Huoluo Xiaoling Dan is a classical prescription commonly used for blood circulation and pain relief in clinic with obvious effects. To make it directly treat lesion and improve the effect, this research optimized the preparation process of Huoluo Xiaoling gel paste and further evaluated its in vitro transdermal absorption performance, so as to provide a scientific basis for its development and utilization. Using primary viscosity, holding viscosity, and sensory score as evaluation indexes, the matrix amount of gel paste was determined by the single factor test and Box-Behnken response surface method. The ultra-performance liquid chromatography(UPLC) method was established to determine the content of eight active ingredients, including Danshensu, ferulic acid, salvianolic acid B, salvianolic acid A, ligustilide, tanshinone Ⅱ_A, 11-keto-β-boswellic(KBA), and 3-acetyl-11-keto-β-boswellic acid(AKBA). A mo-dified Franz diffusion cell method was used to evaluate and compare the absorption properties of the gel paste without volatile oil and with volatile oil microemulsion. The results showed that the optimal prescription for Huoluo Xiaoling gel paste matrix was NP700(1.35 g), glycerol(7.00 g), micropowder silica gel(1.25 g), sodium carboxymethyl cellulose(0.20 g), tartaric acid(0.06 g), and glyceryl aluminum(0.04 g). The mass fractions of eight active ingredients in the paste were successively 0.48, 0.014, 0.95, 0.39, 0.57, 0.055, 0.35, and 0.97 mg·g~(-1). The results of the in vitro transdermal absorption test showed that the addition of the volatile oil or the volatile oil microemulsion promoted the transdermal absorption of the active ingredients, and the law of drug penetration conformed to the zero equation or the Higuchi equation. The gel paste prepared by the optimal prescription has good appearance and adhesion, with no residue, and has the characteristics of skeletal slow-release preparation, which is easy to reduce the number of administration, la-ying a foundation for the development of new external dosage forms of Huoluo Xiaoling Dan.
Administration, Cutaneous ; Skin Absorption ; Chromatography, Liquid ; Oils, Volatile ; Viscosity

In this experiment, Panax notoginseng saponins chitosan nanoparticles(PNS-NPs) were prepared by self-assembly and their appearance, particle size, encapsulation efficiency, drug loading, polydispersity index(PDI), Zeta potential, and microstructure were characterized. The prepared PNS-NPs were intact in structure, with an average particle size of(209±0.258) nm, encapsulation efficiency of 42.34%±0.28%, a drug loading of 37.63%±0.85%, and a Zeta potential of(39.8±3.122) mV. The intestinal absorption of PNS-NPs in rats was further studied. The established HPLC method of PNS was employed to investigate the effects of pH, perfusion rate, and different drugs(PNS raw materials, Xuesaitong Capsules, and PNS-NPs). The absorption rate constant(K_a) and apparent permeability coefficient(P_(app)) in the duodenum, jejunum, ileum, and colon were calculated and analyzed. As illustrated by the results, the intestinal absorption of PNS-NPs was increased in the perfusion solution at pH 6.8(P<0.05), and perfusion rate had no significant effect on the K_a and P_(app) of PNS-NPs. The intestinal absorption of PNS-NPs was significantly different from that of PNS raw materials and Xuesaitong Capsules(P<0.05), and the intestinal absorption of PNS-NPs was significantly improved.
Animals ; Chitosan/pharmacology* ; Intestinal Absorption ; Nanoparticles ; Panax notoginseng/chemistry* ; Rats ; Saponins/pharmacology*

This study aims to establish a method for determination of paeonol(Pae), eugenol(Eug), and piperine(Pip) content in receptor liquid and research on the permeability and pharmacokinetics of Huoxue Zhitong gel patch and microemulsion gel. The Franz diffusion experiment was conducted to assess the percutaneous permeability, and the microdialysis method was employed to assess pharmacokinetics of Huoxue Zhitong gel patch and microemulsion gel. The content of Pae, Eug, and Pip in receptor liquid in vitro and in vivo was determined by HPLC and UPLC-MS. The Q_n and J_(ss) of Pae, Eug, and Pip in the gel patch were significantly higher than those in the microemulsion gel, indicating that the drug release was faster in the gel patch. The C_(max), AUC_(0-760), and MRT of Pae, Eug, and Pip in the gel patch were higher than those in the microemulsion gel, indicating that the gel patch can promote the penetration and prolong the skin residence of the drug. The results of this study provide reference for improving the dosage form of Huoxue Zhitong patch.
Administration, Cutaneous ; Chromatography, Liquid ; Emulsions ; Permeability ; Skin/metabolism* ; Skin Absorption ; Tandem Mass Spectrometry

