A material for preventing tissue adhesion and hemostasis and a method for preparing the same

Abstract

The application discloses a material for preventing tissue adhesion and hemostasis and a preparation method thereof, and relates to the technical field of medical biomaterials.The carboxymethyl cellulose, chitosan and vancomycin / ceftazidime are synergistically matched, so that the three functions of hemostasis, adhesion prevention and antibiosis are integrated;meanwhile, the water absorption and gelation of the carboxymethyl cellulose and the blood coagulation activation of the chitosan can jointly strengthen the hemostasis effect; the tissue barrier function of the chitosan and the gel isolation of the carboxymethyl cellulose can jointly improve the adhesion prevention performance; the broad-spectrum antibiosis of the vancomycin and the ceftazidime can respond to the infection risk in different surgical scenes; the material preparation process is simple, the dosage form can be adjusted according to different surgical scenes, the material has good biocompatibility and can be completely degraded, the problem that the existing medical materials have single function and are difficult to meet the needs of complex surgical wounds is solved, and the material has significant clinical application value.

Description

Technical Field

[0001] This invention belongs to the field of medical biomaterials technology, specifically referring to a material for preventing tissue adhesion and hemostasis, and its preparation method. Background Technology

[0002] In surgical clinical practice, the "complication triangle" consisting of postoperative wound bleeding, tissue adhesion, and infection is the core factor leading to decreased surgical efficacy, prolonged hospital stays, and soaring medical costs, which is particularly prominent in thoracic surgery, obstetrics and gynecology, and soft tissue surgery.

[0003] From a clinical perspective, tissue adhesions, the most common surgical complication, are caused by abnormal fibrous tissue proliferation during wound healing. The consequences vary significantly depending on the location of the adhesion: thoracic adhesions after thoracic surgery can lead to restrictive respiratory dysfunction, causing symptoms such as persistent dry cough and shortness of breath on exertion; severe cases require a second surgery to release the adhesions. In gynecological procedures such as cesarean section or myomectomy, intrauterine adhesions and uterine / abdominal wall adhesions can lead to oligomenorrhea, secondary amenorrhea, and even recurrent miscarriages and infertility, with an incidence rate as high as 30%-60% in women with a history of intrauterine procedures. Soft tissue surgery-related tendon and skin adhesions can cause limited limb movement and muscle atrophy, severely impacting the patient's quality of life. Postoperative bleeding and infection not only directly threaten life—statistics show that 50% of deaths during trauma and surgery are caused by acute massive hemorrhage—infection can further promote adhesion formation by exacerbating local inflammation, creating a vicious cycle of "bleeding-infection-adhesion."

[0004] While existing medical materials have made some progress in single-function applications, they struggle to achieve synergistic multi-effect effects. In hemostatic materials, traditional products such as gelatin sponges and hemostatic gauze rely on physical adsorption or activation of coagulation factors to achieve hemostasis, but lack tissue isolation capabilities, resulting in a postoperative adhesion rate exceeding 40%. Sodium hyaluronate hemostatic membranes, while capable of rapid gelation and wound closure, have poor mechanical strength, easily detaching at high-pressure bleeding sites, and lack antibacterial activity. Regarding anti-adhesion materials, synthetic polymers such as polylactic acid membranes and oxidized regenerated cellulose membranes can form physical barriers, but their poor water absorption makes them unable to cope with surgical wound oozing and exudate, and degradation products easily trigger local inflammatory reactions. Even some composite formulations attempting to integrate hemostasis and anti-adhesion functions, such as chitosan-gelatin composite membranes, rely solely on the cationic antibacterial effect of chitosan for their antibacterial ability, proving ineffective against common clinically resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) and ESBL-producing Escherichia coli. Infections by these resistant bacteria have already led to a postoperative wound healing delay rate of up to 27%.

[0005] Carboxymethyl cellulose, as a natural polysaccharide derivative, possesses excellent water solubility and water absorption and swelling properties, with a water absorption and swelling rate reaching 20-30 times its own weight. It can quickly form a gel layer on the wound surface, closing the vascular ends through physical compression. Chitosan, with its cationic polysaccharide properties, can both activate coagulation factor XII to initiate the intrinsic coagulation pathway and form a dense barrier on the tissue surface, hindering fibroblast migration and collagen deposition, thus inhibiting adhesion formation mechanistically. The combination of these two has become a research hotspot for hemostatic and anti-adhesion materials, but existing compound systems have significant shortcomings: First, the antibacterial spectrum is narrow, only inhibiting mild bacterial flora and unable to cope with mixed infections in complex surgical wounds; second, the material form is limited, mostly in the form of films, making it difficult to adapt to the diverse needs of curved thoracic surgical wounds, obstetric and gynecological cavity wounds, and irregular soft tissue wounds; third, the gel stability is insufficient, easily dissolving and being lost in environments with large amounts of exudate, resulting in a shorter functional duration than during the critical period of wound healing.

