CN110464868B - A kind of silicate clay modified hemostatic material and preparation method thereof - Google Patents

Abstract

The invention provides a silicate clay modified hemostatic material and a preparation method thereof, wherein the hemostatic material is formed by compounding silicate clay and high polymer through electrostatic spinning; the mass ratio of the silicate clay to the high polymer is 0.5-2.5: 1; the silicate clay comprises kaolinite, halloysite, attapulgite or montmorillonite; wherein, part of silicon hydroxyl of the silicate clay is combined with the hydrogen bond of the high polymer, and the rest silicon hydroxyl plays the roles of hemostasis and hydrophily on the surface of the hemostatic material. The method comprises the following steps: firstly, carrying out pretreatment and ultrasonic crushing on silicate clay, then mixing with a high polymer ethanol solution to obtain an electrostatic spinning solution, and finally carrying out electrostatic spinning to obtain the silicate clay modified hemostatic material. The obtained hemostatic material has the advantages of high hemostatic speed, convenient use, favorable wound healing, good biocompatibility, low cost and the like.

Description

Translated fromChinese

一种硅酸盐黏土改性的止血材料及其制备方法A kind of silicate clay modified hemostatic material and preparation method thereof

技术领域technical field

本发明涉及生物医用材料技术领域，特别涉及一种硅酸盐黏土改性的止血材料及其制备方法。The invention relates to the technical field of biomedical materials, in particular to a silicate clay-modified hemostatic material and a preparation method thereof.

背景技术Background technique

新型止血材料的研究与应用是全球医学和生物材料科学领域中的重要课题。无论是临床外科手术，还是各种突发性事故造成人体大量出血，高效的止血材料对于挽救生命具有重要意义。当前临床常用的止血材料有氧化纤维素类、明胶海绵、纤维蛋白胶等不同种类。这些常用的止血材料间止血效果差别很大，应用条件各异，不能完全满足所有急救情况的需求。The research and application of new hemostatic materials is an important topic in the field of global medicine and biomaterials science. Whether it is a clinical surgical operation or a large amount of bleeding in the human body caused by various sudden accidents, efficient hemostatic materials are of great significance for saving lives. Currently, the commonly used hemostatic materials in clinical practice include oxidized cellulose, gelatin sponge, and fibrin glue. The hemostatic effects of these commonly used hemostatic materials are very different, and the application conditions are different, and they cannot fully meet the needs of all emergency situations.

硅酸盐黏土矿物在自然界中分布广泛、种类繁多，是一种宝贵的天然资源。硅酸盐黏土矿物的颗粒细、可塑性强、结合性好，且比表面积大，颗粒上带有负电性，有很好的的物理吸附性和表面化学活性，且具备安全、无毒等优点。硅酸盐黏土矿物在医学领域已被证实具有较好的凝血功能，其可选择性吸收血液中的水，有效浓缩凝血活性物质；使血小板聚集粘附，同时可以激发凝血因子，启动内源性凝血途径，达到凝血目的。Silicate clay minerals are widely distributed and diverse in nature, and are a valuable natural resource. Silicate clay minerals have fine particles, strong plasticity, good bonding, and large specific surface area. The particles are negatively charged, have good physical adsorption and surface chemical activity, and are safe and non-toxic. Silicate clay minerals have been proven to have good coagulation function in the medical field. They can selectively absorb water in the blood and effectively concentrate coagulation active substances; make platelets aggregate and adhere, and at the same time can stimulate coagulation factors and activate endogenous coagulation pathway to achieve the purpose of coagulation.

中国专利CN106039383A公开了一种复方三七白陶土竹纤维止血纱布及其制备方法，该止血纱布包括原生或再生竹纤维材料的基材、结合于所述基材上的止血材料、用于将所述止血材料粘合至所述基材的粘合剂，止血材料包括高岭土或高岭石止血粘土材料以及三七止血粉。上述止血纱布存在以下问题：止血材料的粘附量有限，粘附在基材上的颗粒易脱落，这些会导致其止血能力的降低和后续处理的困难。Chinese patent CN106039383A discloses a compound panax notoginseng white clay bamboo fiber hemostatic gauze and a preparation method thereof. The hemostatic gauze comprises a base material of raw or regenerated bamboo fiber material, a hemostatic material combined with the base material, and used for applying the hemostatic material to the base material. The hemostatic material is bonded to the adhesive of the substrate, and the hemostatic material includes kaolin or kaolinite hemostatic clay material and Panax notoginseng hemostatic powder. The above-mentioned hemostatic gauze has the following problems: the adhesion amount of the hemostatic material is limited, and the particles adhering to the substrate are easily detached, which will lead to the reduction of its hemostatic ability and the difficulty of subsequent treatment.

因此有必要提供一种止血速度快且使用方便、成本低廉的止血材料。Therefore, it is necessary to provide a hemostatic material with fast hemostasis speed, convenient use and low cost.

发明内容SUMMARY OF THE INVENTION

针对现有技术的不足，本发明提供了一种硅酸盐黏土改性的止血材料及其制备方法，其目的是为了用静电纺丝技术将硅酸盐黏土与高聚物复合成结构稳定的止血材料，使该止血材料具有止血速度快、使用方便、成本低廉的优点。In view of the deficiencies of the prior art, the present invention provides a silicate clay-modified hemostatic material and a preparation method thereof. The hemostatic material has the advantages of fast hemostasis, convenient use and low cost.

