CN109663144B - A bioactive degradable surgical suture and preparation method thereof - Google Patents

Abstract

Translated fromChinese

本发明公开了一种具有生物活性的可降解手术缝线及其制备方法，其中，所述通过在具有生物相容性的基体中加入包载生物活性物质的胶原蛋白，进而通过静电纺丝技术制备得到可降解手术缝线。本发明所述缝线均一性好，生物相容性和安全性高，制备方法简单快捷。The invention discloses a bioactive degradable surgical suture and a preparation method thereof, wherein the method comprises adding collagen encapsulating bioactive substances into a matrix with biocompatibility, and then using electrospinning technology. Degradable surgical sutures were prepared. The suture of the invention has good uniformity, high biocompatibility and safety, and the preparation method is simple and quick.

Description

Translated fromChinese

一种具有生物活性的可降解手术缝线及其制备方法A bioactive degradable surgical suture and preparation method thereof

技术领域technical field

本发明属于生物医用材料领域，具体涉及一种具有生物活性的可降解手术缝线及其制备方法。The invention belongs to the field of biomedical materials, in particular to a bioactive degradable surgical suture and a preparation method thereof.

背景技术Background technique

目前临床常用的医用手术缝合线可分为可降解和不可降解缝合线，不可降解缝合线包括丝线、聚丙烯线、聚乙烯线等，其虽然机械性能强，但是不可降解性常常导致术后拆线的痛苦，甚至还需进行手术拆除；可降解线主要包括羊肠线、化学合成线及纯天然胶原蛋白，其能够在体内被降解代谢，无毒无害，减少术后不必要的麻烦和痛苦。At present, the commonly used medical surgical sutures can be divided into degradable and non-degradable sutures. Non-degradable sutures include silk, polypropylene, polyethylene, etc. Although they have strong mechanical properties, their non-degradability often leads to postoperative disassembly. The pain of the thread even requires surgical removal; the degradable thread mainly includes catgut, chemically synthesized thread and pure natural collagen, which can be degraded and metabolized in the body, non-toxic and harmless, reducing unnecessary troubles and complications after operation. pain.

但是，可降解线中的羊肠线(具体如中国发明专利CN1363397A所述)因对人体存在不同程度的排异现象，易引起患者术后排异反应，且缝线抗张强度偏低，临床已显现各种术后不良反应；又如中国发明专利CN201543004U中所述的用于外科缝线、疝和体壁修复网片和防粘连膜片的纤维，其包括聚丙烯芯层、聚偏二氟乙烯皮层，芯层和皮层为同心结构，经复合纺丝形成同心结构复合纤维，此化学合成缝线植入后仍存在不同程度的化学残留，易造成机体皮下硬结，部分患者术后存在皮下瘙痒等问题。目前较为完善的是纯天然胶原蛋白缝合线，取自动物肌腱部位。However, the catgut in the degradable thread (specifically as described in Chinese invention patent CN1363397A) has different degrees of rejection to the human body, which is easy to cause postoperative rejection in patients, and the tensile strength of the suture is low. Various postoperative adverse reactions have been shown; as described in Chinese invention patent CN201543004U for surgical sutures, hernia and body wall repair meshes and fibers for anti-adhesion membranes, which include polypropylene core layer, polyvinylidene The vinyl fluoride skin layer, the core layer and the skin layer are concentric structures, which are formed by composite spinning to form concentric structure composite fibers. After the chemical synthetic suture is implanted, there are still chemical residues to varying degrees, which is easy to cause subcutaneous induration of the body. Some patients have subcutaneous tissue after surgery. itching and other issues. At present, the most perfect is the pure natural collagen suture, which is taken from the tendon of the animal.

然而，上述可降解线仅是起到手术后缝合伤口的作用，经缝合的伤口愈合慢，很容易受周围环境细菌的污染，表现为切口处出现或渗出脓性分泌物等现象，一般采用注射或口服抗生素类药物来治疗，对人体产生的副作用较大。However, the above-mentioned degradable thread is only used to suture the wound after surgery. The sutured wound heals slowly and is easily contaminated by bacteria in the surrounding environment. Injected or oral antibiotics for treatment have greater side effects on the human body.

因此，提供一种加速伤口愈合、副作用小、抗感染及具有生物活性的可降解手术缝线及其制备方法，是目前亟需解决的问题。Therefore, it is an urgent problem to provide a degradable surgical suture with accelerated wound healing, less side effects, anti-infection and biological activity and a preparation method thereof.

发明内容SUMMARY OF THE INVENTION

为了克服上述问题，本发明人进行了锐意研究，结果发现：选用生物相容性强、可降解的材料作为基体，然后加入包载生物活性物质的胶原蛋白，采用静电纺丝技术并设置特定的参数，能够制备得到可吸收降解、生物相容性和安全性高的可降解手术缝合线，从而完成了本发明。In order to overcome the above-mentioned problems, the inventors have carried out keen research and found that: selecting a material with strong biocompatibility and degradability as the matrix, then adding collagen containing bioactive substances, using electrospinning technology and setting specific parameters, the degradable surgical suture thread with high biocompatibility and safety can be prepared, thus completing the present invention.

具体来说，本发明的目的在于提供以下方面：Specifically, the object of the present invention is to provide the following aspects:

第一方面，本发明提供了一种具有生物活性的可降解手术缝线，其中，所述手术缝线由包括以下重量配比的原料制成：In a first aspect, the present invention provides a bioactive degradable surgical suture, wherein the surgical suture is made of raw materials comprising the following weight ratios:

基体 200～1200重量份Matrix 200～1200 parts by weight

负载物 220～240重量份。Load 220-240 parts by weight.

第二方面，本发明提供了一种具有生物活性的可降解手术缝线的制备方法，其中，所述方法包括以下步骤：In a second aspect, the present invention provides a method for preparing a bioactive degradable surgical suture, wherein the method comprises the following steps:

步骤1，制备负载物的溶液；Step 1, prepare the solution of the load;

步骤2，将基体加入负载物溶液中，搅拌均匀，得到聚合物溶液；Step 2, adding the matrix into the load solution, stirring evenly, to obtain a polymer solution;

步骤3，将聚合物溶液制备得到手术缝线。In step 3, the polymer solution is prepared to obtain surgical sutures.

本发明所具有的有益效果包括：The beneficial effects of the present invention include:

(1)本发明所提供的具有生物活性的可降解手术缝线，机械性能强，生物相容性高，安全性高；(1) The bioactive degradable surgical suture provided by the present invention has strong mechanical properties, high biocompatibility and high safety;

(2)本发明所提供的手术缝线，能够在缝合部位释放生长因子，可以减少伤口感染，促进肉芽组织增生和胶原的生成，有效缩短康复时间；(2) The surgical suture provided by the present invention can release growth factors at the suture site, reduce wound infection, promote granulation tissue hyperplasia and collagen production, and effectively shorten recovery time;

(3)本发明所提供的手术缝线，直径小，均一性好；(3) the surgical suture provided by the present invention has a small diameter and good uniformity;

(4)，本发明所提供的手术缝线的制备方法，步骤简单，条件易控，通用性强，适合大规模生产。(4) The preparation method of the surgical suture provided by the present invention has simple steps, easily controllable conditions, strong versatility, and is suitable for large-scale production.

