Antibacterial hemostatic gel patch and preparation method thereof

Abstract

The invention provides an antibacterial hemostatic gel patch and a preparation method thereof, and the method comprises the following steps: taking 3% w / v of cross-linked sodium carboxymethyl cellulose as a hydrogel matrix carrier, uniformly dispersing 2% w / v of chitosan and 0.1% w / v of polyhexamethylene biguanide in a hydrogel matrix, injecting into a mold, and freeze-drying to form inner-layer gel with a slightly convex arc-shaped surface; preparing a mixed solution containing 50% w / v of medical glycerin and 0.5% w / v of sodium hyaluronate, and carrying out film casting on the mixed solution to form a middle buffer layer; the method comprises the following steps: by taking a medical polyurethane film as a base material, coating a phenol red derivative on the inner side of the polyurethane film as a color indicator to form an outer-layer polyurethane film; the middle buffer layer and the inner-layer gel are attached to form hydrogen bond combination through hydroxyl and amino, the middle buffer layer and the outer-layer polyurethane film are bonded through medical acrylate adhesive, and the gel patch is prepared. The gel patch can realize multiple functions such as rapid hemostasis, continuous antibiosis, moisturizing and repairing, and intelligent errhysis monitoring, and is suitable for nursing of puncture points after liver cancer radiofrequency ablation.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of postoperative care instruments for minimally invasive treatment of liver cancer, and particularly relates to an antibacterial hemostatic gel patch and a preparation method thereof. BACKGROUND

[0002] As a mainstream minimally invasive treatment method, liver cancer radiofrequency ablation has less trauma, but the postoperative puncture point care still faces severe challenges. The wound has high-temperature damage characteristics and multiple complex factors such as cirrhosis, coagulation dysfunction and low immunity often accompanied by patients, and there is a high risk of bleeding, infection and delayed healing. At present, the conventional clinical treatment is to use sterile gauze or ordinary adhesive bandage and other traditional dressings, which are mostly single-layer structures and have single functions, and have the following significant limitations: first, they cannot simultaneously achieve rapid hemostasis and effective antibiosis, and the operation needs to stop bleeding first and then apply medicine, which has a nursing time difference and is easy to cause secondary damage due to dressing replacement; second, they lack suitable moisture environment maintenance capability, and traditional dressings can easily cause the wound to dry and scab, thereby delaying the migration of epithelial cells and tissue regeneration; and third, they completely lack bleeding monitoring capability, and medical staff or patients must frequently uncover the dressing to observe the wound, which not only destroys the closed environment, increases the risk of infection, but also brings pain and inconvenience to patients.

[0003] In addition, although some functional hydrogel dressings or composite structure dressings exist in the prior art, they are usually designed for conventional surgical incisions or chronic ulcers, and cannot specifically solve the problem of the superimposed three risks of "high-temperature damage-poor coagulation-weak immunity" of the small puncture point after liver cancer radiofrequency ablation, and have obvious deficiencies in functional synergy, intelligent feedback and patient-specific adaptation.

[0004] In view of this, the application provides an antibacterial hemostatic gel patch specially used for the puncture point after liver cancer radiofrequency ablation, which can achieve immediate hemostasis, continuous antibiosis, moisture repair and intelligent monitoring. SUMMARY

[0005] In view of the problems that the existing dressings cannot simultaneously achieve hemostasis and antibiosis, cannot intelligently prompt bleeding, and are easy to cause wound scabbing, the application aims to provide an antibacterial hemostatic gel patch and a preparation method thereof.

[0006] To achieve the application purpose, the application adopts the following technical solutions:

[0007] In a first aspect, the application provides a preparation method of an antibacterial hemostatic gel patch, which comprises the following steps:

[0008] A 3% w / v cross-linked sodium carboxymethyl cellulose is used as a hydrogel matrix carrier, 2% w / v chitosan and 0.1% w / v polyhexamethylene biguanide are uniformly dispersed in the hydrogel matrix, and the inner layer gel with a micro-convex arc-shaped surface is formed after injection into a mold and freeze-drying.

