[Process of gallnut suppository preparation].

The main objective was to research the process of gallnut suppository preparation with its water extract as the main drug, and evaluate its irritation to rectal mucosa. gallnut extract was obtained by decocting method, and its suppository preparation was obtained by fusion method with semi-synthetic aliphatic esters and rose flower oil as the matrix. Weight difference and in vitro melting time limit of the suppository were assayed and UV-Vis was used to determine the contents of polyphenols, tannin and saccharide. The irritation to colon mucosa was evaluated after successive administration of 14 days to New Zealand white rabbits. Finally, the prescription compositions were determined: semi-synthetic aliphatic esters and rose flower oil with the ratio of 2:1 as the proper matrix, with the drug loading of 54%. The prepared suppository was brown, conical and smooth. The weight difference was (1.43±0.03) g, with an average melting time limit of (17±2) min. The Contents of Polyphenols, tannic and polysaccharide were 332.4, 245.0, 3.3 mg•g-1 respectively in each suppository. The results also showed that the continuous administration had no irritation to rectal mucosa. It can be concluded that the suppository was an acceptable administrate form, whose preparation process was easily controlled, and with no irritation to rectum mucosa.

Thermosensitive and pH-responsive quercus infectoria gall-containing gel with long-lasting anti-inflammatory activity for ulcerative colitis.

In the study, quercus infectoria gall (QIG) was used to develop a pH/thermosensitive gel in situ delivery system for enema administration of to treat acute ulcerative colitis (UC). The QIG ethanol extract pH/temperature-sensitive gel (QIG-pH-TSG) was characterized by using DSC, SEM, rheological and drug release analyses. The therapeutic effect in UC mice of the obtained gel were studied. The gel was maintained in a flowing liquid state under nonphysiological conditions (25 °C) to facilitate drug administration, and was transformed into a pseudoplastic liquid state under physiological conditions (37 °C), which prolonged its retention time in the colon. The gel drug was completely released within 24 h, and the temperature and viscosity of the gel were within the required range. In the in vitro anti-inflammatory test, QIG-pH-TSG decreased the level of TNF-α and IL-6, and increased IL-10 in RAW 264.7 actived by LPS. Moreover, the administration of QIG-pH-TSG resulted in a decrease in the colon histopathological score and an increase in colonic length, and also could reduce the IL-6, TNF-α, and C-reactive protein (CRP) levels in UC mice along with significant increases in IL-10 level in the colon. The QIG-pH-TSG could increase the concentration of QIG at the local inflammatory site and lead to an effective repair of the colonic mucosa. Therefore, the pH/thermosensitive in situ gel may serve as a drug delivery system for QIG to treat UC and overcome the limitations of some existing formulations. These results indicated that this composite gel was effectively in UC mice and the study provided a practical reference for the application of QIG-pH-TSG in the treatment of UC.

Process analytical technology as in-process control tool in semi-continuous manufacturing of PLGA/PEG-PLGA microspheres.

Nowadays, among 3rd generation drug delivery systems, biodegradable polymeric based long-acting injectable depot has achieved tremendous success in clinical application. So far, there have been two dozen of commercial products of Poly (lactic-co-glycolic acid) microspheres available in the market. Recently, continuous manufacturing concept has been successfully applied on oral solid formulation from buzzword to reality. However, the polymeric injectable microspheres are still stayed at batch manufacturing phase due to the lack of understanding of knowledge matrix. In this study, micro-mixer as a plug-and-play emulsification modules, Raman spectroscopy and focused beam reflectance measurement as real-time monitoring modules are integrated into a novel semi-continuous manufacturing streamline to provides more efficient upscaling flexibility in microspheres production. In this end to end semi-continuous manufacturing process, amphiphilic block polymer monomethoxy-poly (ethylene glycol) modified PLGA (mPEG-PLGA) was used for encapsulating Gallic acid. Additionally, with guarantee of good robustness, the correlation relationship between critical process parameters, critical material attributes and critical quality attributes were investigated. The time-space evolution process and mechanism for formation of PEG-PLGA microsphere with particular morphology were elaborated. Altogether, this study firstly established semi-continuous manufacturing streamline for PLGA/PEG-PLGA microspheres, which would not only lower the cost of production, narrow process variability and smaller equipment/environmental footprint but also applied in-process control (IPC) and QbD principle on complicated production process of microspheres. Therefore, this study build confidence in the industrial development of PLGA/PEG-PLGA microspheres and establish best practice standards, which might be a quantum leap for developing PLGA microspheres in the future.

Optimization and Evaluation of the Quercus infectoria Galls Thermosensitive In Situ Gel for Rectal Delivery.

Quercus infectoria galls (QIGs) have a long history of treating ulcerative colitis (UC). The aqueous extract of QIG has an anti-UC effect. However, QIG's enema is easy to leak, and the action time and dose of the drug cannot be controlled well. Thus, QIG is inconvenient to use. This study aims to screen and prepare an optimized thermosensitive in situ gel with slow release and retention. Taking the transition sol-gel temperature (T sol-gel) as the investigation index, the Box-Behnken design response surface method (BBD-RSM) was used to optimize the dosages of Poloxamer 407 (P407), Poloxamer 188 (P188), and hydroxypropyl methyl cellulose (HPMC). Moreover, three formulations were selected, and the in vitro release rates were further optimized. The optimized rates of P407, P188, and HPMC were 24.07%, 1.22%, and 0.60%, respectively, and T sol-gel was 32.8°C ± 0.4°C. The cumulative release of gallic acid in the gel conformed to the first-order kinetic equation, and gallic acid was released entirely within 24 h. In addition, the morphological and chemical characterization of thermosensitive in situ gel demonstrated that excipients did not affect the characteristic functional groups of QIG and that the surface of the QIG gel had a porous and loose structure. Rheological methods showed that the QIG thermosensitive in situ gel was fluid at low temperature and semisolid at gelation temperature. Therefore, the prepared gel was sensitive to temperature and had slow-release, local retention properties.

