Sulfur aluminum chitosan composite hydrogel preparation and preparation method thereof

Abstract

The invention relates to a sucralfate and chitosan composite hydrogel preparation. The sucralfate and chitosan composite hydrogel preparation is prepared from the following raw materials in percentage by mass: 2.97 to 9 percent of sucralfate, 0.2 to 0.33 percent of carboxymethyl chitosan, 0.5 to 1.7 percent of xanthan gum and 0.1 to 0.7 percent of poloxamer 188. According to the sucralfate-chitosan composite hydrogel preparation, the diameter of a staphylococcus aureus inhibition zone is gt; the diameter of the inhibition zone of the copper pseudomonas is gt; the hydrogel has the advantages that the thickness is 35 mm, the antibacterial effect is obvious, the hydrogel system is stable, and the viscosity change rate is reduced by 1t after 30 days; 4%, the pH change rate is reduced lt; 5%.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of medical materials, in particular to a sucralfate composite hydrogel preparation and a preparation method thereof, which is suitable for the nursing of complex wounds such as chronic ulcers, burns, postoperative wounds, diabetic foot and radioactive skin damage. BACKGROUND

[0002] Skin, as the largest defense barrier of the human body, bears multiple important physiological functions: resisting ultraviolet radiation through the stratum corneum, constructing a physical barrier to prevent pathogenic microorganisms from invading, dynamically regulating body temperature balance, and maintaining hydration homeostasis and immune regulation through the epidermal microenvironment. In the contemporary social environment, the destruction of epidermal integrity caused by pathological damage or accidental trauma not only causes pathological pain, but also easily leads to secondary microbial colonization of the wound, resulting in non-healing chronic wounds. This clinical complication not only increases the physical and mental burden of patients, but also significantly increases the diagnosis and treatment pressure of the public health system. Based on this, the development of innovative wound care materials with significant repair function has become an important topic in the field of modern medicine.

[0003] Traditional wound dressings (such as gauze, cotton pad, etc.) often cause secondary damage and delayed healing due to poor air permeability, insufficient moisturizing ability and easy adhesion to the wound. In recent years, hydrogel dressings have become a research hotspot due to their high water content, biocompatibility and biomimetic extracellular matrix characteristics.

[0004] Sucralfate is an alkaline aluminum salt of sucrose sulfate. It is well known that sucralfate tablets and suspensions have been used to treat gastric and duodenal ulcers for several decades. In these agents, sucralfate forms a protective film on the surface of damaged tissue covering the ulcer surface, promoting ulcer healing. It also has the effects of adsorbing pepsin and bile acids, promoting the synthesis of endogenous prostaglandins, and adsorbing epidermal growth factor (EGF), which concentrates at the ulcer site to facilitate mucosal regeneration. SUMMARY

[0005] The present application develops a sucralfate chitosan composite hydrogel preparation. Compared with traditional forms of sucralfate products, the sucralfate chitosan composite hydrogel preparation has stronger ability to adhere to damaged skin sites, and its effect is independent of the pH value of the skin. After sucralfate comes into contact with damaged skin, a protective layer is formed covering the damaged skin site, which rapidly and effectively promotes skin healing and thus prevents infection.

[0006] In the first aspect of the present application, the present application provides a sucralfate chitosan composite hydrogel preparation, which comprises the following mass percentage contents of raw materials: sucralfate 2.97-9%, carboxymethyl chitosan 0.2-0.33%, xanthan gum 0.5-1.7%, and poloxamer 188 0.1-0.7%.

