Nitric oxide gas foaming agent as well as preparation method and application thereof

Abstract

The invention discloses a nitric oxide gas foaming agent as well as a preparation method and application thereof, and belongs to the technical field of biological composite materials, the nitric oxide gas foaming agent comprises gel foam, and the gel foam is semisolid gel formed by dispersing gas in a hydrogel skeleton in a microbubble form; wherein the gas is composed of nitric oxide and nitrogen according to the volume ratio of 1: 10, the prepared gel foam has the advantages of being adjustable in nitric oxide gas content, long in foam maintaining time and high in mechanical strength, the defects of local treatment application of existing nitric oxide gas can be overcome, and in addition, the used materials are auxiliary materials approved by FDA, so that the preparation method is suitable for industrial production. The composition has the advantages of simple components and good safety. The preparation method of the gel foam is simple and controllable to operate, and large-scale production is easy to realize; the gel foam disclosed by the invention has antibacterial, hemostatic, anti-inflammatory and immunoregulation effects, and can be used for repairing wounds of skin and cavity mucosa (gastrointestinal tract and uterus).

Description

Technical Field

[0001] This invention belongs to the field of biocomposite materials technology, specifically relating to a nitric oxide gas foaming agent, its preparation method, and its application. Background Technology

[0002] Bacterial infection is a major cause of slow skin wound healing. Because bacteria at the site of infection often exist in the form of biofilms, most antibacterial drugs cannot effectively penetrate these biofilms to kill bacteria, leading to drug resistance. In recent years, the treatment of bacterial infections with nitric oxide (NO) gas has attracted widespread research interest. NO is a diatomic free radical that can kill bacteria by inducing lipid peroxidation, DNA cleavage, and protein dysfunction, and it is less likely to induce drug resistance. Furthermore, NO can react with free radical superoxide to generate peroxynitrite anions (ONOO-) and dinitrogen trioxide (N2O3), leading to bacterial membrane rupture and bacterial dysfunction. Therefore, NO exhibits excellent antibacterial activity against Gram-positive and Gram-negative bacteria, and even against drug-resistant bacteria.

[0003] Currently, NO treatment systems mainly include nitric oxide gas inhalation, nitric oxide donors, and nitric oxide phospholipid microbubbles. Nitric oxide gas inhalation therapy has advantages such as rapid onset of action and simple administration, but it also has problems such as difficulty in accurately controlling the gas dosage, lung irritation, rapid gas clearance, and low target concentration at wound sites. Nitric oxide donors need to be converted into nitric oxide in vivo through chemical hydrolysis or enzymatic catalysis, and have the advantages of controllable dosage and mild effect. However, nitric oxide phospholipid microbubbles have problems such as low gas loading capacity, gas solution leakage, and difficulty in large-scale production.

[0004] Foam is a dispersion system formed by dispersing gas in the form of microbubbles in a continuous phase. Due to its unique physical structure, it has advantages such as high gas content and ease of preparation. At present, most of the foams studied are those prepared by mixing air with surfactant solutions using special devices, which are used in cosmetics or skin disease treatment. However, foams prepared with surfactants have problems such as weak mechanical strength, easy flow, easy bubble rupture, and short residence time. Summary of the Invention

[0005] The purpose of this invention is to provide a nitric oxide gas foam agent, its preparation method, and its application, in order to solve the problems of traditional foams having weak mechanical strength, short half-life, unadjustable gas concentration, and lack of antibacterial and wound repair activities, thus failing to meet the needs of local nitric oxide treatment.

[0006] To achieve the above objectives, the present invention provides the following technical solution: a nitric oxide gas foaming agent, comprising a gel foam, wherein the gel foam is a semi-solid gel composed of gas dispersed in the form of microbubbles in a hydrogel framework; The gas consists of nitric oxide and nitrogen in a volume ratio of 1:10, and the hydrogel framework is a fibrous aggregate formed by chitosan and sodium alginate solution.

