Antibacterial fiber wound suture containing cannabidiol and preparation method

Abstract

The invention provides an antibacterial fiber wound suture containing cannabidiol and a preparation method. According to the wound suture line, degradable antibacterial fibers serve as a base material, the antibacterial fibers are subjected to graft modification through cationic reagents such as quaternary ammonium salt, and positive charge sites are introduced to the surfaces of the fibers. Cannabidiol is mixed with polyethylene glycol, glycerin and the like, so that the polarity of cannabidiol is improved. Then, the cannabidiol is preliminarily attached to the antibacterial fibers through electrostatic adsorption, and then the antibacterial fibers are baked at the temperature of 40-60 DEG C for 10-15 min. According to the method, cannabidiol can be stably attached to the antibacterial fibers, so that the wound suture line with a stable drug effect is formed. The wound suture line is suitable for surgical suture, in the wound healing process of the suture line, the antibacterial fiber prevents infection, cannabidiol can relieve inflammation and pain, promote wound healing and reduce pain when the suture line is removed, and the wound suture line can be used for general surgery, obstetrics and gynecology and other surgeries.

Description

Technical Field

[0001] This invention belongs to the field of wound suture technology, specifically relating to an antibacterial fiber wound suture containing cannabidiol and its preparation method. Background Technology

[0002] Currently, clinically used wound sutures are mainly divided into two categories: non-degradable (such as silk sutures and nylon sutures) and degradable (such as catgut sutures and polylactic acid synthetic fiber sutures). Degradable sutures, due to their advantages such as eliminating the need for secondary suture removal and reducing patient discomfort, are increasingly widely used in departments such as general surgery and obstetrics and gynecology. To reduce the risk of postoperative infection, some degradable sutures use antibacterial fiber substrates or are coated with antibacterial agents; however, existing antibacterial sutures still require further improvement. Summary of the Invention

[0003] The purpose of this invention is to provide a method for preparing a biodegradable wound suture that combines antibacterial fibers with cannabidiol in a stable manner, and has long-lasting antibacterial, active anti-inflammatory, and healing-promoting effects.

[0004] A method for preparing an antibacterial fiber wound suture containing cannabidiol, comprising the following steps: S1: Antibacterial fiber substrate pretreatment: Degradable antibacterial fibers are ultrasonically cleaned with anhydrous ethanol and vacuum dried for later use; S2: Cationic grafting modification: The pretreated antibacterial fiber is immersed in a quaternary ammonium salt solution and reacted in a constant temperature water bath at 45-55℃ for 1.5-2.5h. After rinsing and drying, modified antibacterial fiber with positively charged sites on the surface is obtained. S3: Cannabidiol polarity adjustment: Mix cannabidiol, polyethylene glycol and glycerin at a mass ratio of 1:(2-4):(1-2) and stir at 35-45℃ for 30-40 min to obtain a cannabidiol mixture; S4: Electrostatic adsorption and low-temperature curing: The modified antibacterial fiber is placed in an electrostatic adsorption device, and under the conditions of 15-25kV voltage and 8-12cm distance, a cannabidiol mixture is sprayed and adsorbed for 20-30min. Then, it is baked at 40-60℃ for 10-15min to obtain antibacterial fiber wound suture containing cannabidiol.

[0005] Optionally, the biodegradable antibacterial fiber in S1 is a polycaprolactone-chitosan composite fiber, wherein the chitosan accounts for 10%-15% of the mass of the polycaprolactone-chitosan composite fiber.

[0006] Optionally, the quaternary ammonium salt solution in S2 is a 3-chloro-2-hydroxypropyltrimethylammonium chloride solution with a mass concentration of 5%-8%.

[0007] Optionally, during the constant temperature water bath reaction in S2, the stirring rate is 200-300 r / min.

[0008] Optionally, the molecular weight of the polyethylene glycol in S3 is 400-600.

[0009] Optionally, the spraying rate of the electrostatic adsorption device in S4 is 0.5-1 mL / min.

[0010] Optionally, the baking temperature in S4 is 50-55℃ and the baking time is 12-14 minutes.

[0011] Optionally, the ultrasonic cleaning power in S1 is 300-400W, and the cleaning time is 12-14min.

[0012] Optionally, the drying temperature after rinsing in S2 is 55-60℃, and the drying time is 1.5-2h.

[0013] An antibacterial fiber wound suture containing cannabidiol was prepared by the above-described method.

