tumor volume measurement and is far from major muscle groups, thus distinguishing the tumor burden from the direct effects of the intervention on specific muscles (such as the gastrocnemius).

[0512] Inoculation procedure: Disinfect the injection site with 75% alcohol. Using a 1mL sterile syringe, draw 100μL of the prepared cell suspension (containing 1×10⁻⁶ cells / mL). 6 (One LLC cell). Pinch the skin, insert the needle horizontally under the skin, and slowly inject the suspension. A wheal will be formed. Slowly withdraw the needle and press gently for a moment to prevent leakage.

[0513] Control group treatment: Mice in the normal control group underwent sham surgery, i.e., they were injected with an equal volume (100 μL) of sterile PBS or culture medium, and the operation steps were exactly the same.

[0514] (4) Successful modeling monitoring and standards Tumor growth monitoring: Starting approximately 5-7 days post-inoculation, measure the long and short diameters of the tumor every 2-3 days using calipers. Calculate using the formula: Volume (mm²) 3 ) = (major axis × minor axis) 2 ) / 2 Calculate the tumor volume. A successful model should exhibit stable exponential growth.

[0515] Monitoring cachexia phenotype: This is the core objective of this experimental modeling.

[0516] Body weight: Weighed every 3 days. A successful cachexia model is characterized by the following: in the later stages of tumor growth (usually 14-21 days after inoculation), although the tumor volume continues to increase, the net body weight (total weight minus tumor weight) or the rate of weight gain of the mice is significantly lower than that of the normal control group.

[0517] Muscle wasting determination: At the end of the experiment (day 21), anatomical weighing revealed that the absolute weight or the ratio of skeletal muscles such as the gastrocnemius and tibialis anterior muscles in the model group was significantly lower than that in the normal control group, which is the standard for the successful cachexia model.

[0518] General observation: Reduced activity, disheveled hair, and hunched back may be observed.

[0519] (5) Key quality control points in the modeling process Aseptic technique: Cell manipulation and seeding are performed entirely in a laminar flow hood or using strict aseptic techniques to avoid accidental infection that could interfere with the model.

[0520] Cell viability and quantity: Ensuring high viability and accurate quantity of seeded cells is key to ensuring tumor growth synchronicity and model consistency.

[0521] Randomization: Strict randomization must be performed before vaccination to offset individual differences.

[0522] Exclusion criteria: Pre-defined criteria, such as mice that do not develop palpable tumors within 1 week after vaccination, mice with ruptured or infected tumors, or mice in extremely poor condition and near death, should be excluded from subsequent analysis.

[0523] In summary, this modeling process successfully simulated the core pathophysiological processes of tumor cachexia by subcutaneously inoculating mice with a quantitative amount of LLC cells and utilizing their stable growth characteristics. This induced progressive weight loss (especially lean body mass loss) and skeletal muscle atrophy in the host over approximately 3 weeks, accompanied by metabolic disorders and inflammation. This provides a reliable experimental platform for evaluating the effectiveness of nutritional interventions.

[0524] 2.2 Experimental Design The experiment lasted for 21 days.

[0525] Record your food intake daily and your weight every 3 days.

[0526] The intraperitoneal glucose tolerance test was conducted on day 18 of the experiment.

[0527] Experiment endpoint, sample collection: Blood: Separate serum for the detection of metabolic and inflammatory markers.

[0528] Tissue: The gastrocnemius and tibialis anterior muscles were precisely separated and weighed; liver samples were collected; and some muscle tissue was rapidly frozen at -80°C for Western blot analysis.

[0529] Tumor: Weigh.

[0530] Urine: Collected in metabolic cages during the last 24 hours of the experiment for the determination of blood urea nitrogen.

[0531] 2.3 Detection Indicators (1) Body composition and muscle mass: Weight change curve, muscle mass / body weight ratio of limbs.

[0532] (2) Nitrogen balance and protein metabolism indicators: 24-hour urinary urea nitrogen: Calculates nitrogen excretion and indirectly reflects the degree of muscle protein breakdown.

[0533] Muscle protein synthesis signaling: The protein expression levels of p-mTOR (Ser2448) and p-p70S6K (Thr389) in gastrocnemius muscle were detected by Western Blot.

[0534] (3) Systemic energy metabolism and glucose metabolism: Serum β-hydroxybutyrate: reflects the liver's ketogenic activity and indicates the level of fat metabolism for energy.

[0535] Area under the curve for fasting blood glucose and glucose tolerance tests.

[0536] Serum insulin levels were used to calculate the HOMA-IR index.

[0537] (4) Systemic inflammation: Serum: TNF-α, IL-6.

[0538] (5) Tumor growth: tumor weight.

[0539] 3. Experimental Results See Table 19 for details.

[0540] Table 19 Comparison of the effects of Example 2 and Example 3

[0541] Note: Data are expressed as mean ± standard deviation. △△ p<0.01 vs normal control group; ## p<0.01 vs tumor model group; &p<0.05, &&p<0.01 vs Example 2 group.

[0542] Experimental Conclusion: This experiment, through multi-dimensional indicators, confirms that the "high-fat-high-protein-low-carbohydrate" nutritional strategy adopted in Module 3 produced a series of unexpected and interrelated synergistic effects: (1) Successful metabolic remodeling: The sharp increase in serum β-hydroxybutyrate level (0.65 mM) in Group 3 of Example 3 proves that this formula successfully induced a fundamental shift in host energy metabolism from glucose oxidation to lipid oxidation, providing the body with more efficient and cleaner ketone body energy.

[0543] (2) Excellent nitrogen-saving and synthesis synergy: The above metabolic switching brought about a significant nitrogen-saving effect (lowest urea nitrogen: 17.1 mg), and at the same time, in synergy with ultra-high doses of HMB / leucine, it activated muscle synthesis signals (p-mTOR / mTOR: 1.05), thereby achieving the strongest muscle protection effect among all modules (gastrocnemius / body weight ratio: 6.2 mg / g).

[0544] (3) Fundamental improvement of metabolic environment: By significantly reducing carbohydrate load, this formula most effectively improves insulin resistance (HOMA-IR: 2.7), creating an optimal internal environment for protein synthesis and overall metabolic health.

[0545] (4) Module 3 is not a simple formulation variant, but is primarily designed for patients with specific metabolic disorders (such as insulin resistance).

[0546] Through a specific macronutrient structure (45% fat, 29% carbohydrates), it forces the body to undergo beneficial metabolic transformations, thereby achieving a qualitative leap in nitrogen conservation, ketosis, and improved insulin sensitivity under the same core component matrix as Example 2 (Balanced) and Example 1 (Basic).

[0547] Experiment 2 in Module 3: Study on the Advantages of Metabolic Intervention Experimental Design: Dynamic Analysis of Multi-Tissue Metabolic Flux Based on Dual Isotope Tracing I. Experimental Objective This experiment aims to go beyond macroscopic phenotypes and demonstrate the unique advantages of the formulation in Example 3 compared to Module 2 from the perspectives of metabolic kinetics and energy substrate utilization, specifically verifying whether its "high-fat-low-carbohydrate" strategy can: 1. Precisely quantify muscle protein turnover: Simultaneously measure synthesis and degradation rates to directly prove the metabolic basis of its "powerful nitrogen saving".

[0548] 2. Revealing the reprogramming of systemic energy metabolism: confirming the formulation-induced ketosis and the metabolic pattern of lipid oxidation as the priority.

[0549] 3. Elucidate the synergistic effects of multi-organ metabolism: Analyze the differences and interactions in energy substrate utilization among tissues such as muscle, liver, and fat.

[0550] II. Experimental Materials and Methods 1. Animal models and grouping Model: Lewis lung cancer (LLC) cachexia C57BL / 6 mouse model, the modeling method is consistent with that in Example 1.

[0551] Grouping (n=10 per group): Normal control group: without tumors, fed standard diet.

[0552] Tumor model group: tumor-bearing, fed a standard diet.

[0553] Example 2 group: tumor-bearing, Example 2 formula feed.

[0554] Example 3 group: tumor-bearing, Example 3 formula feed.

[0555] Intervention period: 21 days.

[0556] 2. Core Technology: Dual Stable Isotope Tracing and Metabolic Cage Analysis [ 13 C6]-glucose and [U- 13 Continuous infusion of C-palmitate: Simultaneous tracking of carbohydrate and fat oxidation rates and metabolic fate.

[0557] D9-phenylalanine pulse injection: used to accurately calculate the protein synthesis rate (FSR) of muscle and liver.

[0558] Indirect calorimetry metabolic cage: At the end of the intervention, the oxygen consumption (VO2) and carbon dioxide production (VCO2) of mice were monitored for 24 consecutive hours to calculate the respiratory quotient (RQ) and energy expenditure, which directly reflects the proportion of energy substrate oxidation throughout the body (the lower the RQ, the higher the proportion of fat oxidation). The respiratory quotient (RQ) is the volume ratio of carbon dioxide production to oxygen consumption in the body.

[0559] 3. Sample Collection and Analysis Samples were collected under tracer steady-state conditions. Blood: Detection of isotope enrichment, β-hydroxybutyrate, free fatty acids, glycerol, and hormones.

[0560] organize: Skeletal muscle (gastrocnemius): Protein synthesis rate (FSR), mitochondrial fatty acid oxidase (CPT1a) activity.

[0561] Liver: gluconeogenesis flux, expression of key enzyme in ketone body production (HMGCS2), and lipid content.

[0562] Quantitative data are shown in Table 20.

[0563] Table 20 Comparison of metabolic effects between Example 2 and Example 3

[0564] Note: △△ p<0.01 vs normal control group; ## p<0.01 vs tumor model group; && p<0.01 vs Example 2 group.

[0565] Module 3, through its specific nutritional structure of "high fat-high protein-low carbohydrate," unexpectedly achieved systemic metabolic reprogramming in the tumor host. This is not only reflected in conventional muscle protection indicators, but more importantly, it is directly confirmed through stable isotope tracing technology that this formula can efficiently switch the host's energy metabolism substrate from glucose-based to fat and ketone body-based (reducing the systemic respiratory quotient from 0.95 to 0.82), while simultaneously increasing muscle protein synthesis rate to an unprecedented high level (≥3.4% / day), achieving the synergistic establishment of a "synthesis-promoting" and "lipid oxidation-promoting" metabolic mode.

[0566] This module's "high-fat-high-protein-low-carbohydrate" structure represents an in-depth exploration of individualized nutrition within a standard framework. Experiments have demonstrated its ability to significantly improve insulin sensitivity and produce a nitrogen-saving effect, providing an effective and standardized nutritional solution for patients with these specific metabolic abnormalities.

[0567] Module 3, Experiment 3: Human Clinical Research Protocol 1. Research Objectives A multicenter, randomized, double-blind, controlled study to evaluate the effects of a high-fat, low-carbohydrate nutritional formula on systemic energy metabolism and body composition in patients with cancer cachexia.

[0568] 2. Research Design Design type: multicenter, randomized, double-blind, parallel controlled.

[0569] Experimental group: Formula of Example 3 (high fat-high protein-low carbohydrate).

[0570] Control group: Formulation of Example 2 (Precision Synergistic).

[0571] 3. Study subjects and grouping Target population: Patients with advanced cancer diagnosed by pathology and exhibiting insulin resistance (HOMA-IR>2.5). Selecting this population allows for precise validation of its targeting effect in improving metabolic disorders.

[0572] Sample size: 40 cases per group (total N=80). The effect size of metabolic indicators was calculated based on the preliminary experiment and met statistical requirements.

[0573] Inclusion criteria: age 18-75 years; PG-SGA score ≥ 4; able to eat orally.

[0574] Randomization and blinding: Centralized stratified randomization is used, and the products are highly similar in appearance, taste and texture.

[0575] 4. Intervention Plan In addition to standard treatment, the target energy requirement is provided daily through research products, ensuring that the nutritional supply is entirely dominated by the research formula.

[0576] Study duration: 4 weeks. This period is sufficient to observe a stable shift in energy metabolism patterns and early changes in body composition.

[0577] 5. Core Observation Indicators and Data Collection Points Data collection points: baseline (day 0), day 14 (±2 days) after intervention, day 28 (±2 days) after intervention, and study endpoint.

[0578] The core of this study is to demonstrate that the formulation in Example 3 can successfully "reprogram" the systemic energy metabolism of the tumor host, that is, to forcibly switch from glucose oxidation as the main process to lipid / ketone body oxidation as the main process. Table 21 shows the key data of this study.

[0579] Table 21 Comparison of clinical trial outcomes between Example 2 and Example 3 (mean ± standard deviation, week 4)

[0580] Module 3 of this invention provides a high-fat, low-carbohydrate nutritional structure with approximately 45% fat energy and approximately 29% carbohydrate energy, achieving a "reprogramming" of the systemic energy metabolism in the tumor host. Metabolic indirect caloric assays confirmed that this formula significantly reduced the patient's average respiratory quotient from 0.87 (glucose oxidation-dominated) in the control group to 0.79 (fat oxidation-dominated) (P<0.001), accompanied by a rise in serum β-hydroxybutyrate levels to 0.85 mmol / L, indicating a nutritional ketogenic state. Particularly unexpectedly, this metabolic shift, while significantly reducing body fat percentage (-1.0% vs -0.2%), not only completely maintained muscle mass but also produced a significant "nitrogen-saving effect" (a 23% reduction in urinary urea nitrogen) and improved insulin sensitivity (HOMA-IR decreased from 3.5 to 2.8). This demonstrates that by providing exogenous fat / ketone bodies as "clean fuel," this invention effectively reduces the metabolic demand for gluconeogenesis from endogenous proteins (muscle), thereby achieving a breakthrough in combating cachexia at the metabolic level.

[0581] This invention introduces "trace elements in specific compound states" to replace "inorganic salts." The selenium element it contains exists in the form of selenomethionine, and its content is 45-60 μg / 100g; the magnesium element it contains exists in the form of magnesium citrate. Conventional formulations use inorganic salts such as sodium selenite and magnesium sulfate, which have low bioavailability and cause significant gastrointestinal irritation. This invention utilizes selenomethionine (organic selenium) and magnesium citrate (organic magnesium) as specific sources. Details are as follows: Selenium: Provided in the form of selenomethionine at a dosage of 40 μg / 100g of finished product.

[0582] Magnesium: Provided in the form of magnesium citrate, at a dosage of 73 mg / 100g of finished product (based on elemental magnesium).

[0583] The experimental demonstration mainly reflects the following: 1. Selenomethionine can be integrated into albumin and muscle protein as a "selenium reservoir" to achieve sustained release and targeted delivery of selenium; magnesium citrate participates in the tricarboxylic acid cycle, its absorption is independent of gastric acid, and it is itself a component of energy metabolism.

[0584] 2. Biomarkers: In animal experiments, the serum glutathione peroxidase activity (GPx, a core indicator of selenium function) in the rats of this study group was 2.1 times that of the sodium selenite group.

[0585] In the treadmill endurance test, the time to exhaustion in this group was significantly longer than that in the inorganic salt group (+40%), accompanied by a 15% decrease in serum insulin levels, demonstrating that it improved overall energy metabolism flexibility.

[0586] 3. In a preliminary study of lung cancer patients, after two weeks of taking the formula (Example 3), the patients' average respiratory quotient decreased from 0.89 to 0.82, as measured by indirect calorimetry, indicating a shift in their energy supply mode from primarily relying on carbohydrates to utilizing more fat and ketone bodies. Simultaneously, the patients' morning serum β-hydroxybutyrate levels increased from 0.1 mM to 0.65 mM, providing the body with an effective alternative energy source.

[0587] Therefore, this invention is not a simple addition of inorganic minerals, but rather utilizes organically compounded trace elements with specific metabolic advantages and bioavailability. It does not address a generalized nutritional support problem, but rather precisely corrects the specific pathophysiological state of "tumor-related energy metabolism disorder," using objective metabolic indicators such as respiratory quotient and blood ketone levels as criteria for determining success.

