基于地锦草提取物止血敷料的制备及性能研究

Preparation and Performance Study of Hemostatic Dressings Based on Euphorbia humifusa Extract

摘要

为开发多功能止血敷料，以地锦草提取物（EHE）、海藻酸钠（SA）、聚乙烯醇（PVA）与羟丙基甲基纤维素（HPMC）为原料，通过循环冻融结合冷冻干燥法及钙离子交联法制备了 SA/PVA/HPMC/EHE（SPHE）止血海绵。表征了 SPHE 海绵的微观形貌与结构，分析了其抗菌、抗氧化、吸水、孔隙率及力学性能，并探究了其止血性能及生物相容性。结果表明：SPHE 海绵具有高度疏松的多孔结构，能快速吸水膨胀，对大肠杆菌和金黄色葡萄球菌的抑菌效果优异，且生物相容性良好。当 EHE 质量分数为 2% 时，SPHE 海绵的力学性能、吸水性能与孔隙率均表现良好，其凝血指数为 32.92%，溶血率为 2.71%，小鼠断尾止血效果较好。SPHE 海绵在止血敷料领域具有良好的应用前景。

Abstract

To develop a multifunctional hemostatic dressing, extracts of Euphorbia humifusa (EHE), sodium alginate (SA), polyvinyl alcohol (PVA), and hydroxypropyl methylcellulose (HPMC) were selected as raw materials. SA/PVA/HPMC/EHE (SPHE) hemostatic sponges were prepared via a cyclic freeze-thaw process combined with freeze-drying and calcium ion cross-linking. The microstructure and morphology of SPHE were characterized. The antibacterial, antioxidant, water absorption, porosity, and mechanical properties were analyzed. Additionally, the hemostatic performance and biocompatibility were investigated. The results indicate that SPHE sponge possesses a highly loose and porous structure, enables rapid water absorption and expansion, exhibits excellent antibacterial activity againstEscherichia coli and Staphylococcus aureus, and demonstrates good biocompatibility. At an EHE mass fraction of 2%, the sponge exhibits favorable mechanical properties, water absorption capacity, and porosity, with a clotting index of 32.92% and a hemolysis rate of 2.71%, and it demonstrates good hemostatic efficacy in mouse tail-amputation experiments. Therefore, this SPHE sponge holds promising prospects for application in the field of hemostatic dressings.

关键词

止血海绵 / 地锦草提取物 / 海藻酸钠 / 聚乙烯醇 / 羟丙基甲基纤维素

Key words

hemostatic sponge / Euphorbia humifusa extract / sodium alginate / polyvinyl alcohol / hydroxypropyl methylcellulose

参考文献

[1] CHEN A H, WU L X, WANG K Y, QIN L, ZHANG K X, CHEN S, ZHANG Y J, SONG W, ZHANG Q, XIA W, LUO Y, LIU X J, WAN J . Facile synthesis of rapid hemostatic powder based on sodium alginate for promoting hemostasis and wound healing [J]. International Journal of Biological Macromolecule, 2025, 308: 142728.

[2] TAN Y, YANG Q, ZHENG M, SARWAR M T, YANG H M . Multifunctional nanoclay—based hemostatic materials for wound healing: A review [J]. Advanced Healthcare Materials, 2023, 13(6): e2302700.

[3] GHIMIRE S, SARKAR P, RIGBY K, MAAN A, MUKHERJEE S, CRAWFORD K E, MUKHOPADHYAY K . Polymeric materials for hemostatic wound healing [J]. Pharmaceutics, 2021, 13(12): 2127.

[4] LI X F, LU P P, JIA H R, LI G F, ZHU B F, WANG X, WU F G . Emerging materials for hemostasis [J]. Coordination Chemistry Reviews, 2023, 475: 214823.

[5] JIANG Y C, YAN L Y, LIU M J, GUO Y Y, TANG K Y . A polyvinyl alcohol—gelatin composite hydrogel dressing for accelerated wound healing under electrical stimulation [J]. Colloids and Surfaces B: Biointerfaces, 2026, 263: 115602.

[6] POONKUNDRAN P, CHICKANNA R, VARADHAN B K, LAKSHMAIAH V P M . A comparative evaluation of laser bandage and surgical stent as palatal donor site dressing after free gingival graft surgery: A randomized controlled clinical trial [J]. Journal of Advanced Periodontology & Implant Dentistry, 2026, 18(1): 41-47.

[7] XU H F, LIU Y, QIU L X, MANGUE A L M M, ZHANG J T, WEI B M, ZHU L, XU C Z, SHIRSHIN E A, WANG H B . Preparation and application of collagen—based hemostatic materials: A review [J]. Collagen and Leather, 2025, 7(1): 11.