为了达到上述目的，本发明提供如下技术方案：In order to achieve the above object, the present invention provides the following technical solutions:

一种硅酸盐黏土改性的止血材料，所述止血材料由硅酸盐黏土与高聚物经静电纺丝复合而成；所述硅酸盐黏土与高聚物质量比为0.5～2.5:1；所述硅酸盐黏土包括高岭石、埃洛石、凹土棒石或蒙脱石；其中，硅酸盐黏土的部分硅羟基与高聚物的氢键结合，剩余部分硅羟基在止血材料表面发挥止血与亲水作用；所述高聚物包括聚乙烯吡咯烷酮、聚乙烯、左旋聚乳酸、聚丙烯酸乙酯或聚乙烯醇。A silicate clay-modified hemostatic material, the hemostatic material is composed of silicate clay and a polymer by electrospinning; the mass ratio of the silicate clay and the polymer is 0.5 to 2.5: 1; the silicate clay includes kaolinite, halloysite, attapulgite or montmorillonite; wherein, part of the silanol groups of the silicate clay is combined with the hydrogen bond of the high polymer, and the remaining part of the silanol groups are in The surface of the hemostatic material exerts hemostatic and hydrophilic effects; the high polymer includes polyvinylpyrrolidone, polyethylene, L-polylactic acid, polyethyl acrylate or polyvinyl alcohol.

优选地，所述硅酸盐黏土为埃洛石，所述埃洛石为分散型埃洛石纳米颗粒，所述止血材料为若干纤维束组成的3D网状结构，所述纤维束由纳米埃洛石通过静电作用与高聚物复合形成。Preferably, the silicate clay is halloysite, the halloysite is dispersed halloysite nanoparticles, the hemostatic material is a 3D network structure composed of several fiber bundles, and the fiber bundles are composed of nano-angstroms. Rockstone is formed by compounding with high polymers through electrostatic interaction.

优选地，所述硅酸盐黏土为凹土棒石，所述凹凸棒石为分散型凹凸棒石纳米颗粒，所述止血材料由分散型凹凸棒石纳米颗粒通过静电作用与高聚物复合形成。Preferably, the silicate clay is attapulgite, the attapulgite is dispersed attapulgite nanoparticles, and the hemostatic material is formed by compounding dispersed attapulgite nanoparticles with a polymer through electrostatic action .

本发明还提供一种上述硅酸盐黏土改性的止血材料的制备方法，包括如下步骤：The present invention also provides a preparation method of the above-mentioned silicate clay modified hemostatic material, comprising the following steps:

(1)将硅酸盐黏土进行预处理和超声破碎；(1) pretreatment and ultrasonic crushing of the silicate clay;

(2)将高聚物溶于乙醇中，制成浓度为0.1～0.3g/mL高聚物乙醇溶液；(2) Dissolving the high polymer in ethanol to prepare a high polymer ethanol solution with a concentration of 0.1-0.3 g/mL;

(3)将步骤(1)处理后的硅酸盐黏土与步骤(2)所得高聚物乙醇溶液混合，得到静电纺丝液；(3) mixing the silicate clay treated in step (1) with the high polymer ethanol solution obtained in step (2) to obtain an electrospinning solution;

其中，硅酸盐黏土与高聚物的质量比为0.5～2.5:1；Among them, the mass ratio of silicate clay to polymer is 0.5-2.5:1;

(4)将步骤(3)所得静电纺丝液进行静电纺丝，得到硅酸盐黏土改性的止血材料；(4) electrospinning the electrospinning solution obtained in step (3) to obtain a silicate clay-modified hemostatic material;

其中，所述硅酸盐黏土包括高岭石、埃洛石、凹土棒石或蒙脱石；所述高聚物包括聚乙烯吡咯烷酮、聚乙烯、左旋聚乳酸、聚丙烯酸乙酯或聚乙烯醇；Wherein, the silicate clay includes kaolinite, halloysite, attapulgite or montmorillonite; the high polymer includes polyvinylpyrrolidone, polyethylene, L-polylactic acid, polyethyl acrylate or polyethylene alcohol;

静电纺丝的参数为：滚筒转速为450～500r/min；接收距离为17～21cm；正极电压为10～12kV；负极电压为2～3kV。The parameters of electrospinning are: the rotating speed of the drum is 450-500 r/min; the receiving distance is 17-21 cm; the positive voltage is 10-12 kV; the negative voltage is 2-3 kV.

优选地，所述硅酸盐黏土为埃洛石、凹土棒石或蒙脱石时，所述预处理包括粉磨、水洗、离心处理。Preferably, when the silicate clay is halloysite, attapulgite or montmorillonite, the pretreatment includes grinding, water washing and centrifugation.

优选地，所述硅酸盐黏土为高岭石时，所述预处理包括粉磨、水洗、离心和柱撑处理。Preferably, when the silicate clay is kaolinite, the pretreatment includes grinding, washing, centrifugation and pillaring.

优选地，所述柱撑处理所用柱撑液为二甲基亚砜水溶液。Preferably, the pillaring liquid used in the pillaring treatment is an aqueous dimethyl sulfoxide solution.

优选地，所述超声破碎功率为400～800W，时间为100～150min。Preferably, the ultrasonic crushing power is 400-800 W, and the time is 100-150 min.

优选地，所述硅酸盐黏土经超声破碎后的颗粒平均尺寸小于1μm。Preferably, the average particle size of the silicate clay after ultrasonication is less than 1 μm.

优选地，静电纺丝的出液速度为0.05mL/min。Preferably, the liquid output rate of electrospinning is 0.05 mL/min.

当硅酸盐黏土为埃洛石时：经过预处理得到的埃洛石纳米管由于具有大量硅羟基和很强的团聚性，能够成纳米管团的形式与高聚物通过氢键相互结合，通过静电纺丝形成无数根纤维束编织成的3D网状薄膜。When the silicate clay is halloysite: the halloysite nanotubes obtained after pretreatment have a large number of silanol groups and strong agglomeration, and can be combined with the polymer through hydrogen bonding in the form of nanotube clusters. A 3D mesh film woven by countless fiber bundles is formed by electrospinning.

