Degradable drug-loaded suture line as well as preparation method and application thereof
The biodegradable drug-loaded sutures prepared by microfluidic spinning technology have solved the problems of low drug loading and poor biocompatibility, achieving effective treatment of adenomyosis and reducing secondary pain and drug side effects for patients.
Patent Information
- Application Number
- CN202511277673.6
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-09-09
- Publication Date
- 2025-10-31
AI Technical Summary
Existing biodegradable sutures have low drug loading capacity and poor biocompatibility, making it difficult to achieve effective treatment for adenomyosis. Furthermore, traditional sutures require suture removal, causing secondary pain.
Biodegradable drug-loaded sutures were prepared using microfluidic spinning technology. By using a microfluidic chip with a T-shaped flow channel structure, the flow rate of the inner and outer fluids was precisely adjusted to form a drug-loaded biodegradable suture, which was then used to suture the skin and deep tissues after surgery for adenomyosis.
It increases drug loading capacity, has good biocompatibility, achieves stable drug release, reduces systemic drug dosage, avoids the pain of suture removal, and reduces the recurrence rate of adenomyosis.
Smart Images
Figure CN120860286A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of absorbable sutures, specifically to a biodegradable drug-loaded suture, its preparation method, and its application. Background Technology
[0002] Adenomyosis is a common gynecological disease. Currently, its drug treatment mainly includes combined oral contraceptives, oral progestins, levonorgestrel-releasing intrauterine system (LNG-IUS), gonadotropin-releasing hormone agonists (GnRH agonists, GnRHa), GnRH antagonists, dinogest, danazol, etc. At the same time, there are some drugs in the experimental stage, such as aromatase inhibitors, antiplatelet drugs, oxytocin antagonists, etc.
[0003] While medication can alleviate symptoms of adenomyosis to some extent, it is difficult to completely cure the lesions. Furthermore, the side effects of these medications should not be underestimated; they may cause endocrine disorders, leading to irregular menstrual cycles, reduced menstrual flow, or amenorrhea. Long-term or high-dose use may also damage liver cells, causing abnormal liver function. Therefore, surgical treatment combined with medication offers greater advantages in eradicating the lesions and preventing recurrence.
[0004] During surgical treatment, postoperative suturing of the skin and deep tissues is necessary. Traditional non-biodegradable surgical sutures have many drawbacks, such as poor degradation, poor biocompatibility, incomplete absorption by the body, easy formation of suture scars, and the need for postoperative medication, leading to repeated drug use. In contrast, drug-loaded sutures have significant advantages. They can release drugs locally and stably, reducing the systemic dosage and thus lowering the adverse reactions associated with hormone therapy. Furthermore, biodegradable sutures play a crucial role in early wound healing, eliminating the need for suture removal after healing and avoiding secondary postoperative pain for patients. However, existing technologies still suffer from low drug loading capacity. Therefore, this invention provides a biodegradable drug-loaded suture, its preparation method, and its applications. Summary of the Invention
[0005] This invention provides a method for preparing biodegradable drug-loaded sutures based on microfluidic spinning technology for use in suturing skin and deep tissues after surgery for adenomyosis. This method increases drug loading, has good biocompatibility, avoids suture removal, and provides stable drug release, avoiding repeated medication.
[0006] On one hand, there is a biodegradable drug-loaded suture, which is composed of a dispersed phase and a continuous phase, wherein the continuous phase forms a uniform coating layer on the surface of the dispersed phase; the dispersed phase includes a biodegradable polymer, an organic solvent and a drug-loaded substance; the continuous phase includes a surfactant and an alcohol solution.
[0007] Furthermore, the degradable polymers in the dispersed phase include any one or more blends of lactic acid, polyglycolic acid, polytrimethylene carbonate, polyβ-hydroxybutyrate, lactic acid-glycolic acid copolymer, and polycaprolactone.
[0008] Furthermore, the organic solvent in the dispersed phase includes any one or more of chloroform, dichloromethane, and ethyl acetate.
[0009] Furthermore, the drug loaded in the dispersed phase includes any one or more of mifepristone and GnRHa drugs.
