CN116036247B - Composition for inhibiting inflammatory response, promoting angiogenesis and wound healing and application thereof - Google Patents

Composition for inhibiting inflammatory response, promoting angiogenesis and wound healing and application thereof Download PDF

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CN116036247B
CN116036247B CN202310064800.9A CN202310064800A CN116036247B CN 116036247 B CN116036247 B CN 116036247B CN 202310064800 A CN202310064800 A CN 202310064800A CN 116036247 B CN116036247 B CN 116036247B
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wound healing
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promoting
wound
beta
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CN116036247A (en
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刘丹
余婧婷
刘文君
李诒光
喻春燕
詹扬
廖群
许锦珍
刘慧莹
边林林
杜娟
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Jiangzhong Pharmaceutical Co Ltd
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Abstract

The invention provides a composition for inhibiting inflammatory reaction, promoting angiogenesis and wound healing and application thereof, wherein the composition comprises the following components in parts by weight: 0.1-100 parts of wheat oligopeptide, 0.1-100 parts of marine fish skin collagen oligopeptide and 0.1-100 parts of blood protein polypeptide. The composition for inhibiting inflammatory reaction, promoting angiogenesis and wound healing provided by the invention is prepared by taking marine fish skin collagen oligopeptide, wheat oligopeptide and blood protein polypeptide as main components and matching chamomile extract and beta-hydroxy-beta-calcium methylbutyrate, and achieves the effects of promoting wound healing and a plurality of links of wound healing by inhibiting inflammatory reaction and promoting angiogenesis reaction, thereby providing important practical significance for developing products for promoting wound healing.

Description

Composition for inhibiting inflammatory response, promoting angiogenesis and wound healing and application thereof
Technical Field
The invention relates to the technical field of medicines, in particular to a composition for inhibiting inflammatory response, promoting angiogenesis and wound healing and application thereof.
Background
The skin is the largest organ of human body, and has the key functions of protecting viscera from pathogen invasion, regulating body temperature and the like. Skin wounds caused by burns, trauma and chronicity negatively affect the quality of life and health of the patient and create significant economic and social burden. Wound healing is a complex dynamic process that can be divided into four phases: coagulation phase, inflammatory phase, proliferation phase and remodeling phase, which overlap in time and space. However, there is still a lack of complete understanding of the wound healing process and mechanism; how to promote wound healing in particular remains a significant clinical challenge. Inflammatory phases generally occur in early wound healing, especially the first three days after debridement, and usually manifest as slight redness, swelling, compression pain, etc. in the wound area. If the wound is polluted seriously, especially the bacteria with stronger pathogenicity, the wound infection is easy to cause, the pus accumulation phenomenon occurs in the wound, and the period of wound healing is greatly prolonged. As a key link of wound healing, angiogenesis provides oxygen, growth factors and immune support for healed tissues, and promoting massive generation of blood vessels in the wound healing stage can enable the tissues to obtain more oxygen and nutrition, so that the healing efficiency and quality are improved, and conversely, the healing rate is reduced by reducing angiogenesis.
The drug treatment is the most main mode of wound treatment, more traditional Chinese medicines and western medicines are used for treating wound healing in combination at present, and the clinical effect is remarkable. Currently, as a result of the clinical emergence of resistance to a variety of antibiotics, it is urgent to find new drugs that promote wound healing. The polypeptide products are small in molecule, high in action selectivity, easy to obtain and free of obvious side effects, so that the polypeptide products currently become the primary choice for treating wound healing.
The existing peptide products for promoting wound healing mainly take collagen peptide as a main raw material, and supplement protein in the wound healing process, so that sufficient protein is provided for wound healing, but the related peptide products are not designed for inflammatory reaction and angiogenesis promotion in the wound healing engineering at present in the blood stage, inflammatory stage, proliferation stage and remodelling stage of wound healing, and the wound healing needs to take a plurality of links into consideration to achieve ideal effects.
Disclosure of Invention
In view of the above, an object of the present invention is to provide a composition and application for inhibiting inflammatory reaction, promoting angiogenesis and wound healing, which can simultaneously promote inflammatory reaction and angiogenesis in the wound healing process.
