A protein composition with good stability, its preparation method and its application

Abstract

The present invention relates to a protein composition with good stability. By weight percentage, the protein composition contains 10 - 40% of hydrolyzed whey protein, any one or a combination of 10 - 40% of soy peptide or collagen peptide, and a pharmaceutically acceptable carrier. Among them, the weight-average molecular weight of the hydrolyzed whey protein is 500 - 1500, and the weight-average molecular weight of any one or a combination of the soy peptide or collagen peptide is 500 - 3000. The protein composition of the present invention is used to provide enteral nutrition for patients with hypoalbuminemia and / or perioperative patients, promote wound (injury) healing, significantly improve the protein nutrition index and intestinal tolerance of patients, significantly reduce the incidence of postoperative complications and the incidence of diarrhea, and has the advantages of high protein content, rapid protein supplementation, high bioavailability, good stability, etc.

Description

Technical Field

[0001] The present invention relates to the field of biomedicine, and in particular to a protein composition with good stability, a preparation method thereof and an application thereof. Background Art

[0002] Patients have increased energy and nutrient intake requirements due to surgery, trauma, and postoperative rehabilitation. Post-illness anorexia, surgical fasting, digestive dysfunction, vomiting, diarrhea, etc. may lead to reduced food intake and cause malnutrition, resulting in reduced protein synthesis in the body, decreased body resistance and immunity, etc., prolonging wound healing time and postoperative rehabilitation time. In severe cases, hypoalbuminemia may occur, including complications such as significant reductions in plasma total protein (less than 60g / L) and serum albumin (less than 35g / L), affecting postoperative wound healing, postoperative rehabilitation and prognosis, and even endangering life and health in severe cases. Timely supplementation of sufficient high-quality protein is beneficial for patients with hypoalbuminemia and / or perioperative patients (such as surgical patients, trauma patients, orthopedic patients, burn patients, patients with eating disorders, patients with gastrointestinal dysfunction, wound healing patients, etc.) to correct the health damage caused by protein malnutrition and promote postoperative rehabilitation.

[0003] The main causes of hypoalbuminemia include increased consumption or insufficient synthesis of albumin to compensate for its metabolism, poor response to exogenous nutrient substrates, etc., and are characterized by long hospitalization time and high mortality rate. Hypoalbuminemia is common in critically ill elderly people, tumors, cirrhosis, nephrotic syndrome and other diseases. Clinical manifestations include weight loss, lower limb edema, low immunity, etc., and severe cases can be life-threatening. Timely correction of the patient's low protein level is conducive to improving the patient's surgical tolerance, promoting surgical wound healing, reducing postoperative complications, and shortening the patient's recovery time. Treatments for hypoalbuminemia include albumin or plasma infusion, hormone therapy, parenteral complete nutrition products, parenteral glutamine, enteral nutritional supplements, etc.

[0004] The "Guidelines for Perioperative Nutritional Support in Adults 2016" pointed out that increasing the protein supply of perioperative patients to 1.5-2.0g / kg / d can achieve ideal treatment effects, especially for patients with major surgical trauma who have higher protein and essential amino acid requirements. The "SCCM / ASPEN Guidelines: Evaluation and Provision of Nutritional Support Therapy for Adult Hazardous Patients 2016" recommends that the protein supplement for burn patients be 1.5-2g / kg / d. The "Guidelines for Nutritional Support for Hazardous Patients in Intensive Care Units in China 2006" and the "ASPEN Guidelines: Guidelines for the Application of Parenteral and Enteral Nutrition in Adult and Pediatric Patients 2002" pointed out that if patients cannot eat orally, enteral nutrition needs to be provided. Patients with normal digestion and absorption function can use whole protein formulas, while patients with abnormal digestion and absorption function are recommended to use pre-digested formulas or monomer formulas (i.e., short peptide formulas).

[0005] Whey protein or protein peptide products have the following defects: first, the protein content is low, and it is difficult to quickly supplement the protein and nutrients needed by patients; second, the stability is poor, and crystallization is easy to occur during the shelf life or storage period; third, patients with abnormal digestion and absorption function have little absorption of whey protein, and even cause adverse reactions such as allergies; fourth, the bioavailability is not high. Therefore, it is urgent to develop a protein composition with high protein content, good stability and high bioavailability to meet clinical needs. Summary of the invention

[0006] The object of the present invention is to provide a protein composition with good stability. The protein composition contains, by weight percentage, 10-40% of hydrolyzed whey protein, 10-40% of any one of soy peptides or collagen peptides or a combination thereof, and a pharmaceutically acceptable carrier, wherein the weight average molecular weight of the hydrolyzed whey protein is 500-1500, and the weight average molecular weight of any one of the soy peptides or collagen peptides or a combination thereof is 500-3000.

[0007] In a preferred technical solution of the present invention, the hydrolyzed whey protein in the protein composition is 15-35% by weight, preferably 20-30%.

[0008] In a preferred technical solution of the present invention, the mass ratio of hydrolyzed whey protein to any one of soy peptides or collagen peptides or a combination thereof in the protein composition is 1-2:1.

