WO2017028626A1 - Absorbable surgical suture and preparation method therefor - Google Patents

Absorbable surgical suture and preparation method therefor Download PDF

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Publication number
WO2017028626A1
WO2017028626A1 PCT/CN2016/087457 CN2016087457W WO2017028626A1 WO 2017028626 A1 WO2017028626 A1 WO 2017028626A1 CN 2016087457 W CN2016087457 W CN 2016087457W WO 2017028626 A1 WO2017028626 A1 WO 2017028626A1
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Prior art keywords
chitosan
surgical suture
absorbable surgical
preparing
spinning
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PCT/CN2016/087457
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French (fr)
Chinese (zh)
Inventor
吴奕光
薛清辉
江长兵
黎剑辉
吴灿光
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深圳市阳光之路生物材料科技有限公司
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Publication of WO2017028626A1 publication Critical patent/WO2017028626A1/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L17/00Materials for surgical sutures or for ligaturing blood vessels ; Materials for prostheses or catheters
    • A61L17/06At least partially resorbable materials
    • A61L17/08At least partially resorbable materials of animal origin, e.g. catgut, collagen
    • DTEXTILES; PAPER
    • D01NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01FCHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
    • D01F9/00Artificial filaments or the like of other substances; Manufacture thereof; Apparatus specially adapted for the manufacture of carbon filaments

Definitions

  • the invention relates to the technical field of biological materials, in particular to an absorbable surgical suture and a preparation method thereof.
  • Surgical sutures have a long history and can be divided into non-absorbable surgical sutures and absorbable surgical sutures according to their performance.
  • the biggest disadvantage of non-absorbable surgical sutures is that the wounds need to be removed after healing, and there are different degrees of tissue reaction.
  • the sutures are easy to leave scars, so they are limited in many surgical operations, especially for sutures of internal tissues.
  • absorbable surgical sutures such as the gut, silk thread and PGA line, which have been applied in practical clinical practice.
  • the absorbable surgical suture can be degraded and absorbed in the human body. It avoids the pain caused by the second operation, and can choose different absorbable surgical sutures according to the actual surgery needs.
  • the domestic patent "Preparation Process of a Chitosan Surgical Suture” discloses a preparation process of a chitosan surgical suture, firstly pouring a chitosan solution into a flat glass tank, Dry at a certain temperature to form a film, cut the film into strips with a mold, put it in a NaOH solution or a mixture of NaOH and ethanol for 5-10 minutes, then rinse with pure water to dry the chitosan suture thick line.
  • the chitosan suture thick line is placed in a saturated solution of chitosan for a period of time, and then taken out, twisted into a filament on a silk reeling machine, stretched and dried, and then immersed in a NaOH solution for 5 to 30 minutes to be taken out, and washed with pure water. Clean is the finished suture.
  • 201010218130.4 discloses a chitosan surgical suture and a manufacturing process thereof, firstly drying a chitosan solution into a film, and the film is in a mold Cut into strips, then put into a mixed solution of NaOH and ethanol The medium is heated, and the mixed solution is raised from 60 ° C to 80 ° C and then lowered to 60 ° C. After the pulsed heating for 60 to 120 minutes, the thick line is sutured by chitosan surgery. Then, the chitosan was sutured and the thick wire was subjected to drawing and coating to obtain a chitosan surgical suture.
  • 201110387194.1 discloses an absorbable surgical suture and a preparation method thereof, firstly dissolving chitosan in an acetic acid solution, and then adding urea And glycerin, fully stirred, filtered, defoamed to obtain a spinning solution; then the wet spinning method to prepare chitosan surgical suture thick line, after washing and drying, oil drying and other post-treatment, to obtain absorbable surgery Suture. Glycerin and urea components are added to the process, resulting in poor biocompatibility of the suture, easy to produce foreign body reaction, and tensile strength is difficult to meet clinical application requirements.
  • the domestic patent "Preparation method of aliphatic polyester-chitosan composite fiber tissue repair scaffold" Application No.
  • chitosan as a partial deacetylated product of chitin, which has a polyglycan (GAG) Similar chemical structures and many excellent properties for tissue engineering scaffolding materials.
  • GAG polyglycan
  • chitosan has poor mechanical properties in supporting tissue cells.
  • synthetic polyester composites are gradually used in tissue engineering, the mixing of chitosan with synthetic polyester with good mechanical properties can effectively improve the mechanical properties of the materials.
  • the fly in the ointment is that this method sacrifices many amino groups and hydroxyl groups on chitosan, and these groups are active groups with improved cell adhesion.
  • the object of the present invention is to provide an absorbable surgical suture and a preparation method thereof, which solve the technical problems that the prior art has a complicated preparation process, and the biocompatibility and mechanical properties cannot be obtained.
  • the present invention provides a method of preparing an absorbable surgical suture comprising the following steps:
  • the squid cartilage chitosan is dissolved to obtain a spinning dope; wherein the squid cartilage chitosan has a degree of deacetylation greater than 60% and a molecular weight greater than 0.5 ⁇ 10 6 ;
  • the spinning in step S2 is wet spinning.
  • the wet spinning comprises the steps of: feeding the spinning dope into a spinneret having an inner diameter of 0.1 to 1.0 mm through a metering pump, and extruding the spinning dope with a pressing force of 10 to 100 N; In the coagulation bath To chitosan monofilament;
  • the components of the coagulation bath comprise, by mass percentage, 4% to 6% of sodium hydroxide, 1% to 3% of ethanol, and the rest are deionized water.
  • step S1 the squid cartilage chitosan is dissolved in a solvent at a ratio of solid to liquid of 1.0:100 to 5.0:100 g/ml to obtain a spinning dope.
  • the solvent is acetic acid having a mass percent concentration of 2%.
  • the spinning dope is further filtered and defoamed.
  • the preparation of the salmon cartilage chitosan in step S1 comprises the following steps:
  • the squid cartilage ⁇ -chitin is dissolved in a NaOH solution having a mass percentage concentration of 30% to 40% at a ratio of solid to liquid of 5.0:100 to 25:100 g/ml, and stirred at 50 to 80 ° C for 1 to 6 hours. After filtration, the first filter residue is obtained;
  • the first filter residue is washed to neutral and then dried to obtain a first salmon cartilage chitosan as the salmon cartilage chitosan of step S1.
  • step S12 the following steps are further included:
  • the first squid cartilage chitosan obtained in step S12 is used as a first intermediate product, and the first intermediate product is dissolved in a mass percentage concentration at a ratio of solid to liquid ratio of 5.0:100 to 25:100 g/ml. 30% ⁇ 40% of the NaOH solution, stirred at 50 ⁇ 80 ° C for 1 ⁇ 6h and then filtered to obtain a second filter residue;
  • the second filter residue is washed to neutrality and then dried to obtain a second salmon cartilage chitosan having a different degree of deacetylation from the first intermediate product as the salmon cartilage chitosan of step S1.
  • step S12 or step S14 the following steps are further included:
  • the first squid cartilage chitosan obtained in step S12 or the second squid cartilage chitosan obtained in step S14 is used as a second intermediate product at a solid-liquid ratio of 5.0:100 to 25:100 g/ml.
  • the second intermediate product is dissolved in a hydrochloric acid solution having a mass percentage concentration of 1% to 5% at room temperature, and sonicated at 60 to 80 ° C for 2 to 8 hours to obtain a mixed solution;
  • the third filter residue is washed to neutrality and then dried to obtain a third salmon cartilage chitosan having a molecular weight different from that of the second intermediate product, as the salmon cartilage chitosan of step S1.
  • the present invention also provides an absorbable surgical suture that can be made using any of the above-described methods of preparing an absorbable surgical suture.
  • Chitin is divided into three crystal forms: ⁇ , ⁇ , and ⁇ . Among them, ⁇ -chitin is mainly distributed in mollusks and diatoms. Compared with ⁇ -chitin, only ⁇ -chitin is present in the molecule. Hydrogen bonds, and hydrogen bonds are weak, the structure is more loose, so ⁇ -chitin has higher reactivity. ⁇ -chitin has not only the safe, non-toxic, natural and biodegradable properties of ⁇ -chitin, but also has higher affinity for various solvents and is easier to chemically modify than ⁇ -chitin.
  • the squid cartilage chitosan and shrimp and crab chitosan prepared by deacetylation of squid cartilage ⁇ -chitin are the only cationic aminopolysaccharides in nature, which not only have natural bioregeneration, biodegradability, and biological phase.
  • Capacitive and antibacterial properties, and the absorbable surgical sutures prepared from the specific molecular weight squid cartilage chitosan (MW>0.5 ⁇ 10 6 ) are better in mechanical properties and can be gradually absorbed by the human body, effectively promoting wound tissue. healing.
  • the invention adopts a specific molecular weight and deacetylation degree of squid cartilage chitosan (DD>60%, MW>0.5 ⁇ 10 6 ) as a raw material, and the monofilament chitosan can be absorbed by the wet spinning technique to absorb the surgical suture. It has a diameter of 0.05 to 0.50 mm, a tensile strength of 10 to 80 N, and an elongation at break of 3% to 15%. It has better toughness and tensile strength than other chitosan surgical sutures, and has a more uniform diameter.