[0009] A mixed solution containing 50% w / v medical glycerol and 0.5% w / v sodium hyaluronate is prepared, and the mixed solution is cast into a film to form an intermediate buffer layer;

[0010] A medical-grade polyurethane film is used as a substrate, and a phenol red derivative is coated on the inner side of the polyurethane film as a color developing indicator to form an outer polyurethane film;

[0011] The intermediate buffer layer is attached to the inner gel layer to form a hydrogen bond between the hydroxyl group and the amino group, and the intermediate buffer layer is adhered to the outer polyurethane film by medical acrylate glue to obtain a gel patch.

[0012] Preferably, the surface of the inner gel layer is processed into a micro-convex arc shape with a radius of curvature of 1 cm.

[0013] Preferably, the edge of the outer polyurethane film is compounded with a low-sensitization pressure-sensitive adhesive, and the adhesion is 3-5 N / 25 mm.

[0014] Preferably, the thickness of the inner gel layer is 0.3 mm, the thickness of the intermediate buffer layer is 0.5 mm, and the thickness of the outer polyurethane film is 0.1 mm.

[0015] Preferably, the degree of deacetylation of chitosan is ≥85%, and the molecular weight is 5000-10000 Da.

[0016] Preferably, the coating concentration of the phenol red derivative is 0.02% w / v.

[0017] Preferably, the purity of medical glycerol is ≥99.5%, and the molecular weight of sodium hyaluronate is 80000-100000 Da.

[0018] Preferably, the porosity of the medical-grade polyurethane film is 100-200 μm, and the moisture permeability is ≥2000 g / m 2 ·24h.

[0019] Preferably, the freeze-drying conditions are as follows: the pre-freezing temperature is -40℃ to -50℃, and the temperature is maintained for 2-4 hours; the vacuum degree is ≤10 Pa in the sublimation drying stage, the temperature is raised to -20℃ and maintained for 10-14 hours; and the temperature is raised to 25℃-30℃ in the desorption drying stage, and the temperature is maintained for 4-6 hours.

[0020] In a second aspect, the present application provides an antibacterial hemostatic gel patch prepared by any of the above methods, which comprises:

[0021] The inner gel layer is formed by a freeze-dried gel containing 3% w / v cross-linked sodium carboxymethyl cellulose, 2% w / v chitosan and 0.1% w / v polyhexamethylene biguanide, and the surface is a micro-convex arc shape with a radius of curvature of 1 cm, and the thickness is 0.3 mm;

[0022] An intermediate buffer layer formed by a cast film containing 50% w / v medical glycerol and 0.5% w / v sodium hyaluronate, with a thickness of 0.5 mm;

[0023] An outer polyurethane film coated with 0.02% w / v phenol red derivative color developing indicator on the inner side, with a thickness of 0.1 mm;

[0024] Among them, the intermediate buffer layer is combined with the inner gel chitosan shell through hydrogen bonds formed by the hydroxyl groups and the amino groups of the chitosan, and is adhered with the outer polyurethane film through medical acrylate glue.

[0025] In summary, compared with the prior art, the antibacterial hemostatic gel patch and the preparation method thereof provided by the present application have the following beneficial effects:

[0026] (1) Functional synergy, significantly improved efficacy: The present application realizes the synchronization and synergy of hemostasis and antibacterial functions by optimizing the formulation of the inner gel layer. Chitosan aggregates red blood cells to stop bleeding quickly due to its positive charge, and polyhexamethylene biguanide has broad-spectrum and high-efficiency bactericidal effect. The two components synergize at the optimal ratio, avoiding the problems caused by high concentration of a single component, and overcoming the time difference disadvantage of traditional dressings that stop bleeding first and then kill bacteria. The dressing can act on the wound surface immediately, effectively reducing postoperative bleeding and infection rate.

[0027] (2) Structural innovation, precise maintenance of healing environment: The unique three-layer composite structure solves the three core needs of wound care. The micro-convex arc design of the inner layer closely fits the concave shape of the puncture point, significantly increasing the contact area and ensuring uniform action and release of the active ingredients. The combination of glycerol and sodium hyaluronate in the intermediate layer precisely constructs and maintains a moist microenvironment conducive to epidermal regeneration through osmotic pressure balance and biological activity, effectively avoiding the delayed healing caused by dry scabbing of the wound under traditional dressings. The outer medical polyurethane film has excellent water resistance and air permeability, which can block the invasion of external liquid and bacteria, while ensuring gas exchange on the wound surface, avoiding secondary infection caused by dampness and heat.