In order to achieve the above purpose, the technical scheme adopted by the invention is as follows:
a composition for inhibiting inflammatory response, promoting angiogenesis and wound healing, comprising the following components in parts by weight:
0.1-100 parts of wheat oligopeptide, 0.1-100 parts of marine fish skin collagen oligopeptide and 0.1-100 parts of blood protein polypeptide.
Optionally, the composition for inhibiting inflammatory reaction, promoting angiogenesis and wound healing further comprises the following components in parts by weight:
0.01-2 parts of chamomile extract, 0.1-20 parts of beta-hydroxy beta-methyl calcium butyrate and 0.01-3 parts of medlar powder.
The invention can be prepared into conventional oral preparations including but not limited to granules, oral liquid and the like by adopting pharmaceutically acceptable preparation processes and auxiliary materials.
The product has the characteristics of low cost, good curative effect, no toxic or side effect due to natural sources.
Optionally, the composition for inhibiting inflammatory reaction, promoting angiogenesis and wound healing further comprises the following components in parts by weight:
0.001-1 part of zinc gluconate, 0.01-5 parts of casein phosphopeptide and 1-100 parts of water-soluble dietary fiber.
Optionally, the composition for inhibiting inflammatory reaction, promoting angiogenesis and wound healing comprises the following components in parts by weight:
0.1-60 parts of wheat oligopeptide, 0.1-60 parts of marine fish skin collagen oligopeptide, 0.1-60 parts of blood protein polypeptide, 0.1-1.5 parts of chamomile extract, 0.5-10 parts of beta-hydroxy-beta-methylbutyrate calcium and 0.1-2 parts of medlar powder.
Optionally, the composition for inhibiting inflammatory reaction, promoting angiogenesis and wound healing comprises the following components in parts by weight:
1.8 parts of wheat oligopeptide, 1.8 parts of marine fish skin collagen oligopeptide, 0.4 part of blood protein polypeptide, 0.1 part of chamomile extract, 1 part of beta-hydroxy-beta-methylbutyrate calcium, 0.2 part of medlar powder and adding water to supplement 100 parts.
The invention also provides application of the composition in preparing medicines for inhibiting inflammatory reaction and promoting angiogenesis and wound healing.
The composition for inhibiting inflammatory reaction, promoting angiogenesis and wound healing and the application thereof provided by the invention are obtained by taking marine fish skin collagen oligopeptide, wheat oligopeptide and blood protein polypeptide as main components and matching chamomile extract and beta-hydroxy-beta-methyl calcium butyrate, and the effects of promoting wound healing are achieved by inhibiting inflammatory reaction and promoting angiogenesis reaction, a plurality of links of wound healing are considered, and important theoretical and practical significance is provided for developing products for promoting wound healing.
In the composition, chamomile extract has the effects of resisting inflammation and relieving pain, beta-hydroxy-beta-methylbutyric acid calcium has the effects of accelerating protein synthesis or preventing proteolysis, medlar powder can enhance immunity, and blood protein polypeptide has the effect of enriching blood. The invention can be prepared by adopting pharmaceutically acceptable preparation process and auxiliary materials, including but not limited to conventional oral preparations such as granules, oral liquid and the like, and has the characteristics of low cost, good curative effect, no toxic or side effect due to natural sources and the like.
Drawings
FIG. 1 is a model set, example 5 and implementation 7 of the wound surface shape variation;
FIG. 2 is hematoxylin and eosin staining of wound tissue in model group, example 5 and example 7;
FIG. 3 shows the distribution of VEGF in the granulation tissue at the wound site in the model group, example 5 and example 7;
FIG. 4 shows the immunofluorescence intensity of CD34 in model set, example 5 and example 7;
FIG. 5 shows the CTGF immunofluorescence intensities of the model set, example 5 and example 7;
FIG. 6 is a graph comparing D-mannitol and fatty acid content in serum for model group, example 5 and example 7.
Detailed Description
The invention will be described more fully hereinafter with reference to the accompanying examples in order to facilitate an understanding of the invention, however, the invention may be embodied in many different forms and is not limited to the examples described herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used herein in the description of the invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. The term "and/or" as used herein includes any and all combinations of one or more of the associated listed items.