[0007] In a preferred embodiment, the volume ratio of the hydrogel to the gas is 1:0.1 to 1:10; In a preferred embodiment, the hydrogel comprises 0.5%–5.0% chitosan, 0.5%–5.0% sodium alginate, and water, and the nitric oxide gel foam contains nitric oxide at a concentration of 50–1000 μmol / L. The volume ratio of the hydrogel to the gas is 1:0.5 to 1:5, wherein the hydrogel comprises 1.0%–3.0% chitosan, 1.0%–3.0% sodium alginate, and water by mass volume, and the nitric oxide gel foam contains nitric oxide at a concentration of 60–500 μmol / L.

[0008] This invention also discloses a method for preparing a nitric oxide gas foaming agent, comprising the following steps: S1. Preparation of chitosan solution: Dissolve chitosan powder in acidic aqueous solution and stir until completely dissolved; S2. Preparation of sodium alginate solution: Dissolve sodium alginate powder in distilled water and stir until completely dissolved; S3. Mixing: Mix the chitosan solution from step S1 with the sodium alginate solution from step S2 at a certain volume ratio of 1:0.5 to 1:3, stir evenly, and prepare a viscous fibrous aggregate. S4. Foaming: The fibrous aggregate solution obtained in step S3 is placed into a sealed foaming bottle, a three-way valve is connected, the air in the bottle is first evacuated, and then a high-pressure mixture of nitric oxide and nitrogen is introduced into the bottle to maintain the pressure in the bottle at 100-600 psi. The foaming bottle is shaken vigorously to disperse the gas into the viscous fibrous aggregate to prepare gel foam.

[0009] In step S3, the chitosan solution and sodium alginate solution are mixed at a certain volume ratio of 1:0.5 to 1:3.

[0010] In a preferred embodiment, the pressure of the foaming bottle is maintained at 200–400 psi.

[0011] The present invention also discloses the application of nitric oxide gas foaming agent, wherein the nitric oxide gas gel foaming agent is applied to promote wound healing in skin diseases such as burns, scalds or diabetic foot.

[0012] This invention also discloses the application of nitric oxide gas foaming agent, which is used in drugs for treating gastritis, ulcerative colitis, and gynecological inflammation caused by Helicobacter pylori.

[0013] The present invention also discloses the application of nitric oxide gas foaming agent, wherein the nitric oxide gas gel foaming agent is used in therapeutic antibacterial drugs.

[0014] The present invention also discloses the application of nitric oxide gas foaming agent, wherein the nitric oxide gas gel foaming agent is used in hemostatic materials.

[0015] Compared with the prior art, the beneficial effects of the present invention are: This nitric oxide gas foam agent is prepared by directly mixing nitric oxide and nitrogen gas and dispersing them under high pressure in a viscous aggregate formed by chitosan and sodium alginate, thus creating a nitric oxide-rich gel foam agent. The gel foam agent is in a semi-solid form, with chitosan-sodium alginate fibrous aggregate as the hydrogel skeleton. The nitric oxide-nitrogen gas mixture is dispersed under high pressure to achieve a stable nitric oxide load. It has a long foam half-life at room temperature and pressure, and has the advantages of adjustable nitric oxide gas content, long foam duration, and high mechanical strength, thus overcoming the shortcomings of existing nitric oxide gas local therapeutic applications.

[0016] This nitric oxide gas foam has moderate mechanical strength, making it resistant to flow and deformation. It can also closely adhere to irregular wounds such as skin burns and diabetic foot ulcers, as well as the mucous membranes of cavities such as the intestines and vagina, filling the gaps in the wound and reducing patient discomfort. At the same time, it has excellent liquid absorption and water retention capabilities and mechanical cushioning properties, which can absorb wound exudate and protect the wound from mechanical damage.

