Composition for digestive tract wound and digestive tract wound gel

文档序号：91793 发布日期：2021-10-12 浏览：21次中文

阅读说明：本技术 用于消化道创面的组合物以及消化道创面凝胶 (Composition for digestive tract wound and digestive tract wound gel ) 是由杜武华林栋青赵素霞黄显峰尹翠竹刁盈盈邓文平邱新林李鹏娥王贵齐于 2020-03-20 设计创作，主要内容包括：本发明涉及医学制剂领域,特别涉及用于消化道创面的组合物以及消化道创面凝胶。本发明提供的创面凝胶能够迅速吸收创面表面的水分、血液、渗出物等液体,形成凝胶保护层；能够减少创面出血、穿孔风险；能够覆盖创面,防止幽门螺旋杆菌等病原微生物与创面接触,有效防止感染的发生,减少抗生素的应用；能够应用于消化道黏膜创面,有效抗击胃酸、胃蛋白酶及其他攻击因子对创面的攻击和侵蚀。(The invention relates to the field of medical preparations, in particular to a composition for a wound surface of a digestive tract and a gel for the wound surface of the digestive tract. The wound surface gel provided by the invention can rapidly absorb moisture, blood, exudate and other liquids on the surface of the wound surface to form a gel protective layer; the risk of bleeding and perforation of the wound surface can be reduced; the wound surface can be covered, pathogenic microorganisms such as helicobacter pylori and the like are prevented from contacting the wound surface, infection is effectively prevented, and the application of antibiotics is reduced; can be applied to the wound surface of the mucous membrane of the digestive tract, and effectively resists the attack and the erosion of gastric acid, pepsin and other attacking factors to the wound surface.)

1. The composition for the wound surface of the digestive tract is characterized by comprising the following components in parts by weight:

the viscose substrate is partially neutralized sodium polyacrylate, and the structural formula of the viscose substrate is shown as a formula I:

in the formula I, the molar ratio of X to Y is 1:4-4:1, and the polymerization degree is 2000-70000.

2. The composition of claim 1, wherein the molar ratio of X to Y in formula I is 4:1, 1:4, 3:7, 2:3, 13:7, 1:3, 1:1, or 3: 1.

3. The composition according to claim 1 or 2, wherein the hygroscopic agent is polyethylene glycol and has a relative molecular weight of 1000 to 20000.

4. The composition of claim 3, wherein the polyethylene glycol has a relative molecular weight of 1000, 20000, 15000, 8000, 6000, 4000, 10000 or 2000.

5. The composition of any one of claims 1 to 4, wherein the thickening agent comprises one or a mixture of two or more of biocompatible starch, hyaluronic acid, sodium alginate, polyethylene glycol and derivatives thereof, polyethylene oxide and derivatives thereof, poloxamer, sodium carboxymethylcellulose, polyvinylpyrrolidone, gelatin, tragacanth, carbomer, chitosan and derivatives thereof, polyvinyl alcohol and derivatives thereof.

6. The composition of claim 5, wherein the biocompatible starch comprises a mixture of one or more of etherified starch, esterified starch, cross-linked starch, grafted starch, or modified starch.

7. The composition of any one of claims 1 to 6, wherein the cross-linking agent comprises one or more of aluminum hydroxide, aluminum glycollate, aluminum chloride, potassium aluminum sulfate dodecahydrate, zinc L-carnosine, magnesium aluminum carbonate, magnesium aluminum hydroxide, magnesium aluminum carbonate, aluminum phosphate, aluminum sucralfate, aluminum clofibrate, and aluminum allantoate.

8. A process for the preparation of a composition according to any one of claims 1 to 6, comprising the steps of:

step 1, heating, stirring and uniformly mixing a viscose substrate, a thickening agent, a cross-linking agent and a moisture absorbent at 60-200 ℃;

and 2, cooling, sieving with a 40-200 mesh sieve, and subpackaging.

9. Use of a composition according to any one of claims 1 to 6 in the preparation of a gut wound gel, dressing or medicament.

10. An alimentary canal wound gel, dressing or medicament comprising a composition according to any one of claims 1 to 6 and a pharmaceutically acceptable excipient.

Technical Field

The invention relates to the field of medical preparations, in particular to a composition for a wound surface of a digestive tract and a gel for the wound surface of the digestive tract.

