Compositions and uses for suppressing inflammatory responses and promoting angiogenesis and wound healing

Abstract

The present invention provides a composition and use for suppressing inflammatory responses and promoting angiogenesis and wound healing, the composition comprising, by weight, 0.1 to 100 parts wheat oligopeptide, 0.1 to 100 parts marine fish skin collagen oligopeptide, and 0.1 to 100 parts hemoglobin polypeptide. The composition for suppressing inflammatory responses and promoting angiogenesis and wound healing provided by the present invention comprises marine fish skin collagen oligopeptide, wheat oligopeptide, and hemoglobin polypeptide as main ingredients, and is formulated with chamomile extract and calcium β-hydroxy-β-methylbutanoate, and achieves the effect of promoting wound healing by suppressing inflammatory responses and promoting angiogenesis, providing important practical significance for the development of products that take into account multiple stages of wound healing and promote wound healing.

Description

[Technical Field]

[0001] The present invention relates to the field of medicine, and in particular to compositions and uses for suppressing inflammatory responses and promoting angiogenesis and wound healing. [Background technology]

[0002] Skin is the largest organ in the human body and has important functions, such as protecting internal organs from pathogen invasion and regulating body temperature. Skin wounds caused by burns, trauma, and chronic diseases adversely affect patients' quality of life and health, resulting in significant economic and social burdens. Wound healing is a complex, dynamic process that can be divided into four phases: blood coagulation, inflammation, proliferation, and remodeling, which overlap in both time and space. However, current understanding of the process and mechanisms of wound healing remains incomplete, and how to promote wound healing remains a major clinical challenge. The inflammatory phase generally occurs early in wound healing, especially within the first three days after debridement surgery. Signs of an inflammatory response, such as mild redness, swelling, and tenderness, are usually present at the wound site. If the wound is severely contaminated with bacteria, particularly pathogenic bacteria, it is susceptible to infection, leading to the development of abscesses and a significant prolongation of the wound healing cycle. As an important part of wound healing, angiogenesis provides oxygen, growth factors, and immune support to healing tissues; promoting the mass production of blood vessels during wound healing allows tissues to obtain more oxygen and nutrients, improving healing efficiency and mass; conversely, reducing angiogenesis reduces the rate of healing.

[0003] Drug therapy is the most common method of wound treatment, and currently, wounds are often treated with a combination of traditional Chinese medicine and Western medicine, with remarkable clinical effectiveness. Currently, due to the clinical emergence of drug resistance to various antibiotics, it is urgent to find new drugs that promote wound healing. Polypeptide products are currently the first choice for wound treatment due to their small molecular size, strong selectivity of action, easy availability, and no obvious side effects.

[0004] Conventional peptide products that promote wound healing mainly use collagen peptides as their main raw material, and mainly replenish proteins during the wound healing process, providing sufficient proteins for wound healing. However, wound healing is divided into hemostasis, inflammation, proliferation, and remodeling stages. Currently, peptide products have not yet been designed to promote inflammatory responses and angiogenesis during the wound healing process. However, wound healing can only achieve ideal results by considering multiple stages simultaneously. Summary of the Invention [Problem to be solved by the invention]

[0005] In view of the above circumstances, the present invention aims to provide a composition and use for suppressing inflammatory responses and promoting angiogenesis and wound healing, which can simultaneously promote inflammatory responses and angiogenesis during the wound healing process. [Means for solving the problem]

[0006] In order to achieve the above object, the present invention employs the following means.

[0007] A composition for suppressing inflammatory responses and promoting angiogenesis and wound healing, comprising, by weight, 0.1 to 100 parts of wheat oligopeptide, 0.1 to 100 parts of marine fish skin collagen oligopeptide, and 0.1 to 100 parts of hemoglobin polypeptide.

[0008] Preferably, the composition for suppressing inflammatory responses and promoting angiogenesis and wound healing further contains, by weight, one or more of: 0.01 to 2 parts of chamomile extract, 0.1 to 20 parts of calcium β-hydroxy-β-methylbutanoate, and 0.01 to 3 parts of goji berry powder.

