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CN115467092A - Preparation method of supported dimethyloxalglycine nanofiber - Google Patents

Preparation method of supported dimethyloxalglycine nanofiber Download PDF

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CN115467092A
CN115467092A CN202211125162.9A CN202211125162A CN115467092A CN 115467092 A CN115467092 A CN 115467092A CN 202211125162 A CN202211125162 A CN 202211125162A CN 115467092 A CN115467092 A CN 115467092A
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dimethyloxalylglycine
preparation
nanofiber
loaded
polycaprolactone
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陶贵录
钟存荻
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Second Hospital of Dalian Medical University
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    • DTEXTILES; PAPER
    • D04BRAIDING; LACE-MAKING; KNITTING; TRIMMINGS; NON-WOVEN FABRICS
    • D04HMAKING TEXTILE FABRICS, e.g. FROM FIBRES OR FILAMENTARY MATERIAL; FABRICS MADE BY SUCH PROCESSES OR APPARATUS, e.g. FELTS, NON-WOVEN FABRICS; COTTON-WOOL; WADDING ; NON-WOVEN FABRICS FROM STAPLE FIBRES, FILAMENTS OR YARNS, BONDED WITH AT LEAST ONE WEB-LIKE MATERIAL DURING THEIR CONSOLIDATION
    • D04H1/00Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres
    • D04H1/70Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres characterised by the method of forming fleeces or layers, e.g. reorientation of fibres
    • D04H1/72Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres characterised by the method of forming fleeces or layers, e.g. reorientation of fibres the fibres being randomly arranged
    • D04H1/728Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres characterised by the method of forming fleeces or layers, e.g. reorientation of fibres the fibres being randomly arranged by electro-spinning
    • DTEXTILES; PAPER
    • D01NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01DMECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
    • D01D5/00Formation of filaments, threads, or the like
    • D01D5/0007Electro-spinning
    • D01D5/0015Electro-spinning characterised by the initial state of the material
    • D01D5/003Electro-spinning characterised by the initial state of the material the material being a polymer solution or dispersion
    • D01D5/0038Electro-spinning characterised by the initial state of the material the material being a polymer solution or dispersion the fibre formed by solvent evaporation, i.e. dry electro-spinning
    • 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
    • D01F1/00General methods for the manufacture of artificial filaments or the like
    • D01F1/02Addition of substances to the spinning solution or to the melt
    • D01F1/10Other agents for modifying properties
    • 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
    • D01F6/00Monocomponent artificial filaments or the like of synthetic polymers; Manufacture thereof
    • D01F6/88Monocomponent artificial filaments or the like of synthetic polymers; Manufacture thereof from mixtures of polycondensation products as major constituent with other polymers or low-molecular-weight compounds
    • D01F6/92Monocomponent artificial filaments or the like of synthetic polymers; Manufacture thereof from mixtures of polycondensation products as major constituent with other polymers or low-molecular-weight compounds of polyesters
    • DTEXTILES; PAPER
    • D04BRAIDING; LACE-MAKING; KNITTING; TRIMMINGS; NON-WOVEN FABRICS
    • D04HMAKING TEXTILE FABRICS, e.g. FROM FIBRES OR FILAMENTARY MATERIAL; FABRICS MADE BY SUCH PROCESSES OR APPARATUS, e.g. FELTS, NON-WOVEN FABRICS; COTTON-WOOL; WADDING ; NON-WOVEN FABRICS FROM STAPLE FIBRES, FILAMENTS OR YARNS, BONDED WITH AT LEAST ONE WEB-LIKE MATERIAL DURING THEIR CONSOLIDATION
    • D04H1/00Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres
    • D04H1/40Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres from fleeces or layers composed of fibres without existing or potential cohesive properties
    • D04H1/42Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres from fleeces or layers composed of fibres without existing or potential cohesive properties characterised by the use of certain kinds of fibres insofar as this use has no preponderant influence on the consolidation of the fleece
    • D04H1/4326Condensation or reaction polymers
    • D04H1/435Polyesters
    • DTEXTILES; PAPER
    • D10INDEXING SCHEME ASSOCIATED WITH SUBLASSES OF SECTION D, RELATING TO TEXTILES
    • D10BINDEXING SCHEME ASSOCIATED WITH SUBLASSES OF SECTION D, RELATING TO TEXTILES
    • D10B2509/00Medical; Hygiene
    • D10B2509/02Bandages, dressings or absorbent pads
    • D10B2509/022Wound dressings