  • the surface is smoother and the cross section is more rounded, which greatly improves the tensile strength of the surgical suture, and solves the problem of insufficient mechanical properties of the biomaterial as a medical absorbable surgical suture; in addition, the absorbable surgical suture only contains the squid cartilage Chitosan has good biocompatibility and human absorbable properties, which avoids the pain of patient's suture removal, and the surgical suture has no inflammatory reaction to surrounding tissues, which can effectively promote the healing of wound tissue, and can be widely used in surgery. Wound ligation, suturing, hemostasis, and suturing of other tissues.
  • the preparation method of an absorbable surgical suture according to the present invention comprises the following steps:
  • the spinning and defoaming spinning dope is wet-spun, dried and stretched to obtain an absorbable surgical suture.
  • the preparation of the squid cartilage chitosan in step S1 comprises:
  • the cartilage cartilage ⁇ -chitin or squid is soft.
  • the chitosan is dissolved in a NaOH solution having a mass percentage concentration of 30% to 40%, stirred at 50 to 80 ° C for 1 to 6 hours, and then filtered to obtain a filter residue;
  • the filter residue obtained in the step S11 is washed to neutrality and then dried to obtain the squid cartilage chitosan used in the step S1.
  • the degree of deacetylation of squid cartilage chitosan was determined by elemental analysis, and the viscosity average molecular weight of squid cartilage chitosan was determined by a dilute solution viscosity method to obtain a series of squid cartilage chitosan as shown in Table 1 below. It can be seen from Table 1 that using different deacetylation conditions (such as alkali concentration, time, temperature), the obtained chimon cartilage chitosan has similar molecular weights and different degrees of deacetylation.
  • the preparation of the squid cartilage chitosan further comprises, after step S12:
  • step S13 Taking the squid cartilage chitosan obtained in step S12 as an intermediate product, the ratio of solid to liquid is 5.0:100. ⁇ 25:100g/ml ratio, the intermediate product is dissolved in a hydrochloric acid solution having a mass percentage concentration of 1% to 5% at room temperature, and sonicated at 60 to 80 ° C for 2 to 8 hours to obtain a mixed solution;
  • the filter residue obtained in the step S14 is washed to neutrality and then dried to obtain a squid cartilage chitosan having a molecular weight different from that of the intermediate product, which is used as the squid cartilage chitosan used in the step S1.
  • the degree of deacetylation of squid cartilage chitosan was determined by elemental analysis.
  • the viscosity average molecular weight of squid cartilage chitosan was determined by dilute solution viscosity method, and a series of squid cartilage chitosan as shown in Table 2 below were obtained. As can be seen from Table 2, by changing the sonication time and/or temperature, the obtained cartilage chitosan has a similar degree of deacetylation and a different molecular weight.
  • CS-150 DD (80.00 ⁇ 0.65)%, MW (1.52 ⁇ 0.25) ⁇ 10 6 carp cartilage chitosan.
  • Embodiment 1 is a diagrammatic representation of Embodiment 1:
  • the preparation method of an absorbable surgical suture according to the present invention comprises the following steps:
  • a spinneret with an inner diameter of 0.8 mm is input through a metering pump. Pressing the spinning dope into the coagulation bath to obtain the chitosan monofilament; wherein the mass percentage of each component of the coagulation bath comprises: sodium hydroxide 4%, ethanol 2%, and the rest is deionized water;
  • the chitosan monofilament was soaked in deionized water to neutrality, and then stretched at room temperature for 10 N and dried for 1 day to obtain a novel chitosan absorbable surgical suture monofilament.
  • the preparation of the squid cartilage chitosan powder in step S1 comprises:
  • the filter residue is washed with deionized water until neutral, and then dried and ground to obtain a squid cartilage chitosan powder.
  • the surgical suture prepared in this example has a diameter of 0.27 mm, a tensile strength of 45.47 N, and a tensile elongation at break of 14.13%.
  • Embodiment 2 is a diagrammatic representation of Embodiment 1:
  • the preparation method of an absorbable surgical suture according to the present invention comprises the following steps:
  • a spinning nozzle with an inner diameter of 0.5 mm is input through a metering pump, and the spinning dope is squeezed into a coagulation bath by a pressure of 60 N to obtain a chitosan monofilament; wherein, each group of the coagulation bath
  • the mass percentage of the fraction includes: 6% sodium hydroxide, 1% ethanol, and the rest is deionized water;
  • the chitosan monofilament was soaked in deionized water to neutrality, and then stretched at room temperature for 10 N and dried for 1 day to obtain a novel chitosan absorbable surgical suture monofilament.
  • the preparation of the squid cartilage chitosan powder in step S1 comprises:
  • the salmon cartilage ⁇ -chitin is dissolved in a mass percentage concentration of 30% NaOH solution, stirred at 50 ° C for 6h and filtered to obtain filter residue;
  • the filter residue is washed with deionized water until neutral, and then dried and ground to obtain a squid cartilage chitosan powder.
  • the surgical suture prepared in this example has a diameter of 0.29 mm, a tensile strength of 45.17 N, and a tensile elongation at break of 14.13%.
  • Embodiment 3 is a diagrammatic representation of Embodiment 3
  • the preparation method of an absorbable surgical suture according to the present invention comprises the following steps:
  • a spinning nozzle with an inner diameter of 1.0 mm is input through a metering pump, and the spinning dope is squeezed into a coagulation bath by a pressure of 100 N to obtain a chitosan monofilament; wherein, each group of the coagulation bath
  • the mass percentage of the fraction includes: 5% sodium hydroxide, 3% ethanol, and the rest is deionized water;
  • the chitosan monofilament was soaked in deionized water to neutrality, and then stretched at room temperature for 10 N and dried for 1 day to obtain a novel chitosan absorbable surgical suture monofilament.
  • the preparation of the squid cartilage chitosan powder in step S1 comprises:
  • the salmon cartilage ⁇ -chitin is dissolved in a mass percentage concentration of 38% NaOH solution, stirred at 60 ° C for 5h and filtered to obtain filter residue;
  • the filter residue is washed with deionized water until neutral, and then dried and ground to obtain a squid cartilage chitosan powder.
  • the surgical suture prepared in this example has a diameter of 0.44 mm, a tensile strength of 45.41 N, and a tensile elongation at break of 14.19%.
  • Embodiment 4 is a diagrammatic representation of Embodiment 4:
  • the preparation method of an absorbable surgical suture according to the present invention comprises the following steps:
  • a spinneret having an inner diameter of 0.8 mm is input through a metering pump, and the spinning dope is extruded into a coagulation bath by a pressure of 80 N to obtain a chitosan monofilament; wherein the coagulation bath groups are
  • the mass percentage of the fraction includes: 4% sodium hydroxide, 2% ethanol, and the rest is deionized water;
  • the chitosan monofilament was soaked in deionized water to neutrality, and then stretched at room temperature for 10 N and dried for 1 day to obtain a novel chitosan absorbable surgical suture monofilament.
  • the preparation of the squid cartilage chitosan powder in step S1 comprises:
  • the salmon cartilage ⁇ -chitin is dissolved in a 40% by mass concentration of NaOH solution, stirred at 70 ° C for 3h and filtered to obtain filter residue;
  • the filter residue is washed with deionized water until neutral, and then dried and ground to obtain a squid cartilage chitosan powder.
  • the surgical suture prepared in this example has a diameter of 0.36 mm, a tensile strength of 45.06 N, and a tensile elongation at break of 14.10%.
  • Embodiment 5 is a diagrammatic representation of Embodiment 5:
  • the preparation method of an absorbable surgical suture according to the present invention comprises the following steps:
  • a spinning nozzle with an inner diameter of 0.8 mm is input through a metering pump, and the spinning dope is squeezed into a coagulation bath by a pressure of 20 N to obtain a chitosan monofilament; wherein, each group of the coagulation bath
  • the mass percentage of the fraction includes: 4% sodium hydroxide, 2% ethanol, and the rest is deionized water;
  • the chitosan monofilament was soaked in deionized water to neutrality, and then stretched at room temperature for 10 N and dried for 1 day to obtain a novel chitosan absorbable surgical suture monofilament.
  • the preparation of the squid cartilage chitosan powder in step S1 comprises:
  • the surgical suture prepared in this example has a diameter of 0.22 mm, a tensile strength of 44.98 N, and a tensile elongation at break of 14.12%.
  • the preparation method of an absorbable surgical suture according to the present invention comprises the following steps:
  • a spinning nozzle with an inner diameter of 0.5 mm is input through a metering pump, and the spinning dope is extruded into a coagulation bath with a pressure of 50 N to obtain a chitosan monofilament; wherein, each group of the coagulation bath
  • the mass percentage of the fraction includes: 4% sodium hydroxide, 2% ethanol, and the rest is deionized water;
  • the chitosan monofilament was soaked in deionized water to neutrality, and then stretched at room temperature for 10 N and dried for 1 day to obtain a novel chitosan absorbable surgical suture monofilament.
  • the preparation of the squid cartilage chitosan powder in step S1 comprises:
  • the surgical suture prepared in this example has a diameter of 0.24 mm, a tensile strength of 45.21 N, and a tensile elongation at break of 14.02%.
  • the preparation method of an absorbable surgical suture according to the present invention comprises the following steps:
  • a spinning nozzle with an inner diameter of 0.3 mm is input through a metering pump, and the spinning dope is squeezed into a coagulation bath by a pressure of 70 N to obtain a chitosan monofilament; wherein, each group of the coagulation bath
  • the mass percentage of the fraction includes: 4% sodium hydroxide, 2% ethanol, and the rest is deionized water;
  • chitosan monofilament is washed with deionized water to neutrality, and then stretched 10N at room temperature and dried 1 Days, the new chitosan absorbs surgical suture monofilaments.
