鳕鱼皮源医用复合止血敷料的制备及性能研究

宋雪; 刘晗; 李昭璇; 李八方; 侯虎

doi:10.12131/20210323

鳕鱼皮源医用复合止血敷料的制备及性能研究

doi: 10.12131/20210323

宋雪^1,,
刘晗¹,
李昭璇¹,
李八方¹,
侯虎^{1, 2, ,}

1.
中国海洋大学食品科学与工程学院，山东青岛 266003
2.
青岛海洋科学与技术试点国家实验室，山东青岛 266237

基金项目: 国家重点研发计划项目 (2019YFD0901905)；山东省泰山学者项目 (tsqn202103033)

详细信息

作者简介:
宋雪：宋　雪 (1997—)，女，硕士研究生，研究方向为水生生物胶原蛋白。E-mail: 291686910@qq.com

通讯作者:
侯　虎 (1984—)，男，教授，博士，从事海洋活性物质研究。E-mail: houhu@ouc.edu.cn, houhuouc@163.com

中图分类号: R 318.08
计量
- 文章访问数: 75
- HTML全文浏览量: 27
- PDF下载量: 3
- 被引次数: 0
出版历程
- 收稿日期: 2021-11-01
- 修回日期: 2021-12-13
- 录用日期: 2022-01-10
- 网络出版日期: 2022-01-28
- 刊出日期: 2022-04-01

Preparation and properties of medical compound hemostasis dressing from Pacific cod skin

SONG Xue^1
,,
LIU Han¹,
LI Zhaoxuan¹,
LI Bafang¹,
HOU Hu^{1, 2
, ,}

1.
College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China
2.
Qingdao Pilot National Laboratory for Marine Science and Technology, Qingdao 266237, China

摘要

摘要: 以太平洋鳕 (Gadus macrocephalus) 鱼皮明胶为原料，通过复配海藻酸钠得到一种可吸收复合止血敷料，并对其机械性能、止血效果、止血机理和生物相容性进行评价。结果表明，明胶质量浓度为10 mg·mL⁻¹时制备的止血敷料具有较高的机械强度。体内止血评价结果显示，复合止血敷料对大鼠股动脉止血、肝创面止血和断尾止血模型均有良好的效果，止血时间分别为 (64±9)、(108±4) 和 (230±25) s，与市售明胶海绵的止血效果相当。复合止血敷料可缩短活化部分凝血活酶时间 (Activated partial thromboplastin time, APTT) 和凝血酶时间 (Thrombin time, TT)，激活内源性凝血系统和共同性凝血途径，以及促进血栓烷素B₂(TXB₂)、血小板第四因子 (PF4) 和P-选择素的释放，达到快速止血效果。生物相容性实验结果证实，该复合敷料无急性毒性、无刺激性且溶血率小于5%，达到医用材料的行业标准。该研究结果为开发新型医用敷料并实现鳕鱼皮高值化利用提供了参考和理论依据。
- 鳕鱼皮明胶 /
- 海藻酸钠 /
- 复合止血海绵 /
- 生物相容性 /
- 止血性能
Abstract: In this study, an absorbable composite hemostatic dressing was prepared by combining sodium alginate with Pacific cod (Gadus macrocephalus) skin gelatin, and its mechanical properties, hemostatic effect, hemostatic mechanism and biocompatibility were evaluated. The results show that the composite hemostatic dressing had high mechanical strength with 1% of gelatin concentration. Results of hemostatic evaluation in vivo indicate that the dressing had good hemostatic effect on the femoral artery, liver wound and tail hemostasis models of rats, and the hemostatic time was (64±9), (108±4) and (230±25) s, respectively, which was similar with the hemostatic effect of commercial gelatin sponge. The dressing could shorten activated partial thromboplastin time (APTT) and thrombin time (TT), which activated endogenous coagulation and common coagulation pathway, and promoted the release of thromboxane-B₂ (TXB₂), platelet factor-4 (PF4) and P-selectin to achieve rapid hemostatic effect. Biocompatibility experiments show that the composite dressing had no acute toxicity or irritation and the hemolysis rate was less than 5%, which meets the standards of medical materials. The study provides reference and theoretical basis for developing new medical dressing and realizing high-value utilization of Pacific cod skin.
- Pacific cod skin gelatin /
- Sodium alginate /
- Composite hemostatic sponge /
- Biocompatibility /
- Hemostatic property