[0588] Experiment 4 in Module 3: Verifying the Metabolic Reprogramming Effect of Nutritional Compositions 1. Experimental Objective In cancer patients with insulin resistance, the Modular 3 formulation, rich in medium-chain triglycerides (MCTs) (MCTs providing 57% of total fat energy), demonstrated clinical benefits in improving systemic insulin resistance and body composition by enhancing fat oxidation and inducing mild ketosis.

[0589] 2. Materials and Methods Research Design: A randomized, double-blind, crossover study was conducted, which included 40 postoperative patients with gastrointestinal tumors who had insulin resistance (HOMA-IR>2.5) (aged 50-70 years, PG-SGA score ≥4).

[0590] Divided into 2 groups, 20 people in each group: Group A: First, the formulation of Example 3 (high MCT formulation, intervention period) was used. After a 4-week washout period, the formulation was switched to the standard whole protein formulation with equal calories (low MCT formulation, control period) for 4 weeks.

[0591] Group B: The intervention sequence was the reverse of Group A. First, the standard whole protein formulation was used (control period). After a 4-week washout period, the formulation of Example 3 was used (intervention period).

[0592] Control of core variables: Total energy and protein intake remained constant throughout the study period for both Group A and Group B. The only variable was the proportion of MCT in the formulated fat.

[0593] Definition of standard whole protein formulation (control period): The formula used was a whole-protein enteral nutrition preparation (Abbott Ensure) with a macronutrient energy ratio that conforms to the conventional ratio (14% protein, 32% fat, and 54% carbohydrates). Its fat source is long-chain vegetable oil (such as corn oil and soybean oil), and it was confirmed that the content of medium-chain triglycerides (MCTs) in the total fat is ≤10%, which is in clear contrast to the formulation in Example 3.

[0594] Washout period design: (1) Duration: 4 weeks.

[0595] (2) Dietary regimen: During the washout period, all subjects received a standard whole protein formula, the specific regimen of which is as follows: Product: Abbott Ensure® enteral nutrition powder, the same as the control group.

[0596] Dosage: The total daily energy supply is 30 kcal / kg (actual body weight), and the daily protein supply is 1.3 g / kg (actual body weight).

[0597] Data Analysis Principles: This study employed a standard crossover design analysis method. After the experiment, the endpoint data of all subjects in the "Example 3 formulation intervention period" were combined into one group (intervention group data), and the endpoint data of all subjects in the "standard whole protein formulation control period" were combined into another group (control group data). Statistical comparisons were then performed between these two groups.

[0598] The principle for determining the dosage of each formulation is to match the standard whole protein formulation during the control period with the intervention period of Example 3 using isothermal matching.

[0599] Isocaloric matching principle: To ensure the rigor of the above comparisons and eliminate the confounding effects of total caloric intake, isocaloric matching was used for the two intervention periods. That is, the total daily caloric intake was first determined based on the energy density of the formulation in Example 3 (e.g., 460 kcal / person / day), and during the standard formulation control period, the subjects were provided with the standard formulation product with the same total caloric intake.

[0600] Detection method: Indirect calorimetry: The resting respiratory quotient (RQ) is measured using a metabolic cart (such as COSMED Quark RMR) once a week.

[0601] β-HB and HOMA-IR: The detection method is the same as in Example 2.

[0602] Body composition: Fat mass and lean body mass were measured by bioelectrical impedance analysis (BIA), and the rate of change was calculated.

[0603] 3. Experimental Results In the crossover controlled clinical study, the metabolic indicators of all subjects at different intervention stages are compared as shown in Table 22.

[0604] Table 22

[0605] The results demonstrate that this crossover controlled clinical study provides direct human evidence for the "metabolic reprogramming" effect of the formulation in Example 3. Data shows that when patients used the formulation of Example 3 of this invention, their resting respiratory quotient (RQ) remained stably at an extremely low level of 0.74, while their serum β-hydroxybutyrate concentration rose to a nutritional ketogenic state of 2.2 mmol / L. These two indicators conclusively prove that the body's primary energy supply mode has switched from glucose oxidation to fat and ketone body oxidation.

[0606] During the 4-week intervention period, patients experienced a significant reduction in fat mass (-5.8%), while lean body mass increased simultaneously (+1.5%), and insulin resistance was significantly improved (HOMA-IR decreased from 4.5 to 2.8). This completely overturns the traditional understanding that "fat reduction" and "muscle preservation" are mutually exclusive, proving that the "clean fat fuel" provided by this module can simultaneously meet the body's energy needs, effectively reduce metabolic burden, and guide metabolism towards protecting and even increasing lean body tissue.

[0607] Example 4: Module Four (Extremely Digestible and High-Energy, Focusing on Ensuring Digestion and Absorption and Repairing the Intestinal Barrier) 1. Design Goals and Concepts Energy ratio: Protein: 22%, Fat: 48%, Carbohydrates: 30%.

[0608] Design concept: For patients who commonly experience gastrointestinal mucositis, malabsorption, or pancreatic exocrine insufficiency during radiotherapy and chemotherapy, the core design principle is "extremely easy to digest and high energy".

[0609] Overall: While maintaining strong anti-inflammatory and anti-muscle loss functions, it greatly reduces the burden on the digestive tract.

[0610] Safety of high fat energy ratio: Clinical data directly prove that although the fat energy ratio is as high as 48%, because it is mainly composed of MCT which is absorbed independently of bile salts and is supplemented by highly efficient medium-chain fatty acid sucrose ester emulsification, the incidence of diarrhea in patients was successfully controlled to below 10%, which is far lower than that in the control group, fully demonstrating its good gastrointestinal tolerance.

[0611] Module Four addresses clinical scenarios involving severe gastrointestinal dysfunction, such as chemotherapy-induced severe diarrhea (Standard C). This module features a revolutionary protein system design: ① The protein is entirely provided by pre-digested short peptides to minimize the digestive burden on the intestines; ② Leucine has been explicitly removed from the amino acid profile. This innovative combination ensures the supply of essential nitrogen sources while prioritizing intestinal tolerability and safety, and retains sufficient glutamine to support intestinal mucosal repair, achieving the triple goals of "non-irritating, easily absorbed, and promoting repair."

[0612] This module is the only one in the system that uses "all-short peptide proteins" and is "leucine-free." This design fundamentally distinguishes it from the complete protein / amino acid systems of modules one through three, and the mixed protein system of module five. Its function is highly focused on ensuring nutrient absorption and safety in extremely vulnerable intestinal conditions, without involving other target interventions such as anti-inflammation or anemia improvement. It is a "protective" nutritional program specifically designed for the most severe gastrointestinal complications.

[0613] 2. Specific preparation method of Example 4 (powder) This method makes key adjustments to the process to address the characteristics of high MCT content and high hydrolyzed protein.

[0614] Step 1: Slurry Preparation (Simplified Process) Because the protein is in the form of hydrolyzed peptides and the carbohydrates are mainly maltodextrin, it has excellent solubility.

[0615] Add purified water at 48°C to the chemical tank.

[0616] While stirring at low speed (1000 rpm), slowly add the following in sequence: most of the maltodextrin (93% of the total maltodextrin), resistant dextrin, isomaltulose, hydrolyzed whey protein peptides, and collagen peptides. Avoid high-speed shearing to prevent further breakage of the hydrolyzed peptide chains or excessive foaming.

[0617] Add the complex minerals and stir until dissolved to obtain the aqueous phase.

[0618] Step 2: Oil phase preparation and gentle emulsification Medium-chain triglyceride oil, fish oil, structured lipids, medium-chain fatty acid sucrose esters (emulsifiers), and fat-soluble vitamins (including vitamin A, vitamin D, vitamin E, and vitamin K1) are mixed and heated to 40°C to obtain the oil phase.

[0619] The oil phase was slowly added to the aqueous phase, and the stirring speed was increased to 5000 rpm, followed by shearing for 12 minutes. Because a highly efficient emulsifier was used and there was no need to encapsulate the intact protein, the required shear force was lower than in the previous examples.

[0620] A stable state can be achieved by homogenizing twice under 150 bar pressure.

[0621] Process parameters are based on the following: Emulsion stability tests show that under a homogenization pressure of 150 bar, the fat globule size D[3,2] of the resulting emulsion is 0.45 μm, and the centrifugal sedimentation rate is <0.5%, indicating the best stability. Pressures below 130 bar result in excessively large particle sizes (>1 μm), which can easily cause fat to float to the surface; pressures above 170 bar may lead to excessive breakage, affecting the texture.

[0622] Step 3: Spray drying The homogenized emulsion is concentrated or blended to achieve a solids content of 52%, which is then used as the feed slurry for spray drying. Spray drying is then performed to obtain a base powder with low moisture content.

[0623] Key process parameters: Inlet air temperature: 170℃ (lower temperature is used due to the presence of a large amount of heat-sensitive MCT and hydrolyzed peptides); Air outlet temperature: 78℃; Atomizer speed: 20,000 rpm.

[0624] Step 4: Dry mixing Premix the remaining maltodextrin with choline tartrate, HMB, glutamine, nucleotides, water-soluble vitamins (i.e., the remaining vitamins).

[0625] The base powder obtained by spray drying is mixed in a three-dimensional mixer for 30 minutes.

[0626] Sieve (70 mesh) and package with nitrogen filling.

[0627] 4. Specific composition and preparation process of structured lipids (1) Specific composition The "structured lipids" described in this formulation are specifically composed of MLM-type (medium-chain-long-chain-medium-chain) structured lipids as defined in this invention. Their core molecular structural features are: medium-chain fatty acids (mainly derived from MCT, such as C8:0 caprylic acid and / or C10:0 decanoic acid) are bonded at the sn-1 and sn-3 positions of a glycerol molecule, and long-chain polyunsaturated fatty acids (mainly derived from fish oil, i.e., eicosapentaenoic acid EPA and docosahexaenoic acid DHA) are bonded at the sn-2 position.

[0628] (2) Preparation process The structured lipid was prepared using a specific enzymatic transesterification process. The specific steps are as follows: Refined medium-chain triglyceride oil and concentrated fish oil (total EPA+DHA content ≥50%) were mixed at a mass ratio of 60:40. Under controlled temperature (65℃) and vacuum conditions (100Pa), 1.3% of an immobilized 1,3-specific lipase (Lipozyme® RM IM derived from Rhizopus oryzae) was added for catalytic reaction for 8 hours. This enzyme selectively catalyzes the cleavage of ester bonds at the sn-1 and sn-3 positions on the glycerol backbone of fish oil and re-esterifies with medium-chain fatty acids provided by MCT, thereby directionally introducing medium-chain fatty acids to the sn-1 and sn-3 positions while maximally retaining the long-chain polyunsaturated fatty acids (EPA / DHA) at the sn-2 position of the fish oil, generating the target MLM-type structured lipid. After the reaction, the product underwent purification steps including enzyme separation, decolorization, and deodorization to obtain a high-purity final product.

[0629] The refining process includes the following steps: Enzyme preparation separation: After the reaction is completed, the immobilized lipase is recovered by filtration or centrifugation to obtain crude transesterified oil.

[0630] Decolorization: The crude oil is heated to 90°C, and activated clay (approximately 1-3% of the oil weight) is added while stirring. This temperature is maintained for 30 minutes to adsorb pigments, phospholipids, and residual trace catalysts. The oil is then filtered to obtain decolorized oil.

[0631] Deodorization: The decolorized oil is placed in a high-vacuum membrane deodorization tower and deodorized for 2 hours under conditions of 190℃ and absolute pressure ≤ 3 mbar by introducing steam to effectively remove free fatty acids, peroxides and volatile odor substances.

[0632] Final filtration and storage: The deodorized oil is cooled to below 40°C and then filtered through a precision filter (such as a 1μm filter bag) to remove any possible solid particles, resulting in a high-purity MLM-type structured lipid product. It is then stored in a nitrogen-filled, light-proof, and low-temperature environment.

[0633] (3) Key points to note In the formulation, 'structured lipids' specifically refers to MLM-type structured lipids prepared by the above-mentioned specific enzymatic transesterification process, wherein the sn-1 and sn-3 positions of the glycerol backbone are mainly medium-chain fatty acids (C8:0 / C10:0) from MCT, and the sn-2 position is a long-chain polyunsaturated fatty acid (EPA / DHA) from fish oil.

[0634] 5. Summary of Example 4 (1) Precise positioning of the target population: clearly targeting cancer patients with severely impaired digestive function.

[0635] (2) Innovative application of nutrient form: The combination of 100% hydrolyzed protein peptides and collagen peptides, as well as a fat system with extremely high MCT, structured lipids and special emulsifiers, constitutes an extremely easily absorbed nutrient composition.

[0636] (3) Differentiation of ingredients: Collagen peptides and medium-chain fatty acid sucrose esters were introduced for the first time, and their synergistic effects on intestinal repair and fat absorption were explained.

[0637] (4) Adaptability of the process: In view of the characteristics of hydrolyzed protein and high MCT, a mild process with low shear, low homogenization pressure and low drying temperature is adopted to reflect the matching between the formulation and the process.

[0638] Experiment 1 in Module 4: Evaluation of the intestinal protective and nutritional rehabilitation effects in a mouse model of chemotherapy-induced enterocolitis 1. Experimental Objective This experiment aims to verify whether Module 4 (fully hydrolyzed protein + high MCT + mucosal repair nutrients) can: (1) To maintain weight and nutritional status more effectively; (2) Significantly reduces inflammatory damage to the intestinal mucosa and promotes barrier repair; (3) Improve the absorption efficiency of nutrients; (4) Through the gut-axis mechanism, it indirectly relieves systemic inflammation and muscle loss.

[0639] 2. Experimental Materials and Methods 2.1 Laboratory Animals and Models Animals: Male BALB / c mice, SPF grade, 6-8 weeks old (more sensitive to chemotherapy drugs).

[0640] Model: A 5-fluorouracil (5-FU)-induced chemotherapy-induced enteritis model was used. This model perfectly simulates the severe gastrointestinal symptoms in clinical radiotherapy and chemotherapy patients.

[0641] Grouping (n=10 per group): Normal control group (Control): injected with physiological saline and allowed free access to maintenance feed for laboratory animals that meets the GB 14924.3 standard.

[0642] Model group: injected with 5-FU (50 mg / kg / day) and allowed free access to the same standard maintenance diet as the normal control group.

[0643] Example 2 group (Exp 2): 5-FU (50 mg / kg / day) was injected, and the feed was allowed to be consumed freely according to the formulation of Example 2 (as a standard complete nutrition control).

[0644] Example 4 group: injected with 5-FU (50mg / kg / day), and allowed free access to the feed formulated in Example 4.

[0645] 2.2 Experimental Design After adaptive feeding, mice in the model group, Example 2 group, and Example 4 group were intraperitoneally injected with 5-FU (50 mg / kg / day) for 5 consecutive days to establish a chemotherapy-induced enteromucosal inflammation model. Mice in the normal control group were injected with an equal volume of physiological saline.

[0646] Starting from the first day of injection, each group was given the corresponding feed, and the experimental period was 14 days.

[0647] Record weight and food intake daily, and assess diarrhea index, with a total score of 0-6.

[0648] Specific evaluation criteria: (1) Stool characteristics (0-3 points): 0 points: Stool is formed and dried; 1 point: The stool is slightly softened, but still basically formed; 2 points: Loose, unformed stool (pasty stool); 3 points: Watery stool.

[0649] (2) Anal condition (0-3 points) 0 points: Anus is clean and dry; 1 point: Slight stains around the anus; 2 points: Obvious stains or redness around the anus; 3 points: Severe staining, redness, or prolapse of the anus.

[0650] At the experimental endpoint, a D-xylose absorption test was conducted. This involved administering a specific concentration of D-xylose solution (e.g., 5% w / v aqueous solution at a dose of 0.1 mL / 10 g body weight) via gavage to assess intestinal absorption function. Samples were then collected afterward. Blood: Separate serum.

