A wound repair medical dressing and a method of making the same

Abstract

The application discloses a kind of wound repair medical dressings and preparation method thereof, it is related to medical dressing technical field.The wound repair medical dressing includes the following weight parts of raw materials: bioactive glass 30-40 parts, sodium alginate 25-35 parts, antibacterial agent 10-20 parts, anti-inflammatory agent 10-15 parts, deionized water 400-600 parts.The quaternary ammonium salt compound is generated by the reaction of N-hexadecyl diethanolamine and 1-chlorododecane, the antibacterial agent is generated by the reaction of quaternary ammonium salt compound and 3-[[4-(pyridine-2-yl sulfamoyl) phenyl] diazenyl] benzoic acid.The wound repair medical dressing prepared by the application has excellent antibacterial performance and anti-inflammatory performance.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of medical dressings, in particular to a wound repair medical dressing and a preparation method thereof. BACKGROUND

[0002] Wound repair, especially the repair of chronic wounds caused by trauma, surgery or diabetes, is an important research direction in current clinical treatment. Existing wound repair dressings mainly rely on biocompatible materials (such as sodium alginate, collagen, etc.) to cover, protect and promote healing of the wound. However, although traditional wound dressings can provide physical protection and reduce the risk of infection, they often lack sufficient antibacterial and anti-inflammatory effects, and cannot effectively deal with bacterial infection and inflammatory response that may occur during the wound healing process, which will adversely affect the healing speed and effect of the wound. In order to improve the efficiency and effect of wound repair, researchers have explored various medical dressings with antibacterial, anti-inflammatory and healing-promoting functions in recent years. For example, natural materials such as bioactive glass and sodium alginate are widely used in wound dressings due to their good biocompatibility and healing-promoting properties. Bioactive glass can regulate the local environment by releasing negative ions to improve the wound healing speed. Sodium alginate can provide effective protection for the wound and promote cell migration and repair due to its natural gel properties and biodegradability. Although these materials have certain effects on promoting wound healing, the existing wound dressings still have problems such as insufficient antibacterial properties and insignificant anti-inflammatory effects. Therefore, it is crucial to develop a new type of wound repair dressing with strong antibacterial and anti-inflammatory effects.

[0003] Chinese invention patent with publication number CN105963771A discloses a medical dressing containing bioactive ingredients and a preparation method thereof. The medical dressing containing bioactive ingredients is prepared from the following ingredients in parts by weight: bioactive glass powder 10-40 parts, liquid paraffin 30-70 parts, medical vaseline 40-80 parts, sodium hyaluronate gel 5-15 parts, acidic amino acid 10-20 parts, mint 0.5-5 parts, and camphor 0.5-5 parts. The medical dressing containing bioactive ingredients provided by the invention does not stimulate the wound to produce pain when used, has significant curative effect on the healing of chronic large-area wounds such as burns, bedsores, diabetic foot, contusions and various skin surface ulcers, and can provide a good microenvironment for the healing of the wound, promote the healing of the wound and inhibit the formation of scars. However, the antibacterial and anti-inflammatory effects of the dressing are still insufficient. SUMMARY

[0004] In view of the deficiencies of the prior art, the present application aims to provide a wound repair medical dressing and a preparation method thereof.

[0005] To achieve the above object, the present application is realized by the following technical solutions.

[0006] A wound repair medical dressing, comprising the following raw materials by weight:

[0007] Bioactive glass 30-40 parts, sodium alginate 25-35 parts, antibacterial agent 10-20 parts, anti-inflammatory agent 10-15 parts, deionized water 400-600 parts;

[0008] The antibacterial agent is prepared by the following method:

[0009] S1: N-hexadecyl diethanolamine reacts with 1-chlorododecane to form a quaternary ammonium salt compound, and the reaction equation is as follows:

[0010]

[0011] S2: The quaternary ammonium salt compound reacts with 3-[[4-(pyridin-2-ylsulfamoyl) phenyl] diazenyl] benzoic acid to form an antibacterial agent, and the reaction equation is as follows:

[0012]

[0013] The anti-inflammatory agent is prepared by the following method:

[0014] N1: Curcumin reacts with phenyl glycidyl ether to form intermediate 1, and the reaction equation is as follows:

[0015]

[0016] N2: Intermediate 1 reacts with 4-aminomethyl phenylacetic acid to form intermediate 2, and the reaction equation is as follows:

[0017]

[0018] N3: Intermediate 2 reacts with 4-((bis((1H-indol-5-yl) methyl) amino) methyl) benzaldehyde to form an anti-inflammatory agent, and the reaction equation is as follows:

[0019]

[0020] In step S1, the molar ratio of N-hexadecyl diethanolamine to 1-chlorododecane is 1:(1.05-1.1).