[0028] (3) Intelligent monitoring, convenient and safe to use: The color developing indicator coated on the inner side of the outer film provides a unique intelligent bleeding feedback function. When bleeding penetrates to the outer layer, the indicator will change color obviously. This mechanism allows medical staff or patients to visually determine the wound condition without removing the dressing, greatly reducing the risk of secondary damage, pain and infection caused by frequent dressing changes, especially suitable for primary hospitals and home care scenarios.

[0029] (4) Strong application targeting, high patient adaptability: The present application is specially designed for the wound characteristics and accompanying symptoms of patients after liver cancer radiofrequency ablation. From the formula, structure to use method, it is adapted to the speciality of the wound and the patient's constitution, showing good clinical adaptability and flexibility.

[0030] (5) Preparation controllable, easy to industrialization: the preparation method of the present application is mature, the parameters are clear, and the reproducibility is good, and it is easy to realize industrial production. The prepared gel patch is small in size, low in cost, and has good market promotion prospect. BRIEF DESCRIPTION OF DRAWINGS

[0031] Other features, objects, and advantages of the present application will become more apparent from the following detailed description of non-limiting embodiments, made with reference to the following drawings:

[0032] Figure 1 is a preparation method flow chart of the antibacterial hemostatic gel patch of the present application;

[0033] Figure 2 is a structural schematic diagram of the antibacterial hemostatic gel patch of the present application.

[0034] The figure legend: 1, inner layer gel, 2, intermediate buffer layer, 3, outer layer polyurethane film. DETAILED DESCRIPTION

[0035] The present application will be further described in detail below in conjunction with the drawings and examples. It can be understood that the specific embodiments described herein are only used to explain the related application, and not to limit the application. In addition, it should be noted that only the parts related to the application are shown in the drawings for ease of description.

[0036] It should be noted that the embodiments in the present application and the features in the embodiments can be combined with each other without conflict. The present application will be described in detail below with reference to the drawings and in conjunction with the embodiments.

[0037] Figure 1 shows a preparation method flow chart of the antibacterial hemostatic gel patch, referring to Figure 1 The preparation method comprises the following steps:

[0038] S1, taking 3% w / v cross-linked sodium carboxymethyl cellulose as a hydrogel matrix carrier, uniformly dispersing 2% w / v chitosan and 0.1% w / v polyhexamethylene biguanide in the hydrogel matrix, injecting into a mold and then performing freeze-drying to form an inner layer gel with a micro-convex arc-shaped surface, and processing the surface of the inner layer gel into a micro-convex arc shape with a curvature radius of 1 cm;

[0039] S2, preparing a mixed solution containing 50% w / v medical glycerol (purity ≥ 99.5%, molecular weight of sodium hyaluronate is 80000-100000 Da) and 0.5% w / v sodium hyaluronate, and flow casting the mixed solution into a film to form an intermediate buffer layer;

[0040] S3, using a medical-grade polyurethane film as a substrate, coating a phenol red derivative (the coating concentration of the phenol red derivative is 0.02% w / v) as a color developing indicator on the inner side of the polyurethane film to form an outer polyurethane film, and the edge of the outer polyurethane film is compounded with a low-sensitization pressure-sensitive adhesive with an adhesive force of 3-5 N / 25 mm;

[0041] S4, the intermediate buffer layer is attached to the inner gel layer to form a hydrogen bond with the amino group through the hydroxyl group, and the intermediate buffer layer is adhered to the outer polyurethane film through a medical acrylic adhesive to obtain a gel patch.

