CN117860875A - Polypeptide composition and application - Google Patents
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Classifications
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/38—Albumins
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/17—Amino acids, peptides or proteins
- A23L33/18—Peptides; Protein hydrolysates
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/17—Amino acids, peptides or proteins
- A23L33/185—Vegetable proteins
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- A61K38/01—Hydrolysed proteins; Derivatives thereof
- A61K38/011—Hydrolysed proteins; Derivatives thereof from plants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/01—Hydrolysed proteins; Derivatives thereof
- A61K38/012—Hydrolysed proteins; Derivatives thereof from animals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
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- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
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- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/08—Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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- Animal Behavior & Ethology (AREA)
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Abstract
The invention discloses a polypeptide composition and application thereof, wherein the polypeptide composition comprises the following components in parts by weight: 20-70 parts of qingxi flower turtle peptide, 10-60 parts of walnut peptide, 5-55 parts of albumin peptide and 15-60 parts of pea peptide. Use of a polypeptide composition for the preparation of a food or medicament for assisting hemodialysis in the treatment of chronic kidney disease. The invention combines 2 animal peptides with 2 plant peptides, the amino acid composition is more comprehensive, and the proportion of the 4 peptides is designed to ensure that the proportion of the amino acid is better, thereby having better bioactivity.
Description
Technical Field
The invention belongs to the technical field of biology, and particularly relates to a polypeptide composition and application thereof.
Background
Chronic Kidney Disease (CKD) is a generic term for heterogeneous diseases that persist for more than 3 months due to abnormalities in kidney structure or function caused by various causes, which is a serious threat to human life and health. CKD is divided into 5 stages according to Glomerular Filtration Rate (GFR). CKD patients are at risk of a range of nutritional disorders, including malnutrition, protein energy consumption, electrolyte disorders, and trace element deficiencies, and nutritional intervention is critical to CKD patients, can slow down disease progression, alleviate symptoms, and reduce patient risk of malnutrition. Elevated systemic levels of inflammatory cytokines such as IL-1, IL-6 and TNF-alpha lead to chronic disease states of increased protein and energy catabolism, muscle decline and weakness, and the alleviation of inflammatory responses is an important intervention in patients with advanced renal disease.
Intestinal tract is the largest immune organ of the human body, and intestinal dysbiosis plays an important role in many chronic diseases, and improving such dysbiosis may be a potential strategy for preventing and managing these diseases. There is a complex interaction between the gut, gut flora and the kidneys (gut-renal axis), through which gut flora composition and metabolites affect renal-related disease progression.
Peptides are structural and functional fragments of proteins, having a molecular weight much smaller than that of the proteins, and peptides having biological activity are called bioactive peptides, and the physiological activity of many proteins is actually exerted by the form of the peptides. Compared with protein, the peptide is easier to be absorbed by human body, and the di-tripeptide can be directly absorbed by transport protein, so that the energy consumption is low and the body metabolism burden is low. The absorption efficiency of the peptide is higher than that of the free amino acid, and there is no competition or inhibition. For patients who cannot absorb certain amino acid well due to diseases, the amino acid can be provided by supplementing peptides containing the amino acid, so that the amino acid has important nutritional value. For patients in CKD 3-5 stage, dietary protein intake needs to be strictly controlled, glomerular filtration load is caused by too high, malnutrition risk is increased due to insufficient intake, and the peptide can well meet the requirements of CKD patients as a substance with nutrition and activity functions.
Disclosure of Invention
Aiming at the problems existing in the prior art, the invention aims to provide a polypeptide composition and application, and the polypeptide composition is realized by the following technical scheme:
a polypeptide composition, which consists of the following components in parts by weight: 20-70 parts of qingxi flower soft-shelled turtle peptide, 10-60 parts of walnut peptide, 5-55 parts of albumin peptide and 15-60 parts of pea peptide, and preferably consists of the following components in parts by weight: 30-60 parts of qingxi flower turtle peptide, 10-50 parts of walnut peptide, 10-45 parts of albumin peptide and 20-50 parts of pea peptide.