Background

After minimally invasive surgery of the digestive tract, wounds and wound surfaces are usually directly exposed on the surface of the digestive tract and stimulated by harmful substances such as bacteria, gastric acid, digestive enzymes and the like, so that the healing difficulty is increased. In recent years, in order to promote the rapid healing of wound surfaces, various wound dressings come into operation, and can be divided into traditional dressings, biological dressings, artificially synthesized dressings, growth factor dressings and the like according to different materials. The wound dressings create a wound hypoxia environment by utilizing the characteristics of different materials, promote the generation of capillary vessels and the removal of necrotic tissues and toxins, strengthen the interaction between growth factors and target cells, avoid the adhesion of new epithelial tissues and dressings, and further relieve the pain of patients. Therefore, the wound dressing can shorten the wound healing time, reduce the waste of resources, greatly reduce the medical workload and meet the requirements of patients.

The prior dressing for the wound surface of the digestive tract can not absorb water rapidly and is bonded to the wound surface of the digestive tract. In the prior art, the dressing for the wound surface of the digestive tract has insufficient water absorption and can not be quickly adhered to the wound surface, or the dressing can not be effectively sprayed on the wound surface due to too strong moisture absorption. And the prior dressing for the wound surface of the digestive tract can not stay on the wound surface of the digestive tract for a long time and provide long-time wound surface protection. The digestive tract wound dressing can be peeled, fall off and disintegrate along with the peristalsis of the digestive tract due to the fact that the digestive tract (esophagus, stomach and intestine) is constantly in the peristalsis state, and long-time wound protection cannot be provided. Therefore, the invention provides a wound dressing which can rapidly absorb water and adhere to a wound surface of a digestive tract to form a gel protective layer, has strong adhesion, can cover the wound surface of the digestive tract for a long time and provides long-time wound surface protection, and the wound dressing is a problem to be solved by the technical personnel in the field.

Disclosure of Invention

In view of the above, the present invention provides a composition for a wound of digestive tract and a gel for a wound of digestive tract. The digestive tract wound surface gel can quickly absorb water and adhere to a digestive tract wound surface to form a gel protective layer, has strong adhesive force, can cover the digestive tract wound surface for a long time, and provides long-time wound surface protection.

In order to achieve the above object, the present invention provides the following technical solutions:

the invention provides a composition for a wound surface of a digestive tract, which comprises the following components in parts by weight:

the viscose substrate is partially neutralized sodium polyacrylate, and the structural formula of the viscose substrate is shown as a formula I:

in the formula I, the molar ratio of X to Y is 1:4-4:1, and the polymerization degree is 2000-70000.

In some embodiments of the invention, the molar ratio of X to Y in formula I is 4:1, 1:4, 3:7, 2:3, 13:7, 1:3, 1:1, or 3: 1.

In some embodiments of the present invention, the moisture absorbent is polyethylene glycol and has a relative molecular weight of 1000 to 20000.

In some embodiments of the invention, the polyethylene glycol has a relative molecular weight of 1000, 20000, 15000, 8000, 6000, 4000, 10000 or 2000.

In some embodiments of the invention, the thickening agent comprises one or a mixture of two or more of biocompatible starch, hyaluronic acid, sodium alginate, polyethylene glycol and derivatives thereof, polyethylene oxide and derivatives thereof, poloxamer, sodium carboxymethylcellulose, polyvinylpyrrolidone, gelatin, tragacanth, carbomer, chitosan and derivatives thereof, polyvinyl alcohol and derivatives thereof.

In some embodiments of the invention, the biocompatible starch comprises a mixture of one or more of etherified starch, esterified starch, cross-linked starch, grafted starch, or modified starch.

In some embodiments of the invention, the cross-linking agent comprises one or more of aluminum hydroxide, aluminum glycollate, aluminum chloride, aluminum potassium sulfate dodecahydrate, zinc L-carnosine, magnesium aluminocarbonate, aluminum magnesium hydroxide, magnesium aluminocarbonate, aluminum phosphate, aluminum thionate, aluminum clofibric acid, and aluminum allantoate.

The invention also provides a preparation method of the composition, which comprises the following steps:

step 1, heating, stirring and uniformly mixing a viscose substrate, a thickening agent, a cross-linking agent and a moisture absorbent at 60-200 ℃;

and 2, cooling, sieving with a 40-200 mesh sieve, and subpackaging.

The invention also provides application of the composition in preparation of digestive tract wound gel or medicines.

