A neural suture and a method of making the same

Abstract

The application discloses a nerve suture thread and a preparation method thereof, and the preparation method comprises the following steps: step one, collagen type I powder, glycerol and glutaraldehyde are mixed according to a weight ratio of 95:(4-10):(1-5); step two, the mixture is preheated and melted, then melt spinning is carried out, and the spun yarn is cooled, stretched and surface treated to obtain a suture thread primary product; step three, a PLGA solution and a dexamethasone solution are mixed according to a volume ratio of 9:(1-6), and the mixed solution is subjected to high-speed shearing emulsification; and step four, the suture thread primary product is coated by using an immersion method, and is subjected to drying and solidification, surface treatment and sterilization treatment to obtain the nerve suture thread. The nerve suture thread prepared by using the preparation method has the advantages that the prepared suture thread can realize sustained release of dexamethasone, is beneficial to reducing inflammatory reaction in the early stage of nerve injury and promoting nerve repair, and dexamethasone also has the effect of reducing foreign body reaction, can reduce the rejection reaction of the body after the suture thread is implanted and improves the biocompatibility of the suture thread.

Description

Technical Field

[0001] The present invention relates to the technical field of medical materials, and in particular to a nerve suture and a preparation method thereof. Background Art

[0002] Peripheral nerve injury is a common type of trauma in clinical practice, accounting for approximately 2-3% of all traumatic injuries. This type of injury not only leads to loss of motor and sensory function but can also cause chronic pain, severely impacting a patient's quality of life. When a peripheral nerve is ruptured, end-to-end epineurial suture is often required to restore nerve continuity and facilitate subsequent regeneration.

[0003] Currently, the commonly used nerve sutures in clinical practice are mainly 6-0, 8-0, or 10-0 absorbable sutures, such as those made of polylactic-co-glycolic acid (PLGA) or polydioxanone (PDS). Although these sutures can achieve mechanical fixation of nerve stumps, they only provide passive support and do not promote nerve repair or regulate the local microenvironment.

[0004] However, a strong inflammatory response will occur in the early stages after peripheral nerve injury. This inflammatory response is the body's normal response to injury, but excessive inflammatory response can produce a series of adverse consequences: 1) Hindering axon regeneration: Excessive inflammatory response will produce a large number of inflammatory factors and free radicals, which may inhibit the expression of nerve growth factor and hinder the extension of axons. 2) Leading to abnormal activation of fibroblasts: In an inflammatory environment, fibroblasts will be overactivated and produce a large amount of extracellular matrix proteins. 3) Causing scar formation and nerve adhesion: Excessive proliferation of extracellular matrix will form scar tissue, causing nerves to adhere to surrounding tissues, affecting the normal sliding and signal transmission of nerves.

[0005] Furthermore, surgical sutures, as foreign bodies implanted in the body, can also cause rejection reactions in the body. This rejection reaction not only aggravates local inflammation but can also lead to fibrosis of the tissue surrounding the sutures, further impairing nerve repair. Summary of the Invention

[0006] The purpose of the present invention is to provide a nerve suture and a preparation method thereof in view of the deficiencies in the prior art.

[0007] To achieve the above object, the technical solution adopted by the present invention is:

[0008] The first aspect is to provide a method for preparing a nerve suture, comprising the following steps:

[0009] Step 1: Mix type I collagen powder, glycerol, and glutaraldehyde in a weight ratio of 95:(4-10):(1-5);

[0010] Step 2: preheating and melting the mixture and then performing melt spinning, cooling, stretching and surface treatment on the spun filaments to obtain a preliminary suture product;

[0011] Step 3, mixing the PLGA solution and the dexamethasone solution in a volume ratio of 9:(1-6), and subjecting the mixed solution to high-speed shear emulsification;

[0012] Step 4: coating the primary suture product by dipping, drying and solidifying, surface treating, and sterilizing to obtain the nerve suture.

[0013] Furthermore, in step 2, the melt spinning process includes: delivering the molten mixture to the spinneret through a metering pump, the spinneret temperature is controlled at 160-180° C., the spinneret hole diameter is 50-100 μm, and the spinning speed is 100-120 m / min.

[0014] Furthermore, in the step 2, nitrogen at 25° C. is used as the cooling medium during the cooling process.

[0015] Furthermore, in the step 2, the stretching process is carried out at 40°C.

[0016] Furthermore, in step 3, the PLGA solution is a 10-15% w / v PLGA (lactic acid: glycolic acid = 75:25) dichloromethane solution; and the dexamethasone solution is a 2-5% w / v dexamethasone methanol solution.

[0017] Furthermore, in step 3, the emulsification treatment is carried out in a water bath at 40-45° C., and high-speed shear emulsification is performed at a speed of 10,000-12,000 rpm for 10-15 minutes, and then 1-1.5% w / v Tween 80 is added as an emulsifier, and emulsification is continued for 5-10 minutes.

[0018] Furthermore, in step 4, the coating process includes: immersing the primary suture product in the emulsified coating solution for 30-40 seconds, air-drying in a 40-45° C. thermostat for 5-8 minutes, and repeating this process 3 times.