[0014] Beneficial effects In this invention, a comprehensive approach involving pretreatment, modification, polarity adjustment, and adsorption curing is used to achieve a stable combination of antibacterial fibers and cannabidiol. The resulting sutures possess long-lasting antibacterial, active anti-inflammatory, and biodegradable properties, making them suitable for multidisciplinary surgical procedures. Detailed Implementation

[0015] Existing antibacterial sutures have the following shortcomings: (1) Insufficient antibacterial durability. Antibacterial components are mostly applied through physical coating and are easily detached during body fluid immersion and tissue healing, leading to an increased risk of infection in the middle and late stages after surgery.

[0016] (2) Poor inflammation control, local inflammatory reactions are likely to occur during the postoperative wound healing process. Existing sutures lack active anti-inflammatory mechanisms and require the use of topical or oral anti-inflammatory drugs, which increases the complexity of treatment.

[0017] (3) Cannabidiol (CBD) loading is difficult. CBD has excellent anti-inflammatory, analgesic and tissue repair effects, but because of its strong lipid solubility and low polarity, it is difficult to stably attach to the fiber surface. In addition, conventional loading methods can easily lead to CBD inactivation and cannot achieve long-term drug release.

[0018] (4) The compatibility of the preparation process is poor. Existing processes that combine functional components with antibacterial fibers (such as high-temperature melting and chemical cross-linking) either destroy the degradation performance of antibacterial fibers or cause the functional components to decompose, making it difficult to achieve the synergistic effect of antibacterial, anti-inflammatory and degradation.

[0019] Based on this, the present invention provides a method for preparing an antibacterial fiber wound suture containing cannabidiol, comprising the following steps: S1: Antibacterial fiber substrate pretreatment: The biodegradable antibacterial fiber is ultrasonically cleaned with anhydrous ethanol and vacuum dried for later use.

[0020] S2: Cationic grafting modification: The pretreated antibacterial fiber is immersed in a quaternary ammonium salt solution and reacted in a constant temperature water bath at 45-55℃ for 1.5-2.5h. After rinsing and drying, modified antibacterial fiber with positively charged sites on the surface is obtained.

[0021] S3: Cannabidiol polarity adjustment: Mix cannabidiol, polyethylene glycol and glycerin at a mass ratio of 1:(2-4):(1-2) and stir at 35-45℃ for 30-40 min to obtain a cannabidiol mixture.

[0022] S4: Electrostatic adsorption and low-temperature curing: The modified antibacterial fiber is placed in an electrostatic adsorption device, and under the conditions of 15-25kV voltage and 8-12cm distance, a cannabidiol mixture is sprayed and adsorbed for 20-30min. Then, it is baked at 40-60℃ for 10-15min to obtain antibacterial fiber wound suture containing cannabidiol.

[0023] In the above embodiments, a comprehensive approach involving pretreatment, modification, polarity adjustment, and adsorption curing is used to achieve a stable combination of antibacterial fibers and cannabidiol. The resulting sutures possess long-lasting antibacterial, active anti-inflammatory, and biodegradable properties, making them suitable for multidisciplinary surgical procedures.

[0024] In this process, quaternary ammonium salt cation grafting modification creates chemically bonded positively charged sites on the surface of the antibacterial fibers, rather than physical coating. These positively charged sites can interact with the negatively charged bacterial cell membranes for a long time, providing a stable basis for cannabidiol (CBD) adhesion and solving the problem of easy detachment of antibacterial components. CBD is introduced as an active anti-inflammatory component, which can exert its anti-inflammatory effect by regulating the secretion of inflammatory factors (such as IL-6 and TNF-α), overcoming the deficiency of existing sutures that only provide antibacterial properties but not anti-inflammatory effects. The polarity of CBD is enhanced by mixing polyethylene glycol and glycerin, allowing it to form electrostatic adsorption with the positively charged sites on the modified antibacterial fiber surface. Low-temperature baking (40-60℃) prevents thermal decomposition of CBD, achieving stable loading and long-lasting release. The entire process is controlled at temperatures below 60℃ to avoid damaging the biodegradable structure of the antibacterial fibers; electrostatic adsorption rather than chemical cross-linking is used to avoid the irritation of tissues by residual chemical reagents, balancing process gentleness and functional stability.

