AU2019210543B1

AU2019210543B1 - Bioactive degradable surgical suture and preparation method thereof

Info

Publication number: AU2019210543B1
Application number: AU2019210543A
Authority: AU
Inventors: Huacheng He; Xiaokun Li; Jiang Wu; Jian Xiao; Hongyu Zhang
Original assignee: Wenzhou Medical University
Current assignee: Wenzhou Medical University
Priority date: 2018-09-30
Filing date: 2019-06-27
Publication date: 2020-02-06
Anticipated expiration: 2039-06-27

Abstract

The present invention discloses a bioactive degradable surgical suture and a preparation method thereof, wherein the degradable surgical suture is prepared by adding collagen entrapping a biologically active substance to a biocompatible base, and then preparing degradable surgical suture by electrospinning. The suture of the present invention has good uniformity, and high biocompatibility and safety, and the preparation method is simple and quick.

Description

TECHNICAL FIELD [0001] The invention belongs to the field of biomedical materials, and particularly relates to a bioactive degradable surgical suture and a preparation method thereof.

BACKGROUND OF THE INVENTION [0002] At present, medical surgical sutures commonly used in clinical practice can be divided into degradable and non-degradable sutures. Non-degradable sutures include silk thread, polypropylene thread, polyethylene thread, etc. Although mechanical properties of non-degradable sutures are strong, non-degradability often leads to pain due to postoperative suture removment, or even surgical removement of suture. Degradable sutures mainly include catgut sutures, chemically synthethic sutures and purely natural collagen, which is degradable and metabolizable in body, non-toxic and harmless, thereby reducing unnecessary troubles and pain after surgery.

[0003] However, the catgut sutures among the degradable sutures (specifically, as described in Chinese patent for invention No. CN1363397A) are liable to cause postoperative rejection in patients due to different degrees of rejection of the human body. The tensile strength of the sutures is low, and various postoperative adverse reactions have been revealed in clinical practice. For another example, Chinese patent for invention No. CN201543004U describes fibers for surgical sutures, hernia and body wall repairing meshes and anti-adhesion membranes, which include a polypropylene core layer and a polyvinylidene fluoride skin layer, forming a concentric structure. After implantation of chemically synthesized sutures, i.e. concentric composite fibers formed by composite spinning, different degrees of chemical residue exist, which is liable to cause subcutaneous induration of the body, and some patients

OP19001 have subcutaneous itching and other issues after operation. At present, the more perfect one is the purely natural collagen suture, which is taken from tendons of animals.

[0004] However, the above-mentioned degradable sutures only serve to suture the wound after surgery. The sutured wound heals slowly and is easily contaminated by bacteria in the surrounding environment, which is manifested by the appearance or exudation of purulent secretions. Generally, injection or oral antibiotics are adopted for treatment, which, however, has serious side effects on the human body.

[0005] Therefore, it is an urgent problem to provide a degradable surgical suture which accelerates wound healing, and has few side effects, infection resistance and biological activity, and a preparation method thereof.

BRIEF SUMMARY OF THE INVENTION [0006] In order to overcome the above problems, the inventors conducted intensive studies and found that, a surgical suture having high absorption-degradability, biocompatibility and safety can be prepared by using a biocompatible, degradable material as a base, then adding collagen entrapping a biologically active substance, and employing electrospinning technology in which specific parameters are set, thereby accomplishing the present invention.

[0007] In particular, it is an object of the present invention to provide the following aspects: [0008] In a first aspect, the present invention provides a bioactive degradable surgical suture, wherein the surgical suture is prepared from raw materials with the following weight ratios: 200 to 1200 parts by weight of base, and

220 to 240 parts by weight of loaded substance.

[0009] In a second aspect, the present invention provides a method of preparing a bioactive degradable surgical suture, wherein the method comprises the following steps:

Step 1, preparing a solution of loaded substance;

Step 2, adding a base to the solution of loaded substance to obtain a polymer solution; and

Step 3, preparing the polymer solution into a surgical suture.

OP19001 [0010] The beneficial effects of the present invention include:

(1) The bioactive degradable surgical suture provided by the invention has strong mechanical properties, high biocompatibility and high safety;

(2) The surgical suture provided by the invention can release growth factors at the sutured site, can reduce wound infection, promote proliferation of granulation tissue and collagen production, and effectively shorten recovery time;

(3) The surgical suture provided by the invention has small diameter and good uniformity;

(4) The preparation method of the surgical suture provided by the invention has the advantages of simple steps, easily-controllable conditions, strong versatility, and suitability for large-scale production.

BRIEF DESCRIPTION OF THE DRAWINGS [0011] Fig. 1 shows schematic diagrams of collogan and growth factor in the surgical suture of the present invneiton.

[0012] Fig. 2 shows the effect of suturing with the surgical suture prepared in Example 1, wherein 2a shows the effect on day 0 after suturing; 2b shows the effect of healing on day 13 after suturing.