[0007] By adopting the above technical solution, this application provides a sucralfate-chitosan composite hydrogel formulation with an inhibition zone diameter >40mm against Staphylococcus aureus and >35mm against Pseudomonas aeruginosa, demonstrating significant antibacterial effects. Furthermore, the hydrogel system is stable, with a viscosity change rate decrease of <4% and a pH change rate decrease of <5% after 30 days. This may be because, on the one hand, sucralfate and carboxymethyl chitosan synergistically enhance antibacterial efficacy through multiple mechanisms such as charge synergy, enhanced physical barrier function, metabolic interference, and biofilm inhibition, while also possessing anti-inflammatory and healing-promoting functions; on the other hand, xanthan gum and poloxamer 188 synergistically enhance the suspension stability and user comfort of the hydrogel through multiple mechanisms such as network structure synergy, dynamic rheological regulation, enhanced suspension stability, and moisture retention.

[0008] Optionally, the mass ratio of sucralfate to carboxymethyl chitosan is (9-40):1.

[0009] Preferably, the mass ratio of sucralfate to carboxymethyl chitosan is (9-14):1.

[0010] By adopting the above technical solution and adjusting the dosage of sucralfate and carboxymethyl chitosan according to the above mass ratio, the mass ratio of sucralfate and carboxymethyl chitosan is (9-14):1, which can ensure that the sucralfate-chitosan composite hydrogel preparation has a good antibacterial effect.

[0011] Optionally, the mass ratio of xanthan gum to poloxamer 188 is (1.85-5.7):1.

[0012] By adopting the above technical solution and adjusting the dosage of xanthan gum and poloxamer 188 according to the above mass ratio, the hydrogel system of the sucralfate chitosan composite hydrogel preparation can be kept stable when the mass ratio of xanthan gum and poloxamer 188 is (1.85-5.7):1.

[0013] Optionally, the sucralfate-chitosan composite hydrogel formulation comprises the following raw materials in the following mass percentages: sucralfate 2.97-9%, carboxymethyl chitosan 0.2-0.33%, xanthan gum 0.5-1.7%, poloxamer 188 0.1-0.7%, SEPINEO P 600 1-4%, sodium methylparaben 0.15-0.2%, with the balance being water.

[0014] Furthermore, sucralfate 2.97-3.08%, carboxymethyl chitosan 0.22-0.33%, xanthan gum 0.5-1.7%, and poloxamer 188 0.1-0.7%.

[0015] Furthermore, sucralfate 2.97-9%, carboxymethyl chitosan 0.2-0.33%, xanthan gum 1.3-1.7%, and poloxamer 188 0.3-0.7%.

[0016] Furthermore, sucralfate 2.97-3.08%, carboxymethyl chitosan 0.22-0.33%, xanthan gum 1.3-1.7%, and poloxamer 188 0.3-0.7%.

[0017] By adopting the above technical solution, SEPINEO P 600 is a highly efficient thickener of a multifunctional liquid polymer. Its chemical name is acrylamide / sodium acryloyldimethyl taurate copolymer / isohexadecane-polysorbate 80 / sorbitan oleate; sodium methylparaben inhibits Gram-positive bacteria (such as Staphylococcus aureus) and fungi (such as Candida albicans).

[0018] In a second aspect of this application, a method for preparing a sucralfate chitosan composite hydrogel formulation as described in the first aspect of this invention is provided, comprising the following preparation steps: S1: Preparation of the first system: Disperse carboxymethyl chitosan, xanthan gum and poloxamer 188 in water and stir evenly to obtain the first system; S2: Preparation of the second system: Add SEPINEO P 600 to water and stir well to obtain the second system; S3: Preparation of sucralfate solution: Add sucralfate to the remaining water, add sodium methylparaben, and disperse evenly to obtain sucralfate solution; S4: Mixing system: Mix the first system, the second system, and the sucralfate solution, and stir to obtain the sucralfate chitosan composite hydrogel formulation.

[0019] Optionally, in step S1, the stirring reaction temperature of the first system is 60-80℃, the stirring time is 30-60 min, and the homogenization time is 5-15 min.

[0020] Optionally, in step S2, the stirring time for the second system is 30-60 min, and the homogenization time is 5-15 min.

[0021] Optionally, in step S3, the ultrasonic dispersion time of the sucralfate solution is 10-30 min.

[0022] Optionally, in step S4, the stirring time for preparing the mixing system is 20-60 minutes.