附图说明Description of drawings

图1示出了本发明所述手术缝线中胶原蛋白和生长因子的示意图；Figure 1 shows a schematic diagram of collagen and growth factors in the surgical suture of the present invention;

图2中的a示出了利用对比例6制备的手术缝线进行缝合后第0天的效果；a in Figure 2 shows the effect on day 0 after suture using the surgical suture prepared in Comparative Example 6;

图2中的b示出了利用对比例6制备的手术缝线缝合后愈合第13天的效果；b in Figure 2 shows the effect of healing on the 13th day after the surgical suture prepared in Comparative Example 6 was sutured;

图3中的a示出了利用实施例1制备的手术缝线进行缝合后第0天的效果；a in Figure 3 shows the effect on day 0 after suture using the surgical suture prepared in Example 1;

图3中的b示出了利用实施例1制备的手术缝线缝合后愈合第13天的效果。b in FIG. 3 shows the effect of healing on the 13th day after the surgical suture prepared in Example 1 was sutured.

具体实施方式Detailed ways

下面通过优选实施方式和实施例对本发明进一步详细说明。通过这些说明，本发明的特点和优点将变得更为清楚明确。The present invention will be described in further detail below through preferred embodiments and examples. The features and advantages of the present invention will become more apparent from these descriptions.

本发明提供了一种具有生物活性的可降解手术缝线，该手术缝线由包括以下重量配比的原料制成：The present invention provides a bioactive degradable surgical suture, which is made of raw materials comprising the following weight ratios:

基体 200～1200重量份Matrix 200～1200 parts by weight

负载物 220～240重量份。Load 220-240 parts by weight.

优选地，所述手术缝线由包括以下重量配比的原料制成：Preferably, the surgical suture is made of raw materials comprising the following weight ratios:

基体 250～1100重量份Matrix 250～1100 parts by weight

负载物 220～240重量份。Load 220-240 parts by weight.

更优选地，所述手术缝线由包括以下重量配比的原料制成：More preferably, the surgical suture is made of raw materials including the following weight ratios:

基体 350～1050重量份Matrix 350～1050 parts by weight

负载物 220～240重量份。Load 220-240 parts by weight.

根据本发明一种优选的实施方式，所述基体为可降解的高分子材料，优选为聚乳酸、聚乙烯醇、聚己内酯、聚乙交酯、聚对二氧环己酮或聚乙丙交酯中的一种或多种。According to a preferred embodiment of the present invention, the matrix is a degradable polymer material, preferably polylactic acid, polyvinyl alcohol, polycaprolactone, polyglycolide, polydioxanone or polyethylene one or more of lactide.

在进一步优选的实施方式中，所述基体为聚乳酸、聚己内酯、聚乙交酯或聚对二氧环己酮中的一种或多种。In a further preferred embodiment, the matrix is one or more of polylactic acid, polycaprolactone, polyglycolide or polydioxanone.

在更进一步优选的实施方式中，所述基体为聚己内酯。In a further preferred embodiment, the matrix is polycaprolactone.

本发明人经过研究发现，聚己内酯具有良好的机械性能和很好的生物相容性，适合内脏器官的缝合，且其可在6～12个月内完全降解成CO₂和H₂O，降解产物可随基体正常代谢排出体外，不会在体内堆积。尤其在膀胱和尿道类的手术缝合过程中，降解产物的堆积容易造成器官的堵塞，危害机体健康，采用本发明中的聚己内酯为缝合线基体材料，能够有效避免此类危害。The inventors have found through research that polycaprolactone has good mechanical properties and good biocompatibility, is suitable for suturing of internal organs, and can be completely degraded into CO₂ and H₂ O within 6-12 months , the degradation products can be excreted with the normal metabolism of the matrix, and will not accumulate in the body. Especially in the surgical suturing of the bladder and urethra, the accumulation of degradation products can easily cause blockage of organs and endanger the health of the body. Using the polycaprolactone in the present invention as the suture base material can effectively avoid such hazards.

根据本发明一种优选的实施方式，所述负载物包括胶原蛋白和生物活性物质。According to a preferred embodiment of the present invention, the loading material includes collagen and biologically active substances.

本发明人经过研究发现，胶原蛋白是动物体普遍存在的一类大分子蛋白，在哺乳动物体内的含量占整个生物体自身总蛋白含量的25％，是具有良好的细胞黏附力的细胞外基质，对皮肤表面的蛋白质分子具有较大的亲和力，有利于组织生长、修复，在手术缝线中添加胶原蛋白，可进一步增加缝线的细胞相容性，促进组织的增生和修复，生物降解安全性高。The inventors have found through research that collagen is a type of macromolecular protein commonly found in animals, and its content in mammals accounts for 25% of the total protein content of the entire organism. It is an extracellular matrix with good cell adhesion. , has a greater affinity for protein molecules on the skin surface, which is conducive to tissue growth and repair. Adding collagen to surgical sutures can further increase the cytocompatibility of sutures, promote tissue proliferation and repair, and biodegradation is safe. Sex is high.

在进一步优选的实施方式中，所述生物活性物质为肽，优选为生长因子。In a further preferred embodiment, the biologically active substance is a peptide, preferably a growth factor.

其中，生长因子作为重要的细胞外信号，能够帮助伤口愈合，同时促进肉芽组织增生和胶原的生成，减少病人后期感染风险。Among them, growth factors, as important extracellular signals, can help wound healing, promote granulation tissue proliferation and collagen production, and reduce the risk of late infection in patients.

在更进一步优选的实施方式中，所述生长因子为碱性成纤维生长因子。In an even further preferred embodiment, the growth factor is basic fibroblast growth factor.

本发明人经过研究发现，碱性成纤维生长因子是重要的促有丝分裂因子，也是形态发生和分化的诱导因子，其主要生物学作用有：促进肉芽组织的形成和创面的愈合；促进微血管形成和改善微循环，参与新生血管形成的全过程；促进成骨细胞的增殖、抑制破骨细胞的形成，能够促进骨形成。The inventors have found through research that basic fibroblast growth factor is an important mitogenic factor and an inducer of morphogenesis and differentiation. Its main biological functions include: promoting the formation of granulation tissue and wound healing; promoting the formation of microvessels and Improve microcirculation, participate in the whole process of neovascularization; promote the proliferation of osteoblasts, inhibit the formation of osteoclasts, and promote bone formation.

在本发明中，将胶原蛋白和碱性成纤维生长因子添加至基体中制备手术缝线，不会改变基体的机械性能，且基体和胶原蛋白也不会对生长因子蛋白质结构产生影响。In the present invention, adding collagen and basic fibroblast growth factor into the matrix to prepare surgical sutures will not change the mechanical properties of the matrix, and the matrix and collagen will not affect the protein structure of the growth factor.

根据本发明一种优选的实施方式中，所述可降解手术缝线的外径为0.6～1.2mm，优选为0.7～1.1mm，更优选为0.8～1.0mm。According to a preferred embodiment of the present invention, the outer diameter of the degradable surgical suture is 0.6-1.2 mm, preferably 0.7-1.1 mm, more preferably 0.8-1.0 mm.

本发明还提供了一种具有生物活性的可降解手术缝线的制备方法，所述方法包括以下步骤：The present invention also provides a method for preparing a bioactive degradable surgical suture, the method comprising the following steps:

步骤1，制备负载物的溶液；Step 1, prepare the solution of the load;

步骤2，将基体加入负载物溶液中，得到聚合物溶液；Step 2, adding the matrix into the load solution to obtain a polymer solution;

步骤3，将聚合物溶液制备得到手术缝线。In step 3, the polymer solution is prepared to obtain surgical sutures.

以下具体地描述本发明所述的手术缝线的制备方法：The following specifically describes the preparation method of the surgical suture of the present invention:

步骤1，制备负载物的溶液。Step 1, prepare a solution of the load.

在本发明中，所述负载物包括胶原蛋白和生长因子，所述负载物溶液的制备包括以下步骤：In the present invention, the loading material includes collagen and growth factors, and the preparation of the loading material solution includes the following steps:

步骤a，称取一定量的胶原蛋白，溶于一定体积的溶剂中，制备得到胶原蛋白溶液。In step a, a certain amount of collagen is weighed and dissolved in a certain volume of solvent to prepare a collagen solution.