[0013] Fig. 3 shows the effect of suturing with the surgical suture prepared in Comparative Example 7, wherein 3a shows the effect on day 0 after suturing; and 3b shows the effect of healing on day 13 after the suturing.

DETAILED DESCRIPTION OF THE INVENTION [0014] The invention will be described in further detail by means of preferred embodiments and examples below.

[0015] The features and advantages of the present invention will become more apparent from the description.

[0016] The present invention provides a bioactive degradable surgical suture, wherein the surgical suture is prepared from raw materials with the following weight ratios:

OP19001

200 to 1200 parts by weight of base, and

220 to 240 parts by weight of loaded substance;

[0017] Preferably, the surgical suture is prepared from raw materials with the following weight ratios:

250 to 1100 parts by weight of the base, and

220 to 230 parts by weight of the loaded substance;

[0018] More preferably, the surgical suture is prepared from raw materials with the following weight ratios:

350 to 1050 parts by weight the base, and

220 to 225 parts by weight of the loaded substance.

[0019] According to one preferred embodiment of the present invention, the base is a degradable polymer material, preferably one or more of polylactic acid, polyvinyl alcohol, polycaprolactone, polyglycolide, polydioxanone, or poly(glycolide-co-L-lactide).

[0020] In a more preferred embodiment, the base is one or more of polylactic acid, polycaprolactone, polyglycolide or polydioxanone.

[0021] In a still more preferred embodiment, the base is polycaprolactone.

[0022] 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 H2O within 6-12 months, and the degradation products can be excreted with normal metabolism of the base without accumulation in the body. Especially in surgical suturing process of bladder and urethra, accumulation of degradation products is likely to cause blockage of organs and endanger the health of the body. Using polycaprolactone of the present invention as a base material of sutures can effectively avoid such hazards.

[0023] According to a preferred embodiment of the invention, the loaded substance comprises collagen and a biologically active substance.

OP19001 [0024] The present inventors have found through research that, collagen is a class of macromolecular protein which is ubiquitous in animals, and accounts for 25% of the total protein content of the whole organism in mammals. Collagen is extracellular matrix with good cell adhesion, has a great affinity to protein molecules on the surface of the skin, and is conducive to tissue growth and repair. Addition of collagen to surgical suture can further improve the cell compatibility of the suture, promote tissue proliferation and repair, and enhance biodegradation safety.

[0025] In a further preferred embodiment, the biologically active substance is a peptide, preferably a growth factor.

[0026] Growth factors are a class of polypeptides that regulate multiple effects such as cell growth and other cellular functions by binding to specific, high-affinity cell membrane receptors. As an important extracellular signal, growth factor can help wound healing, promote proliferation of granulation tissue and collagen production, and reduce the risk of infection in patients.

[0027] In a still further preferred embodiment, the growth factor is a basic fibroblast growth factor or an epidermal growth factor.

[0028] The inventors have found through research that, basic fibroblast growth factor is an important mitogenic factor and an inducing factor for morphogenesis and morphodifferentiation. Its main biological functions include promoting the formation of granulation tissue and healing wounds; promoting microvascular formation and improving microcirculation, participating in the whole process of neovascularization; promoting the proliferation of osteoblasts, inhibiting the formation of osteoclasts, and promoting bone formation. Epidermal growth factor is a heat-resistant single-peptide chain and a strong mitogen, and it can stimulate the proliferation and differentiation of cells in cultured cells and living animals, and promote wound healing.

OP19001 [0029] In the present invention, collagen and a biologically active substance (a growth factor such as basic fibroblast growth factor) are added to the base to prepare a surgical suture without changing the mechanical properties of the base, and the base and collagen will not affect the protein structure of the growth factor.

[0030] According to a preferred embodiment of the present invention, the degradable surgical suture has an outer diameter of 0.6 to 1.2 mm, preferably 0.7 to 1.1 mm, more preferably 0.8 to 1.0 mm.

[0031] The present invention also provides a method of preparing a bioactive degradable surgical suture, which comprises the steps of:

Step 1, preparing a solution of loaded substance;

Step 2, adding the base to the solution of loaded substance to obtain a polymer solution; and Step 3, preparing the polymer solution into a surgical suture.

[0032] The preparation method of the surgical suture according to the present invention is specifically described below:

[0033] Step 1. Prepare a solution of loaded substance.

[0034] In the present invention, the loaded substance comprises collagen and a growth factor, and preparation of the solution of loaded substance comprises the following steps:

Step a, a certain amount of collagen is weighed and dissolved in a certain volume of solvent to prepare a collagen solution.

[0035] According to a preferred embodiment of the invention, the solvent is one or more of acetic acid, phosphoric acid, hydrochloric acid, phosphate buffer solution, hexafluoroisopropanol or water.