[0023] In a third aspect of this application, this application provides the application of the sucralfate chitosan composite hydrogel formulation described in the first aspect of this invention in the preparation of antibacterial drugs.

[0024] Optionally, the antibacterial drug is an anti-Staphylococcus aureus and / or Pseudomonas aeruginosa.

[0025] In a fourth aspect of this application, this application provides the use of the sucralfate chitosan composite hydrogel wound dressing described in the first aspect of this invention in the preparation of a medicament for the care and / or treatment of damaged skin.

[0026] Optionally, the mass ratio of sucralfate to carboxymethyl chitosan is (9-14):1; and the mass ratio of xanthan gum to poloxamer 188 is (1.85-5.7):1.

[0027] In summary, the present invention has at least one of the following beneficial technical effects: 1. This application provides a sucralfate-chitosan composite hydrogel formulation with an inhibition zone diameter >40mm against Staphylococcus aureus and >35mm against Pseudomonas aeruginosa, demonstrating significant antibacterial effects. Furthermore, the hydrogel system is stable, with a viscosity change rate decrease of <4% and a pH change rate decrease of <5% after 30 days. On one hand, sucralfate and carboxymethyl chitosan synergistically enhance antibacterial efficacy through multiple mechanisms, including charge synergy, enhanced physical barrier function, metabolic interference, and biofilm inhibition, while also possessing anti-inflammatory and healing-promoting functions. On the other hand, xanthan gum and poloxamer 188 synergistically enhance the suspension stability and user comfort of the hydrogel through multiple mechanisms, including network structure synergy, dynamic rheological regulation, enhanced suspension stability, and moisture retention.

[0028] 2. This application provides the application of a sucralfate-chitosan composite hydrogel formulation in the preparation of antibacterial drugs. It exhibits a significant antibacterial effect, with an inhibition zone diameter >40 mm against Staphylococcus aureus and >35 mm against Pseudomonas aeruginosa.

[0029] 3. This application provides an application of a sucralfate-aluminum chitosan composite hydrogel wound dressing in the preparation of a dressing for the care and / or treatment of damaged skin. It possesses high quality, safety, and high efficacy, effectively renewing damaged skin and healing uninfected wounds caused by various reasons. Detailed Implementation

[0030] The embodiments of the present invention will be described in detail below with reference to the examples. However, those skilled in the art will understand that the following examples are only for illustrating the present invention and should not be regarded as limiting the scope of the present invention. Specific conditions not specified in the examples shall be carried out according to conventional conditions or conditions recommended by the manufacturer. Reagents or instruments whose manufacturers are not specified are all conventional products that can be purchased commercially.

[0031] Carboxymethyl chitosan was purchased from Huatai Biotechnology (Shaanxi) Co., Ltd., and SEPINEO P 600 was purchased from Sepico (Shanghai) Specialty Chemicals Co., Ltd.

[0032] Example 1 A sucralfate-chitosan composite hydrogel formulation comprises the following raw materials in weight percentages: sucralfate 8%, carboxymethyl chitosan 0.2%, xanthan gum 0.5%, poloxamer 188 0.1%, SEPINEO P 600 2%, sodium methylparaben 0.18%, and the balance being water.

[0033] The mass ratio of sucralfate to carboxymethyl chitosan is 40:1; the mass ratio of xanthan gum to poloxamer 188 is 5:1.

[0034] Preparation method: S1: First system preparation: Carboxymethyl chitosan, xanthan gum and poloxamer 188 were dispersed in 25 wt% deionized water, stirred at 60 °C and 100 rpm for 30 min, and then homogenized at 1000 rpm for 5 min to obtain the first system. S2: Second system preparation: Take another 45 wt% of deionized water, add SEPINEO P 600, stir at 100 rpm for 30 min at room temperature, and then homogenize at 1000 rpm for 5 min to obtain the second system; S3: Preparation of sucralfate solution: Sucralfate was added to the remaining deionized water, sodium methylparaben was added, and the mixture was sonicated for 10 min (frequency 40 kHz) to ensure uniform dispersion, thus obtaining a sucralfate solution. S4: Mixed System The first system, the second system, and the sucralfate solution were mixed and stirred at 100 rpm for 20 min to obtain the sucralfate-chitosan composite hydrogel formulation.