[0009] The present invention can employ conventional oral preparations manufactured using pharmaceutical acceptable preparation processes and additives, and the conventional oral preparations include, but are not limited to, granules, oral liquids, and the like.

[0010] This product has the characteristics of low cost, good therapeutic effect, natural origin and no side effects.

[0011] Preferably, the composition for suppressing inflammatory responses and promoting angiogenesis and wound healing further contains, by weight, one or more of 0.001 to 1 part zinc gluconate, 0.01 to 5 parts casein phosphopeptide, and 1 to 100 parts water-soluble dietary fiber.

[0012] Preferably, the composition for suppressing inflammatory responses and promoting angiogenesis and wound healing contains, by weight, 0.1 to 60 parts of wheat oligopeptide, 0.1 to 60 parts of marine fish skin collagen oligopeptide, 0.1 to 60 parts of hemoglobin polypeptide, 0.1 to 1.5 parts of chamomile extract, 0.5 to 10 parts of calcium β-hydroxy-β-methylbutanoate, and 0.1 to 2 parts of goji berry powder.

[0013] Preferably, the composition for suppressing inflammatory responses and promoting angiogenesis and wound healing comprises, by weight, 1.8 parts wheat oligopeptide, 1.8 parts marine fish skin collagen oligopeptide, 0.4 parts hemoglobin polypeptide, 0.1 parts chamomile extract, 1 part calcium β-hydroxy-β-methylbutanoate, and 0.2 parts goji berry powder, and is made up to 100 parts by adding water.

[0014] The present invention further provides use of the above composition in the manufacture of a medicament for suppressing inflammatory responses and promoting angiogenesis and wound healing.

[0015] The composition and use for suppressing inflammatory responses and promoting angiogenesis and wound healing provided by the present invention comprises marine fish skin collagen oligopeptide, wheat oligopeptide, and hemoglobin polypeptide as main ingredients, and is compounded with chamomile extract and calcium β-hydroxy-β-methylbutanoate. It achieves the effect of promoting wound healing by suppressing inflammatory responses and promoting angiogenesis responses, and provides important theoretical and practical significance for the development of products that take into account multiple stages of wound healing and promote wound healing.

[0016] In the above composition, chamomile extract has anti-inflammatory and analgesic effects, calcium β-hydroxy-β-methylbutanoate has the effect of accelerating protein synthesis or inhibiting protein hydrolysis, goji berry powder can enhance immunity, and hemoglobin polypeptide has a blood-replenishing effect. The present invention can employ conventional oral formulations manufactured using pharmaceutical-acceptable preparation processes and additives, including, but not limited to, granules, oral liquids, etc. The formulations are characterized by low cost, good therapeutic effects, natural origin, and no side effects. [Brief explanation of the drawings]

[0017] [Figure 1] Changes in wound surface shape in the model group, Example 5 and Example 7. [Figure 2] Hematoxylin and eosin staining of wound tissues in the model group, Example 5 and Example 7. [Figure 3] 1 shows the distribution of VEGF in granulation tissue at the wound site in the model group, Example 5, and Example 7. [Figure 4] 1 shows CD34 immunofluorescence intensity in the model group, Example 5, and Example 7. [Figure 5] CTGF immunofluorescence intensity in the model group, Example 5 and Example 7. [Figure 6] FIG. 1 is a diagram comparing the contents of D-mannose and fatty acids in serum in the model group, Example 5, and Example 7. DETAILED DESCRIPTION OF THE INVENTION

[0018] To facilitate understanding of the present invention, the present invention will be described in detail below with reference to examples, but the present invention may be embodied in many different forms and is not limited to the examples set forth herein. On the contrary, the purpose of providing these examples is to provide a more complete disclosure of the present invention.

[0019] Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art. Terms used in the present specification are for the purpose of describing specific embodiments and are not intended to limit the present invention. As used herein, the term "and / or" includes any and all combinations of one or more of the associated listed items.

[0020] The present invention will be further described below by dividing it into several examples. The present invention is not limited to the following specific examples. Appropriate modifications can be made without departing from the spirit of the present invention.

