Preparation of hydrophilic Indigo Naturalis based on polyethylene glycol( PEG) surface film-forming method and evaluation / 中国中药杂志

Polyethylene glycol (PEG) surface film-forming method was used to prepare hydrophilic Indigo Naturalis decoction pieces with stable effect.The preparation process of modified Indigo Naturalis was optimized and its microscopic properties,hydrophilicity,antipyretic efficacy,and safety were systematically evaluated.With equilibrium contact angle as assessment index,the influence of modifier type,modifier dosage,dispersant dosage,and co-grinding time on water solubility of Indigo Naturalis was investigated by single factor test.The results showed that the optimal preparation process was as follows.The 6%PEG6000 is dissolved in 10%anhydrous ethanol solution by sonification and then the mixture is ground with Indigo Naturalis for 2 min.The resultant product is dried on a square tray in an oven at 60℃to remove ethanol and thereby the PEG-modified hydrophilic Indigo Naturalis decoction pieces are yielded.The morphological observation under scanning electron microscope (SEM) indicated that the modified Indigo Naturalis had smoother surface than Indigo Naturalis,and energy spectrometer measurement showed that the nitrogen (N),calcium(Ca),oxygen (O),and silicon (Si) on the surface of modified Indigo Naturalis powder were less than those of Indigo Naturalis powder.Modified Indigo Naturalis had the equilibrium contact angle 18.96°smaller,polar component 22.222 m J·m~(-2)more,and nonpolar component 7.277 m J·m~(-2)smaller than the Indigo Naturalis powder.Multiple light scattering technique was employed to evaluate the dispersion in water and the result demonstrated that the transmittance of Indigo Naturalis and modified Indigo Naturalis was about85%and 75%,respectively,suggesting the higher dispersity of modified Indigo Naturalis.The suspension rate of modified Indigo Naturalis in water was determined by reflux treatment.The result showed that 57%of Indigo Naturalis was not wetted after refluxing for1 h,while the modified Indigo Naturalis was all wetted and dispersed into water.The dissolution of indigo and indirubin of modified Indigo Naturalis increased and the process was more stable.Then,rats were randomized into the blank group,model group,acetaminophen group,Indigo Naturalis group,and hydrophilic Indigo Naturalis group.The temperature changes of rats were observed after administration and the concentration of IL-1βand TNF-αin serum and IL-1βand PGE_2in hypothalamus was measured.The results indicated that the temperature of Indigo Naturalis group and hydrophilic Indigo Naturalis group dropped and the IL-1βlevel of the hydrophilic Indigo Naturalis group decreased (P<0.05) as compared with those in the model group.Thus,both Indigo Naturalis and hydrophilic Indigo Naturalis had antipyretic effect,particularly the hydrophilic Indigo Naturalis.The acute toxicity test of hydrophilic Indigo Naturalis verified that it had no toxicity to rats.In this study,the hydrophilic Indigo Naturalis decoction pieces were prepared with the PEG surface film-forming method,and the antipyretic efficacy and safety were evaluated,which expanded the technological means of powder modification for Chinese medicine and provided a method for clinical use of Chinese medicine.

Key to Indigo Naturalis' oral effectiveness: in vivo and in vitro verification of bile action / 中国中药杂志