根据本发明一种优选的实施方式，所述溶剂为醋酸、磷酸、盐酸、磷酸盐缓冲溶液、六氟异丙醇或水中的一种或多种。According to a preferred embodiment of the present invention, the solvent is one or more of acetic acid, phosphoric acid, hydrochloric acid, phosphate buffer solution, hexafluoroisopropanol or water.

在进一步优选的实施方式中，所述溶剂为醋酸、磷酸盐缓冲溶液、六氟异丙醇或水中的一种或多种。In a further preferred embodiment, the solvent is one or more of acetic acid, phosphate buffer solution, hexafluoroisopropanol or water.

在更进一步优选的实施方式中，所述溶剂为六氟异丙醇和/或水。In a further preferred embodiment, the solvent is hexafluoroisopropanol and/or water.

本发明人经过研究发现，六氟异丙醇的极性很强，易于与多种有机溶剂混合，可以溶解很多高分子聚合物，且挥发性强，在后续制备手术缝线时，纺丝后的溶液残留少，易于除去；而水作为一种绿色环保的溶剂，可有效溶解胶原蛋白和碱性成纤维生长因子，有利于促使胶原蛋白更有效的包载生长因子。The inventors have found through research that hexafluoroisopropanol has strong polarity, is easy to mix with various organic solvents, can dissolve many high molecular polymers, and has strong volatility. In the subsequent preparation of surgical sutures, after spinning As a green and environmentally friendly solvent, water can effectively dissolve collagen and basic fibroblast growth factor, which is conducive to promoting collagen to more effectively encapsulate growth factors.

优选地，所述溶剂为六氟异丙醇和水时，二者的体积比为(8～40)：1，优选为(10～30)：1，更优选为(12～27)：1。Preferably, when the solvent is hexafluoroisopropanol and water, the volume ratio of the two is (8-40):1, preferably (10-30):1, more preferably (12-27):1.

根据本发明一种优选的实施方式，所述胶原蛋白与溶剂在冰浴条件下混合，搅拌至完全溶解。According to a preferred embodiment of the present invention, the collagen and the solvent are mixed in an ice bath and stirred until completely dissolved.

其中，在冰浴下混合能够同时保持胶原蛋白和生长因子的活性。Among them, mixing under an ice bath can maintain the activity of collagen and growth factors at the same time.

在进一步优选的实施方式中，所述搅拌的时间为0.5～2h，优选为0.75～1.5h，更优选为1h。In a further preferred embodiment, the stirring time is 0.5-2 h, preferably 0.75-1.5 h, more preferably 1 h.

其中，待溶液变得澄清，即胶原蛋白完全溶解后停止搅拌。Among them, stop stirring when the solution becomes clear, that is, the collagen is completely dissolved.

根据本发明一种优选的实施方式，所述胶原蛋白的浓度为20～45mg/mL，优选为25～40mg/mL，更优选为27～35mg/mL。According to a preferred embodiment of the present invention, the concentration of the collagen is 20-45 mg/mL, preferably 25-40 mg/mL, and more preferably 27-35 mg/mL.

步骤b，将生长因子加入胶原蛋白溶液中，混合一定时间后，制备得到负载物的溶液。In step b, the growth factor is added to the collagen solution, and after mixing for a certain period of time, a solution of the loaded substance is prepared.

本发明人经过研究发现，生长因子极容易降解，且随着温度的提升降解速度加快，因此，本发明优选将其包载在胶原蛋白溶液中，使得胶原蛋白与生长因子之间通过共价键和氢键连接，形成纳米颗粒(具体如图1所示)，从而提高了生长因子的稳定性，使其能够在缝合部位得到有效释放。The inventors have found through research that growth factors are easily degraded, and the degradation speed increases with the increase of temperature. Therefore, in the present invention, it is preferred to encapsulate it in a collagen solution, so that the collagen and the growth factor pass through covalent bonds. and hydrogen bonds to form nanoparticles (as shown in Figure 1), which improves the stability of growth factors and enables them to be effectively released at the suture site.

在本发明中，所述生长因子优选为碱性成纤维生长因子。In the present invention, the growth factor is preferably basic fibroblast growth factor.

根据本发明一种优选的实施方式，所述混合在冰浴下进行，所述混合时间为18～30h，优选为20～26h，更优选为24h。According to a preferred embodiment of the present invention, the mixing is performed under an ice bath, and the mixing time is 18-30 h, preferably 20-26 h, more preferably 24 h.

其中，在冰浴的过程中需要不停搅拌，以使包载充分、均匀。Among them, it is necessary to keep stirring during the ice bath to make the encapsulation sufficient and uniform.

在本发明中，在冰浴下对生长因子进行包载，能够有效减弱生长因子的降解，且包载时间为18～30h，能够使胶原蛋白对生长因子充分且均匀的包载。当包载时间低于18h时，会导致包载不完全，得到的负载物有效性较低；当包载时间高于30h时，随着时间的延长，包载已经饱和，包载效果不再提升，延长时间会降低效率。In the present invention, encapsulating the growth factor under ice bath can effectively reduce the degradation of the growth factor, and the encapsulation time is 18-30 h, so that the collagen can fully and uniformly encapsulate the growth factor. When the encapsulation time is less than 18h, the encapsulation will be incomplete and the obtained payload will be less effective; when the encapsulation time is higher than 30h, the encapsulation will be saturated with the extension of time, and the encapsulation effect will no longer be effective. Lifting, prolonging the time will reduce the efficiency.

在进一步优选的实施方式中，所述胶原蛋白溶液与生长因子的体积比为(4000～9000)：115，优选为(5000～8500)：115，更优选为(5500～8200)：115。In a further preferred embodiment, the volume ratio of the collagen solution to the growth factor is (4000-9000):115, preferably (5000-8500):115, more preferably (5500-8200):115.

本发明人经过研究发现，当胶原蛋白溶液与生长因子的体积比大于9000:115时，胶原蛋白溶液已对生长因子包载完全，过多的加入胶原蛋白溶液会造成资源浪费，同时会使体系混合不均匀，进而影响后期纺丝，且会影响生长因子的作用效果；当胶原蛋白溶液与生长因子的体积比小于4000:115时，会使部分生长因子不能被包载，进而发生降解，无法起到包载作用。The inventors have found through research that when the volume ratio of collagen solution to growth factor is greater than 9000:115, the collagen solution has completely encapsulated the growth factor. Excessive addition of collagen solution will cause waste of resources, and at the same time make the system The mixing is uneven, which will affect the later spinning, and will affect the effect of growth factors; when the volume ratio of collagen solution and growth factors is less than 4000:115, some growth factors will not be encapsulated, and then degradation will occur. play a role in packaging.

步骤2，将基体加入负载物溶液中，搅拌混匀，得到聚合物溶液。Step 2, adding the matrix into the loading solution, stirring and mixing to obtain a polymer solution.

根据本发明一种优选的实施方式，所述搅拌在冰浴条件下进行，所述搅拌时间为2～4h，优选为2.5～3.5h，更优选为3h。According to a preferred embodiment of the present invention, the stirring is performed under ice bath conditions, and the stirring time is 2-4 h, preferably 2.5-3.5 h, more preferably 3 h.

在进一步优选的实施方式中，所述聚合物溶液中基体与负载物中胶原蛋白的重量比为(200～1200)：225，优选为(250～1100)：225，更优选为(350～1050):225。In a further preferred embodiment, the weight ratio of the matrix to the collagen in the load in the polymer solution is (200-1200):225, preferably (250-1100):225, more preferably (350-1050 ): 225.