[0021] In step S2, the molar ratio of the quaternary ammonium salt compound to 3-[[4-(pyridin-2-ylsulfamoyl) phenyl] diazenyl] benzoic acid is 1:(2.1-2.2).

[0022] The reaction time of step S1 is 23-24h, and the reaction temperature is 70-75℃.

[0023] The reaction time of step S2 is 17-18h, and the reaction temperature is 25-30℃.

[0024] The reaction solvent of step S1 is anhydrous ethanol; and the reaction solvent of step S2 is anhydrous DMF.

[0025] In step N1, the feeding molar ratio of curcumin to phenyl glycidyl ether is 1:2.05.

[0026] In step N2, the feeding molar ratio of intermediate 1 to 4-aminomethyl phenylacetic acid is 1:2.1.

[0027] In step N3, the feeding molar ratio of intermediate 2 to 4-((bis((1H-indol-5-yl)methyl)amino)methyl)benzaldehyde is 1:2.05.

[0028] A preparation method of a wound repair medical dressing, comprising the following steps:

[0029] (1) Take by weight parts: bioactive glass 30-40 parts, sodium alginate 25-35 parts, antibacterial agent 10-20 parts, anti-inflammatory agent 10-15 parts, deionized water 400-600 parts;

[0030] (2) Stir and mix the deionized water and sodium alginate uniformly, add the bioactive glass, antibacterial agent and anti-inflammatory agent, homogenize, and freeze-dry to obtain the wound repair medical dressing.

[0031] Due to the above technical scheme, the beneficial effects of the present application include:

[0032] The wound repair medical dressing prepared by the present application has excellent antibacterial and anti-inflammatory properties, wherein the added antibacterial agent improves the antibacterial property of the wound repair medical dressing through the synergistic effect of quaternary ammonium salt, long-chain alkyl, sulfonamide group and pyridine structure; and the added anti-inflammatory agent improves the anti-inflammatory property of the wound repair medical dressing through the combined effect of curcumin anti-inflammatory core, pH-sensitive Schiff base and indole ring structure. DETAILED DESCRIPTION

[0033] The present application will be further described below in conjunction with examples, but the present application is not limited to these examples.

[0034] Example 1 Preparation of antibacterial agent:

[0035] S1: 250 ml of anhydrous ethanol, 0.1 mol of N-hexadecyl diethanolamine, 0.105 mol of 1-chlorododecane were stirred and mixed uniformly, heated to 70°C, reacted for 24 h, cooled to room temperature, distilled at 40°C under reduced pressure for 3 h, recrystallized with ethyl acetate / anhydrous ethanol (ethyl acetate / anhydrous ethanol V:V = 8:2) (3×200 ml), and dried at 60°C under vacuum for 12 h to obtain a quaternary ammonium salt compound; the nuclear magnetic resonance hydrogen spectrum data are as follows: 1 H NMR (400 MHz, Chloroform- d ) δ 3.93 (t, J = 5.0 Hz, 2H), 3.76(d, J = 5.0 Hz, 4H), 3.47 (d, J = 11.9 Hz, 8H), 1.83 (s, 4H), 1.42 (s, 4H),1.34-1.25 (m, 40H), 0.90 (s, 6H);