[0042] The thickness of the inner gel layer is 0.3 mm, the thickness of the intermediate buffer layer is 0.5 mm, and the thickness of the outer polyurethane film is 0.1 mm. The degree of deacetylation of chitosan is greater than or equal to 85%, and the molecular weight is 5,000-10,000 Da. The porosity of the medical-grade polyurethane film is 100-200 μm, and the moisture permeability is greater than or equal to 2,000 g / m2·24 h. The freeze-drying conditions are as follows: the pre-freezing temperature is -40 to -50℃, and the temperature is maintained for 2-4 hours; the vacuum degree is less than or equal to 10 Pa in the sublimation drying stage, and the temperature is raised to -20℃ and maintained for 10-14 hours; and the temperature is raised to 25-30℃ in the desorption drying stage, and the temperature is maintained for 4-6 hours.

[0043] Figure 2 The structure of the antibacterial hemostatic gel patch of the present application is shown in the schematic diagram of the antibacterial hemostatic gel patch of the present application, as shown in Figure 2 The antibacterial hemostatic gel patch prepared by the above method comprises:

[0044] The inner gel layer 1 is formed by freeze-drying a gel containing 3% w / v cross-linked sodium carboxymethyl cellulose, 2% w / v chitosan and 0.1% w / v polyhexamethylene biguanide, and the surface is a micro-convex arc with a curvature radius of 1 cm, and the thickness is 0.3 mm.

[0045] The intermediate buffer layer 2 is formed by a cast film containing 50% w / v medical glycerol and 0.5% w / v sodium hyaluronate, and the thickness is 0.5 mm.

[0046] The outer polyurethane film 3 is coated with 0.02% w / v phenol red derivative color developing indicator on the inner side, and the thickness is 0.1 mm.

[0047] The intermediate buffer layer is combined with the inner gel layer chitosan through the hydrogen bond formed by the hydroxyl group and the amino group, and is adhered to the outer polyurethane film through a medical acrylic adhesive.

[0048] The clinical use method of the antibacterial hemostatic gel patch prepared by the present application is as follows:

[0049] (1) After the end of radiofrequency ablation of liver cancer, the puncture needle is removed, and the puncture site is immediately pressed with sterile gauze at a pressure of about 50 mmHg for 5 minutes for primary hemostasis. The bloodstains and disinfectant residues on the skin around the puncture site are wiped clean with a sterile cotton swab, and the skin is ensured to be dry.

[0050] (2) The release paper of the outer polyurethane film of the gel patch of the present application is torn to expose the pressure-sensitive adhesive on the edge. The center of the gel patch (i.e. the microconvex arc surface of the inner gel) is aligned with the puncture site, ensuring that it completely covers the wound and the skin around it by at least 5 mm. The pressure-sensitive adhesive area on the edge of the gel patch is gently pressed with the fingers to ensure that it is tightly attached to the skin, with no air bubbles and no edge lifting.

[0051] (3) The first dressing change is performed 24 hours after the operation. Thereafter, it is changed once a day, and is used continuously for 3 days. For patients with severe hypoproteinemia (serum albumin <25 g / L) and slow wound healing, the use can be extended to 5 days.

[0052] (4) During use, there is no need to remove the dressing, and observation can be directly through the outer polyurethane film. If the outer layer has a dark red colored area with a diameter greater than 5 mm, it indicates that there is more bleeding (about 0.1 mL) from the wound, and the dressing needs to be replaced immediately.

[0053] (5) When replacing the dressing, if the outer layer has not colored, first wet the pressure-sensitive adhesive on the edge of the gel patch with normal saline to reduce its adhesion to about 1 N / 25 mm, and then slowly remove it along the tangential direction of the skin. If the outer layer has colored, a sterile cotton swab should be used to wet and soften the scab at the wound site with normal saline, and then the gel patch is gently removed to avoid damaging the newly formed granulation tissue.

[0054] It should be understood that for allergic individuals, the pressure-sensitive adhesive on the edge of the outer polyurethane film can be replaced with silicone adhesive, thereby reducing the skin allergy rate from 3% to 0.5%.

[0055] Through the above use method, the gel patch can effectively solve the problem of poor blood coagulation and easy bleeding infection after the operation of liver cancer patients. Its color feedback mechanism avoids secondary damage caused by frequent removal for inspection, and is particularly suitable for primary hospitals and home nursing scenarios.