步骤3，将聚合物溶液制备得到手术缝线。In step 3, the polymer solution is prepared to obtain surgical sutures.

本发明人经过研究发现，由静电纺丝制得的纤维直径小、均一性好，能够从纳米尺度上模仿天然细胞外基质。因此，在本发明中，优选采用静电纺丝的方法将聚合物溶液制备成手术缝线。The inventors have found through research that the fibers prepared by electrospinning have small diameters and good uniformity, and can imitate natural extracellular matrix from the nanometer scale. Therefore, in the present invention, the electrospinning method is preferably used to prepare the polymer solution into a surgical suture.

其中，静电纺丝技术是在数十千伏的直流电场中，带电聚合物溶液的静电斥力在毛细管尖端克服表面张力形成射流，随着溶剂的挥发，射流固化形成亚微米至纳米级的超细纤维丝，并被接收装置接收。Among them, the electrospinning technology is that in a DC electric field of tens of kilovolts, the electrostatic repulsion of the charged polymer solution overcomes the surface tension at the tip of the capillary to form a jet. With the volatilization of the solvent, the jet solidifies to form sub-micron to nano-scale ultra-fine particles. Fiber filaments are received by the receiving device.

在本发明中，采用静电纺丝装置将聚合物制备得到手术缝线，包括以下步骤：In the present invention, an electrospinning device is used to prepare a surgical suture from a polymer, including the following steps:

步骤I，在装置内装入聚合物溶液。In step 1, the polymer solution is loaded into the device.

其中，将上述制备得到的聚合物溶液装入静电纺丝装置的注射器中，所述注射器的容积为10mL，然后选取细针头纺丝。Wherein, the polymer solution prepared above was put into the syringe of the electrospinning device, and the volume of the syringe was 10 mL, and then a fine needle was selected for spinning.

步骤II，调节装置的各项参数。Step II, adjust various parameters of the device.

其中，所述静电纺丝装置的参数包括输出电压、纺丝针头与接收器的距离、注射泵的推动速度、接收器速度和接收时间。The parameters of the electrospinning device include the output voltage, the distance between the spinning needle and the receiver, the pushing speed of the syringe pump, the speed of the receiver and the receiving time.

根据本发明一种优选的实施方式，所述输出电压为4～22kv优选为4～20kv，更优选为5～17kv。According to a preferred embodiment of the present invention, the output voltage is 4-22kv, preferably 4-20kv, more preferably 5-17kv.

本发明人经过研究发现，所述静电纺丝装置的输出电压为4～22kv，优选为4～20kv，更优选为5～17kv时，制备的得到的手术缝线的直径最小。当输出电压小于4kv时，由于电力不足，纺丝液会以液滴的形式向外喷射；当输出电压高于22kv时，随着电压的增大，制得的纤维直径的减小速度变得极为缓慢，而且会导致纺丝液以电喷雾形式飞离针头，不能正常进行静电纺丝。The inventors have found through research that when the output voltage of the electrospinning device is 4-22 kV, preferably 4-20 kV, more preferably 5-17 kV, the diameter of the prepared surgical suture is the smallest. When the output voltage is less than 4kv, due to insufficient power, the spinning solution will be sprayed outward in the form of droplets; when the output voltage is higher than 22kv, with the increase of the voltage, the decreasing speed of the obtained fiber diameter becomes It is extremely slow and will cause the spinning solution to fly off the needle in the form of an electrospray, preventing normal electrospinning.

根据本发明一种优选的实施方式，所述纺丝针头与接收器的距离为8～20cm，优选为9～18cm，更优选为11～15cm。According to a preferred embodiment of the present invention, the distance between the spinning needle and the receiver is 8-20 cm, preferably 9-18 cm, more preferably 11-15 cm.

本发明人经过研究发现，当纺丝针头与接收器的距离小于8cm时，接收距离太短，纺丝液中的溶剂来不及挥发，易收集到雾状液滴或者是粘连到一起的纤维，会影响纤维的性能；当纺丝针头与接收器的距离大于20cm时，由于接收距离太大，电场力会大大减弱，纤维的均匀性会下降。The inventor found through research that when the distance between the spinning needle and the receiver is less than 8 cm, the receiving distance is too short, the solvent in the spinning solution cannot volatilize in time, and mist droplets or fibers that are stuck together are easily collected, which will cause Affect the performance of the fiber; when the distance between the spinning needle and the receiver is greater than 20cm, because the receiving distance is too large, the electric field force will be greatly weakened, and the uniformity of the fiber will decrease.

根据本发明一种优选的实施方式，所述注射泵的推动速度为0.5～3.8mm/h，优选为0.8～3.6mm/h，更优选为1.0～3.4mm/h。According to a preferred embodiment of the present invention, the pushing speed of the syringe pump is 0.5-3.8 mm/h, preferably 0.8-3.6 mm/h, more preferably 1.0-3.4 mm/h.

其中，所述注射泵用于推动注射器推进纺丝液。Wherein, the syringe pump is used to push the syringe to push the spinning solution.

本发明人经过研究发现，当注射泵的推动速度小于0.5mm/h时，在成丝过程中，电解速度比出液速度快，会使纺丝不连续，出液不够及时，导致丝在形成过程中产生断裂，且会使纤维的排列有序度下降；当注射泵的推动速度大于3.8mm/h，在成丝过程中，电解速度比出液速度慢，导致部分溶液来不及电解，残留在针头，堵塞针头，或以液滴形式溅射在接收器上，导致收集到雾状液滴或者是粘连到一起的纤维，会影响纤维的性能，The inventors have found through research that when the pushing speed of the syringe pump is less than 0.5 mm/h, the electrolysis speed is faster than the liquid discharge speed during the spinning process, which will make the spinning discontinuous, and the liquid discharge will not be timely enough, resulting in the formation of the silk. During the process of breaking, and the order of the fibers will decrease; when the pushing speed of the syringe pump is greater than 3.8mm/h, the electrolysis speed is slower than the liquid discharge speed during the filament formation process, resulting in part of the solution that is too late for electrolysis and remains in the filament. needles, plugging needles, or sputtering on the receiver as droplets, resulting in the collection of mist droplets or fibers that stick together, which can affect fiber performance,

根据本发明一种优选的实施方式，所述接收器的速度为200～400r/min，优选为240～370r/min，更优选为280～320r/min，和/或According to a preferred embodiment of the present invention, the speed of the receiver is 200-400 r/min, preferably 240-370 r/min, more preferably 280-320 r/min, and/or

所述接收时间为4～12min，优选为5～10min。The receiving time is 4-12 minutes, preferably 5-10 minutes.

其中，所述接收器为转盘接收器。Wherein, the receiver is a turntable receiver.

本发明人经过研究发现，在静电纺丝纤维的收集过程中，空气的对流以及接收器的卷绕会对纤维产生进一步的拉伸，使得纤维的平均直径减小。The inventors have found through research that during the collection process of the electrospun fibers, the convection of the air and the winding of the receiver will further stretch the fibers, so that the average diameter of the fibers is reduced.

当接收器的速度小于200r/min时，由于转盘周围空气的对流不足以改变纤维的运动轨迹，使其不能很好地在接收器上形成；当接收器的速度大于400r/min时，转盘周围强烈的空气对流使得纤维靠近接收器时运动轨迹改变，产生断裂，且会使纤维的排列有序度下降。When the speed of the receiver is less than 200r/min, because the convection of the air around the turntable is not enough to change the motion trajectory of the fiber, it cannot be formed on the receiver well; when the speed of the receiver is greater than 400r/min, around the turntable The strong air convection changes the motion trajectory of the fibers when they are close to the receiver, resulting in breakage and a decrease in the order of the fibers.

