Absorbable suture as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of medical instruments, and particularly relates to an absorbable suture and a preparation method and application thereof. Two coatings are loaded, from inside to outside, the first coating is the rapamycin coating with the anti-scar effect, the second coating is the artemisinin coating with the antibacterial and anti-inflammatory effects, and stable loading and slow release of the rapamycin medicine and the artemisinin are achieved through the structure of the two coatings. The suture can release artemisinin in the surgical suture incision inflammation period, infection is prevented, and inflammatory response is reduced. The rapamycin is released in a surgical suture incision scar proliferation period, so that scar proliferation of a surgical incision is prevented and reduced.

Description

Technical Field

[0001] This invention belongs to the field of medical device technology, specifically relating to an absorbable suture, its preparation method, and its application. Background Technology

[0002] In 1975, researchers discovered rapamycin, an antifungal agent, in soil from Easter Island. Later studies revealed its immunosuppressive and antiproliferative properties in mammals. Rapamycin is a specific inhibitor of mammalian target of rapamycin (mTOR). mTOR is a serine / threonine protein kinase that plays a crucial role in cell growth, apoptosis, and proliferation. mTOR can assemble into two complexes, mTORC1 and mTORC2. mTORC1 primarily regulates cell growth and metabolism and is sensitive to rapamycin. mTORC2, on the other hand, primarily regulates cell survival and proliferation and is not sensitive to rapamycin. Rapamycin and its derivatives can reduce mTOR activity, inhibit P70s6k activation, and prevent phosphorylation of ribosomal protein S6, thereby blocking cell proliferation. Several rapamycin-coated stent systems have been approved for marketing, including products for coronary and vertebral arteries. Compared to bare-metal stents, rapamycin-coated stents are significantly more effective in inhibiting restenosis after stent implantation, reducing the risk of secondary interventions, and improving patient prognosis and quality of life.

[0003] The core pathological mechanism of scar formation lies in the activation of the mTOR signaling pathway by local tissue tension signals after skin injury. This promotes excessive proliferation of scar fibroblasts, leading to the abnormal synthesis and deposition of type I and type III collagen, ultimately resulting in hypertrophic scars or keloids. Rapamycin can effectively inhibit the activation of the mTOR signaling pathway, reduce excessive proliferation of scar fibroblasts, thereby inhibiting scar hyperplasia and promoting scarless healing of surgical incisions.

[0004] Artemisinin is mainly extracted directly from Artemisia annua, or semi-synthesized from Artemisia annua by extracting the high-content artemisinic acid. Artemisinin and its derivatives are sesquiterpene lactone compounds containing peroxide groups, mainly including dihydroartemisinin, artemether, artesunate, and arteether. Artemisinin is the most effective drug for treating drug-resistant malaria, and combination therapy with artemisinin-based drugs is currently the most effective and important means of treating malaria. However, in recent years, with in-depth research, more and more other effects of artemisinin have been discovered and applied in research, such as anti-tumor, treatment of pulmonary hypertension, anti-diabetic, embryotoxic, antifungal, immunomodulatory, antiviral, anti-inflammatory, anti-pulmonary fibrosis, antibacterial, and cardiovascular effects. Studies have confirmed that artemisinin has strong antibacterial effects against Bacillus anthracis, Staphylococcus epidermidis, Moraxella catarrhalis, and Corynebacterium diphtheriae, and also has certain antibacterial effects against Mycobacterium tuberculosis, Pseudomonas aeruginosa, Staphylococcus aureus, and Shigella dysenteriae.

[0005] Poly(p-dioxane)hexanone (PDO) is a crystalline polymer specifically designed for use in bioabsorbable sutures. This polymer is synthesized by polymerizing dioxane in the presence of organometallic catalysts (such as diethylzinc or zirconium acetylacetonate) to obtain a high molecular weight polymer suitable for melt extrusion into monofilaments. PDO sutures typically degrade in vivo over 6-12 months. They are absorbed through hydrolysis by intercellular water, and PDO degrades into low-molecular-weight, non-toxic residues that are excreted from the body through normal metabolic pathways: urine, feces, and respiration (exhaled CO2).