[0010] Furthermore, the mass of the drug loading is 5%-20% of the mass of the degradable polymer; the mass of the degradable polymer is 2%-20% of the mass of the organic solvent.
[0011] Furthermore, the surfactant in the continuous phase is any one or a mixture of several of vitamin E polyethylene glycol succinate, sorbitan fatty acid ester, sorbitan fatty acid ester, polyoxyethylene-polyoxypropylene polymer, lecithin, sodium dodecyl sulfate, and poloxamer 188; the alcohol solution is any one or a mixture of several of methanol, ethanol, and isopropanol.
[0012] Furthermore, the mass of the surfactant in the continuous phase is 1%-8% of that in the alcohol solution.
[0013] On the one hand, the steps of the method for preparing biodegradable drug-loaded sutures include: dissolving the loaded drug and biodegradable polymer in an organic solvent to form a microfluidic dispersed phase; dissolving a surfactant in an alcohol solution to form a microfluidic continuous phase; using a microfluidic chip, with the outer phase as the continuous phase and the inner phase as the dispersed phase, injecting the inner and outer phases into T-shaped microchannels through polytetrafluoroethylene tubing, with the inner phase flow rate being 1-200 mL / h and the outer phase flow rate being 10-2000 mL / h, the inner phase polymer forming fibers in the outer phase, followed by stretching, washing, solvent removal, and vacuum drying to obtain the biodegradable drug-loaded suture.
[0014] Furthermore, the flow channel size of the microfluidic chip is 10-500μm.
[0015] On the other hand, the application of biodegradable drug-loaded sutures in the preparation of skin and deep tissue products for suturing after adenomyosis surgery.
[0016] The beneficial effects of this invention are:
[0017] The biodegradable drug-loaded suture introduced in this invention is prepared using advanced microfluidic spinning technology. Specifically, it is manufactured using a microfluidic chip with a T-shaped flow channel structure. During the preparation process, by precisely adjusting the flow rate ratio of the inner and outer fluids, the inner phase fluid is facilitated to form fibers smoothly in this environment, thereby successfully preparing a drug-loaded biodegradable suture. This suture is specifically designed for use in preparing products for suturing skin and deep tissues after adenomyosis surgery.
[0018] This suture exhibits excellent biocompatibility, eliminating the need for suture removal after wound healing and effectively preventing secondary pain for patients. More importantly, the medication loaded within the suture can directly target the myometrium, achieving a stable, long-term drug concentration supply to the target lesion, significantly reducing the inconvenience and hassle of repeated drug administration in clinical treatment. This characteristic enables it to effectively alleviate patient symptoms and reduce the recurrence rate of adenomyosis, demonstrating significant value in clinical applications. Attached Figure Description
[0019] Figure 1 This is a typical microfluidic spinning schematic diagram;
[0020] Figure 2 This is a drug release curve for drug-loaded sutures with different wire diameters. Detailed Implementation
[0021] To make the technical means, creative features, objectives and effects of this invention easier to understand, the invention will be further described below in conjunction with specific embodiments.
[0022] The microfluidic chip was purchased from Juwei Fuzhong Technology Co., Ltd., model Regular Serial 002-01100 micrometer wide T-channel chip.
[0023] Figure 1 A typical microfluidic spinning schematic diagram
[0024] Example 1
[0025] Dissolve 1.5g of dinogest and 10g of PCL in 100mL of dichloromethane to form the internal phase of the microfluidic system.
[0026] 15g of VE-TPGS was fully dissolved in 1000mL of ethanol to form the external phase of the microfluidic system.
[0027] The above solutions were injected into a microfluidic device with a channel size of 300 μm through polytetrafluoroethylene tubing. The internal phase was injected into the internal phase channel at a flow rate of 20 mL / h, and the external phase was injected into the external phase channel at a flow rate of 200 mL / h. The resulting polymer fibers were washed with ethanol, desolventized, and vacuum dried for 8 h under roller tension to obtain the biodegradable drug-loaded suture. The sample was designated S1.
[0028] Example 2
[0029] Dissolve 1.5g of dinogest and 10g of PCL in 100mL of dichloromethane to form the internal phase of the microfluidic system.
