Gel dressing for treating haemorrhoids and preparation method thereof

Abstract

The invention discloses a gel dressing for treating haemorrhoids and a preparation method of the gel dressing. The gel dressing is prepared from the following raw materials in parts by weight: modified chitosan, multifunctional lipidosome, fructo-oligosaccharide, hyaluronic acid, carbomer, glycerol and recombinant human epidermal growth factors. Chitosan has good film-forming property and antibacterial activity, when haemorrhoids are cracked and bleeding due to long-term constipation, a wound surface is in a high-pH and high-ROS environment, the modified chitosan forms a compact protective film on the ulcerated wound surface, the multifunctional lipidosome with contracted film holes and larger particle size is blocked outside, heparin molecules are grafted on the modified chitosan, and the heparin molecules are grafted on the surface of the wound surface. Recombinant human epidermal growth factors are allowed to pass through, and wound healing is accelerated. When the ulceration part is gradually healed, the pH and ROS level return to normal, the protective film of the modified chitosan is expanded, and the multifunctional liposome is diffused and degraded through the protective film to release the pepper extract, the borneol and the menthol. Fructo-oligosaccharide is added to maintain normal flora balance in the anorectum area.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of hemorrhoid treatment drugs, and particularly relates to a gel dressing for hemorrhoid treatment and a preparation method thereof. BACKGROUND

[0002] The gel dressing is favored by the public because of its small side effects, use and remarkable curative effect. Patent No. CN107137498B discloses a traditional Chinese medicine gel for treating hemorrhoids and a preparation method thereof, which comprises the following raw materials: radix notoginseng, cortex phellodendri, spearmint, acacia, zanthoxylum, borneol, spearmint oil and glycerol. Patent No. CN103386076B discloses a mucosa care antibacterial gel composition and application thereof, which comprises the following raw materials: domiphen, propolis, sophora flavescens, curcuma zedoary, menthol and paclitaxel. The above traditional Chinese medicines can effectively treat hemorrhoids, but the effective components of the traditional Chinese medicines have complex properties.

[0003] When a patient is in constipation for a long time, hemorrhoids are aggravated. Since the dry and hard and large feces mechanically scrape and tear the swollen and fragile hemorrhoidal mucosa and perianal skin like rough sand when being discharged, bleeding, ulceration and severe pain are caused. When the traditional Chinese medicines such as borneol, zanthoxylum and menthol in the traditional Chinese medicines are directly exposed to the wound surface in the case of hemorrhoid ulceration and bleeding, the wound surface is stimulated, burning and pain are caused, and even the healing of the wound surface is interfered. SUMMARY

[0004] (1) Technical problem to be solved

[0005] The purpose of the present application is to provide a gel dressing for hemorrhoid treatment and a preparation method thereof, so as to solve the problem that borneol, menthol and zanthoxylum in the gel dressing stimulate the open hemorrhoid ulcer wound and interfere with the healing of the crack.

[0006] (2) Technical scheme

[0007] To achieve the above purpose, on one hand, the present application provides a gel dressing for hemorrhoid treatment, which comprises the following raw materials in parts by weight: modified chitosan 1-2 parts, multifunctional liposome 1.5-3 parts, fructooligosaccharide 2-4 parts, hyaluronic acid 0.3-0.6 parts, carbomer 0.8-1.2 parts and glycerol 4-6 parts.

[0008] Further, the raw materials further comprise recombinant human epidermal growth factor, which accounts for 0.0005-0.001% of the total mass of the raw materials.

[0009] Further, the preparation method of the modified chitosan comprises the following steps:

[0010] S11. Stirring polyacrylic acid is dissolved in MES buffer solution, ice bath cooling is performed, EDC.HCl and NHS are added, activation reaction is performed, and an activated polyacrylic acid solution is obtained.

[0011] S12. Dissolve 4-carboxyphenylboronic acid in anhydrous DMSO, slowly drop into the activated polyacrylic acid solution, react at room temperature, dialysis purification of the obtained reaction solution, freeze-drying to obtain the first compound;

[0012] S13. Stir to dissolve chitosan in acetic acid aqueous solution to obtain a chitosan solution, dissolve phenylboronic acid esterified polyacrylic acid in deionized water, slowly drop into the chitosan solution, add NaOH solution to adjust the pH to 5.0, dialysis purification of the obtained reaction solution, freeze-drying to obtain the second compound;

[0013] S14. Dissolve heparin sodium in MES buffer solution, cool in ice bath, add EDC·HCl and NHS, activate the reaction to obtain an activated heparin solution;

[0014] S15. Disperse the second compound in MES buffer solution, slowly drop the activated heparin solution, react at room temperature, dialysis purification of the obtained reaction solution, freeze-drying to obtain the modified chitosan.

