Special full-nutrient formula mousse product for tumor patients and preparation method of mousse product

Abstract

The invention discloses a full-nutrient formula mousse product special for tumor patients and a preparation method, and relates to the technical field of full-nutrient mousse, and the preparation method comprises the following steps: preparing lipidosome coated with nutrients, preparing nanoparticles coated with trace elements, modifying the surfaces of the lipidosome and the nanoparticles with a targeting substance, and preparing the full-nutrient formula mousse product. All the raw materials are mixed to prepare the full-nutrient mousse, and the full-nutrient mousse has the advantages that some nutrients which have an auxiliary effect on tumor treatment but are poor in stability or difficult to absorb in gastrointestinal tracts are wrapped in nano-particles through a nanotechnology; the surface of the nano-particles is modified with a targeting substance which can be specifically recognized and taken by tumor tissues or immune cells, so that the concentration of the nutrients in a tumor microenvironment or an immune regulation site is improved, the action effect of the nutrients is enhanced, vitamin C is prepared into a nano-liposome wrapped form and is added into mousse, and the mousse has the effect of improving the tumor microenvironment or immune regulation site. Liposome can protect vitamin C from being damaged by gastric acid and enable the vitamin C to be more effectively absorbed by intestinal tracts.

Description

Technical Field

[0001] The invention relates to the technical field of complete nutrition mousse, in particular to a complete nutrition formula mousse product specially used for tumor patients and a preparation method thereof. Background Art

[0002] The current situation of malnutrition in cancer patients is very serious. Cancer can cause malnutrition in patients through a variety of physiological mechanisms. First, the rapid proliferation of tumors will consume a large amount of nutrients in the body. Second, tumors also affect the patient's appetite and digestive function. For example, various anti-tumor treatments lead to weakened eating desire and digestive function. Third, cancer patients will cause inflammatory reactions in the body, releasing a series of cytokines such as TNF-a, IL-1 and IL-6, interfering with the normal nutritional metabolism process, resulting in a decrease in the ability to utilize sugar, accelerated protein decomposition, and increased consumption of muscle and fat tissues.

[0003] Swallowing disorders are also an important cause of nutritional intake disorders. This symptom is common in many cancer patients, especially those with central nervous system and head and neck tumors. It is mostly caused by abnormal oropharyngeal movements due to pathological factors such as central nervous system dysfunction and muscle lesions, or swallowing disorders caused by abnormal anatomical structures such as the mouth, pharynx, larynx, and esophagus. More importantly, poor chewing and swallowing functions will not only limit food choices and reduce the pleasure and ability of eating, but also lead to complications such as aspiration and pneumonia. The main way to overcome the insufficient nutritional intake of this group of people is to use nasogastric feeding or gastrostomy, which increases the difficulty and cost of nursing to a certain extent, and also greatly reduces the quality of life of this group of people.

[0004] Traditional chemotherapy drugs will circulate throughout the body after entering the human body, not only acting on tumor cells, but also causing damage to normal tissue cells, triggering a series of serious side effects. For this reason, we propose a complete nutritional formula mousse product and preparation method specifically for cancer patients. Summary of the invention

[0005] The purpose of the present invention is to provide a complete nutritional formula mousse product specially for tumor patients and a preparation method thereof.

[0006] In order to solve the problems raised in the above background technology, the present invention provides the following technical solutions: a complete nutritional formula mousse product specially for tumor patients and a preparation method thereof, comprising preparing liposomes encapsulated with nutrients, preparing nanoparticles encapsulated with trace elements, modifying the surfaces of liposomes and nanoparticles with targeting substances, and preparing the complete nutritional mousse after mixing various raw materials. The specific operation steps of the preparation method of the complete nutritional formula mousse product specially for tumor patients are as follows:

[0007] Step 1: Prepare protein, carbohydrate, fat and additive raw materials;

[0008] Step 2: preparing liposomes, and encapsulating fat-soluble and water-soluble nutrients in the liposomes at the same time;

[0009] Step 3: preparing nanoparticles using biodegradable polymer materials, and encapsulating the trace elements in the polymer nanoparticles in the form of nanoparticles;

[0010] Step 4: Modifying the surface of liposomes and polymer nanoparticles with targeting agents;

[0011] Step 5: premixing dry raw materials, dissolving and emulsifying fat, and mixing dry and wet raw materials and fat emulsion;

[0012] Step 6: After seasoning and flavoring, make it into a mousse shape and package the prepared mousse product.

[0013] As a further solution of the present invention: in the step 1, the whey protein in the whey is extracted by ultrafiltration technology, polysulfone is selected as the material of the ultrafiltration membrane, the pore size of the ultrafiltration membrane is selected between 1nm and 100nm, the pressure during ultrafiltration is set to 0.1MPa-0.5MPa, the temperature is set to 40℃-50℃, the whey is passed through the ultrafiltration membrane at a speed of 1m / s-5m / s to separate the whey protein, and the whey protein solution is obtained after ultrafiltration, the whey protein solution is dried by spray drying, and the whey protein solution is sprayed through a high-pressure nozzle The whey protein solution is dried by injecting hot air at a temperature of 150°C to 200°C in a countercurrent flow to the whey protein solution in a mist form, thereby obtaining a powdered whey protein product. Maltodextrin is used as a carbohydrate source, and soybean oil, olive oil, fish oil and medium-chain triglycerides are used as fat sources. Vitamin A, vitamin C, vitamin E and B vitamins (including vitamin B1, B2, B6 and B12) are prepared, as well as trace elements of selenium and iodine.