[0056] The antibacterial hemostatic gel patch of the present application realizes excellent effect through the synergistic effect of each layer of functional components: in the inner gel, chitosan binds to the negative charge on the surface of platelet membrane through its positively charged amino group, activates platelet aggregation and promotes the conversion of fibrinogen to fibrin, which can form a hemostatic clot in 3 minutes, and the broad-spectrum antibacterial agent PHMB realizes >99% inhibition rate on common pathogenic bacteria such as Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa by destroying the bacterial cell membrane, and its human cytotoxicity is very low (LD50>5000 mg / kg), forming a translucent hydrogel material closely adhering to the wound surface; the medical glycerol in the middle buffer layer maintains the moist environment of the wound through osmotic pressure balance and promotes the penetration of the inner layer components, and sodium hyaluronate stimulates fibroblast proliferation to accelerate epidermal regeneration; the outer polyurethane film provides physical protection and air permeability, and the phenol red derivative indicator on the inner side changes to dark red when the pH>7.0 blood is encountered, realizing intelligent monitoring of 0.1 mL of bleeding amount, and the three synergistically constitute a complete solution for postoperative care of liver cancer radiofrequency ablation.

[0057] The present application is further described in detail through specific examples below.

[0058] Example 1

[0059] (1) Preparation of the inner gel:

[0060] The cross-linked sodium carboxymethyl cellulose was accurately weighed and dissolved in deionized water to prepare a hydrogel matrix solution with a concentration of 3% w / v. Then, chitosan with a degree of deacetylation ≥85% and a molecular weight of 5000-10000 Da and polyhexamethylene biguanide (PHMB) were accurately weighed according to the mass ratio of 20:1, i.e. added to the above matrix solution at a final concentration of 2% w / v and 0.1% w / v, respectively. A high-speed homogenizer was used to stir and disperse under the condition of 4℃ and light shielding to ensure that the components were uniformly mixed at the nanoscale (distribution deviation ≤5%). The uniformly mixed sol was injected into a specific mold with a micro-convex arc-shaped bottom surface with a curvature radius of 1 cm. Then, freeze-drying was carried out: first, pre-freeze at -50℃ for 4 hours; then, under the condition of vacuum degree ≤10 Pa, the temperature was raised to -20℃ and maintained for 10 hours for sublimation drying; finally, desorption was carried out by increasing the temperature to 30℃ and maintaining for 4 hours. After drying, the mold was removed, and a porous freeze-dried gel inner layer with a thickness of 0.3 mm and a micro-convex arc-shaped surface was obtained. The arc-shaped design is intended to increase the contact area with the depressed wound surface at the puncture point and ensure close adhesion.

[0061] (2) Preparation of the middle buffer layer:

[0062] The medical glycerol with purity ≥ 99.5% and the sodium hyaluronate with molecular weight of 80000-100000 Da were dissolved in deionized water at the concentration of 50% w / v and 0.5% w / v respectively, and mixed to form a uniform solution by stirring. The mixed solution was poured on a flat release film by using a flow casting process, and the gap of the doctor blade was controlled to form a wet film. Then, the wet film was dried and solidified at 40°C to obtain a transparent flow casting film with a thickness of 0.5 mm and rich in moisturizing factors, i.e. the intermediate buffer layer.

[0063] (3) Preparation of the outer polyurethane film:

[0064] The porous film with porosity of 100-200 μm and moisture permeation capacity ≥ 2000 g / m 2 The medical grade polyurethane film with a thickness of 24 h was selected as the substrate. A phenol red derivative was dissolved in a suitable solvent at a concentration of 0.02% w / v, and was uniformly coated on the inner surface of the polyurethane film (i.e. the side in contact with the intermediate layer) by using a precision coating device, and was dried to form a color developing indicator layer. When the phenol red derivative indicator encounters blood with a pH value higher than 7.0 (the normal skin pH value is 4.5-6.0), the conjugated molecular structure of the indicator changes, and the color changes from transparent to dark red, and the color developing sensitivity can reach 0.1 mL of bleeding amount. Subsequently, a low-sensitization acrylate pressure-sensitive adhesive was compounded in the edge area (width of about 2 mm) of the polyurethane film, and the adhesion was controlled to be 3-5 N / 25 mm to ensure firm adhesion to the skin and no edge lifting during use.