[0009] In a preferred technical solution of the present invention, the hydrolysis degree of the hydrolyzed whey protein is 26-50%, preferably 26-40%.

[0010] In a preferred technical solution of the present invention, the weight average molecular weight of the hydrolyzed whey protein is 750-1100.

[0011] In the preferred technical scheme of the present invention, the molecular weight distribution of the hydrolyzed whey protein is as follows: the hydrolyzed whey protein with a molecular weight of less than 375Da accounts for 17.5%, the hydrolyzed whey protein with a molecular weight of 375-750Da accounts for 37.9%, the hydrolyzed whey protein with a molecular weight of 750-1250Da accounts for 25.8%, the hydrolyzed whey protein with a molecular weight of 1250-2500Da accounts for 16.9%, and the hydrolyzed whey protein with a molecular weight greater than 2500Da accounts for 1.9%.

[0012] In a preferred technical solution of the present invention, the protein content in the hydrolyzed whey protein is not less than 80%, preferably not less than 85%.

[0013] In a preferred technical solution of the present invention, the total branched-chain amino acids contained in the hydrolyzed whey protein are not less than 20%, preferably not less than 23.5%.

[0014] In the preferred technical solution of the present invention, the hydrolysis degree of the hydrolyzed whey protein is 26-40%, the weight average molecular weight is 750-1100, the protein content in the hydrolyzed whey protein is not less than 85%, and the total branched-chain amino acids are 20-23.5%.

[0015] In a preferred technical solution of the present invention, the protein composition contains 15-35% by weight of any one of soybean peptides or collagen peptides or a combination thereof, preferably 20-30%.

[0016] In a preferred technical solution of the present invention, the protein content of any one of the soybean peptides or collagen peptides or a combination thereof is not less than 85%, preferably not less than 90%.

[0017] In a preferred technical solution of the present invention, the weight average molecular weight of the collagen peptide is 2000-3000, preferably 2100-2500.

[0018] In the preferred technical scheme of the present invention, the molecular weight distribution of the collagen peptides is as follows: collagen peptides with a molecular weight greater than 10,000Da account for 3.01%, collagen peptides with a molecular weight of 10,000-5,000Da account for 10.46%, collagen peptides with a molecular weight of 5,000-3,000Da account for 12.34%, collagen peptides with a molecular weight of 3,000-2,000Da account for 11.56%, collagen peptides with a molecular weight of 2,000-1,000Da account for 21.84%, collagen peptides with a molecular weight of 1,000-500Da account for 20.45%, collagen peptides with a molecular weight of 500-180Da account for 16.46%, and collagen peptides with a molecular weight less than 180Da account for 3.87%.

[0019] In a preferred technical solution of the present invention, the hydroxyproline content in the collagen peptide is not less than 10%, preferably not less than 12.3%.

[0020] In the preferred technical solution of the present invention, the weight average molecular weight (Mw) of the collagen peptide is 2100-2500, the protein content is greater than 90%, and the hydroxyproline content is 12.3%.

[0021] In a preferred technical solution of the present invention, the weight average molecular weight of the soybean peptide is 400-1000, preferably 500-900.

[0022] In the preferred technical scheme of the present invention, the molecular weight distribution of the soybean peptide is as follows: soybean peptides with a molecular weight greater than 5000Da account for 0.98%, soybean peptides with a molecular weight of 5000-3000Da account for 3.01%, soybean peptides with a molecular weight of 3000-2000Da account for 4.96%, soybean peptides with a molecular weight of 2000-1000Da account for 13.62%, soybean peptides with a molecular weight of 1000-500Da account for 22.04%, soybean peptides with a molecular weight of 500-180Da account for 38.93%, and soybean peptides with a molecular weight of less than 180Da account for 16.46%.

[0023] In a preferred technical solution of the present invention, the pharmaceutically acceptable carrier optionally contains any one of a preservative, an acidity regulator, a sweetener, and a flavor, or a combination thereof.

[0024] In the preferred technical solution of the present invention, the preservative in the composition is 0-0.15% by weight, preferably 0.01-0.05% by weight.

[0025] In a preferred technical solution of the present invention, the preservative is selected from any one of sodium benzoate and potassium sorbate or a combination thereof.

[0026] In a preferred technical solution of the present invention, the acidity regulator is selected from any one of DL-malic acid, sodium malate, phosphoric acid, sodium hydrogen phosphate, sodium dihydrogen phosphate, citric acid, sodium citrate, or a combination thereof.

[0027] In a preferred technical solution of the present invention, the sweetener is selected from any one of mogroside, acesulfame potassium, sucralose, and glucosyl steviol glycoside or a combination thereof.

[0028] In the preferred technical solution of the present invention, the flavor is selected from any one of lemon flavor, concentrated sweet flavor, peach flavor or a combination thereof.

[0029] In a preferred technical solution of the present invention, the composition contains 0-1% of any one of the sweeteners or flavors, preferably 0.01-0.5% by weight.

