Fabrication of Isoniazid/Rifampicin/Poly L-lactic Acid Donut-shaped Implants via Three Dimensional Printing Technique / 中国医学科学院学报

Objective To investigate the possibility of manufacturing dual-drug loaded isoniazid/rifampicin/poly L-lactic acid (PLLA) implant with donut-shaped structure via three-dimensional (3D) printing technique and study the drug release characteristic and biocompatibility of the implant in vitro.Methods PLLA was crushed into particles with diameters around 75-100 μm.Isoniazid and rifampicin bulk drugs were dissolved into the organic dissolvent respectively to be the binding liquid.The 3D printing machine fabricated the donut-shaped implant via binding the PLLA powder layer by layer.Dynamic socking method was used to study the in vitro release characteristics,and cell culture experiment was used to test the cytocompatibility of the implant.Results PLLA slow-release implants were made by using the PLLA powder as matrix and isoniazid/rifampicin organic solvent as binding liquid through 3D printing.The drugs in the implants distributed in nest under electron microscope.The concentrations of both drugs were still higher than the lowest effective bacteriostasis concentration after release for 32 days.Cytotoxicity and direct contact tests indicated that the implants had rare cytotoxicity and favorable biocompatibility. Conclusion The donut-shaped implants can be successfully fabricated using the 3D printing method,which offers a new method for the manufacturing of topical slow-release anti-tuberculosis drugs.

Establishment of near-infrared on-line monitoring model and determination of endpoint in frying process of Hordei Fructus Germinatus / 中国中药杂志

Hordei Fructus Germinatus has been always used by "stir-frying" as a traditional medicine and the endpoint judgment of "fragrant" and "yellow" has been the focus and difficulty in frying process research. In this study, a quantitative calibration model between index components and NIRS was established in order to rapidly detect the contents of reducing sugar, total amino acids, total flavonoids, A420 and moisture; besides, an endpoint judgment method of frying process was put forward based on the "component change rate". Near-infrared spectra of samples with different frying time were collected, and a quantitative analysis model based on near-infrared spectroscopy was established to optimize the parameters such as spectral pretreatment and modeling band. HCA and PLS-DA were used to study the relationship between component and "stir-frying", and the endpoint of frying process was determined. The established calibration model had a good performance that the correlation coefficients between the predicted results and the actual measured values were both more than 0.9, with predicted relative deviations less than 10%. Hordei Fructus Germinatus with different frying time was divided into 4 categories by HCA analysis. PLS-DA analysis showed that total reducing sugar had a significant contribution to distinguishing the Hordei Fructus Germinatus of different frying time. When the change rate of total reducing sugar was 80%, it could judge that the endpoint of frying had been obtained. Results showed that NIRS could not only quickly and accurately determine the contents of reducing sugar, total amino acid, total flavonoid, A420 and moisture in Hordei Fructus Germinatus samples of different frying time, but also judge the endpoint of frying in the process. This study provided a new method for the evaluation and endpoint judgment of "stir-frying" process in research of traditional Chinese medicine.

Dynamic change rules of active ingredients and inactive ingredients from Fructus Hordei Germinatus with frying process / 中国中药杂志

It is not scientific to explain that fried Fructus Hordei Germinatus is more effective than row Fructus Hordei Germinatus in resolving food stagnation from the aspects of amylase, tricine and other "active ingredients". In the present experiment, the contents of active ingredients including quercetin, tricine, kaempferol, catechin, ferulic acid and inactive ingredients including 5-hydroxymethyl furfural, acrylamide in frying process were determined by HPLC. The dynamic change rules of active ingredient and inactive ingredients in the frying process were investigated by HCA, PCA and PLS-DA analysis. The results showed that the Fructus Hordei Germinatus samples with different frying temperatures were classified into 4 groups by HCA and PCA analysis. PLS-DA analysis showed that frying temperature mainly impacted the contents of inactive ingredients including 5-hydroxymethyl furfural and acrylamide, with less effects on the contents of active ingredients. Simultaneously, with the increase of time in frying process, the content of 5-hydroxymethyl furfural was significantly increased from 2 min and became stable at 16 min, while the content of acrylamide was increased continuously from 18 min. Based on the variation of the contents of various ingredients, samples at different frying time were classified into 5 groups. The results showed that the content changes of "inactive ingredients" were closely related to the duration and degree of frying process, and the dynamic change rules of "inactive ingredients" can provide scientific basis for evaluating the frying process and elucidating the efficacy mechanism of Fructus Hordei Germinatus.

Effects of combined administration of Paeoniae Radix Alba on local pharmacokinetics of six aconite alkaloids by skin microdialysis in vivo / 中国中药杂志

The Aconiti Radix Cocta gel and Aconiti Radix Cocta combined with Paeoniae Radix Alba gel were administered to mice. Physiological saline was taken as perfusate. The perfusion rate was 2 μL•min⁻¹ and the microdialysis samples were collected every 0.5 h intervals for eight times. The six aconitine alkaloids concentration in perfusate were determined by HPLC-MS/MS. The concentration-time curves were plotted, and the pharmacokinetic parameters were calculated and analyzed by SPSS. The effects of Paeoniae Radix Alba on transdermal permeation role of six aconitine alkaloids in herb couple of Paeoniae Radix Alba-Aconiti Radix Cocta were investigated. According to the results, Tmax of the three mono-ester aconitum alkaloids of Aconiti Radix Cocta combined with Paeoniae Radix Alba groups were shortened, meanwhile, Cmax and AUC of benzoylaconine and benzoylhypaconine were increased. However, AUC of the three diester-type alkaloids were reduced, with Tmax of hypaconitine prolonged and Cmax lowered. The study suggested that the combined administration of Aconiti Radix Cocta and Paeoniae Radix Alba promoted the transdermal permeation of mono-ester aconitum alkaloids, and inhibited the absorption of parts of diester-type alkaloids. This study proved the decreasing toxicity and increasing efficacy of the combination of Aconiti Radix Cocta and Paeoniae Radix Alba on the transdermal permeation, and provided a reference for studies on the prescription combination regularity and relevant practices.