[0065] (4) Compound assembly of the gel patch:

[0066] The intermediate buffer layer prepared in step S2 was carefully covered on the inner gel prepared in step S1, and a slight pressure was applied to make the hydroxyl groups in the intermediate buffer layer fully contact with the amino groups of chitosan in the inner gel, so that the stable combination of the two was realized through intermolecular hydrogen bonding. Subsequently, a layer of medical acrylate adhesive with a thickness of less than 0.05 mm was coated on the other side of the intermediate buffer layer, and was precisely aligned and attached to the outer polyurethane film (the side with the indicator facing inwards) prepared in step S3, and a slight pressure was applied to ensure that there was no air bubble between the layers and to solidify, and finally a three-layer composite antibacterial hemostatic gel patch with a total thickness of about 0.9 mm was obtained.

[0067] Example 2

[0068] (1) Preparation of the inner gel:

[0069] Accurately weigh 3.0 g of cross-linked sodium carboxymethyl cellulose, dissolve in 97 mL of deionized water, and magnetically stir until completely swollen to obtain a 3% w / v hydrogel matrix carrier. Accurately weigh 2.0 g of chitosan with a degree of deacetylation of 90% and a molecular weight of 8000 Da, and 0.1 g of polyhexamethylene biguanide, and add them to the above-mentioned matrix in batches at 4°C. Use a high-speed shearing disperser (10000 rpm, 10 min) to uniformly disperse them to obtain a uniform viscous sol. Pour the sol into a specially designed mold with a micro-convex arc-shaped cavity with a diameter of 2 cm and a surface curvature radius of 1 cm. Then, perform programmed freeze-drying: first, pre-freeze at -40°C for 2 hours; then, in a freeze dryer with a vacuum degree of ≤10 Pa, raise the shelf temperature to -20°C and maintain it for 14 hours for sublimation drying; finally, perform analytical drying by raising the temperature to 25°C and maintaining it for 6 hours. After the process is completed, demold to obtain an inner layer gel with a thickness of 0.3 mm, a fluffy structure, and a micro-convex arc-shaped surface.

[0070] (2) Preparation of the intermediate buffer layer:

[0071] Accurately weigh 0.5 g of sodium hyaluronate with a molecular weight of 90000 Da, and slowly add it to the above-mentioned solution, stirring until completely dissolved. Finally, make up to 100 mL to obtain a mixed solution containing 50% w / v glycerol and 0.5% w / v sodium hyaluronate. Use a casting film forming machine to cast the mixed solution onto a flat polyester release film, control the gap between the doctor blade to be 0.5 mm, and dry it in a hot air circulating oven at 40°C for 2 hours. After being removed, a 0.5 mm thick, transparent, and flexible intermediate buffer layer film is obtained.

[0072] (3) Preparation of the outer layer polyurethane film:

[0073] Select a porous polyester film with a porosity of 150 μm and a moisture permeability of 2500 g / m 2 · 24h medical grade polyurethane film (thickness 0.1 mm) as the substrate. Accurately weigh 0.02 g of phenol red derivative, dissolve in 100 mL of ethanol-water mixed solvent, and prepare a 0.02% w / v coating solution. Use a slot coating method to uniformly coat the coating solution on the inner surface of the polyurethane film, with a coating amount of 5 g / m 2 , dry at 50°C for 5 minutes to form a color developing indicator layer. The indicator will develop a color reaction when it comes into contact with blood with a pH > 7.0, and through its conjugated structure change, it will present a dark red color with a color developing sensitivity of 0.1 mL. Then, compound medical acrylic pressure-sensitive adhesive (low sensitization) on the edge (width 2 mm) of the polyurethane film, and its adhesion force is determined to be 4.2 ± 0.3 N / 25 mm.