[0651] Small intestinal tissue: Jejunum and ileum tissues from the same location were taken. Part of the tissue was fixed in formalin for pathological analysis, and the rest was frozen at -80°C.

[0652] Colon contents: used for short-chain fatty acid analysis.

[0653] 2.3 Detection Indicators (1) Overall condition and absorption function: Weight change curve, diarrhea index.

[0654] Serum D-xylose concentration: directly reflects the intestinal active absorption capacity.

[0655] (2) Intestinal barrier and inflammation: Jejunal histopathology: villus height and histological damage scoring.

[0656] Jejunal histological damage scoring criteria (0-12 point scale): Villus structure (0-3 points): 0 points: normal, neatly arranged; 1 point: slightly shortened or deformed; 2 points: moderately shortened or fused; 3 points: severely atrophied, shed or disappeared; Epithelial cells (0-3 points): 0 points: intact, no shedding; 1 point: a small amount of apical shedding; 2 points: regional shedding, with visible exposed gaps; 3 points: large-area shedding and necrosis; Inflammatory cell infiltration (0-3 points): 0 points: none; 1 point: a small amount of scattered infiltration in the mucosal layer; 2 points: obvious infiltration in the mucosa and submucosa; 3 points: diffuse severe infiltration, which may be accompanied by abscess formation. crypt structures (0-3 points): 0 points: normal; 1 point: mild dilation; 2 points: moderate dilation and destruction; 3 points: severe destruction and disappearance.

[0657] Serum endotoxins: directly reflect intestinal barrier permeability.

[0658] Jejunal tight junction protein: ZO-1 protein expression (Western Blot or immunohistochemistry).

[0659] (3) Gut microecology: Short-chain fatty acid content in colon contents: butyric acid content.

[0660] (4) Systemic inflammation and muscle wasting: Serum: TNF-α.

[0661] Tibialis anterior muscle weight / body weight ratio.

[0662] 3. Experimental Results Table 23 illustrates the advantages of Example 4 in terms of intestinal protection and absorption function: Table 23 Comparison of the effects of Example 2 and Example 4 on intestinal protection and absorption function

[0663] Note: △△ p<0.01 vs normal control group; ## p<0.01 vs model group; &p<0.05, &&p<0.01 vs Example 2 group.

[0664] 4. Experimental Results Analysis and Conclusions (1) Fundamental improvement in gastrointestinal symptoms and absorption function: Diarrhea Index: The improvement in diarrhea in Example 4 group was extremely significant, proving that it can greatly improve the gastrointestinal side effects caused by chemotherapy.

[0665] D-xylose absorption rate: The absorption level of the group in Example 4 almost returned to the normal level, which is direct evidence of the effectiveness of the "fully hydrolyzed protein + high MCT" easily absorbed system, proving its absorption efficiency advantage.

[0666] (2) Powerful repair of the intestinal barrier: Morphological repair: The villous height and histological score of the Example 4 group were significantly better than those of the Example 2 group (&&), indicating that high doses of vitamin A (300 μg RE) and glutamine had a very good effect on promoting mucosal epithelial repair.

[0667] Barrier function restoration: The results of serum endotoxin levels and ZO-1 protein expression showed that Example 4 was the most effective in repairing the "leaky gut" and maintaining the integrity of tight junctions, which interrupts an important pathway for endotoxin to enter the bloodstream and drive systemic inflammation.

[0668] (3) Maintaining a healthy gut microenvironment: The butyrate levels in Example 4 indicate that even with high MCT and low filled carbohydrates, appropriate amounts of resistant dextrin can still effectively nourish the gut microbiota and produce beneficial metabolites.

[0669] (4) Systemic benefits: Due to the improved intestinal barrier and enhanced absorption efficiency, the group in Example 4 had the lowest level of systemic inflammation (TNF-α) and the most effective inhibition of muscle loss (highest tibialis anterior muscle / body weight ratio).

[0670] 5. Experimental Conclusions This experiment, using a rigorous chemotherapy-induced enteritis model, confirms that: The formulation in Example 4 demonstrates significant advantages in the intervention of chemotherapy-induced enterocolitis through its "zero-digestion" nutrient form, fortified nutrition for mucosal repair (high in Vitamin A and glutamine), and high-energy MCT system. It effectively repairs intestinal damage, restores absorption function, alleviates diarrhea, and indirectly relieves systemic inflammation and muscle wasting by protecting the intestinal barrier, providing a nutritional solution for cancer patients with severely impaired digestive function.

[0671] "Zero digestion" absorption specifically refers to: (1) Protein aspect: Use hydrolyzed protein peptides (especially dipeptides and tripeptides). These short peptides can be directly and completely absorbed into the blood through oligopeptide transporters (such as PEPT1) on intestinal epithelial cells, completely avoiding the series of hydrolysis processes of pepsin and trypsin required for intact proteins.

[0672] (2) Regarding fats: Medium-chain triglycerides are used. MCTs have a unique metabolic pathway, which does not rely on bile salt emulsification to form microparticles, nor does it require sufficient hydrolysis by pancreatic lipase. They can be rapidly absorbed and enter the liver directly through the portal vein.

[0673] (3) Regarding minerals: Amino acid chelated minerals are used. Their absorption mechanism is similar to that of amino acids, without the need for the complex dissociation, competition and recombination process of inorganic salts in the intestine, resulting in high absorption efficiency and minimal gastrointestinal irritation.

[0674] Example 4 shows good results for the specific clinical problem of "impaired digestive function", which makes it a clear scenario division with Example 2 (general precision nutrition) and Example 3 (metabolic intervention).

[0675] Example 4 transforms proteins and fats from their conventional forms into hydrolyzed peptides and MCTs. This is not a simple equivalent replacement, but rather a qualitative leap in efficacy under the specific pathological condition of intestinal mucosal damage (from "nutritious but not absorbable" to "absorbable and repairable").

[0676] Experiment 2 in Module 4: The intestinal protective effect demonstrated in a chemotherapy-induced enterocolitis model Experimental Protocol: Study on Intestinal Absorption and Tissue Distribution Based on Dual Stable Isotope Tracing I. Experimental Objective This experiment aims to go beyond traditional intestinal morphology observation and, from the perspectives of nutrient absorption kinetics and tissue-targeted distribution, empirically demonstrate the unique advantages of the formulation in Example 4 compared to Example 2, specifically verifying whether its "fully hydrolyzed protein + high MCT" system can: 1. Significantly accelerates the intestinal absorption rate of proteins and fats, directly quantifying their "easily digestible" properties.

[0677] 2. To improve the efficiency of targeted delivery of absorbed nutrients to muscle tissue and elucidate the mechanism by which they indirectly protect muscles.

[0678] 3. Maintain efficient overall energy metabolism in cases of severe enteritis.

[0679] 4. Obtain key data that can be used to support quantitative functional claims.

[0680] II. Experimental Materials and Methods 1. Animal models and grouping Model: The BALB / c mouse chemotherapy-induced enteromucositis model induced by 5-fluorouracil (5-FU) was used, which was consistent with the modeling method in Example 4, to ensure the comparability of the experimental basis.

[0681] Grouping (n=10 per group): Normal control group: injected with physiological saline and fed standard feed.

[0682] Model group: injected with 5-FU (50mg / kg / day), fed with standard feed.

[0683] Example 2 group: 5-FU (50mg / kg / day) was injected, and the feed was formulated according to Example 2.

[0684] Example 4 group: 5-FU (50mg / kg / day) was injected, and the feed was formulated according to Example 4.

[0685] Intervention period: 14 days.

[0686] 2. Core Technology: Dual Stable Isotope Tracing and Indirect Calorimetry [ 13 C]-labeled hydrolyzed whey protein peptides: Following an equal-substitution principle, these were added to the feed of Example 4 at a ratio of 3% of the total hydrolyzed whey protein peptide content (e.g., 0.2 g / 100 g feed). Blood levels were detected by mass spectrometry. 13 Enrichment kinetics of C-amino acids to accurately calculate protein uptake and appearance rates.

[0687] The principle of equal substitution in this experimental design means that when formulating the experimental feed of Example 4, an equal mass of [13C]-labeled hydrolyzed whey protein peptides is used to replace an equal mass of unlabeled hydrolyzed whey protein peptides in the formula. Objective: To ensure that the total hydrolyzed whey protein peptide content, total protein content, total energy, and all other nutrients in the experimental and control feeds are completely identical.

[0688] [ 2H8]-β-hydroxybutyrate: At the end of the intervention, a single intraperitoneal injection of 20 mg / kg body weight was administered to trace hepatic ketogenesis and peripheral tissue (especially muscle) utilization of ketone bodies, reflecting the metabolic outcome of high MCT.

[0689] Indirect calorimetry metabolic cage: On days 12-13 of the experiment, oxygen consumption (VO2) and carbon dioxide production (VCO2) were monitored for 24 consecutive hours to calculate the respiratory quotient (RQ) and assess the overall energy substrate utilization pattern.

[0690] 3. Sample Collection and Analysis Postprandial kinetic studies were conducted at the experimental endpoint (day 14), with blood samples collected at different time points (0, 15, 30, 60, 120 minutes) after feeding the isotope-labeled diet.

[0691] Final sample collection: (1) Blood: used to detect isotope enrichment, amino acid profile, β-hydroxybutyrate, and insulin.

[0692] (2) Organization: Jejunum: A segment of the same intestine about 10 cm from the pylorus was taken. A portion was fixed with 4% paraformaldehyde for subsequent histopathological and immunohistochemical analysis; another portion was rapidly frozen at -80°C for the extraction of RNA or protein, and for the detection of tight junction protein (ZO-1, Occludin) expression and inflammatory factor mRNA.

[0693] Gastrocnemius muscle: Both sides of the gastrocnemius muscle were completely dissected, and the wet weight was recorded. A portion was rapidly frozen in liquid nitrogen and then transferred to -80°C for the detection of protein synthesis signals (p-mTOR, p-p70S6K) and [ 13 The amount of C-amino acid incorporated; another portion was fixed with 4% paraformaldehyde for histological analysis.

[0694] Liver: Samples were taken from the same location in the left lobe of the liver and rapidly frozen at -80°C for subsequent analysis of lipid metabolism-related gene expression or metabolites.

[0695] Tumor tissue: If tumor-bearing, completely remove and weigh it.

[0696] The results are shown in Table 24.

[0697] Table 24 Comparison of the effects of dual stable isotope tracing in Examples 2 and 4

[0698] Note: Data are expressed as mean ± standard deviation. # p<0.05, ## p<0.01 vs Model group; &p<0.05, &&p<0.01 vs Example 2 group.

[0699] Table 24 shows the experimental results based on dual stable isotope tracing, which comprehensively reveals the significant synergistic advantages of Example 4 (based on hydrolyzed peptide formulation) compared to Example 2 (based on intact protein formulation) in multiple dimensions: (1) In terms of the efficiency of nutrient substrate absorption and utilization, Example 4 achieved the unity of "acceleration" and "efficiency enhancement".

[0700] Significantly improved absorption kinetics: such as plasma 13 The time to peak concentration (Tmax) of C-leucine in Example 4 (25 ± 5 minutes) was significantly shorter than that in Example 2 (45 ± 8 minutes), demonstrating that the hydrolyzed peptides were absorbed more rapidly. Simultaneously, their plasma... 13 The area under the curve (AUC) of C-leucine was 1.67 times that of the group in Example 2, indicating a significant increase in total absorption.

[0701] Superior metabolic response: The highest postprandial insulin secretion level was observed in Example 4 group (14.5 ± 1.8 μIU / mL), indicating that it can more effectively trigger anabolism signals and create a favorable hormonal environment for protein synthesis.

[0702] (2) In terms of tissue targeting and anabolism activation, Example 4 demonstrates a precise “muscle-directed” effect.

[0703] Enhanced muscle-targeted deposition: 120 minutes postprandial, in muscle tissue 13 The amount of C-labeled amino acids incorporated in the Example 4 group was 2.5 times that of the control group and significantly higher than that in the Example 2 group (1.5 times), directly demonstrating that hydrolyzed peptides are preferentially taken up by muscle tissue and used for protein synthesis.

[0704] Strong activation of the synthetic signaling pathway: The phosphorylation level of the mTOR pathway in muscle (p-mTOR / mTOR) reached its peak (0.9 ± 0.1) in the Example 4 group, and its activation intensity significantly exceeded that of the Example 2 group (0.6 ± 0.1), which explains its excellent ability to promote muscle synthesis from a molecular mechanism perspective.

[0705] (3) In terms of reshaping the whole body energy metabolism pattern, Example 4 achieved a deep switch to fat oxidation.

[0706] A fundamental shift in metabolic substrates: The respiratory quotient (RQ) of animals in the Example 4 group remained stable at a low level of 0.81, significantly lower than that of the Example 2 group (0.89), indicating that their energy supply mainly came from lipid oxidation rather than carbohydrates.

[0707] The ketogenic effect was significantly enhanced: the plasma β-hydroxybutyrate production (AUC) in the Example 4 group was 3.0 times that of the control group and significantly higher than that in the Example 2 group (1.5 times), which confirms that it can efficiently induce nutritional ketosis and provide the body with efficient alternative energy.

[0708] Liver metabolic reprogramming: In Example 4, the gene expression level of CPT1a, a key enzyme in liver fatty acid oxidation, was upregulated to 1.4 times that of the control group and higher than that of Example 2 (0.9 times), providing key molecular evidence for this metabolic switching.

[0709] (4) In terms of gut health and systemic inflammation regulation, Example 4 played a dual protective role of “repair” and “anti-inflammatory”.

[0710] Intestinal barrier structure repair: Example 4 most effectively upregulated the expression of jejunal tight junction proteins ZO-1 and Occludin, restoring them to near-normal levels, indicating that it has excellent repair capabilities for the intestinal mechanical barrier.

[0711] Local and systemic inflammation suppression: The mRNA expression of pro-inflammatory factors (TNF-α, IL-1β) in jejunal tissue was suppressed to the lowest level in the Example 4 group. At the same time, the serum levels of intestinal injury markers diamine oxidase (DAO) and endotoxin also decreased most significantly in the Example 4 group, demonstrating that it can effectively reduce intestinal mucosal damage and permeability, thereby alleviating systemic inflammation.

[0712] Conclusion: The above multi-dimensional data collectively demonstrate that Example 4 of this invention, by employing a specific combination of hydrolyzed peptides, not only surpasses the whole protein formulation in terms of absorption speed and efficiency, but also produces a significant synergistic enhancement effect in three key cachexia pathological processes: promoting targeted muscle synthesis, reshaping the systemic energy metabolism to switch towards fat oxidation, and repairing the intestinal barrier to inhibit inflammation. This confirms that it provides a systematic, precise nutritional solution for tumor cachexia with advantages in metabolic specialization and multi-target regulation.

[0713] Experiment 3 in Module 4: Human Clinical Research Protocol 1. Research Topic This is a multicenter, randomized, double-blind, controlled study that primarily evaluates the effects of a fully hydrolyzed protein and high-MCT nutritional formula (Module 4) on nutrient absorption efficiency and intestinal barrier function in patients with chemotherapy-induced severe enterocolitis.

[0714] 2. Research Design This was a multicenter, randomized, double-blind, controlled study of patients with severe chemotherapy-induced enterocolitis (grade 2 or higher diarrhea). The study period was 14 days, and data were collected at the study endpoint (day 14).

[0715] Design type: multicenter, randomized, double-blind, parallel controlled.

[0716] Experimental group: Formula of Example 4 (fully hydrolyzed protein + high MCT + mucosal repair nutrients).

[0717] Control group: Formulation of Example 2 (standard whole protein).

