Formula powder for phenylketonuria patients and preparation method thereof

Abstract

The invention relates to formula powder for phenylketonuria patients and a preparation method thereof. The invention discloses formula powder for patients with phenylketonuria. Comprising the following components in parts by weight: 100-200 parts of casein glycomacropeptide, 3-20 parts of compound amino acid, 500-700 parts of protein-free fat powder, 150-250 parts of solid corn syrup, 5-20 parts of DHA algal oil powder, 5-20 parts of arachidonic acid powder, 5-10 parts of compound vitamins, 20-60 parts of compound minerals and 0.3-0.7 part of nucleotide. The formula powder for the phenylketonuria patient does not contain phenylalanine. The formula powder is good in taste, easy to accept by infants and beneficial to nutrient intake, growth and development of patients, and the osmotic pressure is low so that symptoms such as diarrhea can be relieved.

Description

Technical Field

[0001] The present invention relates to the field of infant formula for special medical purposes, and in particular provides a formula powder with improved taste for patients with the rare disease phenylketonuria (PKU) and a preparation method thereof. Background Art

[0002] Phenylketonuria (PKU) is a common amino acid metabolic disease. Due to the lack of phenylalanine hydroxylase or reduced activity in the body, phenylalanine cannot be converted into tyrosine and other metabolites through the normal metabolic pathway, thereby enhancing the bypass metabolic pathway, generating phenylpyruvate, phenylacetate and phenyllactic acid, which are excreted in large quantities from the urine, resulting in a metabolic disease called phenylketonuria. Low-phenylalanine diet therapy is currently the only method for treating classic PKU, and its purpose is to prevent brain damage. In addition to dietary therapy, the treatment of atypical phenylketonuria should also supplement a variety of neurotransmitters, such as BH4, 5-hydroxytryptamine, folic acid, etc.

[0003] The patent with publication number CN103462003A discloses a special dietary food for patients with phenylketonuria. The special dietary food is prepared by mixing food-derived casein glycomacropeptide as raw material, adding a variety of essential amino acids for the human body, supplemented with fat, dietary fiber, fruit powder, vitamins, minerals and other nutrients. The special dietary food can be made into powder or granules, taken with warm water or eaten directly, and is easily absorbed and utilized by the human body. It can provide a daily protein source for patients with phenylketonuria, supplement the dietary fiber, vitamins and minerals necessary for the human body, improve the nutritional status of patients with phenylketonuria, and at the same time, it can assist in improving the gastrointestinal flora of patients by adding casein glycomacropeptide, regulate the immune system, and increase the body's immunity.

[0004] In order to reduce the impact of phenylketonuria on children's growth and development, the patent with publication number CN104012659A discloses a formula powder for children with phenylketonuria and its preparation method, which is composed of solid glucose syrup, amino acids, fatty acids, nucleotides, fish oil, dietary fiber, compound vitamins, compound minerals and emulsifiers, and is prepared by a wet preparation process. The formula powder uses specific free amino acids and screens out the appropriate amount of free L-tyrosine and removes phenylalanine, which effectively prevents the occurrence of allergies in infants with phenylketonuria while ensuring the physiological needs of sick children; the components in the formula work synergistically with each other, and are closer to breast milk in terms of absorption, taste and other aspects, so that children can absorb nutrients more fully after taking it, and effectively reduce allergic reactions such as diarrhea.

[0005] The patent with publication number CN107751998A relates to an edible formula powder for patients with phenylketonuria, which contains the following components by weight: 30-85 parts of vegetable oil fat powder, 15-60 parts of complex amino acids, 0.01-1 parts of nucleotides, 2-5 parts of complex vitamins and 2-5 parts of complex minerals, and the edible formula powder does not contain phenylalanine. The edible formula powder is based on fat, carbohydrates, amino acids, vitamins, minerals, etc., with a scientific ratio, which can meet the needs of growth and development of infants and young children, provide energy for the body, supplement the essential amino acids in the growth and development process, and does not add phenylalanine. At the same time, the formula powder does not produce the accumulation of phenylalanine and its ketoacids on the one hand, and on the other hand, it ensures the patient's amino acid intake and maintains the body's normal amino acid metabolism. In addition, the edible formula powder may also contain 0.01-1 parts by weight of complex unsaturated fatty acids to meet the nutritional needs of children aged 0-1 years old, promote brain development, and improve cognitive ability.

[0006] The patent with publication number CN110693031A discloses a formula powder for patients with phenylketonuria and its preparation method, which is prepared from the following components in mass percentage: 60-90% vegetable oil fat powder, 8-20% compound amino acid, 0-6.45% fructo-oligosaccharide (Fos), 0-6.45% galacto-oligosaccharide (Gos), 0.012-0.058% nucleotide, 0.044-0.13% compound vitamin and 1.195-4.717% compound mineral, and the formula powder does not contain phenylalanine. Compared with the prior art, the formula ratio is scientific and can meet the needs of infants and young children for growth and development; wherein: the vegetable oil fat powder contains fat and carbohydrates to provide energy for the body, the compound amino acid supplements the essential amino acids for the growth and development of the human body and does not add phenylalanine, which neither produces the accumulation of phenylalanine and its keto acid, nor ensures the patient's amino acid intake and maintains the body's normal amino acid metabolism.

[0007] The patent with publication number CN113785972A discloses a nutritional powder, preparation method and use for the rare disease phenylketonuria. The nutritional powder is composed of vegetable oil fat powder, compound amino acids, whey protein extract, compound minerals, edible glucose, arachidonic acid oil, compound vitamins, and docosahexaenoic acid oil. The nutritional powder is formulated with reference to the amino acid content in breast milk to ensure balanced amino acid intake for infants and young children, without phenylalanine and other keto acid accumulation, improving body immunity, and at the same time providing all nutrients such as unsaturated fatty acids, vitamins and minerals required for the growth and development of infants and young children.

[0008] However, the above-mentioned prior art has many problems such as unbalanced nutritional components, complicated preparation method, high osmotic pressure, easy to cause diarrhea or poor taste. Summary of the invention

[0009] The following is an overview of the subject matter described in detail herein. This overview is not intended to limit the scope of protection of this application.

[0010] In view of the above-mentioned defects of the prior art, the technical problem to be solved by the present application is to construct an infant formula powder with special medical uses for phenylketonuria with improved taste by using a dynamic ion exchange method. The formula powder has a good taste and is easily accepted by infants, which is beneficial to the patient's nutritional intake and growth and development; at the same time, the formula powder described in the present application has a low osmotic pressure, which is beneficial to alleviating symptoms such as diarrhea.

[0011] The first aspect of the present application provides a formula powder for patients with phenylketonuria, comprising the following components by weight: 100-200 parts by weight of casein glycomacropeptide, 3-20 parts by weight of complex amino acids, 500-700 parts by weight of protein-free fat powder, 150-250 parts by weight of solid corn syrup, 5-20 parts by weight of DHA algae oil powder, 5-20 parts by weight of arachidonic acid powder, 5-10 parts by weight of complex vitamins, 20-60 parts by weight of complex minerals, and 0.3-0.7 parts by weight of nucleotides; the formula powder for patients with phenylketonuria does not contain phenylalanine.

[0012] In an exemplary embodiment, the formula powder for phenylketonuria patients is composed of the following components in parts by weight: 100-200 parts by weight of casein glycomacropeptide, 3-20 parts by weight of complex amino acids, 500-700 parts by weight of protein-free fat powder, 150-250 parts by weight of solid corn syrup, 5-20 parts by weight of DHA algae oil powder, 5-20 parts by weight of arachidonic acid powder, 5-10 parts by weight of complex vitamins, 20-60 parts by weight of complex minerals, and 0.3-0.7 parts by weight of nucleotides; the formula powder does not contain phenylalanine.

[0013] In an exemplary embodiment, the casein glycomacropeptide is a product separated and extracted from a raw material solution containing casein glycomacropeptide.

[0014] In an exemplary embodiment, the casein glycomacropeptide may also be commercially available casein glycomacropeptide.