[0014] As a further scheme of the present invention: in the step 2, the lipid is dissolved in an organic solvent at a temperature of 30°C-40°C, and at the same time, a fat-soluble vitamin solution of vitamins A, D, E and K is dissolved in an organic solvent containing lipids, the concentration of the lipid in the organic solvent is set to 10 mg / mL-50 mg / mL, chloroform is selected as the organic solvent, soybean lecithin and cholesterol are selected as the lipids, and the ratio of the amount of soybean lecithin to the amount of cholesterol is 2-5:1, and at the same time, 1%-10% of the total lipid amount of maleimide-phospholipid is dissolved in chloroform, vitamin C and B group water-soluble vitamins are dissolved in a buffer solution to form an aqueous phase solution, the buffer solution is a phosphate buffer, and the ratio of the organic solvent to the phosphate buffer is 2:1. The volume ratio is between 3-10:1, a phosphate buffer solution containing water-soluble vitamins is added to an organic solvent solution containing lipids, the mixed solution is mixed by ultrasonic stirring, the ultrasonic power is set to 100W-500W, the ultrasonic time is 5min-15min, a water-in-oil (W / O) emulsion is formed, the addition ratio of water-soluble vitamins to fat-soluble vitamins is 10-20:1, and after uniform mixing, the emulsion is added to a rotary evaporator, the temperature of the rotary evaporator is set to 30°C-50°C, the vacuum degree is set to 0.08MPa-0.1MPa, the organic solvent in the emulsion is evaporated, and the emulsion undergoes a phase transition to form a liposome with a water-in-oil-in-water (W / O / W) structure.

[0015] As a further scheme of the present invention: in the step three, the polymer nanoparticles are prepared by an emulsification-solvent volatilization method, a biodegradable polymer is dissolved in an organic solvent, stirred at a temperature of 20°C-30°C for 3h-5h, and the stirring speed is set to 300r / min-500r / min, the polymer is selected from polylactic acid-glycolic acid copolymer, and the organic solvent is selected from dichloromethane, and the concentration of polylactic acid-glycolic acid copolymer in dichloromethane is 10g / L-20g / L, and then selenium and iodine fat-soluble trace elements are dissolved in the organic solvent containing the biodegradable polymer to obtain an organic phase containing fat-soluble trace elements, an emulsifier with a concentration of 1g / L-5g / L is dissolved in deionized water, and the emulsifier is selected from polyvinyl alcohol, and then zinc and iron water-soluble trace elements are dissolved in the deionized water containing the emulsifier to obtain an organic phase containing water-soluble trace elements. The organic phase is added dropwise into the aqueous phase at a speed of 1 mL / min-2 mL / min, and the solution is stirred at 1000 r / min-3000 r / min with a high-speed stirrer for 5 min-10 min to form an oil-in-water (W / O) emulsion. The emulsion is added into a rotary evaporator, and the temperature of the rotary evaporator is set to 30°C-40°C, the rotation speed is set to 50 r / min-100 r / min, and the vacuum degree is set to 0.08 MPa-0.1 MPa. As the organic solvent evaporates, the emulsion system changes, and the polymer gradually aggregates to form nanoparticles. The nanoparticles are collected by centrifugation, and the centrifugal speed is set to 10000 r / min-20000 r / min. After centrifugation for 10 min-30 min, the supernatant is sucked out with a pipette to obtain nanoparticles containing trace elements.

[0016] As a further scheme of the present invention: in the step 4, the targeting substance is connected to the surface of the liposome using the thiol-maleimide click chemistry method, and the liposomes formed by rotary evaporation can expose the maleimide group on the surface of the liposomes. The thiol-modified peptide segment is selected as the targeting substance, and the thiol-containing targeting substance is dissolved in a buffer solution at a concentration of 0.01 mol / L-0.1 mol / L. The peptide segment solution is added to the liposome solution connected with the maleimide group for reaction, and the molar ratio of the peptide segment to the liposome is 1-10:1. The pH value of the reaction system is controlled between 6.5 and 7.5. During the reaction, a magnetic stirrer is used to stir at a speed of 60r / min-100r / min for 2h-6h. After the reaction, the liposomes are separated by high-speed centrifugation, the speed of the centrifuge is set to 5000r / min-10000r / min, and the centrifugation time is set to 10min-30min. After the centrifugation, the supernatant is sucked out using a rubber-tipped pipette to obtain a modified liposome precipitate.