[0036] S2: 500 ml of anhydrous DMF, 0.1 mol of the quaternary ammonium salt compound, 0.21 mol of 3-[[4-(pyridin-2-ylsulfamoyl)phenyl]diazenyl]benzoic acid were stirred and mixed uniformly under nitrogen protection, 0.22 mol of dicyclohexyl carbodiimide and 0.04 mol of 4-dimethylaminopyridine were added, stirred for 15 min, reacted at 25°C for 18 h, filtered, 1000 ml of cold ether was added to the filtrate, and the precipitate was stirred and separated, filtered, and the filter cake was washed with a cold methanol / water mixed solution (methanol / water V:V = 2:1) (3×300 ml), recrystallized with 500 ml of ethyl acetate / methanol (ethyl acetate / methanol V:V = 4:1), and dried at 65°C under vacuum for 12 h to obtain an antibacterial agent; the nuclear magnetic resonance hydrogen spectrum data are as follows: 1 H NMR (400 MHz, Chloroform- d) δ 10.65 (s, 2H), 8.23 (dd, J = 5.0,1.3 Hz, 2H), 8.10 (t, J = 2.0 Hz, 2H), 8.02 (dt, J = 7.5, 2.0 Hz, 2H), 7.98-7.90 (m, 4H), 7.74-7.58 (m, 8H), 7.53 (t, J = 7.5 Hz, 2H), 7.29 (dd, J = 8.0,1.0 Hz, 2H), 7.08 (ddd, J = 8.0, 5.0, 1.0 Hz, 2H), 4.59 (s, 4H), 3.83 (s,4H), 3.47 (s, 4H), 1.79 (s, 4H), 1.42 (s, 4H), 1.36-1.25 (m, 40H), 0.90 (s,6H).

[0037] Example 2 Preparation of the antibacterial agent:

[0038] S1: 250 ml of anhydrous ethanol, 0.1 mol of N-hexadecyl diethanolamine, 0.108 mol of 1-chlorododecane were stirred and mixed uniformly, heated to 70°C, reacted for 24 h, cooled to room temperature, distilled at 40°C under reduced pressure for 3 h, recrystallized with ethyl acetate / anhydrous ethanol (ethyl acetate / anhydrous ethanol V:V = 8:2) (3x200 ml), and dried at 60°C under vacuum for 12 h to obtain a quaternary ammonium salt compound;

[0039] S2: 500 ml of anhydrous DMF, 0.1 mol of the quaternary ammonium salt compound, 0.215 mol of 3-[[4-(pyridin-2-ylsulfamoyl)phenyl]diazenyl]benzoic acid were stirred and mixed uniformly under nitrogen protection, 0.22 mol of dicyclohexyl carbodiimide and 0.04 mol of 4-dimethylaminopyridine were added, stirred for 15 min, reacted at 25°C for 18 h, filtered, 1000 ml of cold ether was added to the filtrate, and the precipitate was stirred and separated, filtered, and the filter cake was washed with a cold methanol / water mixed solution (methanol / water V:V = 2:1) (3x300 ml), recrystallized with 500 ml of ethyl acetate / methanol (ethyl acetate / methanol V:V = 4:1), and dried at 65°C under vacuum for 12 h to obtain the antibacterial agent.

[0040] Example 3 Preparation of the antibacterial agent:

[0041] S1: 250 ml of anhydrous ethanol, 0.1 mol of N-hexadecyl diethanolamine, and 0.11 mol of 1-chlorododecane were stirred and mixed. The mixture was heated to 75 °C and reacted for 23 h. After cooling to room temperature, the mixture was distilled under reduced pressure at 40 °C for 3 h. The mixture was recrystallized from ethyl acetate / anhydrous ethanol (ethyl acetate / anhydrous ethanol V:V=8:2) (3×200 ml) and dried under vacuum at 60 °C for 12 h to obtain the quaternary ammonium salt compound.

[0042] S2: Under nitrogen protection, 500 ml of anhydrous DMF, 0.1 mol of quaternary ammonium salt compound, and 0.22 mol of 3-[[4-(pyridin-2-ylaminosulfonyl)phenyl]diazepine]benzoic acid were stirred and mixed. 0.22 mol of dicyclohexylcarbodiimide and 0.04 mol of 4-dimethylaminopyridine were added, and the mixture was stirred for 15 min. The mixture was reacted at 30 °C for 17 h. After filtration, 1000 ml of cold diethyl ether was added to the filtrate, and the precipitate was stirred to precipitate. After filtration, the filter cake was washed with a cold methanol / water mixture (methanol / water V:V=2:1) ​​(3×300 ml). The mixture was recrystallized with 500 ml of ethyl acetate / methanol (ethyl acetate / methanol V:V=4:1) and dried under vacuum at 65 °C for 12 h to obtain the antibacterial agent.