[0015] In an exemplary embodiment, the method for preparing the casein glycomacropeptide comprises: The pH of the raw material solution containing casein glycomacropeptide is adjusted to 4.5-5.6, and then allowed to stand to remove precipitated foreign proteins to obtain a supernatant; The pH of the supernatant is adjusted to 3.6-4.2 and then added to an exchange column filled with an anion resin. After adsorption, the supernatant is eluted with a sodium chloride solution having an equal volume to the resin, and the eluate is collected; The eluate is desalted and concentrated using an ultrafiltration membrane with a molecular weight cutoff of 4000u-8000u, and then freeze-dried to obtain casein glycomacropeptide.

[0016] In an exemplary embodiment, the raw material liquid is a whey powder solution of 0.02-0.06 g / mL.

[0017] In an exemplary embodiment, the standing time is 2 hours.

[0018] In an exemplary embodiment, the exchange column filled with anion resin is an exchange column filled with 201×4 resin.

[0019] In an exemplary embodiment, in the exchange column, the volume ratio of the supernatant to the resin is (0.5:1) to (2:1).

[0020] In an exemplary embodiment, the concentration of the sodium chloride solution is 0.4 mol / L-0.8 mol / L.

[0021] In an exemplary embodiment, the composite amino acid consists of L-cysteine, L-histidine, L-leucine, L-tyrosine and L-tryptophan to ensure that the amino acid score is qualified and meets the normal growth needs of infants.

[0022] In an exemplary embodiment, the composite amino acid, by weight, consists of: 0.33-2.51 parts of L-cysteine, 0.37-2.82 parts of L-histidine, 1.52-11.57 parts of L-leucine, 1.4-10.66 parts of L-tyrosine and 0.32-2.44 parts of L-tryptophan.

[0023] In an exemplary embodiment, the composite amino acid, by weight, consists of: 0.42 parts of L-cysteine, 0.47 parts of L-histidine, 1.93 parts of L-leucine, 1.78 parts of L-tyrosine and 0.41 parts of L-tryptophan.

[0024] In an exemplary embodiment, the composite amino acid, by weight, consists of: 2.51 parts of L-cysteine, 2.82 parts of L-histidine, 11.57 parts of L-leucine, 10.66 parts of L-tyrosine and 2.44 parts of L-tryptophan.

[0025] In an exemplary embodiment, the composite amino acid, by weight, consists of: 0.33 parts of L-cysteine, 0.37 parts of L-histidine, 1.52 parts of L-leucine, 1.4 parts of L-tyrosine and 0.32 parts of L-tryptophan.

[0026] In an exemplary embodiment, the protein-free fat powder is produced by using edible oil as the main raw material, with or without adding emulsifiers, antioxidants, acidity regulators and other food additives, and is processed through processes such as batching, homogenization, sterilization, spray drying, and packaging.

[0027] In an exemplary embodiment, the protein-free fat powder is produced using raw materials and auxiliary materials that do not contain protein, and the protein content of the protein-free fat powder is ≤0.5g / 100g, and the fat content is ≥30g / 100g.

[0028] In an exemplary embodiment, the source of the edible fat is selected from one or a combination of vegetable fats, animal fats, rapeseed oil, and coconut oil except hydrogenated fats.

[0029] In an exemplary embodiment, the vegetable oil is selected from at least one of rapeseed oil, corn oil, coconut oil, palm oil, sunflower oil, and soybean oil.

[0030] In an exemplary embodiment, the raw materials of the protein-free fat powder include glucose syrup, sunflower oil, rapeseed oil, coconut oil, mixed tocopherol concentrate, ascorbyl palmitate, sodium octenyl succinate starch, mono / diglycerol fatty acid esters, and sodium ascorbate.

[0031] In an exemplary embodiment, the protein-free fat powder is composed of the following by weight: 400-600 parts of glucose syrup, 300-500 parts of edible vegetable blending oil, 80-200 parts of sodium octenyl succinate starch, 10-20 parts of mono- and di-glycerol fatty acid esters, and 1-8 parts of sodium ascorbate.

[0032] In an exemplary embodiment, the edible vegetable blended oil is composed of the following by weight: 70-90 parts of sunflower oil, 100-200 parts of high oleic sunflower oil, 50-200 parts of low erucic acid rapeseed oil, 20-100 parts of coconut oil, 0.1-4 parts of mixed tocopherol concentrate, and 0.01-1 parts of ascorbyl palmitate.

[0033] In an exemplary embodiment, the raw materials of the DHA algae oil powder include: docosahexaenoic acid, sodium ascorbate, glyceryl monostearate, tricalcium phosphate, citric acid, phospholipids and glucose syrup.

[0034] In an exemplary embodiment, the DHA algae oil powder is composed of the following by weight: 200-500 parts of glucose syrup, 200-500 parts of sodium starch octenylsuccinate, 220-320 parts of docosahexaenoic acid oil, 10-60 parts of sodium ascorbate, 1-40 parts of mono- and diglycerol fatty acid esters, 0.2-30 parts of sodium citrate, 1-20 parts of tricalcium phosphate, 0.5-20 parts of phospholipids, and 0.5-20 parts of ascorbyl palmitate.

[0035] In an exemplary embodiment, the raw materials of the arachidonic acid powder include: arachidonic acid powder, sodium ascorbate, glyceryl monostearate, tricalcium phosphate, citric acid and glucose syrup.

[0036] In an exemplary embodiment, the arachidonic acid powder is composed of the following by weight: 200-500 parts of glucose syrup, 200-500 parts of sodium starch octenylsuccinate, 220-320 parts of arachidonic acid oil, 10-60 parts of sodium ascorbate, 1-40 parts of mono- and diglycerol fatty acid esters, 0.2-30 parts of sodium citrate, 1-20 parts of tricalcium phosphate, 0.5-20 parts of phospholipids, and 0.5-20 parts of ascorbyl palmitate.

[0037] In an exemplary embodiment, the nucleotides consist of 5'-adenosine monophosphate, 5'-cytidylic acid disodium, 5'-uridylic acid disodium, 5'-guanylic acid disodium, and 5'-inosinic acid disodium.

[0038] In an exemplary embodiment, the nucleotides are composed of the following components by mass percentage: 15%-25% adenosine 5'-monophosphate, 20%-40% disodium 5'-cytidylate, 20%-30% disodium 5'-uridylate, 6%-10% disodium 5'-guanylate, and 10%-20% disodium 5'-inosinate.

[0039] In an exemplary embodiment, the nucleotides are composed of the following components by mass percentage: 20.3% adenosine 5'-monophosphate, 30% disodium 5'-cytidylate, 24% disodium 5'-uridylate, 6.9% disodium 5'-guanylate, and 13.8% disodium 5'-inosinate.

[0040] In an exemplary embodiment, the nucleotides are composed of the following components in weight percentage: 15% adenosine 5'-monophosphate, 30% disodium 5'-cytidylate, 30% disodium 5'-uridylate, 10% disodium 5'-guanylate, and 15% disodium 5'-inosinate.

[0041] In an exemplary embodiment, the nucleotides are composed of the following components in weight percentage: 25% adenosine 5'-monophosphate, 20% disodium 5'-cytidylate, 30% disodium 5'-uridylate, 10% disodium 5'-guanylate, and 15% disodium 5'-inosinate.

[0042] In an exemplary embodiment, the multivitamin comprises: vitamin A acetate 756250.000~1023161.765 mcg / kg, vitamin D3 16250~21985.294 mcg / kg, mixed tocopherol concentrate 5250.000~7102.941 mg / kg, vitamin K1 81250~109926.471 mcg / kg, vitamin B1 81250-109926.471 mcg / kg, riboflavin 1308375.000-1133595.588mcg / kg, nicotinamide 8471375.000-11461272.059mcg / kg, pantothenic acid 4791875.000-6483125.000mcg / kg, vitamin B6 802000.0000-1085058.824 mcg / kg, D-biotin 30625.000-41433.824mcg / kg, folic acid 138000.000-186705.882mcg / kg, vitamin B 12 2500.000-3382.353 mcg / kg, vitamin C 6617.647-8088.235 mg / kg, choline 158823.529-194117.647mg / kg, iodine 129375.000-175036.765mcg / kg, selenium 25125.000-33992.647mcg / kg, L-carnitine 23823.529-29117.647mg / kg, taurine 53867.647-65838.235mg / kg, inositol 158823.529-194117.647mg / kg.

