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微针滚轮对促进弩药经皮给药透皮吸收的作用及弩药针疗法的安全性:一项实验研究。

Effect of microneedle roller on promoting transdermal absorption of crossbow-medicine liquid via transdermal administration of Traditional Chinese Medicine and the safety of crossbow-medicine needle therapy: An experimental study.

机构信息

School of Acupuncture-Moxibustion and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China.

Guizhou University of Traditional Chinese Medicine, Guiyang, 550025, China.

出版信息

J Ethnopharmacol. 2023 Dec 5;317:116751. doi: 10.1016/j.jep.2023.116751. Epub 2023 Jun 7.

DOI:10.1016/j.jep.2023.116751
PMID:37295573
Abstract

ETHNOPHARMACOLOGY RELEVANCE

Crossbow-medicine needle therapy (microneedle roller combined with crossbow-medicine) is one of the external treatment methods of Miao Medicine in China. It is a way of combining acupuncture with Chinese herbal medicine, which is widely used in clinical treatment of pain.

AIM OF THE STUDY

To observe the transdermal absorption promoting effect of microneedle roller via transdermal administration, and to discuss the transdermal absorption characteristics and the safety of crossbow-medicine needle therapy.

METHODS

Based on the determination of the content of the main components of crossbow-medicine prescription in our previous research, the present experiment was conducted in-vitro and in-vivo experiments and the skin of rats was used as the penetration barrier. For in-vitro experiment, the modified Franz diffusion cell method was used to determine the transdermal absorption rate and 24h cumulative transdermal absorption amount of the active ingredients of crossbow-medicine liquid. For in-vivo experiment, tissue homogenization was applied to compare the skin retention amount and plasma concentration of crossbow-medicine liquid absorbed at different time points via the aforementioned two modes of administration. Furthermore, the effect of crossbow-medicine needle on the morphological structure of rat skin stratum corneum was detected by hematoxylin-eosin (HE) staining. The safety of crossbow-medicine needle therapy was evaluated according to the scoring criteria of the skin irritation test.

RESULTS

  1. In-vitro experiment: In the microneedle-roller group and crossbow-medicine liquid application group, the effect of transdermal delivery was identified in all the four ingredients of anabasine, chlorogenic acid, mesaconitine and hypaconitine. The 24h cumulative transdermal absorption amount and transdermal absorption rate of each ingredient in microneedle-roller group were significantly higher than those in crossbow-medicine liquid application group (all P < 0.05). 2. In-vivo experiment: Both microneedle-roller and crossbow-medicine liquid application could promote the transdermal absorption of the active ingredients of the drug in the skin and retain in the skin structure. After 8h of administration, the total retention amount of anabasine, chlorogenic acid, mesaconitine and hypaconitine in the skin of rats in the former group was significantly higher than that in the latter group (all P < 0.05). 3. HE staining: In the blank group, the stratum corneum showed an evenly zonal distribution on the active epidermis, and had a close connection with the epidermis, without exfoliation or cell dissociation of the stratum corneum. The crossbow-medicine liquid group had a relatively complete stratum corneum, with a small proportion of exfoliation or cell dissociation, loose arrangement and loose connection with the epidermis. In the microneedle-roller group, the skin had pore channels, and the stratum corneum was loose and exfoliated, which showed zonal distribution in a free state and a high degree of separation. The crossbow-medicine needle group had loose the stratum corneum, broken and exfoliated, which was separated from the active epidermis and showed zonal distribution in a free state. 4.

SAFETY

No obvious erythema, edema and skin protuberance were observed in the skin of rats treated with microneedle roller, crossbow-medicine liquid and crossbow-medicine needle. Additionally, the skin irritative response score was 0.

CONCLUSION

Microneedle roller can promote the transdermal absorption of crossbow-medicine liquid, and crossbow-medicine needle therapy has good safety.

摘要

民族药理学相关性

弩药针疗法(微针滚轮联合弩药)是中国苗族医学的一种外部治疗方法。它是一种将针灸与中草药相结合的方法,广泛应用于疼痛的临床治疗。

研究目的

观察微针滚轮经皮给药的透皮促进作用,探讨弩药针疗法的透皮吸收特征和安全性。

方法

基于我们之前研究中弩药处方主要成分的含量测定,本实验进行了体内外实验,以大鼠皮肤为渗透屏障。对于体外实验,采用改良 Franz 扩散池法测定弩药液中活性成分的透皮吸收率和 24 小时累积透皮吸收量。对于体内实验,采用组织匀浆法比较两种给药方式在不同时间点吸收的弩药液的皮肤滞留量和血浆浓度。此外,通过苏木精-伊红(HE)染色检测弩药针对大鼠皮肤角质层形态结构的影响。根据皮肤刺激性试验评分标准评价弩药针疗法的安全性。

结果

  1. 体外实验:在微针滚轮组和弩药液应用组中,四种成分(烟碱、绿原酸、乌头碱和次乌头碱)均表现出经皮传递作用。微针滚轮组中各成分的 24 小时累积透皮吸收量和透皮吸收率均明显高于弩药液应用组(均 P<0.05)。2. 体内实验:微针滚轮和弩药液应用均可促进药物活性成分在皮肤中的透皮吸收并在皮肤结构中保留。给药 8 小时后,前者大鼠皮肤中烟碱、绿原酸、乌头碱和次乌头碱的总滞留量明显高于后者(均 P<0.05)。3. HE 染色:空白组活性表皮角质层呈均匀带状分布,与表皮紧密相连,无角质层剥落或细胞解离。弩药液组角质层相对完整,有少量剥落或细胞解离,排列疏松,与表皮连接松散。微针滚轮组皮肤有孔道,角质层疏松剥落,呈自由状态带状分布,分离度高。弩药针组角质层松散,破裂剥落,与活性表皮分离,呈自由状态带状分布。4. 安全性:微针滚轮、弩药液和弩药针处理的大鼠皮肤未见明显红斑、水肿和皮肤隆起,皮肤刺激性反应评分均为 0。

结论

微针滚轮可以促进弩药液的经皮吸收,弩药针疗法具有良好的安全性。

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