[0035] Example 2 A sucralfate-chitosan composite hydrogel formulation comprises the following raw materials in weight percentages: sucralfate 9%, carboxymethyl chitosan 0.3%, xanthan gum 1%, poloxamer 188 0.3%, SEPINEO P 600 2%, sodium methylparaben 0.18%, and the balance being water.

[0036] The mass ratio of sucralfate to carboxymethyl chitosan was 30:1; the mass ratio of xanthan gum to poloxamer 188 was 3.33:1.

[0037] Preparation method: S1: Preparation of the first system: Carboxymethyl chitosan, xanthan gum and poloxamer 188 were dispersed in 25 wt% deionized water, stirred at 70 °C and 150 rpm for 40 min, and then homogenized at 1500 rpm for 10 min to obtain the first system. S2: Preparation of the second system: Take another 45 wt% of total water volume of deionized water, add SEPINEO P 600, stir at 150 rpm for 40 min at room temperature, and then homogenize at 1500 rpm for 10 min to obtain the second system; S3: Preparation of sucralfate solution: Sucralfate was added to the remaining deionized water, sodium methylparaben was added, and the mixture was sonicated for 20 minutes (frequency 40 kHz) to ensure uniform dispersion, thus obtaining a sucralfate solution. S4: Mixed System The first system, the second system, and the sucralfate solution were mixed and stirred at 200 rpm for 40 min to obtain the sucralfate-chitosan composite hydrogel formulation.

[0038] Example 3 A sucralfate-chitosan composite hydrogel formulation comprises the following raw materials in weight percentages: sucralfate 3%, carboxymethyl chitosan 0.3%, xanthan gum 1.5%, poloxamer 188 0.5%, SEPINEO P 600 2%, sodium methylparaben 0.18%, and the balance being water.

[0039] The mass ratio of sucralfate to carboxymethyl chitosan is 10:1; the mass ratio of xanthan gum to poloxamer 188 is 3:1.

[0040] Preparation method: S1: Preparation of the first system: Carboxymethyl chitosan, xanthan gum and poloxamer 188 were dispersed in 25 wt% deionized water, stirred at 80 °C and 250 rpm for 60 min, and then homogenized at 2000 rpm for 15 min to obtain the first system. S2: Preparation of the second system: Take another 45 wt% deionized water, add SEPINEO P 600, stir at 250 rpm for 60 min at room temperature, and then homogenize at 2000 rpm for 15 min to obtain the second system; S3: Preparation of sucralfate solution: Sucralfate was added to the remaining deionized water, sodium methylparaben was added, and the mixture was sonicated for 30 min (frequency 40 kHz) to ensure uniform dispersion, thus obtaining a sucralfate solution. S4: Mixing and homogenizing: The first system, the second system, and the sucralfate solution were mixed and stirred at 250 rpm for 60 min to obtain the sucralfate-chitosan composite hydrogel formulation.

[0041] Example 4 Example 4 provides a sucralfate-chitosan composite hydrogel formulation, which differs from Example 3 in that the total mass of sucralfate and carboxymethyl chitosan remains unchanged, and the mass ratio of sucralfate to carboxymethyl chitosan is 9:1.

[0042] Specifically, the raw material composition of the sucralfate-chitosan composite hydrogel formulation varies. This embodiment includes the following raw materials by mass percentage: sucralfate 2.97%, carboxymethyl chitosan 0.33%, xanthan gum 1.5%, poloxamer 188 0.5%, SEPINEO P 600 2%, sodium methylparaben 0.18%, and the balance being water.

