Quality control of ethanol extraction process of Corydalis Rhizoma based on quality by design (QbD) / 中草药

Objective: To improve the quality control level of ethanol extraction process of Corydalis Rhizoma (CR) by using quality by design (QbD), so as to meet the extraction requirements of Kedaling Tablets. Methods: The critical process parameters were solvent multiple, extraction time and soaking time, and the critical quality attributes were dry extract rate, content and transfer rate of dehydrocorydaline. The response surface methodology was used to establish the mathematical model between the critical process parameters and the critical quality attributes. The overlapping design space of multiple index design spaces was established to select the optimal operation space, where the process verification was carried out. Results: The operating space parameters of ethanol extraction of CR was 14-24 h of the immersion time, 3.0-4.0 times of the first time solvent multiple, 1.5-2.0 times of the second and third time solvent multiple, and 1.5-2.5 h of the extraction time. Under this operating space, the extraction yield of CR was ranged from 6%-8%, the content of dehydrocorydaline was more than 2.8%, and the transfer rate was not less than 85%. Conclusion: The concept of QbD is helpful to improve the ethanol extraction process of CR, and to obtain a reliable and suitable extraction operation space for the production of Kedaling Tablets.

Quality evaluation of Moutan Cortex Formula Granules / 中国中药杂志

A scientific and perfect quality evaluation system for Moutan Cortex Formula Granules was established,including content determination method,characteristic chromatogram method and mass spectrometry method. The content of paeoniflorin and paeonol in Moutan Cortex Formula Granules was determined by high performance liquid chromatography( HPLC),and the average content was 1. 72% and 1. 42%,respectively. The characteristic chromatogram was used to characterize Moutan Cortex Formula Granules,which contained 7 characteristic peaks,namely gallic acid,p-hydroxybenzoic acid,oxypaeoniflorin,paeoniflorin,tetragalloyl glucose,1,2,3,4,6-penta-O-galloyl-β-D-glucose and paeonol. A total of 40 compounds in Moutan Cortex Formula Granules,including gallic acids,paeoniflorins,paeonols,flavonoids and benzoic acids,were identified by mass spectrometry. In this study,a variety of analytical methods were used to evaluate the quality system of Moutan Cortex Formula Granules,which could play a positive role in improving the level of quality evaluation and process quality control.

Application of fingerprint technology in quality evaluation and process control of traditional Chinese medicine formula granules / 中国中药杂志

The fingerprint technology could reflect the internal chemical characteristics of Chinese herbal medicine or preparation, which has the characteristics of "wholeness" and "fuzziness". It is suitable for evaluating the quality of intermediate and finished products in the production process of traditional Chinese medicine formula granules. In this paper, the applications of high performance liquid chromatography (HPLC), thin layer chromatography (TLC), gas chromatography (GC) and infrared spectrum (IR) fingerprint technology in the quality control of traditional Chinese medicine formula granules were reviewed, and their advantages and disadvantages were analyzed. The aim of this article is to enhance the combined application of various fingerprint technologies in traditional Chinese medicine formula granules. It could provide technical reference for realizing the stability of production process and improving the overall quality of formula granules.

Preparation Technology of Standard Decoction and Formula Granules of Moutan Cortex Containing Volatile Components / 中国药学杂志

OBJECTIVE: To establish the preparation technology of Moutan Cortex standard decoction and formula granules. METHODS: Moutan Cortex standard decoction was prepared by decocting pot and the parameters and fingerprints of 15 batches of decoction were established.To improve the preparation process of Moutan Cortex formula granules, paeonol was quickly recovered by using volatile oil collection device in the process of vacuum concentration, and the collected paeonol was added back to the concent rated solution.Then, the formula granules of Moutan Cortex were prepared by spray drying and dry granulating.The correlation between the decoction pieces, extract, concentrate, powder, formula granules and standard decoction were compared by taking the contents of paeoniflorin, paeonol and fingerprint as indexes. RESULTS: The range of parameters for Moutan Cortex standard decoction(70%-130% of the average value) were as follows:the dry extract rate was 19.46%-36.14%. The content of paeoniflorin was in the range of 1.83%-3.40%, and the transfer rate was 60.32%-100.00%. The content of paeonol was 1.25%-2.33%, and the transfer rate was 14.42%-26.78%.The contents of paeoniflorin and paeonol in the formula granules of Moutan Cortex conformed to the range of standard decoction parameters. CONCLUSION: The parameters of Moutan Cortex standard decoctions prepared by decocting pot are confirmed, and a new preparation process of Moutan Cortex formula granules is established.Both of standard decoction and formula granules have good consistency in the contents of the index components,which could provide a certain scientific basis for the guidance of actual production.

Research progress on active ingredients of traditional Chinese medicines improved insulin resistance based on PPARs targets / 中国中药杂志

Peroxisome proliferator-activated receptors (PPARs) are nuclear transcriptional factors closely related to glucose and lipid metabolism, insulin sensitivity. Activation of PPARs targets treated type 2 diabetes, obesity, hypertension and other metabolic diseases by insulin resistance. Recently, a variety of active ingredients of traditional Chinese medicines (TCMs) have been proved to activate PPARs targets for improving insulin resistance, which has attracted widespread attention at home and abroad. In this paper, we reviewed the pathological mechanisms between insulin resistance and PPARs, and summarized the active ingredients of TCMs improved insulin resistance based on PPARs targets. This paper may provide some theoretical guidance for the development of new drugs and TCMs.