Use of a polypeptide composition for the preparation of a food or medicament for assisting hemodialysis in the treatment of chronic kidney disease.
Further, the use of a polypeptide composition for maintaining or increasing the level of prealbumin in a patient suffering from chronic kidney disease.
Further, the use of the polypeptide composition for modulating the number of neutrophils in blood.
Further, the use of the polypeptide composition for modulating interleukin 6 concentration in blood.
Further, the use of a polypeptide composition for slowing down the rate of elevation of blood ammonia.
Further, the use of the polypeptide composition in inflammatory diseases caused by increased abundance of inflammatory bacteria in the gut.
According to the formula, 2 animal peptides are compounded into 2 plant peptides, the composition of amino acids is more comprehensive, and the proportion of amino acids is better by designing the proportion of 4 peptides. The qingxihua turtle peptide is a rare peptide type and has multiple bioactive functions, and previous researches have found that the qingxihua turtle peptide which is a unique component contains a large amount of antihypertensive peptides and antihyperglycemic peptide fragments, including an angiotensin I converting enzyme inhibitor, a dipeptidyl peptidase IV inhibitor and an alpha-glucosidase inhibitor through comparing with the existing living active peptide database, and in addition, the qingxihua turtle peptide has higher affinity with a plurality of immune receptors and has the activity of regulating immunity. The walnut peptide has the functions of improving memory, relieving fatigue and resisting oxidation. Albumin peptide is a high-quality dietary protein source, is mostly used as a functional raw material in the aspect of immunoregulation, and has the effects of enhancing organism immunity, promoting absorption of nutrient substances such as calcium, iron and the like, regulating intestinal flora and the like. Pea peptide has positive effects in promoting growth of probiotics, regulating intestinal flora balance, regulating immunity, and assisting in lowering blood pressure.
Drawings
FIG. 1 is a bar graph of prealbumin changes before and after intervention in control and intervention groups;
FIG. 2 is a graph showing the percentage of neutrophils and IL-6 change before and after intervention in the control and intervention groups;
FIG. 3 is a graph showing changes in blood ammonia before and after intervention in the control group and the intervention group;
FIG. 4 is a graph showing the variation of alpha diversity of intestinal flora before and after intervention in a control group and an intervention group;
FIG. 5 is a graph showing changes in intestinal flora portal levels before and after intervention in control and intervention groups;
fig. 6 is a graph showing changes in intestinal flora levels before and after intervention in the control group and the intervention group.
Detailed Description
The present invention is described in further detail below in conjunction with specific embodiments to provide a better understanding of the present technical solution.
Case selection
Diagnostic criteria
CKD diagnostic criteria: CKD refers to kidney injury or Glomerular Filtration Rate (GFR)<60ml/min/1.73m 2 More than three months.
CKD staging criteria: referring to the kdaigo 2021 clinical practice guideline, the CKD staging criteria are shown in table 1.
TABLE 1
| Stage by stage | Renal function | GFR(ml/min/1.73m 2 ) |
| 1 | Kidney injury | ≥90 |
| 2 | Kidney injury | 60-89 |
| 3 | Moderate decrease in GFR | 30-59 |
| 4 | GFR severe drop | 15-29 |
| 5 | Renal failure | <15 |
Inclusion criteria:
(1) CKD stage 5 patients undergoing maintenance hemodialysis;
(2) Patients aged 18-70, with unlimited sexuality;
(3) Complete drug usage records are available;
(4) Patients with severe liver function damage and other types of kidney disease;
(5) Patients with clear consciousness and high compliance;
(6) Consent was given to participate in the study, and informed consent was signed.
Exclusion criteria
(1) Patients with complicated heart failure, malignant tumor, edema, etc.;
(2) Patients with infectious diseases just before dialysis;
(3) Patients being treated with immunosuppressants or with autoimmune diseases;
(4) Individuals with impaired functions of important viscera;
(5) Those with disturbance of consciousness;
(6) Conditions or treatments suspected of affecting the gut microbiota including history of abdominal surgery, inflammatory bowel disease, gastrointestinal cancer, transmissible gastroenteritis over the last 4 weeks, continued or recent use of antibiotics over the last 4 weeks, and ingestion of probiotics or prebiotics over the last 4 weeks;
(7) Unwilling to cooperate or poor compliance, and can not be taken according to the requirements and checked by the inspector;
(8) Pregnant or lactating women.