[0043] Example 4: Preparation of 4-((bis((1H-indol-5-yl)methyl)amino)methyl)benzaldehyde:

[0044] Under nitrogen protection, 350 ml of anhydrous tetrahydrofuran, 0.21 mol of 5-(chloromethyl)-1H-indole, and 0.1 mol of 4-(aminomethyl)benzaldehyde were mixed, and 0.21 mol of potassium carbonate was added. The mixture was reacted at 50 °C for 8 h, cooled to room temperature, washed with saturated brine (3 × 150 ml), dried over 20 g of anhydrous magnesium sulfate for 2 h, filtered, and distilled under reduced pressure at 40 °C for 2 h to obtain 4-((bis((1H-indole-5-yl)methyl)amino)methyl)benzaldehyde; the reaction equation is shown below:

[0045]

[0046] Its 1H NMR data are as follows: 1 H NMR (400 MHz, DMSO- d 6 ) δ 11.33 (s, 2H), 9.93 (t,J = 1.0 Hz, 1H), 7.99-7.91 (m, 2H), 7.55 (d, J = 0.6 Hz, 2H), 7.43-7.35 (m,2H), 7.31-7.24 (m, 6H), 6.53 (d, J = 0.5 Hz, 2H), 3.73 (s, 6H).

[0047] Example 5 Preparation of Anti-inflammatory agent:

[0048] N1 : 120 ml of anhydrous DMF, 0.1 mol of curcumin, 0.205 mol of triethylamine were mixed uniformly under nitrogen protection, 150 ml of anhydrous DMF solution containing 0.205 mol of phenyl glycidyl ether was slowly added dropwise, 1 h after dropping, the temperature was raised to 65°C and reacted for 4 h, then cooled to room temperature, 2 h of distillation at 60°C under reduced pressure, 600 ml of cold anhydrous n-hexane was added and stirred to precipitate the sediment, filtered, the filter cake was washed with cold anhydrous n-hexane (3 x 100 ml), and vacuum dried at 60°C for 8 h to obtain intermediate 1; the nuclear magnetic hydrogen spectrum data is as follows: 1 H NMR (400 MHz, DMSO- d 6 ) δ 7.52 (t, J = 1.0 Hz, 2H), 7.31-7.21 (m, 6H), 7.14 (ddd, J = 7.4, 2.0, 1.0 Hz, 2H), 7.02-6.88 (m, 10H), 5.35 (d, J = 5.0 Hz, 2H), 4.06-3.89 (m, 12H), 3.89-3.83 (m, 6H);

[0049] N2: 300 ml of anhydrous DMF, 0.21 mol of 4-aminomethyl phenylacetic acid, 0.22 mol of triethylamine were stirred and mixed uniformly under nitrogen protection, 300 ml of anhydrous DMF solution containing 54.3 g of chloroformic acid-9-fluorenylmethyl ester was slowly added dropwise at 0°C (dropping for 3 h), stirred at 25°C for 4 h; then 0.1 mol of intermediate 1, 0.21 mol of dicyclohexyl carbodiimide and 0.04 mol of 4-dimethylamino pyridine were added, stirred for 15 min, reacted at 25°C for 16 h, filtered, the filtrate was poured into 800 ml of ice water mixture (containing 100 ml of 0.1M HCl), stirred for 30 min; extracted with ethyl acetate (3 x 400 ml), the organic phase was combined and washed with 400 ml of saturated brine, 30 g of anhydrous magnesium sulfate was added and dried for 2 h, filtered, concentrated under reduced pressure at 50°C for 1 h to obtain a concentrated solution, the concentrated solution was added to a mixed solution of 300 ml of DMF and piperidine (the volume ratio of DMF to piperidine was 4:1), deprotected at 25°C for 35 min, then added to 400 ml of 0.1M HCl solution at 0°C, stirred to precipitate the sediment, filtered, washed with 200 ml of cold water, 150 ml of 5wt% sodium bicarbonate solution, 200 ml of cold water in turn, vacuum dried at 60°C for 12 h to obtain intermediate 2; the nuclear magnetic hydrogen spectrum data is as follows: 1 H NMR (400 MHz, DMSO- d 6) δ 7.52 (t, J = 1.0 Hz, 2H), 7.32-7.21 (m, 14H), 7.14 (ddd, J = 7.4,2.0, 1.0 Hz, 2H), 7.00 (s, 2H), 6.98-6.88 (m, 8H), 4.94 (s, 2H), 4.25-4.11(m, 8H), 3.99-3.92 (m, 5H), 3.87 (s, 6H), 3.86 (d, J = 12.4 Hz, 1H), 3.61-3.49 (m, 4H), 3.46 (d, J = 0.7 Hz, 4H);