[0017] This nitric oxide gas foaming agent uses FDA-approved excipients, offering advantages such as simple composition and good safety. The gel foam preparation method is simple, controllable, and easily scaled up for production. The gel foam described in this invention possesses antibacterial, hemostatic, anti-inflammatory, and immunomodulatory effects. Attached Figure Description

[0018] Figure 1 This is a schematic diagram illustrating the preparation process of the gel foam agent of the present invention; Figure 2 The particle size distribution and stability curves of the nitric oxide gel foam agent of the present invention are shown. Figure 3 This is a schematic diagram of the histological evaluation results of the nitric oxide gel foam of the present invention in the treatment of gastritis caused by Helicobacter pylori; Figure 4 This is a schematic diagram of colonic mucosal damage observed by small animal endoscopy to evaluate the efficacy of the nitric oxide gel foam of the present invention in the treatment of ulcerative colitis. Figure 5This diagram illustrates the antibacterial effect of the nitric oxide gel foam agent of the present invention, using the plate count method to evaluate its bactericidal effect on Escherichia coli. Figure 6 The results of the antibacterial effect of the nitric oxide gel foam agent of the present invention are shown in the following diagram: scanning electron microscopy to observe the morphological changes of bacteria and the inhibition zone experiment to evaluate the diffusion antibacterial ability. Figure 7 This diagram illustrates the hemostatic effect of the nitric oxide gel foam agent of the present invention, specifically the evaluation of hemostasis time and bleeding volume using a liver hemorrhage model.

[0019] Figure 8 This is a schematic diagram of the steps in the preparation method of the nitric oxide gas foaming agent of the present invention. Detailed Implementation

[0020] The present invention will be further described below with reference to embodiments.

[0021] The following embodiments are used to illustrate the present invention, but should not be used to limit the scope of protection of the present invention. The conditions in the embodiments can be further adjusted according to specific conditions, and simple improvements to the method of the present invention under the premise of the concept of the present invention are all within the scope of protection claimed by the present invention.

[0022] Please see Figures 1-8 This invention provides a nitric oxide gas foaming agent, comprising a gel foam. The gel foam is a semi-solid gel composed of gas dispersed in the form of microbubbles within a hydrogel framework. The gas consists of nitric oxide and nitrogen in a volume ratio of 1:10. The hydrogel framework is a fibrous aggregate formed by combining chitosan and sodium alginate solution. The volume ratio of hydrogel to gas is 1:0.1 to 1:10. The hydrogel contains 0.5% to 5.0% chitosan, 0.5% to 5.0% sodium alginate, and water. The nitric oxide gel foaming agent contains nitric oxide at a concentration of 50 to 1000 μmol / L. Alternatively, the volume ratio of hydrogel to gas can be 1:0.5 to 1:5, where the hydrogel contains 1.0% to 3.0% chitosan, 1.0% to 3.0% sodium alginate, and water in a mass-to-volume ratio. The nitric oxide gel foaming agent contains nitric oxide at a concentration of 60 to 500 μmol / L.

[0023] This invention also discloses a method for preparing a nitric oxide gas foaming agent, comprising the following steps: S1. Preparation of chitosan solution: Dissolve chitosan powder in acidic aqueous solution and stir until completely dissolved; S2. Preparation of sodium alginate solution: Dissolve sodium alginate powder in distilled water and stir until completely dissolved; S3. Mixing: Mix the chitosan solution from step S1 with the sodium alginate solution from step S2 at a certain volume ratio of 1:0.5 to 1:3, stir evenly, and prepare a viscous fibrous aggregate. S4. Foaming: The fibrous aggregate solution obtained in step S3 is placed into a sealed foaming bottle, a three-way valve is connected, the air in the bottle is first evacuated, and then a high-pressure mixture of nitric oxide and nitrogen is introduced into the bottle to maintain the pressure in the bottle at 100-600 psi. The foaming bottle is shaken vigorously to disperse the gas into the viscous fibrous aggregate to prepare gel foam.

[0024] In step S3, the chitosan solution and sodium alginate solution are mixed at a certain volume ratio of 1:0.5 to 1:3.

[0025] The pressure in the foam bottle is maintained at 200–400 psi.

[0026] Nitric oxide aerogel foam is used to promote wound healing in skin diseases such as burns, scalds, or diabetic foot. Nitric oxide aerogel foam is used in the treatment of gastritis, ulcerative colitis, and gynecological inflammation caused by Helicobacter pylori. It is also used in antibacterial drugs and hemostatic materials.