[0025] In some embodiments, the biodegradable antibacterial fiber in S1 is a polycaprolactone-chitosan composite fiber, wherein chitosan accounts for 10%-15% of the mass of the polycaprolactone-chitosan composite fiber. In this case, by defining specific antibacterial fiber substrates and chitosan content, the degradation rate of the fiber (degradation cycle 15-20 days) can be matched with the wound healing cycle (10-18 days). Simultaneously, chitosan itself possesses natural antibacterial properties, forming a dual antibacterial effect with quaternary ammonium salt modification, thereby enhancing antibacterial durability.

[0026] In some embodiments, the quaternary ammonium salt solution in S2 is a 5%-8% (w / w) solution of 3-chloro-2-hydroxypropyltrimethylammonium chloride. The cationic active groups of 3-chloro-2-hydroxypropyltrimethylammonium chloride have a strong affinity for the hydroxyl groups on the surface of antibacterial fibers, resulting in high grafting efficiency. Furthermore, this quaternary ammonium salt exhibits good biocompatibility, is non-cytotoxic, and avoids irritation to wound tissue.

[0027] In some embodiments, during the constant-temperature water bath reaction in S2, the stirring rate is 200-300 r / min. This specific stirring rate ensures sufficient contact between the antibacterial fibers and the quaternary ammonium salt solution, avoiding uneven surface charge distribution caused by localized reactions, ensuring uniform density of positive charge sites on the surface of each fiber, and improving the uniformity of subsequent cannabidiol loading.

[0028] In some embodiments, the molecular weight of polyethylene glycol in S3 is 400-600. Polyethylene glycol in this molecular weight range is both hydrophilic and lipophilic, effectively improving the dispersibility of cannabidiol in aqueous solutions. Simultaneously, it works synergistically with glycerol to improve the spreadability of the cannabidiol mixture on the fiber surface, preventing agglomeration during loading.

[0029] In some embodiments, the spraying rate of the electrostatic adsorption device in S4 is 0.5-1 mL / min. This spraying rate can control the loading amount of the cannabidiol mixture on the fiber surface, avoiding insufficient anti-inflammatory effect due to too low a loading amount, or adhesion of the fiber surface and affecting the suturing operation due to too high a loading amount.

[0030] In some embodiments, the baking temperature in S4 is 50-55°C, and the baking time is 12-14 minutes. This temperature and time range can promote the stable binding of cannabidiol to the positively charged sites on the fiber surface without thermally decomposing cannabidiol. For example, it can increase the binding strength by 40%-50% and ensure that the cannabidiol release rate remains stable at 60%-70% within 7 days after the procedure.

[0031] In some embodiments, the ultrasonic cleaning power in S1 is 300-400W, and the cleaning time is 12-14 minutes. These ultrasonic parameters can effectively remove residual impurities on the surface of antibacterial fibers, avoid impurities affecting the efficiency of subsequent cation grafting reactions, and at the same time, do not damage the microstructure of the fibers.

[0032] In some embodiments, the drying temperature after rinsing in S2 is 55-60°C, and the drying time is 1.5-2 hours. These drying parameters can quickly remove residual moisture from the fiber surface, prevent moisture from affecting the stability of the quaternary ammonium salt grafted groups, and prevent fiber embrittlement caused by high temperature.

[0033] Another embodiment of the present invention provides an antibacterial fiber wound suture containing cannabidiol, which is prepared by the above-described preparation method. This wound suture simultaneously possesses long-lasting antibacterial properties (bacteriostatic rate ≥90%, lasting for more than 10 days), active anti-inflammatory effects (reducing inflammatory factor content by 40%-50% 3 days post-surgery), and promotes healing (shortening healing time by 20%-30%).

[0034] The following are examples and comparative examples.

[0035] Example 1 The method for preparing the wound suture in this embodiment includes the following steps: S1: Antibacterial Fiber Substrate Pretreatment: The biodegradable antibacterial fiber is ultrasonically cleaned with anhydrous ethanol and vacuum dried for later use. The biodegradable antibacterial fiber is a polycaprolactone-chitosan composite fiber, with chitosan accounting for 12% of the mass of the polycaprolactone-chitosan composite fiber. The ultrasonic cleaning power is 350W, and the cleaning time is 12 minutes.

[0036] S2: Cationic Grafting Modification: Pretreated antibacterial fibers were immersed in a quaternary ammonium salt solution and reacted in a constant temperature water bath at 50℃ for 2 hours. After rinsing and drying, modified antibacterial fibers with positively charged sites on the surface were obtained. The quaternary ammonium salt solution was a 5% (w / w) solution of 3-chloro-2-hydroxypropyltrimethylammonium chloride. During the constant temperature water bath reaction, the stirring rate was 200 r / min. After rinsing, the drying temperature was 55℃, and the drying time was 1.5 hours.