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  • Textile Engineering (AREA)
  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Manufacturing & Machinery (AREA)
  • Dispersion Chemistry (AREA)
  • Mechanical Engineering (AREA)
  • Artificial Filaments (AREA)

Abstract

本发明公开了一种负载二甲基乙二酰甘氨酸纳米纤维的制备方法,制备步骤如下:(1)将聚己内酯和二甲基乙二酰甘氨酸加入二甲基甲酰胺与四氢呋喃的混合溶剂中,在20‑25摄氏度的温度下搅拌8‑14小时,获得均一稳定的溶液;(2)将配置好的溶液进行静电纺丝,得到纳米纤维膜。本发明利用二甲基乙二酰甘氨酸与纳米纤维结合得到有利于创面愈合的材料;且上述方法成本低廉、清洁、绿色、高效。

Figure 202211125162

The invention discloses a method for preparing nanofibers loaded with dimethyloxalylglycine. The preparation steps are as follows: (1) adding polycaprolactone and dimethyloxalylglycine to a mixture of dimethylformamide and tetrahydrofuran Stirring in a solvent for 8-14 hours at a temperature of 20-25 degrees Celsius to obtain a uniform and stable solution; (2) Electrospinning the prepared solution to obtain a nanofiber membrane. The invention utilizes the combination of dimethyloxalylglycine and nanofibers to obtain materials beneficial to wound healing; and the method is low in cost, clean, green and efficient.

Figure 202211125162

Description

一种负载二甲基乙二酰甘氨酸纳米纤维的制备方法A preparation method of loading dimethyloxalylglycine nanofibers

技术领域technical field

本发明涉及一种纳米纤维的制备方法,尤其涉及一种负载二甲基乙二酰甘氨酸纳米纤维的制备方法。The invention relates to a method for preparing nanofibers, in particular to a method for preparing nanofibers loaded with dimethyloxalylglycine.

背景技术Background technique

难治性伤口的生理微环境复杂,针对不同的伤口修复,制备了多种不同的纳米纤维,如定向纳米纤维、载药纳米纤维、高功能和核壳结构纳米纤维。但是传统的纳米纤维敷料对伤口愈合的促进作用有限,大多数功能性纳米纤维在伤口修复中只发挥单一的作用(如抗菌、减少体液流失、促进修复等单一效用),很难满足临床需要。The physiological microenvironment of refractory wounds is complex. A variety of different nanofibers have been prepared for different wound repairs, such as oriented nanofibers, drug-loaded nanofibers, high-function and core-shell nanofibers. However, traditional nanofiber dressings have limited promotion of wound healing, and most functional nanofibers only play a single role in wound repair (such as antibacterial, reducing body fluid loss, promoting repair, etc.), which is difficult to meet clinical needs.

创伤愈合是一个复杂的动态过程,涉及细胞迁移、增殖、分化、多种细胞因子的释放、细胞外基质(ECM)的合成与重构。因此,制备生物活性高、能快速修复难治性创面的修复材料具有重要意义。Wound healing is a complex dynamic process involving cell migration, proliferation, differentiation, release of various cytokines, synthesis and remodeling of extracellular matrix (ECM). Therefore, it is of great significance to prepare repair materials with high bioactivity and rapid repair of refractory wounds.