[0015] Further, the preparation method of the multifunctional liposome comprises the following steps:

[0016] S21. Dissolve PLGA, Zanthoxylum bungeanum extract, borneol and menthol in dichloromethane, vortex to obtain an oil phase;

[0017] S22. Slowly drop the oil phase into 2% PVA aqueous solution, homogenously disperse to obtain a primary emulsion, pour the primary emulsion into 0.5% PVA solution, probe ultrasonic to obtain a re-emulsion, rotary evaporation under magnetic stirring, centrifugal collection of the precipitate of the obtained suspension, wash with ultrapure water, disperse the obtained precipitate in PBS buffer solution to obtain the third compound;

[0018] S23. Dissolve phospholipid, cholesterol and DSPE-PEG2000 in chloroform, rotary evaporation to obtain a lipid film, vacuum drying, add PBS buffer solution, rotary hydration, extrude the suspension through a polycarbonate membrane to obtain the fourth compound;

[0019] S24. Mix the third compound and the fourth compound, probe ultrasonic, dialysis purification of the obtained mixture, freeze-drying to obtain the multifunctional liposome.

[0020] Further, the suspension is sequentially extruded through polycarbonate membranes with diameters of 800 nm, 400 nm and 200 nm, and the particle size of the multifunctional liposome is 200-300 nm.

[0021] On the other hand, based on the same inventive concept, the application further provides a preparation method of a gel dressing for hemorrhoid treatment, which is applied to the gel dressing for hemorrhoid treatment and comprises the following steps:

[0022] S1. Dissolve disodium ethylenediaminetetraacetate in deionized water, slowly add carbomer under magnetic stirring, add glycerol and hyaluronic acid in turn, continue stirring until hydration begins, stand overnight to obtain a first mixture;

[0023] S2. Dissolve recombinant human epidermal growth factor in deionized water to obtain a recombinant human epidermal growth factor solution, dissolve modified chitosan in deionized water, slowly add the recombinant human epidermal growth factor solution to obtain a second mixture;

[0024] S3. Dissolve multifunctional liposomes in deionized water, add oligofructose, vortex to obtain a third mixture;

[0025] S4. Add the second mixture and the third mixture to the first mixture in turn, continue stirring, slowly add triethanolamine solution, stir uniformly with a homogenizer, vacuum degassing, irradiation sterilization to obtain a gel dressing.

[0026] Chitosan itself has good film-forming property and antibacterial property. When hemorrhoids crack and bleed due to long-term constipation, the wound is in a high-pH and high-ROS environment. The benzene borate groups in the modified chitosan are oxidized and broken under the high-ROS environment, changing the molecular conformation. At the same time, the ionization degree of the polyacrylic acid chain of the modified chitosan increases under the high-pH environment, and the chain segment is stretched. At this time, the “pH+ROS” dual response of the modified chitosan makes it quickly form a dense protective film on the broken wound, the membrane pores shrink, allowing smaller particles to pass through. Since the pepper extract, borneol and menthol are loaded with PLGA and wrapped with liposomes, the large molecular weight of PLGA increases the particle size of the multifunctional liposomes, which are blocked outside the protective film. The liposome wrapping prevents the pepper extract, borneol and menthol from being released too early. In addition, in order to avoid affecting the passage of the large molecule recombinant human epidermal growth factor through the protective film, the heparin molecule is grafted on the modified chitosan to specifically capture the recombinant human epidermal growth factor, which passes through the protective film to reach the wound, accelerating wound healing. When the broken part gradually heals, the pH and ROS levels return to normal, the protective film of the modified chitosan expands, and the multifunctional liposomes pass through the protective film smoothly, contact the healed hemorrhoids, and in the tissue fluid environment, the multifunctional liposomes diffuse and degrade, releasing the pepper extract, borneol and menthol for the treatment of hemorrhoids.