[0050] N3: 700 ml of anhydrous DMF, 0.1 mol of intermediate 2, 0.205 mol of 4-((bis((1H-indol-5-yl)methyl)amino)methyl)benzaldehyde were mixed under nitrogen protection, and reacted at 65°C for 7 h. The mixture was cooled to room temperature, slowly added to 1000 ml of cold n-hexane, stirred to precipitate the sediment, filtered, the filter cake was washed with cold n-hexane (3 x 250 ml), and vacuum dried at 60°C for 24 h to obtain the anti-inflammatory agent; the nuclear magnetic resonance hydrogen spectrum data thereof are as follows: 1 H NMR (400 MHz, DMSO- d 6 ) δ 11.33 (s, 4H), 8.33 (t,J = 1.0 Hz, 2H), 7.62-7.49 (m, 10H), 7.36-7.21 (m, 30H), 7.14 (ddd, J = 7.4,2.0, 1.0 Hz, 2H), 7.02-6.89 (m, 10H), 6.53 (d, J = 0.5 Hz, 4H), 4.94 (s, 2H),4.67 (dt, J = 2.7, 0.9 Hz, 4H), 4.25-4.11 (m, 8H), 3.96 (d, J = 12.4 Hz, 2H),3.87 (s, 6H), 3.79-3.67 (m, 12H), 3.61-3.49 (m, 4H)。

[0051] Example 6: Preparation of a wound repair medical dressing:

[0052] (1) Weigh by weight: bioactive glass 30 g, sodium alginate 25 g, antibacterial agent (prepared in Example 2) 10 g, anti-inflammatory agent (prepared in Example 5) 10 g, deionized water 400 g;

[0053] (2) The deionized water and sodium alginate were mixed and stirred at 500 rpm for 2 h, and the bioactive glass, antibacterial agent, and anti-inflammatory agent were added. The mixture was placed in a high-pressure homogenizer and homogenized at 30 MPa for 4 cycles. The mixture was then freeze-dried at -50°C for 24 h to obtain the wound repair medical dressing.

[0054] Example 7 Preparation of a wound repair medical dressing

[0055] (1) The following ingredients were weighed: bioactive glass 35 g, sodium alginate 30 g, antibacterial agent (prepared in Example 3) 15 g, anti-inflammatory agent (prepared in Example 5) 13 g, and deionized water 500 g;

[0056] (2) The deionized water and sodium alginate were mixed and stirred at 500 rpm for 2 h, and the bioactive glass, antibacterial agent, and anti-inflammatory agent were added. The mixture was placed in a high-pressure homogenizer and homogenized at 30 MPa for 4 cycles. The mixture was then freeze-dried at -50°C for 24 h to obtain the wound repair medical dressing.

[0057] Example 8 Preparation of a wound repair medical dressing

[0058] (1) The following ingredients were weighed: bioactive glass 40 g, sodium alginate 35 g, antibacterial agent (prepared in Example 4) 20 g, anti-inflammatory agent (prepared in Example 5) 15 g, and deionized water 600 g;

[0059] (2) The deionized water and sodium alginate were mixed and stirred at 500 rpm for 2 h, and the bioactive glass, antibacterial agent, and anti-inflammatory agent were added. The mixture was placed in a high-pressure homogenizer and homogenized at 30 MPa for 4 cycles. The mixture was then freeze-dried at -50°C for 24 h to obtain the wound repair medical dressing.

[0060] Comparative Example 1

[0061] The wound repair medical dressing was prepared according to the same method as in Example 7, except that the antibacterial agent was replaced with an equal amount of an antibacterial agent prepared by the following method:

[0062] The antibacterial agent was prepared according to the same method as in Example 2, except that the N-hexadecyl diethanolamine in step S1 was replaced with an equal molar amount of N-propyl diethanolamine.

[0063] Comparative Example 2

[0064] The wound repair medical dressing was prepared according to the same method as in Example 7, except that the antibacterial agent was replaced with an equal amount of an antibacterial agent prepared by the following method:

[0065] The antibacterial agent was prepared according to the same method as in Example 2, except that the 1-chlorododecane in step S1 was replaced with an equal molar amount of 1-chloropropane.