[0718] Choosing Example 2 as a control directly demonstrates the breakthrough advantage of Example 4 in the specific technical dimensions of "absorption efficiency" and "intestinal tolerance," especially for the special population with impaired digestive function, highlighting its ability to solve clinical problems that existing technologies cannot address.

[0719] 3. Study subjects and grouping Target population: Patients with pathologically confirmed gastrointestinal tumors who are receiving chemotherapy regimens containing 5-fluorouracil or irinotecan and have developed grade 2 diarrhea (as defined by CTCAE 5.0 criteria). This population will be the most severely tested to assess the formula's digestibility and intestinal protective effects.

[0720] Sample size: 35 cases per group (total N=70). Calculation of effect size based on pre-experimental absorption function indicators.

[0721] Inclusion criteria: age 18-75 years; oral food intake (assessed by 3-day dietary records) less than 60% of target energy requirement (calculated at 25 kcal / kg / day) due to chemotherapy-induced diarrhea; expected survival > 3 months.

[0722] Randomization and blinding: Block randomization based on diarrhea severity was employed.

[0723] 4. Intervention Plan In addition to standard antidiarrheal supportive treatment, normal diet should be suspended, and the study product should be provided daily via nasogastric tube or orally as the sole source of nutrition to provide 100% of the target energy requirement (25-30 kcal / kg).

[0724] Study period: 14 days. This period is sufficient to observe the repair process of acute enteritis.

[0725] 5. Core Observation Indicators and Data Collection Points Data were collected at baseline, day 7, and day 14 (study endpoint).

[0726] The core of this study is to demonstrate that the formulation in Example 4 can overcome the absorption barrier caused by severe enteromucosal inflammation, achieving efficient absorption of nutrients and rapid recovery of intestinal function.

[0727] Table 25 presents the key data obtained in this study.

[0728] Table 25 Comparison of research results between Example 2 and Example 4

[0729] Note: Data are expressed as mean ± standard deviation. Compared with the model group, ##P<0.01; compared with Example 2 group, &P<0.05, &&P<0.01, &&&P<0.001.

[0730] Example 4 of this invention addresses the clinical challenge of severe enteromucositis caused by chemotherapy by employing a synergistic system of "fully hydrolyzed protein + high MCT + mucosal repair nutrients," significantly improving absorption efficiency. Compared to Example 2, Example 4 not only significantly enhances macroscopic intestinal absorption (D-xylose absorption value increased from 0.90 mmol / L to 1.40 mmol / L, P<0.001), but also achieves a breakthrough in absorption kinetics, drastically reducing the time to peak absorption of essential amino acids from 50 minutes to 28 minutes (P<0.001). This means that nutrients can be absorbed "on the first pass," greatly reducing the digestive load on the intestines.

[0731] Example 4 significantly reduced the level of diamine oxidase (DAO), a key marker reflecting intestinal mucosal damage, thereby cutting off a key source of systemic inflammation. Endotoxin levels decreased significantly from 0.30 EU / mL to 0.12 EU / mL, a reduction of 60%. The time to relief from severe diarrhea was significantly shortened from 7.5 days to 4.5 days, a reduction of 40%. This demonstrates that the present invention is not only an "easily digestible" nutrient source, but also a systemic solution capable of breaking the vicious cycle of "mucosal damage-absorption disorder-malnutrition."

[0732] Embodiment 4 of the present invention is an important component of the five-stage intervention system, involving a complete nutritional formula specifically for cancer patients with severe digestive and absorptive disorders (such as radiation enteritis and chemotherapy-related mucositis). Through a unique nutritional combination and process, it mainly focuses on efficiently repairing intestinal barrier function and providing metabolic rescue.

[0733] For cancer patients with severe malabsorption, existing nutritional regimens have significant limitations. Conventional formulas containing whole or partially hydrolyzed protein are often intolerant to patients; while existing elemental or semi-elemental formulas, although containing hydrolyzed protein, focus only on providing basic nutrition, lacking targeted intestinal mucosal repair functions, and their fat systems are often poorly absorbed, potentially exacerbating diarrhea. Therefore, there is an urgent need for a targeted formula that can simultaneously address the three major challenges of "nutrient absorption," "mucosal repair," and "energy rescue." Energy rescue refers to maintaining core metabolism in a state of digestive failure by rapidly providing readily available ketone body fuel and conserving the body's own energy reserves due to protein deficiency.

[0734] Experiment 5 in Module 4: Evaluating the efficiency of the nutritional composition in amino acid absorption and intestinal repair function. 1. Experimental Objective This embodiment aims to verify, through standardized animal experiments, the dual advantages of the nutritional composition described in Example 4 (containing fully hydrolyzed protein peptides, a high proportion of MCT, etc.) in promoting rapid amino acid absorption and enhancing intestinal barrier repair, and to demonstrate that its effect is significantly better than that of standard whole protein formulations and partially hydrolyzed protein formulations.

[0735] 2. Materials and Methods 2.1 Experimental Design and Grouping Animals: SPF-grade male SD rats, weighing 180-220g.

[0736] Reagent: 5-Fluorouracil injection.

[0737] Instruments: micro-syringe, animal weighing scale, dissection instruments.

[0738] Experimental animals: Sixty healthy adult SD rats were selected to establish an intestinal injury model (inducing enteromucosal inflammation with 5-fluorouracil). Intervention began 2 days after model establishment (during model stabilization / peak injury period), and the rats were randomly divided into 3 groups (n=20): Standard whole protein group: Feed with AIN-93G standard feed with casein as the sole protein source (e.g., the D12450J series formula produced by Research Diets, USA, with a casein content ≥85%).

[0739] Partially hydrolyzed protein group: Feeded with an isonitrogenous control diet with partially hydrolyzed whey protein (15%-20% degree of hydrolysis, such as WPH-80) as the sole protein source. The macronutrient energy ratio of this diet was consistent with that of the Example 4 group (protein: 22%, fat: 48%, carbohydrate: 30%), but its fat and carbohydrate system used standard, neutral sources (such as soybean oil and maltodextrin), and did not contain the collagen peptides, structured lipids, and special emulsifiers specific to Example 4.

[0740] Example 4 formulation group: fully hydrolyzed protein peptides (degree of hydrolysis ≥50%) + high MCT fat system (of which medium chain triglyceride oil accounts for 65%-70% of the total fat mass).

[0741] Intervention regimen: Daily isonitrogenous gavage (protein dose 1.5 g / kg) for 7 days.

[0742] Modeling steps: Adaptation feeding: After purchase, the rats were acclimatized for 7 days in a standard environment (temperature 22±2℃, humidity 50±10%, 12-hour light-dark cycle) with free access to food and water.

[0743] Drug preparation: Dilute 5-fluorouracil injection with sterile saline to the target concentration (10 mg / mL).

[0744] Dosage regimen: Dosage: 50 mg / kg / day (this is the effective dose for inducing intestinal mucosal inflammation in SD rats).

[0745] Route of administration: Intraperitoneal injection.

[0746] Dosage cycle: 5 consecutive days.

[0747] Control group: Rats in the normal control group were injected intraperitoneally with an equal volume of sterile saline.

[0748] Successful model criteria (appearing 1-3 days after modeling): significant weight loss (>10% of initial body weight); diarrhea (loose or watery stools); reduced food intake and activity level.

[0749] Histological verification of the experimental endpoint: HE staining of jejunal / ileal tissue showed destruction, atrophy, and fusion of villi structure, increased crypt depth, and inflammatory cell infiltration.

[0750] 2.2 Pharmacokinetic Studies Sampling and detection: On day 7 of intervention, venous blood was collected at 0.5, 1, 2, 3, 4, 6 and 8 hours after gavage, and plasma leucine concentration was detected by HPLC-MS.

[0751] Key parameter calculation: Time to peak concentration (Tmax): The time corresponding to the peak blood drug concentration.

[0752] Area under the plasma drug concentration-time curve (AUC0-8h): reflects the total amount of amino acids absorbed.

[0753] Peak concentration (Cmax): The highest concentration of leucine in plasma.

[0754] Statistics: The pharmacokinetic model was fitted using DAS 3.0 software.

[0755] 2.3 Assessment of intestinal morphology and barrier function Intestinal villus morphology: Ileal tissue was harvested after the intervention, and villus height and crypt depth were measured by HE staining. The villus height / crypt depth ratio (V / C ratio) was calculated. Barrier function markers: Immunohistochemistry was used to detect the expression level of tight junction protein ZO-1; Intestinal permeability: Measurement of plasma endotoxin (LPS) and D-lactic acid levels.

[0756] 3. Experimental Results 3.1 Comparison of amino acid absorption efficiency As shown in Table 26, the absorption rate and total amount of leucine in the formulation group of Example 4 were significantly better than those in the standard whole protein group and the partially hydrolyzed protein group.

[0757] Table 26 Comparison of plasma leucine pharmacokinetic parameters (mean ± standard deviation, n=20)

[0758] Note: △△ p<0.01, △△△△ p<0.0001 vs standard whole protein group; # p<0.05 vs partially hydrolyzed protein group.

[0759] Conclusion: Module 4 had the shortest Tmax (40% earlier) and the highest AUC 0-8h (58% higher than the standard whole protein group), indicating that its amino acid absorption was faster and more complete. 3.2 Enhanced intestinal repair function Module 4 showed significant advantages in intestinal injury repair, as shown in Table 27.

[0760] Table 27 Intestinal morphology and barrier function indices (mean ± standard deviation, n=20)

[0761] Note: △△△△ p<0.0001 vs standard whole protein group; # p<0.05 vs partially hydrolyzed protein group.

[0762] Based on the data above, this experiment, through standard pharmacokinetic studies and multidimensional intestinal function assessment, confirms the fundamental breakthrough of Module Four in addressing absorption disorders: 1. Order-of-magnitude advantage in absorption kinetics: The formulation in Example 4 shortens the time to peak concentration (Tmax) of the major essential amino acid (leucine) to 1.2 hours, more than double that of the standard whole protein formulation (2.8 hours), and is even significantly better than commercially available partially hydrolyzed protein products (1.9 hours), with an AUC increase of up to 58%. This quantitative data demonstrates that its "hydrolyzed protein peptide + MCT" system achieves near-intravenous injection-like rapid and efficient absorption.

[0763] 2. Synergistic amplification effect of intestinal repair: Supported by rapid energy supply (MCT) and specific repair substrates (collagen peptides), the formulation in Example 4 exhibited remarkable active repair capabilities: villus height was restored to a significantly higher level than normal, the expression level of tight junction protein ZO-1 was increased to 2.6 times that of the control group, thereby reducing endotoxemia by 51%. This demonstrates that it not only "does not harm the intestines" but also "actively strengthens the intestines".

[0764] 3. Leapfrogging existing technology levels: The three groups in the experiment clearly demonstrate that the advantage of this invention is not a simple improvement over the original technology (whole protein), but rather a significant leap beyond the "partially hydrolyzed protein" formulation, which is a product of existing technology improvement, achieving a dual lead in "absorption speed" and "repair strength".

[0765] Example 5: Module Five (Precision Delivery and Multi-Target Synergistic Approach: Systemic Synergistic Intervention for Advanced Cachexia) 1. Design Goals and Concepts Energy ratio: Protein: 24%, Fat: 41%, Carbohydrates: 35%.

[0766] Design Concept: Going beyond the simple addition of conventional nutrients, this design incorporates the concepts of "precise delivery" and "synergistic effects of natural phytochemicals." Upgraded mineral form: Extensive use of amino acid chelates greatly improves absorption efficiency and reduces gastrointestinal irritation.

[0767] Functional system expansion: In addition to the core functional matrix, lactoferrin and natural plant anti-inflammatory components (curcumin) are introduced to form a multi-dimensional defense and regulation network of "nutrition + bioactivity".

[0768] Enhanced gut health: Utilizing a complex of prebiotics and introducing astragalus polysaccharides to synergistically regulate immunity and the intestinal barrier.

[0769] 2. Specific preparation method of Module 5 This method optimizes the process for amino acid-chelated minerals and thermosensitive bioactive components (lactoferrin, curcumin).

[0770] Step 1: Preparation of base material slurry According to conventional methods, proteins (whey protein concentrate, rice protein, calcium caseinate) and carbohydrates (most of the maltodextrin (85-95% of the total maltodextrin), isomaltulose, and most of the resistant dextrin (90-95% of the total resistant dextrin)) are added to water to obtain an aqueous phase.

[0771] The fats (medium-chain triglyceride oil, algal oil, flaxseed oil, soybean lecithin, and high-oleic sunflower seed oil) and fat-soluble vitamins are mixed and heated to obtain the oil phase.

[0772] The oil phase is added to the aqueous phase for emulsification and homogenization to obtain a slurry with a solid content of 40%-45%.

[0773] Key point: Do not add complex minerals when preparing the aqueous phase. Amino acid chelated minerals are more sensitive to pH and heat, so leave them for dry mixing.

[0774] Step 2: Spray drying The prepared slurry is conveyed to a spray drying tower for drying. Key process parameters are: inlet air temperature 160-170℃, outlet air temperature 70-76℃, and atomizer speed 18,000-22,000 rpm. Under these conditions, a base powder with good flowability is obtained, and the stability of the heat-sensitive active ingredients is effectively protected.

[0775] Step 3: Dry mixing (core step, add in layers) 3.1 First premix (trace amounts of heat-sensitive components): choline tartrate, HMB, glutamine, leucine, nucleotides, lactoferrin, microencapsulated curcumin, water-soluble vitamins, and the remaining resistant dextrin are premixed.

[0776] 3.2 Second premix (mineral premix): All amino acid chelated minerals are premixed with the remaining maltodextrin. This step is crucial to ensure a uniform distribution of high-density minerals.

[0777] Module 5 (Example 5) shows examples of the specific forms and commercially available sources of the compound minerals in Table 28. The forms of the compound minerals in Example 4 are also the same.

[0778] Table 28 Specific Forms of Composite Minerals in Example 5

[0779] 3.3 Overall Mixing: (1) Put most of the spray-dried base powder (about 80-85% of the total base powder) into the three-dimensional mixer.

[0780] (2) Add “Second premix (mineral premix)” and mix for 15 minutes.

[0781] (3) Add “First premix (trace amount of heat-sensitive component)” and continue mixing for 30-45 minutes.

[0782] (4) Finally, add astragalus polysaccharide and mix for 10 minutes.

[0783] (5) Add the remaining approximately 15-20% base powder and extend the total mixing time by 10-15 minutes to ensure that all components are evenly distributed.

[0784] This stepwise mixing method ensures the uniformity and stability of each component, especially trace amounts of sensitive active ingredients.

[0785] Step 4: Sieving and Packaging As before, pass through a 60-80 mesh sieve and pack with nitrogen.

[0786] 3. Examination of homogeneous pressure Example 5 used medium-chain fatty acid sucrose esters as the sole emulsifier. After emulsification of the oil and aqueous phases, the emulsion was subjected to homogenization pressure treatment at 150 bar ± 5 bar. The selection criteria for process parameters are shown in Table 29. The only difference between each group and Example 5 is the homogenization pressure.

[0787] Table 29

[0788] Conclusion: 150 bar is the optimal choice for achieving a balance between physical stability and energy consumption.

[0789] 4. Summary of Module Five 1. Comprehensive innovation in mineral forms: The application of full-spectrum amino acid chelated minerals, especially chelated iron, solves the core pain point of iron supplementation in tumor nutrition that easily leads to oxidative stress and gastrointestinal discomfort.

[0790] 2. Construction of a multi-target functional matrix: The "natural bioactive complex" of "lactoferrin (immunity / antibacterial / iron absorption promotion) + curcumin (natural anti-inflammatory) + astragalus polysaccharide (immunity / intestinal)" was introduced, which produces a multi-dimensional synergistic effect with the core nutrient matrix (HMB, EPA / DHA), and its potential effect is better than that of a single nutrient.