  • the preparation of the squid cartilage chitosan powder in step S1 comprises:
  • the surgical suture prepared in this example has a diameter of 0.21 mm, a tensile strength of 45.38 N, and a tensile elongation at break of 14.09%.

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Abstract

Disclosed are an absorbable surgical suture and a preparation method therefor. The preparation method comprises the following steps: S1, dissolving squid cartilage chitosan to obtain a spinning solution, the deacetylation degree of the squid cartilage chitosan being greater than 60%, and the molecular weight of the squid cartilage chitosan being greater than 0.5*106; and S2, spinning the spinning solution and then drying to obtain the absorbable surgical suture. The absorbable surgical suture prepared by the method has a mechanical property reaching the requirements of clinical application, can be gradually absorbed by a human body and effectively promote the healing of a wound tissue, and has a better application prospect.

Description

一种可吸收手术缝合线及其制备方法Absorbable surgical suture and preparation method thereof 技术领域Technical field
本发明涉及生物材料技术领域,特别涉及一种可吸收手术缝合线及其制备方法。The invention relates to the technical field of biological materials, in particular to an absorbable surgical suture and a preparation method thereof.
背景技术Background technique
手术缝合线历史悠久,根据其性能不同可分为不可吸收类手术缝合线和可吸收类手术缝合线。不可吸收类手术缝合线最大的缺点是伤口愈合后需要拆线,有不同程度的组织反应,缝合处容易留下疤痕,因此在许多外科手术中受到限制,特别不适合体内组织的缝合。20世纪开始,世界上许多发达国家已经开始研究可吸收手术缝合线,例如羊肠线、真丝线及PGA线等已经在实际临床中得到应用,可吸收手术缝合线在人体内能被降解吸收,避免了二次手术给病人带来的痛苦,而且可以根据实际手术的需要,选用不同的可吸收手术缝合线。我国在可吸收手术缝合线的研究方面起步相对较晚,研究主要集中在聚乙交酯、聚乙丙交酯及聚乳酸等材料的合成、纺丝及体外降解和动物实验。但到目前为止,这些研究大都处于实验室阶段,还有很多关键技术有待解决。迄今为止,国内医院绝大部分外科手术所使用的可吸收手术缝合线主要是进口的丝线、PGLA线及羊肠线。Surgical sutures have a long history and can be divided into non-absorbable surgical sutures and absorbable surgical sutures according to their performance. The biggest disadvantage of non-absorbable surgical sutures is that the wounds need to be removed after healing, and there are different degrees of tissue reaction. The sutures are easy to leave scars, so they are limited in many surgical operations, especially for sutures of internal tissues. Since the beginning of the 20th century, many developed countries in the world have begun to study absorbable surgical sutures, such as the gut, silk thread and PGA line, which have been applied in practical clinical practice. The absorbable surgical suture can be degraded and absorbed in the human body. It avoids the pain caused by the second operation, and can choose different absorbable surgical sutures according to the actual surgery needs. In China, the research on absorbable surgical sutures started relatively late. The research mainly focused on the synthesis, spinning, in vitro degradation and animal experiments of polyglycolide, polyethyl lactide and polylactic acid. But so far, most of these studies are in the laboratory stage, and there are still many key technologies to be solved. So far, the absorbable surgical sutures used in most surgical operations in domestic hospitals are mainly imported silk, PGLA lines and gut lines.
国内专利《一种壳聚糖手术缝合线的制备工艺》(公开号CN03129976.6)公开了一种壳聚糖手术缝合线的制备工艺,首先将壳聚糖溶液倒入平板玻璃槽中,在一定温度下干燥成膜,用模具把膜切割成条状,放入NaOH溶液或者NaOH与乙醇的混合液中加热5~10min后用纯水清洗晾干得壳聚糖缝合粗线。然后,将壳聚糖缝合粗线放到壳聚糖饱和溶液中浸泡一段时间后取出,在捻丝机上捻成细丝,拉伸干燥后放入NaOH溶液中浸泡5~30min取出,纯水清洗干净即为成品缝合线。国内专利《一种壳聚糖手术缝合线及其制作工艺》(申请号201010218130.4)公开了一种壳聚糖手术缝合线及其制作工艺,首先将壳聚糖溶液干燥成膜,将膜在模具上切割成条状,然后放入到NaOH与乙醇的混合溶液 中加热,使混合溶液从60℃升至80℃后在降至60℃,如此循环脉冲式加热60~120min后,即为壳聚糖手术缝合粗线。然后壳聚糖手术缝合粗线经过拉丝、涂膜后得到壳聚糖手术缝合线。以上两种工艺均为先制膜后制线,生产工艺复杂,成本高,且缝合线横截面不够圆滑,摩擦阻力大,同时抗拉强度也不够,临床应用价值不高。国内专利《一种可吸收性手术缝合线及其制备方法》(申请号201110387194.1)公开了一种可吸收性手术缝合线及其制备方法,首先将壳聚糖溶于乙酸溶液中,然后加入尿素和甘油,充分搅拌后,经过滤、脱泡得到纺丝溶液;然后采用湿法纺丝法制备壳聚糖手术缝合粗线线,经过清洗干燥、上油干燥等后处理,得到可吸收性手术缝合线。此工艺过程中添加了甘油及尿素成分,致使缝合线的生物相容性较差,易产生异物反应,且抗张强度难以达到临床应用要求。国内专利《脂肪族聚酯-壳聚糖复合纤维组织修复支架的制备方法》(申请号200810051315)公开了壳聚糖(Chitosan)作为甲壳素的部分脱乙酰基产物,有着与粘多糖(GAG)相似的化学结构,并且有许多适用于组织工程支架材料的优良性质。然而,同其它天然大分子一样,壳聚糖在支撑组织细胞方面的力学性能不好。随着天然大分子与合成聚酯复合材料逐步用在组织工程中,壳聚糖与力学性能良好的合成聚酯的混合可以有效的改善材料的力学性能。美中不足的是此法牺牲了许多壳聚糖上的氨基和羟基,而这些基团正是细胞粘附性得以提高的活性基团。The domestic patent "Preparation Process of a Chitosan Surgical Suture" (Publication No. CN03129976.6) discloses a preparation process of a chitosan surgical suture, firstly pouring a chitosan solution into a flat glass tank, Dry at a certain temperature to form a film, cut the film into strips with a mold, put it in a NaOH solution or a mixture of NaOH and ethanol for 5-10 minutes, then rinse with pure water to dry the chitosan suture thick line. Then, the chitosan suture thick line is placed in a saturated solution of chitosan for a period of time, and then taken out, twisted into a filament on a silk reeling machine, stretched and dried, and then immersed in a NaOH solution for 5 to 30 minutes to be taken out, and washed with pure water. Clean is the finished suture. The domestic patent "a chitosan surgical suture and its manufacturing process" (Application No. 201010218130.4) discloses a chitosan surgical suture and a manufacturing process thereof, firstly drying a chitosan solution into a film, and the film is in a mold Cut into strips, then put into a mixed solution of NaOH and ethanol The medium is heated, and the mixed solution is raised from 60 ° C to 80 ° C and then lowered to 60 ° C. After the pulsed heating for 60 to 120 minutes, the thick line is sutured by chitosan surgery. Then, the chitosan was sutured and the thick wire was subjected to drawing and coating to obtain a chitosan surgical suture. The above two processes are first made after film making, the production process is complicated, the cost is high, the cross section of the suture is not smooth enough, the friction resistance is large, the tensile strength is not enough, and the clinical application value is not high. The domestic patent "an absorbable surgical suture and a preparation method thereof" (Application No. 201110387194.1) discloses an absorbable surgical suture and a preparation method thereof, firstly dissolving chitosan in an acetic acid solution, and then adding urea And glycerin, fully stirred, filtered, defoamed to obtain a spinning solution; then the wet spinning method to prepare chitosan surgical suture thick line, after washing and drying, oil drying and other post-treatment, to obtain absorbable surgery Suture. Glycerin and urea components are added to the process, resulting in poor biocompatibility of the suture, easy to produce foreign body reaction, and tensile strength is difficult to meet clinical application requirements. The domestic patent "Preparation method of aliphatic polyester-chitosan composite fiber tissue repair scaffold" (Application No. 200810051315) discloses chitosan (Chitosan) as a partial deacetylated product of chitin, which has a polyglycan (GAG) Similar chemical structures and many excellent properties for tissue engineering scaffolding materials. However, like other natural macromolecules, chitosan has poor mechanical properties in supporting tissue cells. As natural macromolecules and synthetic polyester composites are gradually used in tissue engineering, the mixing of chitosan with synthetic polyester with good mechanical properties can effectively improve the mechanical properties of the materials. The fly in the ointment is that this method sacrifices many amino groups and hydroxyl groups on chitosan, and these groups are active groups with improved cell adhesion.
发明内容Summary of the invention
本发明目的在于提出一种可吸收手术缝合线及其制备方法,以解决上述现有技术存在的制备工艺复杂、生物相容性与力学性能无法兼得的技术问题。The object of the present invention is to provide an absorbable surgical suture and a preparation method thereof, which solve the technical problems that the prior art has a complicated preparation process, and the biocompatibility and mechanical properties cannot be obtained.