This paper aims to study the difference in the intestinal absorption kinetics of main active components of Sini decoction and its separated recipes and explain the scientificity and rationality of the compatibility of Sini Decoction. A in situ intestinal perfusion rat model was established to evaluate the differences in the absorption of benzoylmesaconine, benzoylaconine, benzoylhypacoitine, mesaconitine, hypaconitine, glycyrrhizic acid, liquiritin and 6-gingerol from Sini Decoction and its separated recipes in the duodenum, jejunum and ileum by high performance liquid chromatography(HPLC). The results indicated that the Sini Decoction group was superior to the Aconiti Lateralis Radix Praeparata group in terms of absorption degree and rate for aconitum alkaloids. The absorption of benzoylmesaconine and hypaconitine in the duodenum, jejunum and ileum was faster and stronger in the Sini Decoction group(P<0.05). The absorption degree of glycyrrhizic acid in the duodenum was significantly higher in the Sini Decoction group than in the Glycyrrhizae Radix et Rhizoma group and the Glycyrrhizae Radix et Rhizoma-Zingiberis Rhizoma group(P<0.05). The absorption rate and degree of 6-gingerol in the ileum in the Sini Decoction group were significantly higher than those in the Zingiberis Rhizoma group(P<0.05). In short, Zingiberis Rhizoma and Glycyrrhizae Radix et Rhizoma can promote the absorption of aconitum alkaloids in different intestinal segments, which reflects the scientific composition of Sini Decoction.
Aconitine/analogs & derivatives* ; Aconitum ; Alkaloids ; Animals ; Catechols ; Drugs, Chinese Herbal ; Fatty Alcohols ; Glycyrrhizic Acid ; Intestinal Absorption ; Kinetics ; Rats

Laportea bulbifera extract is effective in resisting inflammation and shows a good therapeutic effect on rheumatoid arthritis in rats. However, the absorption characteristics of active components in L. bulbifera extract in Caco-2 cells are still unclear, which limits the in-depth development of L. bulbifera resources. The purpose of this study was to investigate the absorption and transport mechanism of the active components of L. bulbifera extract in the Caco-2 cell model and explore the effects of different factors(concentration, time, pH value, temperature, and efflux transporter inhibitor) on its uptake and transport. The results showed that L. bulbifera extract at the concentration of 2.0-8.0 mg·mL~(-1) showed no toxicity to Caco-2 cells. The uptake and transport of L. bulbifera extract in the Caco-2 cell model were concentration-dependent and time-dependent. The main absorption mechanism was passive diffusion, and acidic condition(pH 5.0-6.0) and 37 ℃ were more favorable for drug absorption. P_(app)>1.0×10~(-6 )cm·s~(-1) of each component indicated that L. bulbifera was a moderately absorbed drug. P-gp, MRP2, and BCRP were not involved in its uptake and transport.
Humans ; Rats ; Animals ; Caco-2 Cells ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Intestinal Absorption ; Neoplasm Proteins/metabolism* ; Urticaceae ; Biological Transport ; Plant Extracts/pharmacology*