The invention also provides a gel or a medicament for the wound surface of the digestive tract, which comprises the composition and pharmaceutically acceptable auxiliary materials.

The wound surface gel provided by the invention can rapidly absorb moisture, blood, exudate and other liquids on the surface of the wound surface to form a gel protective layer; the risk of bleeding and perforation of the wound surface can be reduced; the wound surface can be covered, pathogenic microorganisms such as helicobacter pylori and the like are prevented from contacting the wound surface, infection is effectively prevented, and the application of antibiotics is reduced; can be applied to the wound surface of the alimentary canal mucous membrane, and effectively resists the attack and erosion of gastric acid, pepsin and other attack factors to the wound surface

Detailed Description

The invention discloses a composition for a digestive tract wound and a digestive tract wound gel, which can be realized by appropriately improving process parameters by referring to the content. It is expressly intended that all such similar substitutes and modifications which would be obvious to one skilled in the art are deemed to be included in the invention. While the methods and applications of this invention have been described in terms of preferred embodiments, it will be apparent to those of ordinary skill in the art that variations and modifications in the methods and applications described herein, as well as other suitable variations and combinations, may be made to implement and use the techniques of this invention without departing from the spirit and scope of the invention.

The invention provides a digestive tract wound surface gel, which comprises the following components: 5-40 parts of viscose matrix, 20-80 parts of thickening agent, 2-20 parts of cross-linking agent and 5-20 parts of moisture absorbent.

In some embodiments, the adhesive matrix is a partially neutralized sodium polyacrylate having the structure of formula I:

in the formula I, the ratio (molar ratio) of X to Y is 1:4-4:1, and the polymerization degree is 2000-70000.

In some embodiments, the thickening agent comprises one or more of biocompatible starch, hyaluronic acid, sodium alginate, polyethylene glycol and derivative compounds, polyethylene oxide and derivative compounds, poloxamers, sodium carboxymethylcellulose, polyvinylpyrrolidone, gelatin, tragacanth, carbomer, chitosan and derivative compounds, polyvinyl alcohol and derivative compounds.

In some embodiments, the biocompatible starch is selected from one or more of etherified starch, esterified starch, cross-linked starch, grafted starch, modified starch.

In some embodiments, the crosslinking agent comprises one or more of aluminum hydroxide, aluminum glycollate, aluminum chloride, potassium aluminum sulfate dodecahydrate, zinc L-carnosine, magnesium aluminum carbonate, aluminum magnesium hydroxide, magnesium aluminum carbonate, aluminum phosphate, aluminum sucralfate, aluminum clofibric acid, and aluminum allantoate. ,

in some embodiments, the hygroscopic agent is polyethylene glycol with a relative molecular weight of 1000-.

In addition, the invention also provides a preparation method of the digestive tract wound gel, which comprises the following steps:

step 1, heating, stirring and uniformly mixing a viscose substrate, a thickening agent, a cross-linking agent and a moisture absorbent at 60-200 ℃;

and 2, cooling, passing through a 40-200-mesh standard sieve, filling and sealing.

The invention also provides a preparation method of the digestive tract wound gel, the grain size of the prepared wound gel is 40-200 meshes, and the water absorption rate is more than 5 times of the self weight.

The digestive tract wound surface gel provided by the invention is applied to the digestive tract wound surface through an endoscope.

The alimentary canal wound surface gel provided by the invention has the particle size of 40-200 meshes, the water absorption rate is 5 times larger than the self weight, the alimentary canal wound surface gel can quickly absorb water and is bonded to an alimentary canal wound surface to form a gel protective layer, the adhesive force is strong, and the alimentary canal wound surface gel can stay on the alimentary canal wound surface for a long time to provide protection for the wound surface and promote the wound surface to heal.

The composition for the digestive tract wound surface and the raw materials and the reagents used in the digestive tract wound surface gel provided by the invention can be purchased from the market.

The invention is further illustrated by the following examples:

examples 1 to 8

The preparation method comprises the following steps:

(1) heating, mixing and stirring the viscose matrix, the thickening agent, the cross-linking agent and the moisture absorbent at 60-200 ℃, cooling, passing through a 40-200-mesh standard sieve, filling and sealing.

Comparative example

The preparation method comprises the following steps:

(1) and (3) respectively sieving the viscose matrix, the thickening agent, the cross-linking agent and the moisture absorbent through a 40-200-mesh standard sieve, weighing, mixing and stirring uniformly, filling and sealing.