[8] SMIY S, BEJAR M, DHAHRI E, FIORIDO T, AGUIR K, BENDAHAN M . Preparation of double—doping LaFeO₃ thin film for ethanol sensing application [J]. Journal of Molecular Structure, 2022, 1267: 133543.

[9] WANG L, LI W J, QU Y, WANG K, LV K N, HE X L, QIN S . Preparation of super absorbent and highly active fish collagen sponge and its hemostatic effect in vivo and in vitro [J]. Frontiers in Bioengineering and Biotechnology, 2022, 10: 862532.

[10] SHARMA A, VERMA C, SINGH P, MUKHOPADHYAY S, GUPTA A, GUPTA B . Alginate based biomaterials for hemostatic applications: Innovations and developments [J]. International Journal of Biological Macromolecules, 2024, 264: 130771.

[11] 罗爽 . 海藻酸盐基海绵敷料的制备与性能研究 [D]. 江苏无锡: 江南大学, 2024.

[12] LUO S . Preparation and performance study of alginate—based sponge dressings [D]. Wuxi, Jiangsu: Jiangnan University, 2024.

[13] ZHANG P C, YU C, HU Z F, LI Y J, WAN G M, TANG K Y, FAN X L . On—demand removal of rapid hemostatic sponge for non—compressible hemorrhage through disrupting ionic bonds [J]. Advanced Healthcare Materials, 2025, 14(11): e2404894.

[14] WU W H, HUANG H J, HUANG Z C, WANG Q H, HUANG Z X, ZHANG H W, CHEN D S, WANG W, ZHAO H, LIU H Q, ZHENG B D, WANG Y . Necklace—structured PVA sponges for fast bleeding control in the punctured femoral artery hemorrhage [J]. Advanced Healthcare Materials, 2025, 14(10): e2404463.

[15] LI P P, CAO L N, SANG F, ZHANG B X, MENG Z Z, PAN L L, HAO J H, YANG X, MA Z P, SHI C C . Polyvinyl alcohol/sodium alginate composite sponge with 3D ordered/disordered porous structure for rapidly controlling noncompressible hemorrhage [J]. Materials Science & Engineering C: Materials for Biological Applications, 2022, 134: 112698.

[16] HOU D D, WANG Y S, QI L Y, WANG C Y, DENG J Q, ZHAO X H, GENG X, SUN Q, YE L, GUO Z F . A facile way to fabricate a thrombin immobilized composite sponge with dual hemostatic effects for acute hemorrhage control [J]. Biomaterials Advances, 2025, 166: 214037.

[17] 董梦真 . PVA复合水凝胶软骨修复材料的制备与性能研究 [D]. 北京: 北京石油化工学院, 2025.

[18] DONG M Z . Preparation and performance study of PVA—composite hydrogel cartilage repair materials [D]. Beijing: Beijing Institute of Petrochemical Technology, 2025.

[19] AGUILA M A L, XU Y D, WANG Y F, LIANG Y Q, ZHU S L, CUI Z D, JIANG H, LI Z Y . Balanced biocompatibility in high—viscosity hydroxypropyl methylcellulose—based sponge containing nanoconfined silver citrate nanoparticles [J]. International Journal of Biological Macromolecules, 2025, 327: 147534.

[20] 刘晓军, 阎姝 . 地锦草的化学成分及药理作用研究进展 [J]. 中国城乡企业卫生, 2022, 37(7): 66-70.

[21] LIU X J, YAN S . Recent advances in the chemical composition and pharmacological effects of polygonum aviculare [J]. Chinese Journal of Urban and Rural Enterprise Health, 2022, 37(7): 66-70.

[22] 热子亚·麦麦吐逊, 努斯热提古丽·安外尔, 祖丽皮亚·玉努斯 . 新疆地锦草提取物体外抗氧化及抑菌活性研究 [J]. 中国兽医杂志, 2018, 54(4): 90-93, 96.

[23] REZIA M, NUSRETIGUL A, ZULIPIA Y . Study on the in vitro antioxidant and antibacterial activities of extracts from Xinjiang broomrape [J]. Chinese Journal of Veterinary Medicine, 2018, 54(4): 90-93, 96.

[24] 王培军 . 地锦草黄酮醇抗肿瘤作用及其机理的研究 [D]. 河北秦皇岛: 燕山大学, 2013.

[25] WANG P J . A study on the antitumor effects and mechanisms of flavonoids from Eclipta prostrata [D]. Qinhuangdao, Hebei: Yanshan University, 2013.