在埃洛石改性的止血材料中，埃洛石纳米管形成一定大小的埃洛石团，由于硅羟基的作用对高聚物具有一定的吸引力，使得高聚物形成的纤维束变细，整体薄膜孔道结构变多。在止血过程中，一方面更细的纤维束提供更多的空间让血细胞进入，从而更充分的与埃洛石接触，另一方面团聚的埃洛石表现出更强的埃洛石止血特性，能够活化凝固因子XII并激活血小板加速止血。同时薄膜整体亲水性变强更利于快速吸收血液中的水份，使血液变稠提高血细胞浓度并限制血液流动，最终达成止血目的。In the halloysite-modified hemostatic material, the halloysite nanotubes form halloysite clusters of a certain size. Due to the effect of silanols, the polymer has a certain attraction, which makes the fiber bundles formed by the polymer thinner. , the overall film pore structure increases. In the process of hemostasis, on the one hand, thinner fiber bundles provide more space for blood cells to enter, so as to more fully contact halloysite, on the other hand, the agglomerated halloysite shows stronger hemostatic properties of halloysite, Can activate coagulation factor XII and activate platelets to accelerate hemostasis. At the same time, the overall hydrophilicity of the film becomes stronger, which is more conducive to the rapid absorption of water in the blood, which thickens the blood, increases the concentration of blood cells and restricts the blood flow, and finally achieves the purpose of hemostasis.

高聚物由于其本身具有高分子材料的热收缩性，导致其在正常室温环境下会不断的收缩，最终导致其仅保留原面积的10％左右。而且纤维束之间的大量孔道也因为收缩而减少或消失进一步制约薄膜的止血性能。埃洛石加入后，由于埃洛石的硅羟基与高聚物相结合，抑制了高聚物的整体收缩，保留原薄膜面积的70％以上。同时引发了薄膜中小范围的高聚物分子向埃洛石团靠拢的现象，使得高聚物形成的纤维束变细，整体薄膜孔道结构变多。Due to the thermal shrinkage of polymer materials, the polymer will continue to shrink under normal room temperature environment, resulting in only about 10% of its original area remaining. Moreover, a large number of pores between the fiber bundles are also reduced or disappeared due to shrinkage, which further restricts the hemostatic properties of the film. After the halloysite is added, since the silanol groups of the halloysite are combined with the polymer, the overall shrinkage of the polymer is suppressed, and more than 70% of the original film area is retained. At the same time, the phenomenon that small-scale polymer molecules in the film are drawn to the halloysite group, which makes the fiber bundles formed by the polymer become thinner and the overall film pore structure increases.

当硅酸盐黏土为凹凸棒时：预处理得到的凹凸棒石纳米棒由于其棒晶束解离特性和本身具有的大量硅羟基，能够与高聚物通过氢键相互结合，首先通过静电纺丝形成纤维束编织成的3D网状薄膜；然后由于高聚物本身具有高分子材料的热收缩性，3D网状薄膜演变成一张表面有些许凹凸棒石残留颗粒的薄膜。When the silicate clay is attapulgite: the attapulgite nanorods obtained by pretreatment can be combined with the polymer through hydrogen bonding due to the dissociation characteristics of the rod crystal beam and the large amount of silanol groups. The silk forms a 3D mesh film woven by fiber bundles; then, due to the heat shrinkage of the polymer itself, the 3D mesh film evolves into a film with some residual attapulgite particles on the surface.

高聚物由于其本身具有高分子材料的热收缩性，导致其在正常室温环境下会不断的收缩，最终导致其仅保留原面积的10％左右。而且纤维束之间的大量孔道也因为收缩而减少或消失进一步制约薄膜的止血性能。而形成凹土棒石止血膜厚，部分解离的凹凸棒石融合在薄膜中，支撑框架结构，稳定整体结构，抑制高聚物进一步收缩，并且能够保留原薄膜面积的70％以上。Due to the thermal shrinkage of polymer materials, the polymer will continue to shrink under normal room temperature environment, resulting in only about 10% of its original area remaining. Moreover, a large number of pores between the fiber bundles are also reduced or disappeared due to shrinkage, which further restricts the hemostatic properties of the film. The attapulgite hemostatic film is thick, and the partially dissociated attapulgite is fused in the film, supporting the frame structure, stabilizing the overall structure, inhibiting further shrinkage of the polymer, and retaining more than 70% of the original film area.

在薄膜的单根纤维束表面，残留的凹土棒石颗粒充当功能性颗粒，改善了薄膜表面的亲水性，其中的硅氧四面体结构具有一定的止血能力，能够激活血小板加速止血。在止血过程中能够贴合伤口，吸收血浆凝聚血细胞加速止血。On the surface of a single fiber bundle of the film, the residual attapulgite particles act as functional particles to improve the hydrophilicity of the film surface. The silicon-oxygen tetrahedral structure has a certain hemostatic ability, which can activate platelets to accelerate hemostasis. In the process of hemostasis, it can fit the wound, absorb plasma and condense blood cells to accelerate hemostasis.

本发明的上述方案有如下的有益效果：The above-mentioned scheme of the present invention has the following beneficial effects:

(1)本发明首次将具备止血功能的硅酸盐黏土与静电纺丝技术结合，制得一种新型薄膜止血材料，相比于止血敷料粉末或将止血材料粘结在基材上，硅酸盐黏土改性的止血材料在对伤口止血时使用方便，且材料本身的吸水性和粘结性导致其能与创面贴合更加紧密。(1) The present invention combines silicate clay with hemostatic function and electrospinning technology for the first time to prepare a new type of film hemostatic material. The salt clay modified hemostatic material is easy to use when hemostasis the wound, and the water absorption and cohesiveness of the material itself make it fit more closely with the wound surface.