The following examples are provided to further illustrate embodiments of the invention. The embodiments of the present invention are not limited to the following specific embodiments. The modification can be appropriately performed within the scope of the main claim.
Example 1
200g of wheat oligopeptide, 200g of marine fish skin collagen oligopeptide, 50g of blood protein polypeptide, 15g of chamomile extract, 100g of beta-hydroxy-beta-methylbutyric acid calcium, 20g of medlar powder, 200g of water-soluble dietary fiber, 6g of casein phosphopeptide, 2g of zinc gluconate and 285g of sugar powder are taken, all materials are uniformly mixed and then are respectively sieved by a 100-mesh sieve, the uniformly mixed materials are boiled and granulated by using a 10% aqueous solution of povidone K30 as an adhesive, the atomization pressure is controlled to be 0.2Mpa, the material temperature is 42 ℃, the air inlet temperature is 70 ℃, the obtained particles are packaged by aluminum paper, and each bag is packaged by 20-mesh sieve.
Example 2
400g of wheat oligopeptide, 300g of marine fish skin collagen oligopeptide, 100g of blood protein polypeptide, 20g of chamomile extract, 200g of beta-hydroxy-beta-methyl calcium butyrate, 30g of medlar powder and 320g of sugar powder are taken, all materials are uniformly mixed and are respectively sieved by a 100-mesh sieve, the uniformly mixed materials are boiled and granulated by using a 10% aqueous solution of povidone K30 as an adhesive, the atomization pressure is controlled to be 0.2Mpa, the material temperature is 42 ℃, the air inlet temperature is 70 ℃, the obtained granules are granulated by using a 20-mesh sieve, and are packaged by aluminum paper, and each bag is 5g.
Example 3
Taking 300g of wheat oligopeptide, 400g of marine fish skin collagen oligopeptide, 100g of blood protein polypeptide, 20g of chamomile extract, 200g of beta-hydroxy-beta-methyl calcium butyrate, 30g of medlar powder and 320g of sugar powder, uniformly mixing all materials, sieving the materials with a 100-mesh sieve respectively, boiling and granulating the uniformly mixed materials by using a 10% aqueous solution of povidone K30 as an adhesive, controlling the atomization pressure to be 0.2Mpa, controlling the material temperature to be 42 ℃, controlling the air inlet temperature to be 70 ℃, finishing the obtained particles by using a 20-mesh sieve, packaging the particles by using aluminum paper, and packaging each bag by 5g.
Example 4
200g of wheat oligopeptide, 200g of marine fish skin collagen oligopeptide, 100g of blood protein polypeptide and 100g of sugar powder are taken, all materials are mixed uniformly and then respectively pass through a 100-mesh sieve, the uniformly mixed materials are boiled and granulated by using 10% aqueous solution of povidone K30 as an adhesive, the atomization pressure is controlled to be 0.2Mpa, the material temperature is 42 ℃, the air inlet temperature is 70 ℃, the obtained granules are granulated by using a 20-mesh sieve, and the granules are packaged by aluminum paper, wherein each bag is 6g.
Example 5
18g of wheat oligopeptide, 18g of marine fish skin collagen oligopeptide, 4g of blood protein polypeptide, 1g of chamomile extract, 10g of beta-hydroxy-beta-methylbutyric acid calcium, 2g of medlar 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 are taken, 500ml of purified water is added into a batching tank, and the wheat oligopeptide, the marine fish skin collagen oligopeptide, the blood protein polypeptide, the chamomile extract, the beta-hydroxy-beta-methylbutyric acid calcium, the medlar powder, the water-soluble dietary fiber and the isomaltulose are sequentially added and stirred for dissolution. Filtering with plate-frame filter to obtain filtrate. After dissolving sucralose, casein phosphopeptide, zinc gluconate and citric acid with a proper amount of purified water, adding water to 1000ml, stirring for 15 minutes, adding essence, stirring for 10 minutes, and filtering with a 0.45 μm filter element. Filling, sterilizing at 105deg.C for 30 min per bottle 100 ml.