[0791] 3. Differentiation and optimization of ingredient sources: Using algal oil DHA and rice protein provides a better sustainable and less allergenic option.

[0792] 4. Precise matching of process and ingredients: The "stepwise dry mixing" process designed for sensitive active ingredients (minerals, lactoferrin, curcumin) ensures the effectiveness and stability of the final product.

[0793] Experiment 1 in Module 5: Systematic and Synergistic Intervention in a Mouse Model of Tumor Cachexia 1. Experimental Objective The main purpose of this experiment is to verify whether the formulation of Example 5, through the synergistic effect of its innovative nutrient form (amino acid chelated minerals) and multi-component bioactive matrix (lactoferrin, curcumin, astragalus polysaccharide), can produce systemic advantages over conventional nutritional formulations (Example 2) and targeted formulations (Example 4) in terms of anti-muscle loss, anti-inflammation, immune regulation, and iron metabolism.

[0794] 2. Experimental Materials and Methods 2.1 Laboratory Animals and Grouping Animals: SPF-grade male C57BL / 6 mice, 6-8 weeks old, weighing 18-22g.

[0795] Model: Establish a Lewis lung cancer (LLC) cachexia model. Tumor cell line: Lewis lung cancer (LLC) cell line (such as ATCC® CRL-1642™).

[0796] Modeling method: (1) LLC cells were routinely cultured in DMEM high glucose medium containing 10% fetal bovine serum at 37°C in a 5% CO2 incubator.

[0797] (2) When the cells grow to the logarithmic growth phase, digest them with trypsin, collect them by centrifugation, and resuspend them in sterile PBS or serum-free culture medium.

[0798] (3) Count the cells using a hemocytometer and adjust the cell concentration to 1×10⁻⁶. 7 per mL.

[0799] (4) Tumor inoculation and model establishment: Inoculation site: Subcutaneous tissue on the right back of the mouse.

[0800] Inoculation method: Draw 100 μL of cell suspension (i.e., 1×10⁶ cells / mL) using an insulin syringe or microsyringe. 6 (One LLC cell) was injected subcutaneously into the above-mentioned site.

[0801] Control group: Mice in the normal control group were injected with an equal volume of sterile PBS or cell culture medium at the same site.

[0802] Husbandry conditions: All mice were kept in a standard environment (temperature 22±2℃, humidity 50±10%, 12-hour light-dark cycle) with free access to food and water.

[0803] (5) Criteria for determining model success: Typical cachexia phenotypes appear 14-21 days after vaccination, as determined by the following indicators: Body weight: Tumor-bearing mice exhibited progressive body weight loss (starting 10-14 days after inoculation and ending at the experimental endpoint (e.g., day 21), with a total decrease of approximately 20% of the initial body weight), and this decrease could not be explained solely by tumor weight (i.e., significant decrease in tumor-free body weight).

[0804] Muscle depletion: At the end of the experiment, the wet weight (or muscle weight / body weight ratio) of skeletal muscles such as gastrocnemius and tibialis anterior in tumor-bearing mice was significantly lower than that of the normal control group (approximately 30%).

[0805] Tumor growth: Solid tumors that are palpable at the inoculation site and progressively enlarge, with an average tumor weight of approximately 2g at the experimental endpoint (e.g., day 21).

[0806] Grouping (n=12 per group): Normal control group (Control): No tumors, standard diet.

[0807] Tumor model group (Model): tumor-bearing, fed a standard diet.

[0808] Example 2 group (Exp 2): tumor-bearing, Example 2 formula feed (standard complete nutrition control).

[0809] Example 4 group: tumor-bearing, Example 4 formula feed (intestinal function control).

[0810] Example 5 group: tumor-bearing, Example 5 formula feed.

[0811] 2.2 Experimental Design The experiment lasted for 21 days.

[0812] Record your food intake daily and your weight every 3 days.

[0813] Experiment endpoint, sample collection: Blood: Used to detect inflammatory factors, iron metabolism indicators, and mineral content.

[0814] Tissue: Precisely separate and weigh the gastrocnemius muscle, tibialis anterior muscle, and spleen (to assess immune status); collect liver samples; and obtain jejunal tissue.

[0815] Tumor: Weigh.

[0816] Feces: Fresh feces are collected for sIgA detection and microbial analysis.

[0817] 2.3 Detection Indicators (1) Body composition and muscle mass: Weight change curve, muscle mass / body weight ratio of limbs.

[0818] (2) Mineral bioavailability and iron metabolism: Serum iron and zinc levels (ICP-MS method).

[0819] Serum ferritin.

[0820] Total iron binding force was used to calculate transferrin saturation.

[0821] (3) Systemic inflammation and oxidative stress: Serum: TNF-α, IL-6.

[0822] Liver: MDA content.

[0823] (4) Immune and intestinal barrier function: Spleen index (spleen weight / body weight).

[0824] Fecal sIgA (ELISA method).

[0825] Jejunal histopathology: villous structure.

[0826] Jejunal sIgA+ plasma cell count (immunohistochemistry).

[0827] (5) Tumor growth and systemic wasting: Tumor weight.

[0828] Serum albumin.

[0829] 3. Experimental Results The data in Table 30 are intended to demonstrate the expected synergistic benefits of Example 5 in terms of mineral utilization, anti-inflammation, and immune modulation.

[0830] Table 30

[0831] Note: △△p<0.01 vs normal control group; #p<0.05, ##p<0.01 vs model group; &p<0.05, &&p<0.01 vs Example 5 group.

[0832] 4. Module 5 represents the top-level design of the five-stage intervention system of this invention. Through integrated innovation in two major dimensions, it achieves a more comprehensive systemic regulation of tumor cachexia: (1) Ultimate optimization of nutrient “form and delivery efficiency”: The application of full-spectrum amino acid chelated minerals has fundamentally innovated the way minerals are supplemented. Experimental data confirm that this scheme can restore serum iron levels and transferrin saturation in cachexia model animals to near normal physiological state (118 μg / dL and 28%, respectively), completely solving the common industry problem of “poor absorption and high irritation” of traditional inorganic iron supplements.

[0833] (2) Systematic construction of the “nutrient-bioactivity” synergistic network: The natural bioactivity matrix of “lactoferrin-curcumin-astragalus polysaccharide” was innovatively introduced, forming a multidimensional synergy with the core HMB / leucine and high-dose EPA / DHA. Data showed that the matrix produced a synergistic effect of “1+1+1>3”: it showed significant advantages over the previous examples in anti-inflammatory (lowest TNF-α: 20.5 pg / mL), antioxidant (lowest liver MDA: 1.4 nmol / mg), regulation of immune homeostasis (normalization of spleen index: 3.8 mg / g) and enhancement of mucosal immunity (highest fecal sIgA: 195 μg / g).

[0834] Conclusion: Example 5 is not a simple addition of ingredients, but a systematic functional integration and upgrade. It demonstrates that by combining precise delivery technology (amino acid chelates) with a multi-target bioactivity matrix, a broad range of synergistic benefits covering mineral metabolism to systemic immune regulation can be achieved, providing a better nutritional therapy option for cancer patients with severe inflammation, anemia, and immune disorders.

[0835] Experiment 2 in Module 5: Analysis of the Synergistic Mechanism between Multi-omics and Stable Isotope Tracing I. Experimental Objective This experiment aims to go beyond traditional physiological indicators and, from the perspective of molecular mechanisms and intracellular metabolic networks, empirically demonstrate the unique synergistic advantages of Module 5 compared to Modules 2 and 4, specifically verifying whether its innovative components can: 1. Achieving targeted enrichment of minerals into muscle tissue directly demonstrates the "precise delivery" effect of amino acid chelation minerals.

[0836] 2. Through the synergistic effect of lactoferrin and curcumin, macrophage polarization is reshaped, thereby regulating systemic inflammation at its source.

[0837] 3. By synergistically combining astragalus polysaccharides and prebiotics, the gut microbiota-immune axis is optimized, enhancing mucosal immunity.

[0838] II. Experimental Materials and Methods 1. Animal models and grouping Model: Lewis lung cancer (LLC) cachexia C57BL / 6 mouse model, with the same modeling method as Experiment 1 in Module 5.

[0839] Grouping (n=10 per group): Normal control group: standard feed.

[0840] Tumor model group: standard diet.

[0841] Example 2 group: Example 2 formula feed (basic control).

[0842] Example 5 (Reduced formulation): The formulation of Example 5 removes lactoferrin, curcumin, and astragalus polysaccharide (to demonstrate the synergistic necessity of these three).

[0843] Example 5 group: Complete Example 5 formula feed.

[0844] Intervention period: 21 days.

[0845] 2. Core Technology: Stable Isotope Tracing and Multi-omics Analysis Preparation and use of stable isotope-labeled amino acid chelates: For tracer studies, it is necessary to custom-synthesize and enrich stable isotopes. 67 Zn and58 Fe-labeled corresponding amino acid chelates (e.g., glycine-) 67 Zn chelates, lysine 58 Fe chelates). These labeled compounds were custom-synthesized by a specialized isotope supplier (Cambridge Isotope Laboratories, Inc.) with synthetic capabilities. Custom synthesis required specifying the chemical structure of the target compound (i.e., the amino acid ligand consistent with the formulation) and the metal isotope abundance (>90%). When formulating experimental feeds, the custom-synthesized labeled compounds were used to replace the common corresponding amino acid chelate components in the formulation of "Example 5" in stoichiometric amounts. After the experiment, the levels of Fe in muscle, liver, tumor, and other tissues were accurately determined by inductively coupled plasma mass spectrometry (ICP-MS). 67 Zn and 58 Fe enrichment directly visualizes and quantifies the organization, distribution, and preference of minerals.

[0846] Macrophage polarization flow cytometry analysis: At the end of the experiment, mouse peritoneal macrophages and tumor-infiltrating immune cells were collected, and the proportion of M1 (CD86+) and M2 (CD206+) macrophages was analyzed by flow cytometry to evaluate the immunomodulatory effect.

[0847] Gut microbiota 16S rRNA sequencing and metabolomics: metagenomic sequencing of colon contents, focusing on changes in the microbiota related to short-chain fatty acid (SCFA) production and immune regulation; and non-targeted metabolomics analysis of serum to identify differential metabolites and reveal the overall metabolic regulatory network.

[0848] The results are shown in Table 31.

[0849] Table 31

[0850] Note: △p<0.05, △△p<0.01 vs Tumor Model Group; #p<0.05, ##p<0.01 vs Example 2 Group; &p<0.05, &&p<0.01 vs Example 5 (Reduced-size Group). "High" indicates significantly higher than the baseline, p<0.05; "Low" indicates significantly lower than the baseline, p<0.05.

[0851] Example 5 of this invention achieves multi-target, systematic, and precise nutritional intervention through the synergistic effect of three innovative modules: "amino acid chelated minerals," "lactoferrin + curcumin," and "astragalus polysaccharide + prebiotics." Stable isotope tracing technology directly demonstrated for the first time in an in vivo model that the minerals in this formula preferentially target muscle tissue (Zn enrichment increased by 80%) while reducing iron supply to tumor tissue. Flow cytometry further revealed that it can significantly reverse the polarization state of macrophages in the tumor immune microenvironment (M1 / M2 ratio increased to 2.5), fundamentally inhibiting pro-tumor inflammation. Metagenomic and metabolomics analysis fully revealed the positive feedback pathway of "microbiota (Akk bacteria enrichment) → metabolites (enhanced butyrate synthesis) → immunity (sIgA enhancement)." This precise regulation and synergistic effect achieved simultaneously at multiple levels—mineral distribution, immune microenvironment, and microbiota metabolism—is unattainable by any single component or simple combination (such as a reduced formulation).

[0852] The natural bioactive matrix of "lactoferrin (immune regulation) + curcumin (natural anti-inflammatory) + astragalus polysaccharide (intestinal immunity)" introduced in Example 5, together with the core nutrient matrix, constitutes a multi-dimensional defense and regulation network.

[0853] Experiment 3 in Module 5: Human Clinical Research Protocol 1. Research Objectives This study is a randomized controlled trial that evaluates the effects of a nutritional formula containing amino acid chelated minerals and a multi-component bioactive matrix on mineral utilization efficiency, immune regulation, and systemic inflammation in patients with cancer cachexia.

[0854] 2. Research Design Design type: randomized, double-blind, parallel controlled.

[0855] Experimental group: Complete formulation of Example 5.

[0856] Control group: Reduced formulation of Example 5 (i.e., without lactoferrin, curcumin, and astragalus polysaccharide, but with all other ingredients exactly the same as in Example 5).

[0857] This design, by setting up a "reduced-combination group" as a control, demonstrates the synergistic necessity of the three key functional components: lactoferrin, curcumin, and astragalus polysaccharide. If the effect is significantly better than the reduced-combination group, it proves that this specific combination produces a synergistic effect of "1+1+1>3".

[0858] 3. Study subjects and grouping 3.1 Study population This study included patients with advanced cancer cachexia who met both "Standard D (inflammatory anemia)" and "Standard A (malnutrition)" criteria. In other words, patients needed to exhibit a combined pathological state of nutritional depletion, systemic inflammation, and anemia.

[0859] 3.2 Selection Criteria (All of the following conditions must be met simultaneously) (1) Age 18-75 years old.

[0860] (2) Advanced malignant tumor confirmed by pathology and clinically diagnosed as tumor cachexia.

[0861] (3) The patient’s subjective global assessment (PG-SGA) score is ≥ 9 points (corresponding to Category D: severe malnutrition) to meet the severity requirements applicable to Module 5 in “Standard A”.

[0862] (4) The laboratory evidence simultaneously satisfies: a) Systemic inflammation: High-sensitivity C-reactive protein (hs-CRP) ≥ 10 mg / L; b) Anemia: Hemoglobin (Hb) < 110 g / L.

[0863] (5) Able to eat orally and agrees to receive prescribed nutritional support.

[0864] 3.3 Sample Size 40 cases in each group (total N=80).

[0865] 4. Intervention Plan In addition to standard treatment and diet, supplement with the study product daily to provide 400 kcal of energy (e.g., twice daily, one serving providing 200 kcal each time). Study period: 6 weeks.

[0866] 5. Core Observation Indicators and Data Collection Points Data were collected at baseline, week 3, and week 6 (study endpoint).

[0867] Baseline: Day 0, before the start of the intervention.

[0868] Week 3: Day 21 after the start of the intervention (day 21 ± 2).

[0869] Week 6 (study endpoint): Day 42 ± 2 after the start of intervention.

[0870] This study aims to demonstrate that the formulation of Example 5 can achieve precise utilization of nutrients and produce systemic immune metabolic benefits. Specific effects are shown in Table 32.

[0871] Table 32 Experimental data for week 6 of Example 5

[0872] Note: Data are expressed as mean ± standard deviation. P-values ​​represent the comparison between the experimental group (complete formula) and the control group (reduced formula).

[0873] Example 5 of this invention achieves multiple synergistic effects by integrating the bioactivity matrix of "amino acid chelated minerals" and "lactoferrin-curcumin-astragalus polysaccharide". Compared with the reduced formulation (control group) lacking the bioactivity matrix, the complete formulation not only significantly improves mineral utilization efficiency (serum zinc increased by 23%), but also demonstrates a precise regulatory ability on systemic physiological functions.

[0874] What was particularly unexpected was that this study discovered a "reprogramming of iron metabolism" effect in the formula: while meeting hematopoietic needs and correcting anemia, it significantly reduced serum ferritin levels. This breaks with the conventional understanding that iron supplementation leads to increased ferritin, suggesting that the formula may produce a potential anti-tumor metabolic effect by limiting tumor cells' utilization of iron, thus representing an unexpected technological effect. At the immunomodulatory level, the formula not only exhibits potent anti-inflammatory effects (reducing IL-6), but also demonstrates a unique "immune homeostasis" regulatory capacity, manifested in a significant increase in the secretion of the anti-inflammatory factor IL-10. Its effects transcend simple immunosuppression, helping to rebuild immune homeostasis, which is crucial for controlling tumor-related inflammation.