HTML全文

图 1 鳕鱼皮明胶的SDS-PAGE电泳图

Figure 1. SDS-PAGE patterns of Pacific cod skin gelatin

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图 2 复合止血敷料的止血性能评价

Figure 2. Hemostatic evaluation in vivo with different model

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图 3 不同样品对活化部分凝血酶时间、凝血酶原时间和凝血酶时间血小板活性释放因子血栓烷素B₂、血小板第四因子和P-选择素的影响

Figure 3. Effect of different samples on APTT, PT, TT and release of platelet active factors (TXB₂, PF4 and P-selection)

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图 4 注射24 h、48 h和72 h后的皮内刺激情况

Figure 4. Intradermal stimulation at 24^th, 48^th and 72^nd hour after injection

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表 1 不同明胶浓度对复合止血敷料理化性能的影响

Table 1. Physical and chemical properties of composite hemostatic sponge with different gelatin concentration

明胶质量浓度 Gelatin mass concentration/ (mg·mL⁻¹)	抗张强度 Tensile strength/MPa	断裂伸长率 Elongation at break/%	吸水倍数 Water absorption ratio	持水率 Water retention ratio/%	交联度 Degree of crosslinking/%
1	0.010 0±0.003 7^a	7.54±0.37^a	25.47±0.14^a	21.00±0.20^a	88.90±0.50^a
5	0.037 2±0.004 2^b	7.43±1.31^a	31.82±0.80^b	28.03±1.03^b	63.13±0.63^b
10	0.082 3±0.002 2^c	6.81±0.21^a	49.20±2.24^c	30.49±2.18^b	56.68±0.33^c
15	0.085 9±0.003 6^c	3.49±0.72^b	38.15±2.24^d	37.35±2.37^c	43.36±2.86^d
20	0.079 5±0.005 6^c	1.36±0.30^c	23.89±0.34^a	37.99±0.30^c	44.45±0.57^d
注：同列字母不同者表示显著差异 (P<0.05)。 Note: Values with different letters within the same column have significant difference (P<0.05).

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表 2 急性全身毒性试验、皮肤刺激试验和溶血试验结果

Table 2. Results of acute systemic toxicity assay, dermal irritation test and hemolysis ratio

	实验组 Experimental group	阴性对照组 Negative control group	阳性对照组 Positive control group
急性毒性试验 Acute systemic toxicity assay
第0小时体质量 Body mass at 0^th hour/kg	0.167 7±0.008 2	0.174 0±0.004 6	0.185 3±0.005 0
第24小时体质量 Body mass at 24^th hour/kg	0.172 8±0.007 4	0.177 9±0.009 7	0.186 2±0.004 2
第48小时体质量 Body mass at 48^th hour/kg	0.184 3±0.008 3	0.182 9±0.004 9	0.178 5±0.007 4
第72小时体质量 Body mass at 72^nd hour/kg	0.183 9±0.009 8	0.182 7±0.013 7	0.179 8±0.007 5
皮肤刺激试验 Dermal irritation test
第24小时红斑总数 Sum of erythema at 24^th hour/个	4	0
第48小时红斑总数 Sum of erythema at 48^th hour/个	0	0
第72小时红斑总数 Sum of erythema at 72^nd hour/个	0	0
原发性刺激指数 Primary irritation index PII	0.22	0
溶血试验 Hemolysis test
溶血率 Hemolysis ratio/%	1.51±0.30	0.00	100.00

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