[0019] Furthermore, in step 4, drying and curing are carried out in a vacuum drying oven at 37-40° C. for 24-36 hours.

[0020] Furthermore, in step 4, the sterilization treatment is performed by using ethylene oxide gas sterilization at 37-40° C. for 4-6 hours.

[0021] The second aspect is to provide a nerve suture prepared by the above preparation method.

[0022] The present invention adopts the above technical solution, which has the following technical effects compared with the prior art:

[0023] The present invention uses type I collagen with good biocompatibility as a substrate and prepares a suture with excellent mechanical properties through a melt spinning method; PLGA is used as a drug carrier and a uniform and stable dexamethasone coating is formed on the surface of the suture through an emulsification-impregnation method. By controlling the reaction temperature and emulsification technology, agglomeration and local deposition of dexamethasone during the coating process are effectively avoided, thereby achieving uniform distribution of the drug.

[0024] The nerve suture preparation method of the present invention can be used to prepare sutures of three specifications: 6-0, 8-0, and 10-0, to meet the needs of different nerve repair surgeries. The prepared sutures can achieve sustained release of dexamethasone, which is beneficial for reducing the early inflammatory response of nerve damage and promoting nerve repair. Dexamethasone also has the effect of alleviating foreign body reactions, which can reduce the body's rejection reaction after the suture is implanted, thereby improving the biocompatibility of the suture. DETAILED DESCRIPTION

[0025] The present invention will be further described below with reference to specific embodiments, but this is not intended to limit the present invention. It should be noted that, unless there is a conflict, the embodiments and features in the embodiments of the present invention may be combined with each other.

[0026] Example 1

[0027] This embodiment provides a method for preparing a nerve suture, comprising the following steps:

[0028] Step 1: Mix type I collagen powder (medical grade), glycerin (medical grade), and glutaraldehyde (medical grade) in a weight ratio of 95:4:1 and stir thoroughly under vacuum for 30 minutes to ensure uniform mixing;

[0029] Step 2: Melt Spinning:

[0030] 1) Preheating: Place the mixture in a vacuum drying oven at 65°C for 2 hours to remove moisture;

[0031] 2) Melting: Transfer the preheated mixture to the hopper of the melt spinning machine, raise the temperature to 165°C, and maintain it for 30 minutes to fully melt the collagen;

[0032] 3) Spinning: The molten collagen is delivered to the spinneret by a metering pump. The spinneret temperature is controlled at 160-180°C (preferably 160°C), the spinneret hole diameter is 50-100 μm (preferably 80 μm), and the spinning speed is 100-120 m / min (preferably 100 m / min).

[0033] 4) Cooling: The spun tow immediately enters the cooling zone, using 25°C nitrogen as the cooling medium;

[0034] 5) Stretching: The cooled filaments are subjected to hot stretching at 40°C.

[0035] The stretching ratio is 3:1 to 5:1, preferably 4:1, and the wire diameter is controlled to three specifications: 0.07-0.099 mm (6-0 suture), 0.04-0.049 mm (8-0 suture), and 0.02-0.029 mm (10-0 suture);

[0036] 6) Surface treatment: The stretched tow was immersed in a 2% w / v glutaraldehyde aqueous solution for 30 seconds, and then rinsed with deionized water three times for 1 minute each time;

[0037] 7) Drying: Dry in a vacuum drying oven at 40°C for 4 hours.

[0038] Step 3: Mix the PLGA solution and the dexamethasone solution in a volume ratio of 9:1-6, stir at room temperature for 30 minutes, and emulsify the mixed solution in a water bath at 40-45°C (preferably 40°C) at a speed of 10,000-12,000 rpm (preferably 10,000 rpm) for 10-15 minutes (preferably 10 minutes). Then, 1-1.5% w / v (preferably 1% w / v) of Tween 80 is added as an emulsifier, and emulsification is continued for 5-10 minutes (preferably 5 minutes).

[0039] The PLGA solution is a 10-15% w / v (preferably 10% w / v) PLGA (lactic acid: glycolic acid = 75:25) dichloromethane solution; and the dexamethasone solution is a 2-5% w / v (preferably 2% w / v) dexamethasone methanol solution.

[0040] Step 4: Coating by dipping method:

[0041] 1) Immersing the suture prepared in step 2 in the emulsified coating solution for 30-40 seconds (preferably 30 seconds), air-drying in a thermostat at 40-45° C. (preferably 40° C.) for 5 minutes, and repeating the immersion-air-drying process three times to form a multilayer coating;

[0042] 2) Place the coated suture in a vacuum drying oven at 37-40°C (preferably 37°C) for 24 hours to ensure complete evaporation of the solvent;

[0043] 3) Gently rinse the suture surface with PBS buffer (pH = 7.4) to remove the drug that is not firmly adhered, and air-dry naturally under sterile conditions;

[0044] 4) Sterilize with ethylene oxide gas at a temperature of 37-40°C (preferably 37°C) for 4 hours;

[0045] 5) Place the prepared suture in a sterile sealed package and store at 4°C in the dark until ready for use.