Investigation on the optical scan condition for imaging of multi-slice spiral CT liver perfusion in rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Multi-slice CT liver perfusion has been widely used in experimental studies of hemodynamic changes in liver lesions, and is usually performed as an adjunct to a conventional CT examination because of its high temporal and spatial resolution, simple protocol, good reproducibility, and ability to measure hemodynamic changes of liver tissues at the capillary level. Experimental rat models, especially those of induced liver cancer, are often used in studies of hemodynamic changes in liver cancer. Carcinogenesis in rats has a similar pathological progression and characteristics resembling those in human liver cancer; as a result, rat models are often used as ideal animal models in the study of human liver cancer. However, liver perfusion imaging in rats is difficult to perform, because rats' livers are so small that different concentrations, flow rates, and dose of contrast agents during the CT perfusion scanning can influence the quality of liver perfusion images in rats. The purpose of this study, therefore, was to investigate the optimal scan protocol for the imaging of hepatic perfusion using a deconvolution mathematical method in rats by comparing the results of rats in different injection conditions of the contrast agent, including concentration, rate and time.</p><p><b>METHODS</b>Plain CT scan conditions in eighty 2-month-old male Wistar rats were 5.0 mm slice thickness, 5.0 mm interval, 1.0 pitch, 120 kV tube voltage, 60 mA tube current, 512 × 512 matrix, and FOV 9.6 cm. Perfusion scanning was carried out with different concentrations of diatrizoate (19%, 38%, 57%, and 76%), different injection rates (0.3 and 0.5 ml/s), and different injection times (1, 2-3, 4-5, and 6 seconds). The above conditions were randomly matched and adjusted to determine the best perfusion scan protocol. Three-phase contrast-enhanced scanning was performed after CT perfusion. Histological examination of the liver tissues with hematoxylin and eosin stains was done after CT scanning.</p><p><b>RESULTS</b>When the concentration of the contrast agent was 19% or 38%, no pseudo-color map was created. The viscosity increased when the concentration of the contrast agent was 76%; so it is difficult to inject the contrast agent at such a high concentration. Also no pseudo-color map was generated when the injection time was short (1, 2-3, and 4-5 seconds) or the injection rate was low (0.3 ml/s). The best perfusion images and perfusion parameters were obtained during 50 seconds scanning. Each rat was given an injection of 57% diatrizoate at 0.5 ml/s via the tail vein using a high-pressure syringe for 6 seconds. The perfusion parameters included hepatic blood flow (HBF), hepatic blood volume (HBV), mean transit time (MTT) of the contrast agent, capillary permeability-surface area product (PS), hepatic arterial index (HAI), hepatic artery perfusion (HAP), and hepatic portal perfusion (HPP). All these parameters reflected the perfusion status of liver parenchyma in normal rats. Three phases of enhancement were modified according to the time-density curves (TDCs) of the perfusion imaging: hepatic arterial phase (7 seconds), hepatic portal venous phase (15 seconds), and a delayed phase (23-31 seconds). On examination by microscopy, the liver tissues were pathologically normal.</p><p><b>CONCLUSIONS</b>The appropriate protocol with multi-slice spiral CT liver perfusion reflected normal liver hemodynamics in rats. This study laid a solid foundation for further investigation of the physiological characteristics of liver cancer in a rat model, and was an important supplement to and reference for conventional contrast-enhanced CT scans.</p>

HB-1, an acute myeloid leukemic cell line with the capability of infiltrating into the brain in CBA/N mice / 生理学报

An acute myeloid leukemic HB-1 cell line was cloned and established from the spleen cells of irradiated CBA/N mice. Acute myeloma leukemia-like syndrome would be induced in normal CBA/N mice after intravenous injection of HB-1 cells, and the death of mouse happened within about two weeks. In general, leukemic cells transplanted into the mice would infiltrate into the hematopoietic organs, lungs, kidneys and liver. An interesting observation in our study was that HB-1 cells were present not only in the lung, kidney, and liver but also in the cerebrum and cerebellum. It was beyond our expectation that the leukemic cells could go through the blood-brain barrier in most circumstances. On the basis of the observation, we expect that HB-1 cells could be used as a very useful model to elucidate the mechanism of infiltrating the blood-brain barrier for certain type of cells.

The application of denaturing high performance liquid chromatography in detection of novel polymorphisms in PAI-1gene / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To detect single nucleotide polymorphisms(SNPs) in codon region of plasminogen activator inhibitor-1 (PAI-1) gene and associate them with development of coronary artery disease(CAD).</p><p><b>METHODS</b>Denaturing high performance liquid chromatography(DHPLC) and DNA sequencing were used to scan all of exons in PAI-1 gene in 93 CAD patients and 123 control subjects.</p><p><b>RESULTS</b>Two polymorphisms in exon 2, G43A and G49A, which results in missense mutation Ala15Thr and Val17Ile, were found. Heterozygotes for these variants as well as wild type homozygotes were only found in all subjects. The association of genotypes with CAD development and with PAI 1 antigen level were evaluated. The comparison of genotype frequency distribution between two groups revealed that there were more heterozygous carriers of mutation at both polymorphic sites in control than in CAD subjects, but there was no statistically significant difference between them. And genotypes of both polymorphisms were not associated with PAI-1 level.</p><p><b>CONCLUSION</b>Two SNPs in exon 2 of PAI-1 gene were identified by DHPLC method. Both polymorphisms were not associated with the incidence of CAD.</p>