[0021] Example 1 200g of wheat oligopeptide, 200g of marine fish skin collagen oligopeptide, 50g of hemoglobin polypeptide, 15g of chamomile extract, 100g of calcium beta-hydroxy-beta-methylbutanoate, 20g of goji berry powder, 200g of water-soluble dietary fiber, 6g of casein phosphopeptide, 2g of zinc gluconate, and 285g of powdered sugar were taken and mixed uniformly. After that, the mixture was passed through a 100-mesh sieve. The mixture was then granulated by boiling using a 10% aqueous solution of povidone K30 as a binder. The atomization pressure was controlled to 0.2MPa, the material temperature to 42℃, and the intake air temperature to 70℃. The resulting granules were sieved through a 20-mesh sieve and packaged in aluminum foil, with each bag containing 8g.

[0022] Example 2 400g of wheat oligopeptide, 300g of marine fish skin collagen oligopeptide, 100g of hemoglobin polypeptide, 20g of chamomile extract, 200g of calcium beta-hydroxy-beta-methylbutanoate, 30g of goji berry powder, and 320g of powdered sugar were taken and mixed uniformly. After that, the mixture was passed through a 100-mesh sieve. The mixture was then granulated by boiling using a 10% aqueous solution of povidone K30 as a binder. The atomization pressure was controlled to 0.2MPa, the material temperature to 42°C, and the intake air temperature to 70°C. The resulting granules were sieved through a 20-mesh sieve and packaged in aluminum foil, with each bag containing 5g.

[0023] Example 3 300g of wheat oligopeptide, 400g of marine fish skin collagen oligopeptide, 100g of hemoglobin polypeptide, 20g of chamomile extract, 200g of calcium beta-hydroxy-beta-methylbutanoate, 30g of goji berry powder, and 320g of powdered sugar were taken and mixed uniformly. After that, the mixture was passed through a 100-mesh sieve. The mixture was granulated by boiling using a 10% aqueous solution of povidone K30 as a binder. The atomization pressure was controlled to 0.2MPa, the material temperature to 42°C, and the intake air temperature to 70°C. The resulting granules were sieved through a 20-mesh sieve and packaged in aluminum foil, with each bag containing 5g.

[0024] Example 4 200g of wheat oligopeptide, 200g of marine fish skin collagen oligopeptide, 100g of hemoglobin polypeptide, and 100g of powdered sugar were taken, and all the ingredients were mixed uniformly. Then, each was sieved through a 100 mesh sieve. The uniformly mixed ingredients were boiled and granulated using a 10% aqueous solution of povidone K30 as a binder, and the atomization pressure was controlled to 0.2MPa, the material temperature to 42°C, and the intake air temperature to 70°C. The resulting granules were sieved through a 20 mesh sieve and packaged in aluminum foil, with each bag containing 6g.

[0025] Example 5 18g of wheat oligopeptide, 18g of marine fish skin collagen oligopeptide, 4g of hemoglobin polypeptide, 1g of chamomile extract, 10g of calcium β-hydroxy-β-methylbutanoate, 2g of goji berry powder, 10g of water-soluble dietary fiber, 0.4g of casein phosphopeptide, 0.06g of zinc gluconate, 0.15g of sucralose, 2.2g of citric acid, and 8g of isomaltulose were added to a mixing tank with 500ml of purified water. The wheat oligopeptide, marine fish skin collagen oligopeptide, hemoglobin polypeptide, chamomile extract, calcium β-hydroxy-β-methylbutanoate, goji berry powder, water-soluble dietary fiber, and isomaltulose were added in that order and stirred to dissolve. The mixture was then filtered through a plate and frame filter to obtain the filtrate. Sucralose, casein phosphopeptide, zinc gluconate, and citric acid were dissolved in an appropriate amount of purified water, and then added to the filtrate. Water was added to the filtrate until it reached 1000 ml, and the mixture was stirred for 15 minutes. The flavor was added, and the mixture was stirred for another 10 minutes. The mixture was then filtered through a 0.45 μm filter. The resulting mixture was bottled in a volume of 100 ml and sterilized at 105°C for 30 minutes.