为此,本发明提出一种可吸收手术缝合线的制备方法,包括以下步骤:To this end, the present invention provides a method of preparing an absorbable surgical suture comprising the following steps:
S1、将鱿鱼软骨壳聚糖溶解得到纺丝原液;其中,所述鱿鱼软骨壳聚糖的脱乙酰度大于60%、分子量大于0.5×106S1, the squid cartilage chitosan is dissolved to obtain a spinning dope; wherein the squid cartilage chitosan has a degree of deacetylation greater than 60% and a molecular weight greater than 0.5×10 6 ;
S2、对所述纺丝原液纺丝后干燥,得到所述可吸收手术缝合线。S2, drying the spinning dope and drying to obtain the absorbable surgical suture.
优选地,步骤S2中所述纺丝为湿法纺丝。Preferably, the spinning in step S2 is wet spinning.
优选地,所述湿法纺丝包括如下步骤:将所述纺丝原液通过计量泵输入内径为0.1~1.0mm的喷丝头,用10~100N的挤压力将所述纺丝原液挤入凝固浴中得 到壳聚糖单丝;Preferably, the wet spinning comprises the steps of: feeding the spinning dope into a spinneret having an inner diameter of 0.1 to 1.0 mm through a metering pump, and extruding the spinning dope with a pressing force of 10 to 100 N; In the coagulation bath To chitosan monofilament;
其中,所述凝固浴各组分按质量百分比包括:氢氧化钠4%~6%、乙醇1%~3%,其余为去离子水。Wherein, the components of the coagulation bath comprise, by mass percentage, 4% to 6% of sodium hydroxide, 1% to 3% of ethanol, and the rest are deionized water.
优选地,步骤S1中按固液比1.0∶100~5.0∶100g/ml的比例,将所述鱿鱼软骨壳聚糖溶解于溶剂中得到纺丝原液。Preferably, in step S1, the squid cartilage chitosan is dissolved in a solvent at a ratio of solid to liquid of 1.0:100 to 5.0:100 g/ml to obtain a spinning dope.
优选地,所述溶剂为质量百分比浓度2%的醋酸。Preferably, the solvent is acetic acid having a mass percent concentration of 2%.
优选地,步骤S2中对所述纺丝原液纺丝前还包括对所述纺丝原液过滤、脱泡。Preferably, before the spinning of the spinning dope in step S2, the spinning dope is further filtered and defoamed.
优选地,步骤S1中所述鱿鱼软骨壳聚糖的制备包括如下步骤:Preferably, the preparation of the salmon cartilage chitosan in step S1 comprises the following steps:
S11、按固液比5.0∶100~25∶100g/ml的比例,将鱿鱼软骨β-甲壳素溶解于质量百分比浓度30%~40%的NaOH溶液中,在50~80℃下搅拌1~6h后过滤,得到第一滤渣;S11. The squid cartilage β-chitin is dissolved in a NaOH solution having a mass percentage concentration of 30% to 40% at a ratio of solid to liquid of 5.0:100 to 25:100 g/ml, and stirred at 50 to 80 ° C for 1 to 6 hours. After filtration, the first filter residue is obtained;
S12、对所述第一滤渣洗涤至中性后干燥,得到第一鱿鱼软骨壳聚糖,作为步骤S1的鱿鱼软骨壳聚糖。S12. The first filter residue is washed to neutral and then dried to obtain a first salmon cartilage chitosan as the salmon cartilage chitosan of step S1.
优选地,在步骤S12之后还包括如下步骤:Preferably, after step S12, the following steps are further included:
S13、将步骤S12得到的所述第一鱿鱼软骨壳聚糖作为第一中间产物,按固液比5.0∶100~25∶100g/ml的比例,将所述第一中间产物溶解于质量百分比浓度30%~40%的NaOH溶液中,在50~80℃下搅拌1~6h后过滤,得到第二滤渣;S13, the first squid cartilage chitosan obtained in step S12 is used as a first intermediate product, and the first intermediate product is dissolved in a mass percentage concentration at a ratio of solid to liquid ratio of 5.0:100 to 25:100 g/ml. 30% ~ 40% of the NaOH solution, stirred at 50 ~ 80 ° C for 1 ~ 6h and then filtered to obtain a second filter residue;
S14、对所述第二滤渣洗涤至中性后干燥,得到与所述第一中间产物脱乙酰度不同的第二鱿鱼软骨壳聚糖,作为步骤S 1的鱿鱼软骨壳聚糖。S14. The second filter residue is washed to neutrality and then dried to obtain a second salmon cartilage chitosan having a different degree of deacetylation from the first intermediate product as the salmon cartilage chitosan of step S1.
优选地,在步骤S12或步骤S14之后还包括如下步骤:Preferably, after step S12 or step S14, the following steps are further included:
S15、将步骤S12得到的所述第一鱿鱼软骨壳聚糖或步骤S14得到的所述第二鱿鱼软骨壳聚糖作为第二中间产物,按固液比5.0∶100~25∶100g/ml的比例,将所述第二中间产物在室温下溶解于质量百分比浓度1%~5%的盐酸溶液中,在60~80℃下超声处理2~8h,得到混合液;S15, the first squid cartilage chitosan obtained in step S12 or the second squid cartilage chitosan obtained in step S14 is used as a second intermediate product at a solid-liquid ratio of 5.0:100 to 25:100 g/ml. Proportion, the second intermediate product is dissolved in a hydrochloric acid solution having a mass percentage concentration of 1% to 5% at room temperature, and sonicated at 60 to 80 ° C for 2 to 8 hours to obtain a mixed solution;
S16、在所述混合液中加入0.1~1.0mol/L的NaOH溶液调节所述混合液至中性,抽滤得到第三滤渣;S16, adding 0.1~1.0 mol/L NaOH solution to the mixture to adjust the mixture to neutrality, and suction filtration to obtain a third filter residue;
S17、对所述第三滤渣洗涤至中性后干燥,得到与所述第二中间产物分子量不同的第三鱿鱼软骨壳聚糖,作为步骤S1的鱿鱼软骨壳聚糖。 S17. The third filter residue is washed to neutrality and then dried to obtain a third salmon cartilage chitosan having a molecular weight different from that of the second intermediate product, as the salmon cartilage chitosan of step S1.
本发明还提出一种可吸收手术缝合线,使用上述任一项可吸收手术缝合线的制备方法制成。The present invention also provides an absorbable surgical suture that can be made using any of the above-described methods of preparing an absorbable surgical suture.
甲壳素按结构分α、β、γ三种晶型,其中β-甲壳素主要分布于软体动物骨架和硅藻类等生物中,与α-甲壳素相比,β-甲壳素中只存在分子内氢键,且氢键较弱,结构更松散,因此β-甲壳素具有更高的反应活性。β-甲壳素不仅具有α-甲壳素的安全无毒、纯天然和可生物降解等性质,而且还对各种溶剂具有更高的亲和性,比α-甲壳素更易于进行化学改性。由鱿鱼软骨β-甲壳素经脱乙酰化制得的鱿鱼软骨壳聚糖与虾蟹壳壳聚糖均是自然界中唯一的阳离子氨基多糖,其不仅具有天然生物再生性、生物降解性、生物相容性及抗菌性等,且以特定分子量鱿鱼软骨壳聚糖(MW>0.5×106)为原料制备的可吸收手术缝合线力学性能更佳,且能被人体逐渐吸收,有效地促进伤口组织的愈合。Chitin is divided into three crystal forms: α, β, and γ. Among them, β-chitin is mainly distributed in mollusks and diatoms. Compared with α-chitin, only β-chitin is present in the molecule. Hydrogen bonds, and hydrogen bonds are weak, the structure is more loose, so β-chitin has higher reactivity. Β-chitin has not only the safe, non-toxic, natural and biodegradable properties of α-chitin, but also has higher affinity for various solvents and is easier to chemically modify than α-chitin. The squid cartilage chitosan and shrimp and crab chitosan prepared by deacetylation of squid cartilage β-chitin are the only cationic aminopolysaccharides in nature, which not only have natural bioregeneration, biodegradability, and biological phase. Capacitive and antibacterial properties, and the absorbable surgical sutures prepared from the specific molecular weight squid cartilage chitosan (MW>0.5×10 6 ) are better in mechanical properties and can be gradually absorbed by the human body, effectively promoting wound tissue. Healing.
本发明采用特定分子量和脱乙酰度的鱿鱼软骨壳聚糖(DD>60%,MW>0.5×106)为原料,通过湿法纺丝技术制备的单丝状壳聚糖可吸收手术缝合线,其直径为0.05~0.50mm、抗张强度为10~80N、断裂伸长率为3%~15%,较其它壳聚糖手术缝合线具有更好的韧性和抗拉强度,并且直径更加均匀、表面更加光滑、横截面更圆润,大大地提高了手术缝合线的拉伸强度,解决了生物材料作为医用可吸收手术缝合线力学性能不足的问题;此外,可吸收手术缝合线仅包含鱿鱼软骨壳聚糖,具有良好的生物相容性和人体可吸收特性,免除患者拆线痛苦,且手术缝合线对周围组织无炎症反应,能够有效地促进伤口组织的愈合,可广泛用于外科手术中的伤口结扎、缝合、止血以及其他组织的缝合。The invention adopts a specific molecular weight and deacetylation degree of squid cartilage chitosan (DD>60%, MW>0.5×10 6 ) as a raw material, and the monofilament chitosan can be absorbed by the wet spinning technique to absorb the surgical suture. It has a diameter of 0.05 to 0.50 mm, a tensile strength of 10 to 80 N, and an elongation at break of 3% to 15%. It has better toughness and tensile strength than other chitosan surgical sutures, and has a more uniform diameter. The surface is smoother and the cross section is more rounded, which greatly improves the tensile strength of the surgical suture, and solves the problem of insufficient mechanical properties of the biomaterial as a medical absorbable surgical suture; in addition, the absorbable surgical suture only contains the squid cartilage Chitosan has good biocompatibility and human absorbable properties, which avoids the pain of patient's suture removal, and the surgical suture has no inflammatory reaction to surrounding tissues, which can effectively promote the healing of wound tissue, and can be widely used in surgery. Wound ligation, suturing, hemostasis, and suturing of other tissues.