[0046] Verification Example 1

[0047] In order to verify that the nerve suture prepared by the present invention has the effect of sustained release of dexamethasone, the following in vitro experiments were conducted:

[0048] 1) Cut the nerve suture sample (6-0 suture prepared in Example 1) into 5 cm long segments and accurately weigh them;

[0049] 2) Immerse the suture sample in a centrifuge tube containing 10 mL of PBS (pH = 7.4) and place it in a 37°C constant temperature water bath;

[0050] 3) At the predetermined time point, remove 1 mL of supernatant and add 1 mL of fresh PBS;

[0051] 4) Determination of the dexamethasone concentration in the supernatant using HPLC;

[0052] The chromatographic conditions are:

[0053] Chromatographic column: C18 reverse phase column (250mm×4.6mm, 5μm)

[0054] Mobile phase: acetonitrile-water (40:60, v / v)

[0055] Flow rate: 1.0 mL / min

[0056] Detection wavelength: 240nm

[0057] Column temperature: 30°C

[0058] Injection volume: 20 μL 5) Calculate the cumulative release percentage of dexamethasone. The results are shown in Table 1:

[0059] Cumulative release percentage = (cumulative release amount / total amount of dexamethasone in suture) × 100%

[0060] Table 1

[0061] Time (days) Cumulative release percentage (%) 0.5 15.2±3.1 1 25.3±4.2 2 35.1±5.3 4 45.4±6.1 7 55.2±5.9 14 70.3±5.2 21 80.1±4.3 28 85.4±3.2 35 90.2±2.1 42 93.3±1.8 49 95.1±1.2 56 97.2±0.9

[0062] It can be seen that: 1) the release is faster in the initial stage (0-2 days), reaching about 35%, so as to quickly reach the therapeutic concentration.

[0063] 2) The medium term (3-14 days) maintains a steady release, with a release of about 15-20% per week.

[0064] 3) In the later period (after 14 days), the release rate gradually slows down, showing the typical characteristics of a sustained-release curve.

[0065] 4) The cumulative release reached 97% at 56 days (8 weeks), essentially completing the drug release.

[0066] The above description is only a preferred embodiment of the present invention and does not limit the implementation mode and protection scope of the present invention. For those skilled in the art, it should be aware that all solutions obtained by equivalent substitutions and obvious changes made using the contents of the present invention specification should be included in the protection scope of the present invention.

Claims

1. A method for preparing a nerve suture, characterized in that: The steps include: Step 1: Mix type I collagen powder, glycerol, and glutaraldehyde in a weight ratio of 95:(4-10):(1-5); Step 2: preheating and melting the mixture and then performing melt spinning, cooling, stretching and surface treatment on the spun filaments to obtain a preliminary suture product; Step 3, mixing the PLGA solution and the dexamethasone solution in a volume ratio of 9:(1-6), and subjecting the mixed solution to high-speed shear emulsification to obtain an emulsified coating solution; Step 4: Immerse the initial suture in the emulsified coating solution for 30-40 seconds, air-dry in a 40-45°C constant temperature box for 5-8 minutes, repeat this process 3 times, dry and solidify, surface treat, and sterilize to obtain the nerve suture.

2. The method for preparing a nerve suture according to claim 1, wherein: In the step 2, the melt spinning process includes: delivering the molten mixture to the spinneret through a metering pump, the spinneret temperature is controlled at 160-180°C, the spinneret hole diameter is 50-100 μm, and the spinning speed is 100-120 m / min.

3. The method for preparing a nerve suture according to claim 1, wherein: In the second step, nitrogen at 25°C is used as the cooling medium during the cooling process.

4. The method for preparing a nerve suture according to claim 1, wherein: In the step 2, the stretching process is carried out at 40°C.

5. The method for preparing a nerve suture according to claim 1, wherein: In the step 3, the PLGA solution is a 10-15% w / v PLGA dichloromethane solution; the dexamethasone solution is a 2-5% w / v dexamethasone methanol solution; and the ratio of lactic acid to glycolic acid in the PLGA is 75:

25.

6. The method for preparing a nerve suture according to claim 1, characterized in that: In the step 3, the emulsification treatment is carried out in a water bath at 40-45° C., and high-speed shear emulsification is performed at a speed of 10,000-12,000 rpm for 10-15 minutes. Then, 1-1.5% w / v of Tween 80 is added as an emulsifier, and the emulsification is continued for 5-10 minutes.

7. The method for preparing a nerve suture according to claim 1, characterized in that: In the step 4, drying and curing are carried out in a vacuum drying oven at 37-40°C for 24-36 hours.

8. The method for preparing a nerve suture according to claim 1, wherein: In step 4, the sterilization treatment is performed by using ethylene oxide gas sterilization at 37-40°C for 4-6 hours.

9. A nerve suture prepared by the preparation method according to any one of claims 1 to 8.