发明内容Contents of the invention

为解决现有技术的问题,本发明提供一种负载二甲基乙二酰甘氨酸纳米纤维的制备方法,该纳米纤维膜敷料是以聚己内酯和二甲基乙二酰甘氨酸混合物为基材,通过静电纺丝技术制备而成,得到负载二甲基乙二酰甘氨酸纳米复核纤维。这种纳米纤维膜敷料有利于慢性缺血性伤口的愈合。In order to solve the problems of the prior art, the present invention provides a preparation method for loading dimethyloxalylglycine nanofibers, the nanofiber membrane dressing is based on a mixture of polycaprolactone and dimethyloxalylglycine , prepared by electrospinning technology to obtain nano-core fibers loaded with dimethyloxalylglycine. This nanofibrous membrane dressing is beneficial for the healing of chronic ischemic wounds.

本发明解决上述技术问题所采用的技术方案为:The technical solution adopted by the present invention to solve the problems of the technologies described above is:

一种负载二甲基乙二酰甘氨酸纳米纤维的制备方法,包括如下步骤:A preparation method for loading dimethyloxalylglycine nanofibers, comprising the steps of:

(1)将聚己内酯(PCL)和二甲基乙二酰甘氨酸(DMOG)加入到二甲基甲酰胺与四氢呋喃的混合溶剂中,再放置于磁力搅拌器中,在20-25摄氏度的温度下搅拌8-14小时,获得均一稳定的溶液;(1) Add polycaprolactone (PCL) and dimethyloxalylglycine (DMOG) to a mixed solvent of dimethylformamide and tetrahydrofuran, and then place it in a magnetic stirrer at 20-25 degrees Celsius Stir at high temperature for 8-14 hours to obtain a uniform and stable solution;

(2)将配置好的溶液倒入注射器针管中,固定在静电纺丝装置上,进行静电纺丝,得到纳米纤维膜。(2) Pour the prepared solution into a syringe needle tube, fix it on an electrospinning device, and perform electrospinning to obtain a nanofiber membrane.

基于以上技术方案,优选的,步骤(2)中,静电纺丝的电压为6-10kv,喷出流速为0.5-0.7ml/h。Based on the above technical solution, preferably, in step (2), the electrospinning voltage is 6-10kv, and the ejection flow rate is 0.5-0.7ml/h.

基于以上技术方案,优选的,步骤(1)中,所述聚己内酯与二甲基乙二酰甘氨酸的质量比为0.9002:0.3850。Based on the above technical solution, preferably, in step (1), the mass ratio of polycaprolactone to dimethyloxalylglycine is 0.9002:0.3850.

基于以上技术方案,优选的,步骤(1)中,所述二甲基甲酰胺与四氢呋喃的体积比为3:1。Based on the above technical scheme, preferably, in step (1), the volume ratio of dimethylformamide to tetrahydrofuran is 3:1.

基于以上技术方案,优选的,步骤(1)中,聚己内酯和二甲基甲酰胺与四氢呋喃的混合溶剂的比例为0.9002g:4ml。Based on the above technical scheme, preferably, in step (1), the ratio of the mixed solvent of polycaprolactone, dimethylformamide and tetrahydrofuran is 0.9002g: 4ml.

基于以上技术方案,优选的,步骤(2)中,接收滚筒的转速为500-600r/min。Based on the above technical solution, preferably, in step (2), the rotating speed of the receiving drum is 500-600r/min.

基于以上技术方案,优选的,还包括:(3)将得到的纤维膜放置在烘箱中干燥去除溶剂后,得到最后样品。Based on the above technical solution, preferably, it also includes: (3) placing the obtained fiber film in an oven to dry and remove the solvent to obtain the final sample.

基于以上技术方案,优选的,所述干燥的温度为36-38摄氏度,干燥的时间为22-26小时。Based on the above technical solution, preferably, the drying temperature is 36-38 degrees Celsius, and the drying time is 22-26 hours.