Example 6
16g of wheat oligopeptide, 16g of marine fish skin collagen oligopeptide, 8g of blood protein polypeptide, 0.5g of chamomile extract, 20g of beta-hydroxy-beta-methylbutyric acid calcium, 2g of medlar 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 are taken, 500ml of purified water is added into a batching tank, and the wheat oligopeptide, the marine fish skin collagen oligopeptide, the blood protein polypeptide, the chamomile extract, the beta-hydroxy-beta-methylbutyric acid calcium, the medlar powder, the water-soluble dietary fiber and the isomaltulose are sequentially added and stirred for dissolution. Filtering with plate-frame filter to obtain filtrate. After dissolving sucralose, casein phosphopeptide, zinc gluconate and citric acid with a proper amount of purified water, adding water to 1000ml, stirring for 15 minutes, adding essence, stirring for 10 minutes, and filtering with a 0.45 μm filter element. Filling, sterilizing at 105deg.C for 30 min per bottle 100 ml.
Example 7
Taking 20g of wheat oligopeptide, 12g of marine fish skin collagen oligopeptide, 8g of blood protein polypeptide, 1g of chamomile extract, 20g of beta-hydroxy-beta-methylbutyric acid calcium, 2g of medlar powder, 10g of water-soluble dietary fiber, 0.4g of casein phosphopeptide, 0.06g of zinc gluconate, 0.15g of sucralose and 2.0g of citric acid, 8g of isomaltulose, adding 500ml of purified water into a batching tank, and sequentially adding the wheat oligopeptide, the marine fish skin collagen oligopeptide, the blood protein polypeptide, the chamomile extract, the beta-hydroxy-beta-methylbutyric acid calcium, the medlar powder, the water-soluble dietary fiber and the isomaltulose into the batching tank, and stirring to dissolve the materials. Filtering with plate-frame filter to obtain filtrate. After dissolving sucralose, casein phosphopeptide, zinc gluconate and citric acid with a proper amount of purified water, adding water to 1000ml, stirring for 15 minutes, adding essence, stirring for 10 minutes, and filtering with a 0.45 μm filter element. Filling, sterilizing at 105deg.C for 30 min per bottle 100 ml.
Example 8
12g of wheat oligopeptide, 20g of marine fish skin collagen oligopeptide, 8g of blood protein polypeptide, 2g of chamomile extract, 20g of beta-hydroxy-beta-methylbutyrate calcium, 2g of medlar powder, 10g of water-soluble dietary fiber, 0.15g of sucralose, 2.0g of citric acid and 8g of isomaltulose are taken, 500ml of purified water is added into a batching tank, and the wheat oligopeptide, the marine fish skin collagen oligopeptide, the blood protein polypeptide, the chamomile extract, the beta-hydroxy-beta-methylbutyrate calcium, the medlar powder, the water-soluble dietary fiber and the isomaltulose are sequentially added and stirred to be dissolved. Filtering with plate-frame filter to obtain filtrate. After dissolving sucralose and citric acid in a proper amount of purified water, adding the solution into the filtrate, adding water to 1000ml, stirring for 15 minutes, adding essence, stirring for 10 minutes, and filtering with a 0.45 μm filter element. Filling, sterilizing at 105deg.C for 30 min per bottle 100 ml.
In the present invention, the action mechanism of the compositions provided in example 5 and example 7 on wound healing was studied, and specifically includes the following methods:
1. inhibition of inflammatory response, promotion of angiogenesis and wound healing efficacy studies
1. Materials and methods
1.1 raw materials: examples 5 and 7 samples, positive control (yapekuai guaifenesin).
1.2 experimental animals: male Kunming mice, weighing 20-22g,6-8 weeks old, were supplied by Jiangsu Jiuyaokang biotechnology Co., ltd, and were licensed with the number SCXK (Su) 2018-0008.
1.3 experimental conditions: mice were kept in a clean environment in a river-Chinese medicine industry animal experiment center under the license number SYXK 2020-004. Laboratory temperature 24±2 ℃; relative humidity 45-65%; illumination period: 12 (day)/12 (night) hours.
1.4 experimental method:
1.4.1 rats were anesthetized with isoflurane, after which the back of the rats was shaved using a shaver to expose an area of about 3cm x 3cm to the back. Then the dehairing paste is used for dehairing, after 3 to 5 minutes, cotton is dipped with warm water to clean the back dehairing paste, and then the back moisture is wiped by dry cotton.