A review of the phytochemical, pharmacological, pharmacokinetic, and toxicological evaluation of Quercus Infectoria galls.

ETHNOPHARMACOLOGICAL RELEVANCE: Quercus Infectoria galls (QIG) have a long history of use in traditional Chinese medicine and traditional Uyghur medicine for the treatment of diarrhea, hemorrhage, skin disease, and many other human ailments. Medicinal applications of QIG have become increasingly popular in Greece, Asia Minor, Syria, and Iran. AIM OF THE REVIEW: The present paper reviewed the ethnopharmacology, phytochemistry, analytical methods, biological activities, metabolism, pharmacokinetics, toxicology, and drug interactions of QIG to assess the ethnopharmacological uses, explore its therapeutic potential, and identify future opportunities for research. MATERIALS AND METHODS: Information on QIG was gathered via the Internet (using Google Scholar, Baidu Scholar, Elsevier, ACS, Pubmed, Web of Science, CNKI, and EMBASE) and libraries. Additionally, information was also obtained from local books and PhD and MS dissertations. RESULTS: QIG has played an important role in traditional Chinese medicine. The main bioactive metabolites of QIG include tannins, phenolic acids, flavonoids, triterpenoids, and steroids. Scientific studies on the QIG extract and its components have shown its wide range of pharmacological activities, such as cholinesterase- and monoamine oxidase-inhibitory, antitumor, anti-hypertension, antidiabetic, antimicrobial, insecticidal, antiparasitic, antioxidant, and anti-inflammatory. CONCLUSIONS: The ethnopharmacological, phytochemical, pharmacological, and analytical methods of QIG were highlighted in this review, which provides information for future studies and commercial exploration. QIG has a huge potential for pharmaceutical and nutraceutical applications. Moreover, comprehensive toxicity studies of this plant must be conducted to ensure its safety. Additional investigations are recommended to transmute the ethnopharmacological claims of this plant in folklore medicines into scientific rationale-based information. Research on pharmacokinetics studies and potential drug interactions with standard-of-care medications is still limited, which calls for additional studies particularly on humans. Further assessments and clinical trials should be performed before it can be integrated into medicinal practices.

Traditional Uyghur medicine Quercus infectoria galls water extract triggers apoptosis and autophagic cell death in colorectal cancer cells.

BACKGROUND: The water extract of Quercuse infectoria galls (QIG) is the active ingredient of Uyghur medicine Xipayi Kui Jie'an (KJA) which has promising therapeutic effects on Ulcerative Colitis (UC) as an alternative medicine. Considering the relationship between UC and the development of colorectal cancer (CRC), the present work aims to explore the direct anti-CRC activity of QIG extract. METHODS: CCK8 assay and flow cytometry were used to detect cytotoxicity and apoptosis. Transmission electron microscopy (TEM), flow cytometry, laser confocal and western blotting were performed to examine autophagy. We also adopted Reactive Oxygen Assay kit, as well as transwell and wound healing tests to study the underlying mechanism of QIG against CRC cells. RESULTS: First, we found that QIG extract could suppress the viability of CRC cells and trigger caspases-dependent apoptosis. Subsequently, we proved for the first time that QIG extract also triggered autophagic cell death in CRC cells, which together with apoptosis contributed to the cytotoxic effect on CRC cells. Further investigation revealed that QIG-induced cytotoxicity associated with intracellular ROS accumulation which could suppress the AKT/mTOR signaling pathway, and then induce autophagy and inhibit cell growth. Besides, Erk signaling pathway was also involved in the process of autophagic cell death. Moreover, QIG extract also influenced EMT process and inhibited CRC cell migration. CONCLUSION: Altogether, this study provides a basis for the utilization of QIG as an alternative medicine for CRC prevention and treatment.

Investigation into the toxicity of traditional Uyghur medicine Quercus infectoria galls water extract.

OBJECTIVE: Quercus infectoria galls (QIG) is being widely used in Traditional Uyghur Medicine. To gather preclinical safety information for the aqueous extract of QIG, a toxicity study was performed. METHODS: Subject animals were randomized, and divided into exposure and control groups. In the acute toxicity phase, three different doses--5, 7.5, and 10 g/kg, respectively--were administered via enema to imprinting control region (ICR) mice. An experiment using the maximum tolerance dose (MTD) i.e.10 g/kg was also performed. Data were gathered for 14 days, and study parameters were clinical signs, body weight, general behavior, adverse effects and mortality. At the day 14, major organs of the subjects were examined histologically. Chronic toxicity was also evaluated in Wistar rats for over 180 consecutive days. The rats were divided into three groups with different doses of 0.2 g/kg, 0.8 g/kg, and 2 g/kg, QIG. Furthermore, observations were carried out in rabbits to investigate if there were signs of irritation. RESULTS: In comparison to control group, acute, chronic toxicity and mortality were not significantly increased in exposure group. CONCLUSION: Study result suggests that the aqueous extract of QIG is unlikely to have significant toxicity and that clinical trials may proceed safely.