基于以上技术方案,优选的,步骤(1)中,所述聚己内酯的分子量为80000;所述二甲基乙二酰甘氨酸的分子量为175.14;所述二甲基甲酰胺的分子量为73.09;所述二甲基甲酰胺的分子量为72.11。Based on the above technical scheme, preferably, in step (1), the molecular weight of the polycaprolactone is 80000; the molecular weight of the dimethylglycine is 175.14; the molecular weight of the dimethylformamide is 73.09 ; The molecular weight of the dimethylformamide is 72.11.

本发明还涉及保护上述的方法制备的负载二甲基乙二酰甘氨酸纳米纤维。The present invention also relates to the protection of the loaded dimethyloxalylglycine nanofiber prepared by the above method.

静电纺丝纳米纤维以其仿生的纳米纤维结构、高比表面积、大体积比和高孔隙率等优点被广泛应用于伤口敷料和功能材料。聚己内酯是一种十分重要的合成高分子材料,聚己内酯为线性聚酯,熔点低,既可以溶于多种有机溶剂形成溶液型纺丝液,又可以加热到80~160℃形成熔融型纺丝液。聚己内酯作为一种可降解生物相容性材料,已被应用于多个组织的修复研究中。二甲基乙二酰甘氨酸为脯氨酸羟化酶抑制剂,是缺氧诱导因子1α的激动剂,能够抑制细胞内缺氧诱导因子1α的降解,稳定缺氧诱导因子1α的表达,调控细胞内靶基因如血红素加氧酶1、血管内皮生长因子、促红细胞生成素的转录和表达增高,抑制炎症因子的表达从而发挥其保护作用。本发明利用二甲基乙二酰甘氨酸拥有在低氧条件下促进血管新生和创面愈合的功能,有利于治疗慢性难愈性创面。Electrospun nanofibers are widely used in wound dressings and functional materials due to their biomimetic nanofiber structure, high specific surface area, large volume ratio, and high porosity. Polycaprolactone is a very important synthetic polymer material. Polycaprolactone is a linear polyester with a low melting point. It can be dissolved in various organic solvents to form a solution-type spinning solution, and can be heated to 80-160°C A molten spinning solution is formed. As a biodegradable and biocompatible material, polycaprolactone has been applied in the repair research of many tissues. Dimethyloxalylglycine is a proline hydroxylase inhibitor and an agonist of hypoxia-inducible factor 1α, which can inhibit the degradation of intracellular hypoxia-inducible factor 1α, stabilize the expression of hypoxia-inducible factor 1α, and regulate cell The transcription and expression of internal target genes such as heme oxygenase 1, vascular endothelial growth factor, and erythropoietin are increased, and the expression of inflammatory factors is inhibited to exert their protective effect. The invention utilizes dimethyloxalylglycine to have the function of promoting angiogenesis and wound healing under hypoxic conditions, and is beneficial to treating chronic refractory wounds.

本发明的有益效果:Beneficial effects of the present invention:

本发明提供的负载二甲基乙二酰甘氨酸纳米纤维的制备方法,现有产品未见类似的制备方法。本发明将二甲基乙二酰甘氨酸与聚己内酯纳米纤维结合,制备一种兼备上述两种物质优点的纳米纤维材料,是一种慢性缺血性伤口的有效治疗敷料,有利于创面愈合,同时本方法清洁、绿色、高效,且成本低廉。The preparation method of the nanofiber loaded with dimethyloxalylglycine provided by the present invention has no similar preparation method in existing products. The present invention combines dimethyloxalylglycine and polycaprolactone nanofibers to prepare a nanofiber material having the advantages of the above two substances, which is an effective therapeutic dressing for chronic ischemic wounds and is beneficial to wound healing , and at the same time, the method is clean, green, efficient and low in cost.

附图说明Description of drawings

图1为实施例1中制备的负载二甲基乙二酰甘氨酸纳米纤维的透射电镜图;Fig. 1 is the transmission electron micrograph of the loaded dimethyloxalylglycine nanofiber prepared in embodiment 1;

图2为实施例1制备的负载二甲基乙二酰甘氨酸纳米纤维膜的接触角;Fig. 2 is the contact angle of the loaded dimethyloxalylglycine nanofiber film prepared in embodiment 1;

图3为实施例1制备的负载二甲基乙二酰甘氨酸纳米纤维膜的直径孔径比。Fig. 3 is the diameter-to-aperture ratio of the loaded dimethyloxalylglycine nanofiber membrane prepared in Example 1.