[0036] In a further preferred embodiment, the solvent is one or more of acetic acid, phosphate buffer solution, hexafluoroisopropanol or water.

[0037] In a still further preferred embodiment, the solvent is hexafluoroisopropanol and/or water.

OP19001 [0038] The inventors have found through research that, hexafluoroisopropanol is highly polar and easily mixed with various organic solvents, can dissolve many high polymers, and has high volatility. In subsequent preparation of surgical sutures, the solution has less residue after spinning, and is easy to remove; and water as a green solvent can effectively dissolve collagen and basic fibroblast growth factor, which is beneficial to promote collagen to entrap growth factors more effectively.

[0039] 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.

[0040] According to a preferred embodiment of the invention, collagen is mixed with the solvent in ice bath and stirred until completely dissolved.

[0041] In the step, mixing in ice bath can maintain the activity of collagen and growth factors at the same time.

[0042] In a further preferred embodiment, the stirring time is from 0.5 to 2 h, preferably from 0.75 to 1.5 h, more preferably 1 h.

[0043] In the step, stirring is stopped until the solution becomes clear, that is, until the collagen is completely dissolved.

[0044] According to a preferred embodiment of the present invention, the collagen has a concentration of 20 to 45 mg/mL, preferably 25 to 40 mg/mL, more preferably 27 to 35 mg/mL.

[0045] Step b, growth factor is added to the collagen solution, and mixing for a certain period of time to a solution of loaded substance.

[0046] The inventors have found through research that, the growth factor is extremely easy to degrade and the degradation rate is accelerated with the increase of temperature. Therefore, it is preferred in the present invention to entrap growth factor in a collagen solution, so that collagen and the growth factor are connected by covalent bonds and hydrogen bonds to form

OP19001 nanoparticles (specifically as shown in Figure 1), thereby increasing the stability of the growth factor, enabling it to be effectively released at the sutured site.

[0047] In the present invention, the growth factor is preferably a basic fibroblast growth factor or an epidermal growth factor, more preferably a basic fibroblast growth factor.

[0048] According to a preferred embodiment of the invention, the mixing is carried out in ice bath, and the mixing time being 18 to 30 h, preferably 20 to 26 h, more preferably 24 h.

[0049] In the step, continuous stirring is required during the ice bath process to enable sufficient and uniform encapsulation.

[0050] In the present invention, entrapment of the growth factor in ice bath can effectively reduce degradation of the growth factor, and the entrapment time is 18 to 30 h, which enables collagen to fully and uniformly entrap the growth factor. When the entrapment time is lower than 18h, the entrapment is incomplete and the obtained loaded substance is less effective. When the entrapment time is higher than 30 h, the entrapment achieves saturation with the extension of time, and the entrapment effect is no longer improved, and thus time prolongation will reduce efficiency.

[0051] 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 (55008200): 115.

[0052] 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 entrapped the growth factors, and excessive addition of collagen solution will result in waste of resources and uneven mixing of the system, which will affect subsequent spinning and the effect of growth factors; when the volume ratio of the collagen solution to growth factor is less than 4000:115, some growth factors can not be entrapped, and then degradation occurs to them. As a result, entrapment effect cannot be achieved.

OP19001 [0053] Step 2, the base is added to the solution of loaded substance, and stirred and mixed to obtain a polymer solution.

[0054] According to a preferred embodiment of the present invention, stirring is carried out in ice bath, and the stirring time is 2 to 4 hours, preferably 2.5 to 3.5 hours, more preferably 3 hours.

[0055] In a further preferred embodiment, the weight ratio of the base to the collagen in the loaded substance in the polymer solution is (200-1200): 225, preferably (250-1100): 225, more preferably (350-1050): 225.

[0056] Step 3, the polymer solution is prepared into a surgical suture.

[0057] The inventors have found through research that, the fibers obtained by electrospinning have small diameter and good uniformity, and can mimic the natural extracellular matrix from the nanometer scale. Therefore, it is preferred in the present invention to prepare the polymer solution into a surgical suture by electrospinning method.

[0058] In the step, the electrospinning technology is performed in a direct-current electric field with tens of kilovolts, the electrostatic repulsion of the charged polymer solution overcomes the surface tension at the capillary tip to form a jet flow. As the solvent evaporates, the jet flow solidifies to form ultrafine filaments of submicron to nanometer scale, which are received by the receiver.

[0059] In the present invention, the polymer is prepared into the surgical suture using an electrospinning device, which comprises the following steps:

[0060] Step I, a polymer solution is loaded into a device.

[0061] In the step, the polymer solution prepared above is loaded in an injector of an electrospinning device with the volume of the injector being 10 mL, and then a fine needle is selected for spinning.

[0062] Step II, various parameters of the device are adjusted.