[0043] In an exemplary embodiment, the complex minerals include: copper 90097.826-110119.565mcg / kg, iron 1213.044-1482.609mg / kg, magnesium 11523.913-14084.783mg / kg, manganese 44551.087-60275.000mg / kg, sodium 23576.087-28815.217mg / kg, zinc 1213.044-1482.609mg / kg, calcium 121304.348-148260.870mg / kg and chlorine 31304.348-38260.870mg / kg.

[0044] In an exemplary embodiment, the molecular weight distribution of the formula powder for phenylketonuria patients is as follows: <3000 Da accounts for 99.9%, ≤1000 Da accounts for more than 90%, and >3000 Da accounts for 0.1%.

[0045] In an exemplary embodiment, in the formula powder for phenylketonuria patients, the content of casein, soy protein, and whole milk protein allergens is less than 2.5 mg / kg; the content of β-lactoglobulin allergen is less than 0.167 mg / kg; and the content of β-lactoglobulin fragment allergen is less than 5 mg / kg, which can effectively reduce the risk of food protein allergy.

[0046] The second aspect of the present application provides a method for preparing the above-mentioned formula powder for patients with phenylketonuria, the method comprising the following steps: Step 1) Weighing: Weigh the materials according to the formula, and prepare the materials according to the formula after weighing; Step 2) Premixing: Add the composite minerals, arachidonic acid powder, nucleotides, DHA algae oil powder, composite vitamins, and composite amino acids into a premixer in sequence according to the formula requirements, and then add the protein-free fat powder for premixing; Step 3) Feeding and screening: the premixed materials and other raw materials in step 2) are fed into a dry mixing tank according to the feeding requirements for screening; Step 4) Dry mixing: After dry mixing the materials, temporarily store them in a dry mixing tank; Step 5) Metal detection: The material in the dry mixing tank is transported to a metal detector for detection, and after being detected to be free of metal impurities, it is filled; Step 6) Filling: Filling the material according to the set net content to produce a product; Step 7) Packing: adding an outer cover to the product, packing it in a box, and sealing it; Step 8) Palletizing: palletizing the products according to palletizing requirements; Step 9) Warehousing: transporting the product to the finished product warehouse for warehousing; Step 10) Shipping: The product is shipped after passing the inspection.

[0047] In an exemplary embodiment, in step 2), the premixing is eccentric mixing, and its parameters are as follows: the premixing time is 20 minutes, and the premixing speed is 12 r / min.

[0048] In an exemplary embodiment, in step 3), the mesh size of the sieving process is 16-20 meshes.

[0049] In an exemplary embodiment, in step 4), the total mass of the dry mix is ​​200 kg.

[0050] In an exemplary embodiment, in step 4), the dry mixing parameters are as follows: the dry mixing time is 30 min, and the rotation speed is 8 r / min.

[0051] The third aspect of the present application provides a formula powder for phenylketonuria patients prepared by the above method.

[0052] The fourth aspect of the present application provides an infant formula food comprising the above-mentioned formula powder for phenylketonuria patients.

[0053] In an exemplary embodiment, the infant formula is milk powder.

[0054] The fifth aspect of the present application provides an application of the above-mentioned formula powder or infant formula for patients with phenylketonuria in infant food for phenylketonuria.

[0055] In an exemplary embodiment, the invention should include: the formula powder or infant formula food for phenylketonuria patients is used in baby food to control the condition of children with phenylketonuria, improve the intellectual development of children with phenylketonuria, and reduce eczema, diarrhea, abdominal pain, vomiting, nasal congestion, runny nose, etc. caused by allergic reactions.

[0056] Compared with the existing related technologies, this application has the following technical effects: The casein glycomacropeptide prepared in the present application has good solubility and stability, so that it can be evenly dispersed in food and is not prone to precipitation or stratification; after electronic nose analysis, the casein glycomacropeptide is weaker on nitrogen oxide, alcohol and sulfide sensors; the content of high molecular aldehyde substances gradually increases with the progress of process treatment, the types and contents of alkanes and alcohols decrease, and the acid substances are significantly reduced, thereby improving the taste of the formula food.

[0057] In addition, solid corn syrup is added to the product of this application, which significantly improves the overall poor taste caused by exposure to bitter amino acids compared to maltodextrin, and at the same time reduces the probability of gastrointestinal discomfort in children with phenylketonuria; lactose is not used as a carbohydrate source in the formula powder of this application.

[0058] Therefore, the beneficial effects of the present application are: 1) casein glycomacropeptide and a small amount of complex amino acids prepared by dynamic ion exchange method are used as protein sources, and the taste is good; the ratio refers to the amino acid content in breast milk, and the ratio is scientific, which not only ensures the amino acid intake of infants and young children, but also does not produce accumulation of phenylalanine and its keto acid, maintains the body's normal amino acid metabolism, and enhances immunity; 2) provides all nutrients such as energy, protein, carbohydrates, fatty acids, vitamins and minerals required for the growth and development of infants and young children, promotes the normal growth and development of the body, and while the nutrition absorption is more sufficient, the low osmotic pressure effectively reduces allergic reactions such as diarrhea.

[0059] Other features and advantages of the present application will be described in the following description, and partly become apparent from the description, or be understood by implementing the present application. Other advantages of the present application can be realized and obtained by the schemes described in the description. DETAILED DESCRIPTION

[0060] In order to make the purpose, technical solution and advantages of the present application more clear, the embodiments of the present application will be described in detail below. It should be noted that the embodiments and features in the embodiments of the present application can be combined with each other arbitrarily without conflict.

[0061] The present invention is further described in detail below in conjunction with specific examples, but the examples should not be construed as limiting the present invention.

[0062] In the examples and comparative examples of the present application: Protein-free fat powder was purchased from Tianjin Yinhe Weiye Import and Export Co., Ltd.; Corn syrup solids were purchased from Bowling Biotech Co., Ltd.; DHA algae oil powder was purchased from Guangdong Runke Bioengineering Co., Ltd.; Arachidonic acid ARA powder was purchased from Guangdong Runke Bioengineering Co., Ltd.; Multivitamins were purchased from DSM Vitamins (Shanghai) Co., Ltd.; Complex minerals were purchased from DSM Vitamins (Shanghai) Co., Ltd.; Nucleotides were purchased from DSM Vitamins (Shanghai) Co., Ltd.

[0063] Unless otherwise specified, the raw materials in this application are all conventional products on the market.

[0064] Example 1 The preparation method of the casein glycomacropeptide is as follows: A 0.03 g / mL whey powder solution was prepared, and its pH was adjusted to 4.8 and then allowed to stand for 2 hours to precipitate foreign proteins to obtain a supernatant; The pH of the supernatant was adjusted to 4.0 and then added to an exchange column filled with anion resin 201×4, with the volume ratio of the supernatant to the resin being 1:1; after adsorption, the supernatant was eluted with a 0.6 mol / L sodium chloride solution having an equal volume to the resin, and the eluate was collected; The eluate was desalted and concentrated using an ultrafiltration membrane with a molecular weight cutoff of 6000u, and the casein glycomacropeptide product was obtained after freeze-drying.