(2)硅酸盐黏土的部分硅羟基在止血材料中与高聚物的氢键结合，形成稳定结构；剩余部分硅羟基在材料表面发挥止血与亲水作用，得到的止血材料具有性能稳定、止血速度快、使用方便、有利于伤口愈合、生物相容性好、成本低廉的优点。(2) Part of the silanol groups of the silicate clay are combined with the hydrogen bonds of the high polymer in the hemostatic material to form a stable structure; the remaining part of the silanol groups play the role of hemostasis and hydrophilicity on the surface of the material, and the obtained hemostatic material has stable performance, The invention has the advantages of fast hemostasis, convenient use, favorable wound healing, good biocompatibility and low cost.

(3)未加入硅酸盐黏土的高聚物结构不稳定，极容易发生缩聚，导致孔道结构消失，比表面积降低，静电纺丝工艺所带来的结构优势被破坏，止血效果不佳(对比例1)；而经硅酸盐黏土改性后，高聚物的整体收缩得到了抑制，硅酸盐黏土为复合材料整体结构提供支撑，减少其收缩现象，使复合材料的孔道结构变多，止血效果得到提高(实施例1～3)。(3) The structure of the polymer without silicate clay is unstable, and it is very prone to polycondensation, resulting in the disappearance of the pore structure, the reduction of the specific surface area, the destruction of the structural advantages brought by the electrospinning process, and the poor hemostatic effect (for Proportion 1); and after the modification of silicate clay, the overall shrinkage of the polymer is suppressed, and the silicate clay provides support for the overall structure of the composite material, reduces its shrinkage phenomenon, and increases the pore structure of the composite material. The hemostatic effect was improved (Examples 1 to 3).

附图说明Description of drawings

图1为本发明实施例1得到的埃洛石改性的止血材料的SEM图；Fig. 1 is the SEM image of the halloysite-modified hemostatic material obtained in Example 1 of the present invention;

图2为本发明实施例3得到的凹凸棒石改性的止血材料的SEM图；Fig. 2 is the SEM image of the attapulgite-modified hemostatic material obtained in Example 3 of the present invention;

图3为本发明对比例1的聚乙烯吡络烷酮静电纺丝薄膜的SEM图。3 is a SEM image of the polyvinylpyrrolidone electrospinning film of Comparative Example 1 of the present invention.

具体实施方式Detailed ways

为使本发明要解决的技术问题、技术方案和优点更加清楚，下面将结合具体实施例进行详细描述。In order to make the technical problems, technical solutions and advantages to be solved by the present invention more clear, the following will be described in detail with reference to specific embodiments.

实施例1Example 1

(1)埃洛石纳米管的制备：(1) Preparation of halloysite nanotubes:

称取5.0g经粉磨、水洗和离心后的原矿埃洛石，加入500mL去离子水在1500W功率下超声破碎2h，即得埃洛石纳米棒，平均尺寸在1μm以下。Weigh 5.0 g of the halloysite after grinding, washing and centrifugation, add 500 mL of deionized water, and ultrasonically break it for 2 hours at 1500 W to obtain halloysite nanorods with an average size of less than 1 μm.

(2)埃洛石改性的止血材料的制备：(2) Preparation of halloysite-modified hemostatic material:

向10mL无水乙醇中溶解聚乙烯吡咯烷酮1.0g，加入埃洛石纳米棒1.50g，常温下水浴搅拌36h；进行静电纺丝设置滚筒转速为500r/min，针头距滚筒的距离(接收距离)为21cm，出液速度为0.05mL/min，正极电压为10kV，负极电压为2kV，制得埃洛石改性的止血材料，SEM图谱如图1所示：埃洛石改性的止血材料中埃洛石团分布在埃洛石与聚乙烯吡咯烷酮复合纤维束搭接形成的3D网状结构中，所述埃洛石团为埃洛石晶体自身硅羟基产生的静电作用相互吸引形成，所述纤维束以纳米埃洛石通过静电作用与聚乙烯吡咯烷酮复合形成，所述埃洛石团通过静电作用与聚乙烯吡咯烷复合然后与纤维束相连；所述纳米埃洛石为分散型埃洛石纳米颗粒。Dissolve 1.0 g of polyvinylpyrrolidone in 10 mL of absolute ethanol, add 1.50 g of halloysite nanorods, and stir in a water bath for 36 h at room temperature; set the drum speed to 500 r/min for electrospinning, and the distance between the needle and the drum (receiving distance) is 21cm, the liquid discharge rate is 0.05mL/min, the positive electrode voltage is 10kV, and the negative electrode voltage is 2kV, a halloysite-modified hemostatic material is prepared. The SEM spectrum is shown in Figure 1: The halloysite-modified hemostatic material is The halloysite group is distributed in the 3D network structure formed by the overlapping of the halloysite and the polyvinylpyrrolidone composite fiber bundle. The halloysite group is formed by the electrostatic interaction generated by the halloysite crystal itself. The bundle is formed by compounding nano halloysite with polyvinylpyrrolidone through electrostatic interaction, and the halloysite group is compounded with polyvinylpyrrolidine through electrostatic interaction and then connected with the fiber bundle; the nano halloysite is a dispersed type halloysite nanometer. particles.