步骤III，开启装置，制备得到具有生物活性的可降解手术缝线。In step III, the device is opened to prepare bioactive degradable surgical sutures.

其中，连通电源，通过静电纺丝装置制备，完成后收集在转盘接收器上形成的纺丝，得到具有生物活性的可降解手术缝线。Wherein, the power supply is connected, and the electrospinning device is used for preparation, and after completion, the spinning formed on the turntable receiver is collected to obtain bioactive degradable surgical sutures.

实施例Example

以下通过具体实例进一步描述本发明，不过这些实例仅仅是范例性的，并不对本发明的保护范围构成任何限制。The present invention is further described below through specific examples, but these examples are only exemplary and do not constitute any limitation to the protection scope of the present invention.

在以下实施例中：胶原蛋白由大鼠鼠尾胶原提取得到；碱性成纤维生长因子由课题组制备纯化得到；聚己内酯购自美国Sigma-Aldrich；六氟异丙醇购自上海阿拉丁生化科技股份有限公司。In the following examples: collagen was extracted from rat tail collagen; basic fibroblast growth factor was prepared and purified by the research group; polycaprolactone was purchased from Sigma-Aldrich in the United States; hexafluoroisopropanol was purchased from Shanghai A Latin Biochemical Technology Co., Ltd.

实施例1Example 1

(一)称取225mg的胶原蛋白溶于6ml六氟异丙醇和0.5ml水，在冰浴下搅拌1小时，待溶液变得澄清，胶原蛋白完全溶解之后，量取115ul碱性成纤维生长因子包载在胶原中，并置于冰浴条件下搅拌，24h后，向体系中加0.45g聚己内酯，于冰水浴中搅拌3小时，直至整个体系混合均匀，最终得到聚己内酯-胶原复合包载生长因子聚合物。(1) Weigh 225mg of collagen and dissolve it in 6ml of hexafluoroisopropanol and 0.5ml of water, stir under ice bath for 1 hour, after the solution becomes clear and the collagen is completely dissolved, measure 115ul of basic fibroblast growth factor Encapsulated in collagen, and stirred in an ice bath. After 24 hours, 0.45 g of polycaprolactone was added to the system and stirred in an ice-water bath for 3 hours until the whole system was evenly mixed, and finally polycaprolactone- Collagen complex encapsulates growth factor polymers.

(二)采用静电纺丝装置(型号：天津云帆科技YFSP-GⅢ)制备手术缝线，将制备的聚合物溶液放置于10ml注射器中，选取细针头纺丝时控制输出电压5kv，纺丝针头与接收器距离为11cm，注射泵的推动速度控制1.0mm/h，接收器速度保持在280r/min，接收时间控制在5min内，在转盘接收器上形成的纺丝，得到聚己内酯-胶原复合包载生长因子超细纤维线。(2) Use an electrospinning device (model: Tianjin Yunfan Technology YFSP-GⅢ) to prepare surgical sutures, place the prepared polymer solution in a 10ml syringe, select a fine needle for spinning and control the output voltage to 5kv, and the spinning needle The distance from the receiver is 11cm, the pushing speed of the syringe pump is controlled at 1.0mm/h, the speed of the receiver is kept at 280r/min, and the receiving time is controlled within 5min. Collagen complex encapsulates growth factor microfiber threads.

实施例2Example 2

(一)称取225mg的胶原蛋白溶于6.75ml六氟异丙醇和0.25ml水，在冰浴下搅拌1小时，待溶液变得澄清，胶原蛋白完全溶解之后，量取115ul碱性成纤维生长因子包载在胶原中，并置于冰浴条件下搅拌，24h后，向体系中加0.45g聚己内酯，于冰水浴中搅拌3小时，直至整个体系混合均匀，最终得到聚己内酯-胶原复合包载生长因子聚合物。(1) Weigh 225mg of collagen and dissolve it in 6.75ml of hexafluoroisopropanol and 0.25ml of water, and stir for 1 hour in an ice bath. After the solution becomes clear and the collagen is completely dissolved, measure 115ul of alkaline fibroblast growth The factor was loaded in collagen and stirred in an ice bath. After 24 hours, 0.45 g of polycaprolactone was added to the system and stirred in an ice-water bath for 3 hours until the whole system was evenly mixed, and finally polycaprolactone was obtained. - Collagen complex encapsulates growth factor polymers.

(二)采用静电纺丝装置(型号：天津云帆科技YFSP-GⅢ)制备手术缝线，将制备的聚合物溶液放置于10ml注射器中，选取细针头纺丝时控制输出电压7kv，纺丝针头与接收器距离为15cm，注射泵的推动速度控制1.2mm/h，接收器速度保持在320r/min，接收时间控制在6min内，在转盘接收器上形成的纺丝，得到聚己内酯-胶原复合包载生长因子超细纤维线。(2) Use an electrospinning device (model: Tianjin Yunfan Technology YFSP-GⅢ) to prepare surgical sutures, place the prepared polymer solution in a 10ml syringe, select a fine needle for spinning, and control the output voltage to 7kv, and the spinning needle The distance from the receiver is 15cm, the pushing speed of the syringe pump is controlled at 1.2mm/h, the speed of the receiver is kept at 320r/min, and the receiving time is controlled within 6min. Collagen complex encapsulates growth factor microfiber threads.

实施例3Example 3

(一)称取225mg的胶原蛋白溶于6.5ml六氟异丙醇和0.5ml水，在冰浴下搅拌1小时，待溶液变得澄清，胶原蛋白完全溶解之后，量取115ul碱性成纤维生长因子包载在胶原中，并置于冰浴条件下搅拌，24h后，向体系中加0.7g聚己内酯，于冰水浴中搅拌3小时，直至整个体系混合均匀，最终得到聚己内酯-胶原复合包载生长因子聚合物。(1) Weigh 225mg of collagen and dissolve it in 6.5ml of hexafluoroisopropanol and 0.5ml of water, and stir for 1 hour in an ice bath. After the solution becomes clear and the collagen is completely dissolved, measure 115ul of basic fibroblast growth The factor was loaded in collagen and stirred in an ice bath. After 24 hours, 0.7 g of polycaprolactone was added to the system and stirred in an ice-water bath for 3 hours until the whole system was evenly mixed, and finally polycaprolactone was obtained. - Collagen complex encapsulates growth factor polymers.

(二)采用静电纺丝装置(型号：天津云帆科技YFSP-GⅢ)制备手术缝线，将制备的聚合物溶液放置于10ml注射器中，选取细针头纺丝时控制输出电压10kv，纺丝针头与接收器距离为15cm，注射泵的推动速度控制1.2mm/h，接收器速度保持在300r/min，接收时间控制在7min内，在转盘接收器上形成的纺丝，得到聚己内酯-胶原复合包载生长因子超细纤维线。(2) Use an electrospinning device (model: Tianjin Yunfan Technology YFSP-GⅢ) to prepare surgical sutures, place the prepared polymer solution in a 10ml syringe, select a fine needle for spinning, and control the output voltage to 10kv. The distance from the receiver is 15cm, the pushing speed of the syringe pump is controlled at 1.2mm/h, the speed of the receiver is kept at 300r/min, and the receiving time is controlled within 7min. Collagen complex encapsulates growth factor microfiber threads.

