For the minimized phase transtorming risk, the most stable polymorph is generally considered as the desirable solid form for pharmaceutical applications. However, occasionally, the stable form may have some shortcomings such as low solubility, dissolution rate and bioavailability, etc. In that case, the metastable form which is kinetically stable at room or lower temperature could be selected. Using metastable form may result in polymorph transformation in pharmaceutical manufacture and storage. Hence, the knowledge of the transformation between solid forms is essential to the development of the drug materials. In this paper, we will review the recent studies in the area of crystal conversion of polymorphs and hydrates, to illustrate some cases to introduce the types, conditions and mechanisms of the crystalline solid transformation.
Biological Availability ; Chemistry, Pharmaceutical ; methods ; Crystallization ; Drug Stability ; Kinetics ; Pharmaceutical Preparations ; chemistry ; Solubility

Bone Density Conservation Agents ; therapeutic use ; Bone Neoplasms ; complications ; drug therapy ; secondary ; Breast Neoplasms ; pathology ; Diphosphonates ; therapeutic use ; Female ; Humans ; Male ; Pain ; drug therapy ; etiology ; Prostatic Neoplasms ; pathology ; Quality of Life

Adult ; Dimethylformamide ; poisoning ; Female ; Humans ; Occupational Exposure ; Young Adult

This paper aims to develop a method for the determination of aloe-emodin, rhein, chrysophanol and physcion and study the pharmacokinetic properties of four anthraquinones in rat plasma after oral administration of gardenia and rhubarb decoction. The plasma concentrations at different time points of four anthraquinones were determined by HPLC-FLD method. Plasma samples were extracted with liquid-liquid extraction procedure. Plasma samples were separated on a C18 column (4.6 mm x 150 mm, 5 μm), using 0.2% acetic acid and methanol as mobile phase at a flow rate of 1.0 mL min(-1) with gradient elution. The excitation and emission wavelengths were set at 430, 525 nm, respectively. DAS 2.0 software was applied to calculate the pharmacokinetic parameters. The results showed four anthraquinones can be absorbed. The main parameters of aloe-emodin, rhein, chrysophanol and physcion were as follows: C(max) for aloe-emodin was (0.085 ± 0.058), (3.772 ± 1.152), (0.464 ± 0.267), (0.028 ± 0.008) mg x L(-1) respectively; t(max) for rhein was (1.042 ± 0.510), (0.805 ± 0.307), (1.167 ± 0.283), (0.616 ± 0.162) h respectively; t½ for chrysophanol was (3.557 ± 1.250), (6.879 ± 1.126), (5.196 ± 2.032), (4.337 ± 1.816) h; AUC(0-t) for physcion was (0.504 ± 0.130), (9.558 ± 1.106), (2.545 ± 1.554), (0.052 ± 0.018) mg x h x L(-1). This paper developed a selective, accurate and sensitive HPLC-FLD method for the simultaneous determination of four anthraquiones in rat plasma.
Animals ; Anthraquinones ; blood ; pharmacokinetics ; Chromatography, High Pressure Liquid ; instrumentation ; methods ; Drugs, Chinese Herbal ; analysis ; pharmacokinetics ; Male ; Rats ; Rats, Sprague-Dawley

· Vascular endothelial growth factor is indispensable inducing factor in retinalangiogenesis. After the retinal neovascularization of proliferative diabetic retinopathy ( PDR ) patients, it can cause fibrovascular membrane formation, epiretinal membrane fibrosis increased, resulting in traction retinal detachment with further aggravate the condition. The recent research suggests that cytokines promote fibroblast proliferation, movement, adhesion, and secretion of extracellular matrix functions in the diabetic state of the environment changes to profibrogenic state, resulting in the accumulation and fibrosis of extracellular matrix. This paper reviewed the status quo of the correlation between vascular endothelial growth factor and fibrosis-related cytokine.