[0030] In a preferred technical solution of the present invention, the composition comprises, by weight percentage, 10-40% hydrolyzed whey protein, 10-40% soy peptide or collagen peptide or a combination thereof, 0.01-0.05% preservative and 0.01-0.5% sweetener, wherein the sweetener is selected from any one or a combination of acesulfame potassium, sucralose, and glucosyl steviol glycoside, and the preservative is selected from any one or a combination of sodium benzoate and potassium sorbate.

[0031] In a preferred technical solution of the present invention, the composition comprises, by weight percentage, 20% hydrolyzed whey protein, 20% soy peptide or collagen peptide or a combination thereof.

[0032] In the preferred technical scheme of the present invention, the composition comprises, by weight percentage, 20% hydrolyzed whey protein, 20% of any one of soy peptides or collagen peptides or a combination thereof, 0.03% acesulfame potassium, 0.01% sucralose, 0.1% glucosyl steviol glycoside, 0.01% sodium benzoate, and 0.03% potassium sorbate.

[0033] In the preferred technical scheme of the present invention, the composition comprises, by weight percentage, 30% hydrolyzed whey protein, 15% any one of soy peptides or collagen peptides or a combination thereof, 0.03% acesulfame potassium, 0.01% sucralose, 0.1% glucosyl steviol glycoside, 0.01% sodium benzoate and 0.03% potassium sorbate.

[0034] In a preferred technical solution of the present invention, the protein composition is a solution with a pH of 3-pH 4.6, and the balance is water.

[0035] In a preferred technical solution of the present invention, the protein content in the protein composition is not less than 0.3333 g / ml.

[0036] In a preferred technical solution of the present invention, the protein composition is placed at 60° C. for 10 days, and the protein content loss is less than 2%, preferably substantially no loss.

[0037] In a preferred technical solution of the present invention, the protein composition is placed under 4500±500Lx conditions for 10 days, and the protein content loss is less than 2%, preferably substantially no loss.

[0038] Another object of the present invention is to provide a method for preparing a protein composition with good stability. The composition contains, by weight percentage, 10-40% hydrolyzed whey protein, 10-40% of any one or combination of soy peptides or collagen peptides, and a pharmaceutically acceptable carrier. The weight average molecular weight of the hydrolyzed whey protein is 500-1500, and the weight average molecular weight of any one or combination of the soy peptides or collagen peptides is 500-3000. The preparation comprises the following steps: dissolving a required amount of hydrolyzed whey protein in 40-60°C water under stirring, then adding a required amount of any one or combination of soy peptides or collagen peptides and the remaining pharmaceutically acceptable carriers, and stirring until completely dissolved.

[0039] In a preferred technical solution of the present invention, the protein composition is sterilized at 80-90° C. for 10-30 min.

[0040] In a preferred technical solution of the present invention, the hydrolyzed whey protein in the protein composition is 15-35% by weight, preferably 20-30%.

[0041] In a preferred technical solution of the present invention, the mass ratio of hydrolyzed whey protein to any one of soy peptides or collagen peptides or a combination thereof in the protein composition is 1-2:1.

[0042] In a preferred technical solution of the present invention, the hydrolysis degree of the hydrolyzed whey protein is 26-50%, preferably 26-40%.

[0043] In a preferred technical solution of the present invention, the weight average molecular weight of the hydrolyzed whey protein is 750-1100.

[0044] In the preferred technical scheme of the present invention, the molecular weight distribution of the hydrolyzed whey protein is as follows: the hydrolyzed whey protein with a molecular weight of less than 375Da accounts for 17.5%, the hydrolyzed whey protein with a molecular weight of 375-750Da accounts for 37.9%, the hydrolyzed whey protein with a molecular weight of 750-1250Da accounts for 25.8%, the hydrolyzed whey protein with a molecular weight of 1250-2500Da accounts for 16.9%, and the hydrolyzed whey protein with a molecular weight greater than 2500Da accounts for 1.9%.

[0045] In a preferred technical solution of the present invention, the protein content in the hydrolyzed whey protein is not less than 80%, preferably not less than 85%.

[0046] In a preferred technical solution of the present invention, the total branched-chain amino acids contained in the hydrolyzed whey protein are not less than 20%, preferably not less than 23.5%.

[0047] In the preferred technical solution of the present invention, the hydrolysis degree of the hydrolyzed whey protein is 26-40%, the weight average molecular weight is 750-1100, the protein content in the hydrolyzed whey protein is not less than 85%, and the total branched-chain amino acids are 20-23.5%.

[0048] In a preferred technical solution of the present invention, the protein composition contains 15-35% by weight of any one of soybean peptides or collagen peptides or a combination thereof, preferably 20-30%.

[0049] In a preferred technical solution of the present invention, the protein content of any one of the soybean peptides or collagen peptides or a combination thereof is not less than 85%, preferably not less than 90%.

[0050] In a preferred technical solution of the present invention, the weight average molecular weight of the collagen peptide is 2000-3000, preferably 2100-2500.