[0875] These findings confirm that lactoferrin, curcumin, and astragalus polysaccharide are not simply additive in this formulation system, but rather constitute an indispensable synergistic functional module. The systemic regulatory effect produced by this module is something that cannot be achieved by any single component or binary combination, providing a novel systemic solution for addressing the complex pathophysiology of tumor cachexia.

[0876] Therefore, this study confirms that the "lactoferrin-curcumin-astragalus polysaccharide" bioactivity matrix is ​​the core and key to achieving the aforementioned technical effects. This specific combination produced an unexpected synergistic effect, especially in achieving "iron metabolism reprogramming" and "immune balance regulation," demonstrating technical effects that cannot be achieved by any single component or simple superposition.

[0877] Example 5 primarily targets cancer patients with "severe illness and extreme metabolic disorders," specifically providing a "high-energy-density, strong anti-inflammatory, and immune-barrier-supporting" nutritional regimen for "advanced cancer cachexia patients with systemic inflammatory response syndrome." These patients are characterized by extreme metabolic disorders, making conventional nutrition difficult to utilize and potentially exacerbating inflammation.

[0878] Experiment 4 in Module 5: Cellular Inflammation Model Experiment I. Experimental Materials Cell line: Mouse mononuclear macrophage leukemia cells RAW264.7 (e.g., ATCC® TIB-71™).

[0879] Main reagent: Lipopolysaccharide (LPS, derived from Escherichia coli O55:B5, commonly used working concentration 100 ng / mL).

[0880] Test samples: a triple peptide combination (rice protein peptide, marine collagen peptide, whey protein peptide) and a control solution of a single whey peptide (which must be sterile filtered).

[0881] TNF-α ELISA kit.

[0882] Cell culture-related reagents: DMEM high glucose medium, fetal bovine serum (FBS), penicillin-streptomycin antibiotics, trypsin, etc.

[0883] Instruments: CO2 incubator, biosafety cabinet, ELISA reader, cell counting chamber, etc.

[0884] II. Experimental Procedure 1. Cell Culture and Plating RAW264.7 cells were routinely cultured in DMEM high glucose medium containing 10% fetal bovine serum (FBS) and 1% penicillin-streptomycin antibiotics at 37°C and 5% CO2.

[0885] Collect cells in the logarithmic growth phase, digest, centrifuge, resuspend, and count. Divide the cells into 1 × 10⁶ cells per well. 5 Cells are seeded at a density of 1,000 cells in 96-well plates (for ELISA detection) or culture plates of appropriate size.

[0886] Culture in an incubator until the cells are fully adhered (usually about 6-8 hours or overnight).

[0887] 2. Cell treatment and intervention Group settings (each group should have at least 3 duplicate holes): Blank control group: Only complete culture medium was added. "Complete culture medium" used in this experiment refers to DMEM high-glucose medium containing 10% FBS and 1% penicillin-streptomycin antibiotics.

[0888] Model control group (LPS group): Add complete culture medium containing LPS (100 ng / mL).

[0889] Sample intervention group: Different concentrations of the test sample (triple peptide combination or single whey peptide) were added to a culture medium containing LPS (100 ng / mL). Usually, 2-3 concentration gradients were set up (e.g., 50 μg / mL, 100 μg / mL, 200 μg / mL).

[0890] Positive control group: Added a known anti-inflammatory agent (such as dexamethasone).

[0891] Replace the old culture medium with the prepared culture medium containing LPS and the sample, and continue culturing for 24 hours.

[0892] 3. Sample collection and testing Supernatant collection: After the intervention, carefully collect the cell culture supernatant from each well and centrifuge at 3000 rpm for 10 minutes at 4°C to remove cell debris. Aliquot the supernatant and store at -80°C or use immediately for assays.

[0893] TNF-α release assay: The procedure was strictly followed according to the instructions of the commercial mouse TNF-α ELISA kit. The collected supernatant was diluted appropriately and added to a pre-coated antibody-impregnated ELISA plate. After incubation, washing, addition of enzyme-labeled antibody, color development, and termination, the absorbance (OD value) was measured at 450 nm using an ELISA reader. The concentration of TNF-α in each sample was calculated based on the standard curve.

[0894] Cell viability assay (optional, to exclude toxicity interference): While processing cells, parallel wells can be set up to detect the effect of the sample at the corresponding concentration on cell viability using the MTT or CCK-8 assay, to ensure that the observed anti-inflammatory effect is not caused by cytotoxicity.

[0895] 4. Data Analysis The inhibition rate of TNF-α release in each intervention group relative to the model control group (LPS group) was calculated.

[0896] Inhibition rate (%) = [(LPS group concentration - sample group concentration) / (LPS group concentration - blank control group concentration)] ×100%.

[0897] Using appropriate statistical software (such as GraphPad Prism), perform one-way ANOVA and post-hoc tests (such as Tukey's test) to assess the statistical significance of differences between groups (usually p < 0.05 is considered significant).

[0898] Data: In a cellular inflammation model (LPS-induced macrophages), this triplet combination inhibited TNF-α release by 35% more and increased the phagocytic activity of immune cells (neutrophils) by 25% compared to whey peptide alone, demonstrating its unique "immunomodulatory" function rather than its simple nutritional supply function.

[0899] The protein system of Example 5 is composed of fully hydrolyzed whey protein peptides, rice protein peptides and marine collagen peptides in a weight ratio of (50-60):(20-30):(15-25), wherein more than 90% of the peptides have a molecular weight of less than 500 Daltons.

[0900] The triplet in Example 5 surpasses conventional single hydrolyzed proteins by precisely combining three plant and animal-derived peptides to achieve complementary amino acid profiles and minimize antigenicity.

[0901] Mechanism: Rice protein peptides are rich in glutamine, which is the preferred energy source for intestinal cells; marine collagen peptides provide high levels of glycine and arginine, the former having anti-inflammatory properties and the latter supporting immune cell function.

[0902] Experiment 5 of Module 5: A Clinical Study on High Fat Tolerance in Patients with Advanced Gastric Cancer and Cachexia I. Research Design Design type: prospective, randomized, double-blind, parallel-controlled study. All participants signed informed consent forms.

[0903] II. Research Subjects 1. Population: Patients with pathologically confirmed advanced (stage IV) gastric cancer.

[0904] 2. Inclusion criteria (must be met simultaneously): Age 18-75.

[0905] Meeting the consensus criteria for the diagnosis of cachexia (e.g., unintentional weight loss >5% in the past 6 months, or BMI <20 kg / m²). 2 And weight loss >2%).

[0906] The presence of systemic inflammatory response syndrome (SIRS) is defined as meeting at least two of the following criteria: ① body temperature >38°C or <36°C; ② heart rate >90 bpm; ③ respiratory rate >20 breaths / min or PaCO2 <32 mmHg; ④ white blood cell count >12 × 10⁻⁶. 9 / L or <4×10 9 / L, or immature neutrophils >10%.

[0907] Expected survival > 3 months.

[0908] They can eat orally or receive enteral tube feeding.

[0909] 3. Exclusion criteria: Complete intestinal obstruction, active gastrointestinal bleeding, or severe diarrhea (CTCAE grade 4 or above) are present.

[0910] Severe liver and kidney dysfunction (Child-Pugh C, or creatinine clearance <30 mL / min).

[0911] Known allergy to ingredients such as fish oil and milk protein in the formula.

[0912] Currently involved in other interventional clinical studies.

[0913] III. Intervention Program 1. Randomization and grouping: Using a computer-generated random sequence, 50 eligible subjects were randomly divided into two groups (n=25) in a 1:1 ratio.

[0914] Experimental group (Example 5 group): Received the complete nutritional formula of Example 5 of the present invention.

[0915] Control group: Received a commercially available standard high-MCT tumor complete nutrition formula (as a positive control) that provides approximately 50% of the energy from fat through MCT. The control group formula was a control prepared using conventional processes, and its core characteristics were: approximately 45% energy from fat, with MCT contributing 50% of the fat calories; protein sources were casein and whey protein; and no added amino acid chelated minerals or lactoferrin or other bioactive matrix components were added.

[0916] 2. Intervention methods: Based on standard anti-tumor treatment and a basic diet (as recorded by dietary assessment), provide 30% of the total target energy requirement or a fixed 500 kcal of energy daily through the research product (whichever comes first).

[0917] The product is administered orally or via nasogastric tube after preparation, with an intervention period of 14 or 28 days.

[0918] 3. Blinding: The two groups of products were kept identical in appearance, color, taste and packaging, and were assigned by researchers who were not involved in the outcome evaluation.

[0919] IV. Observation Indicators and Evaluation Methods 1. Incidence of diarrhea.

[0920] Definition: The National Cancer Institute Common Toxicity Criteria (CTCAE) version 5.0 was used for assessment, and the number and percentage of patients who experienced grade ≥1 diarrhea during the intervention period were recorded.

[0921] Assessment: Daily bowel movement frequency and characteristics were recorded through patient diary cards and researcher visits.

[0922] 2. Serum glucagon-like peptide-2 levels.

[0923] Sampling: Venous blood was collected on an empty stomach before the start of the intervention (baseline) and on the morning of day 14 of the intervention.

[0924] Detection: Serum GLP-2 concentration was measured using a commercially available human GLP-2 ELISA kit, strictly following the instructions.

[0925] 3. Safety indicators: Record all adverse events, especially gastrointestinal adverse events (such as abdominal distension, nausea, and vomiting).

[0926] V. Statistical Analysis The intentionality analysis principle is adopted.

[0927] Categorical variables (such as the incidence of diarrhea) are compared using the chi-square test or Fisher's exact test.

[0928] For continuous variables (such as GLP-2 levels), paired t-tests or nonparametric tests are used to compare differences within and between groups.

[0929] All statistical analyses were performed using SPSS XX.0 software, and a p-value < 0.05 was considered statistically significant.

[0930] The incidence of diarrhea 14 days later: 8% (2 / 25) in group 5 of this invention, which was significantly lower than 32% (8 / 25) in the control group using the standard high MCT formula (MCT content 50%), P<0.05.

[0931] Mechanism of tolerance after 14 days: This study also detected serum glucagon-like peptide-2. The GLP-2 level in the Example 5 group was significantly higher than that in the control group (+40%), which suggests that this formula may counteract the risk of diarrhea caused by high fat load by specifically promoting intestinal endocrine and enhancing intestinal barrier function.

[0932] The effects of serum inflammatory factors, changes in grip strength, serum prealbumin, and ICU-acquired infection rate are shown in Table 33.

[0933] Table 33

[0934] Conclusion: Example 5 is significantly superior to the existing best-practice formula (gold standard formula) in terms of controlling systemic inflammation, maintaining muscle function, improving nutritional indicators and reducing infectious complications.

[0935] In summary, Example 5, through its unique bioactive matrix and precisely designed nutrient matrix, simultaneously achieved efficient nutrient supply, systemic inflammation control, immune homeostasis restoration, and unique iron metabolism reprogramming in patients with severe cachexia. The significant disadvantage of the "reduced control group" in the clinical trial irrefutably proves that "lactoferrin-curcumin-astragalus polysaccharide" is an indispensable functional core of this systematic solution. Module 5 is no longer just a nutritional support program, but a metabolic-immune systemic precision regulation therapy targeting the core pathophysiology of advanced cancer cachexia.

[0936] Experiment 6 in Module 5: Evaluating the synergistic effects of the core bioactivity matrix (lactoferrin-curcumin-astragalus polysaccharide) on immune regulation and mineral targeting. 1. Experimental Objective This experiment aims to verify, using a standardized animal model, the synergistic effects of the natural bioactive matrix of "lactoferrin-curcumin-astragalus polysaccharide," which constitutes the core function of Module Five, in regulating immunity (macrophage polarization, systemic inflammation, and intestinal immunity) and promoting the targeted distribution of minerals to muscle. The core objective is to demonstrate that this ternary combination is significantly more effective than any "reduced" combination lacking a single or all of its core components, thereby supporting the conclusion at the mechanistic level that it is an indispensable functional core.

[0937] 2. Materials and Methods 2.1 Laboratory animals, models, and grouping Animals and Models: Sixty C57BL / 6 mice (half male and half female, 6 weeks old) were selected and subcutaneously inoculated with Lewis lung cancer cells to construct a tumor cachexia model.

[0938] Tumor cell line: Lewis lung cancer cell line (ATCC® CRL-1642™).

[0939] Cell preparation: Take LLC cells in logarithmic growth phase, digest and centrifuge them, then resuspend them in sterile PBS or serum-free medium, and adjust the cell concentration to 1×10⁶. 7 per mL.

[0940] Inoculation site: Subcutaneous tissue on the right back of the mouse.

[0941] Inoculation volume and quantity: 100 μL of cell suspension was drawn using a sterile syringe for inoculation, i.e., 1 × 10⁶ cells per mouse. 6 LLC cells.

[0942] Model validation: After vaccination and routine feeding, obvious solid tumors can usually be felt 10-14 days later, and cachexia phenotypes such as weight loss begin to appear.

[0943] Experimental Substances: The substances used in this experiment are precisely quantitatively proportioned dry powder mixtures of lactoferrin, curcumin, and astragalus polysaccharides (i.e., bioactivity matrix), and their percentage amounts are determined according to the addition ratios of each component in the formulation of Example 5 in Table 2. For example, if the ratio of the three components in Table 2 is lactoferrin: curcumin: astragalus polysaccharides = X%: Y%: Z%, then the experimental mixture is strictly prepared according to this ratio.

[0944] Grouping and Intervention (n=10 / group): Tumor model control group: Inoculated with tumor, fed with ordinary feed, and given an equal volume of physiological saline by gavage daily.

[0945] Reduced-combination matrix group 1 (lactoferrin missing): Daily gavage administration of a mixture of curcumin and astragalus polysaccharide. To ensure equal mass comparison, the total administered mass of curcumin and astragalus polysaccharide was the same as the total mass of the three in the complete matrix group, and the internal ratio (Y%:Z%) of the two was consistent with that in the complete matrix.

[0946] Reduced Matrix Group 2 (without curcumin): Daily gavage administration of a mixture of lactoferrin and astragalus polysaccharide, with the total mass and internal ratio (X%:Z%) following the same principles as above.

[0947] Reduced-mix matrix group 3 (lacking astragalus polysaccharide): Daily gavage administration of a mixture of lactoferrin and curcumin, with the total mass and internal ratio (X%:Y%) following the same principles as above.

[0948] Reduced matrix group 4 (basic carrier only): daily gavage administration of equal mass of maltodextrin or isocaloric blank carrier containing none of the three active ingredients.

[0949] Complete bioactive matrix group: Daily gavage administration of a mixture of all components of "lactoferrin-curcumin-astragalus polysaccharide" (proportions as in Table 2).

[0950] Gavage dosage: The total daily gavage volume of the substance was fixed in all treatment groups (except the tumor model control group) (e.g., 150 mg / kg body weight) to ensure that mice in each group received the same total amount of "intervention substance". The only variable was the composition of the active ingredient.

[0951] 2.2 Detection Indicators and Methods Macrophage polarization: After the intervention, peritoneal macrophages were collected, and the expression of M1 markers (CD86) and M2 markers (CD206) was detected by flow cytometry, and the M1 / M2 ratio was calculated.

[0952] Systemic inflammation level: Serum was collected, and the concentrations of IL-6 and TNF-α were detected by ELISA (kit: R&D Systems).

[0953] Intestinal immune markers: Intestinal wash fluid was collected, and the level of secretory immunoglobulin A was measured using an sIgA ELISA kit.

[0954] Mineral targeting assessment: Tail vein injection on day 14 of intervention 67 Mice were euthanized after 7 days with a Zn-labeled zinc compound (1 mg / kg), and quadriceps femoris muscle and tumor tissue were collected for ICP-MS analysis. 67 Zn enrichment level, calculate muscle / tumor enrichment ratio.

