表皮细胞生长因子/伤科黄水/聚乙烯醇水凝胶创面敷料的制备及其性能

doi:10.19894/j.issn.1000-0518.250251

摘要/Abstract

摘要：

伤科黄水（Shangkehuangshui，HS）是佛山市中医院的一种院内制剂，用于治疗骨骼损伤以及软组织损伤，具有抗炎消肿、活血化瘀和祛腐生新的功效。目前，临床上一般通过“湿敷”法给药，存在药效短、药物利用率低和操作不便等一些弊端。本文以医用辅料聚乙烯醇（PVA）为辅料，采用辐照法制备了含伤科黄水的水凝胶。该水凝胶拉伸强度可达70 kPa，断裂伸长率达350%以上。同时，体外药物释放实验显示无论HS中生物碱类组分还是非生物碱组分均能实现良好的释放。细胞增殖实验显示加入人源表皮细胞生长因子（Epidermal growth factor， EGF）后，1 d时，在PVA/EGF和PVA/HS水凝胶中培养的NIH3T3数量较PVA组明显增加，约20%； 7 d后可提高30%以上，效果显著（p＜0.0001）。大鼠的皮肤修复实验证明HS/PVA水凝胶具有与伤科黄水制剂湿敷相近的促进皮肤损伤修复效果，且含有EGF的EGF/HS/PVA水凝胶具有更好的促皮肤组织修复能力。总之，采用辐照法制备的EGF/HS/PVA水凝胶产品贴敷能够实现甚至超越“伤科黄水”湿敷的药物效果。

关键词: 聚乙烯醇, 伤科黄水, 表皮细胞生长因子, 载药水凝胶

Abstract:

Shangkehuangshui （HS） is an in-house preparation of Foshan Traditional Chinese Medicine Hospital， used for the treatment of bone and soft tissue injuries. It exhibits anti-inflammatory， hemostatic， blood circulation-promoting， blood stasis-removing， and new tissue growth-enhancing effects. Currently， in clinical practice， HS is predominantly administered via the “wet compress” method， which has several limitations， including short duration of efficacy， low drug utilization rates， and operational inconvenience. In this study， a hydrogel containing HS was prepared using polyvinyl alcohol （PVA） as a medical excipient through irradiation. The hydrogel tensile strength reaches up to 70 kPa， and elongation at break surpasses 350%. Furthermore， in vitro drug release experiments revealed that both alkaloid and non-alkaloid components of HS achieve effective release. Cell proliferation assays indicated that the number of NIH3T3 cells cultured in PVA/EGF and PVA/HS hydrogels increased significantly by approximately 20% compared to the PVA group within one day following the addition of human epidermal growth factor （EGF）. After seven days， the increase exceeded 30%， with statistically significant results （p＜0.0001）. Rat skin repair experiments demonstrated that HS/PVA hydrogel exhibited comparable efficacy in promoting skin damage repair to the wet compress method of Traumatology Yellow Water Preparation. Moreover， EGF/HS/PVA hydrogel containing EGF showed superior capability in enhancing skin tissue repair. In conclusion， the application of EGF/HS/PVA hydrogel products prepared via irradiation can achieve or even surpass the therapeutic effects of Shangkehuangshui wet application.

Key words: Polyvinyl alcohol, Shangkehuangshui, Epidermal growth factor, Wound dressing

中图分类号:

O632

常永丰, 何明丰, 雷凯君, 郑芳昊, 周小松, 武振旭, 焦自学, 章培标. 表皮细胞生长因子/伤科黄水/聚乙烯醇水凝胶创面敷料的制备及其性能[J]. 应用化学, 2025, 42(12): 1649-1660.

Yong-Feng CHANG, Ming-Feng HE, Kai-Jun LEI, Fang-Hao ZHENG, Xiao-Song ZHOU, Zhen-Xu WU, Zi-Xue JIAO, Pei-Biao ZHANG. Preparation and Properties of Epidermal Growth Factor/Shangkehuangshui/Polyvinyl Alcohol Hydrogel Wound Dressing[J]. Chinese Journal of Applied Chemistry, 2025, 42(12): 1649-1660.

图/表 12

图1 （A）不同组别水凝胶的拉伸强度；（B）不同组别水凝胶的断裂伸长率

Fig.1 （A） Tensile strength at break of different groups of hydrogels；（B） Elongation at break of different groups of hydrogels

图2 不同辐照剂量下水凝胶中主要成分在PBS中的释放

Fig.2 Release of hydrogel with different “Shangkehuangshui” content in PBS under different radiation dose

图3 1（A）、3（B）和7 d（C）后水凝胶中不同组分对于细胞活性的影响

Fig.3 Influence of different components in hydrogels on cell activity（A.1 d； B.3 d； C.7 d）

图4 水凝胶中PVA和“伤科黄水”对于细胞活性的影响（1、3和7 d）

Fig.4 Effect of PVA and “Shangkehuangshui” on cell activity in hydrogels （1， 3 and 7 d）

图5 水凝胶中加入EGF生长因子对于细胞活性的影响（1、3和7 d）

Fig.5 The effect of EGF growth factor on cell viability in hydrogels （1， 3 and 7 d）

图6 不同条件下大鼠伤口1、3、7、10和14 d愈合情况A.CON； B.PVA； C.PVA/EGF1； D.PVA/EGF10； E.PVA/EGF100； F.HP； G.HP/EGF10； H.HP/EGF10； I.HP/EGF100