[0051] In the preferred technical scheme of the present invention, the molecular weight distribution of the collagen peptides is as follows: collagen peptides with a molecular weight greater than 10,000Da account for 3.01%, collagen peptides with a molecular weight of 10,000-5,000Da account for 10.46%, collagen peptides with a molecular weight of 5,000-3,000Da account for 12.34%, collagen peptides with a molecular weight of 3,000-2,000Da account for 11.56%, collagen peptides with a molecular weight of 2,000-1,000Da account for 21.84%, collagen peptides with a molecular weight of 1,000-500Da account for 20.45%, collagen peptides with a molecular weight of 500-180Da account for 16.46%, and collagen peptides with a molecular weight less than 180Da account for 3.87%.

[0052] In a preferred technical solution of the present invention, the hydroxyproline content in the collagen peptide is not less than 10%, preferably not less than 12.3%.

[0053] In the preferred technical solution of the present invention, the weight average molecular weight (Mw) of the collagen peptide is 2100-2500, the protein content is greater than 90%, and the hydroxyproline content is 12.3%.

[0054] In a preferred technical solution of the present invention, the weight average molecular weight of the soybean peptide is 400-1000, preferably 500-900.

[0055] In the preferred technical scheme of the present invention, the molecular weight distribution of the soybean peptide is as follows: soybean peptides with a molecular weight greater than 5000Da account for 0.98%, soybean peptides with a molecular weight of 5000-3000Da account for 3.01%, soybean peptides with a molecular weight of 3000-2000Da account for 4.96%, soybean peptides with a molecular weight of 2000-1000Da account for 13.62%, soybean peptides with a molecular weight of 1000-500Da account for 22.04%, soybean peptides with a molecular weight of 500-180Da account for 38.93%, and collagen peptides with a molecular weight of less than 180Da account for 16.46%.

[0056] In a preferred technical solution of the present invention, the pharmaceutically acceptable carrier optionally contains any one of a preservative, an acidity regulator, a sweetener, and a flavor, or a combination thereof.

[0057] In the preferred technical solution of the present invention, the preservative in the composition is 0-0.15% by weight, preferably 0.01-0.05% by weight.

[0058] In a preferred technical solution of the present invention, the preservative is selected from any one of sodium benzoate and potassium sorbate or a combination thereof.

[0059] In a preferred technical solution of the present invention, the acidity regulator is selected from any one of DL-malic acid, sodium malate, phosphoric acid, sodium hydrogen phosphate, sodium dihydrogen phosphate, citric acid, sodium citrate, or a combination thereof.

[0060] In a preferred technical solution of the present invention, the sweetener is selected from any one of mogroside, acesulfame potassium, sucralose, and glucosyl steviol glycoside or a combination thereof.

[0061] In the preferred technical solution of the present invention, the flavor is selected from any one of lemon flavor, concentrated sweet flavor, peach flavor or a combination thereof.

[0062] In a preferred technical solution of the present invention, the composition contains 0-1% of any one of the sweeteners or flavors, preferably 0.01-0.5% by weight.

[0063] In a preferred technical solution of the present invention, the composition comprises, by weight percentage, 10-40% hydrolyzed whey protein, 10-40% soy peptide or collagen peptide or a combination thereof, 0.01-0.05% preservative and 0.01-0.5% sweetener, wherein the sweetener is selected from any one or a combination of acesulfame potassium, sucralose, and glucosyl steviol glycoside, and the preservative is selected from any one or a combination of sodium benzoate and potassium sorbate.

[0064] In a preferred technical solution of the present invention, the composition comprises, by weight percentage, 20% hydrolyzed whey protein, 20% soy peptide or collagen peptide or a combination thereof.

[0065] In the preferred technical scheme of the present invention, the composition comprises, by weight percentage, 20% hydrolyzed whey protein, 20% of any one of soy peptides or collagen peptides or a combination thereof, 0.03% acesulfame potassium, 0.01% sucralose, 0.1% glucosyl steviol glycoside, 0.01% sodium benzoate, and 0.03% potassium sorbate.

[0066] In the preferred technical scheme of the present invention, the composition comprises, by weight percentage, 30% hydrolyzed whey protein, 15% any one of soy peptides or collagen peptides or a combination thereof, 0.03% acesulfame potassium, 0.01% sucralose, 0.1% glucosyl steviol glycoside, 0.01% sodium benzoate and 0.03% potassium sorbate.

[0067] In a preferred technical solution of the present invention, the protein composition is a solution with a pH of 3-pH 4.6, and the balance is water.

[0068] In a preferred technical solution of the present invention, the protein content in the protein composition is not less than 0.3333 g / ml.

[0069] In a preferred technical solution of the present invention, the protein composition is placed at 60° C. for 10 days, and the protein content loss is less than 2%, preferably substantially no loss.

[0070] In a preferred technical solution of the present invention, the protein composition is placed under 4500±500Lx conditions for 10 days, and the protein content loss is less than 2%, preferably substantially no loss.