[0066] Comparative Example 3

[0067] The raw material composition and the preparation method of the wound repair medical dressing are basically the same as those of Example 7, except that the antibacterial agent is replaced by an equal weight of an antibacterial agent prepared by the following method:

[0068] The preparation method of the antibacterial agent is basically the same as that of Example 2, except that 3-[[4-(pyridin-2-ylsulfamoyl)phenyl]diazenyl]benzoic acid in step S2 is replaced by an equal molar amount of 3-(phenylazo)benzoic acid (CAS No.: 14474-22-7).

[0069] Comparative Example 4

[0070] The raw material composition and the preparation method of the wound repair medical dressing are basically the same as those of Example 7, except that the anti-inflammatory agent is replaced by an equal weight of the intermediate 2 prepared in step N2 of Example 5.

[0071] Comparative Example 5

[0072] The raw material composition and the preparation method of the wound repair medical dressing are basically the same as those of Example 7, except that the anti-inflammatory agent is replaced by an equal weight of an anti-inflammatory agent prepared by the following method:

[0073] The preparation method of the anti-inflammatory agent is basically the same as that of Example 5, except that 4-((bis((1H-indol-5-yl)methyl)amino)methyl)benzaldehyde in step N3 is replaced by an equal molar amount of 4-(((1H-indol-5-yl)methyl)aminomethyl)benzaldehyde;

[0074] The preparation method of 4-(((1H-indol-5-yl)methyl)aminomethyl)benzaldehyde is as follows:

[0075] Under nitrogen protection, 250 ml of anhydrous tetrahydrofuran, 0.105 mol of 5-(chloromethyl)-1H-indole, and 0.1 mol of 4-(aminomethyl)benzaldehyde are mixed, 0.11 mol of potassium carbonate is added, and the mixture is reacted at 50°C for 8 h, cooled to room temperature, washed with saturated brine (3×100 ml), dried with 20 g of anhydrous magnesium sulfate for 2 h, filtered, and distilled at 40°C under reduced pressure for 2 h to obtain ((1H-indol-5-yl)methyl)aminomethyl)benzaldehyde.

[0076] Comparative Example 6

[0077] The raw material composition and the preparation method of the wound repair medical dressing are basically the same as those of Example 7, except that the anti-inflammatory agent is replaced by an equal weight of an anti-inflammatory agent prepared by the following method:

[0078] The preparation method of the anti-inflammatory agent is basically the same as that in Embodiment 5, except that the amount of 4-((bis((1H-indol-5-yl)methyl)amino)methyl)benzaldehyde in step N3 is replaced by 0.105 mol.

[0079] The bioactive glass used in the examples and comparative examples of the present application is HQ-BG45s-D1 of medical grade produced by Kunshan Huaguo Technology New Material Co., Ltd.; the number average molecular weight of sodium alginate is 10 kDa; and the CAS number of 3-[[4-(pyridin-2-ylsulfamoyl)phenyl]diazenyl]benzoic acid is 88247-54-5.

[0080] The wound repair medical dressings prepared in Examples 6-8 and Comparative Examples 1-6 are subjected to antibacterial performance and anti-inflammatory performance tests, and the test results are shown in Table 1.

[0081] Antibacterial performance test: the wound repair medical dressings prepared in Examples 6-8 and Comparative Examples 1-6 are cut into a uniform circular shape (8 mm in diameter and 1 mm in thickness), placed in a glass bottle with a lid containing PBS buffer (0.1 M, pH = 7.4), sterilized by high-pressure steam at 120°C for 15 min, and then cooled in a ventilated clean bench and sterilized by ultraviolet irradiation for 1 h. The test strain is Staphylococcus aureus. A single colony is picked from the test strain, and the bacterial concentration is diluted to 10 8 CFU / ml with physiological saline. 100 μl of the bacterial solution is dropped on the LB solid culture medium, and the bacterial solution is uniformly coated with a coating rod. The cut sample to be tested is attached, sealed, and then placed in a 37°C biochemical incubator for constant temperature culture. After 24 h, the bacterial growth on the culture medium is observed and the size of the inhibition zone is recorded.

[0082] Anti-inflammatory performance test: the wound repair medical dressings prepared in Examples 6-8 and Comparative Examples 1-6 are cut into a uniform circular shape (8 mm in diameter and 1 mm in thickness); and a wound repair medical dressing prepared without adding an anti-inflammatory agent (the raw material composition and preparation method of the wound repair medical dressing are basically the same as those in Embodiment 7, except that no anti-inflammatory agent is added in the components) is used as a control.