实施例4Example 4

(一)称取225mg的胶原蛋白溶于6.75ml六氟异丙醇和0.25ml水，在冰浴下搅拌1小时，待溶液变得澄清，胶原蛋白完全溶解之后，量取115ul碱性成纤维生长因子包载在胶原中，并置于冰浴条件下搅拌，24h后，向体系中加0.7g聚己内酯，于冰水浴中搅拌3小时，直至整个体系混合均匀，最终得到聚己内酯-胶原复合包载生长因子聚合物。(1) Weigh 225mg of collagen and dissolve it in 6.75ml of hexafluoroisopropanol and 0.25ml of water, and stir for 1 hour in an ice bath. After the solution becomes clear and the collagen is completely dissolved, measure 115ul of alkaline fibroblast growth The factor was loaded in collagen and stirred in an ice bath. After 24 hours, 0.7 g of polycaprolactone was added to the system and stirred in an ice-water bath for 3 hours until the whole system was evenly mixed, and finally polycaprolactone was obtained. - Collagen complex encapsulates growth factor polymers.

(二)采用静电纺丝装置(型号：天津云帆科技YFSP-GⅢ)制备手术缝线，将制备的聚合物溶液放置于10ml注射器中，选取细针头纺丝时控制输出电压15kv，纺丝针头与接收器距离为14cm，注射泵的推动速度控制2.1mm/h，接收器速度保持在300r/min，接收时间控制在7min内，在转盘接收器上形成的纺丝，得到聚己内酯-胶原复合包载生长因子超细纤维线。(2) Use an electrospinning device (model: Tianjin Yunfan Technology YFSP-GⅢ) to prepare surgical sutures, place the prepared polymer solution in a 10ml syringe, select a fine needle for spinning, and control the output voltage to 15kv. The distance from the receiver is 14cm, the pushing speed of the syringe pump is controlled at 2.1mm/h, the speed of the receiver is kept at 300r/min, and the receiving time is controlled within 7min. Collagen complex encapsulates growth factor microfiber threads.

实施例5Example 5

(一)称取225mg的胶原蛋白溶于6.75ml六氟异丙醇和0.25ml水，在冰浴下搅拌1小时，待溶液变得澄清，胶原蛋白完全溶解之后，量取115ul碱性成纤维生长因子包载在胶原中，并置于冰浴条件下搅拌，24h后，向体系中加0.7g聚己内酯，于冰水浴中搅拌3小时，直至整个体系混合均匀，最终得到聚己内酯-胶原复合包载生长因子聚合物。(1) Weigh 225mg of collagen and dissolve it in 6.75ml of hexafluoroisopropanol and 0.25ml of water, and stir for 1 hour in an ice bath. After the solution becomes clear and the collagen is completely dissolved, measure 115ul of alkaline fibroblast growth The factor was loaded in collagen and stirred in an ice bath. After 24 hours, 0.7 g of polycaprolactone was added to the system and stirred in an ice-water bath for 3 hours until the whole system was evenly mixed, and finally polycaprolactone was obtained. - Collagen complex encapsulates growth factor polymers.

(二)采用静电纺丝装置(型号：天津云帆科技YFSP-GⅢ)制备手术缝线，将制备的聚合物溶液放置于10ml注射器中，选取细针头纺丝时控制输出电压17kv，纺丝针头与接收器距离为13cm，注射泵的推动速度控制2.1mm/h，接收器速度保持在300r/min，接收时间控制在7min内，在转盘接收器上形成的纺丝，得到聚己内酯-胶原复合包载生长因子超细纤维线。(2) Use an electrospinning device (model: Tianjin Yunfan Technology YFSP-GⅢ) to prepare surgical sutures, place the prepared polymer solution in a 10ml syringe, select a fine needle for spinning and control the output voltage to 17kv, and the spinning needle The distance from the receiver is 13cm, the pushing speed of the syringe pump is controlled at 2.1mm/h, the speed of the receiver is kept at 300r/min, and the receiving time is controlled within 7min. Collagen complex encapsulates growth factor microfiber threads.

实施例6Example 6

(一)称取225mg的胶原蛋白溶于7ml六氟异丙醇，在冰浴下搅拌1小时，待溶液变得澄清，胶原蛋白完全溶解之后，量取115ul碱性成纤维生长因子包载在胶原中，并置于冰浴条件下搅拌，24h后，向体系中加0.45g聚己内酯，于冰水浴中搅拌3小时，直至整个体系混合均匀，最终得到聚己内酯-胶原复合包载生长因子聚合物。(1) Weigh 225mg of collagen and dissolve it in 7ml of hexafluoroisopropanol, stir under ice bath for 1 hour, after the solution becomes clear and the collagen is completely dissolved, weigh 115ul of basic fibroblast growth factor to be contained in the Collagen was placed in an ice bath and stirred. After 24 hours, 0.45 g of polycaprolactone was added to the system, and the mixture was stirred in an ice water bath for 3 hours until the whole system was evenly mixed, and finally a polycaprolactone-collagen composite package was obtained. Growth factor loaded polymers.

(二)采用静电纺丝装置(型号：天津云帆科技YFSP-GⅢ)制备手术缝线，将制备的聚合物溶液放置于10ml注射器中，选取细针头纺丝时控制输出电压5kv，纺丝针头与接收器距离为13cm，注射泵的推动速度控制3.2mm/h，接收器速度保持在300r/min，接收时间控制在7min内，在转盘接收器上形成的纺丝，得到聚己内酯-胶原复合包载生长因子超细纤维线。(2) Use an electrospinning device (model: Tianjin Yunfan Technology YFSP-GⅢ) to prepare surgical sutures, place the prepared polymer solution in a 10ml syringe, select a fine needle for spinning and control the output voltage to 5kv, and the spinning needle The distance from the receiver is 13cm, the pushing speed of the syringe pump is controlled at 3.2mm/h, the speed of the receiver is kept at 300r/min, and the receiving time is controlled within 7min. Collagen complex encapsulates growth factor microfiber threads.

实施例7Example 7

(一)称取225mg的胶原蛋白溶于7ml六氟异丙醇，在冰浴下搅拌1小时，待溶液变得澄清，胶原蛋白完全溶解之后，量取115ul碱性成纤维生长因子包载在胶原中，并置于冰浴条件下搅拌，24h后，向体系中加0.7g聚己内酯，于冰水浴中搅拌3小时，直至整个体系混合均匀，最终得到聚己内酯-胶原复合包载生长因子聚合物。(1) Weigh 225mg of collagen and dissolve it in 7ml of hexafluoroisopropanol, stir under ice bath for 1 hour, after the solution becomes clear and the collagen is completely dissolved, weigh 115ul of basic fibroblast growth factor to be contained in the The collagen was placed in an ice bath and stirred. After 24 hours, 0.7 g of polycaprolactone was added to the system, and the mixture was stirred in an ice-water bath for 3 hours until the whole system was evenly mixed, and finally a polycaprolactone-collagen composite package was obtained. Growth factor loaded polymers.

(二)采用静电纺丝装置(型号：天津云帆科技YFSP-GⅢ)制备手术缝线，将制备的聚合物溶液放置于10ml注射器中，选取细针头纺丝时控制输出电压12kv，纺丝针头与接收器距离为13cm，注射泵的推动速度控制3.4mm/h，接收器速度保持在300r/min，接收时间控制在7min内，在转盘接收器上形成的纺丝，得到聚己内酯-胶原复合包载生长因子超细纤维线。(2) Use an electrospinning device (model: Tianjin Yunfan Technology YFSP-GⅢ) to prepare surgical sutures, place the prepared polymer solution in a 10ml syringe, select a fine needle for spinning, and control the output voltage to 12kv, and the spinning needle The distance from the receiver is 13cm, the pushing speed of the syringe pump is controlled at 3.4mm/h, the speed of the receiver is kept at 300r/min, and the receiving time is controlled within 7min. Collagen complex encapsulates growth factor microfiber threads.