[0006] Surgical incisions undergo four phases after closure: hemostasis, inflammation, proliferation, and remodeling. The hemostasis phase lasts from minutes to hours; the inflammation phase lasts 1-3 days; the proliferation phase lasts 3-21 days; and the remodeling phase lasts from weeks to years. Inhibition of scar hyperplasia primarily occurs during the inflammation and proliferation phases. Currently, surgical sutures focus only on closure and fixation of the incision, with insufficient attention paid to antibacterial and anti-inflammatory effects and the inhibition of scar hyperplasia. Summary of the Invention

[0007] To address the above problems, the present invention provides a seam thread, comprising a seam thread body and a coating.

[0008] Furthermore, the suture body includes PDO and collagen.

[0009] Furthermore, the mass ratio of PDO to collagen is 5-7:3-5.

[0010] Furthermore, the coating includes a rapamycin coating and an artemisinin coating.

[0011] Furthermore, the drug mass fraction of the rapamycin coating is 0.1%–1%.

[0012] Furthermore, the artemisinin coating comprises artemisinin and a plasticizer.

[0013] Furthermore, the artemisinin has a mass fraction of 0.5%–1.0%.

[0014] Furthermore, the plasticizer is 0.1%–0.3% glycerol.

[0015] Furthermore, the artemisinin coating has a thickness of 5-7 μm.

[0016] The present invention has the following beneficial effects:

[0017] This invention provides an absorbable surgical suture with the function of inhibiting scar hyperplasia after surgical incision closure, its preparation method, and clinical applications. It is particularly suitable for the prevention and treatment of postoperative skin incision scars and can be widely used in suturing for various surgical procedures. By loading two coating layers, from the inside out, the first layer is a rapamycin coating with anti-scarring properties, and the second layer is an artemisinin coating with antibacterial and anti-inflammatory properties. This two-layer coating structure achieves stable loading and sustained release of rapamycin and artemisinin. The suture can release artemisinin during the inflammatory phase of the surgical incision, preventing infection and reducing the inflammatory response. It also releases rapamycin during the scar proliferation phase, preventing and reducing scar hyperplasia. This achieves four major functions: suturing, antibacterial, anti-inflammatory, and anti-scarring, filling the technological gap in existing surgical sutures that only focus on suturing function and lack antibacterial, anti-inflammatory, and anti-scarring interventions. Detailed Implementation

[0018] Various exemplary embodiments of the present invention are now described in detail. Unless otherwise specified, the methods used in the embodiments are conventional methods, and the reagents used are commercially available reagents or reagents prepared using conventional methods. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, characteristics, and embodiments of the present invention.

[0019] It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the invention. Furthermore, with respect to numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Any stated value or intermediate value within a stated range, as well as each smaller range between any other stated value or intermediate value within said range, is also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0020] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.

[0021] Various modifications and variations can be made to the specific embodiments described in this specification without departing from the scope or spirit of the invention, as will be apparent to those skilled in the art. Other embodiments derived from this specification will also be readily apparent to those skilled in the art. This specification and embodiments are merely exemplary.

[0022] The terms “include,” “including,” “have,” “contain,” etc., used in this article are all open-ended terms, meaning that they include but are not limited to.

[0023] Example 1: Preparation of Seam Seam Thread

[0024] Phase 1: Raw Material Preparation and Pretreatment

[0025] Selection and drying of polymer materials:

[0026] Selection: Select poly(p-dioxanone) (PDO) suitable for solution spinning.

[0027] Drying: Place the polymer particles / powder in a vacuum drying oven and dry at 50-60°C for at least 12 hours. This step is crucial to remove moisture and prevent the formation of bubbles or hydrolytic degradation of the polymer during spinning.