[0065] Example 2 A formula powder for infants with phenylketonuria with improved taste, comprising the following components in parts by weight: 141.56 parts of casein glycomacropeptide powder in Example 1, 3.94 parts of complex amino acids, 605 parts of protein-free fat powder, 177.2 parts of solid corn syrup, 9 parts of DHA algae oil powder, 10 parts of arachidonic acid ARA powder, 6.8 parts of complex vitamins, 46 parts of complex minerals, and 0.5 parts of nucleotides; The composite amino acid is composed of the following components in parts by weight: 0.33 parts of L-cysteine, 0.37 parts of L-histidine, 1.52 parts of L-leucine, 1.4 parts of L-tyrosine and 0.32 parts of L-tryptophan; The protein-free fat powder is composed of the following parts by weight: 498 parts of glucose syrup, 385 parts of edible vegetable blending oil, 100 parts of sodium octenyl succinate starch, 15 parts of mono- and di-glycerol fatty acid esters, and 2 parts of sodium ascorbate; The edible vegetable blended oil is composed of the following parts by weight: 76.92 parts of sunflower oil, 153.83 parts of high oleic acid sunflower oil, 96.13 parts of low erucic acid rapeseed oil, 57.69 parts of coconut oil, 0.39 parts of mixed tocopherol concentrate, and 0.04 parts of ascorbyl palmitate; The DHA algae oil powder is composed of the following by weight: 354 parts of glucose syrup, 300 parts of sodium starch octenylsuccinate, 230 parts of docosahexaenoic acid oil, 59 parts of sodium ascorbate, 33 parts of mono- and diglycerol fatty acid esters, 10 parts of sodium citrate, 8 parts of tricalcium phosphate, 5 parts of phospholipids, and 1 part of ascorbyl palmitate; The arachidonic acid powder is composed of the following by weight: 360 parts of glucose syrup, 300 parts of sodium octenyl succinate starch, 230 parts of arachidonic acid oil, 53 parts of sodium ascorbate, 33 parts of mono- and di-glycerol fatty acid esters, 10 parts of sodium citrate, 8 parts of tricalcium phosphate, 5 parts of phospholipids, and 1 part of ascorbyl palmitate; The multivitamin comprises: vitamin A acetate 889705.8825mcg / kg, vitamin D3 19117.647mcg / kg, mixed tocopherol concentrate 6176.4705mg / kg, vitamin K 195588.2355mcg / kg, vitamin B 195588.2355mcg / kg, riboflavin 1220985.294mcg / kg, nicotinamide 9966323.5295mcg / kg, pantothenic acid 5637500mcg / kg, vitamin B 6943529.412mcg / kg, D-biotin 72058.824mcg / kg, folic acid 162352.941mcg / kg, vitamin B 12 2941.1765 mcg / kg, vitamin C 7352.941mg / kg, choline 176470.588mg / kg, iodine 152205.8825mcg / kg, selenium 29558.8235mcg / kg, L-carnitine 26470.588mg / kg, taurine 59852.941mg / kg, inositol 176470.588mg / kg; The composite minerals include: copper 100108.6955mcg / kg, iron 1347.8265mg / kg, magnesium 12804.348mg / kg, manganese 52413.0435mg / kg, sodium 26196.0435mg / kg, zinc 1347.8265mg / kg, calcium 134782.609mg / kg and chlorine 34782.609mg / kg; The nucleotides are composed of the following components in weight percentage: 20.3% of 5'-adenosine monophosphate, 30% of 5'-cytidylic acid disodium, 24% of 5'-uridylic acid disodium, 6.9% of 5'-guanylic acid disodium, and 13.8% of 5'-inosinic acid disodium.

[0066] The preparation steps of the formula powder include: Step 1) Weighing: Weigh the materials according to the formula, and prepare the materials according to the formula after weighing; Step 2) Premixing: Compound minerals, arachidonic acid (ARA) powder, nucleotides, DHA algae oil powder, compound vitamins, and compound amino acids are sequentially put into a premixer according to the formula requirements, and then the protein-free fat powder is put into the premixer for premixing; the premixing is eccentric mixing, and its parameters are as follows: the premixing time is 20 min, and the premixing speed is 12 r / min; Step 3) Feeding and screening: the premixed materials and other raw materials in step 2) are fed into a dry mixing tank according to the feeding requirements and screened at a mesh size of 16-20; Step 4) Dry mixing: dry mix the sieved materials in step 3) and temporarily store them in a dry mixing tank; in this embodiment, the total amount of dry mixing is 200 kg, and the dry mixing parameters are as follows: dry mixing time is 30 min, and the rotation speed is 8 r / min; Step 5) Metal detection: The materials in the dry mix tank are transported to the metal detector for detection, and after being detected to be free of metal impurities, they are filled; Step 6) Filling: Fill the material in step 5) according to the set net content to make the product; Step 7) Packing: Add outer covers to the products, pack them in boxes, and seal them; Step 8) Palletizing: Palletize the products according to the palletizing requirements; Step 9) Warehousing: transport the products to the finished product warehouse for storage; Step 10) Shipping: The product will be shipped after passing the inspection.

[0067] Example 3 A formula powder for infants with phenylketonuria with improved taste, comprising the following components in parts by weight: 100 parts of casein glycomacropeptide powder of Example 1, 5 parts of complex amino acids, 500 parts of protein-free fat powder, 150 parts of solid corn syrup, 5 parts of DHA algae oil powder, 5 parts of arachidonic acid ARA powder, 5 parts of complex vitamins, 20 parts of complex minerals, and 0.3 parts of nucleotides; wherein: The composite amino acid is composed of the following components in parts by weight: 0.42 parts of L-cysteine, 0.47 parts of L-histidine, 1.93 parts of L-leucine, 1.78 parts of L-tyrosine and 0.41 parts of L-tryptophan; The protein-free fat powder is composed of the following parts by weight: 599 parts of glucose syrup, 300 parts of edible vegetable blending oil, 90 parts of sodium octenyl succinate starch, 10 parts of mono- and di-glycerol fatty acid esters, and 1 part of sodium ascorbate; The edible vegetable blended oil is composed of the following components by weight: 70 parts of sunflower oil, 100 parts of high oleic acid sunflower oil, 109.89 parts of low erucic acid rapeseed oil, 20 parts of coconut oil, 0.1 parts of mixed tocopherol concentrate, and 0.01 parts of ascorbyl palmitate; The DHA algae oil powder is composed of the following by weight: 466.8 parts of glucose syrup, 300 parts of sodium starch octenylsuccinate, 220 parts of docosahexaenoic acid oil, 10 parts of sodium ascorbate, 1 part of mono- and di-glycerol fatty acid esters, 0.2 parts of sodium citrate, 1 part of tricalcium phosphate, 0.5 parts of phospholipids, and 0.5 parts of ascorbyl palmitate; The arachidonic acid powder is composed of the following parts by weight: 466.8 parts of glucose syrup, 300 parts of sodium starch octenylsuccinate, 220 parts of arachidonic acid oil, 10 parts of sodium ascorbate, 1 part of mono- and di-glycerol fatty acid esters, 0.2 parts of sodium citrate, 1 part of tricalcium phosphate, 0.5 parts of phospholipids, and 0.5 parts of ascorbyl palmitate; The nucleotides are composed of the following components in weight percentage: 15% adenosine 5'-monophosphate, 30% disodium 5'-cytidylate, 30% disodium 5'-uridylate, 10% disodium 5'-guanylate, and 15% disodium 5'-inosinate; The multivitamin contains: vitamin A acetate 756250mcg / kg, vitamin D316250mcg / kg, mixed tocopherol concentrate 5250mg / kg, vitamin K181250mcg / kg, vitamin B1837875mcg / kg, riboflavin 1308375mcg / kg, niacinamide 8471375mcg / kg, pantothenic acid 4791875mcg / kg, vitamin B6802000mcg / kg, D-biotin 30625mcg / kg, folic acid 138000mcg / kg, vitamin B 12 2500 mcg / kg, vitamin C 6617.647mg / kg, choline 158823.529mg / kg, iodine 129375mcg / kg, selenium 25125mcg / kg, L-carnitine 23823.529mg / kg, taurine 53867.647mg / kg, inositol 158823.529mg / kg; The composite minerals include: copper 100108.6955mcg / kg, iron 1347.8265mg / kg, magnesium 12804.348mg / kg, manganese 52413.0435mg / kg, sodium 26196.0435mg / kg, zinc 1347.8265mg / kg, calcium 134782.609mg / kg and chlorine 34782.609mg / kg; The preparation method of the formula powder is the same as that of Example 2.