[0043] Example 5 Example 5 provides a sucralfate-chitosan composite hydrogel formulation, which differs from Example 3 in that the total mass of sucralfate and carboxymethyl chitosan remains unchanged, and the mass ratio of sucralfate to carboxymethyl chitosan is 14:1.

[0044] Specifically, the raw material composition of the sucralfate-chitosan composite hydrogel formulation varies. This embodiment includes the following raw materials by mass percentage: sucralfate 3.08%, carboxymethyl chitosan 0.22%, xanthan gum 1.5%, poloxamer 188 0.5%, SEPINEO P 600 2%, sodium methylparaben 0.18%, and the balance being water.

[0045] Example 6 Example 6 provides a sucralfate chitosan composite hydrogel formulation, which differs from Example 3 in that the total mass of xanthan gum and poloxamer 188 remains unchanged, and the mass ratio of xanthan gum to poloxamer 188 is 1.85:1.

[0046] Specifically, the raw material composition of the sucralfate-chitosan composite hydrogel formulation varies. This embodiment includes the following raw materials by mass percentage: sucralfate 3%, carboxymethyl chitosan 0.3%, xanthan gum 1.3%, poloxamer 188 0.7%, SEPINEO P 600 2%, sodium methylparaben 0.18%, and the balance being water.

[0047] Example 7 Example 7 provides a sucralfate chitosan composite hydrogel formulation, which differs from Example 3 in that the total mass of xanthan gum and poloxamer 188 remains unchanged, and the mass ratio of xanthan gum to poloxamer 188 is 5.7:1.

[0048] Specifically, the raw material composition of the sucralfate-chitosan composite hydrogel formulation varies. This embodiment includes the following raw materials by mass percentage: sucralfate 3%, carboxymethyl chitosan 0.3%, xanthan gum 1.7%, poloxamer 188 0.3%, SEPINEO P 600 2%, sodium methylparaben 0.18%, and the balance being water.

[0049] Comparative Example 1 Comparative Example 1 provides a sucralfate-chitosan composite hydrogel formulation, which differs from Example 3 in that sucralfate is replaced by carboxymethyl chitosan in equal mass.

[0050] Specifically, the raw material composition of the sucralfate chitosan composite hydrogel formulation is different. This comparative example includes the following raw materials by mass percentage: carboxymethyl chitosan 3.3%, xanthan gum 1.5%, poloxamer 188 0.5%, SEPINEO P 600 2%, sodium methylparaben 0.18%, and the balance being water.

[0051] Comparative Example 2 Comparative Example 2 provides a sucralfate-chitosan composite hydrogel formulation, which differs from Example 3 in that carboxymethyl chitosan is replaced by sucralfate in equal mass.

[0052] Specifically, the raw material composition of the sucralfate-chitosan composite hydrogel formulation is different. This comparative example includes the following raw materials by mass percentage: sucralfate 3.3%, xanthan gum 1.5%, poloxamer 188 0.5%, SEPINEO P 600 2%, sodium methylparaben 0.18%, and the balance being water.

[0053] Comparative Example 3 Comparative Example 3 provides a sucralfate chitosan composite hydrogel formulation, which differs from Example 3 in that xanthan gum is replaced with poloxamer 188 by mass.

[0054] Specifically, the raw material composition of the sucralfate-chitosan composite hydrogel formulation is different. This comparative example includes the following raw materials by mass percentage: sucralfate 3%, carboxymethyl chitosan 0.3%, poloxamer 188 2.0%, SEPINEO P 600 2%, sodium methylparaben 0.18%, and the balance being water.

[0055] Comparative Example 4 Comparative Example 4 provides a sucralfate chitosan composite hydrogel formulation, which differs from Example 3 in that poloxamer 188 is replaced with xanthan gum by mass.

[0056] Specifically, the raw material composition of the sucralfate-chitosan composite hydrogel formulation is different. This comparative example includes the following raw materials by mass percentage: sucralfate 3%, carboxymethyl chitosan 0.3%, xanthan gum 2.0%, SEPINEO P 600 2%, sodium methylparaben 0.18%, and the balance being water.