[0027] Since the bacteriostatic effect of the modified chitosan and the pepper extract can destroy the normal flora balance of the anorectal area, leading to ecological imbalance, the addition of fructo-oligosaccharides in the dressing promotes the growth of beneficial bacteria such as bifidobacteria and lactobacilli, and helps to regulate the normal flora of the anorectal area. In addition, in order to avoid the agglomeration of the modified chitosan and the multifunctional liposome, hyaluronic acid is added to help diffusion, and the hyaluronic acid can also lock a large amount of water, creating a moist, closed and low-oxygen environment for the wound, accelerating the migration of epithelial cells and wound healing.

[0028] In summary, due to the adoption of the technical solutions described above, the beneficial effects of the present application are:

[0029] 1. The addition of modified chitosan and multifunctional liposomes can prevent the formation of a protective film that contains pepper extract, borneol and menthol, which can prevent the occurrence of stinging pain. During the wound healing period, the modified chitosan pores expand, and the multifunctional liposomes pass through, releasing the pepper extract, borneol and menthol, which can treat hemorrhoids.

[0030] 2. The grafting of heparin on the surface of the modified chitosan allows the protective film to also penetrate macromolecular protein growth factors during the hemorrhoid rupture period, promoting wound healing.

[0031] 3. The addition of fructo-oligosaccharides avoids the bacteriostatic effect of the modified chitosan and the pepper extract, which can destroy the normal flora balance of the anorectal area, and the addition of hyaluronic acid can create a moist healing environment. BRIEF DESCRIPTION OF DRAWINGS

[0032] Figure 1 is a preparation flowchart of the gel dressing of Example 1. DETAILED DESCRIPTION

[0033] The technical solutions in the embodiments of the present application will be described clearly and completely below in combination with the drawings in the embodiments of the present application. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of protection of the present application.

[0034] Example 1: The present embodiment discloses a gel dressing for hemorrhoid treatment, which comprises the following raw materials in parts by weight: modified chitosan 1 part, multifunctional liposome 1.5 parts, fructo-oligosaccharide 2 parts, hyaluronic acid 0.3 parts, carbomer 0.8 parts, glycerol 4 parts.

[0035] The raw materials also include recombinant human epidermal growth factor, which accounts for 0.0005% of the total mass of the raw materials.

[0036] The preparation method of the modified chitosan comprises the following steps:

[0037] S11. Stirring polyacrylic acid is dissolved in MES buffer solution, ice bath cooling, adding EDC·HCl and NHS, activation reaction, to obtain the activated polyacrylic acid solution;

[0038] S12. 4-carboxyphenylboronic acid is dissolved in anhydrous DMSO, slowly added to the activated polyacrylic acid solution, room temperature reaction, the reaction solution is purified by dialysis, freeze-drying to obtain the first compound;

[0039] S13. Chitosan is dissolved in acetic acid aqueous solution to obtain a chitosan solution, and the phenylboronic acid esterified polyacrylic acid is dissolved in deionized water, slowly added to the chitosan solution, and NaOH solution is added to adjust the pH to 5.0, the reaction solution is purified by dialysis, freeze-drying to obtain the second compound;

[0040] S14. Sodium heparin is dissolved in MES buffer solution, ice bath cooling, adding EDC·HCl and NHS, activation reaction, to obtain the activated heparin solution;

[0041] S15. The second compound is dispersed in MES buffer solution, and the activated heparin solution is slowly added, and the reaction is carried out at room temperature, the reaction solution is purified by dialysis, freeze-drying to obtain the modified chitosan.

[0042] The preparation method of the multifunctional liposome comprises the following steps:

[0043] S21. PLGA, Zanthoxylum bungeanum extract, borneol and menthol are dissolved in dichloromethane, and vortexed to obtain an oil phase;

[0044] S22. The oil phase is slowly added to a 2% PVA aqueous solution, homogenously dispersed to obtain a primary emulsion, the primary emulsion is poured into a 0.5% PVA solution, and a probe ultrasonic is used to obtain a re-emulsion, which is rotary evaporated under magnetic stirring, the obtained suspension is centrifuged to collect the precipitate, which is washed with ultrapure water, and the obtained precipitate is dispersed in PBS buffer solution to obtain a third compound;

[0045] S23. Phospholipid, cholesterol and DSPE-PEG2000 are dissolved in chloroform, rotary evaporated to obtain a lipid film, vacuum dried, added with PBS buffer solution, and rotary hydrated to obtain a suspension, which is extruded through a polycarbonate membrane to obtain a fourth compound;

[0046] S24. The third compound and the fourth compound are mixed, and a probe ultrasonic is used to obtain a mixed solution, which is purified by dialysis, freeze-dried to obtain a multifunctional liposome.