[0028] Preparation and dispersion (pre-dispersion) of rapamycin nanoparticles:

[0029] Weigh out the measured amount of rapamycin nanoparticle powder (e.g., ultimately accounting for 1%–5% w / w of the dry weight of the fiber).

[0030] Disperse it in a small amount of solvent compatible with the spinning solvent (for example, if the main solvent is dichloromethane, rapamycin can be dispersed in a small amount of acetone first). Sonicate using a probe sonicator in an ice bath under light-protected conditions for 15–30 minutes to obtain a highly uniform and stable rapamycin nanodispersion for later use.

[0031] Preparation of spinning solvent:

[0032] Choose a solvent that can fully dissolve the polymer but has minimal impact on the activity of rapamycin. For PDO, use hexafluoroisopropanol (HFIP) or a mixture of dichloromethane (DCM) / N,N-dimethylformamide (DMF). The solvent must be stored in a sealed container to prevent moisture absorption.

[0033] Second stage: Preparation of spinning solution

[0034] Preparation of polymer solutions:

[0035] The dried polymer material is dissolved in a selected solvent in a light-proof, airtight container.

[0036] Typical concentration: Prepare a 5%–15% (w / v) polymer solution. For example, dissolve 2g of dry PDO in 20mL of HFIP and stir magnetically for 6–12 hours until completely dissolved to obtain a clear, viscous solution.

[0037] Mixing and final dispersion:

[0038] The pre-prepared rapamycin nanodispersion was slowly added dropwise to the continuously stirred polymer solution.

[0039] After the addition is complete, continue stirring in the dark for 2-4 hours to ensure that the rapamycin nanoparticles are evenly distributed in the polymer solution.

[0040] If necessary, the mixture should be subjected to short-term, low-power ultrasonic treatment (5-10 minutes, ice bath) to completely break down any possible agglomerates and form a homogeneous, bubble-free drug-loaded spinning solution.

[0041] Phase 3: Solution spinning and shaping

[0042] Spinning device setup:

[0043] Dry-wet spinning:

[0044] Transfer the spinning solution into the syringe of the spinning pump (such as an injection pump), and install the spinneret (the size is selected according to the required suture diameter, such as 0.2-0.5 mm).

[0045] Coagulation bath preparation: Choose a liquid that is miscible with the solvent but can promote polymer coagulation. For HFIP solutions, use silicone oil or ethanol as the coagulation bath; for DCM solutions, use ethanol or methanol. Place the coagulation bath below the spinning head.

[0046] Spinning process:

[0047] Start the spinning pump and expel the spinning solution from the spinneret at a constant low speed (e.g., 0.5-2 mL / h).

[0048] The extruded nascent fiber stream first passes through an air gap (dry section) several centimeters long, allowing some solvent to evaporate and the fiber surface to be initially cured.

[0049] The fiber then enters the coagulation bath, where the remaining solvent and non-solvent (coagulation bath) undergo diffusion exchange, and the polymer is completely solidified and precipitated, with the rapamycin nanoparticles encapsulated in the solidified polymer matrix.

[0050] The cured fibers are pulled out of the coagulation bath by a guide roller system.

[0051] Stretch and orientation:

[0052] To improve the mechanical strength of the fiber, the nascent fiber is stretched.

[0053] By controlling the speed difference between two sets of guide rollers, the fiber is stretched 2-4 times at a temperature higher than the glass transition temperature but much lower than the melting point, so that the polymer chains are oriented along the fiber axis.

[0054] Rapamycin solution preparation: Dissolve rapamycin (purity ≥98%) in anhydrous ethanol (analytical grade, water content ≤0.1%), stir magnetically (500 r / min) for 30 min to prepare a rapamycin ethanol solution with a concentration of 15 mg / mL, filter through a 0.22 μm organic phase filter membrane to remove impurity particles and avoid clogging the spinneret orifice during spinning.