[0017] As a further scheme of the present invention: in the step 4, a phosphate with a pH value between 7.0 and 8.5 is used as a buffer solution, nanoparticles containing trace elements are dispersed in the buffer solution to prepare a nanoparticle dispersion, a trans-cyclooctene-PEG4-active ester reagent is selected, the active ester reagent is added to the nanoparticle dispersion, the molar ratio of the active ester reagent to the amino group on the surface of the nanoparticle is 1.2-1.5:1, the reaction is carried out at a temperature of 20°C-30°C for 12h-24h, a magnetic stirrer is used to stir at a speed of 60r / min-100r / min during the reaction, after the reaction, the target molecule is added to the nanoparticle dispersion connected with the active ester reagent, the reaction is carried out at a temperature of 20°C-30°C for 12h-24h, a magnetic stirrer is used to stir at a speed of 60r / min-100r / min during the reaction, and after the reaction, the target molecule is added to the nanoparticle dispersion connected with the active ester reagent, the reaction is carried out at a temperature of 20°C-30°C for 12h-24h, a magnetic stirrer is used to stir at a speed of 60r / min-100r / min during the reaction, and after the reaction, the nanoparticles are passivated by a dialysis method, and the concentration is 10mol / L-100mol / L. l / L phosphate is used as the dialysate, and the dialysis bag containing the nanoparticles is added into the dialysis container containing the phosphate dialysis solution. The volume of the phosphate dialysis solution is 50-100 times the volume of the nanoparticles. The dialysis time is set to 12-24h, and the phosphate dialysis solution is replaced every 4h. After the dialysis is completed, the modified nanoparticles are obtained in the dialysis bag.

[0018] As a further scheme of the present invention: in the step five, the dry raw materials of flour, milk powder, powdered sugar, salt, baking soda and baking powder are added into the blender, and stirred at a speed of 50 r / min-150 r / min for 3 min-5 min, butter, corn oil and animal fat fat raw materials are added into the blender, and lecithin accounting for 0.5%-5% of the total mass of fat is added, and stirred at a speed of 200 r / min-500 r / min for 5 min-10 min, the mixed dry raw materials, modified nanoparticles and modified liposome precipitate are added to the container where the emulsified fat emulsion is located, and stirred at a speed of 200 r / min-300 r / min for 5 min-10 min to obtain a uniformly mixed mousse paste.

[0019] As a further scheme of the present invention: in the step six, fruit puree accounting for 10%-20% of the total amount of the mousse is selected as a seasoning, the fruit puree is added to the mousse paste and mixed, and then the seasoned mousse paste is mixed with the whipped cream, and a silicone spatula is used to flip upward from the bottom of the container to form a uniform mousse shape, and the mousse is squeezed into a self-supporting bag using a piping bag. The self-supporting bag has an easy-tear opening and a capacity set to 50g-100g. The outer layer of the self-supporting bag is made of polyester material, the middle layer is made of aluminum foil material, and the inner layer is made of polyethylene material, and the raw materials, nutritional ingredients, production date and storage information of the mousse are printed on the outer layer.

[0020] In addition, the present invention also provides a special complete nutritional formula mousse product for tumor patients and a method for preparing the special complete nutritional formula mousse product for tumor patients: the special complete nutritional formula mousse product for tumor patients uses liposomes to encapsulate fat-soluble and water-soluble nutrients, uses polymer nanoparticles to encapsulate trace elements, and connects targeting objects on the surface of liposomes and nanoparticles for directional recognition.

[0021] By adopting the above technical solution, compared with the prior art, the beneficial effects of the present invention are:

[0022] 1. The present invention uses nanotechnology to encapsulate some nutrients that have an auxiliary effect on tumor treatment but have poor stability or difficulty in absorption in the gastrointestinal tract into nanoparticles. The target modified on the surface of the nanoparticles can be specifically recognized and taken up by tumor tissues or immune cells, thereby increasing the concentration of these nutrients in the tumor microenvironment or immune regulation sites and enhancing their effects. Vitamin C is added to the mousse in the form of nanoliposome encapsulation. The liposome can protect vitamin C from gastric acid damage and enable it to be more effectively absorbed by the intestine. Then, by modifying the targeting molecules on the surface of the liposomes, it can be targeted and enriched around the tumor tissue, thereby improving the local antioxidant capacity, reducing the damage of tumor oxidative stress to normal tissues, and at the same time helping to enhance the efficacy of chemotherapy drugs;

[0023] 2. The present invention achieves precise positioning of tumor cells by modifying the targeting agent on the surface of liposomes and nanoparticles, so that the drug can be more effectively concentrated in the tumor tissue, avoiding excessive distribution of the drug in normal tissues, reducing the side effects of the drug on normal tissues, and increasing the drug concentration in the tumor site. The drug mainly works in the tumor site, reducing the distribution in other normal tissues, and can reduce the systemic toxicity of the drug, which helps to improve the quality of life of patients during the treatment process and enable them to better accept the treatment;

[0024] 3. The present invention changes the food texture by adding xanthan gum and gelatin compounding agents, so that the mousse has the characteristics of homogeneity, smoothness and easy aggregation. It can be easily crushed by the tongue without chewing and is easy to swallow. The formed food mass is not easy to remain in the oropharynx, which greatly reduces the difficulty of chewing and eating, and can effectively avoid the occurrence of choking and aspiration pneumonia. According to the characteristics of tumor patients' nutritional metabolism and immune inflammatory response, a special nutritional formula for tumor patients is designed, while taking into account the needs of patients, and a fine mud-like semi-solid food texture is made to achieve the purpose of both fully supplementing nutrition and facilitating the intake of patients with dysphagia. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 This is a schematic diagram of the steps for preparing a complete nutritional formula mousse product specially formulated for cancer patients in an embodiment of the present invention. DETAILED DESCRIPTION

[0026] The specific embodiments of the present invention are further described below in conjunction with the accompanying drawings. It should be noted that the description of these embodiments is used to help understand the present invention, but does not constitute a limitation of the present invention. In addition, the technical features involved in the various embodiments of the present invention described below can be combined with each other as long as they do not conflict with each other.