[0047] The suspension is sequentially extruded through polycarbonate membranes with diameters of 800 nm, 400 nm and 200 nm, and the particle size of the multifunctional liposome is 200 nm.

[0048] It should be noted that the pore size of the protective film formed by the modified chitosan is usually between 10-50 nm after shrinkage, allowing small molecule compounds to pass through, and large molecule compounds are intercepted, so the particle size of the multifunctional liposome needs to be much larger than 50 nm. By using high molecular weight PLGA and controlling the concentration of PLGA in the organic phase, multifunctional liposomes of 200-300 nm are obtained, preventing the multifunctional liposomes from passing through the shrunk pore membrane due to their small particle size, releasing menthol, menthol and pepper extract, stimulating the wound, and affecting healing.

[0049] The preparation method of the gel dressing for hemorrhoid treatment comprises the following steps:

[0050] S1. Dissolve disodium ethylenediaminetetraacetate in deionized water, slowly add carbomer under magnetic stirring, and sequentially add glycerol and hyaluronic acid. Continue stirring until hydration begins. Let stand overnight to obtain a first mixture;

[0051] S2. Dissolve recombinant human epidermal growth factor in deionized water to obtain a recombinant human epidermal growth factor solution. Dissolve modified chitosan in deionized water, and slowly add the recombinant human epidermal growth factor solution to obtain a second mixture;

[0052] S3. Dissolve multifunctional liposomes in deionized water, add oligofructose, and vortex to obtain a third mixture;

[0053] S4. Sequentially add the second mixture and the third mixture to the first mixture, continue stirring, slowly add triethanolamine solution, and stir uniformly with a homogenizer. Vacuum degassing, irradiation sterilization, to obtain a gel dressing.

[0054] It should be noted that, as Figure 1 The preparation of the gel dressing is shown in the schematic diagram. The gel base matrix, pretreated modified chitosan and multifunctional liposomes need to be prepared first, and then all the materials are mixed, in order to avoid uneven mixing of carbomer after gelation, and to protect the activity of active ingredients. In the steps containing recombinant human epidermal growth factor and multifunctional liposomes, gentle and low-speed stirring is required to avoid damaging the structure.

[0055] Example 2: This example is based on Example 1, and differs from Example 1 in that it includes the following weight fractions of raw materials: modified chitosan 1.5 parts, multifunctional liposomes 2 parts, oligofructose 3 parts, hyaluronic acid 0.45 parts, carbomer 1 part, glycerol 5 parts.

[0056] The other components and preparation methods are the same as in Example 1.

[0057] Example 3: This example is based on Example 1, except that in this example the raw materials include the following components in parts by weight: modified chitosan 2 parts, multifunctional liposome 3 parts, fructooligosaccharide 4 parts, hyaluronic acid 0.6 parts, carbomer 1.2 parts, and glycerol 6 parts.

[0058] The other components and the preparation method are the same as in Example 1.

[0059] Example 4: This example is based on Example 1, except that in this example the raw materials further include recombinant human epidermal growth factor, which accounts for 0.001% of the total mass of the raw materials.

[0060] The other components and the preparation method are the same as in Example 1.

[0061] Example 5: This example is based on Example 1, except that in this example the particle size of the multifunctional liposome is 300 nm.

[0062] The other components and the preparation method are the same as in Example 1.

[0063] Comparative Example 1: This comparative example is based on Example 1, except that in this comparative example the particle size of the multifunctional liposome is 50 nm.

[0064] The other components and the preparation method are the same as in Example 1.

[0065] Comparative Example 2: This comparative example is based on Example 1, except that in this comparative example the modified chitosan does not have grafted phenylboronic acid ester groups.

[0066] The preparation method of the modified chitosan includes the following steps:

[0067] S11. Polyacrylic acid is stirred and dissolved in MES buffer, cooled in an ice bath, EDC-HCl and NHS are added, and an activation reaction is performed to obtain an activated polyacrylic acid solution;

[0068] S12. Chitosan is stirred and dissolved in an aqueous acetic acid solution to obtain a chitosan solution. The activated polyacrylic acid solution is slowly added dropwise to the chitosan solution, and a NaOH solution is added to adjust the pH to 5.0. The resulting reaction solution is purified by dialysis, freeze-dried, and the second compound is obtained.