[0068] Example 4 A formula powder for infants with phenylketonuria with improved taste, comprising the following components in parts by weight: 200 parts of casein glycomacropeptide powder of Example 1, 30 parts of complex amino acids, 700 parts of protein-free fat powder, 250 parts of solid corn syrup, 20 parts of DHA algae oil powder, 20 parts of arachidonic acid ARA powder, 10 parts of complex vitamins, 60 parts of complex minerals, and 0.7 parts of nucleotides; wherein: The composite amino acid is composed of the following components in parts by weight: 2.51 parts of L-cysteine, 2.82 parts of L-histidine, 11.57 parts of L-leucine, 10.66 parts of L-tyrosine and 2.44 parts of L-tryptophan; The protein-free fat powder is composed of the following by weight: 400 parts of glucose syrup, 500 parts of edible vegetable blending oil, 80 parts of sodium octenyl succinate starch, 12 parts of mono- and di-glycerol fatty acid esters, and 8 parts of sodium ascorbate; The edible vegetable blended oil is composed of the following components by weight: 90 parts of sunflower oil, 185 parts of high oleic acid sunflower oil, 200 parts of low erucic acid rapeseed oil, 20 parts of coconut oil, 4 parts of mixed tocopherol concentrate, and 1 part of ascorbyl palmitate; The DHA algae oil powder is composed of the following by weight: 290 parts of glucose syrup, 200 parts of sodium starch octenylsuccinate, 320 parts of docosahexaenoic acid oil, 60 parts of sodium ascorbate, 40 parts of mono- and diglycerol fatty acid esters, 30 parts of sodium citrate, 20 parts of tricalcium phosphate, 20 parts of phospholipids, and 20 parts of ascorbyl palmitate; The arachidonic acid powder is composed of the following by weight: 290 parts of glucose syrup, 200 parts of sodium starch octenylsuccinate, 320 parts of arachidonic acid oil, 60 parts of sodium ascorbate, 40 parts of mono- and di-glycerol fatty acid esters, 30 parts of sodium citrate, 20 parts of tricalcium phosphate, 20 parts of phospholipids, and 20 parts of ascorbyl palmitate; The nucleotides are composed of the following components in weight percentage: 25% adenosine 5'-monophosphate, 20% disodium 5'-cytidylate, 30% disodium 5'-uridylate, 10% disodium 5'-guanylate, and 15% disodium 5'-inosinate; The multivitamin comprises: vitamin A acetate 1023161.765mcg / kg, vitamin D3 21985.294mcg / kg, mixed tocopherol concentrate 7102.941mg / kg, vitamin K1109926.471mcg / kg, vitamin B11133595.588mcg / kg, riboflavin 1770154.412mcg / kg, nicotinamide 11461272.059mcg / kg, pantothenic acid 6483125mcg / kg, vitamin B6 1085058.824mcg / kg, D-biotin 41433.824mcg / kg, folic acid 186705.882mcg / kg, vitamin B 123382.353mcg / kg, vitamin C 8088.235mg / kg, choline 1944117.647mg / kg, iodine 152205.8825mcg / kg, selenium 29558.8235mcg / kg, L-carnitine 29117.647mg / kg, taurine 65838.235mg / kg, inositol 194117.647mg / kg; The complex minerals include: copper 110119.565mcg / kg, iron 1482.609mg / kg, magnesium 14084.783mg / kg, manganese 60275mg / kg, sodium 28815.217mg / kg, zinc 1482.609mg / kg, calcium 148260.870mg / kg and chlorine 38260.870mg / kg.

[0069] The preparation method of the formula powder is the same as that of Example 2.

[0070] Comparative Example 1: A formula powder for infants with phenylketonuria with improved taste, comprising the following components in parts by weight: 80 parts of casein glycomacropeptide powder in Example 1, 2.9 parts of complex amino acids, 480 parts of protein-free fat powder, 406.1 parts of solid corn syrup, 4 parts of DHA algae oil powder, 4 parts of arachidonic acid ARA powder, 4.8 parts of complex vitamins, 18 parts of complex minerals, and 0.2 parts of nucleotides; The composite amino acid is composed of the following components in parts by weight: 0.29 parts of L-cysteine, 0.27 parts of L-histidine, 1.02 parts of L-leucine, 1.2 parts of L-tyrosine and 0.12 parts of L-tryptophan; The protein-free fat powder is composed of the following parts by weight: 491.5 parts of glucose syrup, 290 parts of edible vegetable blending oil, 210 parts of sodium octenyl succinate starch, 8 parts of mono- and di-glycerol fatty acid esters, and 0.5 parts of sodium ascorbate; The edible vegetable blended oil is composed of the following components by weight: 60 parts of sunflower oil, 90 parts of high oleic acid sunflower oil, 40 parts of low erucic acid rapeseed oil, 194.89 parts of coconut oil, 0.1 parts of mixed tocopherol concentrate, and 0.01 parts of ascorbyl palmitate; The DHA algae oil powder is composed of the following by weight: 180 parts of glucose syrup, 8.8 parts of sodium starch octenylsuccinate, 200 parts of docosahexaenoic acid oil, 8 parts of sodium ascorbate, 1 part of mono- and di-glycerol fatty acid esters, 0.2 parts of sodium citrate, 1 part of tricalcium phosphate, 0.5 parts of phospholipids, and 0.5 parts of ascorbyl palmitate; The arachidonic acid powder is composed of the following parts by weight: 180 parts of glucose syrup, 608.8 parts of sodium starch octenylsuccinate, 200 parts of arachidonic acid oil, 8 parts of sodium ascorbate, 1 part of mono- and di-glycerol fatty acid esters, 0.2 parts of sodium citrate, 1 part of tricalcium phosphate, 0.5 parts of phospholipids, and 0.5 parts of ascorbyl palmitate; The nucleotides are composed of the following components in weight percentage: 13% adenosine 5'-monophosphate, 18% disodium 5'-cytidylate, 18% disodium 5'-uridylate, 5% disodium 5'-guanylate, and 44% disodium 5'-inosinate; The multivitamin contains: vitamin A acetate 72600mcg / kg, vitamin D315110mcg / kg, mixed tocopherol concentrate 5098mg / kg, vitamin K179588mcg / kg, vitamin B180588.2355mcg / kg, riboflavin 1000985.294mcg / kg, niacinamide 7966323.5295mcg / kg, pantothenic acid 4637500mcg / kg, vitamin B6643529.412mcg / kg, D-biotin 22058.824mcg / kg, folic acid 102352.941mcg / kg, vitamin B 12 1800.1765 mcg / kg, vitamin C 5352.941mg / kg, choline 126470.588mg / kg, iodine 112205.8825mcg / kg, selenium 22558.8235mcg / kg, L-carnitine 20470.588mg / kg, taurine 50852.941mg / kg, inositol 136470.588mg / kg; The composite minerals include: copper 80108.6955mcg / kg, iron 1047.8265mg / kg, magnesium 10804.348mg / kg, manganese 40413.0435mg / kg, sodium 20196.0435mg / kg, zinc 1047.8265mg / kg, calcium 104782.609mg / kg and chlorine 30782.609mg / kg; The preparation method of the formula powder is the same as that of Example 2.