[0026] Example 6 16g of wheat oligopeptide, 16g of marine fish skin collagen oligopeptide, 8g of hemoglobin polypeptide, 0.5g of chamomile extract, 20g of calcium β-hydroxy-β-methylbutanoate, 2g of goji berry powder, 10g of water-soluble dietary fiber, 0.4g of casein phosphopeptide, 0.06g of zinc gluconate, 0.15g of sucralose, 2.2g of citric acid, and 8g of isomaltulose were added to a mixing tank with 500ml of purified water. The wheat oligopeptide, marine fish skin collagen oligopeptide, hemoglobin polypeptide, chamomile extract, calcium β-hydroxy-β-methylbutanoate, goji berry powder, water-soluble dietary fiber, and isomaltulose were added sequentially and stirred to dissolve. The mixture was filtered through a plate and frame filter to obtain the filtrate. Sucralose, casein phosphopeptide, zinc gluconate, and citric acid were dissolved in an appropriate amount of purified water, and then added to the filtrate. Water was added to the filtrate until it reached 1000 ml, and the mixture was stirred for 15 minutes. The flavor was added, and the mixture was stirred for another 10 minutes. The mixture was then filtered through a 0.45 μm filter. The resulting mixture was bottled in a volume of 100 ml and sterilized at 105°C for 30 minutes.

[0027] Example 7 20g of wheat oligopeptide, 12g of marine fish skin collagen oligopeptide, 8g of hemoglobin polypeptide, 1g of chamomile extract, 20g of calcium β-hydroxy-β-methylbutanoate, 2g of goji berry powder, 10g of water-soluble dietary fiber, 0.4g of casein phosphopeptide, 0.06g of zinc gluconate, 0.15g of sucralose, 2.0g of citric acid, and 8g of isomaltulose were added to a mixing tank with 500ml of purified water. Wheat oligopeptide, marine fish skin collagen oligopeptide, hemoglobin polypeptide, chamomile extract, calcium β-hydroxy-β-methylbutanoate, goji berry powder, water-soluble dietary fiber, and isomaltulose were added in that order and stirred to dissolve. The mixture was filtered through a plate and frame filter to obtain the filtrate. Sucralose, casein phosphopeptide, zinc gluconate, and citric acid were dissolved in an appropriate amount of purified water, and then added to the filtrate. Water was added to the filtrate until it reached 1000 ml, and the mixture was stirred for 15 minutes. The flavor was added, and the mixture was stirred for another 10 minutes. The mixture was then filtered through a 0.45 μm filter. The resulting mixture was bottled in a volume of 100 ml and sterilized at 105°C for 30 minutes.

[0028] Example 8 12g of wheat oligopeptide, 20g of marine fish skin collagen oligopeptide, 8g of hemoglobin polypeptide, 2g of chamomile extract, 20g of calcium β-hydroxy-β-methylbutanoate, 2g of goji berry powder, 10g of water-soluble dietary fiber, 0.15g of sucralose, 2.0g of citric acid, and 8g of isomaltulose were added to a mixing tank with 500ml of purified water. The wheat oligopeptide, marine fish skin collagen oligopeptide, hemoglobin polypeptide, chamomile extract, calcium β-hydroxy-β-methylbutanoate, goji berry powder, water-soluble dietary fiber, and isomaltulose were added sequentially and stirred to dissolve. The mixture was filtered through a plate and frame filter to obtain the filtrate. The sucralose and citric acid were dissolved in an appropriate amount of purified water, added to the filtrate, and water was added to make up to 1000ml. The mixture was stirred for 15 minutes, flavor was added, and the mixture was stirred for another 10 minutes. The mixture was then filtered through a 0.45μm filter. The contents were filled to 100 ml per bottle and sterilized at 105°C for 30 minutes.

[0029] In the present invention, the mechanism of action of the compositions provided in Examples 5 and 7 on wound healing was studied, specifically including the following methods:

[0030] 1. Research into the effects of suppressing inflammatory responses and promoting angiogenesis and wound healing 1. Materials and Methods 1.1 Materials: Samples of Examples 5 and 7, positive control (Abbott Abound).