[0069] S13. Sodium heparin is dissolved in MES buffer, cooled in an ice bath, EDC-HCl and NHS are added, and an activation reaction is performed to obtain an activated heparin solution;

[0070] S14. The second compound is dispersed in MES buffer, and the activated heparin solution is slowly added dropwise. The reaction is carried out at room temperature. The resulting reaction solution is purified by dialysis, freeze-dried, and the modified chitosan is obtained.

[0071] Other components and preparation methods are the same as those in Example 1.

[0072] Comparative Example 3: The comparative example is based on Example 1, and different from Example 1 is that the modified chitosan in the comparative example is not grafted with polyacrylic acid chains.

[0073] The preparation method of the modified chitosan comprises the following steps:

[0074] S11. Dissolve 4-carboxyphenylboronic acid in anhydrous DMSO to obtain a 4-carboxyphenylboronic acid solution;

[0075] S12. Stir and dissolve chitosan in an acetic acid aqueous solution to obtain a chitosan solution, slowly drop the 4-carboxyphenylboronic acid solution into the chitosan solution, and add a NaOH solution to adjust the pH to 5.0, then purify the obtained reaction liquid by dialysis, and freeze-dry to obtain the second compound;

[0076] S13. Dissolve sodium heparin in a MES buffer solution, cool in an ice bath, add EDC·HCl and NHS, activate the reaction, and obtain an activated heparin solution;

[0077] S14. Disperse the second compound in the MES buffer solution, slowly drop the activated heparin solution, and react at room temperature, then purify the obtained reaction liquid by dialysis, and freeze-dry to obtain the modified chitosan.

[0078] Other components and preparation methods are the same as those in Example 1.

[0079] Comparative Example 4: The comparative example is based on Example 1, and different from Example 1 is that the modified chitosan in the comparative example is not grafted with heparin.

[0080] The preparation method of the modified chitosan comprises the following steps:

[0081] S11. Stir and dissolve polyacrylic acid in a MES buffer solution, cool in an ice bath, add EDC·HCl and NHS, activate the reaction, and obtain an activated polyacrylic acid solution;

[0082] S12. Dissolve 4-carboxyphenylboronic acid in anhydrous DMSO, slowly drop into the activated polyacrylic acid solution, react at room temperature, purify the obtained reaction liquid by dialysis, and freeze-dry to obtain the first compound;

[0083] S13. Stir and dissolve chitosan in an acetic acid aqueous solution to obtain a chitosan solution, dissolve the phenylboronic acid esterified polyacrylic acid in deionized water, slowly drop into the chitosan solution, add a NaOH solution to adjust the pH to 5.0, then purify the obtained reaction liquid by dialysis, and freeze-dry to obtain the modified chitosan.

[0084] Other components and preparation methods are the same as those in Example 1.

[0085] Comparative Example 5: This comparative example is based on Example 1, except that the comparative example does not use PLGA for drug loading.

[0086] The preparation method of the multifunctional liposome comprises the following steps:

[0087] S21. Dissolve the phospholipid, cholesterol, DSPE-PEG2000, Zanthoxylum extract, borneol, menthol in chloroform, rotary evaporation, vacuum drying, add PBS buffer, rotary hydration, the obtained suspension is extruded through a polycarbonate membrane, dialysis purification, and the multifunctional liposome is obtained;

[0088] The other components and preparation methods are the same as in Example 1.

[0089] Comparative Example 6: This comparative example is based on Example 1, except that the comparative example does not use the lipid shell of PLGA for inclusion.

[0090] The preparation method of the multifunctional liposome comprises the following steps:

[0091] S21. Dissolve the PLGA, Zanthoxylum extract, borneol, menthol in dichloromethane, vortex, and obtain an oil phase;

[0092] S22. Slowly add the oil phase to a 2% PVA aqueous solution, homogenously disperse, obtain a primary emulsion, pour the primary emulsion into a 0.5% PVA solution, probe sonicate, obtain a double emulsion, rotary evaporation under magnetic stirring, centrifuge the obtained suspension to collect the precipitate, wash with ultrapure water, freeze-dry, and obtain the multifunctional liposome.

[0093] The other components and preparation methods are the same as in Example 1.

[0094] Comparative Example 7: This comparative example is based on Example 1, except that the comparative example does not add modified chitosan.

[0095] The other components and preparation methods are the same as in Example 1.

[0096] Comparative Example 8: This comparative example is based on Example 1, except that the comparative example does not add the multifunctional liposome.