OP19001 [0063] In the step, the parameters of the electrospinning device include an output voltage, a distance between the spinning needle and the receiver, a pushing speed of the injection pump, a receiver speed, and a receiving time.

[0064] According to a preferred embodiment of the invention, the output voltage is 4 to 22 kV, preferably 4 to 20 kV, more preferably 5 to 17 kV.

[0065] The inventors have found through research that, when the output voltage of the electrospinning device is 4 to 22 kV, preferably 4 to 20 kV, and more preferably 5 to 17 kV, the diameter of the obtained surgical suture is the smallest. When the output voltage is less than 4kV, the spinning solution will be sprayed outward in the form of droplets due to insufficient power; when the output voltage is higher than 22kV, the reduction in the diameter of the produced fiber becomes very slow as the voltage increases, and it will make the spinning solution fly away from the needle in the form of an electrospray, such that electrospinning cannot be performed normally.

[0066] According to a preferred embodiment of the invention, the distance between the spinning needle and the receiver is 8-20 cm, preferably 9-18 cm, more preferably 11-15 cm.

[0067] The inventors have 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, such that there is not enough time for the solvent in the spinning solution to volatilize, and it is liable to collect atomized droplets or the fibers stuck together, thereby affecting the performance of the fiber. When the distance between the spinning needle and the receiver is greater than 20 cm, since the receiving distance is too large, the electric field force is greatly weakened, and the uniformity of the fibers is lowered.

[0068] According to a preferred embodiment of the invention, the injection pump has a pushing speed of 0.5 to 3.8 mm/h, preferably 0.8 to 3.6 mm/h, more preferably 1.0 to 3.4 mm/h.

OP19001 [0069] In the step, the injection pump is used to drive the injector to push the spinning solution.

[0070] The inventors have found through research that, when the pushing speed of the injection pump is less than 0.5 mm/h, in the process of filament formation, the electrolytic speed is greater than the solution discharge speed, which causes discontinuous spinning, and the solution is not discharged timely, resulting in breakage in the formation of filaments and decrease in the order of arrangement of fibers. When the pushing speed of the injection pump is greater than 3.8 mm/h, the electrolytic speed is smaller than the solution discharge speed during the filament formation process, such that there is not enough time for some of the solution to be electrolyzed, and the solution remains in the needle and clogs the needle, or sputters in the form of droplets on the receiver, resulting in collection of atomized droplets or fibers stuck together, thereby affecting the performance of the fiber.

[0071] According to a preferred embodiment of the present invention, the speed of the receiver is 200 to 400r/min, preferably 240 to 370r/min, more preferably 280 to 320r/min, and the receiving time is 4 to 12min. It is preferably 5 to 10 min.

[0072] In the step, the receiver is a turntable receiver.

[0073] The inventors have found through research that, during the collection of the electrospun fibers, the convection of the air and the winding of the receiver cause further stretching of the fibers, so that the average diameter of the fibers is reduced.

[0074] When the speed of the receiver is less than 200r/min, the convection of the air around the turntable is insufficient to change the trajectory of the fiber, so that it cannot be formed well on the receiver; when the speed of the receiver is greater than 400r/min, the strong air convection around the turntable changes the trajectory of the fibers as they approach the receiver. As a result, breakage occurs, and arrangement order of the fibers is decreased.

[0075] Step III, the device is started to prepare a bioactive degradable surgical suture.

OP19001 [0076] In the step, the power source is swhiched on, and preparation is performed using an electrospinning device. After the preparation is completed, the filaments formed on the turntable receiver are collected to obtain bioactive degradable surgical sutures.

EXAMPLS [0077] The invention is further described by the following examples, but these examples are merely exemplary and not intended to limit the scope of the invention.

[0078] In the following examples, collagen is extracted from rat tail collagen; basic fibroblast growth factor is prepared and purified by the research group; polycaprolactone is purchased from Sigma-Aldrich, USA; hexafluoroisopropanol is purchased from Shanghai Latin Biotechnology Co., Ltd.

EXAMPLE 1 [0079] (1) 225 mg of collagen were weighed and dissolved in 6 mL of hexafluoro isopropanol and 0.5 mL of water, and stirred for 1 hour in ice bath. After the solution became clear and collagen was completely dissolved, 115 pL of basic fibroblast growth factor was taken and entrapped in collagan. The resultant mixture was stirred in ice bath for 24 hours, and 0.45 g of polycaprolactone was added to the system and stirred in ice water bath for 3 hours until the whole system was uniformly mixed, so as to obtain finally a polymer in which polycaprolactone-collagen composite entraps growth factor.