1.4.2 cleaning and disinfecting the rat back experimental area with iodophor, then pressing down on the rat back (basically ensuring the same position of each molding) with a skin sampler with the diameter of 10mm in a rotating way, forming a small notch, and removing the skin with an ophthalmic forceps and an ophthalmic scissors to form a circular wound with the diameter of 10 mm.
1.4.3 wound area measurement: rats were kept flat, photographed at the same height using an industrial high definition camera and subjected to primary wound measurement.
1.4.4 each group was followed daily by administration of the corresponding drug and wound area measurements were made on days 2, 3, 6, 10, 12, 14, respectively. The mice were anesthetized with isoflurane and photographed at the same height to make wound area measurements.
1.4.5 wound healing rate: wound area was photographed and measured with a camera every 2 days, and wound healing rate (wound healing rate, WHR) was calculated.
WHR=(D 0 -D n )/D 0 ×100%
Wherein: WHR is the wound healing rate WHR,%; d (D) 0 Diameter, cm, of the initial wound shape; d (D) n Is the diameter of the shape of the unhealed wound, cm.
1.4.6 sampling: after administration, 3d and 14d, the whole wound surface and normal skin tissues 5mm away from the wound edge are respectively sheared, and respectively placed in 4% paraformaldehyde for fixation and liquid nitrogen preservation.
1.4.7 pathology and immunohistochemistry: the new skin at the wound of the rat was excised, and the skin tissue was fixed in paraformaldehyde and embedded in paraffin. A 5 μm section of paraffin embedded skin was prepared for further experiments. H & E staining and Masson staining were used to examine mucosal lesions. For immunohistochemistry, the sections were incubated with anti-CD 34 protein and CTGF protein antibodies at 4 ℃. All results were observed by microscopy.
1.4.8 data analysis: data are expressed as mean.+ -. Standard deviation (mean.+ -. SEM), analyzed using One-way ANOVA, and then compared pairwise between groups using Dunnet method. The analysis results were statistically significant with P <0.05 and P <0.001 considered extremely significant differences. All data were analyzed using GraphPad Prism 8.0 statistical software package.
1.5 results
1.5.1 wound morphology Change observations
The healing of each group is shown in figure 1, and on day 2 after molding, animals of each group had crusted, no fluid exuded, and wound shrinkage was not evident, whereas on day 4 after molding, animals of the model group began crusting. On days 4, 6 and 10 after molding, the wound surface crusts of each group are continuously hardened, the surface around the wound is uneven, the skin shrinkage of the wound edge is obvious, wherein the skin shrinkage speed of the wound of each administration group is better than that of the model group. On day 12 after moulding, most of the mice in each group had fallen off the scab, and the healed sites began to grow hair, and each group was further scab. On day 14 after molding, each administration group presents flesh red new skin, the new flesh has complete tissue, and has better healing condition than the control group, and no hypertrophic scar and keloid generation.
1.5.2 healing Rate and scar reduction Rate
The wound surface area was photographed and measured with a camera every 2 days, and the measurement results were shown in table 1, according to the wound healing rate = (wound area on day 0 after molding-wound area on day of measurement)/(wound area on day 0 after molding) calculated result of 100%:
table 1: wound healing rate of mice
Note that: * Representing significance between Model and around, p <0.05, p < 0.01;
# represents significance between Model and Chuuun, # p <0.05, # p < 0.01;
significance between Model and improved Chuuun, p <0.05, p < 0.01.
As can be seen from Table 1, on day 3 of molding, the wound healing rates were close to 40% between each group, with no significant difference (P > 0.05) between the dosing group and the model group. On day 4 of modeling, the healing rate was significantly higher for each dosing group than for the model group. On day 6 of modeling, the healing rate was significantly higher for each dosing group than for the model group, with example 7 being better than for yapekuai and example 5. The healing rate was significantly higher for each of the dosing groups than for the model groups on days 8, 10 and 12 of modeling. On the 14 th day of molding, the wound healing rate of each group reaches more than 90%, the wound healing process is basically finished, and no significant difference (P is more than 0.05) exists between each group.