[0057] Comparative Example 5 Comparative Example 5 provides a sucralfate chitosan composite hydrogel formulation, which differs from Example 3 in that carboxymethyl chitosan is replaced by chitosan in equal mass.

[0058] Specifically, the raw material composition of the sucralfate-chitosan composite hydrogel formulation is different. This comparative example includes the following raw materials by mass percentage: sucralfate 3%, chitosan 0.3%, xanthan gum 1.5%, poloxamer 188 0.5%, SEPINEO P600 2%, sodium methylparaben 0.18%, and the balance being water.

[0059] Comparative Example 6 Comparative Example 6 provides a sucralfate chitosan composite hydrogel formulation, which differs from Example 3 in that xanthan gum is replaced with carrageenan by mass.

[0060] Specifically, the raw material composition of the sucralfate-chitosan composite hydrogel formulation is different. This comparative example includes the following raw materials by mass percentage: sucralfate 3%, carboxymethyl chitosan 0.3%, carrageenan 1.5%, poloxamer 188 0.5%, SEPINEO P 600 2%, sodium methylparaben 0.18%, and the balance being water.

[0061] Performance testing and analysis (1) Stability performance test The samples prepared in Examples 1-7 and Comparative Examples 1-6 were placed in an oven at 40°C and periodically removed for observation and testing. The test results are shown in Table 1. Table 1 Stability Performance Test Based on Examples 1-3 and Table 1, it can be seen that Example 3 exhibits the lowest decrease in both viscosity and pH change rates, and the sample does not separate into layers. This may be because the mass percentages of xanthan gum and poloxamer 188 in Example 3 are higher than those in Examples 1-2, or it may be influenced by the stirring rate, stirring time, homogenization rate, homogenization time, and ultrasonic dispersion time. Therefore, on the one hand, higher contents of xanthan gum and poloxamer 188 may result in a more stable hydrogel system; on the other hand, the preparation process in Example 3 may be optimal, with the following parameters: stirring rate of 250 rpm, stirring time of 60 min; homogenization rate of 2000 rpm, homogenization time of 15 min; and ultrasonic dispersion time of 30 min.

[0062] As can be seen from Examples 3-5 and Table 1, adjusting the mass ratio of sucralfate and carboxymethyl chitosan has little effect on the stability of the hydrogel system.

[0063] Based on Examples 3, 6-7, and Table 1, it can be seen that when the mass ratio of xanthan gum to poloxamer 188 is 3:1, the decrease rate of viscosity and pH is the lowest, and the hydrogel system is the most stable. Therefore, adjusting the mass ratio of xanthan gum to poloxamer 188 affects the rate of change of viscosity and pH, and thus the stability of the hydrogel system.

[0064] Based on Example 3, Comparative Examples 1-2 and Table 1, it can be seen that the thioaluminose and carboxymethyl chitosan components in the system have little effect on the stability of the hydrogel system.

[0065] Based on Example 3, Comparative Examples 3-4 and Table 1, it can be seen that when xanthan gum or poloxamer 188 is used alone in the system, the sample exhibits obvious stratification and the viscosity change rate decreases significantly. Therefore, it can be concluded that the synergistic effect of xanthan gum and poloxamer 188 has a significant promoting effect on the stability of the hydrogel system.

[0066] As can be seen from Example 3, Comparative Example 5 and Table 1, replacing carboxymethyl chitosan with chitosan by mass has little impact on the stability of the hydrogel system.

[0067] As can be seen from Example 3, Comparative Example 6 and Table 1, replacing xanthan gum with carrageenan by the same mass significantly reduced the viscosity change rate. This may be because carrageenan and poloxamer 188 are physically incompatible, leading to a decrease in the stability of the hydrogel system.

