Antineoplastic Agents ; administration & dosage ; pharmacology ; Drug Delivery Systems ; Humans ; Liposomes ; administration & dosage ; pharmacology ; Sesquiterpenes ; administration & dosage ; pharmacology

A HPLC-MS/MS multiple-reaction monitoring (MRM) quantitative analysis was made to establish a determination method for drug concentrations of costunolide (Co) and dehydrocostuslactone (De) in blood samples in the positive ion mode, with diazepam as the internal standard substance, in order to study the pharmacokinetic process of sesquiterpene lactones costunolide and dehydrocostuslactone after the oral administration of Weichang'an pills, and provide an theoretical basis for further studies on the substance basis for the anti-diarrhea effect of Weichang'an pills. In the blood samples, Co and De showed a good linearity within concentration ranges 0.700 0-769.7, 2.510-956.0 μg x L(-1), respectively. The results of precision, stability and recovery experiences proved the stability and reliability of the plasma concentration determination method. After the oral administration, the concentrations of Co and De in plasma increased with the increase in dose, with T(max) between 10.65-12.98 h, indicating a long time to reach peak plasma concentrations; C(max) of costunolide and dehydrocostuslactone ranged between 3.750-5.450,15.34-44.52 μg x L(-1), respectively. The in vivo adsorption of Co and De conformed to the one-compartment model, with a longer time to attain the peak plasma concentrations. These results provided an experimental basis for revealing the active substance basis and clinical medication of Weichang'an pills.
Administration, Oral ; Animals ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; pharmacokinetics ; Lactones ; administration & dosage ; blood ; pharmacokinetics ; Male ; Rats ; Rats, Wistar ; Sesquiterpenes ; administration & dosage ; blood ; pharmacokinetics ; Tablets ; administration & dosage ; chemistry ; pharmacokinetics

Solid dispersions technique was used to solidify buagafuran and improve buagafuran in vitro dissolution and stability. Buagafuran solid dispersions were prepared separately using PVPK30, PEG6000 and Poloxamer188 at various weight ratios as carriers. The status of buagafuran in solid dispersions was determined by using DSC and IR. The solubility, content and in vitro dissolution of pure drug and the solid dispersions were detected by using HPLC. When buagafuran/carrier was 1:5 or less, the drug existed in a solid dispersion form. Three kinds of carriers all can improve buagafuran dispersibility and in vitro dissolution. Accelerating experiment showed that buagafuran/PVPK30 < or = 1:10 solid dispersions was ageing-resistant, and the aspect, content and in vitro dissolution did not change after storaged over 3 months, but PEG6000, Poloxamer188 and a lower ratio PVPK30 solid dispersions became aged. Buagafuran/PVPK30 < or = 1:10 solid dispersions can be developed as buagafuran oral drug delivery carrier.
Anti-Anxiety Agents ; administration & dosage ; chemistry ; Drug Carriers ; Drug Delivery Systems ; Drug Stability ; Drug Storage ; Poloxamer ; chemistry ; Polyethylene Glycols ; chemistry ; Povidone ; chemistry ; Powders ; Sesquiterpenes ; administration & dosage ; chemistry ; Solubility

To research databases of Cochrane library, Web of Science, PubMed, FMJS, CBM, VIP, CNKI and Wanfang Data Konwledge Service Platform by computers as at July 5, 2012, which was supplemented with other search results. The findings were included into randomized controlled trials (RCTs) of elemene injection combined with cisplatin chemotherapeuties in treating small cell lung cancer (NSCLC). Data was separately collected by two researchers for literature quality evaluation, and a Meta analysis was made with RevMan 5. 2 software, in order to assess the efficacy and safety of elemene injection combined with cisplatin chemotherapeutics in treating NSCLC. Totally 11 RCTs or 844 cases were included. Meta analysis results suggested that compared with cisplatin chemotherapy alone, the combination of elemene injection and cisplatin chemotherapeutics showed a higher clinical benefit rate ( OR = 2. 03, 95% CI:1.43-2. 88, P <0. 000 1) and a better quality of life (OR = 3.23, 95% CI:2. 20-4. 74, P <0. 000 01). Besides,the combination could also reduce leucopenia (OR =0. 50, 95% CI:0. 33-0. 76, P <0. 001) , and thrombocytopenia (OR =0. 38, 95% CI:0. 16-0. 85, P <0. 02), increase CD4 (MD = 3.32, 95% C1:2. 94-3.70, P <0. 000 01), and CD4/CD8 (MD = 0. 36, 95% CI:0. 28-0. 44, P < 0. 000 01) , and relieve gastrointestinal reactions such as nausea and vomiting (OR = 0. 37, 95% CI: 0. 19-0. 71, P = 0. 003). The analysis indicates that elemene can enhance the chemotherapeutic effect on NSCLC, improve the quality of life, and reduce adverse effect of platinum-contained chemotherapeutics, thereby being worth promoting in clinic.
Carcinoma, Non-Small-Cell Lung ; drug therapy ; Cisplatin ; administration & dosage ; therapeutic use ; Humans ; Injections ; Randomized Controlled Trials as Topic ; Sesquiterpenes ; administration & dosage ; therapeutic use