[0006] The introduction of antibiotics has provided a solution to the antibacterial challenge: vancomycin, a glycopeptide antibiotic, has a bactericidal rate of over 98% against Gram-positive bacteria; gentamicin, an aminoglycoside antibiotic, has an inhibition rate of over 90% against Gram-negative bacteria. Combining the two can achieve broad-spectrum antibacterial coverage. However, simply mixing antibiotics with biomaterials can easily lead to drug burst release, causing not only a sudden increase in local drug concentration leading to toxic reactions, but also the proliferation of drug-resistant bacteria due to insufficient drug concentration in the later stages. Therefore, how to construct composite biomaterials with synergistic functions of hemostasis, anti-adhesion, and antibacterial action, controllable drug release, and morphology adaptable to various scenarios has become the key to overcoming existing technological bottlenecks. Summary of the Invention

[0007] The purpose of this invention is to provide a material for preventing tissue adhesion and hemostasis, and its preparation method. This invention achieves the integration of three major functions—hemostasis, anti-adhesion, and antibacterial—through the synergistic combination of carboxymethyl cellulose, chitosan, and vancomycin / gentamicin. Simultaneously, the water-absorbing gelation effect of carboxymethyl cellulose and the coagulation-activating effect of chitosan jointly enhance the hemostatic effect; the tissue barrier function of chitosan and the gelation isolation effect of carboxymethyl cellulose synergistically improve the anti-adhesion performance; the broad-spectrum antibacterial effects of vancomycin and gentamicin can specifically address the infection risks in different surgical scenarios. The material preparation process of this invention is simple, the dosage form can be adjusted according to different surgical scenarios, it has good biocompatibility and is completely degradable, solving the problem of existing medical materials having limited functionality and failing to meet the needs of complex surgical wounds, and has significant clinical application value.

[0008] To achieve the above objectives, the technical solution adopted by the present invention is as follows: a material for preventing tissue adhesion and hemostasis and its preparation method, wherein the material for preventing tissue adhesion and hemostasis comprises the following components in parts by weight: 30%~60% carboxymethyl cellulose; 10%~50% chitosan; 2%~20% antibiotics; and 2%~20% excipients.

[0009] Preferably, the material for preventing tissue adhesion and stopping bleeding comprises the following components in parts by weight: 30%~40% carboxymethyl cellulose; 20%~40% chitosan; 5%~10% antibiotics; and 5%~15% excipients.

[0010] Preferably, the degree of substitution of the carboxymethyl cellulose is 0.9-1.1.

[0011] Preferably, the degree of deacetylation of the chitosan is greater than or equal to 90%.

[0012] Preferably, the antibiotic includes one or more of vancomycin and gentamicin.

[0013] Preferably, the excipients consist of plasticizers, pH adjusters, and deionized water.

[0014] Preferably, the plasticizer comprises one or more of glycerol, polyethylene glycol, propylene glycol, and sorbitol.

[0015] Preferably, the pH adjuster includes one or more of citric acid, lactic acid, and acetic acid.

[0016] The present invention also provides a method for preparing a material for preventing tissue adhesion and stopping bleeding, the preparation method comprising the following steps: (1) Pretreatment: Place carboxymethyl cellulose in a vacuum drying oven at 60-70℃ and dry for 4-6 hours to remove moisture; dissolve chitosan in 1%-2% acetic acid solution and stir until completely dissolved to form a chitosan solution with a mass concentration of 5%-10% for later use; (2) Preparation of antibiotic solution: Take the prescribed amount of vancomycin or gentamicin, add deionized water, and sonicate to dissolve it at a power of 300-500W for 5-10 minutes to form an antibiotic solution with a mass concentration of 10%-20% for later use. (3) Preparation of composite gel: Add the pretreated carboxymethyl cellulose to the chitosan solution and stir at 300-500 r / min for 30-60 min under constant temperature water bath conditions of 30-40℃ to form a uniform CMC-CS mixture; then slowly add antibiotic solution, continue stirring for 20-30 min, then add glycerol and citric acid, adjust the pH to 6.5-7.5, and stir until the mixture is a transparent gel. (4) Molding and drying: Pour the composite gel into a mold and freeze-dry it at -40 to -30°C for 12-24 hours to remove the solvent and obtain the dried composite material. Finally, aseptically package it to obtain the finished product. It can be designed as a film, sponge or granules according to the surgical scenario: film for thoracic surgery with a thickness of 0.1-0.2 mm; sponge for obstetrics and gynecology surgery with a pore size of 50-100 μm; and granules for soft tissue surgery with a particle size of 0.5-1 mm.

