Abstract：
BACKGROUND: 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.
OBJECTIVE: 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.
RESULTS: 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.
CONCLUSIONS: Microneedle roller can promote the transdermal absorption of crossbow-medicine liquid, and crossbow-medicine needle therapy has good safety.
OBJECTIVE: 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.
RESULTS: 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.
CONCLUSIONS: Microneedle roller can promote the transdermal absorption of crossbow-medicine liquid, and crossbow-medicine needle therapy has good safety.
摘要：
背景：十字弓药物针疗法（微针辊结合十字弓药物）是中国苗医的外治法之一。这是一种将针灸与中草药相结合的方法，疼痛的临床治疗中广泛使用。
目的：观察微针辊经皮给药对经皮吸收的促进作用，并讨论了经弓药物针疗法的透皮吸收特性和安全性。
方法：根据我们先前研究中对弓药方主要成分含量的测定，本实验进行了体外和体内实验，并以大鼠皮肤为穿透屏障。对于体外实验，采用改良的Franz扩散池法测定经弓药液有效成分的透皮吸收速率和24h累积透皮吸收量。对于体内实验，采用组织匀浆法比较上述两种给药方式在不同时间点吸收的十字弓药液的皮肤滞留量和血浆浓度。此外，用苏木精-伊红(HE)染色检测弓药针对大鼠皮肤角质层形态结构的影响。根据皮肤刺激试验的评分标准,评价经弓-药针治疗的安全性。
结果：1.体外实验:微针-滚针组和弓-药液给药组,在所有四种成分中都确定了透皮给药的效果，绿原酸,新乌头碱和次乌头碱。微针辊组各成分的24h累积透皮吸收量和透皮吸收率均显著高于罗弓药液组(均P<0.05)。2.体内实验:微针辊和弓药液应用均能促进药物活性成分在皮肤中的透皮吸收，并保留在皮肤结构中。给药8h后，Anabasine的总滞留量，绿原酸,前一组大鼠皮肤中的新乌头碱和次乌头碱含量明显高于后一组(均P<0.05)。3.HE染色:空白组,角质层在活跃的表皮上表现出均匀的带状分布，与表皮有密切的联系，角质层没有脱落或细胞解离。十字药液组角质层比较完整,一小部分脱落或细胞解离，松散的排列和与表皮的松散连接。在微针辊组中，皮肤有毛孔通道，角质层松散脱落，表现为自由状态的带状分布和高度分离。弓药针组角质层松弛，破碎和脱落，与活性表皮分离，呈游离状态的带状分布。4.
结果：无明显红斑，在用微针滚轮处理的大鼠皮肤中观察到水肿和皮肤隆起，十字弓-药液和十字弓-药针。此外,皮肤刺激反应评分为0。
结论：微针辊能促进十字弓药液的透皮吸收，和十字弓药物针治疗具有良好的安全性。
目的：观察微针辊经皮给药对经皮吸收的促进作用，并讨论了经弓药物针疗法的透皮吸收特性和安全性。
方法：根据我们先前研究中对弓药方主要成分含量的测定，本实验进行了体外和体内实验，并以大鼠皮肤为穿透屏障。对于体外实验，采用改良的Franz扩散池法测定经弓药液有效成分的透皮吸收速率和24h累积透皮吸收量。对于体内实验，采用组织匀浆法比较上述两种给药方式在不同时间点吸收的十字弓药液的皮肤滞留量和血浆浓度。此外，用苏木精-伊红(HE)染色检测弓药针对大鼠皮肤角质层形态结构的影响。根据皮肤刺激试验的评分标准,评价经弓-药针治疗的安全性。
结果：1.体外实验:微针-滚针组和弓-药液给药组,在所有四种成分中都确定了透皮给药的效果，绿原酸,新乌头碱和次乌头碱。微针辊组各成分的24h累积透皮吸收量和透皮吸收率均显著高于罗弓药液组(均P<0.05)。2.体内实验:微针辊和弓药液应用均能促进药物活性成分在皮肤中的透皮吸收，并保留在皮肤结构中。给药8h后，Anabasine的总滞留量，绿原酸,前一组大鼠皮肤中的新乌头碱和次乌头碱含量明显高于后一组(均P<0.05)。3.HE染色:空白组,角质层在活跃的表皮上表现出均匀的带状分布，与表皮有密切的联系，角质层没有脱落或细胞解离。十字药液组角质层比较完整,一小部分脱落或细胞解离，松散的排列和与表皮的松散连接。在微针辊组中，皮肤有毛孔通道，角质层松散脱落，表现为自由状态的带状分布和高度分离。弓药针组角质层松弛，破碎和脱落，与活性表皮分离，呈游离状态的带状分布。4.
结果：无明显红斑，在用微针滚轮处理的大鼠皮肤中观察到水肿和皮肤隆起，十字弓-药液和十字弓-药针。此外,皮肤刺激反应评分为0。
结论：微针辊能促进十字弓药液的透皮吸收，和十字弓药物针治疗具有良好的安全性。