Effect example 1 gel formation time of digestive tract wound surface gel

The samples were taken in examples 1, 2, 3, 4, 5, 6,

Example 7, example 8, comparative example 2 and comparative example 4 each 2.0g were evenly distributed in a dish containing 10g of water, water was absorbed to form a gel, the time to complete gel formation was recorded, the test was repeated 10 times for each sample, and the arithmetic mean of the gel formation times for the samples was calculated.

TABLE 1

Sample (I)	Gel formation time
		Example 1	Instantaneous moment of action^b
Example 2	Instantaneous moment of action^b
		Example 3	Instantaneous moment of action^b
Example 4	Instantaneous moment of action^b
		Example 5	Instantaneous moment of action^b
Example 6	Instantaneous moment of action^b
		Example 7	Instantaneous moment of action^b
Example 8	Instantaneous moment of action^b
		Comparative example 2	28min^a
Comparative example 4	26min^a

Note: the different lower case letters indicate significant differences at the 5% level.

The results of Table 1 show that all formulations obtained in the examples of the present invention, which contain polyethylene glycol (having a relative molecular weight of 1000-20000) in the gel of the digestive tract, are capable of instantly absorbing water to form a gel, while comparative example 2, which does not contain polyethylene glycol, has a water-absorbing gel-forming time of 28min and comparative example 4, which contains polyethylene glycol and is prepared by a direct mixing process, has a water-absorbing gel-forming time of 26 min.

The inventors have surprisingly found that materials also containing polyethylene glycol, prepared by different preparation processes, have very different gel forming times. The gel preparation for the wound surface of the digestive tract prepared by the preparation process can instantly absorb water to form gel, and the gel preparation for the wound surface of the digestive tract prepared by the direct mixing process can form gel only after a long time.

The results of comparison between the two groups using the Tam-Black-Ni test using the IBM-sp standards 23 statistical treatment analysis showed significant differences in gel formation times for the examples compared to comparative examples 2 and 4(P < 0.05).

Effect example 2 gel adhesion to digestive tract wound surface

2.0g of each of example 1, example 2, example 3, example 4, example 5, example 6, example 7, example 8, comparative example 1 and comparative example 3 was uniformly distributed in a dish containing 10g of water, and water was absorbed to form a gel, and the gel was measured according to the method for measuring the adhesive strength of 0952, published by pharmacopoeia of the people's republic of China, 2015 edition, and the arithmetic mean of the adhesive strengths of the samples was calculated.

TABLE 2

Sample (I)	Average value of adhesive force (mN)
		Example 1	6280^a
Example 2	8430^a
		Example 3	7650^a
Example 4	8160^a
		Example 5	6930^a
Example 6	6540^a
		Example 7	7360^a
Example 8	7520^a
		Comparative example 1	1260^b
Comparative example 3	1470^b

Note: the different lower case letters indicate significant differences at the 5% level.

The results in Table 2 show that the total preparation obtained in the inventive example contains sodium polyacrylate gel, the gel formed after water absorption has good adhesion, the gel adhesion is 6540-8430 mN, which is obviously better than the digestive tract gel without sodium polyacrylate, and the gel adhesion of comparative example 1 and comparative example 3 is only 1260mN and 1470 mN.

The IBM sps standards 23 is adopted for statistical processing analysis, Kruskal-wallis H (K) test is adopted for analysis, the result shows that P is less than 0.05, the overall difference between the groups of the research is statistically significant, and the results show that the difference between the two groups (P is less than 0.05) is significant by adopting Tam Black Ni test.

Effect example 3 spray applicability test

Samples having particle sizes of 30 mesh, 40 mesh, 100 mesh, 200 mesh and 270 mesh were prepared according to the formulation and preparation method of example 5, respectively.

Samples having particle diameters of 40 mesh, 100 mesh and 200 mesh were prepared according to the preparation method of comparative example 5.

An endoscope system composed of an electronic endoscope host (CV-260/CLV-260, olympus medical corporation) and an electronic gastroscope (GIF-Q260J, olympus medical corporation) was used, and example 5(30 mesh, 40 mesh, 100 mesh, 200 mesh, 270 mesh), comparative example 5(40 mesh, 100 mesh, 200 mesh), was sprayed in a simulated gastric anatomy model by a powder spraying system (composed of an air pump, an air filter, a handle, a delivery pipe, WEYY-FJ, Shandongwei high pharmaceutical industry Co., Ltd.) under the same test conditions, and each sample was subjected to 100 tests, and the number of times of clogging of the sample in the delivery pipe of the powder spraying system during the spraying process of the test samples was counted.