[0017] The beneficial effects of the present invention using the above structure are as follows: (1) The present invention achieves the integration of three major functions of "hemostasis-anti-adhesion-antibacterial" through the synergistic combination of carboxymethyl cellulose, chitosan and vancomycin / gentamicin; (2) The water-absorbing gelation effect of carboxymethyl cellulose and the coagulation activation effect of chitosan in the present invention jointly enhance the hemostatic effect; the tissue barrier function of chitosan and the gel isolation effect of carboxymethyl cellulose synergistically improve the anti-adhesion performance; the broad-spectrum antibacterial effect of vancomycin and gentamicin can specifically address the infection risk of different surgical scenarios; (3) The material preparation process of the present invention is simple, the dosage form can be adjusted according to different surgical scenarios, it has good biocompatibility and can be completely degraded, solving the problem that existing medical materials have single function and are difficult to meet the needs of complex surgical wounds, and has significant clinical application value. Attached Figure Description

[0018] Figure 1 The hemostatic time of a material for preventing tissue adhesion and stopping bleeding.

[0019] The accompanying drawings are provided to further illustrate the invention and form part of the specification. They are used together with the embodiments of the invention to explain the invention and do not constitute a limitation thereof. Detailed Implementation

[0020] The technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings of the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0021] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those familiar to those skilled in the art. Furthermore, any methods and materials similar to or equivalent to those described herein may be applied to this invention. The preferred embodiments and materials described herein are for illustrative purposes only and do not limit the scope of this application.

[0022] Unless otherwise specified, the experimental methods used in the following examples are conventional methods; unless otherwise specified, the experimental materials and test strains used in the following examples were purchased from commercial channels. Example

[0023] A material for preventing tissue adhesion and hemostasis and its preparation method The material for preventing tissue adhesion and stopping bleeding comprises the following components in parts by weight: 30% carboxymethyl cellulose; 40% chitosan; 5% antibiotics; and 15% excipients.

[0024] The degree of substitution of the carboxymethyl cellulose is 0.9-1.1; the degree of deacetylation of the chitosan is greater than or equal to 90%; the antibiotic is vancomycin; the excipients consist of a plasticizer, a pH adjuster, and deionized water; the plasticizer is glycerol; and the pH adjuster is citric acid.

[0025] The present invention also provides a method for preparing a material for preventing tissue adhesion and stopping bleeding, the preparation method comprising the following steps: (1) Pretreatment: Place carboxymethyl cellulose in a vacuum drying oven at 60-70℃ and dry for 4-6 hours to remove moisture; dissolve chitosan in 1%-2% acetic acid solution and stir until completely dissolved to form a chitosan solution with a mass concentration of 5%-10% for later use; (2) Preparation of antibiotic solution: Take the prescribed amount of vancomycin or gentamicin, add deionized water, and sonicate to dissolve it at a power of 300-500W for 5-10 minutes to form an antibiotic solution with a mass concentration of 10%-20% for later use. (3) Preparation of composite gel: Add the pretreated carboxymethyl cellulose to the chitosan solution and stir at 300-500 r / min for 30-60 min under constant temperature water bath conditions of 30-40℃ to form a uniform CMC-CS mixture; then slowly add antibiotic solution, continue stirring for 20-30 min, then add glycerol and citric acid, adjust the pH to 6.5-7.5, and stir until the mixture is a transparent gel. (4) Molding and drying: Pour the composite gel into a mold and freeze-dry it at -40 to -30°C for 12-24 hours to remove the solvent and obtain the dried composite material. Finally, aseptically package it to obtain the finished product. It can be designed as a film, sponge or granules according to the surgical scenario: film for thoracic surgery with a thickness of 0.1-0.2 mm; sponge for obstetrics and gynecology surgery with a pore size of 50-100 μm; and granules for soft tissue surgery with a particle size of 0.5-1 mm. Example

[0026] A material for preventing tissue adhesion and hemostasis and its preparation method The material for preventing tissue adhesion and stopping bleeding comprises the following components in parts by weight: 40% carboxymethyl cellulose; 20% chitosan; 10% antibiotics; and 5% excipients.

[0027] The degree of substitution of the carboxymethyl cellulose is 0.9-1.1; the degree of deacetylation of the chitosan is greater than or equal to 90%; the antibiotic is vancomycin; the excipients consist of a plasticizer, a pH adjuster, and deionized water; the plasticizer is glycerol; and the pH adjuster is citric acid.

[0028] The present invention also provides a method for preparing a material for preventing tissue adhesion and stopping bleeding, wherein the preparation method is performed in accordance with Example 1. Example

[0029] A material for preventing tissue adhesion and hemostasis and its preparation method The material for preventing tissue adhesion and stopping bleeding comprises the following components in parts by weight: 35% carboxymethyl cellulose; 30% chitosan; 8% antibiotics; and 10% excipients.