[0027] Example 1 Gel foam preparation: Chitosan (CH) solution and sodium alginate (SA) aqueous solution were prepared according to Table 1, and mixed at a volume ratio of 1:1. The mixture was stirred continuously for more than 4 hours to obtain a viscous coagulant solution. 100 mL of the coagulated solution was poured into a special steel cylinder (capacity 500 mL), and the air inside the cylinder was removed by vacuum pumping for 6 hours. Then, high-pressure nitrogen gas rich in NO (different proportions, see Table 1) was introduced into the sealed steel cylinder. The pressure inside the cylinder was adjusted and maintained to the value shown in Table 1. The steel cylinder was shaken vigorously for 10 minutes to fully mix the gas and liquid inside the cylinder, and finally, gel foam was obtained.

[0028] Example 2 Preparation of chitosan solution foam: Prepare a chitosan (CH) solution and stir continuously for more than 4 hours to obtain a viscous and clear polymer solution; take 100 mL of polymer solution and pour it into a special steel bottle (capacity 500 mL), vacuum pump for 6 hours to remove air from the bottle, then introduce high-pressure nitrogen rich in NO into the sealed steel bottle, adjust and maintain the pressure inside the bottle to the value shown in Table 1, and shake the steel bottle vigorously for 10 minutes to fully mix the gas and liquid inside the bottle to prepare chitosan solution foam.

[0029] Example 3 Preparation of sodium alginate solution foam: Prepare sodium alginate (SA) solution and stir continuously for more than 4 hours to obtain a viscous and clear polymer solution; take 100 mL of polymer solution and pour it into a special steel bottle (capacity 500 mL), vacuum pump for 6 hours to remove air from the bottle, then introduce high-pressure nitrogen gas rich in NO into the sealed steel bottle, adjust and maintain the pressure inside the bottle to the value shown in Table 1, and shake the steel bottle vigorously for 10 minutes to fully mix the gas and liquid inside the bottle to prepare chitosan solution foam.

[0030] Example 4 Determination of the volume ratio of gas to hydrogel in gel foam: Take 10 mL of foam sample and place it in a graduated cylinder to measure its initial volume (V0); after the volume containing foam is completely defoamed by ultrasonication in a water bath, measure the remaining liquid volume (V1); calculate the volume ratio of gas to hydrogel in the foam = (V0 - V1): V1.

[0031] Example 5 Determination of the half-life (t1 / 2) of gel foam bubbles: Take 10 mL of foam sample and place it in a graduated cylinder to measure its initial volume (V0). Let it stand at room temperature and record the volume (Vt) of residual foam at different time points. Calculate the residual foam ratio (F) (%) at each time point = Vt / V0 × 100. Plot F against t and calculate the time when 50% of the foam dissipates, which is t1 / 2.

[0032] Example 6 Mechanical strength determination of gel foam: The viscoelastic modulus of the foam was determined using a rotational rheometer (DHR-2, TA Instruments, USA). Frequency sweeps (0.1–10 rad / s) were performed at constant strain (1%) to assess frequency-dependent viscoelasticity, with each measurement repeated three times, and the average storage modulus (G') was calculated.

[0033] Example 7 NO loading determination: 0.5 mL of foam was added to 1.5 mL of PBS, and the foam was ruptured by vortex sonication. Then, it was centrifuged (3000×g, 10 min), and the supernatant was collected. The NO content was detected using the Griess kit (S0021S, Beyotime).

[0034] Example 8 Cytotoxicity: Cells were distributed at a rate of 1 × 10⁶ cells per well. 4Cells were seeded at a density of [number] cells per well in 96-well plates and cultured overnight to allow them to adhere. Subsequently, the medium was replaced with culture medium containing different concentrations of CHSF or LA-CHSF and cultured for another 12 h. Furthermore, the NO concentration in LA-CHSF-NO was controlled by adjusting the aeration time, and the cells were co-incubated for 12 h. A blank control group containing only blank medium and a control group of untreated normal cells were also included. After co-incubation, [number] cells were added to each well. The solution was incubated for another 40 minutes, and the absorbance at 450 nm was measured using a microplate reader.