Objective To evaluate the efficacy,adverse events of gemcitabine vs.5-FU with radiotherapy for locally advanced pancreatic carcinomas.Methods Between January 2007 and January 2011,a total of 56 patients with locally advanced pancreatic carcinomas was included and clinical data were retrospectively analyzed.All patients received 3-DCRT radiotherapy with individual dose of 1.8 ～ 2 Gy,5 times per week,and total dose of 45 ～ 50.4 Gy for 25 ～ 28 fractions,and received concurrent chemotherapy (5-FU or gemcitabine).The patients (n =30) in gemcitabine group were treated with gemcitabine (500 rng/m2 at the 1st,8th,15th,22nd day,at 10 mg · (m2)-1 · min-1,through micro-pump) during radiotherapy; 3 weeks after radiotherapy the patients received gemcitabine infusion at a dose of 800 mg · (m2)-1 · d-1,one time per week,for 3 or 4 cycles.The patients (n =26) in 5-FU group were treated with 5-FU (500 mg/m2 at the 1 ～ 5th day per week,IV),the cycle was repeated every 2 weeks during radiotherapy; 3 weeks later the patients received 5-FU infusion at a dose of 800 mg · (m2)-1 · d-1,the 1st ～5th day per week,the cycle was repeated every 2 weeks ; with a total of 3 or 4 cycles.The efficacy and adverse events were observed,and the patients were followed until June 2013,and the median survival,1 year and 2 year survival was calculated.Results Of the 56 patients,the overall response (CR + PR) rate was 73.2％,and it was 65.3％ in radiotherapy with 5-FU group,80.0％ in radiotherapy with gemcitabine group (P ＜ 0.05).The overall one and two year survival rate was 48.2％ and 14.3％,while median survival was 15.2 months,and the corresponding values were 42.3％,11.5％,13.3 months in radiotherapy with 5-FU group,and 53.3％,16.7％,16.6 months in radiotherapy with gemcitabine group,and the survival difference between the two groups was not statistically significant (P =0.071).At the end of treatment,the pain-relief rate (VAS score ＜4) of the 56 patients was 83.3％,it was 75.0％ in 5-FU group and 90.0％ in gemcitabine group.In radiotherapy with gemcitabine group,the incidence of 3～ 4 grade myelosuppression was significantly higher than that in radiotherapy with 5-FU group,and the difference between the two groups was statistically significant (20.0％ vs 7.6％,P ＜ 0.05).Conclusions For the locally advanced pancreatic carcinomas,radiotherapy with gemcitabine can improve pain-relief and prolong survival compared with radiotherapy with 5-FU,but the incidence of adverse event of myelosuppression is higher.

Objective To investigate the correlation between dose volume histogram(DVH)of tumor targets and organs at risk(OAR)at CT-image based 192Ir brachytherapy and effects and complications for patients with locally advanced cervical cancer. Methods Ten patients with FIGO stage ⅢB cervical cancer received CT image-based 192Ir intracavitary brachytherapy after 54 Gy of three-dimentional four-field pelvic external beam radiotherapy and concurrent weekly cisplatin chemotherapy. Before each brachytherapy,CT images were acquired with applicators in place. Gross tumor volume(GTV), clinical target volume (CTV)and OAR were contoured and inverse treatment planning was designed and optimized by using PLATO treatment planning system. Conventional two-dimensional plans were also designed for comparison.The total intracavitary brachytherapy dose was 30 -42 Gy in 5 -7 fractions. The patients were followed, and the local control and complications were analyzed. The biologically equivalent dose(BED)and biologically equivalent dose in 2 Gy fractions(BED2)for GTV, CTV and OAR were calculated. The minimum dose in the most irradiated tissue volume 2 cm3(D2 cm3)adjacent to the applicator of the sigmoid colon, rectum,bladder and small bowel was determined from the DVH. Results The 1-year local pelvic control rate was 90% and grade 1-2 late complication of sigmoid colon and rectum was 50%. No grade 3 or more complications developed. On CT-image based planning, the BED and BED2 to 90% of the CTV(D90)were 95.50 Gy ± 7. 81 Gy and 79. 73 Gy ± 6. 57 Gy. The BED and BED2 to 90% of the GTV(D90)were 101.86 Gy ± 7.27 Gy and 84. 95 Gy ± 6. 1 Gy. The volume enclosed by 90% of prescribed dose(V90)for GTV and CTV were 92% ±4% and 87% ±7% respectively. The D2cm3 for rectum and sigmoid colon were 74. 97 Gy ±1.64 Gy and 67. 93 Gy ± 4. 30 Gy(EQD2, α/β = 3). Comparing with 2D brachytherapy plans , CT - image based planning has improved D90 and V90 for GTV and CTV with similar dose at point A and rectum reference point. Conclusions Computer tomography-image based 192Ir brachytherapy has resulted in the better dose distribution to the tumor targets with excellent tumor control and acceptable toxicity.