(3)止血实验：(3) Hemostasis experiment:

大鼠以10％水合氯醛(0.3ml/100g)腹腔内注射麻醉，仰卧位固定，消毒，取腹部正中切口长约5cm，逐层剪开皮肤、肌肉及腹膜，暴露肝脏。将肝脏右叶充分暴露后在其正中以尖刀划取1×1cm的正方形边界，深约0.5cm。以组织剪将边界内肝组织去除，并以组织镊刮除创面，使肝脏创面出现明显渗血。将实施例1制得的止血材料置于创面，充分覆盖并贴附肝组织，以医用纱布于材料外侧创面上方适当压迫并计时，记录渗血完全停止时间为120秒。The rats were anesthetized by intraperitoneal injection of 10% chloral hydrate (0.3ml/100g), fixed in the supine position, and disinfected. After fully exposing the right lobe of the liver, a 1 × 1 cm square border was drawn in the middle with a sharp knife, with a depth of about 0.5 cm. The liver tissue within the border was removed with tissue scissors, and the wound surface was scraped with tissue forceps, so that the liver wound surface had obvious blood oozing. The hemostatic material prepared in Example 1 was placed on the wound surface, fully covered and attached to the liver tissue, and the medical gauze was appropriately pressed over the wound surface outside the material and timed, and the complete stop time of bleeding was recorded as 120 seconds.

实施例2Example 2

(1)埃洛石纳米管的制备：(1) Preparation of halloysite nanotubes:

称取5.0g经粉磨、水洗和离心后的原矿埃洛石，加入500mL去离子水在1500W功率下超声破碎2h，即得埃洛石纳米棒，平均尺寸在1μm以下。Weigh 5.0 g of the halloysite after grinding, washing and centrifugation, add 500 mL of deionized water, and ultrasonically break it for 2 hours at 1500 W to obtain halloysite nanorods with an average size of less than 1 μm.

(2)埃洛石改性的止血材料的制备：(2) Preparation of halloysite-modified hemostatic material:

向10mL无水乙醇中溶解聚乙烯吡咯烷酮1.0g，加入埃洛石纳米棒0.50g，常温下水浴搅拌36h；进行静电纺丝设置滚筒转速为500r/min，针头距滚筒的距离为21cm，出液速度为0.05mL/min，正极电压为10kV，负极电压为2kV，制得埃洛石改性的止血材料。Dissolve 1.0 g of polyvinylpyrrolidone in 10 mL of absolute ethanol, add 0.50 g of halloysite nanorods, and stir in a water bath for 36 h at room temperature; set the drum speed to 500 r/min for electrospinning, the distance between the needle and the drum is 21 cm, and the liquid is discharged. The speed was 0.05 mL/min, the positive voltage was 10 kV, and the negative voltage was 2 kV to prepare a halloysite-modified hemostatic material.

(3)止血实验：(3) Hemostasis experiment:

大鼠以10％水合氯醛(0.3ml/100g)腹腔内注射麻醉，仰卧位固定，消毒，取腹部正中切口长约5cm，逐层剪开皮肤、肌肉及腹膜，暴露肝脏。将肝脏右叶充分暴露后在其正中以尖刀划取1×1cm的正方形边界，深约0.5cm。以组织剪将边界内肝组织去除，并以组织镊刮除创面，使肝脏创面出现明显渗血。将实施例1制得的止血材料置于创面，充分覆盖并贴附肝组织，以医用纱布于材料外侧创面上方适当压迫并计时，记录渗血完全停止时间为125秒。The rats were anesthetized by intraperitoneal injection of 10% chloral hydrate (0.3ml/100g), fixed in the supine position, and disinfected. After fully exposing the right lobe of the liver, a 1 × 1 cm square border was drawn in the middle with a sharp knife, with a depth of about 0.5 cm. The liver tissue within the border was removed with tissue scissors, and the wound surface was scraped with tissue forceps, so that the liver wound surface had obvious blood oozing. The hemostatic material prepared in Example 1 was placed on the wound surface, fully covered and attached to the liver tissue, and the medical gauze was appropriately pressed over the wound surface outside the material and timed, and the complete stop time of bleeding was recorded as 125 seconds.

实施例3Example 3

(1)凹凸棒石纳米棒的制备：(1) Preparation of attapulgite nanorods:

称取5.0g经粉磨、水洗和离心后的原矿凹凸棒石，加入500mL去离子水在1500W功率下超声破碎2h，即得凹凸棒石纳米棒，平均长度在2μm以下。Weigh 5.0 g of attapulgite after grinding, washing and centrifugation, add 500 mL of deionized water, and ultrasonically break it for 2 hours at a power of 1500 W to obtain attapulgite nanorods with an average length of less than 2 μm.

(2)凹凸棒改性的止血材料的制备：(2) Preparation of attapulgite modified hemostatic material:

向10mL无水乙醇中溶解聚乙烯吡咯烷酮1.0g，加入凹凸棒石纳米棒1.50g，常温下水浴搅拌36h；进行静电纺丝设置滚筒转速为500r/min，针头距滚筒的距离为21cm，出液速度为0.05mL/min，正极电压为10kV，负极电压为2kV。制得凹凸棒石改性的止血材料，SEM图谱如图2所示：该止血材料为表面粗糙薄膜结构，所述薄膜以部分棒晶束解离后的凹凸棒石通过静电作用与聚乙烯吡咯烷酮复合作为薄膜主体，薄膜表面部分棒晶束解离的凹凸棒通过部分硅羟基与薄膜相连，另外一部分暴露在外形成表面粗糙的结构同时发挥止血以及亲水作用；所述纳米凹凸棒石为分散型凹凸棒石纳米颗粒；所述凹凸棒石部分棒晶束解离为在预处理时经过超声破碎、碾磨和冷冻干燥发生的现象。Dissolve 1.0 g of polyvinylpyrrolidone in 10 mL of absolute ethanol, add 1.50 g of attapulgite nanorods, and stir in a water bath for 36 h at room temperature; set the drum speed to 500 r/min for electrospinning, the distance between the needle and the drum is 21 cm, and the liquid is discharged. The speed was 0.05 mL/min, the positive voltage was 10 kV, and the negative voltage was 2 kV. A hemostatic material modified by attapulgite was prepared, and the SEM spectrum is shown in Figure 2: the hemostatic material has a rough surface film structure. As the main body of the film, the attapulgite on the surface of the film partially dissociated by the rod crystal beams is connected to the film through part of the silanol groups, and the other part is exposed to form a rough surface structure while exerting hemostatic and hydrophilic effects; the nano attapulgite is a dispersed type Attapulgite nanoparticles; the dissociation of the attapulgite partial rod crystal bundles is a phenomenon that occurs through ultrasonication, milling and freeze-drying during pretreatment.

(3)止血实验：(3) Hemostasis experiment:

大鼠以10％水合氯醛(0.3ml/100g)腹腔内注射麻醉，仰卧位固定，消毒，取腹部正中切口长约5cm，逐层剪开皮肤、肌肉及腹膜，暴露肝脏。将肝脏右叶充分暴露后在其正中以尖刀划取1×1cm的正方形边界，深约0.5cm。以组织剪将边界内肝组织去除，并以组织镊刮除创面，使肝脏创面出现明显渗血。将实施例2制得的止血材料置于创面，充分覆盖并贴附肝组织，以医用纱布于材料外侧创面上方适当压迫并计时，记录渗血完全停止时间为140秒。The rats were anesthetized by intraperitoneal injection of 10% chloral hydrate (0.3ml/100g), fixed in the supine position, and disinfected. After fully exposing the right lobe of the liver, a 1 × 1 cm square border was drawn in the middle with a sharp knife, with a depth of about 0.5 cm. The liver tissue within the border was removed with tissue scissors, and the wound surface was scraped with tissue forceps, so that the liver wound surface had obvious blood oozing. The hemostatic material prepared in Example 2 was placed on the wound surface, fully covered and attached to the liver tissue, properly compressed with a medical gauze above the wound surface outside the material and timed, and the complete stop time of bleeding was recorded as 140 seconds.

实施例4Example 4

(1)高岭石纳米片的制备：(1) Preparation of kaolinite nanosheets:

称取10.0g经粉磨、水洗和离心后的原矿高岭石，加入90mL二甲基亚砜，10mL去离子水。在70℃下水域搅拌36h得到高岭石柱撑液。将高岭石柱撑液在1500W功率下超声破碎2h，即得高岭石纳米片，平均尺寸在1μm以下。Weigh 10.0 g of the raw kaolinite after grinding, washing and centrifugation, add 90 mL of dimethyl sulfoxide and 10 mL of deionized water. The water was stirred at 70 °C for 36 h to obtain a kaolinite pillared liquid. The kaolinite pillared liquid was ultrasonically broken for 2 hours at a power of 1500W to obtain kaolinite nanosheets with an average size of less than 1 μm.

(2)高岭石改性的止血材料的制备：(2) Preparation of kaolinite-modified hemostatic material:

向10mL无水乙醇中溶解聚乙烯吡咯烷酮1.0g，加入高岭石纳米片2.40g，常温下水浴搅拌36h；进行静电纺丝设置滚筒转速为500r/min，针头距滚筒的距离为21cm，出液速度为0.05mL/min，正极电压为10kV，负极电压为2kV，制得高岭土改性的止血材料。Dissolve 1.0 g of polyvinylpyrrolidone in 10 mL of absolute ethanol, add 2.40 g of kaolinite nanosheets, and stir in a water bath for 36 hours at room temperature; set the drum speed to 500 r/min for electrospinning, the distance between the needle and the drum is 21 cm, and the liquid is discharged. The speed was 0.05 mL/min, the positive voltage was 10 kV, and the negative voltage was 2 kV to prepare a kaolin-modified hemostatic material.

(3)止血实验：(3) Hemostasis experiment:

大鼠以10％水合氯醛(0.3ml/100g)腹腔内注射麻醉，仰卧位固定，消毒，取腹部正中切口长约5cm，逐层剪开皮肤、肌肉及腹膜，暴露肝脏。将肝脏右叶充分暴露后在其正中以尖刀划取1×1cm的正方形边界，深约0.5cm。以组织剪将边界内肝组织去除，并以组织镊刮除创面，使肝脏创面出现明显渗血。将预先准备好的止血材料置于创面，充分覆盖并贴附肝组织，以医用纱布于材料外侧创面上方适当压迫并计时，记录渗血完全停止时间为100秒。The rats were anesthetized by intraperitoneal injection of 10% chloral hydrate (0.3ml/100g), fixed in the supine position, and disinfected. After fully exposing the right lobe of the liver, a 1 × 1 cm square border was drawn in the middle with a sharp knife, with a depth of about 0.5 cm. The liver tissue within the border was removed with tissue scissors, and the wound surface was scraped with tissue forceps, so that the liver wound surface had obvious blood oozing. The pre-prepared hemostatic material was placed on the wound surface, fully covered and attached to the liver tissue, and the medical gauze was used to press the material outside the wound surface appropriately and timed, and the time for complete cessation of bleeding was recorded as 100 seconds.