Examples
Taking 20-70 parts of qingxi flower soft-shelled turtle peptide, 10-60 parts of walnut peptide, 5-55 parts of albumin peptide and 15-60 parts of pea peptide, and fully and uniformly mixing to obtain the polypeptide composition. More preferably, 30-60 parts of Qingxi flower turtle peptide, 10-50 parts of walnut peptide, 10-45 parts of albumin peptide and 20-50 parts of pea peptide.
The eligible 20 patients were randomly averaged into two groups, an intervention group and a control group, with 4 weeks of intervention. In the normal continuous hemodialysis process of the intervention group patients, the polypeptide is orally taken for nutritional intervention, 2 parts of the polypeptide composition are taken every day, 2g each in the morning and evening, and 100-200mL of warm water, milk and the like are taken. The control group of patients only maintained the original hemodialysis treatment. Both groups of patients keep the original diet structure and habit, do not change life work, exercise habit and the like, follow the doctor's advice, and avoid taking proteins, peptides and other products of the same type during the intervention.
Basic information (including age, sex, BMI, creatinine, blood urea nitrogen) was collected from the patient at the early stage of the experiment, and pre-serum albumin, blood ammonia, neutrophil percentage, IL-6 and intestinal flora were determined before and after intervention.
Intestinal flora detection method: 1) DNA extraction 1.5mL of each sample was taken, bacterial genomic DNA in the sample was extracted using a DNA extraction kit, dissolved in 100. Mu.L of buffer TE, and sent to Bio-company for 16S rDNA sequencing; 2) Sequencing, namely performing double-end sequencing of 2×300bp by using a Miseq sequencer to obtain original off-machine data, splicing, quality control and chimera filtering to obtain final effective data; 3) And carrying out 97% similarity clustering on the effective data by data processing, and filtering to obtain the final OTU abundance and representative sequence.
The data were statistically analyzed using SPSS26.0 software, the results were expressed as mean.+ -. Standard deviation, the group comparisons were analyzed by variance analysis, the group comparisons were tested by paired t-test, and the differences were considered statistically significant if P < 0.05. The data were plotted using origin9.0 software.
Verification result
The test collects 20 patients meeting the conditions, and adopts a random grouping method to divide the patients into an intervention group and a control group, wherein the intervention group comprises 10 patients and the control group comprises 10 patients. 5 women and men in the intervention group had average ages of 59.8+ -5.41 years and BMI of 21.7+ -5.12 kg/m 2 The method comprises the steps of carrying out a first treatment on the surface of the Control group of 4 men, 6 women, average age 61.8+ -4.66 years, BMI mean 22.5+ -4.09 kg/m 2 . Both groups of patients had very high concentrations of creatinine and urea nitrogen in the blood, reflecting their poor renal status, see table 2.
Table 2: creatinine and urea nitrogen statistics for CKD stage 5 patients
| Group of | Number of examples | Blood creatinine (mu mol/L) | Blood urea nitrogen (mmol/L) |
| Control group | 10 | 773.3±232.9 | 21.3±3.90 |
| Intervention group | 10 | 741.0±190.6 | 19.6±4.74 |
The prealbumin is an index capable of reflecting the nutrition condition of the organism and the synthesis function of liver cells, and has short half-life and higher sensitivity compared with the albumin. The pre-albumin index of the control group is reduced by 28mg/L after 4 weeks, the intervention group is only increased by 7mg/L, as shown in figure 1, and the polypeptide composition can maintain or increase the pre-albumin level of the chronic kidney disease patients and improve the organism nutrition status to a certain extent although the data in the two groups are not significantly different.