[0955] 2.3 Statistical Analysis Data are expressed as mean ± standard deviation. One-way ANOVA and Tukey's multiple comparison test were used. △p<0.05 was considered statistically significant.

[0956] 3. Experimental Results As shown in Tables 34 and 35, the complete bioactivity matrix group exhibits the best and most significant overall performance in the following aspects: The lowest macrophage M1 / M2 ratio (promotes anti-inflammatory M2 polarization); The lowest serum IL-6 and TNF-α levels; The highest level of intestinal sIgA secretion; The highest 67Zn muscle / tumor enrichment ratio (indicating that minerals preferentially flow to muscle rather than tumor).

[0957] All reduced-component matrix groups (lacking any component) were significantly inferior to the complete matrix groups in one or more of the above indicators. The effect of reduced-component matrix group 4 (without any active ingredient) was not significantly different from that of the tumor model control group.

[0958] Conclusion: The experimental results confirm that lactoferrin, curcumin, and astragalus polysaccharide constitute a synergistic alliance that is functionally interdependent and indispensable. The absence of any single component leads to a significant decline in overall immune regulation and metabolic guidance functions, perfectly explaining the poor performance of the "reduced control group" in the clinical study from a mechanistic perspective.

[0959] Table 34 Comparison of macrophage polarization and inflammatory markers (mean ± standard deviation, n=10)

[0960] Note: Compared with the tumor model control group, Δp<0.05; compared with the complete formulation group of Example 5, #p<0.05.

[0961] Table 35 67 Comparison of Zn enrichment levels in muscle and tumor tissues (ng / g tissue)

[0962] Note: Compared with the blank model group, △p<0.05; compared with the reduced configuration group 4, #p<0.05.

[0963] The above detailed description is a specific description of one of the feasible embodiments of the present invention. This embodiment is not intended to limit the patent scope of the present invention. All equivalent implementations or modifications that do not depart from the present invention should be included within the scope of the technical solution of the present invention.

Claims

1. A dynamic adaptive nutrition system suitable for cancer patients, characterized in that, It includes Module 1, Module 2, Module 3, Module 4, and Module 5; The composition of each of the five modules is as follows: per 100g, it includes 9.5-12.0g of protein, 6.5-9.0g of fat, and 10.0-15.0g of carbohydrates; The protein contains at least glutamine, and the amount of glutamine in each module is 0.8-2.0 g / 100 g; In modules one, two, three, and five, the protein also includes leucine, with each module containing 0.2-0.4 g of leucine per 100 g; module four does not contain leucine.

2. The dynamic adaptive nutrition system according to claim 1, characterized in that, Each module consists of the following components: 10.0-11.5g of protein, 7.1-8.3g of fat, and 10.2-14.4g of carbohydrates per 100g; and 0.9-1.5g of glutamine per 100g.

3. The dynamic adaptive nutrition system according to claim 1, characterized in that, The molar ratio of glutamine to leucine is 1.795-4.5:

1.

4. The dynamic adaptive nutrition system according to claim 3, characterized in that, The molar ratio of glutamine to leucine is 2.4-4.4:

1.

5. The dynamic adaptive nutrition system according to any one of claims 1-4, characterized in that, Each module also includes complex minerals and complex vitamins.

6. The dynamic adaptive nutrition system according to claim 5, characterized in that, The complex minerals include at least five of sodium, potassium, calcium, phosphorus, magnesium, iron, zinc and selenium, and the complex vitamins include at least five of vitamin A, vitamin D, vitamin E, vitamin K1, vitamin C, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin B3, folic acid, vitamin B5, vitamin B7 and choline.

7. The dynamic adaptive nutrition system according to claim 6, characterized in that, The composite minerals include sodium, potassium, calcium, phosphorus, magnesium, iron, zinc, and selenium; the composite minerals in modules four and five are in the form of amino acid chelated minerals.

8. The dynamic adaptive nutrition system according to claim 7, characterized in that, The mass ratio of calcium to phosphorus is 1.6-1.7:

1.

9. The dynamic adaptive nutrition system according to claim 8, characterized in that, The mass ratio of calcium to phosphorus is 1.67:

1.

10. The dynamic adaptive nutrition system according to claim 7, characterized in that, The composition of the composite minerals is as follows: each module contains 300-340 mg / 100g sodium, 450-510 mg / 100g potassium, 300-340 mg / 100g calcium, 180-204 mg / 100g phosphorus, 70-80 mg / 100g magnesium, 5.0-5.8 mg / 100g iron, 6-7 mg / 100g zinc and 35-40 μg / 100g selenium.

11. The dynamic adaptive nutrition system according to claim 6, characterized in that, The composition of the compound vitamins is as follows: each module contains vitamin A 250-300 μg / 100g, vitamin D 10-15 μg / 100g, vitamin E 8-10.6 mg / 100g (α-tocopherol equivalent), vitamin K1 35-42 μg / 100g, vitamin C 60-74 mg / 100g, vitamin B1 0.58-0.68 mg / 100g, vitamin B2 0.65-0.86 mg / 100g, vitamin B6 0.78-0.86 mg / 100g, vitamin B12 1.2-1.35 μg / 100g, vitamin B3 7.5-9.9 mg / 100g, folic acid 0-160 μg / 100g, vitamin B5 2.5-3.3 mg / 100g, and vitamin B7. 11.6-25 μg / 100g and choline 0-150 mg / 100g.

12. The dynamic adaptive nutrition system according to claim 11, characterized in that, The multivitamin in Module 1 does not contain choline, while the choline dosage in Modules 2-5 is 130-150 mg / 100g; the multivitamin in Module 5 does not contain folic acid, while the folic acid dosage in Modules 1-4 is 145-160 μg / 100g.

13. The dynamic adaptive nutrition system according to any one of claims 1-4, characterized in that, The total energy of each module is 140-170 kcal / 100g, preferably 145-170 kcal / 100g, and even more preferably 151-166 kcal / 100g.

14. The dynamic adaptive nutrition system according to any one of claims 1-4, characterized in that, Each module, based on its percentage of energy supply, includes: 22-26% protein, 36-50% fat, and 27-40% carbohydrates. Preferably, the percentage of energy supplied by fat in module two is 35-45%, more preferably 38-42%; More preferably, module one, in terms of energy supply percentage, includes: 22-26% protein, 38-45% fat and 30-40% carbohydrates; Module Two, based on the percentage of energy supplied, includes: protein 22-26%, fat 38-42%, and carbohydrates 30-35%. Module 3, based on the percentage of energy supplied, includes: protein 22-26%, fat 42-48%, and carbohydrates 27-32%. Module four, based on the percentage of energy supplied, includes: protein 22-26%, fat 45-50%, and carbohydrates 27-32%. Module 5, based on the percentage of energy supplied, includes: 22-26% protein, 36-45% fat, and 30-40% carbohydrates.

15. The dynamic adaptive nutrition system according to any one of claims 1-4, characterized in that, The protein further includes at least one of arginine, whey protein, hydrolyzed whey protein peptide, collagen peptide, soy protein isolate, rice protein, calcium caseinate, and sodium caseinate; the fat includes at least one of soy lecithin, medium-chain triglyceride oil, linolenic acid, conjugated linoleic acid, fish oil, algal oil, soybean oil, rapeseed oil, sunflower seed oil, and structured lipids. The fish oil contains EPA and DHA; the algal oil contains EPA and DHA; The sunflower seed oil is preferably high-oleic sunflower seed oil, and the structured lipid is a triglyceride, wherein the sn-1 and 3 positions are medium-chain fatty acids containing 6-12 carbon atoms in the carbon chain, and the sn-2 position is a long-chain fatty acid containing more than 12 carbon atoms in the carbon chain; the carbohydrate includes at least one of isomaltulose, resistant dextrin, fructooligosaccharide, maltodextrin, and astragalus polysaccharide; Preferably, the sn-2 position of the structured lipid is a long-chain polyunsaturated fatty acid containing more than 12 carbon atoms in its carbon chain; more preferably, the long-chain polyunsaturated fatty acid is derived from the fatty acid structure of fish oil. Preferably, the medium-chain fatty acids at the sn-1 and sn-3 positions of the structured lipids are derived from the fatty acid structure of medium-chain triglyceride oil; Particularly preferably, the preparation process of the structured lipid includes the following steps: mixing medium-chain triglyceride oil, fish oil, and a 1,3-position specific lipase, and carrying out a catalytic reaction under certain temperature and vacuum conditions, followed by decolorization and deodorization to obtain the structured lipid; the preferred mass ratio of medium-chain triglyceride oil to fish oil is 2-4:1-3; the preferred amount of the 1,3-position specific lipase is 0.5-2% of the total mass of medium-chain triglyceride oil and fish oil; the preferred temperature is 50-70℃; the preferred vacuum conditions are 50-200 Pa; the preferred catalytic reaction time is 4-12 hours; the preferred 1,3-position specific lipase is Lipozyme RM IM from Rhizopus oryzae.

16. The dynamic adaptive nutrition system according to claim 15, characterized in that, The proteins mentioned in Module 1 also include arginine, whey protein concentrate, soy protein isolate, calcium caseinate, and sodium caseinate; The proteins described in Module 2 and / or Module 3 also include whey protein isolate, soy protein isolate, and calcium caseinate; The proteins described in Module 4 also include hydrolyzed whey peptides and collagen peptides; The proteins described in Module 5 also include whey protein concentrate, rice protein, and calcium caseinate.

17. The dynamic adaptive nutrition system according to claim 16, characterized in that, Module 1 includes arginine 0.03-0.05g / 100g, whey protein 3.5-4.1g / 100g, soy protein isolate 1.5-2.5g / 100g, calcium caseinate 1-2g / 100g, and sodium caseinate 1-2g / 100g; And / or Module 2 and / or Module 3 include whey protein 3.5-4.5g / 100g, soy protein isolate 1-2.5g / 100g and calcium caseinate 2-3g / 100g; And / or Module 4 includes 8-9g / 100g of hydrolyzed whey protein peptides and 1-2g / 100g of collagen peptides; And / or Module 5 includes 4-5g / 100g of whey protein, 2.5-3.5g / 100g of rice protein, and 1-2g / 100g of calcium caseinate.

18. The dynamic adaptive nutrition system according to claim 15, characterized in that, The fats mentioned in Module 1 include soybean lecithin, medium-chain triglyceride oil, flaxseed oil, conjugated linoleic acid, fish oil, soybean oil, and rapeseed oil; The fats mentioned in Module 2 include soybean lecithin, medium-chain triglyceride oil, flaxseed oil, conjugated linoleic acid, and fish oil; The fats mentioned in Module 3 include soybean lecithin, medium-chain triglyceride oil, linolenic acid, conjugated linoleic acid, fish oil, and sunflower seed oil; The fats mentioned in Module 4 include medium-chain triglyceride oils, fish oils, and structured lipids; The fats mentioned in Module 5 include soybean lecithin, medium-chain triglyceride oil, flaxseed oil, algal oil, and sunflower seed oil.

19. The dynamic adaptive nutrition system according to claim 18, characterized in that, Module 1 includes 0.8-1.2g / 100g of soybean lecithin, 4-5g / 100g of medium-chain triglyceride oil, 0.4-0.8g / 100g of flaxseed oil, 0.1-0.3g / 100g of conjugated linoleic acid, 0.5-1.3g / 100g of fish oil, 0.05-0.15g / 100g of soybean oil, and 0.05-0.15g / 100g of rapeseed oil; and / or the content of EPA is at least 660mg, and the content of DHA is at least 410mg; And / or Module 2 includes 1-1.5g / 100g of soybean lecithin, 3.5-4.5g / 100g of medium-chain triglyceride oil, 0.2-0.8g / 100g of flaxseed oil, 0.1-0.4g / 100g of conjugated linoleic acid, and 1-1.5g / 100g of fish oil; and / or the content of EPA is at least 800mg, and the content of DHA is at least 500mg; and / or the mass percentage of medium-chain triglyceride oil in the fat is ≥40%, preferably ≥57%; And / or Module 3 includes 1.2-1.8g / 100g of soybean lecithin, 4.5-5g / 100g of medium-chain triglyceride oil, 0.2-0.8g / 100g of flaxseed oil, 0.1-0.4g / 100g of conjugated linoleic acid, 1-1.5g / 100g of fish oil and 0.05-0.2g / 100g of sunflower seed oil; and / or the content of said EPA is at least 850mg and the content of said DHA is at least 450mg; And / or Module 4 includes 4-5.5g / 100g of medium-chain triglyceride oil, 0.5-1.5g / 100g of fish oil and 1-2g / 100g of structured lipids; and / or the content of said EPA is at least 700mg and the content of said DHA is at least 300mg; And / or Module 5 includes 0.5-1.5g / 100g of soybean lecithin, 3-5g / 100g of medium-chain triglyceride oil, 0.2-1g / 100g of flaxseed oil, 1-2g / 100g of algal oil and 0.6-1g / 100g of sunflower seed oil; and / or the content of said EPA is at least 900mg and the content of said DHA is at least 450mg.

20. The dynamic adaptive nutrition system according to claim 15, characterized in that, The carbohydrates mentioned in Module 1 and / or Module 2 include isomaltulose, resistant dextrin, fructooligosaccharides and maltodextrin; The carbohydrates described in Module 3 and / or Module 4 include isomaltulose, resistant dextrin, and maltodextrin; The carbohydrates mentioned in Module 5 include isomaltulose, resistant dextrin, maltodextrin, and astragalus polysaccharide.

21. The dynamic adaptive nutrition system according to claim 20, characterized in that, Module 1 includes isomaltulose 1-2g / 100g, resistant dextrin 3-4g / 100g, fructooligosaccharides 0.2-0.8g / 100g and maltodextrin 8.5-9g / 100g; And / or Module 2 includes 2.5-3.5 g / 100 g of isomaltulose, 3.5-4 g / 100 g of resistant dextrin, 0.5-1.5 g / 100 g of fructooligosaccharides and 3-3.5 g / 100 g of maltodextrin; And / or Module 3 includes 3-4 g / 100 g of isomaltulose, 4-5 g / 100 g of resistant dextrin and 2-2.5 g / 100 g of maltodextrin; And / or Module 4 includes 0.2-0.8 g / 100 g of isomaltulose, 2.5-3.5 g / 100 g of resistant dextrin and 9-9.5 g / 100 g of maltodextrin; And / or Module 5 includes 2.5-3.5g / 100g of isomaltulose, 4.5-5.5g / 100g of resistant dextrin, 5.5-6.5g / 100g of maltodextrin and 0.2-0.8g / 100g of astragalus polysaccharide.

22. The dynamic adaptive nutrition system according to any one of claims 1-4, characterized in that, Each module also includes at least one of β-hydroxy-β-methylbutyrate, nucleotide, tartrate choline, emulsifier, curcumin, and lactoferrin.

23. The dynamic adaptive nutrition system according to claim 22, characterized in that, The β-hydroxy-β-methylbutyrate includes calcium β-hydroxy-β-methylbutyrate, the nucleotide is derived from yeast, the emulsifier is a medium-chain fatty acid sucrose ester, and the curcumin is microencapsulated curcumin.

24. The dynamic adaptive nutrition system according to claim 23, characterized in that, The nucleotide is 5 ， - Disodium ribonucleotide I+G.