[0027] The present invention discloses a complete nutritional formula mousse product specially for tumor patients and a preparation method thereof, comprising preparing liposomes encapsulating nutrients, preparing nanoparticles encapsulating trace elements, modifying the surfaces of liposomes and nanoparticles with targeting substances, and mixing various raw materials to prepare the complete nutritional mousse. The specific operation steps of the preparation method of the complete nutritional formula mousse product specially for tumor patients are as follows:

[0028] Step 1: Prepare protein, carbohydrate, fat and additive raw materials;

[0029] Step 2: preparing liposomes, and encapsulating fat-soluble and water-soluble nutrients in the liposomes at the same time;

[0030] Step 3: preparing nanoparticles using biodegradable polymer materials, and encapsulating the trace elements in the polymer nanoparticles in the form of nanoparticles;

[0031] Step 4: Modifying the surface of liposomes and polymer nanoparticles with targeting agents;

[0032] Step 5: premixing dry raw materials, dissolving and emulsifying fat, and mixing dry and wet raw materials and fat emulsion;

[0033] Step 6: After seasoning and flavoring, make it into a mousse shape and package the prepared mousse product.

[0034] In one embodiment of the present invention: in step 1, whey protein in whey is extracted by ultrafiltration technology, polysulfone is selected as the material of ultrafiltration membrane, the pore size of ultrafiltration membrane is selected between 1nm-100nm, the pressure during ultrafiltration is set to 0.1MPa-0.5MPa, the temperature is set to 40℃-50℃, the whey is passed through the ultrafiltration membrane at a speed of 1m / s-5m / s to separate the whey protein, and a whey protein solution is obtained after ultrafiltration, the whey protein solution is dried by spray drying, and the whey protein solution is sprayed by a high-pressure nozzle. The whey protein solution is dried by injecting hot air at a temperature of 150°C to 200°C in a countercurrent flow to the whey protein solution in a mist form, thereby obtaining a powdered whey protein product. Maltodextrin is used as a carbohydrate source, and soybean oil, olive oil, fish oil and medium-chain triglycerides are used as fat sources. Vitamin A, vitamin C, vitamin E and B vitamins (including vitamin B1, B2, B6 and B12) are prepared, as well as trace elements of selenium and iodine.

[0035] In one embodiment of the present invention: in step 2, a lipid is dissolved in an organic solvent at a temperature of 30°C-40°C, and a fat-soluble vitamin solution of vitamins A, D, E and K is dissolved in an organic solvent containing lipids, the concentration of the lipid in the organic solvent is set to 10 mg / mL-50 mg / mL, chloroform is selected as the organic solvent, soybean lecithin and cholesterol are selected as the lipids, and the ratio of the amount of soybean lecithin to the amount of cholesterol is 2-5:1, and at the same time, 1%-10% of the total lipid amount of maleimide-phospholipid is dissolved in chloroform, vitamin C and B group water-soluble vitamins are dissolved in a buffer to form an aqueous phase solution, the buffer is a phosphate buffer, and the ratio of the organic solvent to the phosphate buffer is 2:1. The volume ratio is between 3-10:1, a phosphate buffer solution containing water-soluble vitamins is added to an organic solvent solution containing lipids, the mixed solution is mixed by ultrasonic stirring, the ultrasonic power is set to 100W-500W, the ultrasonic time is 5min-15min, a water-in-oil (W / O) emulsion is formed, the addition ratio of water-soluble vitamins to fat-soluble vitamins is 10-20:1, and after uniform mixing, the emulsion is added to a rotary evaporator, the temperature of the rotary evaporator is set to 30°C-50°C, the vacuum degree is set to 0.08MPa-0.1MPa, the organic solvent in the emulsion is evaporated, and the emulsion undergoes a phase transition to form a liposome with a water-in-oil-in-water (W / O / W) structure.

[0036] In one embodiment of the present invention: in step 3, the polymer nanoparticles are prepared by an emulsification-solvent volatilization method, a biodegradable polymer is dissolved in an organic solvent, stirred at a temperature of 20°C-30°C for 3h-5h, and the stirring speed is set to 300r / min-500r / min, the polymer is selected from polylactic acid-glycolic acid copolymer, and the organic solvent is selected from dichloromethane, and the concentration of polylactic acid-glycolic acid copolymer in dichloromethane is 10g / L-20g / L, and then selenium and iodine fat-soluble trace elements are dissolved in the organic solvent containing the biodegradable polymer to obtain an organic phase containing fat-soluble trace elements, an emulsifier with a concentration of 1g / L-5g / L is dissolved in deionized water, and the emulsifier is selected from polyvinyl alcohol, and then zinc and iron water-soluble trace elements are dissolved in the deionized water containing the emulsifier to obtain water-soluble trace elements. The organic phase is added dropwise into the aqueous phase at a speed of 1 mL / min-2 mL / min, and the solution is stirred at 1000 r / min-3000 r / min with a high-speed stirrer for 5 min-10 min to form an oil-in-water (W / O) emulsion. The emulsion is added into a rotary evaporator, and the temperature of the rotary evaporator is set to 30°C-40°C, the rotation speed is set to 50 r / min-100 r / min, and the vacuum degree is set to 0.08 MPa-0.1 MPa. As the organic solvent evaporates, the emulsion system changes, and the polymer gradually aggregates to form nanoparticles. The nanoparticles are collected by centrifugation, and the centrifugal speed is set to 10000 r / min-20000 r / min. After centrifugation for 10 min-30 min, the supernatant is sucked out with a pipette to obtain nanoparticles containing trace elements.