Antineoplastic Agents, Phytogenic ; administration & dosage ; pharmacology ; Apoptosis ; drug effects ; Cell Line, Tumor ; Dose-Response Relationship, Drug ; Glioma ; pathology ; Humans ; Sesquiterpenes ; administration & dosage ; pharmacology ; Time Factors

OBJECTIVETo determine the main factors which affect the percutaneous penetration of artesunate and provide efficient data for the artesunate transdermal delivery system.

METHODTransdermal speed constant and accumulative amount of 12 hours were used for the estimations of various reservior vehicles, and the supplement orthodox design was used to study the effect of pH, various proportion of IPA/Water/IPM, and drug concentration.

RESULTDrug concentration and pH were the main factors which affected the percutaneous penetration of artesunate.

CONCLUSIONThe suitable reservior vehicle can prompt the percutaneous penetration of artesunate, and artesunate TTS will be made with further studies.

2-Propanol ; pharmacology ; Administration, Cutaneous ; Animals ; Antimalarials ; administration & dosage ; pharmacokinetics ; Artemisinins ; administration & dosage ; pharmacokinetics ; Drug Carriers ; Drug Delivery Systems ; Hydrogen-Ion Concentration ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Sesquiterpenes ; administration & dosage ; pharmacokinetics ; Skin Absorption ; drug effects

AIMTo investigate the excretion of beta-elemene from the respiratory tracts in male Spraque-Dawley rats.

METHODSAfter a single administration of beta-elemene to rats at the dosage of 75 mg x kg(-1) (i.v. or i.p.), the exhaled gases were collected and concentrated at various time points. The residues were analyzed by gas chromatography.

RESULTSA minor amount of unchanged beta-elemene was excreted via rat respiratory tracts after iv and ip administration of a single dose. The cumulative excretion were 1.41% and 0.51% respectively.

CONCLUSIONThe results demonstrated that unchanged beta-elemene excretes from rat respiratory tracts, but may not be the main elimination pathway in rats.

Animals ; Chromatography, Gas ; Curcuma ; chemistry ; Infusions, Parenteral ; Injections, Intravenous ; Male ; Plants, Medicinal ; chemistry ; Rats ; Rats, Sprague-Dawley ; Respiratory System ; metabolism ; Sesquiterpenes ; administration & dosage ; isolation & purification ; pharmacokinetics

BACKGROUND: Malignant pleural effusion (MPE) refers to pleural effusion which arises from primary malignant tumor of pleura or other pleural metastatic tumors. Injection of elemene in chest makes good effect on the treatment of MPE, and is widely used in clinic. Adverse effects also exist, but the severe adverse effects and relevant managements are rarely reported. The aim of this study is to observe the adverse reactions induced by the treatment of malignant pleural effusion through elemene injection and to explore the solutions. METHODS: A retrospective analysis was made on 14 cases of patients receiving intra-pleural injections with elemene, and the incidence of severe adverse reactions of 7 cases were disscussed in detail. RESULTS: Most of the severe adverse reactions caused by elemene were severe chest pain, dyspnea, wheezing, clouding of consciousness and coagulopathy. CONCLUSIONS Strict screening, full preprocessing and close monitoring are necessary to prevent serious adverse reactions caused by elemene injection in the treatment of malignant pleural effusion.
Aged ; Female ; Humans ; Injections ; Male ; Middle Aged ; Pleural Effusion, Malignant ; drug therapy ; Retrospective Studies ; Sesquiterpenes ; administration & dosage ; adverse effects ; therapeutic use ; Thorax

OBJECTIVETo observe the synergistic effect of beta-elemene Injection (betaI) combined Paclitaxel Injection (PI) on breast cancer MB-468 cells and to study possible mechanisms.