[0055] Phase 4: Post-processing

[0056] Drying and alcohol removal: The semi-finished product was placed in a vacuum drying oven (temperature 45℃, vacuum degree -0.095MPa) and dried for 5 hours. The residual ethanol content was detected by gas chromatograph (model: GC-2014) and found to be ≤0.1% to avoid postoperative local irritation.

[0057] Polishing treatment: Place the dried suture into a special suture polishing machine (model: MP-01), use a wool polishing wheel, rotate at 600 r / min, polish for 12 min, so that the surface roughness of the suture Ra≤0.2μm, reducing frictional damage to the skin tissue during suturing;

[0058] Fifth stage: Vacuum-assisted outer coating

[0059] Evenly wrap the suture body around the suture roller (15cm in diameter, 30cm in length), and cover the roller surface with a silicone layer (2mm thick) to avoid damaging the suture surface; place the roller into the coating treatment tank (50cm in diameter, 80cm in height) and seal the tank door; start the vacuum pump to evacuate the coating treatment tank to -0.080MPa and maintain the pressure for 8 minutes; open the flow control valve and inject the coating liquid into the coating treatment tank at a rate of 0.8mL / min, while maintaining the vacuum state for 20 minutes—the vacuum drainage effect allows the coating liquid to adhere evenly to the suture surface;

[0060] Phase 6: Final Processing

[0061] Drying and alcohol removal: The semi-finished product was placed in a vacuum drying oven (temperature 45℃, vacuum degree -0.095MPa) and dried for 5 hours. The residual ethanol content was detected by gas chromatograph (model: GC-2014) and found to be ≤0.1% to avoid postoperative local irritation.

[0062] Polishing treatment: Place the dried suture into a special suture polishing machine (model: MP-01), use a wool polishing wheel, rotate at 600 r / min, polish for 12 min, so that the surface roughness of the suture Ra≤0.2μm, reducing frictional damage to the skin tissue during suturing;

[0063] Needle fitting and fixation: Select medical-grade stainless steel suture needles (model: 1 / 2 round needle, specification: 3 / 8, needle tip edge polished with nano-level polishing), insert one end of the suture into the needle hole at the end of the needle, and fix it by welding with a laser welding machine (model: YAG-100). The diameter of the welding point is ≤0.3mm, and the connection strength is ≥8N.

[0064] Sterilization and Packaging: The sutures are placed in a cobalt source irradiation sterilization chamber and sterilized by 20kGy Co60-γ ray radiation. After sterilization, they are vacuum-packed in an aseptic environment using an aluminum-plastic composite film and stored away from light.

[0065] Example 2: Application of anti-scarring surgical sutures

[0066] This suture is mainly used for the prevention and treatment of postoperative skin incision scars. Its core application is intradermal dermal suture (burying the suture in the dermis to avoid epidermal irritation, reduce inflammation, and minimize scarring caused by foreign body reactions). Specific usage methods and clinical advantages are as follows:

[0067] (1) How to use

[0068] Preoperative preparation:

[0069] Remove the sutures from the aseptic packaging and visually inspect them for any damage or peeling of the surface coating, and check that the needle tip is sharp (without curling or deformation).

[0070] Suturing procedure (taking a linear facial incision as an example)

[0071] Incision treatment: Trim the edges of the skin incision neatly, stop the bleeding completely, and rinse the incision with saline.

[0072] Suturing method: Intradermal continuous suture is used. The needle is inserted from one end of the incision, with the needle tip vertically inserted into the dermis (2-3mm deep), and the needle is exited from the dermis on the opposite side of the incision. The suture is parallel to the direction of the incision, with a suture spacing of 3-5mm. The suture tension should be such that the edges of the incision are slightly everted (avoiding excessive tightness which may cause skin ischemia, and excessive looseness which may cause poor incision closure).

[0073] Finish suturing: Tie a knot at the other end of the incision, leaving a 5mm thread end (to avoid the knot being too short and causing loosening). No need to remove the sutures (the sutures will completely degrade in 8-12 weeks).