实施例8Example 8

(一)称取225mg的胶原蛋白溶于6.75ml六氟异丙醇和0.25ml水，在冰浴下搅拌1小时，待溶液变得澄清，胶原蛋白完全溶解之后，量取115ul碱性成纤维生长因子包载在胶原中，并置于冰浴条件下搅拌，24h后，向体系中加0.95g聚己内酯，于冰水浴中搅拌3小时，直至整个体系混合均匀，最终得到聚己内酯-胶原复合包载生长因子聚合物。(1) Weigh 225mg of collagen and dissolve it in 6.75ml of hexafluoroisopropanol and 0.25ml of water, and stir for 1 hour in an ice bath. After the solution becomes clear and the collagen is completely dissolved, measure 115ul of alkaline fibroblast growth The factor was loaded in collagen and stirred in an ice bath. After 24 hours, 0.95 g of polycaprolactone was added to the system and stirred in an ice water bath for 3 hours until the whole system was evenly mixed, and finally polycaprolactone was obtained. - Collagen complex encapsulates growth factor polymers.

(二)采用静电纺丝装置(型号：天津云帆科技YFSP-GⅢ)制备手术缝线，将制备的聚合物溶液放置于10ml注射器中，选取细针头纺丝时控制输出电压12kv，纺丝针头与接收器距离为13cm，注射泵的推动速度控制3.3mm/h，接收器速度保持在300r/min，接收时间控制在7min内，在转盘接收器上形成的纺丝，得到聚己内酯-胶原复合包载生长因子超细纤维线。(2) Use an electrospinning device (model: Tianjin Yunfan Technology YFSP-GⅢ) to prepare surgical sutures, place the prepared polymer solution in a 10ml syringe, select a fine needle for spinning, and control the output voltage to 12kv, and the spinning needle The distance from the receiver is 13cm, the pushing speed of the syringe pump is controlled at 3.3mm/h, the speed of the receiver is kept at 300r/min, and the receiving time is controlled within 7min. Collagen complex encapsulates growth factor microfiber threads.

实施例9Example 9

(一)称取225mg的胶原蛋白溶于7ml六氟异丙醇和0.25ml水，在冰浴下搅拌1小时，待溶液变得澄清，胶原蛋白完全溶解之后，量取115ul碱性成纤维生长因子包载在胶原中，并置于冰浴条件下搅拌，24h后，向体系中加0.45g聚己内酯，于冰水浴中搅拌3小时，直至整个体系混合均匀，最终得到聚己内酯-胶原复合包载生长因子聚合物。(1) Weigh 225mg of collagen and dissolve it in 7ml of hexafluoroisopropanol and 0.25ml of water, stir for 1 hour in an ice bath, until the solution becomes clear and the collagen is completely dissolved, measure 115ul of basic fibroblast growth factor Encapsulated in collagen, and stirred in an ice bath. After 24 hours, 0.45 g of polycaprolactone was added to the system and stirred in an ice-water bath for 3 hours until the whole system was evenly mixed, and finally polycaprolactone- Collagen complex encapsulates growth factor polymers.

(二)采用静电纺丝装置(型号：天津云帆科技YFSP-GⅢ)制备手术缝线，将制备的聚合物溶液放置于10ml注射器中，选取细针头纺丝时控制输出电压11kv，纺丝针头与接收器距离为13cm，注射泵的推动速度控制3.3mm/h，接收器速度保持在300r/min，接收时间控制在7min内，在转盘接收器上形成的纺丝，得到聚己内酯-胶原复合包载生长因子超细纤维线。(2) Use an electrospinning device (model: Tianjin Yunfan Technology YFSP-GⅢ) to prepare surgical sutures, place the prepared polymer solution in a 10ml syringe, select a fine needle for spinning, and control the output voltage to 11kv, and the spinning needle The distance from the receiver is 13cm, the pushing speed of the syringe pump is controlled at 3.3mm/h, the speed of the receiver is kept at 300r/min, and the receiving time is controlled within 7min. Collagen complex encapsulates growth factor microfiber threads.

实施例10Example 10

(一)称取225mg的胶原蛋白溶于7ml六氟异丙醇和0.25ml水，在冰浴下搅拌1小时，待溶液变得澄清，胶原蛋白完全溶解之后，量取115ul碱性成纤维生长因子包载在胶原中，并置于冰浴条件下搅拌，24h后，向体系中加0.7g聚己内酯，于冰水浴中搅拌3小时，直至整个体系混合均匀，最终得到聚己内酯-胶原复合包载生长因子聚合物。(1) Weigh 225mg of collagen and dissolve it in 7ml of hexafluoroisopropanol and 0.25ml of water, stir for 1 hour in an ice bath, until the solution becomes clear and the collagen is completely dissolved, measure 115ul of basic fibroblast growth factor Encapsulated in collagen, and stirred in an ice bath. After 24 hours, 0.7 g of polycaprolactone was added to the system and stirred in an ice-water bath for 3 hours until the whole system was evenly mixed, and finally polycaprolactone- Collagen complex encapsulates growth factor polymers.

(二)采用静电纺丝装置(型号：天津云帆科技YFSP-GⅢ)制备手术缝线，将制备的聚合物溶液放置于10ml注射器中，选取细针头纺丝时控制输出电压12kv，纺丝针头与接收器距离为13cm，注射泵的推动速度控制1.2mm/h，接收器速度保持在300r/min，接收时间控制在7min内，在转盘接收器上形成的纺丝，得到聚己内酯-胶原复合包载生长因子超细纤维线。(2) Use an electrospinning device (model: Tianjin Yunfan Technology YFSP-GⅢ) to prepare surgical sutures, place the prepared polymer solution in a 10ml syringe, select a fine needle for spinning, and control the output voltage to 12kv, and the spinning needle The distance from the receiver is 13cm, the pushing speed of the syringe pump is controlled at 1.2mm/h, the speed of the receiver is kept at 300r/min, and the receiving time is controlled within 7min. Collagen complex encapsulates growth factor microfiber threads.

实施例11Example 11

本实施例所用方法与实施例1相似，区别仅在于，所述输出电压为4kv。The method used in this embodiment is similar to that in Embodiment 1, the only difference is that the output voltage is 4kv.

实施例12Example 12

本实施例所用方法与实施例1相似，区别仅在于，所述输出电压为22kv。The method used in this embodiment is similar to that in Embodiment 1, and the only difference is that the output voltage is 22kv.

实施例13Example 13

本实施例所用方法与实施例6相似，区别仅在于，所述注射泵的推动速度为0.5mm/h。The method used in this example is similar to that in Example 6, the only difference is that the pushing speed of the syringe pump is 0.5 mm/h.

实施例14Example 14

本实施例所用方法与实施例6相似，区别仅在于，所述注射泵的推动速度为3.8mm/h。The method used in this example is similar to that in Example 6, the only difference is that the pushing speed of the syringe pump is 3.8 mm/h.

对比例Comparative ratio

对比例1Comparative Example 1

本对比例所用方法与实施例5相似，区别在于，所述胶原蛋白的溶剂为磷酸缓冲溶液。The method used in this comparative example is similar to that of Example 5, except that the solvent of the collagen is a phosphate buffer solution.

对比例2Comparative Example 2

本对比例所用方法与实施例5相似，区别在于，所述输出电压为3kv。The method used in this comparative example is similar to that of Example 5, except that the output voltage is 3kv.

对比例3Comparative Example 3

本对比例所用方法与实施例5相似，区别在于，所述输出电压为25kv。The method used in this comparative example is similar to that of Example 5, except that the output voltage is 25kv.

对比例4Comparative Example 4

本对比例所用方法与实施例5相似，区别在于，所述注射泵的推进速度为0.3mm/h。The method used in this comparative example is similar to that in Example 5, except that the advancing speed of the syringe pump is 0.3 mm/h.