METHODSBreast cancer MB-468 cells were treated with betaI (2.5, 5.0, 10.0, 20.0, 40.0, 80.0, 160.0, 320.0, and 640.0 microg/mL), PI (0.00100, 0.00200, 0.00400, 0.00800, 0.01600, 0.03125, 0.06250, 0.12500, and 0.25000 microg/mL), and betaI combined PI for 24 h and 48 h respectively. Cell proliferation was determined using SRB assay. Cell apoptosis and cell cycle phase distribution were detected using flow cytometry. The post-intervention expressions of cell cycle proteins [cyclin-dependent kinase (CDK1), cyclin-B1, P21(cip1), and P27(kip1)] were detected by Western blot.

RESULTSBeta-elemene or paclitaxel inhibited the growth of MB-468 cell line. The IC50 and IC20 values treated with beta-elemene for 24 h were 34.20 and 52.59 microg/mL and for 48 h were 10.15 and 17.81 microg/mL respectively, while the IC50 values treated with paclitaxel for 24 h and 48 h were 2.449 and 1.698 microg/mL respectively. Beta-elemene (20 and 40 microg/mL respectively) and Paclitaxel (0.016 and 0.008 microg/mL respectively) synergistically inhibited cell proliferation of MB-468 cells, with Q value > 1.15. Beta-elemene alone (52.59 microg/mL) apparently decreased the expression of cyclin-B1 protein. The expression of cyclin-B1 protein in the combined group was also lower than that in the PI group (1.698 microg/mL). The expression of P27(kip1) was up-regulated when compared with that in the betaI group or the PI group.

CONCLUSIONBeta-elemene had synergistic effect with Paclitaxel, and its possible mechanism might be correlated with down-regulating the cell cycle protein cyclin-B1 expression and up-regulating the P27(kip1) expression.

Antineoplastic Agents, Phytogenic ; administration & dosage ; pharmacology ; Breast Neoplasms ; drug therapy ; Cell Cycle ; drug effects ; Cell Cycle Proteins ; metabolism ; Cell Line, Tumor ; Drug Synergism ; Female ; Humans ; Paclitaxel ; administration & dosage ; pharmacology ; Sesquiterpenes ; administration & dosage ; pharmacology

OBJECTIVETo investigate the efficiency, safety, and possible mechanisms of Qingre Buyi Decoction (QBD) in the treatment of acute radiation proctitis (ARP).

METHODSThis study was a single center, prospective, single blind, randomized, and placebo-controlled clinical trial. A total of 60 patients with ARP was equally and randomly distributed into the control group (conventional treatment) and the combination group (conventional treatment plus QBD). The changes of main Chinese medicine clinical symptoms and signs, including stomachache, diarrhea, mucous or bloody stool before and after treatment, and their adverse reactions were observed after the two-week treatment. Also, D-lactate and diamine oxidase (DAO) levels, hepatic and renal function were measured. Cure rates, effective rates, and recurrence rates were compared between the two groups.

RESULTSThe blood levels of both DAO and D-lactate were significantly decreased in the combination group as compared with those in the control group (P<0.05 or P<0.01). All main clinical symptoms and signs were alleviated more significantly in the combination group (P<0.01). The main symptom scores also were significantly decreased after treatment in the control group (P<0.01), except those for mucous or bloody stool (P>0.05). Compared to the control group, the improvements of stomachache, diarrhea, defecation dysfunction, and stool blood in the combination group were significantly better (P<0.05 or P<0.01). For the combination group, the curative rate, effective rate, and recurrence rate was 76.67%, 16.67%, and 6.67%, respectively. On the other hand, for the control group, the rate was 53.33%, 16.67%, and 30.00%, respectively. The total curative effect was significantly better in the combination group than in the control group (P<0.05). However, the recurrence rate was similar between the two groups (P>0.05). The hepatic and renal function remained normal in both groups (P>0.05). In addition, no severe adverse event was found in both groups.

CONCLUSIONSAddition of QBD to the conventional treatment can effectively alleviate the damage of intestinal mucosal barrier function and improve all main clinical symptoms and signs of the ARP. The combination of conventional treatment with Chinese herbal medicine QBD is effective and safe for ARP.

Acute Disease ; Adult ; Aged ; Anti-Inflammatory Agents ; administration & dosage ; Azulenes ; administration & dosage ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; administration & dosage ; adverse effects ; therapeutic use ; Female ; Gastrointestinal Agents ; administration & dosage ; Glutamine ; administration & dosage ; Humans ; Integrative Medicine ; methods ; Male ; Middle Aged ; Norfloxacin ; administration & dosage ; Pain ; complications ; Proctitis ; complications ; drug therapy ; Sesquiterpenes ; administration & dosage ; Silicates ; administration & dosage ; Single-Blind Method ; Treatment Outcome