TABLE 3

	Number of blockages in 100 trials
		Example 5(30 mesh)	57^c
Example 5(40 mesh)	2^a
		Example 5(100 mesh)	0^a
Example 5(200 mesh)	0^a
		Example 5(270 mesh)	46^b,c
COMPARATIVE EXAMPLE 5(40 mesh)	41^b,c
		COMPARATIVE EXAMPLE 5(100 mesh)	29^b
COMPARATIVE EXAMPLE 5(200 mesh)	33^b

Note: the different lower case letters indicate significant differences at the 5% level.

Samples having particle diameters of 30 mesh, 40 mesh, 100 mesh, 200 mesh, and 270 mesh were prepared according to the preparation method of example 5, respectively, and each sample was subjected to 100 tests, and the number of clogging times in 100 tests was 57 times, 2 times, 0 times, and 46 times, respectively.

It is fully proved that the preparation with the particle size of 40-200 meshes obtained in the embodiment of the invention has good adaptability of a spraying system, and the adaptability of the spraying system is poor when the particle size is too large or too small.

According to the production method of comparative example 5, samples having particle diameters of 40 mesh, 100 mesh and 200 mesh were respectively prepared, each sample was subjected to 100 tests, and the number of times of clogging in 100 tests was divided into 41 times, 29 times and 33 times, respectively.

It is found by comparing example 5 with comparative example 5 that the preparation processes of the two are the same, the material types are the same, the particle sizes are the same, only the polyethylene glycol content is different, and the spraying system is still easy to block. It is well documented that too high a level of polyethylene glycol affects the spray system compatibility of the formulation.

Statistical processing analysis by IBM sps statistics 23, chi-square test, and P as a result

Less than 0.05, which indicates that the blocking times among the groups in the study have statistical significance and have differences. The results of the pairwise comparison show that: according to the preparation method of example 5, samples of 40 meshes, 100 meshes and 200 meshes are prepared, and the plugging times of the samples are different from those of comparative example 5(40 meshes), comparative example (100 meshes) and comparative example (200 meshes), and the plugging times of example 5(270 meshes) and comparative example 5(40 meshes) are not significantly different.

Effect example 4 application of digestive tract wound gel in animal experiment

1. Test animals: the pigs for the experimental animals qualified by inspection and quarantine have 80 heads and the weight of 32-36 kg. The feeding of the residue, the sugar-containing liquid diet and the clear water was stopped 2 days before the test.

2. The test method comprises the following steps:

80 pigs for experimental animals were randomly divided into 4 groups of 20 pigs each, and Endoscopic Submucosal Dissection (ESD) of the stomach was performed. Each pig was subjected to 2 ESD surgeries and post-operatively sprayed on the wound surface using example 4, example 5, comparative example 2, comparative example 3, respectively. Each sample was individually covered for 40 wounds.

2. The test steps are as follows:

1) and a label

After the surgical site is identified, the surgical site is electrocoagulated with an electrotome for marking.

2) Sub-mucosal injection

0.9% physiological sodium chloride solution and 0.002% methylene blue solution are injected under the mucosa at multiple points outside the mark points at the edge of the operation part, the focus is lifted and separated from the muscular layer.

3) Cutting open

The mucosa is incised along the outer edge of the marked point using an electrotome.

4) Sub-mucosal loose connective tissue exfoliation

The submucosal loose connective tissue was separated using an electrotome. Over time, the fluid injected under the mucosa is gradually absorbed, and the injection under the mucosa can be repeated if necessary to maintain the sufficient lifting of the mucosa.

5) And covering of wound surface

After the operation, the visible bleeding points of the wound surface are treated by electrocoagulation hemostasis, and then the spraying systems (consisting of an air pump, an air filter, a handle and a conveying pipe) are used for respectively spraying the samples of example 4, example 5, the control sample 2 and the control sample 3 on the surface of the wound surface, and each wound surface is sprayed with 2.0g of the sample.