[0097] The other components and preparation methods are the same as in Example 1.

[0098] Comparative Example 9: This comparative example is based on Example 1, except that the comparative example does not add fructooligosaccharides and hyaluronic acid.

[0099] The other components and preparation methods are the same as in Example 1.

[0100] Test verification:

[0101] 1. In vitro experiment

[0102] Using Franz diffusion cell, the gel dressing prepared by each example and comparative example is placed in the donor cell, and the broken period medium (pH = 7.4-8.0, appropriate amount of H2O2) and the healing period medium (pH = 6.0-7.0) are used in the receptor cell, respectively, and samples are taken at 0, 4, 8, 12, 24 hours, and the concentrations of zanthoxylum bungeanum extract, borneol and menthol in the broken period and healing period are detected by HPLC, and the 24-hour drug cumulative release rate is calculated, and the concentration of recombinant human epidermal growth factor in the broken period is detected by HPLC, and the 24-hour recombinant human epidermal growth factor cumulative release rate is calculated.

[0103] Table 1. Drug cumulative release rate and recombinant human epidermal growth factor cumulative release rate of each test group

[0104]

[0105] As shown in Table 1, the drug cumulative release rate in the broken period and healing period and the cumulative release rate of recombinant human epidermal growth factor in the broken period of each test group are shown. As can be seen from the comparison of Example 1 and Comparative Example 1, when the particle size of the multifunctional liposome is small, the protective film formed by the modified chitosan cannot intercept the multifunctional liposome to release the drug. As can be seen from the comparison of Example 1 and Comparative Examples 2-3 and Comparative Examples 5-6, the cumulative release amount of the drug in the broken period of Example 1 is lower, and in the healing period, it is higher, indicating that the protective film formed by the modified chitosan has a "pH+ROS" dual response. Under the dual action of phenylboronic ester groups and polyacrylic acid chains, the membrane pores shrink, and the large molecular weight PLGA is preloaded with drugs, and the liposome protects the PLGA, preventing the multifunctional liposome from passing through the protective film and releasing the drug in advance. In the healing period of the wound, the protective film expands, and the multifunctional liposome passes through the protective film smoothly, contacts the healing hemorrhoids, and in the tissue fluid environment, the multifunctional liposome diffuses and degrades, releasing zanthoxylum bungeanum extract, borneol and menthol. As can be seen from the comparison of Example 1 and Comparative Example 4, the modified chitosan does not allow the passage of large molecular weight multifunctional liposomes, but by grafting heparin, it specifically binds with recombinant human epidermal growth factor, allowing large molecular weight recombinant human epidermal growth factor to pass through the protective film in the broken period.

[0106] 2. Animal model experiment

[0107] Take 140 experimental rats, 10 in each test group, male, body weight 180-220g, adaptive feeding for 5 days, fasting for 12 hours before the test, intraperitoneal anesthesia with sodium pentobarbital 40mg / kg, gently insert the microsyringe into the anus, slowly inject 20% acetic acid solution 10-20μL, 24 hours after the operation, observe the perianal obvious redness, congestion, even erosion or bleeding, which is the success of modeling. The prepared gel dressing is gently applied to the perianal area of the rats, 1-2 times a day for 7 days, and the appearance of the perianal area is observed. After the rats are dissected, 3cm of intestinal segment is taken from the anus, and the ratio of the area of the ulcerated mucosa to the total mucosa is observed. The average value of the ratio of each group of 10 rats is calculated.

[0108] Table 2. Appearance of perianal area after drug administration in each test group and average ulcer area ratio in each group

[0109]

[0110] As shown in Table 2, the appearance of the perianal area of the rats in each test group after drug administration and the average ulcer area ratio in each group are shown. Comparison of Example 1 and Comparative Example 7 shows that the results of not containing modified chitosan are that the perianal ulceration of the rats in Comparative Example 7 is more serious, indicating that the protective film formed by the modified chitosan allows the recombinant human epidermal growth factor to pass through during the ulceration period, promoting wound healing, and during the healing period, the multifunctional liposome releases the pepper extract, borneol and menthol through the protective film, promoting the recovery of hemorrhoids. Comparison of Example 1 and Comparative Example 8 shows that without multifunctional liposomes, the pepper extract, borneol and menthol can indeed promote the recovery of hemorrhoids.