[0037] In one embodiment of the present invention: in step 4, the targeting substance is connected to the surface of liposomes using thiol-maleimide click chemistry, and the liposomes formed by rotary evaporation can expose the maleimide group on the surface of the liposomes. The thiol-modified peptide is selected as the targeting substance, and the thiol-containing targeting substance is dissolved in a buffer solution at a concentration of 0.01 mol / L-0.1 mol / L. The peptide solution is added to the liposome solution connected with the maleimide group for reaction. The molar ratio of the peptide to the liposome is 1-10:1, and the pH value of the reaction system is controlled between 6.5 and 7.5. During the reaction, a magnetic stirrer is used to stir at a speed of 60 r / min-100 r / min for 2h-6h. After the reaction, the liposomes are separated by high-speed centrifugation, the speed of the centrifuge is set to 5000 r / min-10000 r / min, and the centrifugation time is set to 10min-30min. After the centrifugation, the supernatant is sucked out using a rubber-tipped pipette to obtain a modified liposome precipitate.

[0038] In one embodiment of the present invention: in step 4, a phosphate with a pH value between 7.0 and 8.5 is used as a buffer, nanoparticles containing trace elements are dispersed in the buffer to prepare a nanoparticle dispersion, a trans-cyclooctene-PEG4-active ester reagent is selected, the active ester reagent is added to the nanoparticle dispersion, the molar ratio of the active ester reagent to the amino group on the surface of the nanoparticle is 1.2-1.5:1, the reaction is carried out at a temperature of 20°C-30°C for 12h-24h, a magnetic stirrer is used to stir at a speed of 60r / min-100r / min during the reaction, after the reaction, the target molecule is added to the nanoparticle dispersion connected with the active ester reagent, the reaction is carried out at a temperature of 20°C-30°C for 12h-24h, a magnetic stirrer is used to stir at a speed of 60r / min-100r / min during the reaction, and after the reaction, the target molecule is added to the nanoparticle dispersion connected with the active ester reagent, the reaction is carried out at a temperature of 20°C-30°C for 12h-24h, a magnetic stirrer is used to stir at a speed of 60r / min-100r / min during the reaction, and after the reaction, the nanoparticles are passivated by a dialysis method, and the concentration is 10mol / L-100mol / L. l / L phosphate is used as the dialysate, and the dialysis bag containing the nanoparticles is added into the dialysis container containing the phosphate dialysis solution. The volume of the phosphate dialysis solution is 50-100 times the volume of the nanoparticles. The dialysis time is set to 12-24h, and the phosphate dialysis solution is replaced every 4h. After the dialysis is completed, the modified nanoparticles are obtained in the dialysis bag.

[0039] In one embodiment of the present invention: in step five, the dry ingredients of flour, milk powder, powdered sugar, salt, baking soda and baking powder are added into a blender, and stirred at a speed of 50 r / min-150 r / min for 3 min-5 min, butter, corn oil and animal fat fat raw materials are added into the blender, and lecithin accounting for 0.5%-5% of the total mass of fat is added, and stirred at a speed of 200 r / min-500 r / min for 5 min-10 min, the mixed dry ingredients, modified nanoparticles and modified liposome precipitate are added to the container where the emulsified fat emulsion is located, and stirred at a speed of 200 r / min-300 r / min for 5 min-10 min to obtain a uniformly mixed mousse paste.

[0040] In one embodiment of the present invention: in step six, fruit puree accounting for 10%-20% of the total amount of mousse is selected as seasoning, the fruit puree is added to the mousse paste and mixed, and then the seasoned mousse paste is mixed with whipped cream, and a silicone spatula is used to flip upward from the bottom of the container to form a uniform mousse, and a piping bag is used to squeeze the mousse into a self-supporting bag, the self-supporting bag has an easy-tear opening, and the capacity is set to 50g-100g. The outer layer of the self-supporting bag is made of polyester material, the middle layer is made of aluminum foil material, and the inner layer is made of polyethylene material, and the raw materials, nutritional ingredients, production date and storage information of the mousse are printed on the outer layer.

[0041] In addition, the present invention also provides a special complete nutritional formula mousse product for tumor patients and a method for preparing the special complete nutritional formula mousse product for tumor patients: the special complete nutritional formula mousse product for tumor patients uses liposomes to encapsulate fat-soluble and water-soluble nutrients, uses polymer nanoparticles to encapsulate trace elements, and connects targeting objects on the surface of liposomes and nanoparticles for directional recognition.