[0071] Another object of the present invention is to provide a use of the protein composition of the present invention in preparing a product for supplementing the protein and nutrition required by patients with hypoproteinemia, patients with pressure ulcers and / or perioperative patients.

[0072] In a preferred technical solution of the present invention, the perioperative patient is selected from any one of surgical patients, trauma patients, orthopedic patients, burn patients, eating disorder patients, gastrointestinal dysfunction patients, and wound healing patients.

[0073] Unless otherwise specified, when the present invention relates to the percentage between liquids, the percentage is volume / volume percentage; when the present invention relates to the percentage between liquids and solids, the percentage is volume / weight percentage; when the present invention relates to the percentage between solids and liquids, the percentage is weight / volume percentage; the rest are weight / weight percentages.

[0074] Unless otherwise specified, the present invention uses a hydroxyproline (Hyp) assay kit (alkaline hydrolysis method) to detect the hydroxyproline content in amino acids. The PUSH score in the present invention is a pressure sore healing scoring scale, which was revised by the American Pressure Sore Expert Group in 1998 as a quantitative scoring method for evaluating the healing effect of pressure sores. It has strong clinical operability and helps to directly, effectively and objectively evaluate the wound healing situation. The scale includes three dimensions: wound area, exudate volume and tissue type. The wound area range is 0-24cm 2 , assigned a score of 1-10; the amount of exudate is divided into 4 levels: none (0 points), a small amount (1 point), a moderate amount (2 points) and a large amount (3 points); the wound tissue type is divided into 5 levels: intact skin (0 points), epithelial tissue (1 point), granulation tissue (2 points), slough tissue (3 points) and necrotic tissue (4 points). The sum of the scores of the three dimensions is used to evaluate the healing of the patient's pressure injury. The total score ranges from 0 to 17 points, with 0 representing wound healing. A decrease in the total push score indicates that the pressure injury has improved; an increase in the total score indicates that the pressure injury has worsened.

[0075] Compared with the prior art, the present invention has the following beneficial technical effects:

[0076] 1. The protein composition of the present invention is scientifically formulated with any one or a combination of hydrolyzed whey protein and collagen peptides or soy peptides and their proportions. The protein composition is used for enteral nutrition for patients with hypoalbuminemia and / or perioperative patients, provides high-quality protein and nutrients required for metabolism to patients through the gastrointestinal tract, effectively maintains the integrity of the intestinal barrier function and mucosal structure, and synergistically utilizes hydrolyzed whey protein (such as 23.5% total branched-chain amino acids) and any one or a combination of collagen peptides (such as 12.3% hydroxyproline) or soy peptides to quickly supplement the protein and nutrients urgently needed by patients, promote wound (injury) healing, significantly improve the protein nutrition index and intestinal tolerance of patients, significantly reduce the incidence of postoperative complications and diarrhea, and has the advantages of high protein content (the protein content in the composition is not less than 0.3333 g / ml), rapid protein supplementation, high bioavailability (after taking it for six days, the prealbumin increases by 2 times; after taking it for 18 days, the prealbumin increases by 16 times), good stability (no crystallization occurs under high temperature and long-term storage), etc.

[0077] 2. The preparation method of the protein composition of the present invention has the advantages of simple operation, environmental protection, and suitability for large-scale industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0078] Figure 1 The protein composition of the present invention is used for supplementing the protein and nutrition required by ICU patients;

[0079] Figure 2 The protein composition of the present invention is studied for promoting wound healing. DETAILED DESCRIPTION

[0080] The present invention will be described below with reference to examples, but the present invention is not limited to the examples.

[0081] The hydrolyzed whey protein, collagen peptide and soy peptide in the specific embodiment are all commercially available, and their molecular weight distribution is shown in Table 1. The hydrolysis degree of the hydrolyzed whey protein is 26-30%, the protein content is not less than 85%, and the total branched-chain amino acids are 23.5%. The weight average molecular weight (Mw) of the collagen peptide is 2381, the protein content is not less than 91%, and the hydroxyproline content is 12.3%; the weight average molecular weight (Mw) of the soy peptide is 753.

[0082] Table 1

[0083]

[0084] Example 1 Preparation of the protein composition of the present invention

[0085] Composition of the protein composition:

[0086]

[0087] The preparation of the protein composition comprises the following steps: dissolving a required amount of hydrolyzed whey protein in 40-60°C water under stirring, adding a required amount of collagen peptide, DL-malic acid, phosphoric acid, glucosyl stevioside, acesulfame potassium, sucralose, potassium sorbate, sodium benzoate, concentrated sweet flavor and peach flavor, stirring until completely dissolved, adding water to make the volume 100 ml, and sterilizing it at 80-90°C for 20 minutes to obtain a protein composition with a pH of 4.5.

[0088] Example 2 Preparation of the protein composition of the present invention

[0089] Composition of the protein composition:

[0090]

[0091]

[0092] The preparation of the protein composition comprises the following steps: dissolving a required amount of hydrolyzed whey protein in 40-60°C water under stirring, adding a required amount of collagen peptide, DL-malic acid and phosphoric acid, stirring until completely dissolved, adding water to make the volume 100ml, and sterilizing it at 80-90°C for 20min to obtain a protein composition with a pH of 4.5.