Neutrophils play a very important role in the blood's nonspecific cellular immune system, the first line of defense against a large number of microorganisms that is cell-mediated. The percentage of normal neutrophils in adult blood ranges from 50% to 70%, with higher or lower levels affecting the development of various chronic inflammatory diseases. The control group's neutrophil percentage increased to 71.33% at the end of the intervention experiment, increased by 1.43% and the intervention group decreased from 67.25% to 61.91%. IL-6, interleukin-6, is elevated during infection and inflammatory response, has the function of regulating immune and acute phase response, is an important pro-inflammatory cytokine, and is often used as one of inflammatory markers. The control group IL-6 baseline was at normal level, increased by 0.77pg/mL at the end, the intervention group baseline was greater than the clinical normal value of 7pg/mL, and the polypeptide composition decreased from 9.14pg/mL to 7.38pg/mL after 4 weeks of intervention, alleviating the inflammatory response in the body, as shown in FIG. 2.
In a normal organism, metabolic dynamic balance of kidney ammonia, damage to kidney can lead to impaired function, damage to metabolic balance, reduced ability of kidney to metabolize ammonia and increased blood ammonia. The control group had a significant increase in blood ammonia of 47.92umol/L after 4 weeks and the intervention group had an increase in blood ammonia of 15.33umol/L, but there was no statistical significance before and after intervention, as shown in FIG. 3. The blood ammonia increase value of the intervention group is less than one third of that of the control group, and the increase amplitude is greatly reduced. The presence of significant interactions in blood ammonia with group and time means that the difference in blood ammonia between the intervention group and the control group at the same time point will become greater over time. The intervention of the polypeptide composition is beneficial to slowing down the blood ammonia rising speed of patients, and has positive effect on patients with continuous and rapid rising of blood ammonia.
The intestinal tract is the largest immune organ of the human body, has close relation with the immunity of the organism, and the intestinal tract participates in regulating the ammonia level in blood, and the benefits of the polypeptide composition for reducing inflammatory reaction and slowing down blood ammonia rise are presumed to be related to the intestinal tract. By analyzing the microorganisms of the fecal sample, the shannon values of the control group were significantly reduced after 4 weeks, i.e., the alpha diversity was significantly reduced, meaning that chronic kidney disease would disrupt the intestinal flora balance. The shannon value does not change significantly after 4 weeks of intervention of the polypeptide composition, which indicates that the polypeptide composition does not change the alpha diversity of intestinal flora and can positively regulate the adverse effect of intestinal tract caused by diseases. Compared with a control group, the polypeptide composition reduces the abundance of inflammation-related bacteria after 4 weeks of intervention, regulates inflammatory reaction, and enables the inflammatory reaction to maintain inflammation steady state, thereby enhancing organism immunity; the polypeptide composition increases the abundance of beneficial intestinal bacteria and reduces the potential pathogenic bacteria. Thus, the polypeptide composition may mediate an organic inflammatory response through the abundance of gut inflammation-associated bacteria, as shown in fig. 4-6.
Claims (8)
1. The polypeptide composition is characterized by comprising the following components in parts by weight: 20-70 parts of qingxi flower turtle peptide, 10-60 parts of walnut peptide, 5-55 parts of albumin peptide and 15-60 parts of pea peptide.
2. A polypeptide composition according to claim 1, characterized in that it consists of the following components in parts by weight: 30-60 parts of qingxi flower turtle peptide, 10-50 parts of walnut peptide, 10-45 parts of albumin peptide and 20-50 parts of pea peptide.
3. Use of a polypeptide composition according to claim 1 or 2 for the preparation of a food or medicament for assisting hemodialysis in the treatment of chronic kidney disease.
4. The use according to claim 3, wherein the polypeptide composition is for use in maintaining or increasing the prealbumin level in a patient suffering from chronic kidney disease.
5. The use according to claim 3, wherein the polypeptide composition is for modulating the number of neutrophils in blood.
6. The use according to claim 3, characterized in that the polypeptide composition is used for regulating the interleukin 6 concentration in blood.
7. The use according to claim 3, wherein the polypeptide composition is used to slow down the rate of increase of blood ammonia.
8. The use according to claim 3, wherein the polypeptide composition is used in inflammatory diseases caused by increased abundance of inflammatory bacteria in the gut.
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