[0042] Example 1. Complete nutritional formula for mousse texture tumors: carbohydrates 50g / 100g (200kcal / 100g): maltodextrin 51g (95%), oligofructose 0.3g, oligogalactose 0.3g, white sugar 1.4g; protein 31g / 100g (124.8kcal / 100g): whey protein powder 30g (80%), sodium caseinate 8g (90%), fat 18.8g / 100g (169.2kcal / 100g): soybean oil 5g, olive oil 5g, fish oil 2g, medium chain triglycerides 6.8g; total energy about 494kcal l / 100g----Carbohydrate: Protein: Fat = 41%: 25%: 34%; Vitamins: Vitamin A acetate 0.45mg, folic acid 0.05mg, thiamine hydrochloride (vitamin B1) 0.69mg, riboflavin (vitamin B2) 0.74mg, niacinamide (vitamin B3) 4mg, D-calcium pantothenate (vitamin B5) 2.5mg, pyridoxine hydrochloride (vitamin B6) 0.75mg, cyanocobalamin (vitamin B12) 0.001mg, L-sodium ascorbate (vitamin C) 47mg, d la-Tocopherol acetate (vitamin E) 15mg, cholecalciferol (vitamin D3) 0.003mg, phytonadione (vitamin K1) 0.025mg, choline chloride (choline) 120mg, D-biotin 0.018mg, L-carnitine 52mg, taurine 52mg; minerals: sodium dihydrogen phosphate 400mg, potassium chloride 680mg, copper sulfate 0.67mg, magnesium chloride 108mg, ferrous sulfate 15.2mg, zinc sulfate 7.5mg, manganese sulfate 1.2mg, chromium chloride 0.05mg, calcium gluconate 3.034g, potassium iodide 0.01mg, sodium selenite 0.04mg, sodium citrate 16mg; three major immune nutrients: arginine 1g, w-3 fatty acids 1.2g, nucleotides 10mg, glutamine 1g.

[0043] Example 2: A two-step emulsification method is used to prepare liposomes with a water-in-oil-in-water (W / O / W) structure. In the first step, a W / O emulsion is prepared. Soybean lecithin and cholesterol are dissolved in a chloroform solvent at a temperature of 30° C. At the same time, a fat-soluble vitamin solution of vitamins A, D, E and K is dissolved in a chloroform solvent containing lipids at a concentration of 50 mg / mL. The ratio of the amount of soybean lecithin to the amount of cholesterol is 3:1. At the same time, maleimide-phospholipids accounting for 5% of the total lipid content are dissolved in chloroform. Maleimide can react rapidly with sulfhydryl groups to achieve the connection of the target. Vitamin C and B water-soluble vitamins are dissolved in a phosphate buffer to form an aqueous phase solution. The volume ratio of the organic solvent to the phosphate buffer is between 5:1. A phosphate buffer solution of water-soluble vitamins is added to an organic solvent solution containing lipids, and the mixed solution is mixed by ultrasonic stirring. The ultrasonic power is set to 400 W. After 10 minutes of ultrasonic time, a water-in-oil (W / O) emulsion is formed. In the second step, a W / O / W emulsion is prepared. The addition ratio of water-soluble vitamins to fat-soluble vitamins is 10-20:1. Since water-soluble vitamins cannot be stored in large quantities in the body, their content in supplements is usually relatively high. After mixing evenly, the emulsion is added to a rotary evaporator. The temperature of the rotary evaporator is set to 40°C and the vacuum degree is set to 0.1 MPa. The organic solvent in the emulsion is evaporated, and the emulsion undergoes a phase transition to form liposomes with a water-in-oil-in-water (W / O / W) structure.

[0044] Example 3: Nanoparticles containing trace elements are dispersed in a phosphate buffer with a pH value of 7.0 to prepare a nanoparticle dispersion, and then a trans-cyclooctene-PEG4-active ester reagent is added to the nanoparticle dispersion, the molar ratio of the active ester reagent to the amino group on the surface of the nanoparticles is 1.2:1, and the reaction is carried out at a temperature of 25°C for 12 hours. During the reaction, a magnetic stirrer is used to stir at a speed of 100 r / min. After the reaction, the target molecule is added to the nanoparticle dispersion connected with the active ester reagent, and the reaction is carried out at a temperature of 25°C for 16 hours. During the reaction, a magnetic stirrer is used to stir at a speed of 80 r / min. After the reaction, the nanoparticles are passivated by dialysis method, and the concentration of 50 mo l / L phosphate was used as the dialysate, and the dialysis bag containing the nanoparticles was added into the dialysis container containing the phosphate dialysis solution. The volume of the phosphate dialysis solution was 50 times the volume of the nanoparticles. The dialysis time was set to 24h, and the phosphate dialysis solution was replaced every 4h. After the dialysis was completed, the modified nanoparticles were obtained in the dialysis bag.

[0045] As attached Figure 1 As shown, the surface-modified W / O / W liposomes and biodegradable nanoparticles can accurately deliver nutrients and drugs to target sites, improve the therapeutic effects of nutrients and drugs, and have adjustable degradation rates and good biocompatibility.

[0046] The embodiments of the present invention are described in detail above with reference to the accompanying drawings, but the present invention is not limited to the described embodiments. For those skilled in the art, various changes, modifications, substitutions and variations of these embodiments are made without departing from the principles and spirit of the present invention, and still fall within the scope of protection of the present invention.

[0047] In the description of the specification, the description with reference to the terms "one embodiment", "example", "specific example", etc. means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representation of the above terms does not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any one or more embodiments or examples in a suitable manner.

[0048] The above contents are merely examples and explanations of the present invention. Various modifications or additions to the specific embodiments described or replacements in similar ways by technicians in the technical field shall fall within the protection scope of the present invention as long as they do not deviate from the invention or exceed the scope defined by the claims.