[0030] 15g of VE-TPGS was fully dissolved in 1000mL of ethanol to form the external phase of the microfluidic system.
[0031] The above solutions were injected into a microfluidic device with a channel size of 300 μm through polytetrafluoroethylene tubing. The internal phase was injected into the internal phase channel at a flow rate of 100 mL / h, and the external phase was injected into the external phase channel at a flow rate of 200 mL / h. The resulting polymer fibers were washed with ethanol, desolventized, and vacuum dried for 8 hours under roller tension to obtain the biodegradable drug-loaded suture. This sample was designated S2.
[0032] Example 3
[0033] Dissolve 1.5g of dinogest and 10g of PCL in 100mL of dichloromethane to form the internal phase of the microfluidic system.
[0034] 15g of VE-TPGS was fully dissolved in 1000mL of ethanol to form the external phase of the microfluidic system.
[0035] The above solutions were injected into a microfluidic device with a channel size of 300 μm through polytetrafluoroethylene tubing. The internal phase was injected into the internal phase channel at a flow rate of 20 mL / h, and the external phase was injected into the external phase channel at a flow rate of 1000 mL / h. The resulting polymer fibers were then washed with ethanol, desolventized, and vacuum dried for 8 h under roller tension to obtain the biodegradable drug-loaded suture. This sample was designated S3.
[0036] Example 4
[0037] 2g of mifepristone and 8g of polyglycolic acid (PGA) were fully dissolved in 80mL of chloroform to form the internal phase of the microfluidic system.
[0038] 10g of lecithin was fully dissolved in 800mL of methanol to form the external phase of the microfluidic system.
[0039] The above solutions were injected into a microfluidic device with a channel size of 500 μm through polytetrafluoroethylene tubing. The internal phase was injected into the internal phase channel at a flow rate of 50 mL / h, and the external phase was injected into the external phase channel at a flow rate of 500 mL / h. The resulting polymer fibers were washed with deionized water under roller tension, desolventized, and vacuum dried for 10 h to obtain the biodegradable drug-loaded suture. The sample was designated S4.
[0040] Example 5
[0041] 1 g of leuprolide and 12 g of lactic acid-glycolic acid copolymer (PLGA) were fully dissolved in 120 mL of ethyl acetate to form the microfluidic internal phase.
[0042] 18g of sodium dodecyl sulfate (SDS) was fully dissolved in 1200mL of isopropanol to form the external phase of the microfluidic system.
[0043] The above solutions were injected into a microfluidic device with a channel size of 200 μm through polytetrafluoroethylene tubing. The internal phase was injected into the internal phase channel at a flow rate of 150 mL / h, and the external phase was injected into the external phase channel at a flow rate of 1500 mL / h. The resulting polymer fibers were washed with anhydrous ethanol under roller tension, desolventized, and vacuum dried for 10 h to obtain the biodegradable drug-loaded suture. The sample was designated S5.
[0044] Example 6
[0045] 1.8 g of dexamethasone and 9 g of polytrimethylene carbonate (PTMC) were fully dissolved in 90 mL of dichloromethane to form the internal phase of the microfluidic system.
[0046] 13.5 g of poloxamer 188 was fully dissolved in 900 mL of a 1:1 mixture of ethanol and methanol to form the external phase of the microfluidic system.
[0047] The above solutions were injected into a microfluidic device with a channel size of 400 μm through polytetrafluoroethylene tubing. The internal phase was injected into the internal phase channel at a flow rate of 30 mL / h, and the external phase was injected into the external phase channel at a flow rate of 300 mL / h. The resulting polymer fibers were washed with deionized water under roller tension, desolventized, and vacuum dried for 9 h to obtain the biodegradable drug-loaded suture. The sample was designated S6.
[0048] Example 7
[0049] 1.2 g of dydrogesterone and 11 g of poly(β-hydroxybutyrate) (PHB) were fully dissolved in 110 mL of chloroform to form the microfluidic internal phase.
[0050] 16.5g of vitamin E polyethylene glycol succinate (VE-TPGS) was fully dissolved in 1100mL of ethanol to form the external phase of the microfluidic system.