[0080] (2) Surgical sutures were prepared using an electrospinning device (Model: Tianjin Yunfan Technology YFSP-G III). The obtained polymer solution was loaded in a 10 ml injector, and a fine needle was selected for spinning. Meanwhile, the output voltage was controlled to be 5 kv, the distance between the spinning needle and the receiver was controlled to be 11 cm, the pushing speed of the injection pump was controlled to be 1.0 mm/h, the speed of the receiver was controlled to be 280 r/min, and the receiving time was controlled within 5 min. The filaments formed on the turntable receiver were collected to obtain superfine fibers in which polycaprolactone-collagen composite entraps growth factor.

OP19001

EXAMPLE 2 [0081] (1) 225 mg of collagen were weighed and dissolved in 6.75 mL of hexafluoroisopropanol and 0.25 mL of water, and stirred for 1 hour in ice bath. After the solution became clear and collagen was completely dissolved, 115 pL of basic fibroblast growth factor was taken and entrapped in collagan. The resultant mixture was stirred in ice bath for 24 hours, and 0.45 g of polycaprolactone was added to the system and stirred in ice water bath for 3 hours until the whole system was uniformly mixed, so as to obtain finally a polymer in which polycaprolactone-collagen composite entraps growth factor.

[0082] (2) Surgical sutures were prepared using an electrospinning device (Model: Tianjin Yunfan Technology YFSP-G III). The obtained polymer solution was loaded in a 10 ml injector, and a fine needle was selected for spinning. Meanwhile, the output voltage was controlled to be 7 kv, the distance between the spinning needle and the receiver was controlled to be 15 cm, the pushing speed of the injection pump was controlled to be 1.2 mm/h, the speed of the receiver was controlled to be 320 r/min, and the receiving time was controlled within 6 min. The filaments formed on the turntable receiver were collected to obtain superfine fibers in which polycaprolactone-collagen composite entraps growth factor.

EXAMPLE 3 [0083] (1) 225 mg of collagen were weighed and dissolved in 6.5 mL of hexafluoroisopropanol and 0.5 mL of water, and stirred for 1 hour in ice bath. After the solution became clear and collagen was completely dissolved, 115 pL of basic fibroblast growth factor was taken and entrapped in collagan. The resultant mixture was stirred in ice bath for 24 hours, and 0.7 g of polycaprolactone was added to the system and stirred in ice water bath for 3 hours until the whole system was uniformly mixed, so as to obtain finally a polymer in which polycaprolactone-collagen composite entraps growth factor.

[0084] (2) Surgical sutures were prepared using an electrospinning device (Model: Tianjin Yunfan Technology YFSP-G III). The obtained polymer solution was loaded in a 10 ml

OP19001 injector, and a fine needle was selected for spinning. Meanwhile, the output voltage was controlled to be 10 kv, the distance between the spinning needle and the receiver was controlled to be 15 cm, the pushing speed of the injection pump was controlled to be 1.2 mm/h, the speed of the receiver was controlled to be 300 r/min, and the receiving time was controlled within 7 min. The filaments formed on the turntable receiver were collected to obtain superfine fibers in which polycaprolactone-collagen composite entraps growth factor.

EXAMPLE 4 [0085] (1) 225 mg of collagen were weighed and dissolved in 6.75 mL of hexafluoroisopropanol and 0.25 mL of water, and stirred for 1 hour in ice bath. After the solution became clear and collagen was completely dissolved, 115 pL of basic fibroblast growth factor was taken and entrapped in collagan. The resultant mixture was stirred in ice bath for 24 hours, and 0.7 g of polycaprolactone was added to the system and stirred in ice water bath for 3 hours until the whole system was uniformly mixed, so as to obtain finally a polymer in which polycaprolactone-collagen composite entraps growth factor.

[0086] (2) Surgical sutures were prepared using an electrospinning device (Model: Tianjin Yunfan Technology YFSP-G III). The obtained polymer solution was loaded in a 10 ml injector, and a fine needle was selected for spinning. Meanwhile, the output voltage was controlled to be 15 kv, the distance between the spinning needle and the receiver was controlled to be 14 cm, the pushing speed of the injection pump was controlled to be 2.1 mm/h, the speed of the receiver was controlled to be 300 r/min, and the receiving time was controlled within 7 min. The filaments formed on the turntable receiver were collected to obtain superfine fibers in which polycaprolactone-collagen composite entraps growth factor.

EXAMPLE 5 [0087] (1) 225 mg of collagen were weighed and dissolved in 6.75 mL of hexafluoroisopropanol and 0.25 mL of water, and stirred for 1 hour in ice bath. After the solution became clear and collagen was completely dissolved, 115 pL of basic fibroblast

OP19001 growth factor was taken and entrapped in collagan. The resultant mixture was stirred in ice bath for 24 hours, and 0.7 g of polycaprolactone was added to the system and stirred in ice water bath for 3 hours until the whole system was uniformly mixed, so as to obtain finally a polymer in which polycaprolactone-collagen composite entraps growth factor.