[0049] The above description is only a preferred specific implementation manner of the present invention, but the protection scope of the present invention is not limited thereto. Any technician familiar with the technical field can make equivalent replacements or changes according to the technical scheme and inventive concept of the present invention within the technical scope disclosed by the present invention, which should be covered by the protection scope of the present invention.

Claims

1. A method for preparing a complete nutritional formula mousse product for tumor patients, comprising preparing liposomes encapsulating nutrients, preparing nanoparticles encapsulating trace elements, modifying the surfaces of liposomes and nanoparticles with targeting substances, and mixing various raw materials to prepare a complete nutritional mousse, characterized in that: The specific steps of the preparation method of the mousse product with complete nutritional formula specially formulated for tumor patients are as follows: Step 1: Prepare protein, carbohydrate, fat and additive raw materials; Step 2: preparing liposomes, and encapsulating fat-soluble and water-soluble nutrients in the liposomes at the same time; Step 3: preparing nanoparticles using biodegradable polymer materials, and encapsulating the trace elements in the polymer nanoparticles in the form of nanoparticles; Step 4: Modifying the surface of liposomes and polymer nanoparticles with targeting agents; Step 5: premixing dry raw materials, dissolving and emulsifying fat, and mixing dry and wet raw materials and fat emulsion; Step 6: After seasoning and flavoring, make it into a mousse shape and package the prepared mousse product.

2. The method for preparing a complete nutritional formula mousse product for tumor patients according to claim 1, characterized in that: In the step 1, the whey protein in the whey is extracted by ultrafiltration technology, polysulfone is selected as the material of the ultrafiltration membrane, the pore size of the ultrafiltration membrane is selected between 1nm and 100nm, the pressure during ultrafiltration is set to 0.1MPa-0.5MPa, the temperature is set to 40°C-50°C, the whey is passed through the ultrafiltration membrane at a speed of 1m / s-5m / s to separate the whey protein, and a whey protein solution is obtained after ultrafiltration, the whey protein solution is dried by spray drying, and the whey protein solution is sprayed into a drying tower through a high-pressure nozzle. The pressure of the high-pressure nozzle is set to 10MPa-20MPa, and hot air with a temperature of 150℃-200℃ is sprayed in counterflow to the whey protein solution in a droplet form to dry the whey protein solution to obtain a powdered whey protein product. Maltodextrin is selected as the carbohydrate source, soybean oil, olive oil, fish oil and medium-chain triglycerides are selected as the fat source, vitamin A, vitamin C, vitamin E and B vitamins (including vitamin B1, B2, B6, B12) are prepared, and selenium and iodine trace elements are prepared.

3. The method for preparing a complete nutritional formula mousse product for tumor patients according to claim 2, characterized in that: In the step 2, lipids are dissolved in an organic solvent at a temperature of 30° C. to 40° C., and a fat-soluble vitamin solution of vitamins A, D, E and K is dissolved in an organic solvent containing lipids, the concentration of the lipids in the organic solvent is set to 10 mg / mL to 50 mg / mL, chloroform is selected as the organic solvent, soybean lecithin and cholesterol are selected as the lipids, and the ratio of the amount of soybean lecithin to the amount of cholesterol is 2-5:1, and at the same time, maleimide-phospholipids accounting for 1% to 10% of the total lipid amount are dissolved in chloroform, and vitamin C and B group water-soluble vitamins are dissolved in a buffer solution to form an aqueous phase solution, the buffer solution is a phosphate buffer, and the volume ratio of the organic solvent to the phosphate buffer is 3-4:

1. The invention discloses a method for preparing a liposome comprising the steps of: adding a phosphate buffer solution containing water-soluble vitamins to an organic solvent solution containing lipids at a ratio of 10:1 to 10:1, mixing the mixed solution by ultrasonic stirring, setting the ultrasonic power to 100W-500W, and forming an oil-in-water (W / O) emulsion after an ultrasonic time of 5min-15min, wherein the adding ratio of water-soluble vitamins to fat-soluble vitamins is 10-20:1, and after uniform mixing, adding the emulsion to a rotary evaporator, setting the temperature of the rotary evaporator to 30°C-50°C, and setting the vacuum degree to 0.08MPa-0.1MPa, so that the organic solvent in the emulsion evaporates, and the emulsion undergoes a phase transition to form a liposome with a water-in-oil-in-water (W / O / W) structure.