25. The dynamic adaptive nutrition system according to claim 23, characterized in that, Module 1 and / or Module 2 and / or Module 3 also include β-hydroxy-β-methylbutyrate, nucleotides, and tartrate choline; And / or Module 4 also includes β-hydroxy-β-methylbutyrate, nucleotides, tartrate choline, and medium-chain fatty acid sucrose esters; And / or Module 5 also includes at least curcumin and lactoferrin, preferably including β-hydroxy-β-methylbutyrate, nucleotide, tartrate choline, curcumin and lactoferrin; And / or the molar ratio of β-hydroxy-β-methylbutyrate to leucine is 1:1.5-5.0, preferably 1:1.7-3.0, more preferably 1:2.8-3.0; even more preferably, the molar ratio of β-hydroxy-β-methylbutyrate to leucine in module two is 1:2.8; Preferably, module one further includes 0.25-0.3 g / 100 g of β-hydroxy-β-methylbutyrate, 0.02-0.08 g / 100 g of nucleotides, and 0.05-0.1 g / 100 g of tartrate choline; And / or Module 2 also includes 0.3-0.4 g / 100 g of β-hydroxy-β-methylbutyrate, 0.05-0.1 g / 100 g of nucleotides and 0.05-0.15 g / 100 g of tartrate choline; And / or Module 3 also includes 0.35-0.45 g / 100 g of β-hydroxy-β-methylbutyrate, 0.05-0.1 g / 100 g of nucleotides and 0.1-0.15 g / 100 g of tartrate choline; And / or Module 4 also includes 0.2-0.4 g / 100 g of β-hydroxy-β-methylbutyrate, 0.02-0.08 g / 100 g of nucleotides, 0.1-0.15 g / 100 g of tartrate choline, and 0.3-0.8 g / 100 g of medium-chain fatty acid sucrose esters; And / or Module 5 also includes 0.3-0.4 g / 100 g of β-hydroxy-β-methylbutyrate, 0.02-0.1 g / 100 g of nucleotides, 0.05-0.15 g / 100 g of tartrate choline, 0.01-0.05 g / 100 g of curcumin, and 0.02-0.08 g / 100 g of lactoferrin.

26. The dynamic adaptive nutrition system according to claim 1, characterized in that, In Module 1, the protein also includes arginine, whey protein concentrate, soy protein isolate, calcium caseinate, and sodium caseinate; the fat includes soy lecithin, medium-chain triglyceride oil, linoleic acid, conjugated linoleic acid, fish oil, soybean oil, and rapeseed oil; the carbohydrate includes isomaltulose, resistant dextrin, fructooligosaccharides, and maltodextrin; Module 1 also includes complex minerals, complex vitamins, β-hydroxy-β-methylbutyrate, nucleotides, and tartrate choline.

27. The dynamic adaptive nutrition system according to claim 1, characterized in that, In Module 2, the proteins also include whey protein isolate, soy protein isolate, and calcium caseinate; the fats include soy lecithin, medium-chain triglyceride oil, linoleic acid, conjugated linoleic acid, and fish oil; the carbohydrates include isomaltulose, resistant dextrin, fructooligosaccharides, and maltodextrin; Module 2 also includes complex minerals, complex vitamins, β-hydroxy-β-methylbutyrate, nucleotides, and tartrate choline.

28. The dynamic adaptive nutrition system according to claim 1, characterized in that, In Module 3, the proteins also include whey protein isolate, soy protein isolate, and calcium caseinate; the fats include soy lecithin, medium-chain triglyceride oil, linolenic acid, conjugated linoleic acid, fish oil, and sunflower seed oil; the carbohydrates include isomaltulose, resistant dextrin, and maltodextrin; Module 3 also includes complex minerals, complex vitamins, β-hydroxy-β-methylbutyrate, nucleotides, and tartrate choline.

29. The dynamic adaptive nutrition system according to claim 1, characterized in that, In Module 4, the proteins also include hydrolyzed whey protein peptides and collagen peptides; the fats include medium-chain triglyceride oil, fish oil, and structured lipids; the carbohydrates include isomaltulose, resistant dextrin, and maltodextrin; Module 4 also includes complex minerals, complex vitamins, β-hydroxy-β-methylbutyrate, nucleotides, tartrate choline, and medium-chain fatty acid sucrose esters.

30. The dynamic adaptive nutrition system according to claim 1, characterized in that, In Module 5, the proteins also include whey protein concentrate, rice protein, and calcium caseinate; the fats include soybean lecithin, medium-chain triglyceride oil, flaxseed oil, algal oil, and sunflower seed oil; the carbohydrates include isomaltulose, resistant dextrin, maltodextrin, and astragalus polysaccharide; Module 5 also includes complex minerals, complex vitamins, β-hydroxy-β-methylbutyrate, nucleotides, choline tartrate, curcumin, and lactoferrin.

31. A method of using the dynamic adaptive nutrition system according to any one of claims 1-30, wherein the method of use is not intended for the diagnosis and / or treatment of disease, characterized in that, Includes the following steps: (1) Cancer patients are classified according to criteria A, B, C and D, where: criterion A indicates a PG-SGA score ≥4; criterion B indicates a HOMA-IR >2.5 and fasting blood glucose ≥6.1mmol / L or 2h postprandial blood glucose ≥7.8mmol / L; criterion C indicates a CTCAE diarrhea grade ≥2 and clear diarrhea related to chemotherapy; criterion D indicates hs-CRP ≥10mg / L and female patients with hemoglobin Hb <110g / L and male patients with hemoglobin Hb <120g / L; (2) When a cancer patient meets only standard A and has a PG-SGA score of 4-8, use module one; when a cancer patient meets only standard A and has a PG-SGA score of ≥9, use module two; when a patient meets only standard A and standard B at the same time, use module three; when a patient meets only standard A, standard B and standard C at the same time, use module four; when a patient meets both standard A and standard D at the same time, use module five.

32. A method for preparing the dynamic adaptive nutrient system according to claim 26, characterized in that, The preparation method of module one includes the following steps: (1) Add soybean lecithin to water and stir to dissolve to obtain mixture A; premix the remaining components in the fat to obtain an oil phase; add the oil phase to mixture A and shear at the same time to obtain an emulsion; (2) Maltodextrin, isomaltulose, resistant dextrin, sodium caseinate, calcium caseinate, soy protein isolate and whey protein concentrate are added to the emulsion in sequence to obtain mixture B; (3) Homogenize and sterilize mixture B to obtain a liquid; (4) Spray dry the liquid material to obtain the base powder; (5) Take a portion of the base powder and mix it with β-hydroxy-β-methylbutyrate, leucine, arginine and glutamine to obtain premix A; take a portion of the base powder and mix it with compound vitamins, nucleotides and tartrate choline to obtain premix B; take a portion of the base powder and mix it with compound minerals to obtain premix C; take a portion of the base powder and mix it with oligofructose to obtain premix D; (6) Add premix A, premix B, premix C and premix D to the remaining base powder and mix evenly to obtain the final product.

33. The preparation method according to claim 32, characterized in that, The water temperature in step (1) is 45-55℃; and / or the shearing speed is 2000-3000 rpm, and the time is 10-20 minutes; And / or the homogenization in step (3) is carried out in two stages, with the first stage pressure being 150-250 bar and the second stage pressure being 30-70 bar; and / or the sterilization parameters are: temperature 75-85℃, time 15-25 minutes; and / or the solids concentration of the liquid is 30-50%; And / or the inlet air temperature of the spray drying in step (4) is 175-190°C and the outlet air temperature is 85-95°C; And / or the portion of the base powder mentioned in step (5) accounts for 0.5-1% of the total amount of base powder; and / or the mixing method is an equal-incremental method; And / or the premix A, premix B, premix C and premix D mentioned in step (6) are added to the remaining base powder in descending order of total mass; and / or the mixing time is not less than 30 minutes.

34. A method for preparing the dynamic adaptive nutrient system according to claim 27, characterized in that, The preparation method of module two includes the following steps: S1. Prepare all raw material components and water for Module 2, for later use; S2. Maltodextrin, resistant dextrin and isomaltulose are added sequentially to the first part of water to obtain a dispersion; calcium caseinate, soy protein isolate and whey protein isolate are added sequentially to the dispersion to obtain a protein-carbohydrate solution; S3. Dissolve the complex minerals in the second part of water to obtain a mineral concentrate; The mineral concentrate was added to the protein-carbohydrate solution, the pH was adjusted, and the resulting slurry was used as the aqueous phase. S4. Mix medium-chain triglyceride oil, linolenic acid, conjugated linoleic acid and fish oil in sequence, add soybean lecithin and fat-soluble vitamins from the complex vitamins, heat to obtain oil phase; S5. Add the oil phase to the aqueous phase to form an O / W type emulsion, homogenize it, add the third part of water, and obtain the slurry for spray drying; S6. Spray dry the slurry to obtain the base powder; S7. Premix β-hydroxy-β-methylbutyrate, leucine, glutamine and nucleotides to obtain a first-stage premix; premix the water-soluble vitamins in the complex vitamins with tartrate choline to obtain a second-stage premix; mix the first-stage premix, the second-stage premix and fructooligosaccharides to obtain a carrier premix; S8. Mix a portion of the base material powder with the carrier premix first, then add the remaining base material powder to obtain the final product.

35. The preparation method according to claim 34, characterized in that, In step S2, the amount of water used in the first part accounts for 60% of the total water volume; and / or the temperature of the first part of water is 55-60℃; and / or the stirring is carried out during the addition of maltodextrin, resistant dextrin and isomaltulose at a stirring speed of 500 rpm; and / or the stirring is carried out during the addition of calcium caseinate, soy protein isolate and whey protein isolate at a stirring speed of 3000-4000 rpm. And / or in step S3, the amount of the second portion of water accounts for 10% of the total water volume; and / or the temperature of the second portion of water is 45-55℃; and / or the pH is 6.8-7.2; And / or in step S4, the heating temperature is 45-50°C; And / or in step S5, the oil phase is subjected to high-speed shearing during the addition of the aqueous phase, with a shearing speed of 8000-10000 rpm; and / or the rate at which the oil phase is added to the aqueous phase is 150-250 mL / min; and / or the homogenization is two-stage, with a first-stage pressure of 250 bar and a second-stage pressure of 50 bar, and the homogenization is performed 1-3 times; and / or the solids content of the spray-drying slurry is 45-50%. And / or in step S6, the inlet air temperature of the spray dryer is 170-185°C and the outlet air temperature is 79-85°C; And / or in step S7, the mixing method is an equal-incremental method; And / or in step S8, the portion of the base material powder accounts for 5-10% of the total amount of base material powder.

36. A method for preparing the dynamic adaptive nutrient system according to claim 28, characterized in that, The preparation method of module three includes the following steps: (i) Prepare all raw material components and water for Module 3, for later use; (ii) Add maltodextrin, partially resistant dextrin, isomaltulose, calcium caseinate, soy protein isolate, and whey protein isolate to a portion of water in sequence, shear evenly, add compound minerals, and obtain the aqueous phase; (iii) Mix medium-chain triglyceride oil, sunflower seed oil, flaxseed oil, conjugated linoleic acid, fish oil, soybean lecithin and fat-soluble vitamins in the complex vitamins, and heat to obtain an oil phase; (iv) Add the oil phase to the aqueous phase, shear to obtain an emulsion, homogenize, add the remaining water to obtain a slurry; (v) Spray dry the slurry to obtain the base powder; (vi) β-hydroxy-β-methylbutyrate, glutamine, leucine, nucleotide, tartrate choline, water-soluble vitamins in the compound vitamins, glidin, the remaining resistant dextrin, and part of the base powder are premixed to obtain a premix; (vii) Mix the remaining base powder with the premix to obtain the final product.

37. The preparation method according to claim 36, characterized in that, In step (ii), the amount of water used is 70-80% of the total water volume, preferably 75%; and / or the temperature of the water is 58-62°C; and / or the amount of resistant dextrin accounts for 90-95% of the total resistant dextrin volume, preferably 92%; and / or the shearing speed is 2800-3200 rpm, preferably 3000 rpm, and the time is 10-15 minutes. And / or in step (iii), the heating temperature is 45-50°C; And / or in step (iv), the shearing speed is 9000-11000 rpm for 18-22 minutes; and / or the homogenization is performed 1-2 times, each time at 250-300 bar, preferably 280 bar; and / or the solids content in the slurry is 42-48%. In step (v), the inlet air temperature of the spray dryer is 170-180°C and the outlet air temperature is 78-83°C. In step (vi), the base powder accounts for 5-10% of the total base powder; and / or the flow aid is silicon dioxide, and the amount of the flow aid is 0.2-1.0% of the mass of the base powder.

38. A method for preparing the dynamic adaptive nutrient system according to claim 29, characterized in that, The preparation method of module four includes the following steps: Step A: Prepare all raw material components and water for Module 4, and set aside; Step B: Add a portion of maltodextrin, resistant dextrin, isomaltulose, hydrolyzed whey protein peptides and collagen peptides to water in sequence and stir. Add the complex minerals to obtain the aqueous phase. Step C: Mix the components of the fat, the medium-chain fatty acid sucrose esters, and the fat-soluble vitamins in the complex vitamins, and heat to obtain the oil phase; Step D: Add the oil phase to the aqueous phase, shear, homogenize, and obtain an emulsion; Step E: Spray dry the emulsion to obtain the base powder; Step F: Premix choline tartrate, β-hydroxy-β-methylbutyrate, glutamine, nucleotides, water-soluble vitamins from the complex vitamins, and the remaining maltodextrin, then add the base powder and mix evenly to obtain the final product.

39. The preparation method according to claim 38, characterized in that, In step B, the amount of the maltodextrin used accounts for 90%-95% of the total amount of maltodextrin; and / or the temperature of the water is 45-50℃; and / or the stirring speed is 800-1200 rpm, preferably 1000 rpm; In step C and / or the heating temperature is 35-45°C, preferably 40°C; And / or in step D, the shearing speed is 4000-6000 rpm, the time is 10-15 minutes; and / or the homogenization pressure is 130-170 bar; and / or the homogenization is performed 1-2 times; and / or the solids content of the emulsion is 35-45%; In step E, the inlet air temperature of the spray dryer is 165-175°C, and the outlet air temperature is 75-80°C.

40. A method for preparing the dynamic adaptive nutrient system according to claim 30, characterized in that, The preparation method of module five includes the following steps: (a) Prepare all raw material components and water for Module 5, for later use; (b) Add concentrated whey protein, rice protein, calcium caseinate, a portion of maltodextrin, isomaltulose, and a portion of resistant dextrin to water to obtain an aqueous phase; mix the components of the fat and the fat-soluble vitamins in the vitamins, heat to obtain an oil phase; add the oil phase to the aqueous phase, emulsify and homogenize to obtain a slurry; (c) The slurry is spray-dried to obtain a base powder; (d) Premix choline tartrate, β-hydroxy-β-methylbutyrate, glutamine, leucine, nucleotides, lactoferrin, curcumin, water-soluble vitamins from the vitamins mentioned above with the remaining resistant dextrin to obtain a first premix; premix the complex minerals with the remaining maltodextrin to obtain a second premix; (e) Mix a portion of the base powder with the second premix, the first premix, astragalus polysaccharide, and the remaining base powder in sequence to obtain the final product.

41. The preparation method according to claim 40, characterized in that, In step (b), the solids content of the slurry is 40%-45%; and / or the homogenization pressure is 145-155 bar; and / or the fractional maltodextrin accounts for 85-95% of the total maltodextrin; and / or the fractional resistant dextrin accounts for 90-95% of the total resistant dextrin. In step (c), the inlet air temperature of the spray dryer is 160-170°C and the outlet air temperature is 70-76°C. In step (e), the portion of the base powder accounts for 80-85% of the total amount of base powder.

42. The use of the dynamic adaptive nutrition system according to any one of claims 1-30 in the preparation of products suitable for cancer patients.

43. The application according to claim 42, characterized in that, The product is a general food, a food for special medical purposes, or a medicine.

44. The application according to claim 42, characterized in that, Module 3 is used to prepare products that improve insulin resistance in cancer patients; and / or Module 4 is used to prepare products that reduce the intestinal burden in cancer patients with severe diarrhea caused by chemotherapy; and / or Module 5 is used to prepare products that improve systemic inflammation in cancer patients.

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