[0037] S3: Cannabidiol polarity adjustment: Cannabidiol, polyethylene glycol, and glycerin were mixed at a mass ratio of 1:3:1.5 and stirred at 40°C for 35 minutes to obtain a cannabidiol mixture. The molecular weight of polyethylene glycol was 400.

[0038] S4: Electrostatic Adsorption and Low-Temperature Curing: Modified antibacterial fibers were placed in an electrostatic adsorption device. Under conditions of 20kV voltage and 10cm distance, a cannabidiol mixture was sprayed and adsorbed for 25min. Subsequently, it was baked at 50℃ for 13min to obtain antibacterial fiber wound sutures containing cannabidiol. The spraying rate of the electrostatic adsorption device was 0.8mL / min.

[0039] The preparation methods of the wound sutures in other embodiments and comparative examples are similar to those in Example 1.

[0040] The main parameters in the preparation methods of wound sutures in Examples 1-5 are as follows.

[0041]

[0042] Comparative Example 1 The difference compared to Example 1 is that S2 is not performed, i.e., no cation grafting modification is performed.

[0043] Comparative Example 2 The difference from Example 1 is that S3 is not performed and cannabidiol is not added to the wound suture.

[0044] Comparative Example 3 The difference compared to Example 1 is that the baking temperature in S4 is 70°C.

[0045] Test case (1) Antibacterial properties The sutures from each embodiment and comparative example were cut into 1cm long segments and placed in bacterial solution for shaking incubation at 37°C. Samples were taken after 1, 7, and 10 days of incubation, and the inhibition rate was calculated using the plate count method. The inhibition rate was calculated as follows: inhibition rate = (number of colonies in the blank group - number of colonies in the experimental group) / number of colonies in the blank group × 100%. The test results are as follows.

[0046]

[0047] Examples 1-5 maintained an inhibition rate of approximately 90% against both bacteria for 10 days, with Example 3 showing the best antibacterial effect. Comparative Example 1 (without cationic modification) showed a significantly reduced inhibition rate to below 65% after 7 days due to the easy shedding of antibacterial components. Comparative Example 2 (without cannabidiol) exhibited antibacterial effects, but its inhibition rate was lower than that of the examples after 10 days due to the lack of synergistic anti-inflammatory effects of cannabidiol. Comparative Example 3 (high-temperature baking) showed slightly less durable antibacterial activity than the examples due to the decomposition of some quaternary ammonium salt groups.

[0048] (2) Cannabidiol loading and release performance test Initial loading: High performance liquid chromatography (HPLC) was used with a C18 column (250 mm × 4.6 mm, 5 μm), a mobile phase of methanol-water (85:15, v / v), and a detection wavelength of 280 nm. The suture was cut into small pieces and extracted with methanol by ultrasonication for 30 min. The concentration of cannabidiol in the extract was determined, and the initial loading was calculated based on the suture mass.

[0049] Release rate on day 7 postoperatively: The suture was placed in simulated body fluid (PBS buffer, pH=7.4) and oscillated at 37°C. Samples were taken on day 7, and the cannabidiol content in the released fluid was determined by the above HPLC method. Release rate = release amount / initial loading amount × 100%.

[0050] Binding fastness: Referring to GB / T3921-2008 Textiles - Tests for color fastness to washing, the suture was rubbed in PBS buffer at 40℃ for 30 min (rubbing rate 60 times / min). The residual cannabidiol content after rubbing was then measured. Binding fastness = residual amount after rubbing / initial loading amount × 100%. The results are as follows.

[0051]

[0052] The initial loading of Examples 1-5 was all above 5.5 mg / g, and the release rate remained stable at 60%-70% after 7 days, with a binding strength exceeding 84%, indicating that cannabidiol can be stably loaded and slowly released through cationic modification and low-temperature baking. Comparative Example 1 (without cationic modification) lacked electrostatic adsorption, resulting in a low initial loading, poor binding strength, and a release rate of only 32.5% after 7 days. Comparative Example 3 (high-temperature baking) showed lower initial loading and release stability than the Examples due to partial decomposition of cannabidiol.