[0031] 1.2 Experimental animals: Male Kunming mice, weighing 20-22g, aged 6-8 weeks, provided by GemPharmatech Co., Ltd., license number SCXK(Su)2018-0008.

[0032] 1.3 Experimental conditions: Mice were kept in the Jiangzhong Pharmaceutical Animal Experiment Center, license number SYXK(▲Cancer▼)2020-004, in a clean environment. The laboratory temperature was 24±2°C, the relative humidity was 45-65%, and the light cycle was 12 (day) / 12 (night).

[0033] 1.4 Experimental Method: 1.4.1 Rats were anesthetized with isoflurane. After anesthesia, the rat's back was shaved using a shaver to expose an area of ​​approximately 3 cm x 3 cm on the back. Hair was then removed using hair removal cream. After 3-5 minutes, the hair removal cream was thoroughly washed off the back with a cotton ball soaked in warm water, and then the back was wiped dry with dry cotton balls.

[0034] 1.4.2 The experimental area on the back of the rat was cleaned and disinfected using iodophor, and then a 10 mm diameter skin sampler was used to rotate and press down on the back of the rat (ensuring that the position of each model construction was basically the same) to form a small notch. Then, the skin was removed using ophthalmic forceps and ophthalmic scissors to form a 10 mm diameter circular wound.

[0035] 1.4.3 Wound area measurement: The rats were placed on their sides and photographed at the same height using an industrial high-resolution camera to perform the initial wound area measurement.

[0036] 1.4.4 Each group was subsequently administered the corresponding drug daily, and wound area measurements were performed on days 2, 3, 6, 10, 12, and 14. Rats anesthetized with isoflurane were photographed at the same height and wound area measurements were performed.

[0037] 1.4.5 Wound healing rate: The wound area was photographed and measured every two days, and the wound healing rate (WHR) was calculated.

[0038] WHR=(D0-D n ) / D0×100% Where: WHR is the wound healing rate (WHR, %), DO is the diameter of the early wound shape (cm), and D n is the diameter of the unhealed wound (cm).

[0039] 1.4.6 Samples: 3 days and 14 days after administration, normal skin tissues were excised from the entire wound surface and 5 mm from the wound edge, respectively, and fixed in 4% paraformaldehyde and stored in liquid nitrogen.

[0040] 1.4.7 Pathology and immunohistochemistry: The newly formed skin at the wound site of the rats was excised, and the skin tissue was fixed in paraformaldehyde and embedded in paraffin. 5 μm sections of the paraffin-embedded skin were prepared and subjected to further experiments. H&E staining and Masson staining were used to examine mucosal injury. For immunohistochemistry, the sections were incubated with anti-CD34 protein and anti-CTGF protein antibodies at 4°C. All results were observed under a microscope.

[0041] 1.4.8 Data Analysis: Data were expressed as mean ± standard deviation (SEM). One-way ANOVA was used, and comparisons between groups were performed in pairs using Dunnett's test. Differences were considered statistically significant when P<0.05, and highly significant when P<0.001. All data were analyzed using the GraphPad Prism 8.0 statistical software package.

[0042] 1.5 results 1.5.1 Observation of changes in wound surface morphology As shown in Figure 1, on day 2 after model construction, all animals in each treatment group had formed scabs, no exudation, and no obvious wound contraction. However, on day 4 after model construction, animals in the model group began to form scabs. On days 4, 6, and 10 after model construction, the scabs on the wound surface of each group became hard, the surface around the wound was not smooth, and there was obvious skin contraction at the wound edge. Here, the rate of wound skin contraction in each treatment group was faster than that of the model group. On day 12 after model construction, most rats in each group had lost scabs, hair began to grow in the healed area, and each group further contracted the scab. On day 14 after model construction, all rats in each treatment group exhibited flesh-red new skin, with complete new flesh-colored tissue. Healing was better than in the control group, and there was no development of hypertrophic scars or keloids.