[0093] Example 3 Preparation of the protein composition of the present invention

[0094] Composition of the protein composition:

[0095]

[0096] The preparation of the protein composition comprises the following steps: dissolving a required amount of hydrolyzed whey protein in 40-60°C water under stirring, adding a required amount of collagen peptide, DL-malic acid and phosphoric acid, stirring until completely dissolved, adding water to make the volume 100ml, and sterilizing it at 80-90°C for 20min to obtain a protein composition with a pH of 4.5.

[0097] Example 4 Preparation of the protein composition of the present invention

[0098] Composition of the protein composition:

[0099]

[0100] The preparation of the protein composition comprises the following steps: dissolving a required amount of hydrolyzed whey protein in 40-60°C water under stirring, adding a required amount of soybean peptide, DL-malic acid and phosphoric acid, stirring until completely dissolved, adding water to make the volume 100ml, and sterilizing it at 80-90°C for 20min to obtain a protein composition with a pH of 4.5.

[0101] Comparative Example 1

[0102] Composition of the protein composition:

[0103]

[0104] The preparation of the protein composition comprises the following steps: dissolving a required amount of hydrolyzed whey protein in 40-60°C water under stirring, adding a required amount of collagen peptide, DL-malic acid and phosphoric acid, stirring until completely dissolved, adding water to make the volume 100ml, and sterilizing it at 80-90°C for 20min to obtain a protein composition with a pH of 4.5.

[0105] Comparative Example 2

[0106] Composition of the protein composition:

[0107]

[0108]

[0109] The preparation of the protein composition includes the following steps: dissolving the required amount of collagen peptide in 40-60°C water under stirring, adding the required amount of DL-malic acid and phosphoric acid, stirring until completely dissolved, adding water to make the volume 100 ml, and then sterilizing it at 80-90°C for 20 minutes to obtain a protein composition with a pH of 4.5.

[0110] Comparative Example 3

[0111] Composition of the protein composition:

[0112] Components Dosage(g) Hydrolyzed Whey Protein 40 DL-Malic Acid 2 Phosphoric acid 0.1 Glucosyl Stevioside 0.1 Acesulfame K 0.03 Sucralose 0.01 Potassium Sorbate 0.03 Sodium Benzoate 0.01 Concentrated sweet flavor 0.1 Peach flavor 0.1

[0113] The preparation of the protein composition comprises the following steps: dissolving a required amount of hydrolyzed whey protein in 40-60°C water under stirring, adding a required amount of DL-malic acid and phosphoric acid, stirring until completely dissolved, adding water to make the volume 100 ml, and sterilizing it at 80-90°C for 20 minutes to obtain a protein composition with a pH of 4.5.

[0114] Test Example 1 Investigation on the stability of the protein composition of the present invention

[0115] The compositions of Example 1 and Comparative Example 1 were placed at 60°C for 10 days, and their shapes, energy values, protein contents and other indicators were observed and tested every day. During the inspection period, the color, smell and tissue state of the composition of Example 1 all met the quality requirements, and no foreign matter was visible to normal vision, and the energy value and protein content were basically not lost. The protein composition of Comparative Example 1 crystallized on the second day.

[0116] The composition of Example 1 was placed under 4500±500Lx for 10 days, and its shape, energy value, protein content and other indicators were observed and tested every day. During the inspection period, the color, smell and tissue state of the composition of Example 1 all met the quality requirements, and no foreign matter was visible to normal vision, and the energy value and protein content were basically not lost. The protein composition of Comparative Example 1 crystallized on the second day.

[0117] Test Example 2 The protein composition of the present invention is used to supplement the protein and nutrition required by ICU patients

[0118] Twenty ICU patients were selected as subjects. The subjects were aged 35-70 years old, and there was no significant statistical difference in age, disease type, gender, etc. (P>0.05). The vital signs were basically stable, there was no serious liver and kidney dysfunction, and nutritional support was more than 4 days. The 20 subjects were randomly divided into 2 groups, 10 in each group. Group 1: The patients took 30 ml of the protein composition of Example 1 orally each time, 3 times / day, for 18 days; Group 2: The patients took 30 ml of the protein composition of Comparative Example 3 orally each time, 3 times / day, for 18 days. The changes in prealbumin in patients on the 6th, 10th, and 18th days of continuous use and the diarrhea during the use were observed. The results show that the protein composition of the present invention rapidly increases the patient's prealbumin level (p<0.05) ( Figure 1 ) and significantly reduced the incidence of diarrhea in patients (from 11% to 8%).

[0119] Test Example 3 Study on the effect of the protein composition of the present invention on promoting wound healing

[0120] Twenty patients with pressure ulcers were selected as subjects and randomly divided into two groups, 10 in each group. There was no significant difference in age, disease type, gender, etc. (P>0.05). Inclusion criteria: male and female patients aged 18-70 years old in hospital or outpatient clinics; diagnosed with stage II or III pressure ulcers; body mass index of 18.5-34.9kg / m 2 ; Show 80cm 2of pressure ulcer surface area (the product of the major and minor diameters of the wound surface); in patients with stage II or III pressure ulcers, PUSH score ≥ 5 points, who were likely to heal during the 6-month study period; and showed moderate exudate production and Braden score ≥ 6 points.