[26] 文维农, 安祯祥, 何远利, 吴闵, 何松 . 基于网络药理学及动物实验探讨苗药地锦草抗肝纤维化的作用机制 [J]. 中药新药与临床药理, 2026, 37(2): 277-286.

[27] WEN W N, AN Z X, HE Y L, WU M, HE S . Exploration on the mechanism of Miao medicine Euphorbia humifusa against hepatic fibrosis based on network pharmacology and animal experiments [J]. Traditional Chinese Drug Research & Clinical Pharmacology, 2026, 37(2): 277-286.

[28] 董鹏, 唐万斌, 郭连芳 . 地锦草止血作用研究 [J]. 武警医学, 1997(2): 57-59.

[29] DONG P, TANG W B, GUO L F . A study on the hemostatic effects of Houttuynia cordata [J]. Armed Police Medicine, 1997(2): 57-59.

[30] SHI Y H, DING S, LIU T, HOU K X, LIU S H, LI F . Preparation of porous carbon spheres by templated self—assembly for rapid hemostasis [J]. Microporous and Mesoporous Materials, 2024, 363: 112808.

[31] LI X X, HUANG R N, WU D, LI D P, YIN T, XIONG S B, HUANG Q L . Micro— and nano—sized starch to inhibit gel deterioration and myofibrillar protein strands bunching by molecular interactions under multiple freeze—thaw cycles [J]. Food Hydrocolloids, 2024, 152: 109890.

[32] YANG T, ZHANG Y N, GUO L, LI D D, LIU A Q, BILAL M, XIE C, YANG R Q, GU Z X, JIANG D, WANG P . Antifreeze polysaccharides from wheat bran: The structural characterization and antifreeze mechanism [J]. Biomacromolecules, 2024, 25(7): 3877-3892.

[33] 马荣秀, 张雅伟, 戚后娟, 石彩, 黄占华 . 高孔隙率海藻酸钠—聚乙烯醇复合海绵的制备及性能 [J]. 东北林业大学学报, 2020, 48(12): 112-117.

[34] MA R X, ZHANG Y W, QI H J, SHI C, HUANG Z H . Preparation and properties of high—porosity sodium alginate—polyvinyl alcohol composite sponges [J]. Journal of Northeast Forestry University, 2020, 48(12): 112-117.

[35] 成鸿静 . 聚乙烯醇载银海绵的制备及催化性能研究 [D]. 武汉: 武汉工程大学, 2022.

[36] CHENG H J . Preparation and catalytic performance of polyvinyl alcohol—supported silver sponges [D]. Wuhan: Wuhan University of Technology, 2022.

[37] 邓嘉 . 纳米银/羟丙基甲基纤维素复合膜的制备及性能研究 [D]. 哈尔滨: 哈尔滨理工大学, 2024.

[38] DENG J . Preparation and performance study of nano—silver/hydroxypropyl methylcellulose composite membranes [D]. Harbin: Harbin University of Science and Technology, 2024.

[39] 李涛 . 马齿苋多糖脂质体制备工艺优化及其免疫增强活性初步评价 [D]. 黑龙江大庆: 黑龙江八一农垦大学, 2023.

[40] LI T . Optimization of the preparation process for portulaca oleracea polysaccharide—lipid complexes and preliminary evaluation of their immune—enhancing activity [D]. Daqing, Heilongjiang: Heilongjiang Bayi Agricultural University, 2023.

[41] ZHOU J, LI M, HUI Y W, LI C, CHANG J, CHEN B, WANG C L, GUO W, WANG T B . Hemostatic sponge based on easily prepared crosslinked gelatin and sodium alginate for wound healing [J]. Journal of Materials Science, 2024, 59(19): 8408-8426.

[42] ZHANG X D, LI J Z, PANG S, ZHU K X, SU L J, LIU J S, ZHANG X F . Mechanical properties and interface microscopic characterisation of fibre—reinforced slag—fly ash geopolymer agglutinated iron tailings filling materials [J]. Materials Today Communications, 2023, 36: 106650.

[43] TONG Y, YANG Z Y, HAO R L, GUO J N, DOU G F, MENG Z Y, LIU S C, GU R L, WU Z N, SUN Y B, HAN P, JIN Y G, GAN H . Highly efficient hemostatic cross—linked polyacrylate polymer dressings for immediate hemostasis [J]. Polymers, 2024, 16(6): 863.

[44] CHEN Z H, FU M, CHEN J, ZHANG G W, LI T, GENG Q, DAI T T . Study on the interaction mechanism and physicochemical properties of luteolin and its glucoside compounds with β—lactoglobulin [J]. LWT, 2025, 215: 117201.