[0074] Postoperative care:

[0075] Postoperative dressing changes are routine to prevent incision infection; no additional anti-scarring medication is required. Follow-up examinations are conducted at 1 month and 3 months postoperatively to assess scar formation.

[0076] (2) Clinical advantages

[0077] Early intervention: anti-inflammatory and antibacterial treatment during the inflammatory phase, and anti-scar hyperplasia treatment during the proliferative phase, intervening 2-4 weeks earlier than traditional topical medications;

[0078] Reduce the burden of medical visits for patients: No need for long-term medication or multiple treatments after surgery;

[0079] Strong temporal sequence: It releases artemisinin during the inflammatory phase for anti-inflammatory and antibacterial effects, and releases rapamycin during the proliferative phase to combat scar hyperplasia;

[0080] Wide range of applications: It can be used for surgical incision suturing in different parts of the body, such as the face, abdomen, and joints.

[0081] (III) Beneficial Effects

[0082] The anti-scarring surgical suture and its preparation method of the present invention have the following significant advantages compared with the prior art:

[0083] Achieving simultaneous "suture-antibacterial-anti-inflammatory-anti-scarring" processes fills a technological gap.

[0084] For the first time, artemisinin and rapamycin are loaded into absorbable surgical sutures, enabling antibacterial, anti-inflammatory, and anti-scarring effects to begin during the skin incision suturing stage. This blocks scar formation at its source and solves the core problem of "delayed postoperative intervention" in traditional anti-scarring methods.

[0085] The dual-coating drug loading method flexibly adapts to the needs of wound healing.

[0086] Rapamycin is dispersed throughout the suture layer, with a drug release cycle of 8-12 weeks, and continuously inhibits scar hyperplasia during the proliferative and remodeling phases of the incision.

[0087] Artemisinin is distributed on the surface of the suture and achieves high-concentration release within 7 days, which can exert antibacterial and anti-inflammatory effects during the inflammatory phase of the incision.

[0088] Both coatings achieve uniform drug distribution and stable release through process optimization, without any issues of "burst release" or "detachment".

[0089] Balancing mechanical properties and biocompatibility to meet clinical suturing needs.

[0090] By optimizing the polymer material ratio and spinning process, the suture breaking strength is ≥10N and the knot strength is ≥8N, which can withstand the operational tension of surgical suturing; the degradation cycle is 12 weeks, which matches the skin healing process (epidermal healing 7-14 days, dermal repair 4-8 weeks), and the degradation products are safe and non-toxic; animal experiments show that the inflammatory cell infiltration rate is <5% within 7 days after suture implantation, with no obvious tissue stimulation and a biocompatibility grade of 0.

[0091] The embodiments described above are merely preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Various modifications and improvements made by those skilled in the art to the technical solutions of the present invention without departing from the spirit of the present invention should fall within the protection scope defined by the claims of the present invention.

Claims

1. An absorbable suture, characterized in that, Includes the suture body and the coating.

2. The absorbable suture according to claim 1, characterized in that, The suture body includes PDO and collagen.

3. The absorbable suture according to claim 2, characterized in that, The mass ratio of PDO to collagen is 5-7:3-5.

4. The absorbable suture according to claim 1, characterized in that, The coating includes a rapamycin coating and an artemisinin coating.

5. The absorbable suture according to claim 4, characterized in that, The rapamycin coating has a drug mass fraction of 0.1%–1%.

6. The absorbable suture according to claim 4, characterized in that, The artemisinin coating comprises artemisinin and a plasticizer.

7. The absorbable suture according to claim 6, characterized in that, The artemisinin mass fraction is 0.5%–1.0%.

8. The absorbable suture according to claim 6, characterized in that, The plasticizer is 0.1%–0.3% glycerol.

9. The absorbable suture according to claim 4, characterized in that, The thickness of the artemisinin coating is 5-7 μm.