具体实施方式detailed description

下述非限定性实施例可以使本领域的普通技术人员更全面地理解本发明,但不以任何方式限制本发明。The following non-limiting examples can enable those skilled in the art to understand the present invention more fully, but do not limit the present invention in any way.

实施例1Example 1

(1)利用天平分别取0.9002g聚己内酯和0.3850g二甲基乙二酰甘氨酸,倒入3ml二甲基甲酰胺与1ml四氢呋喃的混合溶剂中;(1) Take 0.9002g polycaprolactone and 0.3850g dimethyloxalylglycine respectively with a balance, and pour them into a mixed solvent of 3ml dimethylformamide and 1ml tetrahydrofuran;

(2)室温下,放置于磁力搅拌器搅拌过夜,获得均一稳定的溶液;(2) At room temperature, place it on a magnetic stirrer and stir overnight to obtain a uniform and stable solution;

(3)将配置好的溶液倒入5ml注射器针管中,固定在静电纺丝装置,设定电压8kv,流速0.6ml/h,接收滚筒转速550r/min,进行静电纺丝,得到纳米纤维膜;(3) Pour the configured solution into the needle tube of a 5ml syringe, fix it on the electrospinning device, set the voltage to 8kv, the flow rate to 0.6ml/h, and the rotating speed of the receiving drum to 550r/min, and perform electrospinning to obtain a nanofiber film;

(4)将得到的纤维膜放置在37摄氏度烘箱中,干燥24小时,去除溶剂,得到最后样品。(4) The obtained fiber film was placed in an oven at 37 degrees Celsius, dried for 24 hours, and the solvent was removed to obtain the final sample.

图1为实施例1中制备的负载二甲基乙二酰甘氨酸纳米纤维的透射电镜图;如图1所示,所得产物主要以连续光滑纤维形式存在,直径大多集中在1-2μm范围内,随机堆叠成无纺布形态。Fig. 1 is the transmission electron micrograph of the loaded dimethyloxalylglycine nanofiber prepared in embodiment 1; As shown in Fig. 1, the resulting product mainly exists in the form of continuous smooth fibers, and the diameters are mostly concentrated in the range of 1-2 μm. Randomly stacked into a non-woven form.

图2为实施例1制备的负载二甲基乙二酰甘氨酸纳米纤维膜的接触角;如图2所示,所得产物的接触角为106.8度。Fig. 2 is the contact angle of the loaded dimethyloxalylglycine nanofiber membrane prepared in Example 1; as shown in Fig. 2, the contact angle of the obtained product is 106.8 degrees.

图3为实施例1制备的负载二甲基乙二酰甘氨酸纳米纤维膜的直径孔径比。如图3所示,所得产物随机选取16处进行直径与相邻空间(孔径)的对比,纤维孔径直径比均匀。Fig. 3 is the diameter-to-aperture ratio of the loaded dimethyloxalylglycine nanofiber membrane prepared in Example 1. As shown in Figure 3, 16 positions of the obtained product were randomly selected for comparison of the diameter and the adjacent space (aperture), and the ratio of fiber pore diameter to diameter was uniform.

Claims (10)