[0068] (2) Damaged skin loses its barrier function and is highly susceptible to bacterial and microbial infection. Therefore, the antibacterial ability of hydrogels is one of the most important properties when used as wound dressings. In this experiment, common Staphylococcus aureus and Pseudomonas aeruginosa were selected as experimental bacteria for antibacterial testing. 200 mg of each sample was taken, sterilized, and then placed on a coating of 10... 6 The bacterial culture was placed on agar medium containing cfu / mL bacteria. The agar plates were incubated in a 37℃ incubator for 24 hours, and then removed to observe bacterial growth. The experimental results are shown in Table 2. Table 2 Antibacterial Performance Test Based on Examples 1-3 and Table 2, it can be seen that the mass percentages of thioaluminose and carboxymethyl chitosan in Example 3 are higher than those in Examples 1-2. Example 3 exhibits the largest inhibition zone diameter against Staphylococcus aureus and Pseudomonas aeruginosa, superior to Examples 1-2. Therefore, it can be concluded that the higher the content of thioaluminose and carboxymethyl chitosan, the larger the inhibition zone diameter against Staphylococcus aureus and Pseudomonas aeruginosa may be.

[0069] Based on Examples 3-5 and Table 2, it can be seen that in Example 3, the mass ratio of sucralfate to carboxymethyl chitosan was 10:1. Example 3 exhibited the largest inhibition zone diameter against Staphylococcus aureus and Pseudomonas aeruginosa, which was superior to Examples 4-5. Therefore, adjusting the ratio of sucralfate to carboxymethyl chitosan can affect the diameter of the inhibition zone against Staphylococcus aureus and Pseudomonas aeruginosa.

[0070] Based on Examples 3, 6-7 and Table 2, it can be seen that changing the mass ratio of xanthan gum to poloxamer 188 has little effect on the diameter of the inhibition zone against Staphylococcus aureus and Pseudomonas aeruginosa.

[0071] Based on Example 3, Comparative Examples 1-2, and Table 2, it can be seen that when sucralfate or carboxymethyl chitosan is used alone in the sucralfate-chitosan composite hydrogel formulation, the diameter of the inhibition zone against Staphylococcus aureus and Pseudomonas aeruginosa is significantly reduced. Therefore, the synergistic effect of sucralfate and carboxymethyl chitosan can significantly enhance antibacterial efficacy.

[0072] Based on Example 3, Comparative Examples 3-4 and Table 2, it can be seen that xanthan gum and poloxamer 188 have little effect on the diameter of the inhibition zone of Staphylococcus aureus and Pseudomonas aeruginosa.

[0073] As can be seen from Example 3, Comparative Example 5 and Table 2, replacing carboxymethyl chitosan with chitosan by mass significantly reduced the diameter of the inhibition zone against Staphylococcus aureus and Pseudomonas aeruginosa.

[0074] Based on Example 3, Comparative Example 6, and Table 2, it can be seen that replacing xanthan gum with carrageenan by the same amount has little effect on the diameter of the inhibition zone of Staphylococcus aureus and Pseudomonas aeruginosa.

[0075] (3) Wound healing test The experimental animals were male rats. The rats' backs were treated with 8% sodium sulfide solution to remove hair, covering an area of ​​approximately 2 × 2 cm. 2 Twenty-four hours later, sodium pentobarbital was administered intraperitoneally. After successful anesthesia, the rats were scalded with 80°C water for 15 seconds to induce burns on their backs. The burn area was 2×2cm. 2 After injury, 5 ml of physiological saline was administered intraperitoneally, followed by drug administration 2 hours later. 0.5 g of the sucralfate-chitosan composite hydrogel preparations obtained in Example 3 and Comparative Examples 1-2 were applied to the wound surface as experimental groups 1-3, respectively. Application was repeated for 5 days, once daily at 0.5 g per application. The wound healing rate was observed and calculated on day 14. Ten animals were used in each group, and the average healing rate was recorded.