[0035] Example 9 Gel foam treatment for gastritis caused by Helicobacter pylori: Eight-week-old male C57BL / 6 mice were randomly divided into two groups: a blank control group (n = 5) and a gel foam group (n = 5).

[0036] Prior to infection, mice were fasted and administered 5% sodium bicarbonate solution by gavage to neutralize gastric acid. Subsequently, every other day at the same time point, mice were administered 200 μL of Helicobacter pylori bacterial suspension (10 μL / mL). 8 (CFU / mL), for two weeks. One week after the end of infection, mice in the blank control group were administered 300 μL of physiological saline by gavage once daily, while mice in the gel foam group were administered 300 μL of gel foam by gavage once daily for one week.

[0037] Mice were sacrificed the day after the last administration, and gastric tissue was collected for subsequent biochemical and histological analysis. The results showed that Helicobacter pylori infection led to thinning of the gastric mucus layer and loss of mucus particles, while gel foam intervention significantly promoted mucus secretion.

[0038] Immunohistochemical results of Helicobacter pylori showed that the gel foam had a significant inhibitory effect on Helicobacter pylori colonization in the stomach.

[0039] Example 10 Gel foam therapy for ulcerative colitis: Mice were given tap water containing 3.5% DSS for 5 consecutive days to induce acute ulcerative colitis.

[0040] Mice with DSS-induced ulcerative colitis were randomly divided into two groups (n=5): the DSS model group (physiological saline, 150 μL / mouse) and the gel foam group (150 μL). The DSS solution was changed every two days. Mice in each group were administered physiological saline or foam rectally on days 3, 5, 7, and 9 of the experiment.

[0041] Meanwhile, on day 10 of the experiment, the colonic mucosa of mice was observed using a small animal endoscope (Shenyang University, China).

[0042] Mice were sacrificed on day 10 of the experiment, and colons were collected for further analysis. Small animal endoscopy revealed ulceration, hemorrhage, and fibrosis of the mucosa in the control group mice on day 10, indicating severe progression of colitis.

[0043] The mucosal damage in the gel foam group mice was significantly reduced, with no obvious bleeding points or ulcer areas, indicating that the epithelial structure was well repaired.

[0044] H&E staining was used to further assess the histopathological changes. As shown in the figure, the colon tissue of the control group mice showed obvious crypt collapse, extensive infiltration of inflammatory cells, and destruction of the epithelial structure. After gel foam treatment, the above pathological features were significantly alleviated, the number of inflammatory cells was significantly reduced, the crypts were intact, and the epithelial arrangement was regular.

[0045] Example 11 Antibacterial activity of gel foam: Escherichia coli (E. coli) was selected as an opportunistic pathogen, and the antibacterial activity of gel foam was evaluated by plate counting method.

[0046] Bacterial suspension (1×10) 5 Add CFU / mL (1 mL) to a shake flask, then add 500 μL of PBS or gel foam (containing 40 μM NO), and incubate at 37℃ and 100 rpm for 24 h with shaking. Take 100 μL of bacterial culture from each treatment group and perform serial dilutions. Take 10 μL of the diluted solution and spread it evenly on LB agar plates. Incubate overnight at 37℃. Observe and count the colonies on the plates. The results show that gel foam exhibits the strongest bactericidal effect, reducing the viable number of E. coli by 86.7%.

[0047] Example 12 Hemostatic effect of gel foam: To systematically evaluate the hemostatic effect and clinical applicability of foam materials, this study used an animal model of acute visceral hemorrhage for verification. The liver was chosen as the target organ mainly because of its rich blood supply and the difficulty in achieving effective hemostasis through compression.

[0048] Eight-week-old male ICR mice were anesthetized and fixed, followed by abdominal surgery to expose the middle lobe of the liver. To calculate the amount of bleeding, pre-weighed filter paper (mass denoted as W0) was placed under the liver. A standardized incision (4–5 mm long × 3 mm deep) was made on the liver surface using a sterile scalpel to establish a liver injury model. Immediately after bleeding occurred, 100 μL of sample or control gauze (5 mm × 2.5 mm) was applied. After complete hemostasis, the material was carefully removed, and the mass of blood absorbed by the filter paper was weighed (denoted as W1). The hemostatic effect was evaluated by the amount of bleeding, calculated as W1 - W0. The results showed that the bleeding from the wound treated with gel foam was reduced to 85.0 mg, significantly lower than that in the control group.