1.5.3H & E staining
As shown in fig. 2, several mice (n=6) were sacrificed per group on day 4 post-treatment and tissues were H & E stained. It can be seen that none of the wounds of each group healed completely, with the formation of granulation tissue starting in the full layer of dermal tissue and re-epithelialization of the wound border area. Wherein the model group granulation tissue was immature in development and strong inflammatory infiltration of lymphocytes, interstitial edema and hemorrhage were observed. Example 5, example 7 and yapekuai-guaifenesin, the whole layer of skin and subcutaneous tissue at the wound edge moves toward the center, and the wound gradually shrinks; although there was also a different degree of inflammatory cell infiltration, the granulation tissue was more mature than in the model group, indicating that each intervention group had some effect in promoting wound healing.
1.5.4VEGF grouping
VEGF (vascular endothelial growth factor) plays a vital 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 at the earliest 3 days after injury. Thus, expression of VEGF in the granulation tissue area during wound healing represents the number of new blood vessels.
By detecting the distribution of VEGF in the granulation tissue of the wound part on the 4 th day after modeling through immunohistochemistry, as shown in figure 3, VEGF positive cells are brown, and the VEGF expression of the wound after the intervention of the yapekuai healin is not significantly different compared with that of a model group; whereas example 5 and example 7, in the dry prognosis, dispersed VEGF was observed in both infiltrating inflammatory cells and fibroblast-like cells in connective tissue at the wound site, and had a higher VEGF positive cell rate compared to model and yapeku-guaifenesin intervention groups. The results indicate that examples 5 and 7 are able to promote angiogenic responses during the wound healing process.
1.5.5CD34 immunofluorescence
Because wound healing requires angiogenesis, immunofluorescent staining of CD34 is used as a vascular system marker to study wound angiogenesis. As shown in FIG. 4, DAPI shows blue fluorescence and CD34 shows red fluorescence on each group of wound beds, indicating that there is a certain amount of neovascularization during wound healing, wherein the red fluorescence of example 5 and example 7 is greater than that of the model group, indicating that example 5 and example 7 both significantly increase the number of neovascularization, meaning that example 5 and example 7 promote angiogenesis and promote vascular network remodeling and wound healing. Furthermore, the yapekuai group did not show denser neovasculature at the wound site compared to the model group.
1.5.6CTGF immunofluorescence
Connective Tissue Growth Factor (CTGF) has a positive effect on the production of mature, well-organized and vascularized granulation tissue during the early wound healing phase. The distribution of CTGF in the wound on day 4 after molding was analyzed using immunofluorescence, DAPI blue fluorescence, CTGF red fluorescence, as shown in fig. 5, which is a representative image of the presence and distribution of CTGF positive cells in each group of wound healing regions, and the results indicate that example 5, example 7, and the quick healing group each showed more red fluorescence, i.e., more CTGF positive cells, than the model group. Wherein example 5 and example 7 fluoresce more red than the yapekine group, demonstrating that example 5 and example 7 interventions better promote cell adhesion, migration and proliferation than yapekine interventions at early stages of wound healing, thereby promoting the wound repair process.
1.5.7 transfer rate histology analysis- -identification of potential differential metabolites
The UPLC-TOF/MS is adopted for sample separation and data acquisition, each component can be well separated in a positive ion mode and a negative ion mode, the retention time and the peak area of each group are different, the model group, the example 5 and the example 7 are distributed in different quadrant areas, the separation degree is good, and the difference of serum metabolites of mice in each group is large. Meanwhile, mice were given potential differential metabolites common to example 5 and example 7 as shown in table 2.