[0083] The dressings are sterilized by irradiation with a 15 kGy dose of γ-rays, and the sterile dressings are placed in a 96-well plate and inoculated with RAW264.7 cells at a cell concentration of 5×10 3 CFU / ml. 2The flask was placed in a 95% humidity, 37°C and 5% CO2 environment for expansion culture, and fresh complete culture medium was replaced every other day. The culture solution used during the culture process consisted of 90 vol.% H-DMEM and 10 vol.% FBS. The RAW264.7 cells used in the experiment were cells of the 3rd to 6th generation. After 3 days of culture, the cells growing on the sample were digested using 0.25 wt% trypsin / EDTA, and then centrifuged at 1000 r / min for 5 min. The cells were blocked using a 1 wt% BSA PBS solution, washed 3 times with PBS after 30 min of blocking, and then CD11c (eBioscience) and CD206 (eBioscience) straight-label antibodies were added and incubated at room temperature for 30 min. The cells were then washed 3 times with PBS, placed in serum-free DMEM culture medium (containing 1 wt% penicillin-streptomycin), and then 1 μg / ml lipopolysaccharide (E. coli O111:B4) was added to induce inflammation for 2 h. A blank control group (only culture medium) and a lipopolysaccharide control group (lipopolysaccharide + culture medium) were set up. After 24 h of culture, the supernatant was taken, and the concentrations of TNF-α and IL-6 were detected using an ELISA kit. The inflammation factor inhibition rate was (lipopolysaccharide control group concentration - experimental group concentration) / lipopolysaccharide control group concentration x 100%.

[0084] Table 1

[0085]

[0086] As can be seen from the data in Table 1, the wound repair medical dressings prepared in Examples 6-8 of the present application have excellent antibacterial and anti-inflammatory properties.

[0087] The wound repair medical dressing prepared in Examples 6-8 of the present application has good antibacterial performance, mainly because the added antibacterial agent has quaternary ammonium salt, long-chain alkyl, sulfonamide group and pyridine structure. Among them, the quaternary ammonium salt structure has a positive charge, which can destroy the bacterial cell membrane through electrostatic action; the long-chain alkyl can enhance the hydrophobic interaction with the bacterial cell membrane, assist the quaternary ammonium salt structure to penetrate the membrane structure, and improve the antibacterial efficiency; the sulfonamide group in the sulfonamide group is a strong electron-withdrawing group, which can increase the polarity and water solubility of the molecule, so that the antibacterial agent can better dissolve and diffuse in the aqueous wound environment, increase the probability of contacting bacteria, and the N-H bond in the sulfonamide group can form a hydrogen bond with the polar group on the surface of the bacterial cell membrane, enhance the specific binding ability of the molecule and the bacteria, and assist the quaternary ammonium salt group to play a role; the nitrogen atom on the pyridine ring has a lone pair of electrons, which can act as an electron donor to coordinate with essential metal ions of bacteria to form stable complexes, in addition, the pyridine ring has an electron-withdrawing effect, which can enhance the positive charge density of the quaternary ammonium salt cation, improve the electrostatic attraction to the bacterial cell membrane, strengthen the membrane destruction efficiency, and synergistically improve the antibacterial performance of the wound repair medical dressing. The antibacterial agent used in Comparative Example 1 and Comparative Example 2 has poor hydrophobic interaction with the bacterial cell membrane, and the antibacterial agent used in Comparative Example 3 lacks sulfonamide groups and pyridine groups, which limits the ability to destroy the bacterial cell membrane, resulting in poor antibacterial performance of the prepared wound repair medical dressing.