具体实施方式detailed description
本发明提出的一种可吸收手术缝合线的制备方法,包括以下步骤:The preparation method of an absorbable surgical suture according to the present invention comprises the following steps:
S1、按固液比1.0∶100~5.0∶100g/ml的比例,将脱乙酰度大于60%、分子量大于0.5×106的鱿鱼软骨壳聚糖溶解得到纺丝原液;S1, according to the ratio of solid-liquid ratio of 1.0:100-5.0:100g/ml, the chitosan chitosan having a degree of deacetylation of more than 60% and a molecular weight of more than 0.5×10 6 is dissolved to obtain a spinning dope;
S2、对过滤、脱泡后的纺丝原液湿法纺丝,干燥、拉伸得到可吸收手术缝合线。S2. The spinning and defoaming spinning dope is wet-spun, dried and stretched to obtain an absorbable surgical suture.
其中,步骤S1中鱿鱼软骨壳聚糖的制备包括:Wherein, the preparation of the squid cartilage chitosan in step S1 comprises:
S11、按固液比5.0∶100~25∶100g/ml的比例,将鱿鱼软骨β-甲壳素或鱿鱼软 骨壳聚糖溶解于质量百分比浓度30%~40%的NaOH溶液中,在50~80℃下搅拌1~6h后过滤,得到滤渣;S11. According to the ratio of solid to liquid ratio of 5.0:100 to 25:100 g/ml, the cartilage cartilage β-chitin or squid is soft. The chitosan is dissolved in a NaOH solution having a mass percentage concentration of 30% to 40%, stirred at 50 to 80 ° C for 1 to 6 hours, and then filtered to obtain a filter residue;
S12、对步骤S11得到的滤渣洗涤至中性后干燥,得到步骤S1所用的鱿鱼软骨壳聚糖。S12. The filter residue obtained in the step S11 is washed to neutrality and then dried to obtain the squid cartilage chitosan used in the step S1.
通过元素分析法测定鱿鱼软骨壳聚糖的脱乙酰度,稀溶液粘度法测定鱿鱼软骨壳聚糖的粘均分子量,得到如下表1所示的一系列鱿鱼软骨壳聚糖。由表1可看出,采用不同的脱乙酰条件(如碱浓度、时间、温度),得到的鱿鱼软骨壳聚糖的分子量相近,而脱乙酰度不同。The degree of deacetylation of squid cartilage chitosan was determined by elemental analysis, and the viscosity average molecular weight of squid cartilage chitosan was determined by a dilute solution viscosity method to obtain a series of squid cartilage chitosan as shown in Table 1 below. It can be seen from Table 1 that using different deacetylation conditions (such as alkali concentration, time, temperature), the obtained chimon cartilage chitosan has similar molecular weights and different degrees of deacetylation.
Figure PCTCN2016087457-appb-000001
Figure PCTCN2016087457-appb-000001
表1Table 1
其中,among them,
β-chitin:鱿鱼软骨β-甲壳素;--chitin: salmon cartilage β-chitin;
2+1a:脱乙酰两次,第一次2h,第二次1h;2+1 a : deacetylation twice, the first 2h, the second 1h;
2+1+16:脱乙酰三次,第一次2h,第二次1h,第三次1h;2+1+1 6 : three times of deacetylation, the first 2h, the second 1h, the third 1h;
1+1+1+1+1c:脱乙酰五次,每次1h;1+1+1+1+1 c : deacetylation five times, each time 1h;
CS-75d:CS-75在70℃超声处理2h;CS-75 d : CS-75 was sonicated at 70 ° C for 2 h;
Nile:不完全溶解,无法测定粘均分子量。Nil e : Not completely dissolved, the viscosity average molecular weight could not be determined.
更进一步地,鱿鱼软骨壳聚糖的制备在步骤S12之后还包括:Further, the preparation of the squid cartilage chitosan further comprises, after step S12:
S13、将步骤S12得到的鱿鱼软骨壳聚糖作为中间产物,按固液比5.0∶100 ~25∶100g/ml的比例,将中间产物在室温下溶解于质量百分比浓度1%~5%的盐酸溶液中,在60~80℃下超声处理2~8h,得到混合液;S13. Taking the squid cartilage chitosan obtained in step S12 as an intermediate product, the ratio of solid to liquid is 5.0:100. ~25:100g/ml ratio, the intermediate product is dissolved in a hydrochloric acid solution having a mass percentage concentration of 1% to 5% at room temperature, and sonicated at 60 to 80 ° C for 2 to 8 hours to obtain a mixed solution;
S14、在混合液中加入0.1~1.0mol/L的NaOH溶液调节混合液至中性,抽滤得到滤渣;S14, adding 0.1~1.0mol/L NaOH solution to the mixture to adjust the mixture to neutrality, and suction filtration to obtain filter residue;
S15、对步骤S14得到的滤渣洗涤至中性后干燥,得到与中间产物分子量不同的鱿鱼软骨壳聚糖,作为步骤S1所用的鱿鱼软骨壳聚糖。S15. The filter residue obtained in the step S14 is washed to neutrality and then dried to obtain a squid cartilage chitosan having a molecular weight different from that of the intermediate product, which is used as the squid cartilage chitosan used in the step S1.
仍然通过元素分析法测定鱿鱼软骨壳聚糖的脱乙酰度,稀溶液粘度法测定鱿鱼软骨壳聚糖的粘均分子量,得到如下表2所示的一系列鱿鱼软骨壳聚糖。由表2可看出,通过改变超声处理时间和/或温度,得到的鱿鱼软骨壳聚糖的脱乙酰度相近,而分子量不同。The degree of deacetylation of squid cartilage chitosan was determined by elemental analysis. The viscosity average molecular weight of squid cartilage chitosan was determined by dilute solution viscosity method, and a series of squid cartilage chitosan as shown in Table 2 below were obtained. As can be seen from Table 2, by changing the sonication time and/or temperature, the obtained cartilage chitosan has a similar degree of deacetylation and a different molecular weight.
Figure PCTCN2016087457-appb-000002
Figure PCTCN2016087457-appb-000002
表2Table 2
其中,among them,
β-chitin:鱿鱼软骨β-甲壳素;--chitin: salmon cartilage β-chitin;
CS-150:DD(80.00±0.65)%、MW(1.52±0.25)×106的鱿鱼软骨壳聚糖。CS-150: DD (80.00 ± 0.65)%, MW (1.52 ± 0.25) × 10 6 carp cartilage chitosan.
以下通过优选的实施例对本发明进行详细说明。The invention is described in detail below by means of preferred embodiments.
实施例一:Embodiment 1:
本发明提出的一种可吸收手术缝合线的制备方法,包括以下步骤:The preparation method of an absorbable surgical suture according to the present invention comprises the following steps:
S1、将2.0g鱿鱼软骨壳聚糖(DD=75.70%,MW=1.20×106)粉末溶解于50ml、质量百分比浓度2%的醋酸溶液中,在磁力搅拌器的作用下搅拌2h,待完全溶解后,得到纺丝原液;S1, 2.0g of squid cartilage chitosan (DD=75.70%, MW=1.20×10 6 ) powder was dissolved in 50ml, 2% by mass concentration of acetic acid solution, stirred under the action of magnetic stirrer for 2h, to be completely After dissolution, a spinning dope is obtained;
S2、对纺丝原液过滤、脱泡后,通过计量泵输入内径0.8mm的喷丝头,用 40N的压力将纺丝原液挤入凝固浴中得到壳聚糖单丝;其中,凝固浴各组分的质量百分比包括:氢氧化钠4%、乙醇2%,其余为去离子水;S2. After filtering and defoaming the spinning dope, a spinneret with an inner diameter of 0.8 mm is input through a metering pump. Pressing the spinning dope into the coagulation bath to obtain the chitosan monofilament; wherein the mass percentage of each component of the coagulation bath comprises: sodium hydroxide 4%, ethanol 2%, and the rest is deionized water;
S3、壳聚糖单丝用去离子水浸泡清洗至中性后,在室温下拉伸10N并晾干1天,得到新型壳聚糖可吸收手术缝合线单丝。S3. The chitosan monofilament was soaked in deionized water to neutrality, and then stretched at room temperature for 10 N and dried for 1 day to obtain a novel chitosan absorbable surgical suture monofilament.