4. The method for preparing a complete nutritional formula mousse product for tumor patients according to claim 2, characterized in that: In the step 3, the polymer nanoparticles are prepared by using an emulsification-solvent volatilization method, a biodegradable polymer is dissolved in an organic solvent, stirred at a temperature of 20° C.-30° C. for 3 h-5 h, and a stirring speed is set to 300 r / min-500 r / min, the polymer is selected from polylactic acid-glycolic acid copolymer, and the organic solvent is selected from dichloromethane, and the concentration of polylactic acid-glycolic acid copolymer in dichloromethane is 10 g / L-20 g / L, and then selenium and iodine fat-soluble trace elements are dissolved in the organic solvent containing the biodegradable polymer to obtain an organic phase containing fat-soluble trace elements, an emulsifier with a concentration of 1 g / L-5 g / L is dissolved in deionized water, and the emulsifier is selected from polyvinyl alcohol, and then zinc and iron water-soluble trace elements are dissolved in the deionized water containing the emulsifier to obtain an aqueous phase containing water-soluble trace elements. , the organic phase is added dropwise to the aqueous phase at a rate of 1 mL / min-2 mL / min, and the solution is stirred at 1000 r / min-3000 r / min with a high-speed stirrer for 5 min-10 min to form an oil-in-water (W / O) emulsion, and the emulsion is added to a rotary evaporator, the temperature of the rotary evaporator is set to 30°C-40°C, the rotation speed is set to 50 r / min-100 r / min, and the vacuum degree is set to 0.08 MPa-0.1 MPa. As the organic solvent evaporates, the emulsion system changes, and the polymer gradually aggregates to form nanoparticles. The nanoparticles are collected by centrifugation, and the centrifugal speed is set to 10000 r / min-20000 r / min. After centrifugation for 10 min-30 min, the supernatant is sucked out with a pipette to obtain nanoparticles containing trace elements.

5. The method for preparing a complete nutritional formula mousse product for tumor patients according to claim 3, characterized in that: In the step 4, the targeting substance is connected to the surface of the liposome using the thiol-maleimide click chemistry method. The liposomes formed by rotary evaporation can expose the maleimide group on the surface of the liposomes. The thiol-modified peptide segment is selected as the targeting substance, and the thiol-containing targeting substance is dissolved in a buffer solution at a concentration of 0.01 mol / L-0.1 mol / L. The peptide segment solution is added to the liposome solution connected with the maleimide group for reaction. The molar ratio of the peptide segment to the liposome is 1-10:1, and the pH value of the reaction system is controlled between 6.5 and 7.

5. During the reaction, a magnetic stirrer is used to stir at a speed of 60 r / min-100 r / min for 2h-6h. After the reaction, the liposomes are separated by high-speed centrifugation. The speed of the centrifuge is set to 5000 r / min-10000 r / min, and the centrifugation time is set to 10min-30min. After the centrifugation, the supernatant is sucked out using a rubber-tipped pipette to obtain a modified liposome precipitate.

6. The method for preparing a complete nutritional formula mousse product for tumor patients according to claim 4, characterized in that: In the step 4, a phosphate with a pH value between 7.0 and 8.5 is used as a buffer, nanoparticles containing trace elements are dispersed in the buffer to prepare a nanoparticle dispersion, a trans-cyclooctene-PEG4-active ester reagent is selected, the active ester reagent is added to the nanoparticle dispersion, the molar ratio of the active ester reagent to the amino group on the surface of the nanoparticle is 1.2-1.5:1, the reaction is carried out at a temperature of 20° C. to 30° C. for 12 h to 24 h, and a magnetic stirrer is used to stir at a speed of 60 r / min to 100 r / min during the reaction. After the reaction is completed, the target molecule is added to the nanoparticles connected with the active ester reagent. The nanoparticles are passivated by dialysis after the reaction is completed. Phosphate with a concentration of 10 mol / L-100 mol / L is used as the dialysate. The dialysis bag containing the nanoparticles is added to the dialysis container containing the phosphate dialysate. The volume of the phosphate dialysate is 50-100 times the volume of the nanoparticles. The dialysis time is set to 12-24 hours. The phosphate dialysate is replaced every 4 hours. After the dialysis is completed, the modified nanoparticles in the dialysis bag are obtained.

7. The method for preparing a complete nutritional formula mousse product for tumor patients according to claim 6, characterized in that: In the step 5, the dry raw materials of flour, milk powder, powdered sugar, salt, baking soda and baking powder are added into a blender, and stirred at a speed of 50 r / min-150 r / min for 3 min-5 min, butter, corn oil and animal fat fat raw materials are added into the blender, and lecithin accounting for 0.5%-5% of the total mass of fat is added, and stirred at a speed of 200 r / min-500 r / min for 5 min-10 min, and the mixed dry raw materials, modified nanoparticles and modified liposome precipitate are added into a container where the emulsified fat emulsion is located, and stirred at a speed of 200 r / min-300 r / min for 5 min-10 min to obtain a uniformly mixed mousse paste.

8. The method for preparing a complete nutritional formula mousse product for tumor patients according to claim 7, characterized in that: In the step six, fruit puree accounting for 10%-20% of the total amount of the mousse is selected as a seasoning, the fruit puree is added to the mousse paste and mixed, and then the seasoned mousse paste is mixed with the whipped cream, and a silicone spatula is used to flip upward from the bottom of the container to form a uniform mousse shape, and a piping bag is used to squeeze the mousse into a self-supporting bag, the self-supporting bag has an easy-tear opening, and the capacity is set to 50g-100g. The outer layer of the self-supporting bag is made of polyester material, the middle layer is made of aluminum foil material, and the inner layer is made of polyethylene material, and the raw materials, nutritional ingredients, production date and storage information of the mousse are printed on the outer layer.

9. A complete nutritional formula mousse product for tumor patients applicable to the preparation method of the complete nutritional formula mousse product for tumor patients according to any one of claims 1 to 8, characterized in that: The complete nutritional formula mousse product specially formulated for tumor patients uses liposomes to encapsulate fat-soluble and water-soluble nutrients, uses polymer nanoparticles to encapsulate trace elements, and connects targeting objects on the surfaces of liposomes and nanoparticles for directional recognition.

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