[0043] 1.5.2 Healing rate and scar reduction rate The wound area was photographed and measured every two days with a camera, and the results were calculated according to the following formula: wound healing rate = (wound area on day 0 after model construction - wound area on the day of measurement) / (wound area on day 0 after model construction) * 100%. The measurement results are shown in Table 1.

[0044] [Table 1]

[0045] Note: * denotes significant difference between Model and Abound, * denotes p<0.05, and ** denotes p<0.01.

[0046] # denotes significant difference between Model and Chueun, # denotes p<0.05, and ## denotes p<0.01.

[0047] $ indicates a significant difference between Model and Improved Chueun, $ indicates p<0.05, and $$ indicates p<0.01.

[0048] As can be seen from Table 1, on the third day of model construction, the wound healing rates of each group were close to 40%, with no significant difference between the treatment groups and the model group (P>0.05). On the fourth day of model construction, the healing rates of each treatment group were significantly higher than that of the model group. On the sixth day of model construction, the healing rates of each treatment group were significantly higher than that of the model group, with Example 7 showing a better healing rate than Abbott Abound and Example 5. On the eighth, tenth, and twelfth days of model construction, the healing rates of each treatment group were significantly higher than that of the model group. On the 14th day of model construction, the wound healing rate of each group reached over 90%, indicating that the wound healing process was nearly complete, with no significant difference between the groups (P>0.05).

[0049] 1.5.3 H&E staining As shown in Figure 2, on the fourth day after treatment, several mice (n = 6) per group were sacrificed, and the tissues were subjected to H&E staining. None of the wounds in each group were completely healed, and granulation tissue was observed throughout the entire dermal tissue, and re-epithelialization of the wound edge area was initiated. Here, the development of granulation tissue in the model group was immature, and strong lymphocytic inflammatory infiltration, interstitial edema, and hemorrhage were observed. In the Example 5, Example 7, and Abbott Abound groups, the full-thickness skin and subcutaneous tissue at the wound edge shifted to the center, and the wound gradually contracted. Although there were varying degrees of inflammatory cell infiltration, the granulation tissue was more mature than in the model group, indicating that each intervention group had a certain effect on promoting wound healing.

[0050] 1.5.4VEGF histochemistry VEGF (vascular endothelial growth factor) plays an important role in the proliferative phase of wound healing, promoting endothelial cell migration, differentiation, and tube formation, which are key factors in the early stages of angiogenesis. Studies have shown that new blood vessels appear earliest on the third day after injury. Therefore, during the wound healing process, the expression of VEGF in the granulation tissue area indicates the number of new blood vessels.

[0051] Immunohistochemistry was used to detect the distribution of VEGF in the granulation tissue of the wound on day 4 after model construction. As shown in Figure 3, VEGF-positive cells were brownish, and there was no significant difference in VEGF expression in the wound treated with Abbott Abound compared to the model group. In contrast, after treatment with Examples 5 and 7, dispersed VEGF was observed in both infiltrating inflammatory cells and fibroblast-like cells in the connective tissue of the wound, and the proportion of VEGF-positive cells was higher than in the model group and Abbott Abound treatment group. These results demonstrate that Examples 5 and 7 can promote angiogenesis during wound healing.

[0052] 1.5.5 CD34 immunofluorescence Because angiogenesis is necessary for wound healing, we investigated wound angiogenesis using immunofluorescent staining of CD34 as a vasculature marker. As shown in Figure 4, DAPI in the wounds of each group exhibited blue fluorescence, while CD34 exhibited red fluorescence, indicating that a certain amount of new blood vessels was generated in each group during the wound healing process. The red fluorescence in Examples 5 and 7 was greater than that in the model group, indicating a significant increase in the number of new blood vessels in both Examples 5 and 7, indicating that Examples 5 and 7 promoted angiogenesis, vascular network reorganization, and wound healing. Furthermore, the Abbott Abound group did not exhibit denser new blood vessels at the wound site than the model group.