对比例1Comparative Example 1

(1)聚乙烯吡络烷酮静电纺丝薄膜制备：(1) Preparation of polyvinylpyrrolidone electrospinning film:

向10mL无水乙醇中溶解聚乙烯吡咯烷酮1.0g，常温下水浴搅拌36h；进行静电纺丝设置滚筒转速为500r/min，针头距滚筒的距离为21cm，出液速度为0.05mL/min，正极电压为10kV，负极电压为2kV。制得埃洛石静电纺丝薄膜，SEM图谱如图3所示：由图3可知PVP膜收缩程度大，PVP丝严重缩聚导致膜中的孔道几乎全部消失。Dissolve 1.0 g of polyvinylpyrrolidone in 10 mL of absolute ethanol, and stir in a water bath for 36 h at room temperature; set the drum speed to 500 r/min for electrospinning, the distance between the needle and the drum is 21 cm, the liquid discharge speed is 0.05 mL/min, and the positive voltage is is 10kV, and the negative voltage is 2kV. The halloysite electrospinning film was prepared, and the SEM pattern is shown in Figure 3: It can be seen from Figure 3 that the PVP film has a large degree of shrinkage, and the severe polycondensation of the PVP silk causes almost all the pores in the film to disappear.

(2)止血实验：(2) Hemostasis experiment:

大鼠以10％水合氯醛(0.3ml/100g)腹腔内注射麻醉，仰卧位固定，消毒，取腹部正中切口长约5cm，逐层剪开皮肤、肌肉及腹膜，暴露肝脏。将肝脏右叶充分暴露后在其正中以尖刀划取1×1cm的正方形边界，深约0.5cm。以组织剪将边界内肝组织去除，并以组织镊刮除创面，使肝脏创面出现明显渗血。将对比例1制得的埃洛石静电纺丝薄膜置于创面，充分覆盖并贴附肝组织，以医用纱布于材料外侧创面上方适当压迫并计时，记录渗血完全停止时间为360秒。The rats were anesthetized by intraperitoneal injection of 10% chloral hydrate (0.3ml/100g), fixed in the supine position, and disinfected. After fully exposing the right lobe of the liver, a 1 × 1 cm square border was drawn in the middle with a sharp knife, with a depth of about 0.5 cm. The liver tissue within the border was removed with tissue scissors, and the wound surface was scraped with tissue forceps, so that the liver wound surface had obvious blood oozing. The halloysite electrospinning film prepared in Comparative Example 1 was placed on the wound surface, fully covered and attached to the liver tissue, and the medical gauze was appropriately pressed over the wound surface outside the material and timed, and the complete stop time of bleeding was recorded as 360 seconds.

以上所述是本发明的优选实施方式，应当指出，对于本技术领域的普通技术人员来说，在不脱离本发明所述原理的前提下，还可以作出若干改进和润饰，这些改进和润饰也应视为本发明的保护范围。The above are the preferred embodiments of the present invention. It should be pointed out that for those skilled in the art, without departing from the principles of the present invention, several improvements and modifications can be made. It should be regarded as the protection scope of the present invention.

Claims (4)