[0051] The above solutions were injected into a microfluidic device with a channel size of 600 μm through polytetrafluoroethylene tubing. The internal phase was injected into the internal phase channel at a flow rate of 80 mL / h, and the external phase was injected into the external phase channel at a flow rate of 800 mL / h. The resulting polymer fibers were washed with anhydrous ethanol under roller tension, desolventized, and vacuum dried for 7 h to obtain the biodegradable drug-loaded suture. The sample was designated S7.
[0052] Example 8
[0053] 2.2 g of hydrocortisone, 7 g of polycaprolactone (PCL) and polyglycolic acid (PGA) in a 1:1 ratio were fully dissolved in 70 mL of ethyl acetate to form the microfluidic internal phase.
[0054] 10.5 g of dehydrated sorbitan fatty acid ester (Span) was fully dissolved in 700 mL of isopropanol to form the external phase of the microfluidic system.
[0055] The above solutions were injected into a microfluidic device with a channel size of 150 μm through polytetrafluoroethylene tubing. The internal phase was injected into the internal phase channel at a flow rate of 180 mL / h, and the external phase was injected into the external phase channel at a flow rate of 1800 mL / h. The resulting polymer fibers were washed with deionized water under roller tension, desolventized, and vacuum dried for 11 h to obtain the biodegradable drug-loaded suture. The sample was designated S8.
[0056] test
[0057] Suture wire diameter measurement:
[0058] An optical microscope was used to measure the wire diameter at eight different locations for each sample using a scale. For samples S1, S2, and S3 in the above embodiments, the wire diameter was measured using an optical microscope.
[0059] Determination of drug loading in sutures:
[0060] First, a quantitative working curve for the drug was established. A small amount of the drug was dissolved in dichloromethane, and its UV-Vis absorption spectrum was measured in a quartz cuvette, using the maximum peak value as the detection wavelength. Subsequently, standard solutions of dichloromethane with drug concentrations of 0, 0.001, 0.01, and 0.1 mg / mL were prepared, and the corresponding UV absorbance values at different drug concentrations were measured to create a working curve of concentration versus absorbance. A precise mass (m1) of drug-loaded suture was weighed, dissolved in dichloromethane, and its UV absorbance value was measured. The drug content (m2) was calculated using the working curve, and the drug loading was calculated as m2 / m1 × 100%.
[0061] For samples S1, S2, and S3 in the above examples, 1 mg of dinogest was accurately weighed and dissolved in 1 mL of dichloromethane to prepare a 1 mg / mL solution. The UV-Vis absorption spectrum of the drug was measured in a quartz cuvette, with a maximum absorption wavelength of 300 nm. The above solution was diluted with dichloromethane to prepare standard solutions with drug concentrations of 0, 0.001, 0.01, and 0.1 mg / mL, respectively. The absorbance of the corresponding solutions was measured at the maximum absorption wavelength of 300 nm to create a working curve of concentration versus absorbance.
[0062] Accurately weigh 10 mg of drug-loaded sutures from samples S1, S2, and S3, dissolve them in 2 mL of dichloromethane to prepare a 5 mg / mL solution, and measure the absorbance at the maximum absorption wavelength of 300 nm. Calculate the content of dinogest in each sample and the corresponding drug loading using the working curve.
[0063] The test results are summarized in Table 1. Based on the results, the relationship between the internal and external phase flow rates during the preparation process and the diameter and drug loading of the biodegradable drug-loaded suture was determined: when the internal phase was injected into the internal phase channel at a flow rate of 100 mL / h and the external phase was injected into the external phase channel at a flow rate of 200 mL / h, S2 had the largest suture diameter; when the internal phase was injected into the internal phase channel at a flow rate of 20 mL / h and the external phase was injected into the external phase channel at a flow rate of 200 mL / h, S1 had the largest drug loading.
[0064] The sustained-release curves of drug-loaded sutures with filament diameters of 100 μm and 200 μm are shown below. Figure 2 As shown, it can be concluded that the biodegradable drug-loaded suture has a sustained-release effect.