Bufalin is an active compound of the traditional Chinese medicine Chansu, which exhibits significant anti-tumor activities in many solid tumors and leukemia cell lines. Bufalin could introduce apoptosis, reverse drug-resistance, and prevent migration and invasion of tumor cells. This paper reviewed the latest research progress of the in vitro and in vivo anti-tumor effect and mechanism of bufalin on a series of cancers, such as hepatocellular carcinoma, lung cancer, colon cancer, gastric cancer, leukemia, bladder cancer, and its formulation study is also summarized for the reference of its further study and application.
Animals ; Antineoplastic Agents ; chemistry ; pharmacology ; therapeutic use ; Bufanolides ; chemistry ; pharmacology ; therapeutic use ; Chemistry, Pharmaceutical ; methods ; Neoplasms ; drug therapy ; pathology

OBJECTIVETo investigate the protective effects of Yuyin Ruangan Decoction(YRD, traditional Chinese medicine) on experimental hepatic injury in mice.

METHODSThe mice were randomly divided into control group, model group and YRD low, middle and high dose group(n = 11). By ip injection of D-GalN, CCk or thioacetamide (TAA), three models of hepatic injury mice were established to investigate the effects of YRD through detecting the indexes of liver function in serum and, the content of antioxidant system in the hepatic tissue.

RESULTSYRD could decrease the content of alanine aminotransferase (ALT)and aspartate aminotransferase (AST) in serum and that of malonaldehyde (MDA) in the hepatic tissue, upregulate the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the hepatic tissue. Furthermore, the above effects were dosedependent in a certain degree. CoNCLUSION: YRD has some protection effects on the model of experimental hepatic injury in mouse.

Alanine Transaminase ; blood ; Animals ; Antioxidants ; metabolism ; Aspartate Aminotransferases ; blood ; Chemical and Drug Induced Liver Injury ; drug therapy ; Drugs, Chinese Herbal ; pharmacology ; Glutathione Peroxidase ; metabolism ; Liver ; drug effects ; enzymology ; Malondialdehyde ; metabolism ; Mice ; Superoxide Dismutase ; metabolism

OBJECTIVETo explore the imaging characteristics and operation outcomes of intramedullary schwannoma in thoracolumbar spine.

METHODSFrom June 2005 to December 2012,17 patients with intramedullary schwannoma in thoracolumbar spine were operated through posterior approach, including 11 males and 6 females with an average age of 53 years old ranging from 46 to 67 years old. The courses of disease ranged from 3 to 5 years (averaged 3.3 years). Thoracic patients manifested chest and back pain,numbness and inability on lower limb gradually, unsteady gait. Lumbar patients manifested low back pain,radiating pain and numbness on lower limb, intermittent claudication. Preoperative VAS score was 5 to 8 with an average of 6.12. Eleven patients suffered from never injury, 4 cases were grade C, 5 cases were grade D and 2 cases were grade E according to Frankel classification. Three patients were injured on thoracic segments, 5 patients were on thoracolumbar segments, 3 patients on lumbar segments and 6 patients on lumbosacral segment confirmed by CT and MRI. Five patients were epidural, 12 were intradural extramedullary. Six patients underwent spinal decompression and tumor resection simply, eleven patients underwent spinal decompression, tumor resection, internal fixation and bone graft fusion.

RESULTSNo injury of blood vessel or spinal cord occurred during operation, cutting healed well. All patients were followed up from 12 to 60 months with an average of 32 months. Chest and back pain, low back pain, radiating pain and numbness on lower limb were improved significantly. VAS score at final follow-up was 0 to 3 (averaged 1.5). According to Frankel classification, 5 cases were grade D, and 6 cases were grade E at final follow-up.

CONCLUSIONMRI is an effective method in diagnosis of intramedullary schwannoma in thoracolumbar spine. Operative method is choosed by imaging expression, and the aim is effectively decompression of spine, reconstruction of stability of spine.

Aged ; Female ; Humans ; Lumbar Vertebrae ; surgery ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neurilemmoma ; pathology ; surgery ; Spinal Neoplasms ; pathology ; surgery ; Thoracic Vertebrae ; surgery