[0071] Comparative Example 2: A formula powder for infants with phenylketonuria with improved taste, comprising the following components in parts by weight: 220 parts of casein glycomacropeptide powder in Example 1, 40 parts of complex amino acids, 480 parts of protein-free fat powder, 141.2 parts of solid corn syrup, 22 parts of DHA algae oil powder, 22 parts of arachidonic acid ARA powder, 12 parts of complex vitamins, 62 parts of complex minerals, and 0.8 parts of nucleotides; The composite amino acid is composed of the following components in parts by weight: 2.95 parts of L-cysteine, 2.75 parts of L-histidine, 12.2 parts of L-leucine, 12.2 parts of L-tyrosine and 1.22 parts of L-tryptophan; The protein-free fat powder is composed of the following parts by weight: 228 parts of glucose syrup, 520 parts of edible vegetable blending oil, 220 parts of sodium octenyl succinate starch, 22 parts of mono- and di-glycerol fatty acid esters, and 10 parts of sodium ascorbate; The edible vegetable blended oil is composed of the following components by weight: 93 parts of sunflower oil, 210 parts of high oleic acid sunflower oil, 205 parts of low erucic acid rapeseed oil, 5 parts of coconut oil, 5 parts of mixed tocopherol concentrate, and 2 parts of ascorbyl palmitate; The DHA algae oil powder is composed of the following by weight: 288 parts of glucose syrup, 180 parts of sodium starch octenylsuccinate, 330 parts of docosahexaenoic acid oil, 62 parts of sodium ascorbate, 42 parts of mono- and di-glycerol fatty acid esters, 32 parts of sodium citrate, 22 parts of tricalcium phosphate, 22 parts of phospholipids, and 22 parts of ascorbyl palmitate; The arachidonic acid powder is composed of the following by weight: 288 parts of glucose syrup, 180 parts of sodium starch octenylsuccinate, 330 parts of arachidonic acid oil, 62 parts of sodium ascorbate, 42 parts of mono- and diglycerol fatty acid esters, 32 parts of sodium citrate, 22 parts of tricalcium phosphate, 22 parts of phospholipids, and 22 parts of ascorbyl palmitate; The multivitamin comprises: vitamin A acetate 104600161mcg / kg, vitamin D325110mcg / kg, mixed tocopherol concentrate 8098mg / kg, vitamin K1129588mcg / kg, vitamin B11200588.2355mcg / kg, riboflavin 1900985.294mcg / kg, niacinamide 13006323.5295mcg / kg, pantothenic acid 7897500mcg / kg, vitamin B6 1203529.412mcg / kg, D-biotin 52058.824mcg / kg, folic acid 192352.941mcg / kg, vitamin B 12 4800.1765 mcg / kg, vitamin C 9352.941mg / kg, choline 216470.588mg / kg, iodine 192205.8825mcg / kg, selenium 42558.8235mcg / kg, L-carnitine 32470.588mg / kg, taurine 70852.941mg / kg, inositol 210470.588mg / kg; The composite minerals include: copper 130108.6955mcg / kg, iron 10547.8265mg / kg, magnesium 15804.348mg / kg, manganese 70413.0435mg / kg, sodium 29196.0435mg / kg, zinc 1847.8265mg / kg, calcium 164782.609mg / kg and chlorine 39782.609mg / kg; The nucleotides are composed of the following components in weight percentage: 45% of 5'-adenosine monophosphate, 18% of 5'-cytidylic acid disodium, 15% of 5'-uridylic acid disodium, 4% of 5'-guanylic acid disodium, and 18% of 5'-inosinic acid disodium.

[0072] The preparation method of the formula powder is the same as that of Example 2.

[0073] test: 1. Detection of molecular weight distribution Method: The sample was dissolved in the mobile phase and measured by a high performance liquid chromatography system equipped with a gel permeation chromatography column and a UV detector. The sample components were separated according to their relative molecular weights, and peptides and proteins were measured at 214nm, 220nm or 280nm. The relative molecular weights and distribution ranges of different components were calculated by chromatographic data processing.

[0074] Reagents and standards: Water: Secondary water; Sodium dihydrogen phosphate dihydrate (NaH2PO4): analytical grade; Ammonium chloride (NH4Cl): analytical grade; Acetonitrile (CH3CN): chromatographic grade; Trifluoroacetic acid (TFA): chromatographic grade; Cytochrome C: MW12384; Aprotinin: MW6512; Bacillus enzyme: MW1423; Tyrosine-Tyrosine-Arg: MW451; Tyrosine-Tyrosine-Tyrosine: MW189.

[0075] Instruments and equipment: High performance liquid chromatograph: with UV detector; electronic balance (sensitivity 0.1 mg and 0.01 mg).

[0076] Chromatographic conditions: Chromatographic column: TSKgel G2000 SWXL300mmx7.8mm or equivalent.

[0077] Mobile phase: 75% A (0.0375M sodium dihydrogen phosphate dihydrate + 0.375M ammonium chloride solution): 25% B (acetonitrile) (v / v), containing 0.1% (v / v) trifluoroacetic acid; Detection wavelength: 214 nm; Flow rate: 0.5 mL / min; Column temperature: 30℃.

[0078] Preparation of relative molecular mass calibration curve: Prepare 5 standards with different relative molecular masses with mobile phase, filter through microporous membrane and measure to obtain chromatogram of standard. Perform curve fitting with relative molecular mass and corresponding retention time to obtain relative molecular mass calibration curve and equation.

[0079] Sample treatment: Weigh an appropriate amount of sample into a volumetric flask, add mobile phase to dissolve, mix well and filter, and measure the filtrate after filtering through a microporous filter membrane.

[0080] Calculation of relative molecular mass distribution: Substitute the sample's chromatographic data retention time into the calibration curve for calculation to obtain the sample's relative molecular mass and its distribution range. Use the peak area normalization method to calculate the distribution of different relative molecular mass intervals, and calculate according to the following formula:

[0081] In the above formula: X—the mass fraction of protein hydrolysate in a certain relative molecular mass range in the sample to the total protein hydrolysate, %; A—Peak area of ​​protein hydrolysate in a certain relative molecular mass range; A —The sum of the peak areas in each interval, with the calculation result retained to one decimal place.

[0082] Repeatability: The absolute difference between two independent measurement results obtained under repeatability conditions shall not exceed 15% of the arithmetic mean of the two measurement results.

[0083] The molecular weight distribution of the products in Examples 2-4 and Comparative Examples 1-2 was tested using the above-mentioned testing method. The results are shown in Table 1.

[0084] Table 1 Molecular weight distribution

[0085] The results show that the molecular weight distribution of the formula powder in Examples 2-4 is that <3000 Da accounts for 99.9%, ≤1000 Da accounts for more than 90%, and >3000 Da accounts for only 0.1%.

[0086] According to the test results, the lower the content of molecular weight <3000Da, the more effectively it can reduce the probability of allergic reactions. In the formula powder of comparative examples 1-2, the content of >1000Da accounts for 3.5%-5.1%, and the probability of causing allergic reactions is relatively higher.

[0087] 2. Taste test The taste differences between Example 2 and commercially available food 1 (the commercially available food was purchased from overseas) were evaluated, and the results are shown in Table 2.

[0088] A total of 16 people participated in this test, and the overall taste preference was measured using a 9-point pleasure scale (9→1 means extremely like→extremely dislike, <5 points means dislike).

[0089] Table 2 Overall taste preference

[0090] Note: The same letters under each indicator indicate no significant difference at the 5% significance level, and different letters indicate significant difference at the 5% significance level.

[0091] From the results, it can be seen that the product of Example 2 is significantly better than commercially available foods in terms of overall preference, sweetness, and fishy smell, and is also better than commercially available foods in terms of bitterness, odor, and thickness, which is consistent with the results of electronic nose analysis; after electronic nose analysis, casein glycomacropeptide is weaker on nitrogen oxide, alcohol, and sulfide sensors. The content of high molecular weight aldehyde substances gradually increases with the progress of process treatment, the types and contents of alkanes and alcohols decrease, and the acid substances are significantly reduced, thereby improving the taste of the formula food. In addition, solid corn syrup is added to the product of Example 2, which significantly improves the problem of poor taste caused by exposure to bitter amino acids compared to maltodextrin.

[0092] 3. Dispersibility test The overall mixing effects of Example 2 and commercially available food 1 were measured respectively. The specific results are shown in Table 3, and the scoring details are shown in Table 4.

[0093] Table 3 Analysis of brewing characteristics

[0094] Table 4 Scoring criteria for reconciliation

[0095] 4. Allergy protein content test The allergenic protein content of the formula powder in Examples 2-4 and Comparative Examples 1-2 was analyzed, and the detection was carried out by ELISA sandwich enzyme-linked immunosorbent assay to quantitatively detect casein, soy protein, whole milk protein, β-lactoglobulin, and β-lactoglobulin fragments in the formula food, and the results are shown in Table 5. Among them, the detection limit of casein, soy protein, and whole milk protein allergens is 2.5 mg / kg; the detection limit of β-lactoglobulin allergen is 0.167 mg / kg; and the detection limit of β-lactoglobulin fragment allergen is 5 mg / kg.