The present study is to investigate the absorption characteristics of the main components in Polygonum orientale extract in normal and isoproterenol-induced myocardial ischemia model rats with everted intestinal sac models. Intestinal sac fluid samples were collected in different part of intestine(duodenum, jejunum, ileum, colon) at different time after administration of different concentration of P. orientale extract(5.0,10.0, 20.0 mg·mL~(-1)). An UPLC-TQD method was employed for the determination of six components including orientin, isoorientin, vitexin, protocatechuic acid, kaempferol-3-O-β-D-glucoside and quercitrin in the intestinal sac samples. The absorption rate and cumulative absorption were calculated to analyze the intestinal absorption characteristics of six components in normal and myocardial ischemia model rats. The P-glycoprotein(P-gp) inhibitor was applied to investigate influence of intestinal absorption of six components in P. orientale extract. The results showed that the main absorption sites were concentrated on the duodenum at low concentration, while they were the colon at the medium concentration and the ileum at high concentration in control groups. In the condition of myocardial ischemia model, the main absorption sites focus on the ileum and jejunum at low concentration; the main absorption sites were in the ileum at the medium concentration and main absorption sites were the duodenum and ileum at high concentration. Compared with the normal group, the absorption rate and cumulative absorption of the six components significantly decreased in the model group. P-gp inhibitor markedly increased the absorption rate and cumulative absorption of six components in the model group, inferring that the 6 components may be the substrates of P-gp, and the mechanism needs further study. In this study, it is revealed that the six components of P. orientale extract can be absorbed into the intestinal sac, and it is an effective method to assess the intestinal absorption characteristics of P. orientale extract through everted intestinal sac model, providing data support for the clinical application and further development of P. orientale.
Animals ; Intestinal Absorption ; Intestines ; Isoproterenol ; Myocardial Ischemia/chemically induced* ; Polygonum ; Rats ; Rats, Sprague-Dawley

To compare the effect of hot or warm property of Chinese medicine(CM) on the skin toxicity of essential oils(EOs) as penetration enhancer in vitro and in vivo, and explore the mechanism. EOs were extracted from WIM of Bichengqie(Litseae Fructus), Dingxiang(Flos Syzygii Aromatici), Huajiao(Pericarpium Zanthoxyli Bungeani), and Xiaohuixiang(Fructus Foeniculi) with warm property, and Ganjiang(Rhizoma Zingiberis), Gaoliangjiang(Rhizoma Alpiniae Officinari), Hujiao(Fructus Piperis), and Wuzhuyu(Fructus Evodiae Rutaecarpae) with hot property, respectively. Then the in vitro toxicity was evaluated by human keratinocyte cytotoxicity. In vivo skin irritation potency was also evaluated through pathological observation after topical administration. The components, especially those located in stratum corneum, were analyzed by GC-MS. The main components, namely monoterpenes and sesquiterpenes, of EOs extracted from CM with hot property,were detected for the interaction with keratino-lipid ceramide 3 by molecular simulation technology; and the interaction energy value was calculated based on the optimal conformation. It was found that the skin cell toxicity of EOs from CM with hot property was significantly higher than that of EOs from CM with warm property. However, there was no significant difference between them by in vivo skin irritation evaluation. Whether from CM with hot property or warm property, EOs showed a significant reduced toxicity compared with azone. Sesquiterpenes(33.56%±19.38%) were found to be one of the main components in EOs from CM with hot property, while almost no sesquiterpenes was found in EOs from CM with warm property. After topical administration of EOs from CM with hot property, sesquiterpenes were demonstrated to be prone to locate in stratum corneum. The results of molecular simulation also revealed that the interaction between sesquiterpenes and ceramide 3 was significantly stronger than that of monoterpenes(P<0.01). In conclusion, the location of sesquiterpenes in stratum corneum resulted in the significant difference between in vitro skin cell toxicity and in vivo skin irritation potency. The EOs from CM with hot property shall be taken into account for further development of potent penetration enhancer.
Humans ; Monoterpenes/metabolism* ; Oils, Volatile/toxicity* ; Sesquiterpenes/metabolism* ; Skin/metabolism* ; Skin Absorption

The rat everted intestinal sac model was adopted to investigate the absorption of total flavonoids from Coreopsis tinctoria in different intestinal segments. Cyaniding-3-O-β-D-glucoside, chlorogenic acid, flavanomarein, quercetagetin-7-O-β-D-glucoside, iso-okanin, marein and 3,5-dicaffeoylquinic acid which as the major chemical components of total flavonoids from C. tinctoria were selec-ted as the study objects to evaluate the absorption characteristics of each component in different intestinal segments. The results showed that the absorption of seven components of total flavonoids at different intestinal segments was in consistent with zero order absorption rate. The K_a of chlorogenic acid, flavanomarein, quercetagetin-7-O-β-D-glucoside, isookanin and 3,5-dicaffeoylquinic acid increased with increasing of concentration of total flavonoids(P<0.05), indicating that the intestinal absorption of these five components was passive transport. The K_a of cyaniding-3-O-β-D-glucoside and marein showed a weak concentration dependence, suggesting that the absorption of them may be an positive and passive co-existing mode. The result of absorption in different intestinal segments showed that cyaniding-3-O-β-D-glucoside, chlorogenic acid, flavanomarein, quercetagetin-7-O-β-D-glucoside, marein and 3,5-dicaffeoylquinic acid were mainly absorbed in ileum, while isookanin was mainly absorbed in jejunum. The total flavonoids of C. tinctoria are selectively absorbed in intestinal tract, the rat everted intestinal sac model can be used to evaluate the multi-component intestinal absorption characteristics of total flavonoids from C. tinctoria.
Animals ; Chlorogenic Acid ; Coreopsis ; Flavonoids ; Intestinal Absorption ; Plant Extracts ; Rats