其中,步骤S1中鱿鱼软骨壳聚糖粉末的制备包括:Wherein, the preparation of the squid cartilage chitosan powder in step S1 comprises:
S11、按固液比为5.0∶100g/ml的比例,将鱿鱼软骨β-甲壳素溶解于质量百分比浓度34%的NaOH溶液中,在80℃下搅拌2h后过滤得到滤渣;S11, in a solid-liquid ratio of 5.0:100g / ml ratio, the salmon cartilage β-chitin is dissolved in a mass percentage concentration of 34% NaOH solution, stirred at 80 ° C for 2h and filtered to obtain filter residue;
S12、对滤渣用去离子水洗涤至中性后烘干、研磨,得到鱿鱼软骨壳聚糖粉末。S12. The filter residue is washed with deionized water until neutral, and then dried and ground to obtain a squid cartilage chitosan powder.
本实施例制备的手术缝合线直径为0.27mm,抗张强度为45.47N,断裂伸张率为14.13%。The surgical suture prepared in this example has a diameter of 0.27 mm, a tensile strength of 45.47 N, and a tensile elongation at break of 14.13%.
实施例二:Embodiment 2:
本发明提出的一种可吸收手术缝合线的制备方法,包括以下步骤:The preparation method of an absorbable surgical suture according to the present invention comprises the following steps:
S1、将2.2g鱿鱼软骨壳聚糖(DD=79.99%,MW=1.15×106)粉末溶解于50ml、质量百分比浓度2%的醋酸溶液中,在磁力搅拌器的作用下搅拌2h,待完全溶解后,得到纺丝原液;S1, 2.2g of squid cartilage chitosan (DD=79.99%, MW=1.15×10 6 ) powder was dissolved in 50ml, 2% by mass concentration of acetic acid solution, stirred under the action of magnetic stirrer for 2h, to be completely After dissolution, a spinning dope is obtained;
S2、对纺丝原液过滤、脱泡后,通过计量泵输入内径0.5mm的喷丝头,用60N的压力将纺丝原液挤入凝固浴中得到壳聚糖单丝;其中,凝固浴各组分的质量百分比包括:氢氧化钠6%、乙醇1%,其余为去离子水;S2. After filtering and defoaming the spinning dope, a spinning nozzle with an inner diameter of 0.5 mm is input through a metering pump, and the spinning dope is squeezed into a coagulation bath by a pressure of 60 N to obtain a chitosan monofilament; wherein, each group of the coagulation bath The mass percentage of the fraction includes: 6% sodium hydroxide, 1% ethanol, and the rest is deionized water;
S3、壳聚糖单丝用去离子水浸泡清洗至中性后,在室温下拉伸10N并晾干1天,得到新型壳聚糖可吸收手术缝合线单丝。S3. The chitosan monofilament was soaked in deionized water to neutrality, and then stretched at room temperature for 10 N and dried for 1 day to obtain a novel chitosan absorbable surgical suture monofilament.
其中,步骤S1中鱿鱼软骨壳聚糖粉末的制备包括:Wherein, the preparation of the squid cartilage chitosan powder in step S1 comprises:
S11、按固液比为25∶100g/ml的比例,将鱿鱼软骨β-甲壳素溶解于质量百分比浓度30%的NaOH溶液中,在50℃下搅拌6h后过滤得到滤渣;S11, in a solid-liquid ratio of 25:100g / ml ratio, the salmon cartilage β-chitin is dissolved in a mass percentage concentration of 30% NaOH solution, stirred at 50 ° C for 6h and filtered to obtain filter residue;
S12、对滤渣用去离子水洗涤至中性后烘干、研磨,得到鱿鱼软骨壳聚糖粉末。S12. The filter residue is washed with deionized water until neutral, and then dried and ground to obtain a squid cartilage chitosan powder.
本实施例制备的手术缝合线直径为0.29mm,抗张强度为45.17N,断裂伸张率为14.13%。 The surgical suture prepared in this example has a diameter of 0.29 mm, a tensile strength of 45.17 N, and a tensile elongation at break of 14.13%.
实施例三:Embodiment 3:
本发明提出的一种可吸收手术缝合线的制备方法,包括以下步骤:The preparation method of an absorbable surgical suture according to the present invention comprises the following steps:
S1、将1.0g鱿鱼软骨壳聚糖(DD=84.48%,MW=1.13×106)粉末溶解于50ml、质量百分比浓度2%的醋酸溶液中,在磁力搅拌器的作用下搅拌2h,待完全溶解后,得到纺丝原液;S1, 1.0 g of squid cartilage chitosan (DD=84.48%, MW=1.13×10 6 ) powder was dissolved in 50 ml of 2% by mass acetic acid solution, stirred under the action of a magnetic stirrer for 2 h, to be completely After dissolution, a spinning dope is obtained;
S2、对纺丝原液过滤、脱泡后,通过计量泵输入内径1.0mm的喷丝头,用100N的压力将纺丝原液挤入凝固浴中得到壳聚糖单丝;其中,凝固浴各组分的质量百分比包括:氢氧化钠5%、乙醇3%,其余为去离子水;S2. After filtering and defoaming the spinning dope, a spinning nozzle with an inner diameter of 1.0 mm is input through a metering pump, and the spinning dope is squeezed into a coagulation bath by a pressure of 100 N to obtain a chitosan monofilament; wherein, each group of the coagulation bath The mass percentage of the fraction includes: 5% sodium hydroxide, 3% ethanol, and the rest is deionized water;
S3、壳聚糖单丝用去离子水浸泡清洗至中性后,在室温下拉伸10N并晾干1天,得到新型壳聚糖可吸收手术缝合线单丝。S3. The chitosan monofilament was soaked in deionized water to neutrality, and then stretched at room temperature for 10 N and dried for 1 day to obtain a novel chitosan absorbable surgical suture monofilament.
其中,步骤S1中鱿鱼软骨壳聚糖粉末的制备包括:Wherein, the preparation of the squid cartilage chitosan powder in step S1 comprises:
S11、按固液比为10∶100g/ml的比例,将鱿鱼软骨β-甲壳素溶解于质量百分比浓度38%的NaOH溶液中,在60℃下搅拌5h后过滤得到滤渣;S11, in a solid-liquid ratio of 10:100g / ml ratio, the salmon cartilage β-chitin is dissolved in a mass percentage concentration of 38% NaOH solution, stirred at 60 ° C for 5h and filtered to obtain filter residue;
S12、对滤渣用去离子水洗涤至中性后烘干、研磨,得到鱿鱼软骨壳聚糖粉末。S12. The filter residue is washed with deionized water until neutral, and then dried and ground to obtain a squid cartilage chitosan powder.
本实施例制备的手术缝合线直径为0.44mm,抗张强度为45.41N,断裂伸张率为14.19%。The surgical suture prepared in this example has a diameter of 0.44 mm, a tensile strength of 45.41 N, and a tensile elongation at break of 14.19%.
实施例四:Embodiment 4:
本发明提出的一种可吸收手术缝合线的制备方法,包括以下步骤:The preparation method of an absorbable surgical suture according to the present invention comprises the following steps:
S1、将1.8g鱿鱼软骨壳聚糖(DD=80.00%,MW=1.52×106)粉末溶解于50ml、质量百分比浓度2%的醋酸溶液中,在磁力搅拌器的作用下搅拌2h,待完全溶解后,得到纺丝原液;S1, 1.8g squid cartilage chitosan (DD=80.00%, MW=1.52×10 6 ) powder was dissolved in 50ml, 2% by mass concentration of acetic acid solution, stirred under the action of magnetic stirrer for 2h, to be completely After dissolution, a spinning dope is obtained;
S2、对纺丝原液过滤、脱泡后,通过计量泵输入内径0.8mm的喷丝头,用80N的压力将纺丝原液挤入凝固浴中得到壳聚糖单丝;其中,凝固浴各组分的质量百分比包括:氢氧化钠4%、乙醇2%,其余为去离子水;S2. After filtering and defoaming the spinning dope, a spinneret having an inner diameter of 0.8 mm is input through a metering pump, and the spinning dope is extruded into a coagulation bath by a pressure of 80 N to obtain a chitosan monofilament; wherein the coagulation bath groups are The mass percentage of the fraction includes: 4% sodium hydroxide, 2% ethanol, and the rest is deionized water;
S3、壳聚糖单丝用去离子水浸泡清洗至中性后,在室温下拉伸10N并晾干1天,得到新型壳聚糖可吸收手术缝合线单丝。 S3. The chitosan monofilament was soaked in deionized water to neutrality, and then stretched at room temperature for 10 N and dried for 1 day to obtain a novel chitosan absorbable surgical suture monofilament.
其中,步骤S1中鱿鱼软骨壳聚糖粉末的制备包括:Wherein, the preparation of the squid cartilage chitosan powder in step S1 comprises:
S11、按固液比为15∶100g/ml的比例,将鱿鱼软骨β-甲壳素溶解于质量百分比浓度为40%的NaOH溶液中,在70℃下搅拌3h后过滤得到滤渣;S11, in a solid-liquid ratio of 15:100g / ml ratio, the salmon cartilage β-chitin is dissolved in a 40% by mass concentration of NaOH solution, stirred at 70 ° C for 3h and filtered to obtain filter residue;
S12、对滤渣用去离子水洗涤至中性后烘干、研磨,得到鱿鱼软骨壳聚糖粉末。S12. The filter residue is washed with deionized water until neutral, and then dried and ground to obtain a squid cartilage chitosan powder.