[0088] (2) Surgical sutures were prepared using an electrospinning device (Model: Tianjin Yunfan Technology YFSP-G III). The obtained polymer solution was loaded in a 10 ml injector, and a fine needle was selected for spinning. Meanwhile, the output voltage was controlled to be 17 kv, the distance between the spinning needle and the receiver was controlled to be 13 cm, the pushing speed of the injection pump was controlled to be 2.1 mm/h, the speed of the receiver was controlled to be 300 r/min, and the receiving time was controlled within 7 min. The filaments formed on the turntable receiver were collected to obtain superfine fibers in which polycaprolactone-collagen composite entraps growth factor.

EXAMPLE 6 [0089] (1) 225 mg of collagen were weighed and dissolved in 7 mL of hexafluoro isopropanol, and stirred for 1 hour in ice bath. After the solution became clear and collagen was completely dissolved, 115 pL of basic fibroblast growth factor was taken and entrapped in collagan. The resultant mixture was stirred in ice bath for 24 hours, and 0.45 g of polycaprolactone was added to the system and stirred in ice water bath for 3 hours until the whole system was uniformly mixed, so as to obtain finally a polymer in which polycaprolactone-collagen composite entraps growth factor.

[0090] (2) Surgical sutures were prepared using an electrospinning device (Model: Tianjin Yunfan Technology YFSP-G III). The obtained polymer solution was loaded in a 10 ml injector, and a fine needle was selected for spinning. Meanwhile, the output voltage was controlled to be 5 kv, the distance between the spinning needle and the receiver was controlled to be 13 cm, the pushing speed of the injection pump was controlled to be 3.2 mm/h, the speed of the receiver was controlled to be 300 r/min, and the receiving time was

OP19001 controlled within 7 min. The filaments formed on the turntable receiver were collected to obtain superfine fibers in which polycaprolactone-collagen composite entraps growth factor.

EXAMPLE 7 [0091] (1) 225 mg of collagen were weighed and dissolved in 7 mL of hexafluoro isopropanol, and stirred for 1 hour in ice bath. After the solution became clear and collagen was completely dissolved, 115 pL of basic fibroblast growth factor was taken and entrapped in collagan. The resultant mixture was stirred in ice bath for 24 hours, and 0.7 g of polycaprolactone was added to the system and stirred in ice water bath for 3 hours until the whole system was uniformly mixed, so as to obtain finally a polymer in which polycaprolactone-collagen composite entraps growth factor.

[0092] (2) Surgical sutures were prepared using an electrospinning device (Model: Tianjin Yunfan Technology YFSP-G III). The obtained polymer solution was loaded in a 10 ml injector, and a fine needle was selected for spinning. Meanwhile, the output voltage was controlled to be 12 kv, the distance between the spinning needle and the receiver was controlled to be 13 cm, the pushing speed of the injection pump was controlled to be 3.4 mm/h, the speed of the receiver was controlled to be 300 r/min, and the receiving time was controlled within 7 min. The filaments formed on the turntable receiver were collected to obtain superfine fibers in which polycaprolactone-collagen composite entraps growth factor.

EXAMPLE 8 [0093] (1) 225 mg of collagen were weighed and dissolved in 6.75 mL of hexafluoroisopropanol and 0.25 mL of water, and stirred for 1 hour in ice bath. After the solution became clear and collagen was completely dissolved, 115 pL of basic fibroblast growth factor was taken and entrapped in collagan. The resultant mixture was stirred in ice bath for 24 hours, and 0.95 g of polycaprolactone was added to the system and stirred in ice water bath for 3 hours until the whole system was uniformly mixed, so as to obtain finally a polymer in which polycaprolactone-collagen composite entraps growth factor.

OP19001 [0094] (2) Surgical sutures were prepared using an electrospinning device (Model: Tianjin Yunfan Technology YFSP-G III). The obtained polymer solution was loaded in a 10 ml injector, and a fine needle was selected for spinning. Meanwhile, the output voltage was controlled to be 12 kv, the distance between the spinning needle and the receiver was controlled to be 13 cm, the pushing speed of the injection pump was controlled to be 3.3 mm/h, the speed of the receiver was controlled to be 300 r/min, and the receiving time was controlled within 7 min. The filaments formed on the turntable receiver were collected to obtain superfine fibers in which polycaprolactone-collagen composite entraps growth factor.

EXAMPLE 9 [0095] (1) 225 mg of collagen were weighed and dissolved in 7 mL of hexafluoro isopropanol and 0.25 ml of water, and stirred for 1 hour in ice bath. After the solution became clear and collagen was completely dissolved, 115 pL of basic fibroblast growth factor was taken and entrapped in collagan. The resultant mixture was stirred in ice bath for 24 hours, and 0.45 g of polycaprolactone was added to the system and stirred in ice water bath for 3 hours until the whole system was uniformly mixed, so as to obtain finally a polymer in which polycaprolactone-collagen composite entraps growth factor.