The absorption is the key to the resulted efficacy of orally administered drugs and the small intestine is the main site to absorb the orally administered drug. In this paper, internationally recognized human colon adenocarcinoma cell line(Caco-2) monola-yer model which can simulate small intestinal epithelial cell was used to comparatively study the absorption and transportation diffe-rences of total coumarins and main individual coumarin in Angelica dahurica 'Yubaizhi' by separately using 6-and 12-well plates. It was found that apparent permeability coefficient(P_(app)) values of oxypeucedanin hydrate, byakangelicin and phellopterin were at the quantitative degree of 1 × 10~(-5) cm·s~(-1) when the individual administration was conducted independently, indicating that they were well-absorbed compounds. P_(app) ratio of their bi-directional transportation was close to 1, indicating that they can be absorbed across Caco-2 monolayer by passive diffusion mechanism without carrier mediation during the transportation. The similar trend of transportation was also observed for imperatorin, isoimperatorin and bergapten. The P_(app) values of oxypeucedanin hydrate, byakangelicin and bergapten were at quantitative degree of 1 × 10~(-5) cm·s~(-1) when the administration of total coumarins in Angelica dahurica 'Yubaizhi' was conducted, indicating that they were well-absorbed compounds. The results were consistent with those of independent administration of individual coumarins. Whereas, the P_(app) values of imperatorin, phellopterin and isoimperatorin in the total coumarins decreased, indicating that the interaction between compounds may exist although the P_(app) value ratio of bi-directional transportation was between 0.5 and 1.5. The results laid the foundation for intestinal absorption study of Angelica dahurica 'Yubaizhi' coumarins in compound Chinese medicine.
Angelica ; Caco-2 Cells ; Coumarins ; Drugs, Chinese Herbal ; Humans ; Intestinal Absorption ; Plant Roots

To study the effect of self-assembled nanoparticles from Shaoyao Gancao Decoction(SGD-SAN) on the encapsulation, in vitro release and intestinal absorption of the main components of Baishao. Particle size analysis and morphological observation were used to verify the formation of SGD-SAN in the decoction. The entrapment efficiency(EE) of SGD-SAN on the main components of Baishao was determined by ultrafiltration centrifugation. The dialysis bag method was used to study the in vitro release of the main components of Baishao with pH 6.8 phosphate buffer solution as the release media. Single-pass intestinal perfusion study was performed to investigate the effect of SGD-SAN on the absorption of the main components of Baishao. The results showed that there were nanoparticles in the SGD, and the particle sizes and PDI of SGD-SAN were about 200 nm and 0.38, respectively. SGD-SAN was irregularly spherical under transmission electron microscope(TEM). The EEs of albiflorin, paeoniflorin and benzoylpaeoniflorin in SGD-SAN were 33.78%±1.03%,33.61%±0.90%,88.53%±0.58%, respectively. The release characteristics of albiflorin, paeoniflorin and benzoylpaeoniflorin from SGD-SAN showed a slow-release effect on pH 6.8 phosphate buffer solution media. SGD-SAN could significantly enhance the absorption of albiflorin, paeoniflorin and benzoylpaeoniflorin in the ileum. The results of this study indicated that SAN could be formed during the mixed decoction of Baishao and Gancao, and SGD-SAN could encapsulate the components of Baishao, with a certain slow-release effect, and the formation of SAN facilitated the absorption of drugs in the ileum.
Drugs, Chinese Herbal ; Intestinal Absorption ; Intestines ; Nanoparticles