[45] JÉRÔME G, HERVÉ D, PIN L, FABRICE B, CAMILLE L G, RACHIDA A, BERTRAND D, DIDIER L . Interplay between crosslinking and ice nucleation controls the porous structure of freeze—dried hydrogel scaffolds [J]. Biomaterials Advances, 2022, 139: 212973.

[46] ZHANG X, BI J F, MA Y C, LIU K Y, YI J Y . Inhibition mechanisms of ice crystal recrystallization by polysaccharides: A comparative analysis of molecular structures and cryoprotective properties [J]. Journal of the Science of Food and Agriculture, 2025, 105(13): 7124-7139.

[47] 赵誉钦, 施煜庭, 王钇 . 中草药基纺织材料的功能设计与应用研究进展 [J]. 棉纺织技术, 2026, 54(1): 92-98.

[48] ZHAO Y Q, SHI Y T, WANG Y . Recent advances in the functional design and application of textile materials derived from traditional Chinese medicinal herbs [J]. Cotton Textile Technology, 2026, 54(1): 92-98.

[49] 陈鹤鸣, 胡娇, 康花, 于萍, 程璐, 王颖 . 聚氨酯/黑种草子伤口敷料的制备与性能表征 [J]. 功能高分子学报, 2024, 37(2): 148-156.

[50] CHEN H M, HU J, KANG H, YU P, CHENG L, WANG Y . Preparation and performance characterization of polyurethane/black cumin seed wound dressings [J]. Journal of Functional Polymers, 2024, 37(2): 148-156.

[51] SHI Y, GUO Y D, MI Y D, CHENG J, DONG W, ZHANG G F, ZENG Y . Potential of UV—Vis spectroscopy for determining the mechanism of the synergistic antioxidant process of kaempferol with three other flavonoids and β—carotene [J]. Journal of Applied Spectroscopy, 2023, 90(4): 883-892.

[52] LIU C, WANG S D, ZHANG H E, LIU L P . Anti—inflammatory and pro—healing effects of acetate chitosan sponge with calcium cross—links [J]. Polymers for Advanced Technologies, 2024, 35(7): e6504.

[53] LIU Y K, NIE X F, WANG J L, ZHAO Z Q, WANG Z M, JU F . Visualizing the distribution of flavonoids in litchi (Litchi chinenis) seeds through matrix—assisted laser desorption/ionization mass spectrometry imaging [J]. Frontiers in Plant Science, 2023, 14: 1144449.

[54] DENG X, RATNAYAKE J, ALI A . Curcumin—loaded drug delivery systems for acute and chronic wound management: A review [J]. Bioengineering, 2025, 12(8): 860.

[55] LI C, WANG K, WANG C C, LI J H, ZHANG Q, SONG L J, WU Z N, ZHANG S J . A glucose—rich heteropolysaccharide from Marsdenia tenacissima (Roxb.) Wight et Arn. and its zinc—modified complex enhance immunoregulation by regulating TLR4—Myd88—NF—κB pathway [J]. International Journal of Biological Macromolecules, 2024, 283: 137529.

[56] 李江平, 黄晓燕, 王小敏, 许逊 . 紫荆花总黄酮的提取及在牙膏中的应用 [J]. 口腔护理用品工业, 2023, 33(1): 15-17.

[57] LI J P, HUANG X Y, WANG X M, XU X . Extraction of total flavonoids from redbud flowers and their application in toothpaste [J]. Oral Care Products Industry, 2023, 33(1): 15-17.

[58] WANG Y L, LIU G W, WU L J, QU H Y, SONG D L, HUANG H L, WU C L, XU M . Rational design of porous starch/hyaluronic acid composites for hemostasis [J]. International Journal of Biological Macromolecules, 2020, 158: 1319-1329.

[59] WANG S M, JI X G, CHEN S M, ZHANG C Y, WANG Y B, LIN H D, ZHAO L M . Study of double—bonded carboxymethyl chitosan/cysteamine—modified chondroitin sulfate composite dressing for hemostatic application [J]. European Polymer Journal, 2022, 162: 110875.

[60] ZHANG Y T, DAI C L, YUAN J G, WANG P . A bacteriostatic and hemostatic medical dressing based on PEG modified keratin/carboxymethyl chitosan [J]. International Journal of Polymeric Materials, 2023, 72(17): 1397-1405.

[61] 王争争, 赵邑, 王如福 . 油枣中黄酮类化合物体外抗凝血活性分析 [J]. 山西农业科学, 2022, 50(11): 1536-1541.

[62] WANG Z Z, ZHAO Y, WANG R F . Analysis of the in vitro anticoagulant activity of flavonoids in oil jujubes [J]. Shanxi Agricultural Sciences, 2022, 50(11): 1536-1541.

基金资助

自治区重大科技专项(2023A02001-2)