[0053] 1.5.6 CTGF immunofluorescence During the early stage of wound healing, connective tissue growth factor (CTGF) plays a positive role in the development of mature, well-structured, and vascularized granulation tissue. Immunofluorescence analysis of the distribution of CTGF in wounds on day 4 after model construction showed blue fluorescence for DAPI and red fluorescence for CTGF. Figure 5 shows representative images of the presence and distribution of CTGF-positive cells in the wound healing area of ​​each group. As can be seen, Example 5, Example 7, and Abound groups all showed more red fluorescence, i.e., more CTGF-positive cells, than the model group. Here, red fluorescence was greater in Example 5 and Example 7 than in the Abbott Abound group, indicating that the interventions in Example 5 and Example 7 promoted cell adhesion, migration, and proliferation better than Abbott Abound during the early stage of wound healing, thereby facilitating the wound repair process.

[0054] 1.5.7 Transcriptomics analysis--Identification of potentially differential metabolites Sample separation and data collection were performed using UPLC-TOF / MS, and the components were well separated in positive and negative ion mode. There were certain differences in retention time and peak area between each group, and the model group, Example 5, and Example 7 were all distributed in different quadrants, indicating good separation and significant differences in the serum metabolites of mice in each group. At the same time, the potential differential metabolites common to Example 5 and Example 7 administered to mice are shown in Table 2.

[0055] [Table 2]

[0056] Note: VIP: Variable Projection Importance of the substance in the group contrast by the OPLS-DA model FC: The fold relationship of the substance between two groups in the group contrast experiment P: P value of the substance by t-test in the comparison of the groups, where P value = probability of rejection even if the hypothesis is correct = number of negative results / total number of results, and the test probability for the sample data

[0057] The nine differential metabolites selected as potential biomarkers for wound healing include 3-hydroxydecanoic acid, D-mannose, L-cysteine ​​sulfinic acid, ethoxyquin, linolenic acid and its derivatives, fatty acids, fatty acyl groups, glycerol, and glycerophospholipids. D-mannose is an epimer of glucose and exists primarily as an α- or β-pyranose isomer. It is directly utilized in the human body to synthesize glycoproteins and inhibit inflammatory responses during wound healing. The effects of bioactive lipids primarily occur during the inflammatory phase of wound healing. Furthermore, it has been reported that fatty acid analogs and their receptor agonists can be used in part to modulate inflammation and immune responses during wound healing. As can be seen from the results in Figure 6, the D-mannose and fatty acid contents in the serum of Examples 5 and 7 were both higher than those of the model group, with the D-mannose content being higher in Example 7 and the fatty acid content being higher in Example 5. By increasing the fatty acid levels in the serum, Examples 5 and 7 exerted the effect of suppressing inflammation levels in the early stage of wound healing and promoting wound healing.

[0058] It should be understood that the above-described examples merely represent some embodiments of the present invention, and the description is specific and detailed, but does not limit the patent scope of the present invention. It should be noted that those skilled in the art can make multiple modifications and improvements without departing from the concept of the present invention, and all of these fall within the scope of protection of the present invention. Therefore, the scope of protection of the patent of the present invention is subject to the scope of the appended claims.

Claims

1. A composition for suppressing inflammatory responses and promoting angiogenesis and wound healing, comprising, by weight, 0.1 to 100 parts of wheat oligopeptide, 0.1 to 100 parts of marine fish skin collagen oligopeptide, 0.1 to 100 parts of hemoglobin polypeptide, 0.01 to 2 parts of chamomile extract, 0.1 to 20 parts of calcium β-hydroxy-β-methylbutanoate, 0.01 to 3 parts of goji berry powder, 0.001 to 1 part of zinc gluconate, 0.01 to 5 parts of casein phosphopeptide, and 1 to 100 parts of water-soluble dietary fiber.

2. 10. Use of the composition of claim 1 in the manufacture of a medicament for promoting wound healing, wherein the composition is for promoting angiogenic responses in the wound healing process, promoting angiogenesis and facilitating vascular network reconstruction and wound healing, promoting the wound repair process by promoting cell adhesion, migration and proliferation in the early stage of wound healing, and increasing fatty acid levels in the serum, thereby exerting the effect of suppressing inflammation levels in the early stage of wound healing and exerting the effect of promoting wound healing.

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