[0088] The wound repair medical dressing prepared in Examples 6-8 of the present application has good anti-inflammatory performance, mainly because the added anti-inflammatory agent has a curcumin anti-inflammatory core, a pH-sensitive Schiff base bond, and an indole ring structure. Among them, the curcumin core can inhibit inflammation through multiple mechanisms such as inhibition of the MAPK pathway and chelation of metal ions, while the dimethoxy can interact with the unsaturated fatty acid chains of the cell membrane phospholipids through π-π stacking, prolonging the residence time of the molecule in the local inflammation, and enhancing the anti-inflammatory persistence; the indole ring can bind to COX enzymes to prevent the process of COX enzymes catalyzing arachidonic acid into prostaglandin, thereby exerting an anti-inflammatory effect; the Schiff base has pH-dependent hydrolysis characteristics, which can be selectively broken at the inflammation site to achieve targeted release of the anti-inflammatory components of curcumin and indole ring, avoiding systemic toxicity. The structures in the anti-inflammatory agent synergistically improve the anti-inflammatory performance of the wound repair medical dressing. In Comparative Example 4, the anti-inflammatory agent is replaced by intermediate 2, which lacks the synergistic effect of the pH-sensitive Schiff base bond and the indole ring structure, resulting in poor anti-inflammatory performance of the prepared wound repair medical dressing; in Comparative Example 5, the anti-inflammatory agent used has a reduced indole ring structure, which reduces the effect of preventing COX enzymes from catalyzing arachidonic acid into prostaglandin, resulting in weakened anti-inflammatory effect of the wound repair medical dressing; in Comparative Example 6, the anti-inflammatory agent used contains only one pH-sensitive Schiff base bond, which weakens the synergistic targeting ability of the anti-inflammatory components of curcumin and indole ring, resulting in poor anti-inflammatory performance of the wound repair medical dressing.

[0089] The above is only the preferred embodiment of the present application, and is not used to limit the present application; but for the ordinary skilled in the art without departing from the scope of the present application technical scheme, can use the above disclosed technical content and make some changes, modifications and evolution of equivalent changes, are equivalent embodiments of the present application; at the same time, any equivalent changes, modifications and evolution of the above embodiments according to the essential technology of the present application, still belong to the protection scope of the present application technical scheme.

Claims

1. A wound repair medical dressing, characterized by, The raw materials include the following weight parts: biological active glass 30-40 parts, sodium alginate 25-35 parts, antibacterial agent 10-20 parts, anti-inflammatory agent 10-15 parts, deionized water 400-600 parts; The antibacterial agent is prepared by the following method: S1: N-hexadecyl diethanolamine reacts with 1-chlorododecane to generate a quaternary ammonium salt compound, S2: the quaternary ammonium salt compound reacts with 3-[[4-(pyridin-2-ylsulfamoyl) phenyl] diazenyl] benzoic acid to generate an antibacterial agent; The anti-inflammatory agent is prepared by the following method: N1: curcumin reacts with phenyl glycidyl ether to generate intermediate 1, N2: intermediate 1 reacts with 4-aminomethyl phenylacetic acid to generate intermediate 2, N3: intermediate 2 reacts with 4-((bis((1H-indol-5-yl) methyl) amino) methyl) benzaldehyde to generate an anti-inflammatory agent.

2. The wound repair medical dressing according to claim 1, characterized in that In step S1, the molar ratio of N-hexadecyl diethanolamine to 1-chlorododecane is 1:(1.05-1.1).

3. The wound repair medical dressing according to claim 1, wherein In step S2, the molar ratio of the quaternary ammonium salt compound to 3-[[4-(pyridin-2-ylsulfamoyl) phenyl] diazenyl] benzoic acid is 1:(2.1-2.2).

4. The wound care dressing of claim 1, wherein The reaction time of step S1 is 23-24 h, and the reaction temperature is 70-75℃.

5. The wound repair medical dressing of claim 1, wherein, The reaction time of step S2 is 17-18 h, and the reaction temperature is 25-30℃.

6. The wound repair medical dressing of claim 1, wherein, The reaction solvent of step S1 is anhydrous ethanol; the reaction solvent of step S2 is anhydrous DMF.

7. The wound care dressing of claim 1, wherein In step N1, the molar ratio of curcumin to phenyl glycidyl ether is 1:2.

05.

8. The wound repair medical dressing of claim 1, wherein, In step N2, the molar ratio of intermediate 1 to 4-aminomethyl phenylacetic acid is 1:2.

1.

9. The wound repair medical dressing of claim 1, wherein, In step N3, the molar ratio of intermediate 2 to 4-((bis((1H-indol-5-yl) methyl) amino) methyl) benzaldehyde is 1:2.

05.

10. A method of preparing a wound repair medical dressing according to any one of claims 1 to 9, characterized in that, The following steps are included: (1) weigh the following by weight parts: biological active glass 30-40 parts, sodium alginate 25-35 parts, antibacterial agent 10-20 parts, anti-inflammatory agent 10-15 parts, deionized water 400-600 parts; (2) stir and mix the deionized water and sodium alginate, add the biological active glass, antibacterial agent, and anti-inflammatory agent, homogenize, and freeze-dry to obtain a wound repair medical dressing.

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