4. Evaluation index of test

(1) Postsurgical bleeding on the wound surface delayed (observed on days 2 and 7 after surgery);

(2) the red and swollen condition of the wound surface after the operation (observed on the 2 nd and 7 th days after the operation).

TABLE 4

Note: the different lower case letters indicate significant differences at the 5% level.

The results in table 4 show that the preparations of examples 4 and 5 provided by the present invention can reduce delayed bleeding and red swelling of the wound surface, and improve safety.

In the process of gastrointestinal endoscopic submucosa peeling surgery (ESD), the wounds are covered by using a comparative example 2 and a comparative example 3 after the surgery, and in 40 wounds of each group of samples, the 2 nd-day delayed bleeding wounds after the surgery are respectively 9 and 7, and the 7 th-day delayed bleeding wounds are respectively 2 and 1. The number of the red and swollen wound surfaces on the 2 nd day after operation is respectively 8 and 9, and the number of the red and swollen wound surfaces on the 7 th day is respectively 3 and 4.

During gastrointestinal endoscopic submucosal dissection surgery (ESD), the wounds were covered with the formulations of examples 4 and 5 after surgery, and of 40 wounds per group of samples, 0 of 2 nd and 0 of 7 th postsurgical late bleeding wounds were observed. The number of the red and swollen wound surfaces is 0 and 1 respectively on the 2 nd day after operation, and the number of the red and swollen wound surfaces is 0 on the 7 th day.

The IBM sps statistics 23 was used for statistical processing analysis, and chi-square test was used, and the result showed that P is less than 0.05, which indicates that the differences in the number of delayed hemorrhages of each group of the study at the 2 nd day after surgery have statistical significance. The results of the comparison between groups show that: the differences of example 4 and example 5 from comparative example 2 and comparative example 3 respectively exist, the postoperative 7 th day delayed bleeding wound surface has P > 0.05, and no difference exists among four groups. The wound surface red and swollen P of the wound surface on the 2 nd day after the operation is less than 0.05, and the difference exists among the four groups, so the method has statistical significance. On the 2 nd day after operation, the wound surface is red and swollen, and the difference exists between the example 4 and the comparative examples 2 and 3, the prescription of the example 4 is more favorable for eliminating the wound surface red and swollen, the difference exists between the example 5 and the comparative examples 3, and the difference does not exist between the example 5 and the comparative examples 2, and the sodium polyacrylate is more favorable for eliminating the wound surface red and swollen than the polyethylene glycol.

The wound surface red and swollen P of the 7 th day after the operation is more than 0.05, and no difference exists among the four groups, so the statistical significance is avoided.

Effect example 5 application of digestive tract wound gel in animal experiment

2. The test method comprises the following steps:

2. The test steps are as follows:

1) and a label

After the surgical site is identified, the surgical site is electrocoagulated with an electrotome for marking.

2) Sub-mucosal injection

3) Cutting open

The mucosa is incised along the outer edge of the marked point using an electrotome.

4) Sub-mucosal loose connective tissue exfoliation

5) And covering of wound surface

4. Evaluation index of test

Wound healing after surgery (4 th, 8 th week after surgery).

TABLE 5

	Postoperative wound healing rate (average)	Eight weeks wound healing rate after operation (average)
			Example 4	75％^a	100％^a
Example 5	73％^a	100％^a
			Comparative example 2	47％^b	93％^a
Comparative example 3	43％^b	94％^a

Note: the different lower case letters indicate significant differences at the 5% level.

The results in table 5 show that the preparations of examples 4 and 5 provided by the present invention can promote the healing of the wound surface.

In the process of gastrointestinal endoscopic submucosa peeling surgery (ESD), wounds are covered by using the comparative example 2 and the comparative example 3 after the surgery, and in 40 wounds of each group of samples, the healing rates of the wounds around the surgery are 47% and 43% respectively, and the healing rates of the wounds around the surgery are 93% and 94% respectively.

In the course of gastrointestinal endoscopic submucosal dissection surgery (ESD), wounds were covered with the preparations of example 4 and example 5 after surgery, and in 40 wounds in each group of samples, the healing rates of the wounds around the postoperative period were 75% and 73%, respectively, and the healing rates of the wounds around the postoperative period were 100%, respectively.

The results of statistical processing analysis using IBM sps statistics 23, using SNK test, show that: the examples are significantly different from the control samples (P < 0.05). The wound healing rate after eight weeks of operation has no significant difference among groups.

The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.

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