[0049] Table 1. Formulation and preparation process parameters of aerogel foam agent; ; ; Table 2. Characteristic parameters of the aerogel foam prepared in the examples ; Note: Y indicates that a uniform semi-solid gel foam can be formed; N indicates that it cannot be formed or collapses rapidly; "—" indicates that a stable foam cannot be formed or cannot be measured.

[0050] In the table, compared with pairs 1-4, it can be seen that the concentrations of chitosan and sodium alginate in groups 1-6 have a significant impact on the formation and performance of gel foam.

[0051] When the concentrations of chitosan and sodium alginate are within the range of 0.5% to 5.0% (groups 1-6), uniform semi-solid gel foams (all with Y gelation characteristics) can be formed. The NO concentration initially decreases and then stabilizes with increasing concentration. The foam half-life and storage modulus increase with increasing concentration, and the cell viability is above 95%, indicating that the gel foams prepared within this concentration range have good stability and biocompatibility. Group 4 (concentration 3.0%) exhibits the best overall performance, with a gas:gel volume ratio of 1:0.5, a NO concentration of 80 μmol / L, a foam half-life of 2.0 h, a storage modulus of 280 Pa, and a cell viability of 120%. When the concentration is below 0.5% (for groups 1-2) or above 5.0% (for groups 3-4), uniform gel foams (all with N gelation characteristics) cannot be formed, indicating that stable foam formulations cannot be obtained when the concentration exceeds the scope of the claims.

[0052] Compared with groups 5-8, groups 4 and 7-11 show that the volume ratio of chitosan to sodium alginate has a significant impact on the performance of the gel foam. When the volume ratio of chitosan to sodium alginate is in the range of 1:0.5 to 1:3 (groups 4 and 7-11), uniform semi-solid gel foam can be formed. The NO concentration is between 80 and 150 μmol / L. The foam half-life first increases and then decreases with the increase of sodium alginate ratio. Group 4 (CH:SA=1:1) has the longest foam half-life (2.0 h), the highest storage modulus (280 Pa), and the highest cell viability (120%).

[0053] When the volume ratio is less than 1:0.5 (for 5) or greater than 1:3 (for 6), or when only a single polymer is used (for 7-8), uniform gel foam cannot be formed, indicating that the synergistic effect of chitosan and sodium alginate is the key to forming stable gel foam.

[0054] Compared with groups 9-11, groups 4 and 12-14 show that the internal pressure of the bottle has a significant impact on the performance of the gel foam. When the internal pressure is in the range of 100-600 psi (groups 4 and 12-14), a uniform semi-solid gel foam can be formed. With increasing pressure, the gas:gel volume ratio gradually increases (from 1:0.3 to 1:0.6), the NO concentration gradually decreases (from 120 μmol / L to 65 μmol / L), and the foam half-life and storage modulus both improve.

[0055] Group 4 (400 psi) showed the best overall performance. When the pressure was below 100 psi (for 9) or above 600 psi (for 10-11), uniform gel foam could not be formed, indicating that too low a pressure would not result in effective foaming, while too high a pressure might cause the foam to break or become unstable.

[0056] Based on the above analysis, the nitric oxide gas gel foam agent of the present invention can form a uniform and stable semi-solid gel foam within the range of the claims, including chitosan concentration of 0.5%–5.0%, sodium alginate concentration of 0.5%–5.0%, chitosan:sodium alginate volume ratio of 1:0.5–1:3, and bottle pressure of 100–600 psi. This foam exhibits good foam stability (foam half-life of 0.5–3.0 h), mechanical strength (storage modulus of 50–400 Pa), and biocompatibility (cell viability >95%). Among these, the optimal conditions are chitosan concentration of 3.0%, sodium alginate concentration of 3.0%, chitosan:sodium alginate volume ratio of 1:1, and bottle pressure of 400 psi. The resulting gel foam has a gas:gel volume ratio of 1:0.5, a NO concentration of 80 μmol / L, a foam half-life of 2.0 h, a storage modulus of 280 Pa, and a cell viability of 120%, demonstrating the best foam characteristics and biocompatibility. None of the comparative examples exceeding the scope of the claims could form a uniform and stable gel foam, verifying the rationality of the scope of the claims and the superiority of the technical solution.