[0096] (2) Surgical sutures were prepared using an electrospinning device (Model: Tianjin Yunfan Technology YFSP-G III). The obtained polymer solution was loaded in a 10 ml injector, and a fine needle was selected for spinning. Meanwhile, the output voltage was controlled to be 11 kv, the distance between the spinning needle and the receiver was controlled to be 13 cm, the pushing speed of the injection pump was controlled to be 3.3 mm/h, the speed of the receiver was controlled to be 300 r/min, and the receiving time was controlled within 7 min. The filaments formed on the turntable receiver were collected to obtain superfine fibers in which polycaprolactone-collagen composite entraps growth factor.

EXAMPLE 10

OP19001 [0097] (1) 225 mg of collagen were weighed and dissolved in 7 mL of hexafluoro isopropanol and 0.25 ml of water, and stirred for 1 hour in ice bath. After the solution became clear and collagen was completely dissolved, 115 pL of basic fibroblast growth factor was taken and entrapped in co Hagan. The resultant mixture was stirred in ice bath for 24 hours, and 0.7 g of polycaprolactone was added to the system and stirred in ice water bath for 3 hours until the whole system was uniformly mixed, so as to obtain finally a polymer in which polycaprolactone-collagen composite entraps growth factor.

[0098] (2) Surgical sutures were prepared using an electrospinning device (Model: Tianjin Yunfan Technology YFSP-G III). The obtained polymer solution was loaded in a 10 ml injector, and a fine needle was selected for spinning. Meanwhile, the output voltage was controlled to be 12 kv, the distance between the spinning needle and the receiver was controlled to be 13 cm, the pushing speed of the injection pump was controlled to be 1.2 mm/h, the speed of the receiver was controlled to be 300 r/min, and the receiving time was controlled within 7 min. The filaments formed on the turntable receiver were collected to obtain superfine fibers in which polycaprolactone-collagen composite entraps growth factor.

EXAMPLE 11 [0099] The method used in this example was similar to that of example 1, except that the output voltage was 4 kV.

EXAMPLE 12 [00100] The method used in this example was similar to that of example 1, except that the output voltage was 22 kV.

EXAMPLE 13 [00101] The method used in this example was similar to that of example 6, except that the pushing speed of the injection pump was 0.5 mm/h.

EXAMPLE 14

OP19001 [00102] The method used in this example was similar to that of example 6, except that the pushing speed of the injection pump was 3.8 mm/h.

EXAMPLE 15 [00103] The method used in this example was similar to that of example 5, except that

115 pL of epidermal growth factor was measured and entrapped in collagen.

EXAMPLE 16 [00104] The method used in this example was similar to that of example 5, except that

0.45 g of polyglycolide was added to the system.

COMPARATIVE EXAMPLES COMPARATIVE EXAMPLE 1 [00105] The method used in this comparative example was similar to that of example 5, except that the solvent of collagen was phosphate buffer solution.

COMPARATIVE EXAMPLE 2 [00106] The method used in this comparative example was similar to that of example 5, except that the output voltage was 3 kv.

COMPARATIVE EXAMPLE 3 [00107] The method used in this comparative example was similar to that of example 5, except that the output voltage was 25 kv.

COMPARATIVE EXAMPLE 4 [00108] The method used in this comparative example was similar to that of example 5, except that the pushing speed of the injection pumpu was 0.3 mm/h.

COMPARATIVE EXAMPLE 5 [00109] The method used in this comparative example was similar to that of example 5, except that the pushing speed of the injection pumpu was 4.0 mm/h.

COMPARATIVE EXAMPLE 6

OP19001 [00110] The method used in this comparative example was similar to that of example 5, except that 225 mg of collagen was weighed and dissolved in 3.5 mL of hexafluoroisopropanol and 0.25 ml of water.

COMPARATIVE EXAMPLE 7 [00111] The method used in this comparative example was similar to that of example 5, except that no basic fibroblast growth factor is entrapped in the collagen solution.

[00112] The performance parameters of the surgical sutures prepared in the above Examples 1 to 14 and Comparative Examples 1 to 5 were detected, and the results are shown in Table 1.

[00113] Table 1: Comparison of performance of the surgical sutures prepared in

Examples 1 to 16 and Comparative Examples 1 to 6

	Diameter	Tensile strength	Modulus	Degradation time
Example 1	4	3	3	+
Example 2	4	3	3	+
Example 3	3	3	3	+
Example 4	4	4	4	+
Example 5	5	5	5	+
Example 6	3	3	3	+
Example 7	3	3	3	+
Example 8	3	4	4	+
Example 9	4	3	2	+
Example 10	3	3	3	+
Example 11	3	3	3	+
Example 12	4	3	3	+
Example 13	3	3	3	+
Example 14	3	3	3	+
Example 15	5	5	5	+