[0074] (4) Gel patch compounding:

[0075] The intermediate buffer layer is evenly coated on the inner layer gel, and is slightly pressed to be tightly combined through intermolecular forces (hydrogen bonds formed between hydroxyl groups of glycerol in the intermediate buffer layer and amino groups of chitosan in the inner layer gel). Then, a medical acrylate adhesive (for interlayer compounding) with a thickness of less than 0.05 mm is uniformly coated on the other side of the intermediate buffer layer, and the outer layer polyurethane film (the side coated with the color developing agent faces inward) is aligned and attached thereto, and is pressed by a roller pressing device (pressure 0.2 MPa) to ensure that there is no air bubble between the layers, so as to obtain the final three-layer composite antibacterial hemostatic gel patch.

[0076] Example 3: Performance comparison test example

[0077] The gel patches prepared in Example 1 and Example 2 (hereinafter referred to as gel patch 1 and gel patch 2) are subjected to the following performance tests and compared with common products on the market.

[0078] (1) In vitro coagulation performance test:

[0079] Test method: According to the relevant methods in Chinese Pharmacopoeia 2020 edition volume four. Fresh rabbit anticoagulant whole blood is taken, calcium chloride solution is added and recalcified, and then is contacted with gel patch 1, gel patch 2, ordinary sterile gauze and a certain brand of water gel dressing on the market respectively, and is reacted at 37℃ constant temperature. The activated partial thromboplastin time (APTT) and thrombin time (TT) are measured.

[0080] The test results are as follows:

[0081] Test Group APTT (sec) TT (sec) Blank control (whole blood) 35.2±1.5 16.8±0.9 Plain sterile gauze 29.8±1.2 14.5±0.7 Commercially available hydrocolloid dressing 33.5±1.8 15.9±0.8 Gelatex 1 (Example 1) 23.1±0.9 11.8±0.6 Gelatex 2 (Example 2) 22.4±0.8 11.2±0.5

[0082] The shorter the APTT and TT time is, the faster the coagulation speed is. It can be seen from the above data that the coagulation time of the gel patches prepared in the two examples of the application is significantly shorter than that of each group, that is, the gel patches prepared in the application have excellent and stable rapid hemostatic efficiency. The effect of Example 2 is slightly better because some parameters (such as the molecular weight of chitosan 8000 Da) are in a more preferred range.

[0083] (2) In vitro antibacterial performance test:

[0084] Test method: Agar diffusion method (bacteriostatic circle test) is adopted. The bacterial suspension of Staphylococcus aureus (ATCC 6538), Escherichia coli (ATCC 8739) and Pseudomonas aeruginosa (ATCC 9027) is coated on a nutrient agar plate. The gel patch 1, the gel patch 2, the gel patch without PHMB and the 0.1% w / v silver nitrate dressing piece are respectively pasted. After 24 hours of culture at 37℃, the diameter of the bacteriostatic circle is measured.

[0085] The test results are as follows:

[0086]

[0087] It can be seen that the gel patch prepared by the two embodiments of the present application produces obvious inhibition zones for the three common pathogenic bacteria, and the effect is better than that of the 0.1% w / v silver nitrate dressing patch, that is, the gel patch prepared by the present application has broad-spectrum and strong antibacterial effect. The subtle differences in effect are due to the fact that embodiment 2 may have more optimized component dispersity.

[0088] (3) Clinical trial effect statistics:

[0089] Test method: 90 patients after radiofrequency ablation of liver cancer in xx hospital were collected and randomly divided into three groups. Group A used gel patch 1, group B used gel patch 2, and group C used ordinary sterile gauze. Each group had 30 cases. The incidence of bleeding at the puncture point within 24 hours after operation, the number of dressing changes and the patient's pain score (VAS) were recorded.

[0090] The test results are as follows:

[0091]

[0092] It can be seen that the gel patch prepared by the two embodiments of the present application can significantly reduce the incidence of postoperative bleeding and the number of changes, and relieve the pain of patients, and the comprehensive nursing effect is significantly better than that of ordinary sterile gauze. Embodiment 2 performs slightly better because the process parameters are more optimized. The results fully prove the reliability and repeatability of the preparation method of the present application.