[0030] The degree of substitution of the carboxymethyl cellulose is 0.9-1.1; the degree of deacetylation of the chitosan is greater than or equal to 90%; the antibiotic is vancomycin; the excipients consist of a plasticizer, a pH adjuster, and deionized water; the plasticizer is glycerol; and the pH adjuster is citric acid.

[0031] The present invention also provides a method for preparing a material for preventing tissue adhesion and stopping bleeding, wherein the preparation method is performed in accordance with Example 1.

[0032] Experimental Example 1 The Influence of a Preparation Method of a Material for Hemostasis that Prevents Tissue Adhesion on Hemostatic Efficacy The materials for preventing tissue adhesion and stopping bleeding prepared in Examples 1-3 of this invention were used as experimental materials and divided into Example 1 group, Example 2 group, Example 3 group, and control group, with the control group using traditional gelatin hemostatic sponge. Eighty healthy SD rats weighing 200-250g were randomly divided into 4 groups. A rat liver puncture bleeding model was established, and the wound was covered with the four materials respectively, and the average hemostasis time was recorded.

[0033] Results analysis: such as Figure 1 As shown, the hemostasis time of groups 1-3 in Examples 1 to 3 was much shorter than that of the control group, with group 3 in Example 3 having the shortest hemostasis time.

[0034] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

[0035] The present invention and its embodiments have been described above. This description is not restrictive, and the accompanying drawings are only one embodiment of the present invention; the actual structure is not limited thereto. In conclusion, if those skilled in the art are inspired by this description and design similar structures and embodiments without departing from the spirit of the invention, such designs should fall within the protection scope of the present invention.

Claims

1. A material for preventing tissue adhesion and stopping bleeding, characterized in that: The material for preventing tissue adhesion and stopping bleeding comprises the following components in parts by weight: 30%~60% carboxymethyl cellulose; 10%~50% chitosan; 2%~20% antibiotics; and 2%~20% excipients.

2. The material for preventing tissue adhesion and stopping bleeding according to claim 1, characterized in that: The material for preventing tissue adhesion and stopping bleeding comprises the following components in parts by weight: 30%~40% carboxymethyl cellulose; 20%~40% chitosan; 5%~10% antibiotics; and 5%~15% excipients.

3. The material for preventing tissue adhesion and stopping bleeding according to claim 2, characterized in that: The degree of substitution of the carboxymethyl cellulose is 0.9-1.

1.

4. The material for preventing tissue adhesion and stopping bleeding according to claim 3, characterized in that: The degree of deacetylation of the chitosan is greater than or equal to 90%.

5. The material for preventing tissue adhesion and stopping bleeding according to claim 4, characterized in that: The antibiotics include one or more of vancomycin and gentamicin.

6. The material for preventing tissue adhesion and stopping bleeding according to claim 5, characterized in that: The excipients consist of plasticizers, pH adjusters, and deionized water.

7. The material for preventing tissue adhesion and stopping bleeding according to claim 6, characterized in that: The plasticizer comprises one or more of glycerol, polyethylene glycol, propylene glycol, and sorbitol.

8. The material for preventing tissue adhesion and stopping bleeding according to claim 7, characterized in that: The pH adjuster includes one or more of citric acid, lactic acid, and acetic acid.

9. A method for preparing a material for preventing tissue adhesion and stopping bleeding according to claim 8, characterized in that: The preparation method includes the following steps: (1) Pretreatment: Place carboxymethyl cellulose in a vacuum drying oven at 60-70℃ and dry for 4-6 hours to remove moisture; dissolve chitosan in 1%-2% acetic acid solution and stir until completely dissolved to form a chitosan solution with a mass concentration of 5%-10% for later use; (2) Preparation of antibiotic solution: Take the prescribed amount of vancomycin or gentamicin, add deionized water, and sonicate to dissolve it at a power of 300-500W for 5-10 minutes to form an antibiotic solution with a mass concentration of 10%-20% for later use. (3) Preparation of composite gel: Add the pretreated carboxymethyl cellulose to the chitosan solution and stir at 300-500 r / min for 30-60 min under constant temperature water bath conditions of 30-40℃ to form a uniform CMC-CS mixture; then slowly add antibiotic solution, continue stirring for 20-30 min, then add glycerol and citric acid, adjust the pH to 6.5-7.5, and stir until the mixture is a transparent gel. (4) Molding and drying: Pour the composite gel into a mold and freeze-dry it at -40 to -30°C for 12-24 hours to remove the solvent and obtain the dried composite material. Finally, aseptically package it to obtain the finished product. It can be designed as a film, sponge or granules according to the surgical scenario: film for thoracic surgery with a thickness of 0.1-0.2 mm; sponge for obstetrics and gynecology surgery with a pore size of 50-100 μm; and granules for soft tissue surgery with a particle size of 0.5-1 mm.

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