OP19001

Example 16	5	4	4	+
Comparative Example 1	/	/	/	/
Comparative Example 2	1	1	1	+++
Comparative Example 3	2	2	2	+++
Comparative Example 4	3	2	2	+++
Comparative Example 5	3	2	2	+++
Comparative Example 6	/	/	/	/

[00114] In the above table 1, the diameter, tensile strength and modulues are all represented by “1”, “2”, “3”, “4” and “5”. For diameter, “1” represents the largest diameter, and “5” represents the smallest diameter. For tensile strength, “1” represents the smallest tensile strength, and “5” represents the largest tensile strength. For modulus, “1” represents the smallest modulus, and “5” represents the largest modulus. The symbol “+” represents a degradation time of 1 to 10 days, the symbol “++” represents a degradation time of 11 to 20 days, and the symbol “+++” represents a degradation time of 21 to 30 days. The symbol represents that filaments cannot be formed.

[00115] It can be seen from Table 1 that, the surgical sutures prepared in Examples 1 to 16 of the present invention have smaller diameters than those of the comparative examples, and the tensile strength and modulus are superior to those of the sutures of the comparative examples, and the degradation time is much less than that of the sutures of the comparative examples.

EXPERIMENTAL EXAMPLE

OP19001 [00116] The surgical sutures prepared in Example 1 and Comparative Example 7 of the present invention were applied to a mouse epidermal suture model. The sutures were smoothly knotted during the suturing process, had certain toughness and tension, and showed no suture breakage.

[00117] On the 13^th day of healing, the healing of the epidermis of the mice is shown in Figs. 2 and 3.

[00118] It can be seen from 2b in Fig. 2 that, the surgical suture prepared in Example 1 of the present invention has completely degraded during the healing process, without redness and swelling of skin or suture breakage, and the wound healing is completed. The wound healing in the case of suturing with the suture of Comparative Example 7 is shown in 3b of Fig. 3. The wound has an apparent unhealed surface, and the surgical suture which cannot be degraded can be seen.

[00119] It can be seen that, because of containing a biologically active factor, the surgical suture prepared in Example 1 of the present invention shows a speed of repairing the wound tissue which is significantly faster than the surgical suture of Comparative Example 7 in which no growth factor is added.

[00120] The present invention has been described in detail above with reference to the preferred embodiments and exemplary examples, which are not to be construed as limiting to the present invention. Those skilled in the art will appreciate that various equivalent substitutions, modifications, and improvements may be made to the technical solution of the present invention and embodiments thereof without departing from the spirit and scope of the invention, and all of these fall within the scope covered by the present invention.

Claims

CLAIMS:

1. A method of preparing a bioactive degradable surgical suture, comprising the steps of:

dissolving collagen in hexafluoroisopropanol and water, entrapping basic fibroblast growth factor in said collagen; adding polycaprolactone and uniformly mixing to obtain a polymer solution in which polycaprolactone-collagen composite entraps growth factor;

electrospinning the obtained polymer solution to obtain a superfine surgical suture using the following parameters:

the output voltage is 4 to 22 kV;

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

the pushing speed of the injection pump is 0.5 to 3.8 mm/h;

the receiver is a turntable receiver with a speed of 200 to 400 r/min; and the receiving time is 4 to 12 min.

2. The method according to claim 1 wherein electrospinning the obtained polymer solution to obtain a superfine surgical suture using the following parameters:

the output voltage is 17 kV;

the distance between the spinning needle and receiver is 13 cm;

the pushing speed of the injection pump is 2.1 mm/h;

the receiver is a turntable receiver with a speed of 300 r/min; and the receiving time is 7 min.

3. A method of preparing a bioactive degradable surgical suture, comprising the following steps:

(1) 225 mg of collagen were weighed and dissolved in 6.75 mL of hexafluoroisopropanol and 0.25 mL of water, and stirred for 1 hour in ice bath; after the solution became clear and collagen was completely dissolved, 115 pL of basic fibroblast growth factor was taken and entrapped in collagan; the resultant mixture

2019210543 13 Jan 2020 was stirred in ice bath for 24 hours, and 0.7 g of polycaprolactone was added to the system and stirred in ice water bath for 3 hours until the whole system was uniformly mixed, so as to obtain finally a polymer in which polycaprolactone-collagen composite entraps growth factor;
(2) surgical sutures were prepared using an electrospinning device: the obtained polymer solution from (1) was loaded in a 10 ml injector, and a fine needle was selected for spinning; meanwhile, the output voltage was controlled to be 17 kv, the distance between the spinning needle and the receiver was controlled to be 13 cm, the pushing speed of the injection pump was controlled to be 2.1 mm/h, the speed of the receiver was controlled to be 300 r/min, and the receiving time was controlled within 7 min; the filaments formed on the turntable receiver were collected to obtain superfine fibers in which polycaprolactone-collagen composite entraps growth factor.