[0121] Exclusion criteria: pregnant or breastfeeding women; women of childbearing age who are not taking adequate contraceptive measures; patients with stage IV pressure ulcers; patients who are fed through a catheter; patients with diabetic foot ulcers; patients who have received immunotherapy or cytotoxic chemotherapy within 60 days before inclusion; patients who have taken systemic steroids within 30 days before inclusion; patients who have received local treatment other than steroids within 7 days before inclusion; patients who are positive for human immunodeficiency virus, hepatitis B virus, or hepatitis C virus; patients with existing demyelinating diseases; patients with liver, kidney, or metabolic diseases that may interfere with their participation in or completion of the study; patients with arterial or venous diseases that may cause ulcerated wounds; patients with a history of estab, diabetes, and fasting blood glucose level 200mg dl-1; patients with any condition that may interfere with wound healing (such as connective tissue disorders, immune disorders or clinical obesity); malnourished patients; patients with trauma caused by malignant tumors; patients with burns or scalds; patients who have used any form of free alternative medicine in the past 2 months; patients known to show hypersensitivity to protein products; patients with any skin disease or condition that may interfere with the appropriate evaluation or treatment of ulcers; current smokers; patients who have participated in any other clinical research within 3 months before this trial; patients who are unwilling or unable to comply with the study procedures; patients who are considered unsuitable by the investigator for any reason.

[0122] Group 1: patients took 30 ml of the protein composition of Example 1 orally, 3 times a day, for 16 weeks; Group 2: patients took 30 ml of the protein composition of Comparative Example 2 orally, 3 times a day, for 16 weeks. The wound area (cm 2 ), and calculate the push score at the same time, the results are shown in Figure 2 a. Figure 2 b. The protein composition of the present invention significantly promotes wound healing in patients (p<0.05).

[0123] The above description of the specific embodiments of the present invention does not limit the present invention. Those skilled in the art may make various changes or modifications based on the present invention. As long as they do not depart from the spirit of the present invention, they should all fall within the scope of protection of the claims of the present invention.

Claims

1. A protein composition with good stability, calculated by weight percentage, the protein composition consists of 10-40% hydrolyzed whey protein, 10-40% collagen peptide, and a pharmaceutically acceptable carrier and water. The mass ratio of hydrolyzed whey protein to collagen peptide in the protein composition is 1:

1. Among them, The weight-average molecular weight of the hydrolyzed whey protein is 500-1500, the degree of hydrolysis of the hydrolyzed whey protein is 26-50%, and the protein content in the hydrolyzed whey protein is not less than 80%. The weight-average molecular weight of the collagen peptide is 2000-3000, and the protein content of the collagen peptide is not less than 85%. The molecular weight distribution of the hydrolyzed whey protein is as follows: the proportion of hydrolyzed whey protein with a molecular weight less than 375Da is 17.5%, the proportion of hydrolyzed whey protein with a molecular weight of 375-750Da is 37.9%, the proportion of hydrolyzed whey protein with a molecular weight of 750-1250Da is 25.8%, the proportion of hydrolyzed whey protein with a molecular weight of 1250-2500Da is 16.9%, and the proportion of hydrolyzed whey protein with a molecular weight greater than 2500Da is 1.9%. The molecular weight distribution of the collagen peptide is as follows: the proportion of collagen peptide with a molecular weight greater than 10000Da is 3.01%, the proportion of collagen peptide with a molecular weight of 10000-5000Da is 10.46%, the proportion of collagen peptide with a molecular weight of 5000-3000Da is 12.34%, the proportion of collagen peptide with a molecular weight of 3000-2000Da is 11.56%, the proportion of collagen peptide with a molecular weight of 2000-1000Da is 21.84%, the proportion of collagen peptide with a molecular weight of 1000-500Da is 20.45%, the proportion of collagen peptide with a molecular weight of 500-180Da is 16.46%, and the proportion of collagen peptide with a molecular weight less than 180Da is 3.87%.

2. The protein composition according to claim 1, calculated by weight percentage, the hydrolyzed whey protein in the protein composition is 15-35%.

3. The protein composition according to claim 2, calculated by weight percentage, the hydrolyzed whey protein in the protein composition is 20-30%.

4. The protein composition according to claim 1, the degree of hydrolysis of the hydrolyzed whey protein is 26-40%.

5. The protein composition according to claim 1, the weight-average molecular weight of the hydrolyzed whey protein is 750-1100.

6. The protein composition according to claim 1, the protein content in the hydrolyzed whey protein is not less than 85%.

7. The protein composition according to claim 1, the total branched-chain amino acids contained in the hydrolyzed whey protein are not less than 20%.