[0093] The above description is only the preferred embodiments of the present application and the explanation of the applied technical principles. Those skilled in the art should understand that the scope of the invention involved in the present application is not limited to the technical solutions formed by the specific combination of the above technical features, and should also cover other technical solutions formed by any combination of the above technical features or their equivalent features without departing from the above inventive concept. For example, the above features are replaced with the technical features disclosed in the present application (but not limited to) having similar functions to form technical solutions.

Claims

1. A method for preparing an antibacterial hemostatic gel patch, characterized in that, The method includes the following steps: Using 3% w / v crosslinked sodium carboxymethyl cellulose as the hydrogel matrix carrier, 2% w / v chitosan and 0.1% w / v polyhexamethylene biguanide were uniformly dispersed in the hydrogel matrix, injected into a mold and then freeze-dried to form an inner layer gel with a slightly convex arc-shaped surface. Prepare a mixed solution containing 50% w / v medical glycerin and 0.5% w / v sodium hyaluronate, and cast the mixed solution into a film to form an intermediate buffer layer; Using a medical-grade polyurethane membrane as a substrate, a phenol red derivative is coated on the inner side of the polyurethane membrane as a colorimetric indicator to form an outer polyurethane membrane. The intermediate buffer layer is bonded to the inner gel layer, allowing them to form hydrogen bonds through hydroxyl and amino groups. The intermediate buffer layer is then bonded to the outer polyurethane film using medical acrylate adhesive to obtain a gel patch.

2. The method for preparing the antibacterial hemostatic gel patch according to claim 1, characterized in that, The surface of the inner gel is processed into a slightly convex arc shape with a radius of curvature of 1 cm.

3. The method for preparing the antibacterial hemostatic gel patch according to claim 1, characterized in that, The outer polyurethane film is coated with a low-allergenic pressure-sensitive adhesive at its edge, with an adhesion force of 3-5 N / 25 mm.

4. The method for preparing the antibacterial hemostatic gel patch according to claim 1, characterized in that, The inner gel layer has a thickness of 0.3 mm, the middle buffer layer has a thickness of 0.5 mm, and the outer polyurethane film has a thickness of 0.1 mm.

5. The method for preparing the antibacterial hemostatic gel patch according to claim 1, characterized in that, The degree of deacetylation of the chitosan is ≥85%, and the molecular weight is 5000-10000 Da.

6. The method for preparing the antibacterial hemostatic gel patch according to claim 1, characterized in that, The coating concentration of the phenol red derivative is 0.02% w / v.

7. The method for preparing the antibacterial hemostatic gel patch according to claim 1, characterized in that, The purity of the medical glycerin is ≥99.5%, and the molecular weight of the sodium hyaluronate is 80,000-100,000 Da.

8. The method for preparing the antibacterial hemostatic gel patch according to claim 1, characterized in that, The medical-grade polyurethane membrane has a porosity of 100-200 μm and a moisture permeability ≥2000 g / m³. 2 ·24h.

9. The method for preparing the antibacterial hemostatic gel patch according to claim 1, characterized in that, The freeze-drying conditions are as follows: the pre-freezing temperature is -40℃ to -50℃ and maintained for 2-4 hours; the vacuum degree is ≤10Pa during the sublimation drying stage, and the temperature is raised to -20℃ and maintained for 10-14 hours; the temperature is raised to 25℃-30℃ during the desorption drying stage and maintained for 4-6 hours.

10. An antibacterial hemostatic gel patch prepared by the method according to any one of claims 1-9, characterized in that, The gel patch includes: The inner gel is formed by freeze-dried gel containing 3% w / v crosslinked sodium carboxymethyl cellulose, 2% w / v chitosan and 0.1% w / v polyhexamethylene biguanide. Its surface is a slightly convex arc with a radius of curvature of 1 cm and a thickness of 0.3 mm. The intermediate buffer layer is formed of a cast film containing 50% w / v medical glycerin and 0.5% w / v sodium hyaluronate, with a thickness of 0.5 mm; The outer polyurethane film has a 0.02% w / v phenol red derivative color indicator coated on its inner side, with a thickness of 0.1 mm. The intermediate buffer layer is bonded to the amino groups of the inner gel chitosan by hydrogen bonds through its hydroxyl groups, and is bonded to the outer polyurethane film by medical acrylate adhesive.

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