对比例5Comparative Example 5

本对比例所用方法与实施例5相似，区别在于，所述注射泵的推进速度为4.0mm/h。The method used in this comparative example is similar to that of Example 5, except that the advancing speed of the syringe pump is 4.0 mm/h.

对比例6Comparative Example 6

本对比例所用方法与实施例5相似，区别在于，胶原蛋白溶液中不包载碱性成纤维生长因子。The method used in this comparative example is similar to that in Example 5, except that the collagen solution does not contain basic fibroblast growth factor.

实验例Experimental example

实验例1Experimental example 1

对上述实施例1～14和对比例1～5中制备得到的手术缝线的性能参数进行检测，结果如表1所示。The performance parameters of the surgical sutures prepared in the above Examples 1-14 and Comparative Examples 1-5 were tested, and the results are shown in Table 1.

表1实施例1～14和对比例1～5中制备得到的手术缝线的性能比较Table 1 Performance comparison of surgical sutures prepared in Examples 1-14 and Comparative Examples 1-5

其中，直径、抗张强度和模量均用“1”，“2”，“3”，“4”，“5”表示。直径“1”为最粗，“5”为最细；抗张强度“1”为最小，“5”为最大；模量“1”为最小，“5”为最大；降解时间“+”为1～10天，“++”为11～20天，“+++”为21～30天。“/”为无法成丝。Among them, the diameter, tensile strength and modulus are represented by "1", "2", "3", "4", "5". Diameter "1" is the thickest, "5" is the thinnest; tensile strength "1" is the smallest, "5" is the largest; modulus "1" is the smallest, "5" is the largest; degradation time "+" is 1 to 10 days, "++" is 11 to 20 days, and "+++" is 21 to 30 days. "/" means that the wire cannot be formed.

由表1可知，本发明实施例1～14中制备得到的手术缝线，其直径较对比例小，抗张强度和模量均优于对比例中的缝线，降解时间远少于对比例中的缝线降解时间。It can be seen from Table 1 that the diameter of the surgical sutures prepared in Examples 1 to 14 of the present invention is smaller than that of the comparative example, the tensile strength and modulus are better than those of the suture in the comparative example, and the degradation time is much shorter than that of the comparative example. Suture degradation time in .

实验例2Experimental example 2

将本发明实施例1和对比例6中制备的手术缝合线应用于小鼠表皮缝合模型，在缝合过程中能够顺利打结，具有一定的韧性和张力，没有出现缝合线断裂的现象。The surgical sutures prepared in Example 1 and Comparative Example 6 of the present invention were applied to the mouse epidermal suture model, and the knots could be smoothly tied during the suture process, with certain toughness and tension, and no suture breakage occurred.

在愈合后第13天，所述小鼠表皮的愈合情况如图2和图3所示。On the 13th day after healing, the healing status of the mouse epidermis is shown in Figures 2 and 3 .

由图2中的b可知，本发明实施例1所制备的手术缝合线在愈合的过程中已经完全降解，且皮肤没有任何红肿现象，也没有崩线，伤口愈合较为完成；而对比例6中的手术缝合线缝合的伤口愈合情况如图3中的b所示，伤口具有明显的未愈合面，且能够看到无法降解的手术缝线。It can be seen from b in Figure 2 that the surgical suture prepared in Example 1 of the present invention has been completely degraded during the healing process, and the skin does not have any redness and swelling, and there is no collapse of the suture, and the wound healing is relatively complete; The wound healing situation of the surgical suture suture is shown in b in Figure 3. The wound has an obvious unhealed surface, and the non-degradable surgical suture can be seen.

由此可知，本发明实施例1中制备的手术缝合线由于包含生物活性因子，其对伤口组织的修复速度明显快于对比例6中未加入生长因子的手术缝合线。It can be seen that the surgical suture prepared in Example 1 of the present invention can repair wound tissue significantly faster than the surgical suture without growth factor in Comparative Example 6 because it contains bioactive factors.

以上结合具体实施方式和范例性实例对本发明进行了详细说明，不过这些说明并不能理解为对本发明的限制。本领域技术人员理解，在不偏离本发明精神和范围的情况下，可以对本发明技术方案及其实施方式进行多种等价替换、修饰或改进，这些均落入本发明的范围内。The present invention has been described in detail above in conjunction with specific embodiments and exemplary examples, but these descriptions should not be construed as limiting the present invention. Those skilled in the art understand that, without departing from the spirit and scope of the present invention, various equivalent replacements, modifications or improvements can be made to the technical solutions of the present invention and the embodiments thereof, which all fall within the scope of the present invention.

Claims (8)

1. A degradable surgical suture with bioactivity is characterized in that the surgical suture is prepared from the following raw materials in parts by weight:

200-1200 parts by weight of a base

220 to 240 parts by weight of a load,

the matrix is one or more of polylactic acid, polycaprolactone, polyglycolide or polydioxanone;

the load comprises collagen and bioactive substances, the bioactive substances are basic fibroblast growth factors,

the surgical suture is prepared by a method comprising the steps of:

step 1, preparing a solution of a load,

the preparation of the load solution comprises the following steps:

step a, weighing a certain amount of collagen, dissolving the collagen in a certain volume of solvent to prepare a collagen solution,

b, adding the basic fibroblast growth factor into the collagen solution, and mixing for a certain time to prepare a solution of a load;

the volume ratio of the collagen solution to the growth factor is (4000-9000): 115, 115;

step 2, adding the matrix into the load solution, and uniformly stirring to obtain a polymer solution, wherein the weight ratio of the matrix in the polymer solution to the collagen in the load is (200-1200): 225, a step of mixing;

step 3, preparing the polymer solution to obtain the surgical suture,

preparing the polymer solution into the surgical suture by adopting an electrostatic spinning device, comprising the following steps:

step I, filling a polymer solution into the device;

step II, adjusting various parameters of the device; the parameters comprise output voltage, the distance between a spinning needle and a receiver, the pushing speed of an injection pump, the speed of the receiver and receiving time;

the pushing speed of the injection pump is 0.5-3.8 mm/h,

the speed of the receiver is 200-400 r/min,

the output voltage is 4-22 kv,

the distance between the spinning needle head and the receiver is 8-20 cm;

and step III, opening the device to prepare the degradable surgical suture with bioactivity.

2. A method of preparing a surgical suture as claimed in claim 1, comprising the steps of:

step 1, preparing a solution of a load;

step 2, adding the matrix into the load solution, and uniformly stirring to obtain a polymer solution;

and 3, preparing the polymer solution to obtain the surgical suture.

3. The method of claim 2, wherein in step 1, the preparation of the loading solution comprises the steps of:

step a, weighing a certain amount of collagen, and dissolving the collagen in a solvent with a certain volume to prepare a collagen solution;

and b, adding the growth factor into the collagen solution, and mixing for a certain time to prepare a solution of the loading substance.

4. The process of claim 2, wherein in step a, the solvent is hexafluoroisopropanol, or

A mixture of hexafluoroisopropanol and water.

5. The method according to claim 3, wherein the volume ratio of the collagen solution to the growth factor is (5000-8500): 115.

6. the method of claim 2, wherein the step 3 of preparing the polymer solution into the surgical suture by using an electrospinning device comprises the steps of:

step I, filling a polymer solution into the device;

step II, adjusting various parameters of the device;

step III, opening the device to prepare the degradable surgical suture with bioactivity;

in the step II, the parameters comprise output voltage, the distance between the spinning needle and the receiver, the pushing speed of the injection pump, the speed of the receiver and receiving time.

7. The method of claim 6, wherein the output voltage is 4-22 kv, and/or

The distance between the spinning needle head and the receiver is 8-20 cm.

8. The method according to claim 6, wherein the driving speed of the injection pump is 0.8-3.6 mm/h.

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