本实施例制备的手术缝合线直径为0.36mm,抗张强度为45.06N,断裂伸张率为14.10%。The surgical suture prepared in this example has a diameter of 0.36 mm, a tensile strength of 45.06 N, and a tensile elongation at break of 14.10%.
实施例五:Embodiment 5:
本发明提出的一种可吸收手术缝合线的制备方法,包括以下步骤:The preparation method of an absorbable surgical suture according to the present invention comprises the following steps:
S1、将1.5g鱿鱼软骨壳聚糖(DD=80.12%,MW=1.2×106)粉末溶解于50ml、质量百分比浓度2%的醋酸溶液中,在磁力搅拌器的作用下搅拌2h,待完全溶解后,得到纺丝原液;S1, 1.5g of squid cartilage chitosan (DD=80.12%, MW=1.2×10 6 ) powder was dissolved in 50ml, 2% by mass concentration of acetic acid solution, stirred under the action of magnetic stirrer for 2h, to be completely After dissolution, a spinning dope is obtained;
S2、对纺丝原液过滤、脱泡后,通过计量泵输入内径0.8mm的喷丝头,用20N的压力将纺丝原液挤入凝固浴中得到壳聚糖单丝;其中,凝固浴各组分的质量百分比包括:氢氧化钠4%、乙醇2%,其余为去离子水;S2. After filtering and defoaming the spinning dope, a spinning nozzle with an inner diameter of 0.8 mm is input through a metering pump, and the spinning dope is squeezed into a coagulation bath by a pressure of 20 N to obtain a chitosan monofilament; wherein, each group of the coagulation bath The mass percentage of the fraction includes: 4% sodium hydroxide, 2% ethanol, and the rest is deionized water;
S3、壳聚糖单丝用去离子水浸泡清洗至中性后,在室温下拉伸10N并晾干1天,得到新型壳聚糖可吸收手术缝合线单丝。S3. The chitosan monofilament was soaked in deionized water to neutrality, and then stretched at room temperature for 10 N and dried for 1 day to obtain a novel chitosan absorbable surgical suture monofilament.
其中,步骤S1中鱿鱼软骨壳聚糖粉末的制备包括:Wherein, the preparation of the squid cartilage chitosan powder in step S1 comprises:
S11、按固液比为15∶100g/ml的比例,将实施例4中制备的鱿鱼软骨壳聚糖(DD=80.00%,Mw=1.52×106)粉末在室温下溶解于质量百分比浓度1%的盐酸溶液中,置于超声波清洗器内在60℃超声处理2.5h;S11. The squid cartilage chitosan (DD=80.00%, Mw=1.52×10 6 ) powder prepared in Example 4 was dissolved at a mass concentration of 1 at a ratio of solid to liquid ratio of 15:100 g/ml. % hydrochloric acid solution, placed in an ultrasonic cleaner at 60 ° C for 2.5 h;
S12、加入1mol/L的NaOH溶液调节溶液至中性,抽滤,对抽滤后得到的滤渣依次用去离子水和无水乙醇反复洗涤,置于60℃鼓风干燥箱内干燥、研磨,得到鱿鱼软骨壳聚糖粉末。S12, adding 1mol/L NaOH solution to adjust the solution to neutrality, suction filtration, and the filter residue obtained by suction filtration is repeatedly washed with deionized water and absolute ethanol, and dried and ground in a blast drying oven at 60 °C. The squid cartilage chitosan powder was obtained.
本实施例制备的手术缝合线直径为0.22mm,抗张强度为44.98N,断裂伸张率为14.12%。 The surgical suture prepared in this example has a diameter of 0.22 mm, a tensile strength of 44.98 N, and a tensile elongation at break of 14.12%.
实施例六:Example 6:
本发明提出的一种可吸收手术缝合线的制备方法,包括以下步骤:The preparation method of an absorbable surgical suture according to the present invention comprises the following steps:
S1、将2.0g鱿鱼软骨壳聚糖(DD=79.51%,MW=0.91×106)粉末溶解于50ml、质量百分比浓度2%的醋酸溶液中,在磁力搅拌器的作用下搅拌2h,待完全溶解后,得到纺丝原液;S1, 2.0g of squid cartilage chitosan (DD=79.51%, MW=0.91×10 6 ) powder was dissolved in 50ml, 2% by mass concentration of acetic acid solution, stirred under the action of magnetic stirrer for 2h, to be completely After dissolution, a spinning dope is obtained;
S2、对纺丝原液过滤、脱泡后,通过计量泵输入内径0.5mm的喷丝头,用50N的压力将纺丝原液挤入凝固浴中得到壳聚糖单丝;其中,凝固浴各组分的质量百分比包括:氢氧化钠4%、乙醇2%,其余为去离子水;S2. After filtering and defoaming the spinning dope, a spinning nozzle with an inner diameter of 0.5 mm is input through a metering pump, and the spinning dope is extruded into a coagulation bath with a pressure of 50 N to obtain a chitosan monofilament; wherein, each group of the coagulation bath The mass percentage of the fraction includes: 4% sodium hydroxide, 2% ethanol, and the rest is deionized water;
S3、壳聚糖单丝用去离子水浸泡清洗至中性后,在室温下拉伸10N并晾干1天,得到新型壳聚糖可吸收手术缝合线单丝。S3. The chitosan monofilament was soaked in deionized water to neutrality, and then stretched at room temperature for 10 N and dried for 1 day to obtain a novel chitosan absorbable surgical suture monofilament.
其中,步骤S1中鱿鱼软骨壳聚糖粉末的制备包括:Wherein, the preparation of the squid cartilage chitosan powder in step S1 comprises:
S11、按固液比为10∶100g/ml的比例,将实施例4中制备的鱿鱼软骨壳聚糖(DD=80.00%,Mw=1.52×106)粉末在室温下溶解于质量百分比浓度5%的盐酸溶液中,置于超声波清洗器内在80℃超声处理4h;S11, the squid cartilage chitosan (DD=80.00%, Mw=1.52×10 6 ) powder prepared in Example 4 was dissolved at a mass concentration of 5 at a ratio of solid to liquid ratio of 10:100 g/ml. % hydrochloric acid solution, placed in an ultrasonic cleaner at 80 ° C for 4 h;
S12、加入0.8mol/L的NaOH溶液调节溶液至中性,抽滤,对抽滤后得到的滤渣依次用去离子水和无水乙醇反复洗涤滤渣,置于60℃鼓风干燥箱内干燥、研磨,得到鱿鱼软骨壳聚糖粉末。S12, adding 0.8 mol / L NaOH solution to adjust the solution to neutral, suction filtration, the filter residue obtained after suction filtration is repeatedly washed with deionized water and absolute ethanol, and placed in a blast drying oven at 60 ° C, Grinding to obtain a salmon cartilage chitosan powder.
本实施例制备的手术缝合线直径为0.24mm,抗张强度为45.21N,断裂伸张率为14.02%。The surgical suture prepared in this example has a diameter of 0.24 mm, a tensile strength of 45.21 N, and a tensile elongation at break of 14.02%.
实施例七:Example 7:
本发明提出的一种可吸收手术缝合线的制备方法,包括以下步骤:The preparation method of an absorbable surgical suture according to the present invention comprises the following steps:
S1、将2.5g鱿鱼软骨壳聚糖(DD=78.71%,MW=0.62×106)粉末溶解于50ml、质量百分比浓度2%的醋酸溶液中,在磁力搅拌器的作用下搅拌2h,待完全溶解后,得到纺丝原液;S1, 2.5g salmon cartilage chitosan (DD=78.71%, MW=0.62×10 6 ) powder was dissolved in 50ml, 2% by mass concentration of acetic acid solution, stirred under the action of magnetic stirrer for 2h, to be completely After dissolution, a spinning dope is obtained;
S2、对纺丝原液过滤、脱泡后,通过计量泵输入内径0.3mm的喷丝头,用70N的压力将纺丝原液挤入凝固浴中得到壳聚糖单丝;其中,凝固浴各组分的质量百分比包括:氢氧化钠4%、乙醇2%,其余为去离子水;S2. After filtering and defoaming the spinning dope, a spinning nozzle with an inner diameter of 0.3 mm is input through a metering pump, and the spinning dope is squeezed into a coagulation bath by a pressure of 70 N to obtain a chitosan monofilament; wherein, each group of the coagulation bath The mass percentage of the fraction includes: 4% sodium hydroxide, 2% ethanol, and the rest is deionized water;
S3、壳聚糖单丝用去离子水浸泡清洗至中性后,在室温下拉伸10N并晾干1 天,得到新型壳聚糖可吸收手术缝合线单丝。S3, chitosan monofilament is washed with deionized water to neutrality, and then stretched 10N at room temperature and dried 1 Days, the new chitosan absorbs surgical suture monofilaments.
其中,步骤S1中鱿鱼软骨壳聚糖粉末的制备包括:Wherein, the preparation of the squid cartilage chitosan powder in step S1 comprises:
S11、按固液比为15∶100g/ml的比例,将实施例4中制备的鱿鱼软骨壳聚糖(DD=80.00%,Mw=1.52×106)粉末在室温下溶解于质量百分比浓度为3%的盐酸溶液中,置于超声波清洗器内在70℃超声处理8h;S11, the squid cartilage chitosan (DD=80.00%, Mw=1.52×10 6 ) powder prepared in Example 4 was dissolved in a mass percentage at room temperature according to a ratio of solid to liquid ratio of 15:100 g/ml. In a 3% hydrochloric acid solution, placed in an ultrasonic cleaner at 70 ° C for 8 h;
S12、加入0.3mol/L的NaOH溶液调节溶液至中性,抽滤,对抽滤后得到的滤渣依次用去离子水和无水乙醇反复洗涤滤渣,置于60℃鼓风干燥箱内干燥、研磨,得到鱿鱼软骨壳聚糖粉末。S12, adding 0.3 mol / L NaOH solution to adjust the solution to neutral, suction filtration, the filter residue obtained after suction filtration is repeatedly washed with deionized water and absolute ethanol, and placed in a blast drying oven at 60 ° C, Grinding to obtain a salmon cartilage chitosan powder.