8. The protein composition according to claim 7, the total branched-chain amino acids contained in the hydrolyzed whey protein are not less than 23.5%.

9. The protein composition according to claim 1, the degree of hydrolysis of the hydrolyzed whey protein is 30-40%, the weight-average molecular weight is 750-1100, the protein content in the hydrolyzed whey protein is not less than 85%, and the total branched-chain amino acids are 20-23.5%.

10. The protein composition according to claim 1, wherein the collagen peptide contained in the protein composition is 15-35% by weight.

11. The protein composition according to claim 10, wherein the collagen peptide contained in the protein composition is 20-30% by weight.

12. The protein composition according to claim 1, wherein the protein content in the collagen peptide is not less than 90%.

13. The protein composition according to claim 1, wherein the weight-average molecular weight of the collagen peptide is 2100-2500.

14. The protein composition according to claim 1, wherein the hydroxyproline content in the collagen peptide is not less than 10%.

15. The protein composition according to claim 14, wherein the hydroxyproline content in the collagen peptide is not less than 12.3%.

16. The protein composition according to claim 1, wherein the weight-average molecular weight (Mw) of the collagen peptide is 2100-2500, the protein is greater than 90%, and the hydroxyproline content is 12.3%.

17. The protein composition according to claim 1, wherein the pharmaceutically acceptable carrier optionally contains any one or a combination of preservatives, acidity flavoring agents, sweeteners, and fragrances.

18. The protein composition according to claim 17, wherein the preservative in the composition is 0-0.15% by weight.

19. The protein composition according to claim 18, wherein the preservative in the composition is 0.01-0.05% by weight.

20. The protein composition according to claim 17, wherein the preservative is selected from any one or a combination of sodium benzoate and potassium sorbate.

21. The protein composition according to claim 17, wherein the acidity regulator is selected from any one or a combination of DL-malic acid, sodium malate, phosphoric acid, sodium hydrogen phosphate, sodium dihydrogen phosphate, citric acid, and sodium citrate.

22. The protein composition according to claim 17, wherein the sweetener is selected from any one or a combination of mogroside, acesulfame potassium, sucralose, and glucosyl stevioside.

23. The protein composition according to claim 17, wherein the fragrance is selected from any one or a combination of lemon essence, concentrated sweet fragrance, and peach essence.

24. The protein composition according to claim 17, wherein any one of the sweetener or fragrance contained in the composition is 0-1% by weight.

25. The protein composition according to claim 24, wherein any one of the sweetener or fragrance contained in the composition is 0.01-0.5% by weight.

26. The protein composition according to claim 17, wherein the hydrolyzed whey protein in the composition is 10-40%, the collagen peptide is 10-40%, the preservative is 0.01-0.05%, and the sweetener is 0.01-0.5%, wherein, the sweetener is selected from any one or a combination of acesulfame potassium, sucralose, and glucosyl stevioside, and the preservative is selected from any one or a combination of sodium benzoate and potassium sorbate.

27. The protein composition according to claim 1, wherein the hydrolyzed whey protein in the composition is 20% and the collagen peptide is 20% by weight.

28. The protein composition according to claim 26, wherein, by weight percentage, the hydrolyzed whey protein in the composition is 20%, the collagen peptide is 20%, acesulfame potassium is 0.03%, sucralose is 0.01%, glucosyl stevioside is 0.1%, sodium benzoate is 0.01%, and potassium sorbate is 0.03%.

29. The protein composition according to any one of claims 1-28, wherein the protein composition is a solution with a pH of 3 - 4.6, and the balance is water.

30. The protein composition according to any one of claims 1-28, wherein the protein content in the protein composition is not less than 0.3333 g / ml.

31. The protein composition according to any one of claims 1-28, when the protein composition is placed at 60 °C for 10 days, the loss of its protein content is less than 2%.

32. The protein composition according to claim 31, when the protein composition is placed at 60 °C for 10 days, its protein content has basically no loss.

33. The protein composition according to any one of claims 1-28, when the protein composition is placed under the condition of 4500 ± 500 Lx for 10 days, the loss of its protein content is less than 2%.

34. The protein composition according to claim 33, when the protein composition is placed under the condition of 4500 ± 500 Lx for 10 days, its protein content has basically no loss.

35. The preparation method of the protein composition with good stability according to any one of claims 1-34, the preparation comprises the following steps: under stirring conditions, dissolve the required amount of hydrolyzed whey protein in water at 40-60 °C, then add the required amount of collagen peptide and the remaining pharmaceutically acceptable carriers, and stir until completely dissolved to obtain the product.

36. The method according to claim 35, wherein the protein composition is sterilized at 80-90 °C for 10-30 min.

37. The application of the protein composition with good stability according to any one of claims 1-34 in the preparation of products for supplementing protein and nutrition required by patients with hypoproteinemia, pressure ulcers, and perioperative patients.

38. The application according to claim 37, wherein the perioperative patients are selected from any one of surgical patients, trauma patients, orthopedic patients, burn patients, patients with eating disorders, patients with gastrointestinal dysfunction, and patients with wound healing.

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