[0065] Table 1 shows the wire diameter and drug loading of the biodegradable drug-loaded sutures in the examples.
[0066] sample S1 S2 S3 Wire diameter (μm) 176±25 212±31 137±23 Drug loading (%) 12.3±2.8 11.8±1.9 10.5±1.4
[0067] The foregoing has shown and described the basic principles, main features, and advantages of the present invention. It will be apparent to those skilled in the art that the invention is not limited to the details of the exemplary embodiments described above, and that the invention can be implemented in other specific forms without departing from its spirit or essential characteristics. Therefore, the embodiments should be considered illustrative and non-limiting in all respects, and the scope of the invention is defined by the appended claims rather than the foregoing description. Thus, all variations falling within the meaning and scope of equivalents of the claims are intended to be included within the scope of the invention. No reference numerals in the claims should be construed as limiting the scope of the claims.
[0068] Furthermore, it should be understood that although this specification describes embodiments, not every embodiment contains only one independent technical solution. This narrative style is merely for clarity. Those skilled in the art should consider the specification as a whole, and the technical solutions in each embodiment can also be appropriately combined to form other embodiments that can be understood by those skilled in the art.
Claims
1. A biodegradable drug-loaded suture, characterized in that, The biodegradable drug-loaded suture consists of a dispersed phase and a continuous phase, with the continuous phase forming a uniform coating layer on the surface of the dispersed phase. The dispersed phase includes a biodegradable polymer, an organic solvent, and a drug-loaded component. The continuous phase includes a surfactant and an alcohol solution.
2. The biodegradable drug-loaded suture according to claim 1, characterized in that, The biodegradable polymer in the dispersed phase includes any one or more blends of lactic acid, polyglycolic acid, polytrimethylene carbonate, polyβ-hydroxybutyrate, lactic acid-hydroxyacetic acid copolymer, and polycaprolactone.
3. The biodegradable drug-loaded suture according to claim 1, characterized in that, The organic solvent in the dispersed phase includes any one or more of chloroform, dichloromethane, and ethyl acetate.
4. The biodegradable drug-loaded suture according to claim 1, characterized in that, The drug loaded in the dispersed phase includes any one or more of mifepristone and GnRHa drugs.
5. The biodegradable drug-loaded suture according to claim 1, characterized in that, The mass of the drug-loaded component is 5%-20% of the mass of the biodegradable polymer; the mass of the biodegradable polymer is 2%-20% of the mass of the organic solvent.
6. The biodegradable drug-loaded suture according to claim 1, characterized in that, The surfactant in the continuous phase is any one or a mixture of several of the following: vitamin E polyethylene glycol succinate, sorbitan fatty acid ester, sorbitan fatty acid ester, polyoxyethylene-polyoxypropylene polymer, lecithin, sodium dodecyl sulfate, and poloxamer 188; the alcohol solution is any one or a mixture of several of the following: methanol, ethanol, and isopropanol.
7. The biodegradable drug-loaded suture according to claim 1, characterized in that, The mass of the surfactant in the continuous phase is 1%-8% of the mass of the alcohol solution.
8. A method for preparing a biodegradable drug-loaded suture according to any one of claims 1-9, characterized in that the step... include: The loaded drug and biodegradable polymer are dissolved in an organic solvent to form a microfluidic dispersed phase; the surfactant is dissolved in an alcohol solution to form a microfluidic continuous phase. Using a microfluidic chip, the outer phase is a continuous phase and the inner phase is a dispersed phase. The inner and outer phases are injected into a T-shaped microchannel through polytetrafluoroethylene tubing. The flow rate of the inner phase is 1-200 mL / h and the flow rate of the outer phase is 10-2000 mL / h. The polymer in the inner phase forms fibers in the outer phase. After stretching, washing, desolventizing and vacuum drying are performed to obtain a biodegradable drug-loaded suture.
9. The biodegradable drug-loaded suture according to claim 9, characterized in that, The microfluidic chip has a flow channel size of 10-500μm.
10. The use of the biodegradable drug-loaded suture according to any one of claims 1-7 in the preparation of skin and deep tissue products for suturing adenomyosis surgery.