Fig.6 Healing status of rat wounds in 1， 3， 7， 10 and 14 d under different conditions

图7 不同材料下14 d大鼠伤口组织切片染色（H&E）A.CON； B.PVA； C.PVA/EGF1； D.PVA/EGF10； E.PVA/EGF100； F.HP； G.HP/EGF1； H.HP/EGF10； I.HP/EGF100

Fig.7 H&E staining of wound margin on 14 d

图8 不同材料下14 d大鼠伤口组织切片染色（Masson）A.CON； B.PVA； C.PVA/EGF1； D.PVA/EGF10； E.PVA/EGF100； F.HP； G.HP/EGF1； H.HP/EGF10； I.HP/EGF100

Fig.8 Staining of 14 d rat wound tissue slices under different materials （Masson）

图9 伤口组织的免疫荧光染色分析A.CON； B.PVA； C.PVA/EGF1； D.PVA/EGF10； E.PVA/EGF100； F.HP； G.HP/EGF1； H.HP/EGF10； I.HP/EGF100

Fig.9 Immunofluorescence staining analysis of wound tissue

表1 不同组别皮肤创伤大鼠的血常规

Table 1 Routine blood count of mice with skin trauma in different groups

	MOD	PVA	PVA/EGF1	PVA/EGF10	PVA/EGF100	HP/EGF	HP/EGF1	HP/EGF10	HP/EGF100
10^-9·L·WBC	12.8	6.6	16.1	13.3	6.3	7.7	7.4	8.3	10.4
10^-9·L·LYM	11.1	4.8	13.0	9.6	5.0	6.4	6.0	6.2	8.5
10^-9·L·MO	0.3	0.2	0.3	0.5	0.2	0.1	0.1	0.3	0.2
10^-9·L·GRAN	1.4	1.6	2.8	3.2	1.1	1.2	1.3	1.8	1.7
LYM/%	86.6	73.0	80.5	72.4	79.1	82.4	80.1	74.3	81.4
MO/%	2.7	3.2	2.1	3.9	2.8	1.9	2.0	3.5	2.0
GRAN/%	10.7	23.8	17.4	23.7	18.1	15.7	17.9	22.2	16.6
10^-12·L·RBC	5.66	6.61	4.98	4.13	4.99	6.27	5.52	6.09	5.81
HGB/（g?L^-1）	124	146	139	89	104	129	120	121	119
HCT/%	32.9	38.5	30.6	26.0	27.9	34.6	32.5	32.3	32.7
MCV/fL	58.3	58.3	61.6	63.1	56.0	55.3	59.0	53.1	56.4
MCH/pg	21.9	22.0	27.9	21.5	20.8	20.5	21.7	19.8	20.4
MCHC/（g?L^-1）	376	379	454	342	372	372	369	374	363
RDW/%	12.1	12.5	16.1	14.3	12.4	12.6	12.2	12.5	11.7
10^-9·L·PLT	1184	439	740	906	534	791	584	823	694
MPV/fL	6.2	7.4	6.3	7.8	7.8	6.9	6.7	7.0	6.2
PDW	16.6	17.3	17.3	17.4	17.6	16.6	17.0	17.0	16.6
PCT/%	0.32	0.324	0.001	0.001	0.416	0.545	0.391	0.576	0.430

表2 正常大鼠的血液指标参考范围

Table 2 Reference range of blood parameters in normal mice

Blood parameter	10^-12 RBC/L	10^-9 PLT/L	10^-9 WBC/L	LYM/%	MO/%
Reference range	6.36~9.42	592~2972	1.8~10.7	55.8~91.6	6.6~38.9

表3 不同组别皮肤创伤大鼠的肝肾功能

Table 3 Liver and kidney function in different groups of mice with skin trauma

	MOD	PVA	PVA/EGF1	PVA/EGF10	PVA/EGF100	HP/EGF	HP/EGF1	HP/EGF10	HP/EGF100
UREA/（mol?L^-1）	2.728	7.581	5.774	8.920	6.806	6.491	6.258	6.297	8.126
CREA/（μmol?L^-1）	19.776	48.790	35.739	35.194	48.265	41.917	38.441	41.370	36.679
UA/（μmol?L^-1）	72.830	42.397	105.011	60.451	72.492	51.843	42.836	66.561	64.561
AST/（U?L^-1）	75.756	97.828	72.874	73.987	111.194	99.854	98.395	119.196	70.174
ALT/（U?L^-1）	14.452	22.385	26.184	34.680	39.945	33.075	31.484	35.652	32.171
ALP/（U?L^-1）	45.145	148.724	98.412	149.387	116.321	132.186	137.857	146.472	163.149
TBA/（μmol?L^-1）	24.806	23.440	9.656	14.849	11.812	15.310	33.232	17.144	174.140
ALB/（U?L^-1）	14.946	30.967	30.856	25.255	27.999	29.573	30.700	31.072	27.772
γ-GT/（U?L^-1）	3.153	0.090	0.758	0.881	6.191	1.022	2.889	2.532	5.901
TBIL/（μmol?L^-1）	18.377	9.836	12.194	10.784	9.527	12.395	10.637	7.307	3.299
DBIL/（μmol?L^-1）	11.913	2.313	5.328	1.538	3.033	4.015	2.989	2.575	1.418

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