Translated fromChinese

1.一种硅酸盐黏土改性的止血材料，其特征在于，所述止血材料由硅酸盐黏土与高聚物经静电纺丝复合而成；所述硅酸盐黏土与高聚物的质量比为0.5～2.5:1；所述硅酸盐黏土包括高岭石、埃洛石、凹凸棒石或蒙脱石；其中，硅酸盐黏土的部分硅羟基与高聚物的氢键结合，剩余部分硅羟基在止血材料表面发挥止血与亲水作用；所述高聚物包括聚乙烯吡咯烷酮、聚乙烯、左旋聚乳酸、聚丙烯酸乙酯或聚乙烯醇；1. a hemostatic material modified by silicate clay, is characterized in that, described hemostatic material is compounded by silicate clay and high polymer through electrospinning; The mass ratio is 0.5 to 2.5:1; the silicate clay includes kaolinite, halloysite, attapulgite or montmorillonite; wherein, part of the silanol groups of the silicate clay is combined with the hydrogen bond of the high polymer , and the remaining part of the silanols exerts hemostatic and hydrophilic effects on the surface of the hemostatic material; the high polymer includes polyvinylpyrrolidone, polyethylene, L-polylactic acid, polyethyl acrylate or polyvinyl alcohol;其中，所述硅酸盐黏土为埃洛石，所述埃洛石为分散型埃洛石纳米颗粒，所述止血材料为若干纤维束组成的3D网状结构，所述纤维束由纳米埃洛石通过静电作用与高聚物复合形成；Wherein, the silicate clay is halloysite, the halloysite is dispersed halloysite nanoparticles, the hemostatic material is a 3D network structure composed of several fiber bundles, and the fiber bundles are composed of nano-halloysite The stone is formed by compounding with the polymer through electrostatic interaction;其中，所述硅酸盐黏土为凹凸棒石，所述凹凸棒石为分散型凹凸棒石纳米颗粒，所述止血材料由分散型凹凸棒石纳米颗粒通过静电作用与高聚物复合形成；Wherein, the silicate clay is attapulgite, the attapulgite is dispersed attapulgite nanoparticles, and the hemostatic material is formed by composite attapulgite nanoparticles with a polymer through electrostatic action;所述止血材料的制备方法包括如下步骤：The preparation method of the hemostatic material comprises the following steps:(1)将硅酸盐黏土进行预处理和超声破碎；(1) pretreatment and ultrasonic crushing of the silicate clay;所述硅酸盐黏土经超声破碎后的颗粒平均尺寸小于1μm；The average particle size of the silicate clay after ultrasonic crushing is less than 1 μm;(2)将高聚物溶于乙醇中，制成浓度为0.1～0.3g/mL高聚物乙醇溶液；(2) Dissolving the high polymer in ethanol to prepare a high polymer ethanol solution with a concentration of 0.1-0.3 g/mL;(3)将步骤(1)处理后的硅酸盐黏土与步骤(2)所得高聚物乙醇溶液混合，得到静电纺丝液；(3) mixing the silicate clay treated in step (1) with the high polymer ethanol solution obtained in step (2) to obtain an electrospinning solution;其中，硅酸盐黏土与高聚物的质量比为0.5～2.5:1；Among them, the mass ratio of silicate clay to polymer is 0.5-2.5:1;(4)将步骤(3)所得静电纺丝液进行静电纺丝，得到硅酸盐黏土改性的止血材料；(4) electrospinning the electrospinning solution obtained in step (3) to obtain a silicate clay-modified hemostatic material;其中，所述硅酸盐黏土包括高岭石、埃洛石、凹凸棒石或蒙脱石；所述高聚物包括聚乙烯吡咯烷酮、聚乙烯、左旋聚乳酸、聚丙烯酸乙酯或聚乙烯醇；Wherein, the silicate clay includes kaolinite, halloysite, attapulgite or montmorillonite; the high polymer includes polyvinylpyrrolidone, polyethylene, L-polylactic acid, polyethyl acrylate or polyvinyl alcohol ;静电纺丝的参数为：滚筒转速为450～500r/min；接收距离为17～21cm；正极电压为10～12kV；负极电压为2～3kV；The parameters of electrospinning are: the rotating speed of the drum is 450～500r/min; the receiving distance is 17～21cm; the positive voltage is 10～12kV; the negative voltage is 2～3kV;其中，所述硅酸盐黏土为埃洛石、凹凸棒石或蒙脱石时，所述预处理包括粉磨、水洗、离心处理；Wherein, when the silicate clay is halloysite, attapulgite or montmorillonite, the pretreatment includes grinding, washing and centrifugation;其中，所述硅酸盐黏土为高岭石时，所述预处理包括粉磨、水洗、离心和柱撑处理；Wherein, when the silicate clay is kaolinite, the pretreatment includes grinding, washing, centrifugation and pillaring;其中，所述柱撑处理所用柱撑液为二甲基亚砜水溶液。Wherein, the pillaring liquid used in the pillaring treatment is an aqueous dimethyl sulfoxide solution.2.一种如权利要求1所述的硅酸盐黏土改性的止血材料的制备方法，其特征在于，包括如下步骤：2. a preparation method of the hemostatic material of silicate clay modification as claimed in claim 1, is characterized in that, comprises the steps:(1)将硅酸盐黏土进行预处理和超声破碎；(1) pretreatment and ultrasonic crushing of the silicate clay;所述硅酸盐黏土经超声破碎后的颗粒平均尺寸小于1μm；The average particle size of the silicate clay after ultrasonic crushing is less than 1 μm;(2)将高聚物溶于乙醇中，制成浓度为0.1～0.3g/mL高聚物乙醇溶液；(2) Dissolving the high polymer in ethanol to prepare a high polymer ethanol solution with a concentration of 0.1-0.3 g/mL;(3)将步骤(1)处理后的硅酸盐黏土与步骤(2)所得高聚物乙醇溶液混合，得到静电纺丝液；(3) mixing the silicate clay treated in step (1) with the high polymer ethanol solution obtained in step (2) to obtain an electrospinning solution;其中，硅酸盐黏土与高聚物的质量比为0.5～2.5:1；Among them, the mass ratio of silicate clay to polymer is 0.5-2.5:1;(4)将步骤(3)所得静电纺丝液进行静电纺丝，得到硅酸盐黏土改性的止血材料；(4) electrospinning the electrospinning solution obtained in step (3) to obtain a silicate clay-modified hemostatic material;其中，所述硅酸盐黏土包括高岭石、埃洛石、凹凸棒石或蒙脱石；所述高聚物包括聚乙烯吡咯烷酮、聚乙烯、左旋聚乳酸、聚丙烯酸乙酯或聚乙烯醇；Wherein, the silicate clay includes kaolinite, halloysite, attapulgite or montmorillonite; the high polymer includes polyvinylpyrrolidone, polyethylene, L-polylactic acid, polyethyl acrylate or polyvinyl alcohol ;静电纺丝的参数为：滚筒转速为450～500r/min；接收距离为17～21cm；正极电压为10～12kV；负极电压为2～3kV；The parameters of electrospinning are: the rotating speed of the drum is 450~500r/min; the receiving distance is 17~21cm; the positive voltage is 10~12kV; the negative voltage is 2~3kV;其中，所述硅酸盐黏土为埃洛石、凹凸棒石或蒙脱石时，所述预处理包括粉磨、水洗、离心处理；Wherein, when the silicate clay is halloysite, attapulgite or montmorillonite, the pretreatment includes grinding, washing and centrifugation;其中，所述硅酸盐黏土为高岭石时，所述预处理包括粉磨、水洗、离心和柱撑处理；Wherein, when the silicate clay is kaolinite, the pretreatment includes grinding, washing, centrifugation and pillaring;其中，所述柱撑处理所用柱撑液为二甲基亚砜水溶液。Wherein, the pillaring liquid used in the pillaring treatment is an aqueous dimethyl sulfoxide solution.3.根据权利要求2所述制备方法，其特征在于，所述超声破碎功率为400～800W，时间为100～150min。3 . The preparation method according to claim 2 , wherein the ultrasonic crushing power is 400-800 W, and the time is 100-150 min. 4 .4.根据权利要求2所述制备方法，其特征在于，静电纺丝的出液速度为0.05mL/min。4 . The preparation method according to claim 2 , wherein the liquid discharge rate of the electrospinning is 0.05 mL/min. 5 .

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