[0096] Table 5 Allergic protein content

[0097] The results showed that the content of food protein allergens in Examples 2-4 were all lower than the detection limit, and the content of food protein allergens in Comparative Examples 1-2 were all higher than the detection limit, indicating that the infant formula powder for phenylketonuria in the present application can play a role in reducing the risk of food protein allergy.

[0098] 5. Analysis of the impact on intelligence of children with phenylketonuria and observation of allergic reactions during medication Analysis of the effects of the formula powder in Example 2 and commercially available food 1 on the intelligence of children with phenylketonuria and observation of allergic reactions during consumption.

[0099] Test children: 24 children with phenylketonuria who were screened and diagnosed were selected. All infants were tested for intelligence using the Wechsler Children's Intelligence Scale (C-WYCSI). The scores of the infants for language, arithmetic, patterns, etc. were combined as the judgment results. The test evaluation criteria are in line with the diagnostic criteria of the 2019 Consensus on Dietary Treatment and Nutritional Management of Phenylalanine Hydroxylase Deficiency and the 2023 Expert Consensus on Diagnosis and Management of Neonatal Cow's Milk Protein Allergy. Among the 24 children in this group, there were 12 males and 12 females; the age was 3-6 weeks, with an average of (5.1±1.2) weeks; the course of the disease was 8-20d. The manifestations of allergic symptoms in children are shown in Table 6.

[0100] Treatment method: The children were randomly divided into two groups, one group took the commercially available formula food 1 normally, and the other group took the formula powder of Example 2 of the present application instead. The feeding time was 3 weeks, and the stool characteristics were observed. Medical staff conducted telephone follow-up on allergic symptoms after 1 week, 2 weeks and 3 weeks of feeding. The changes in the children's intelligence development were recorded and compared before and after 3 weeks of consumption. The statistical results of intelligence analysis before and after treatment are shown in Table 7.

[0101] Evaluation indicators: observe and record the effect of nutritional treatment on the children. Remarkable treatment results: the child's symptoms improve significantly within one week after treatment; effective: the child's symptoms improve within two weeks after treatment; ineffective: the child's symptoms do not change significantly within three weeks after treatment.

[0102] Statistical methods: Each variable is expressed as x±s. The t test was used, and P<0.05 was considered to be statistically significant.

[0103] Conclusion: Compared with the common formula, the results of various intelligence performances have changed significantly after using the formula powder of Example 2 of the present application. While controlling the disease, the intelligence development of the children has been effectively improved. The special design of the formula for the allergic reactions of the children has effectively reduced the allergic reactions such as eczema, diarrhea, abdominal pain, vomiting, nasal congestion, and runny nose shown by the children. Therefore, the children taking the formula powder of the present application have good clinical efficacy and innovation.

[0104] Table 6 Statistics of allergic symptoms in 24 children with phenylketonuria (times / three weeks; average number of allergies in each group)

[0105] Table 7 Observation on the effect of the formula of this application and the common formula on the market on improving the intelligence of children

[0106] The test results of allergic symptoms and intellectual performance of infants using the formula powder of Example 2 are the best. The main reasons may be: 1) Compared with other formulas, casein glycomacropeptide and a small amount of complex amino acids are added to the product of the present application, and the nutritional ingredients are closer to the proportion required by the human body; 2) α-casein and β-lactoglobulin are the most common causes of milk protein allergic reactions. The present application uses a dynamic ion exchange method to decompose α-casein and β-lactoglobulin that cause allergic reactions, reduce the allergen content, and then use an ultrafiltration membrane to absorb flavor compounds and phenylalanine, so that the whey protein extract does not contain phenylalanine and allergens, improves the taste and effectively reduces allergic reactions such as eczema, diarrhea, abdominal pain, vomiting, nasal congestion, runny nose, etc. shown by infants; 3) In the experimental group of the product of the present application, the intellectual performance of infants is also better than that of ordinary formulas, which effectively reduces the occurrence of allergic reactions while controlling the disease and improves the intellectual development of children.

[0107] Therefore, children taking the formula of the application have a good clinical effect and are beneficial to the growth and development of children.

[0108] 6. Test on the effect of lowering blood phenylalanine Experimental subjects: 50 phenylketonuria model mice, half male and half female, weighing 100-140 g.

[0109] Experimental method: After feeding the experimental mice with feed that complies with GB / 14924.2 "Standard for Hygienic Feed for Laboratory Animals" for 3 days, blood was collected from the tail vein to detect the phenylalanine content in the blood, which was calculated as the initial phenylalanine concentration. Randomly divided into 2 groups (25 in each group, half male and half female), one group fed with a customized mouse diet containing only bovine whey protein was set as the control group, and the other group was fed with the formula powder prepared in Example 2 of this application, with 6g of feed each time, and 5mL of distilled water was fed at the same time, for 14 days, and blood was collected from the tail vein on the 14th day to detect the phenylalanine content in the serum, which was calculated as the phenylalanine concentration after the experiment, and the results are shown in Table 8.

[0110] Table 8 Determination of phenylalanine concentration in rat blood

[0111] As can be seen from Table 8, compared with the control group, Example 2 can effectively control the phenylalanine content in the blood of phenylketonuria model mice, has a good effect of reducing phenylalanine concentration, and prevents and treats phenylketonuria or hyperphenylalaninemia. The main reason is that the dynamic ion exchange method used in the formula powder of Example 2 can further decompose phenylalanine, and there is no phenylalanine, which reduces the concentration of phenylalanine in the blood. During the feeding process, all test mice grew well and no adverse reactions occurred, indicating that the safety of the formula powder of this application is good.

[0112] 7. Osmotic pressure test The osmotic pressure of Example 2 and commercially available food 1 was tested using a freezing point osmometer. The results are shown in Table 9.

[0113] Table 9 Osmotic pressure determination

[0114] It can be seen from Table 9 that the osmotic pressure of the product in Example 2 is lower than that of commercially available products.

[0115] In summary, in the formula product of the present application: 1) casein glycomacropeptide and a small amount of complex amino acids prepared by dynamic ion exchange method are used as protein sources, and have a good taste; the ratio thereof refers to the amino acid content in breast milk, and the ratio is scientific; it can ensure the amino acid intake of infants and young children without producing the accumulation of phenylalanine and its ketoacids, thereby maintaining the normal amino acid metabolism of the body and enhancing immunity; 2) it provides all nutrients such as energy, protein, carbohydrates, fatty acids, vitamins and minerals required for the growth and development of infants and young children, promotes the normal growth and development of the body, and while the nutrient absorption is more sufficient, the low osmotic pressure effectively reduces allergic reactions such as diarrhea.

[0116] In addition, the molecular weight distribution in the formula powder for phenylketonuria patients in this application is 99.9% <3000Da, more than 90% ≤1000 Da, and only 0.1% >3000Da. From the test results, the lower the molecular weight <3000Da, the more effectively it can reduce the probability of allergic reactions; the content of casein, soy protein, and whole milk protein allergens are all lower than 2.5 mg / kg; the content of β-lactoglobulin allergens is lower than 0.167 mg / kg; the content of β-lactoglobulin fragment allergens is lower than 5 mg / kg; the overall preference, sweetness, and fishy smell are significantly better than commercially available foods, and the bitterness, odor, and thickness are also better than commercially available foods; solid corn syrup is also added, which significantly improves the problem of poor taste caused by exposure to bitter amino acids compared to maltodextrin.

[0117] Compared with the common formula, the formula powder of the present application effectively improves the intellectual development of children while controlling the disease, and is specially designed for children's allergic reactions, effectively reducing allergic reactions such as eczema, diarrhea, abdominal pain, vomiting, nasal congestion, runny nose, etc. Therefore, children taking the formula powder of the present application have good clinical efficacy and innovation, and can also effectively reduce the concentration of phenylalanine and prevent and treat phenylketonuria or hyperphenylalaninemia.