TABLE 2 identification of potential differential metabolites common to example 5 and example 7
Note that: VIP variable projection importance of the substance on the set of comparison OPLS-DA models
FC: fold relationship of the substance between the comparative two experiments
P-the P-value obtained by t-test of the substance in the set of comparisons, P-value = probability that the hypothesis is correct but rejected = number of negative results/total number of results, is a probability of test on the sample data
The 9 differential metabolites selected are used as potential biomarkers in the wound healing process and mainly comprise 3-hydroxydecanoic acid, D-mannose, L-cystein, ethoxyquinoline, linolenic acid and derivatives thereof, fatty acyl, glycerolipid, glycerophospholipid and the like. Wherein D-mannose is an epimer of glucose, exists mainly in the form of an alpha-or beta-pyranose isomer, is directly utilized to synthesize glycoprotein in a human body, and has the effect of inhibiting inflammatory reaction in the wound healing process. The action of bioactive lipids occurs mainly in the inflammatory phase of the wound healing process. It has been further reported that topical use of fatty acid analogues and their receptor agonists can modulate inflammatory and immune responses during wound healing. As is clear from the results of fig. 6, the serum D-mannitol and fatty acid content in examples 5 and 7 were higher than those in the model group, the D-mannitol content in example 7 was higher, the fatty acid substance content in example 5 was higher, and examples 5 and 7 exert an effect of suppressing the inflammatory level in early wound healing by increasing the fatty acid level in serum, thereby exerting an effect of promoting wound healing.
The above embodiments represent only a few embodiments of the present invention, which are described in more detail and are not to be construed as limiting the scope of the present invention. It should be noted that it will be apparent to those skilled in the art that several variations and modifications can be made without departing from the spirit of the invention, which are all within the scope of the invention. Accordingly, the scope of protection of the present invention is to be determined by the appended claims.

Claims (2)

1. A composition for inhibiting inflammatory response, promoting angiogenesis and wound healing, comprising the following components in parts by weight:
0.1-100 parts of wheat oligopeptide, 0.1-100 parts of marine fish skin collagen oligopeptide, 0.1-100 parts of blood protein polypeptide, 0.01-2 parts of chamomile extract, 0.1-20 parts of beta-hydroxy-beta-methylbutyrate calcium, 0.01-3 parts of medlar powder, 0.001-1 part of zinc gluconate, 0.01-5 parts of casein phosphopeptide and 1-100 parts of water-soluble dietary fiber.
2. Use of a composition according to claim 1 for the manufacture of a medicament for promoting wound healing, for promoting angiogenesis in a wound healing process, for promoting angiogenesis and promoting vascular network remodeling and wound healing, for promoting cell adhesion, migration and proliferation at an early stage of wound healing, thereby promoting a wound repair process, and for exerting an effect of inhibiting inflammatory levels at an early stage of wound healing by increasing fatty acid levels in serum, thereby exerting an effect of promoting wound healing.
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Families Citing this family (1)

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Citations (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101455405A (en) * 2009-01-04 2009-06-17 江中药业股份有限公司 Food or medicine capable of promoting wound healing after operation
CN101461934A (en) * 2009-01-04 2009-06-24 江中药业股份有限公司 Application of small-molecule peptide in preparing medicament and food for promoting wound healing after operation
CN102049037A (en) * 2009-11-06 2011-05-11 李勇 Application of ocean collagen peptide in process of preparing diabetes wound healing medicaments and foods
CN103845721A (en) * 2012-11-29 2014-06-11 江中药业股份有限公司 Composition for control of radiation damage or chemotherapy damage and preparation method thereof
CN103845722A (en) * 2012-11-29 2014-06-11 江中药业股份有限公司 Oligopeptide composition for control of radiation damage or chemotherapy damage and preparation method thereof
CN105311061A (en) * 2014-05-31 2016-02-10 陈光健 Pharmaceutical composition having wound surface healing effect, preparation method and applications thereof
CN106962923A (en) * 2017-03-22 2017-07-21 深圳太太药业有限公司 It is a kind of for it is physically weak, after being ill, the ocean dietary composition taken good care of of operation and preparation method thereof
CN108339112A (en) * 2016-12-30 2018-07-31 亚宝药业集团股份有限公司 A kind of alimentation composition for promoting wound healing, bedsore reparation, postoperative stress ulcer healing
CN109757734A (en) * 2019-03-01 2019-05-17 上海傅克化学科技有限公司 A kind of polypeptide oral liquor and preparation method thereof
CN110585272A (en) * 2019-10-23 2019-12-20 湖北精耕生物工程有限公司 Bacteriostatic scar-removing liquid and preparation method thereof
CN111436597A (en) * 2020-04-01 2020-07-24 山东若尧特医食品有限公司 Lipid chain peptide and production process thereof
CN111632075A (en) * 2020-05-27 2020-09-08 广州赛琅生物技术有限公司 Exosome preparation for promoting skin wound healing and preparation method thereof
CN111802646A (en) * 2020-05-14 2020-10-23 河北康睿达脂质有限公司 A nutritional composition for preventing muscle decay and its preparation method
WO2022165700A1 (en) * 2021-02-04 2022-08-11 吴达镕 Polypeptide nutrition powder and preparation method therefor
CN115634279A (en) * 2022-04-14 2023-01-24 吉林农业科技学院 Deer blood peptide hydrogel and application thereof in preparing medicine for treating diabetic skin injury

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19634959A1 (en) * 1996-08-29 1998-03-05 Karl Aulbach Ointment for treating wounds, etc.