1.一种负载二甲基乙二酰甘氨酸纳米纤维的制备方法,其特征在于,包括如下步骤:1. a preparation method of loading dimethyloxalylglycine nanofiber, is characterized in that, comprises the steps: (1)将聚己内酯和二甲基乙二酰甘氨酸加入到二甲基甲酰胺与四氢呋喃的混合溶剂中,再放置于磁力搅拌器中,在20-25摄氏度的温度下搅拌8-14小时,获得均一稳定的溶液;(1) Add polycaprolactone and dimethyloxalylglycine to a mixed solvent of dimethylformamide and tetrahydrofuran, place it in a magnetic stirrer, and stir for 8-14 hours at a temperature of 20-25 degrees Celsius. hours, to obtain a uniform and stable solution; (2)将配置好的溶液进行静电纺丝,得到纳米纤维膜。(2) Electrospinning the configured solution to obtain a nanofiber membrane. 2.根据权利要求1所述的负载二甲基乙二酰甘氨酸纳米纤维的制备方法,其特征在于,步骤(2)中,静电纺丝的电压为6-10kv,喷出流速为0.5-0.7ml/h。2. the preparation method of loading dimethyloxalylglycine nanofiber according to claim 1 is characterized in that, in step (2), the voltage of electrospinning is 6-10kv, and ejection flow rate is 0.5-0.7 ml/h. 3.根据权利要求1所述的负载二甲基乙二酰甘氨酸纳米纤维的制备方法,其特征在于,步骤(1)中,所述的聚己内酯与二甲基乙二酰甘氨酸的质量比为0.9002:0.3850。3. the preparation method of load dimethyloxalylglycine nanofiber according to claim 1, is characterized in that, in step (1), the quality of described polycaprolactone and dimethyloxalylglycine The ratio is 0.9002:0.3850. 4.根据权利要求1所述的负载二甲基乙二酰甘氨酸纳米纤维的制备方法,其特征在于,步骤(1)中,所述二甲基甲酰胺与四氢呋喃的体积比为3:1。4. the preparation method of loaded dimethyloxalylglycine nanofiber according to claim 1, is characterized in that, in step (1), the volume ratio of described dimethylformamide and tetrahydrofuran is 3:1. 5.根据权利要求1所述的负载二甲基乙二酰甘氨酸纳米纤维的制备方法,其特征在于,步骤(1)中,聚己内酯和二甲基甲酰胺与四氢呋喃的混合溶剂的比例为0.9002g:4ml。5. the preparation method of load dimethyloxalylglycine nanofiber according to claim 1 is characterized in that, in step (1), the ratio of the mixed solvent of polycaprolactone and dimethylformamide and tetrahydrofuran It is 0.9002g:4ml. 6.根据权利要求1所述的负载二甲基乙二酰甘氨酸纳米纤维的制备方法,其特征在于,步骤(2)中,接收滚筒的转速为500-600r/min。6. The preparation method of loaded dimethyloxalylglycine nanofibers according to claim 1, characterized in that, in step (2), the rotating speed of the receiving drum is 500-600r/min. 7.根据权利要求1所述的负载二甲基乙二酰甘氨酸纳米纤维的制备方法,其特征在于,还包括:(3)将得到的纤维膜放置在烘箱中干燥,得到最后样品。7. The preparation method of loaded dimethyloxalylglycine nanofibers according to claim 1, further comprising: (3) placing the obtained fiber film in an oven to dry to obtain the final sample. 8.根据权利要求1所述的负载二甲基乙二酰甘氨酸纳米纤维的制备方法,其特征在于,所述干燥的温度为36-38摄氏度,干燥的时间为22-26小时。8. The preparation method of loaded dimethyloxalylglycine nanofibers according to claim 1, characterized in that, the drying temperature is 36-38 degrees Celsius, and the drying time is 22-26 hours. 9.根据权利要求1所述的负载二甲基乙二酰甘氨酸纳米纤维的制备方法,其特征在于步骤(1)中,所述聚己内酯的分子量为80000。9. The preparation method of loaded dimethyloxalylglycine nanofibers according to claim 1, characterized in that in step (1), the molecular weight of the polycaprolactone is 80,000. 10.权利要求1-9中任意一项所述的方法制备的负载二甲基乙二酰甘氨酸纳米纤维。10. The loaded dimethyloxalylglycine nanofiber prepared by the method according to any one of claims 1-9.
CN202211125162.9A 2022-09-15 2022-09-15 Preparation method of supported dimethyloxalglycine nanofiber Pending CN115467092A (en)

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