[0057] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A nitric oxide gas foaming agent, comprising gel foam, characterized in that: The gel foam is a semi-solid gel composed of gas dispersed in the form of microbubbles in a hydrogel framework. The gas consists of nitric oxide and nitrogen in a volume ratio of 1:10, and the hydrogel framework is a fibrous aggregate formed by chitosan and sodium alginate solution.

2. The nitric oxide gas foaming agent according to claim 1, characterized in that: The volume ratio of the hydrogel to the gas is 1:0.1 to 1:10; The hydrogel contains 0.5%~5.0% chitosan, 0.5%~5.0% sodium alginate and water, and the nitric oxide gel foam contains nitric oxide at a concentration of 50~1000 μmol / L. The volume ratio of the hydrogel to the gas is 1:0.5~1:5, wherein the hydrogel contains 1.0%~3.0% chitosan, 1.0%~3.0% sodium alginate and water by mass / volume, and the nitric oxide gel foam contains nitric oxide at a concentration of 60~500 μmol / L.

3. A method for preparing a nitric oxide gas foaming agent, characterized in that, Includes the following steps: S1. Preparation of chitosan solution: Dissolve chitosan powder in acidic aqueous solution and stir until completely dissolved; S2. Preparation of sodium alginate solution: Dissolve sodium alginate powder in distilled water and stir until completely dissolved; S3. Mixing: Mix the chitosan solution from step S1 with the sodium alginate solution from step S2 at a certain volume ratio of 1:0.5 to 1:3, stir evenly, and prepare a viscous fibrous aggregate. S4. Foaming: The fibrous aggregate solution obtained in step S3 is placed into a sealed foaming bottle, a three-way valve is connected, the air in the bottle is first evacuated, and then a high-pressure mixture of nitric oxide and nitrogen is introduced into the bottle to maintain the pressure in the bottle at 100-600 psi. The foaming bottle is shaken vigorously to disperse the gas into the viscous fibrous aggregate to prepare gel foam.

4. The method for preparing a nitric oxide gas foaming agent according to claim 3, characterized in that: In step S3, the chitosan solution and sodium alginate solution are mixed at a certain volume ratio of 1:0.5 to 1:

3.

5. The method for preparing a nitric oxide gas foaming agent according to claim 3, characterized in that: The pressure in the foaming bottle is maintained at 200–400 psi.

6. Application of nitric oxide gas foaming agent, characterized in that, The nitric oxide gas foaming agent is prepared by any one of the nitric oxide gas foaming agent preparation methods according to claims 3-5, and the nitric oxide gas gel foaming agent is applied to promote wound healing in skin diseases such as skin burns, scalds, or diabetic foot.

7. Application of nitric oxide gas foaming agent, characterized in that, The nitric oxide gas foaming agent is prepared by any one of the nitric oxide gas foaming agent preparation methods according to claims 3-5, and the nitric oxide gas gel foaming agent is used in the treatment of gastritis, ulcerative colitis, enteritis and gynecological inflammation caused by Helicobacter pylori.

8. Application of nitric oxide gas foaming agent, characterized in that, The nitric oxide gas foaming agent is prepared by any one of the nitric oxide gas foaming agent preparation methods according to claims 3-5, and the nitric oxide gas gel foaming agent is used in therapeutic antibacterial drugs.

9. Application of nitric oxide gas foaming agent, characterized in that, The nitric oxide gas foaming agent is prepared by any one of the nitric oxide gas foaming agent preparation methods according to claims 3-5, and the nitric oxide gas gel foaming agent is used in hemostatic materials.

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