FR2910815B1 (en) * 2006-12-28 2010-10-29 Expanscience Lab COMPOSITION COMPRISING AN EXTRACT OF QUINOA SEEDS
CN105077270A (en) * 2015-07-16 2015-11-25 上海冬泽特医食品有限公司 Nutrient supplemented composite powder as well as preparation method and use thereof
JP7114458B2 (en) * 2015-09-16 2022-08-08 メタボリック・テクノロジーズ,インコーポレーテッド Compositions and methods of use of β-hydroxy-β-methylbutyrate (HMB) to enhance recovery from soft tissue trauma
CN116036247B (en) * 2023-02-03 2024-04-05 江中药业股份有限公司 Composition for inhibiting inflammatory response, promoting angiogenesis and wound healing and application thereof

Patent Citations (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101461934A (en) * 2009-01-04 2009-06-24 江中药业股份有限公司 Application of small-molecule peptide in preparing medicament and food for promoting wound healing after operation
CN101455405A (en) * 2009-01-04 2009-06-17 江中药业股份有限公司 Food or medicine capable of promoting wound healing after operation
CN102049037A (en) * 2009-11-06 2011-05-11 李勇 Application of ocean collagen peptide in process of preparing diabetes wound healing medicaments and foods
CN103845721A (en) * 2012-11-29 2014-06-11 江中药业股份有限公司 Composition for control of radiation damage or chemotherapy damage and preparation method thereof
CN103845722A (en) * 2012-11-29 2014-06-11 江中药业股份有限公司 Oligopeptide composition for control of radiation damage or chemotherapy damage and preparation method thereof
CN105311061A (en) * 2014-05-31 2016-02-10 陈光健 Pharmaceutical composition having wound surface healing effect, preparation method and applications thereof
CN108339112A (en) * 2016-12-30 2018-07-31 亚宝药业集团股份有限公司 A kind of alimentation composition for promoting wound healing, bedsore reparation, postoperative stress ulcer healing
CN106962923A (en) * 2017-03-22 2017-07-21 深圳太太药业有限公司 It is a kind of for it is physically weak, after being ill, the ocean dietary composition taken good care of of operation and preparation method thereof
CN109757734A (en) * 2019-03-01 2019-05-17 上海傅克化学科技有限公司 A kind of polypeptide oral liquor and preparation method thereof
CN110585272A (en) * 2019-10-23 2019-12-20 湖北精耕生物工程有限公司 Bacteriostatic scar-removing liquid and preparation method thereof
CN111436597A (en) * 2020-04-01 2020-07-24 山东若尧特医食品有限公司 Lipid chain peptide and production process thereof
CN111802646A (en) * 2020-05-14 2020-10-23 河北康睿达脂质有限公司 A nutritional composition for preventing muscle decay and its preparation method
CN111632075A (en) * 2020-05-27 2020-09-08 广州赛琅生物技术有限公司 Exosome preparation for promoting skin wound healing and preparation method thereof
WO2022165700A1 (en) * 2021-02-04 2022-08-11 吴达镕 Polypeptide nutrition powder and preparation method therefor
CN115634279A (en) * 2022-04-14 2023-01-24 吉林农业科技学院 Deer blood peptide hydrogel and application thereof in preparing medicine for treating diabetic skin injury

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
初元口服液;江中集团;百度百科;第1-3页 *
心脑血管疾病探秘(三)血液垃圾清除剂-血肽;贝杉国际浙江省中心;微信;1-6 *

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