[0076] The wound healing rate was calculated as follows: First, the wound was traced on translucent paper. Then, using this as a template, uniform pieces of cardboard were cut to the same size. The cardboard pieces were then weighed, and the weight indirectly represented the wound area. The wound healing rate was calculated using the following formula: Wound healing rate (%) = (Original wound area - Unhealed wound area) / Original wound area. Pathological examination was performed to assess the quality of wound healing, and the healing time was determined based on the healing progress. The wound healing rate on day 14 was calculated, and the experimental results are shown in Table 3 below. Table 3 Based on Example 3, Comparative Examples 1-2, and Table 3, it can be seen that when sucralfate or carboxymethyl chitosan is used alone in the sucralfate-chitosan composite hydrogel formulation, the wound healing rate is significantly reduced. Therefore, the synergistic effect of sucralfate and carboxymethyl chitosan can significantly improve the wound healing rate.

[0077] The application of this invention is not limited to the specific examples described herein, and its techniques and features can be modified and substituted in various ways without departing from the scope defined by the claims. Those skilled in the art can implement this invention based on the information provided and recognize that changes and improvements can be made while maintaining the invention. Therefore, the actual scope of application of this invention should be determined according to the claims, and not limited to the embodiments described herein. All technical solutions formed by equivalent substitutions or equivalent transformations are within the protection scope of this invention.

Claims

1. A sucralfate-chitosan composite hydrogel formulation, characterized in that, The raw materials include the following percentages by weight: sucralfate 2.97-9%, carboxymethyl chitosan 0.2-0.33%, xanthan gum 0.5-1.7%, and poloxamer 188 0.1-0.7%.

2. The sucralfate-chitosan composite hydrogel formulation according to claim 1, characterized in that, The mass ratio of sucralfate to carboxymethyl chitosan is (9-40):

1.

3. The sucralfate-chitosan composite hydrogel formulation according to claim 1, characterized in that, The mass ratio of xanthan gum to poloxamer 188 is (1.85-5.7):

1.

4. The sucralfate-chitosan composite hydrogel formulation according to claim 1, characterized in that, The raw materials include the following percentages by weight: sucralfate 2.97-9%, carboxymethyl chitosan 0.2-0.33%, xanthan gum 0.5-1.7%, poloxamer 188 0.1-0.7%, SEPINEO P 600 1-4%, sodium methylparaben 0.15-0.2%, with the balance being water.

5. A method for preparing a sucralfate-chitosan composite hydrogel formulation according to claim 4, characterized in that, The preparation steps include the following: S1: Preparation of the first system: Disperse carboxymethyl chitosan, xanthan gum and poloxamer 188 in water and stir evenly to obtain the first system; S2: Preparation of the second system: Add SEPINEO P 600 to water and stir well to obtain the second system; S3: Preparation of sucralfate solution: Add sucralfate to the remaining water, add sodium methylparaben, and disperse evenly to obtain sucralfate solution; S4: Mixing system: Mix the first system, the second system, and the sucralfate solution, and stir to obtain the sucralfate chitosan composite hydrogel formulation.

6. The method for preparing a sucralfate-chitosan composite hydrogel formulation according to claim 5, characterized in that, In step S1, the stirring reaction temperature of the first system is 60-80℃, the stirring time is 30-60 min, and the homogenization time is 5-15 min.

7. The preparation method of the sucralfate-chitosan composite hydrogel formulation according to claim 5, characterized in that, In step S2, the stirring time for the second system is 30-60 min, and the homogenization time is 5-15 min.

8. The use of the sucralfate chitosan composite hydrogel formulation according to any one of claims 1-4 in the preparation of antibacterial drugs.

9. The application of the sucralfate-chitosan composite hydrogel formulation according to claim 8 in the preparation of antibacterial drugs, characterized in that, The antibacterial drug is an antimicrobial drug against Staphylococcus aureus and / or Pseudomonas aeruginosa.

10. The use of the sucralfate chitosan composite hydrogel wound dressing according to any one of claims 1-4 in the preparation of a medicament for the care and / or treatment of damaged skin.

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