[0053] (3) Antibacterial properties SPF-grade BALB / c mice (weighing 20-22g) were selected. A 1cm × 1cm full-thickness skin defect was created on the back of each mouse, and the wound was sutured using the sutures specified in the respective examples and comparative examples. Three days post-surgery, the mice were sacrificed, and 0.5cm of tissue around the wound was harvested. The levels of IL-6 and TNF-α in the tissue were detected using enzyme-linked immunosorbent assay (ELISA). The kit was purchased from Beijing Zhongshan Jinqiao Biotechnology Co., Ltd., and the procedure was strictly performed according to the kit instructions. The results are as follows.

[0054]

[0055] In Examples 1-5, the levels of IL-6 and TNF-α in the wound tissue were significantly lower than in the comparative examples, with Example 3 showing the lowest level of inflammatory factors, indicating that cannabidiol can effectively inhibit the inflammatory response. Comparative Example 2 (without cannabidiol) had a high level of inflammatory factors due to the lack of anti-inflammatory components. Although Comparative Examples 1 and 3 contained cannabidiol, their anti-inflammatory effects were weaker than those of the examples due to unstable loading or partial inactivation.

[0056] (4) Healing performance Using the aforementioned mouse wound model, wound healing was observed daily. Wound images were taken with a digital camera, and the wound healing area was calculated using ImageJ software. The time to complete epithelialization (no redness, swelling, or exudation, and complete epidermal coverage) was defined as the healing time. Ten mice were tested in each group, and the average value was taken. The results are as follows.

[0057]

[0058] The wound healing time for Examples 1-5 was within 14 days, with Example 3 showing the fastest healing speed. Comparative Examples 1-3, due to insufficient antibacterial and anti-inflammatory effects, had significantly prolonged healing times, with Comparative Example 2 (without cannabidiol) showing the longest healing time. This indicates that the synergistic effect of cannabidiol and antibacterial fibers can effectively promote wound healing.

[0059] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

[0060] For those skilled in the art, based on the ideas of this invention, there will be changes in the specific implementation methods and application scope. Therefore, the content of this specification should not be construed as a limitation of this invention.

Claims

1. A method for preparing an antibacterial fiber wound suture containing cannabidiol, characterized in that, Includes the following steps: S1: Antibacterial fiber substrate pretreatment: Degradable antibacterial fibers are ultrasonically cleaned with anhydrous ethanol and vacuum dried for later use; S2: Cationic grafting modification: The pretreated antibacterial fiber is immersed in a quaternary ammonium salt solution and reacted in a constant temperature water bath at 45-55℃ for 1.5-2.5h. After rinsing and drying, modified antibacterial fiber with positively charged sites on the surface is obtained. S3: Cannabidiol polarity adjustment: Mix cannabidiol, polyethylene glycol and glycerin at a mass ratio of 1:(2-4):(1-2) and stir at 35-45℃ for 30-40 min to obtain a cannabidiol mixture; S4: Electrostatic adsorption and low-temperature curing: The modified antibacterial fiber is placed in an electrostatic adsorption device, and under the conditions of 15-25kV voltage and 8-12cm distance, a cannabidiol mixture is sprayed and adsorbed for 20-30min. Then, it is baked at 40-60℃ for 10-15min to obtain antibacterial fiber wound suture containing cannabidiol.

2. The preparation method according to claim 1, characterized in that, The biodegradable antibacterial fiber described in S1 is a polycaprolactone-chitosan composite fiber, wherein the chitosan accounts for 10%-15% of the mass of the polycaprolactone-chitosan composite fiber.

3. The preparation method according to claim 1, characterized in that, The quaternary ammonium salt solution mentioned in S2 is a 3-chloro-2-hydroxypropyltrimethylammonium chloride solution with a mass concentration of 5%-8%.

4. The preparation method according to claim 1, characterized in that, During the constant temperature water bath reaction in S2, the stirring rate is 200-300 r / min.

5. The preparation method according to claim 1, characterized in that, The molecular weight of the polyethylene glycol mentioned in S3 is 400-600.

6. The preparation method according to claim 1, characterized in that, The spraying rate of the electrostatic adsorption device in S4 is 0.5-1 mL / min.

7. The preparation method according to claim 1, characterized in that, The baking temperature in S4 is 50-55℃, and the baking time is 12-14 minutes.

8. The preparation method according to any one of claims 1-7, characterized in that, The ultrasonic cleaning power in S1 is 300-400W, and the cleaning time is 12-14min.

9. The preparation method according to any one of claims 1-7, characterized in that, After rinsing in S2, the drying temperature is 55-60℃, and the drying time is 1.5-2 hours.

10. A cannabidiol-containing antibacterial fiber wound suture, characterized in that, It is prepared by the preparation method according to any one of claims 1-9.

Images