[0111] The above only describes the preferred embodiments of the present application and does not limit the protection scope of the present application. Any modifications, equivalent replacements and improvements made by those skilled in the art within the spirit and principles of the present application shall be included in the protection scope of the present application.

Claims

1. A gel dressing for hemorrhoid treatment, characterized by, The raw materials include the following components in parts by weight: 1-2 parts of modified chitosan, 1.5-3 parts of multifunctional liposome, 2-4 parts of fructooligosaccharide, 0.3-0.6 parts of hyaluronic acid, 0.8-1.2 parts of carbomer, and 4-6 parts of glycerol.

2. A gel dressing for hemorrhoid treatment according to claim 1, characterized in that, The raw materials further include recombinant human epidermal growth factor, accounting for 0.0005-0.001% of the total mass of the raw materials.

3. The gel dressing for hemorrhoid treatment according to claim 1, wherein The preparation method of the modified chitosan comprises the following steps: S11. stirring and dissolving polyacrylic acid in MES buffer solution, ice bath cooling, adding EDC·HCl and NHS, activation reaction, obtaining an activated polyacrylic acid solution; S12. dissolving 4-carboxyphenylboronic acid in anhydrous DMSO, slowly adding to the activated polyacrylic acid solution, room temperature reaction, dialysis purification of the obtained reaction solution, freeze-drying, obtaining a first compound; S13. stirring and dissolving chitosan in acetic acid aqueous solution, obtaining a chitosan solution, dissolving benzene boronic acid esterified polyacrylic acid in deionized water, slowly adding to the chitosan solution, adding NaOH solution to adjust pH to 5.0, dialysis purification of the obtained reaction solution, freeze-drying, obtaining a second compound; S14. dissolving heparin sodium in MES buffer solution, ice bath cooling, adding EDC·HCl and NHS, activation reaction, obtaining an activated heparin solution; S15. dispersing the second compound in MES buffer solution, slowly adding the activated heparin solution, reaction at room temperature, dialysis purification of the obtained reaction solution, freeze-drying, obtaining modified chitosan.

4. The gel dressing for hemorrhoid treatment according to claim 1, wherein The preparation method of the multifunctional liposome comprises the following steps: S21. dissolving PLGA, Zanthoxylum bungeanum extract, borneol and menthol in dichloromethane, vortexing and oscillating, obtaining an oil phase; S22. slowly adding the oil phase to 2% PVA aqueous solution, homogenously dispersing, obtaining a primary emulsion, pouring the primary emulsion into 0.5% PVA solution, probe ultrasonic, obtaining a complex emulsion, rotary evaporation under magnetic stirring, centrifugally collecting the precipitate of the obtained suspension, washing with ultrapure water, dispersing the obtained precipitate in PBS buffer solution, obtaining a third compound; S23. dissolving phospholipid, cholesterol and DSPE-PEG2000 in chloroform, rotary evaporation, vacuum drying of the obtained lipid film, adding PBS buffer solution, rotary hydration, extruding the obtained suspension through a polycarbonate membrane, obtaining a fourth compound; S24. mixing the third compound and the fourth compound, probe ultrasonic, dialysis purification of the obtained mixed solution, freeze-drying, obtaining a multifunctional liposome.

5. A gel dressing for hemorrhoid treatment according to claim 4, characterized in that, The suspension is sequentially extruded through polycarbonate membranes with pore sizes of 800 nm, 400 nm and 200 nm, and the particle size of the multifunctional liposome is 200-300 nm.

6. A method for preparing a gel dressing for hemorrhoid treatment, which is used for preparing a gel dressing for hemorrhoid treatment according to any one of claims 1 to 5, characterized in that, The method comprises the following steps: S1. dissolving disodium ethylenediaminetetraacetate in deionized water, slowly adding carbomer under magnetic stirring, sequentially adding glycerol and hyaluronic acid, continuously stirring until hydration begins, standing overnight, obtaining a first mixture; S2. dissolving recombinant human epidermal growth factor in deionized water, obtaining a recombinant human epidermal growth factor solution, dissolving modified chitosan in deionized water, slowly adding the recombinant human epidermal growth factor solution, obtaining a second mixture; S3. Dissolve the multifunctional liposome in deionized water, add oligofructose, vortex to obtain a third mixture; S4. Add the second mixture and the third mixture to the first mixture in sequence, continuously stir, slowly add the triethanolamine solution, stir uniformly with a homogenizer, vacuum degassing, irradiation sterilization, to obtain a gel dressing.

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