[0118] The above embodiments describe in detail the formula powder for phenylketonuria patients and the preparation method thereof. Although the embodiments of the present application have been shown and described above, it can be understood that the above embodiments are exemplary and cannot be understood as limiting the present application. A person of ordinary skill in the art can change, modify, replace and modify the above embodiments within the scope of the present application.

Claims

1. A formula powder for patients with phenylketonuria, characterized in that: By weight, it includes the following components: 100-200 parts by weight of casein glycomacropeptide, 3-20 parts by weight of complex amino acids, 500-700 parts by weight of protein-free fat powder, 150-250 parts by weight of solid corn syrup, 5-20 parts by weight of DHA algae oil powder, 5-20 parts by weight of arachidonic acid powder, 5-10 parts by weight of complex vitamins, 20-60 parts by weight of complex minerals, and 0.3-0.7 parts by weight of nucleotides; the formula powder for patients with phenylketonuria does not contain phenylalanine.

2. The formula powder for phenylketonuria patients according to claim 1, characterized in that: The casein glycomacropeptide is a product separated and extracted from a raw material solution containing casein glycomacropeptide, wherein the preparation method of the casein glycomacropeptide comprises: The raw material solution containing casein glycomacropeptide is adjusted to pH 4.5-5.6 and then allowed to stand to remove precipitated foreign proteins to obtain a supernatant; The pH of the supernatant is adjusted to 3.6-4.2 and then added to an exchange column filled with an anion resin. After adsorption, the supernatant is eluted with a sodium chloride solution having an equal volume to the resin, and the eluate is collected; The eluate is desalted and concentrated using an ultrafiltration membrane with a molecular weight cutoff of 4000u-8000u, and then freeze-dried to obtain casein glycomacropeptide.

3. The formula powder for phenylketonuria patients according to claim 2, characterized in that: The raw material liquid is a whey powder solution of 0.02-0.06 g / mL; and / or The exchange column filled with anion resin is an exchange column filled with 201×4 resin; and / or In the exchange column, the volume ratio of the sample to the resin is (0.5:1) to (2:1); and / or The concentration of the sodium chloride solution is 0.4 mol / L-0.8 mol / L.

4. The formula powder for phenylketonuria patients according to any one of claims 1 to 3, characterized in that: The protein-free fat powder is produced using raw materials and auxiliary materials that do not contain protein, and the protein-free fat powder has a protein content of ≤0.5g / 100g and a fat content of ≥30g / 100g; Optionally, the protein-free fat powder is composed of the following parts by weight: 400-600 parts of glucose syrup, 300-500 parts of edible vegetable blending oil, 80-200 parts of sodium octenyl succinate starch, 10-20 parts of mono- and di-glycerol fatty acid esters, and 1-8 parts of sodium ascorbate; Optionally, the edible vegetable blended oil is composed of the following by weight: 70-90 parts of sunflower oil, 100-200 parts of high oleic sunflower oil, 50-200 parts of low erucic acid rapeseed oil, 20-100 parts of coconut oil, 0.1-4 parts of mixed tocopherol concentrate, and 0.01-1 parts of ascorbyl palmitate.

5. The formula powder for phenylketonuria patients according to any one of claims 1 to 3, characterized in that: The DHA algae oil powder is composed of the following by weight: 200-500 parts of glucose syrup, 200-500 parts of sodium starch octenylsuccinate, 220-320 parts of docosahexaenoic acid oil, 10-60 parts of sodium ascorbate, 1-40 parts of mono- and diglycerol fatty acid esters, 0.2-30 parts of sodium citrate, 1-20 parts of tricalcium phosphate, 0.5-20 parts of phospholipids, and 0.5-20 parts of ascorbyl palmitate; and / or The arachidonic acid powder is composed of the following by weight: 200-500 parts of glucose syrup, 200-500 parts of sodium starch octenylsuccinate, 220-320 parts of arachidonic acid oil, 10-60 parts of sodium ascorbate, 1-40 parts of mono- and diglycerol fatty acid esters, 0.2-30 parts of sodium citrate, 1-20 parts of tricalcium phosphate, 0.5-20 parts of phospholipids, and 0.5-20 parts of ascorbyl palmitate; and / or The composite amino acid, by weight, consists of: 0.33-2.51 parts of L-cysteine, 0.37-2.82 parts of L-histidine, 1.52-11.57 parts of L-leucine, 1.4-10.66 parts of L-tyrosine and 0.32-2.44 parts of L-tryptophan; and / or The nucleotides are composed of the following components by mass percentage: 15%-25% of 5'-adenosine monophosphate, 20%-40% of 5'-cytidylic acid disodium, 20%-30% of 5'-uridylic acid disodium, 6%-10% of 5'-guanylic acid disodium, and 10%-20% of 5'-inosinic acid disodium.

6. The formula powder for phenylketonuria patients according to any one of claims 1 to 3, characterized in that: The multivitamin comprises: vitamin A acetate 756250.000-1023161.765 mcg / kg, vitamin D3 16250-21985.294 mcg / kg, mixed tocopherol concentrate 5250.000-7102.941 mg / kg, vitamin K181250-109926.471 mcg / kg, vitamin B181250-109926.471 mcg / kg, riboflavin 1308375.000-1133595.588 mcg / kg, nicotinamide 8471375.000-11461272.059 mcg / kg, pantothenic acid 4791875.000-6483125.000 mcg / kg, vitamin B6 802000.0000-1085058.824 mcg / kg, D-biotin 30625.000-41433.824 mcg / kg, folic acid 138000.000-186705.882 mcg / kg, vitamin B 12 2500.000-3382.353mcg / kg, vitamin C 6617.647-8088.235 mg / kg, choline 158823.529-194117.647mg / kg, iodine 129375.000-175036.765mcg / kg, selenium 25125.000-33992.647mcg / kg, L-carnitine 23823.529-29117.647mg / kg, taurine 53867.647-65838.235mg / kg, inositol 158823.529-194117.647mg / kg; and / or The complex minerals include: copper 90097.826-110119.565mcg / kg, iron 1213.044-1482.609mg / kg, magnesium 11523.913-14084.783mg / kg, manganese 44551.087-60275.000mg / kg, sodium 23576.087-28815.217mg / kg, zinc 1213.044-1482.609mg / kg, calcium 121304.348-148260.870mg / kg and chlorine 31304.348-38260.870mg / kg.

7. The formula powder for phenylketonuria patients according to any one of claims 1 to 3, characterized in that: The molecular weight distribution of the formula powder for patients with phenylketonuria is: 99.9% of the formula powder is less than 3000 Da, more than 90% of the formula powder is less than 1000 Da, and 0.1% of the formula powder is greater than 3000 Da.

8. A method for preparing a formula powder for phenylketonuria patients according to any one of claims 1 to 7, characterized in that: The method comprises the following steps: Step 1) Weighing: Weigh the materials according to the formula, and prepare the materials according to the formula after weighing; Step 2) Premixing: Add the composite minerals, arachidonic acid powder, nucleotides, DHA algae oil powder, composite vitamins, and composite amino acids into a premixer in sequence according to the formula requirements, and then add the protein-free fat powder for premixing; Step 3) Feeding and screening: the premixed materials and other raw materials in step 2) are fed into a dry mixing tank according to the feeding requirements and screened; optionally, the mesh size of the screening process is 16-20 meshes; Step 4) Dry mixing: After dry mixing the materials, temporarily store them in a dry mixing tank; Step 5) Metal detection: The material in the dry mixing tank is transported to a metal detector for detection, and after being detected to be free of metal impurities, it is filled; Step 6) Filling: Filling the material according to the set net content to produce a product; Step 7) Packing: adding an outer cover to the product, packing it in a box, and sealing it; Step 8) Palletizing: palletizing the products according to palletizing requirements; Step 9) Warehousing: transporting the product to the finished product warehouse for warehousing; Step 10) Shipping: The product is shipped after passing the inspection.

9. A formula powder for phenylketonuria patients prepared by the method of claim 8.

10. An infant formula food comprising the formula powder for phenylketonuria patients according to any one of claims 1 to 7 and 9, wherein: The infant formula food is milk powder.

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