Indigo Naturalis( IN) is mainly composed of 10% organic matter and 90% inorganic matter,with a poor wettability and strong hydrophobicity. Indigo,indirubin and effective ingredients are almost insoluble in water. And how it exerts its effect after oral administration still needs to be revealed. For this reason,this study put forward the hypothesis that " Indigo Naturalis forms a slightly soluble calcium carbonate carrier in a strong acid environment of gastric fluid,and organic substances are solubilized in the bile environment of intestinal fluid",and then verified the hypothesis. First,the dissolution apparatus was used to simulate the change process of IN in different digestive fluid,and the effects of low-dose and normal bile on the dissolution of inorganic substances and the release of organic substances were compared. After the surface morphology and element changes of IN in different digestive fluid were observed,it was found that bile is the key to promoting the dissolution of organic and inorganic substances in IN. Furthermore,the rat fever model induced by 2,4-dinitrophenol was used to study the antipyretic effect of IN in normal rats and bile duct ligation rats. It was found that the antipyretic effect of IN on normal rats was better than that of bile duct ligation rats. The above results indicated that after oral administration of IN,the calcium carbonate carrier was transformed into a slightly soluble state in acidic gastric fluid,and a small amount of organic matter was released. When IN entered the intestinal fluid mixed with bile,the carrier dissolved in a large amount,and indigo and indirubin were dissolved in a large amount,so as to absorb the blood and exert the effect. This study has a certain significance for guiding clinical application of IN. For patients with insufficient bile secretion( such as bile duct resection),oral administration with IN may not be effective and shall be paid attention.

HPLC Fingerprint Analysis of Liposoluble and Water-soluble Fractions of Xiaojinwan / 中国实验方剂学杂志

Objective:High performance liquid chromatography (HPLC) fingerprints of liposoluble and water-soluble fractions of Xiaojinwan were established and the similarity of fingerprints was evaluated, so as to explore the quality consistency of Xiaojinwan. Method:Chromatographic separation was carried out on Welch Ultimate AQ-C18 column (4.6 mm×250 mm, 5 μm) with the mobile phase of 0.1% phosphoric acid solution (A)-acetonitrile (B) for gradient elution (liposoluble fraction of 0-5 min, 40%B; 5-10 min, 40%-50%B; 10-20 min, 50%-60%B; 20-30 min, 60%-65%B; 30-40 min, 65%-70%B; 40-50 min, 70%-80%B; 50-60 min, 80%-90%B; 60-65 min, 90%-95%B; 65-75 min, 95%-100%B; 75-80 min, 100%B; water-soluble fraction of 0-20 min, 2%-5%B; 20-30 min, 5%-10%B; 30-37 min, 10%-20%B; 37-45 min, 20%-30%B; 45-50 min, 30%-40%B; 50-58 min, 40%B), the flow rate was 1 mL·min-1, the column temperature was 30 ℃. The detection wavelengths of the liposoluble and water-soluble fractions were 202, 250 nm, and their injection volumes were 10, 20 μL, respectively. A total of 30 batches of Xiaojinwan from five manufacturers were detected by HPLC, the chromatographic peaks of each part were analyzed by principal component analysis (PCA) and identified. Result:A total of 55 chromatographic peaks were detected in the fingerprints, and the similarity of fingerprint of 30 batches of Xiaojinwan was quite different. The relative standard deviations (RSDs) of fingerprint similarity of liposoluble and water-soluble fractions of Xiaojinwan were 21.5% and 32.8%, respectively. There were significant differences in the quality of samples from different manufacturers and the same manufacturer, and the chemical consistency evaluation results were dominated by liposoluble fraction, and the main reason for the chemical difference of this preparation was the composition of Liquidambaris Resina. Conclusion:The quality consistency of Xiaojinwan is poor. The establishment of two-fraction fingerprint provides a new idea for the overall quality evaluation and control of Xiaojinwan, and can provide a reference for the quality consistency evaluation of traditional pills.

Systematic review and comment on modern study of Xiaojin Pills / 中国中药杂志

Xiaojin Pill, was firstly recorded in Life-saving Manual of Diagnosis and Treatment of External Diseases, with its primitive name of "Xiaojin Dan". Xiaojin Pill is a classic prescription for treating carbuncle and it is the first choice for Chinese medicine in the clinical treatment of hyperplasia of mammary glands. In this paper, the literature reports on Xiaojin Pills were summarized and the historical evolution, material basis, pharmacological action, quality control and other problems were systematically discussed to explore the potential problems in every aspect of the development status, and put forward the development countermeasures, providing reference for the modernization research and development of Xiaojin Pills.