本实施例制备的手术缝合线直径为0.21mm,抗张强度为45.38N,断裂伸张率为14.09%。The surgical suture prepared in this example has a diameter of 0.21 mm, a tensile strength of 45.38 N, and a tensile elongation at break of 14.09%.
本领域技术人员将认识到,对以上描述做出众多变通是可能的,所以实施例仅是用来描述一个或多个特定实施方式。Those skilled in the art will recognize that many variations are possible in the above description, and thus the embodiments are only used to describe one or more specific embodiments.
尽管已经描述和叙述了被看作本发明的示范实施例,本领域技术人员将会明白,可以对其作出各种改变和替换,而不会脱离本发明的精神。另外,可以做出许多修改以将特定情况适配到本发明的教义,而不会脱离在此描述的本发明中心概念。所以,本发明不受限于在此披露的特定实施例,但本发明可能还包括属于本发明范围的所有实施例及其等同物。 While the invention has been described and described with reference to the embodiments of the embodiments In addition, many modifications may be made to adapt a particular situation to the teachings of the invention, without departing from the inventive concept. Therefore, the invention is not limited to the specific embodiments disclosed herein, but the invention may also include all embodiments and equivalents thereof.

Claims (10)

  1. 一种可吸收手术缝合线的制备方法,其特征在于,包括以下步骤:A method for preparing an absorbable surgical suture, comprising the steps of:
    S1、将鱿鱼软骨壳聚糖溶解得到纺丝原液;其中,所述鱿鱼软骨壳聚糖的脱乙酰度大于60%、分子量大于0.5×106S1, the squid cartilage chitosan is dissolved to obtain a spinning dope; wherein the squid cartilage chitosan has a degree of deacetylation greater than 60% and a molecular weight greater than 0.5×10 6 ;
    S2、对所述纺丝原液纺丝后干燥,得到所述可吸收手术缝合线。S2, drying the spinning dope and drying to obtain the absorbable surgical suture.
  2. 如权利要求1所述的可吸收手术缝合线的制备方法,其特征在于,步骤S2中所述纺丝为湿法纺丝。A method of preparing an absorbable surgical suture according to claim 1, wherein said spinning in step S2 is wet spinning.
  3. 如权利要求2所述的可吸收手术缝合线制备方法,其特征在于,所述湿法纺丝包括如下步骤:将所述纺丝原液通过计量泵输入内径为0.1~1.0mm的喷丝头,用10~100N的挤压力将所述纺丝原液挤入凝固浴中得到壳聚糖单丝;The method for preparing an absorbable surgical suture according to claim 2, wherein the wet spinning comprises the steps of: feeding the spinning dope into a spinneret having an inner diameter of 0.1 to 1.0 mm through a metering pump; Pressing the spinning dope into a coagulation bath with a pressing force of 10 to 100 N to obtain a chitosan monofilament;
    其中,所述凝固浴各组分按质量百分比包括:氢氧化钠4%~6%、乙醇1%~3%,其余为去离子水。Wherein, the components of the coagulation bath comprise, by mass percentage, 4% to 6% of sodium hydroxide, 1% to 3% of ethanol, and the rest are deionized water.
  4. 如权利要求1所述的可吸收手术缝合线的制备方法,其特征在于,步骤S1中按固液比1.0∶100~5.0∶100g/ml的比例,将所述鱿鱼软骨壳聚糖溶解于溶剂中得到纺丝原液。The method for preparing an absorbable surgical suture according to claim 1, wherein in step S1, the squid cartilage chitosan is dissolved in a solvent at a ratio of solid to liquid of 1.0:100 to 5.0:100 g/ml. The spinning dope is obtained.
  5. 如权利要求4所述的可吸收手术缝合线的制备方法,其特征在于,所述溶剂为质量百分比浓度2%的醋酸。The method of preparing an absorbable surgical suture according to claim 4, wherein the solvent is acetic acid having a mass percent concentration of 2%.
  6. 如权利要求1所述的可吸收手术缝合线的制备方法,其特征在于,步骤S2中对所述纺丝原液纺丝前还包括对所述纺丝原液过滤、脱泡。The method for preparing an absorbable surgical suture according to claim 1, wherein the spinning dope further comprises filtering and defoaming the spinning dope before spinning the spinning dope in step S2.
  7. 如权利要求1所述的可吸收手术缝合线的制备方法,其特征在于,步骤S1中所述鱿鱼软骨壳聚糖的制备包括如下步骤:The method for preparing an absorbable surgical suture according to claim 1, wherein the preparation of the salmon cartilage chitosan in step S1 comprises the following steps:
    S11、按固液比5.0∶100~25∶100g/ml的比例,将鱿鱼软骨β-甲壳素溶解于质量百分比浓度30%~40%的NaOH溶液中,在50~80℃下搅拌1~6h后过滤,得到第一滤渣;S11. The squid cartilage β-chitin is dissolved in a NaOH solution having a mass percentage concentration of 30% to 40% at a ratio of solid to liquid of 5.0:100 to 25:100 g/ml, and stirred at 50 to 80 ° C for 1 to 6 hours. After filtration, the first filter residue is obtained;
    S12、对所述第一滤渣洗涤至中性后干燥,得到第一鱿鱼软骨壳聚糖,作为步骤S1的鱿鱼软骨壳聚糖。S12. The first filter residue is washed to neutral and then dried to obtain a first salmon cartilage chitosan as the salmon cartilage chitosan of step S1.
  8. 如权利要求7所述的可吸收手术缝合线的制备方法,其特征在于,在步骤S12之后还包括如下步骤:The method for preparing an absorbable surgical suture according to claim 7, further comprising the following steps after step S12:
    S13、将步骤S12得到的所述第一鱿鱼软骨壳聚糖作为第一中间产物,按固 液比5.0∶100~25∶100g/ml的比例,将所述第一中间产物溶解于质量百分比浓度30%~40%的NaOH溶液中,在50~80℃下搅拌1~6h后过滤,得到第二滤渣;S13. The first salmon cartilage chitosan obtained in step S12 is used as a first intermediate product, and is solidified. The first intermediate product is dissolved in a NaOH solution having a mass percentage concentration of 30% to 40% at a liquid ratio of 5.0:100 to 25:100 g/ml, and stirred at 50 to 80 ° C for 1 to 6 hours, followed by filtration. Second filter residue;
    S14、对所述第二滤渣洗涤至中性后干燥,得到与所述第一中间产物脱乙酰度不同的第二鱿鱼软骨壳聚糖,作为步骤S1的鱿鱼软骨壳聚糖。S14. The second filter residue is washed to neutrality and then dried to obtain a second salmon cartilage chitosan having a different degree of deacetylation from the first intermediate product as the salmon cartilage chitosan of step S1.
  9. 如权利要求7或8所述的可吸收手术缝合线的制备方法,其特征在于,在步骤S12或步骤S14之后还包括如下步骤:The method for preparing an absorbable surgical suture according to claim 7 or 8, further comprising the following steps after step S12 or step S14:
    S15、将步骤S12得到的所述第一鱿鱼软骨壳聚糖或步骤S14得到的所述第二鱿鱼软骨壳聚糖作为第二中间产物,按固液比5.0∶100~25∶100g/ml的比例,将所述第二中间产物在室温下溶解于质量百分比浓度1%~5%的盐酸溶液中,在60~80℃下超声处理2~8h,得到混合液;S15, the first squid cartilage chitosan obtained in step S12 or the second squid cartilage chitosan obtained in step S14 is used as a second intermediate product at a solid-liquid ratio of 5.0:100 to 25:100 g/ml. Proportion, the second intermediate product is dissolved in a hydrochloric acid solution having a mass percentage concentration of 1% to 5% at room temperature, and sonicated at 60 to 80 ° C for 2 to 8 hours to obtain a mixed solution;
    S16、在所述混合液中加入0.1~1.0mol/L的NaOH溶液调节所述混合液至中性,抽滤得到第三滤渣;S16, adding 0.1~1.0 mol/L NaOH solution to the mixture to adjust the mixture to neutrality, and suction filtration to obtain a third filter residue;
    S17、对所述第三滤渣洗涤至中性后干燥,得到与所述第二中间产物分子量不同的第三鱿鱼软骨壳聚糖,作为步骤S1的鱿鱼软骨壳聚糖。S17. The third filter residue is washed to neutrality and then dried to obtain a third salmon cartilage chitosan having a molecular weight different from that of the second intermediate product, as the salmon cartilage chitosan of step S1.
  10. 一种可吸收手术缝合线,其特征在于,使用权利要求1~9任一项所述可吸收手术缝合线的制备方法制成。 An absorbable surgical suture, which is produced by the method for preparing an absorbable surgical suture according to any one of claims 1-9.
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