OBJECTIVESTo supply clinical data for drug selextion in the treatment of erectile dysfunction through intracavernosal injection.

METHODSFifty-six ED patients were randomly classified into 2 groups and received phentolamine along with papaverine (for group 1) or phentolamine, papaverine and ligustrazin hydrochloride(for group 2).

RESULTSPatients in group 2 enjoyed a longer time of erection. More patients in group 2 succeeded in having enough erection time and hardness to complete sexual intercourse (P < 0.05).

CONCLUSIONSThe extrainjection of ligustrazin hydrochloride injection can help prolong erection duration and hardness and reduce tubercles that might occur in the corpus carvernosal. Therefore it is a safe and inexpensive drug in the intracarvernous injection treatment.

Adult ; Erectile Dysfunction ; drug therapy ; Humans ; Injections ; Male ; Middle Aged ; Papaverine ; administration & dosage ; Phentolamine ; administration & dosage ; Pyrazines ; administration & dosage

The purpose of this study was to prepare tetramethylpyrazine hydrochloride transdermal gel and to study its permeation ability in vitro. The skin permeation ability was evaluated by Valian-Chien permeation cells with isolated rat skin. The concentration of tetramethylpyrazine in samples was determined by HPLC. The optimal formulation was composed with 5% azone, 5% peppermint oil, 8% sodium carboxymethylcellulose and 8% tetramethylpyrazine hydrochloride. The accumulative permeation amount of the gel was (6 731.87 +/- 102.31) microg x cm(-2) in 12 h,and the permeation rate was (535.02 +/- 33.89) microg x cm(-2) x h(-1). The release profile in vitro was in line with zero-order formulation. Tetramethylpyrazine hydrochloride gel prepared in the study would be developed as a novel transdermal preparation.
Administration, Cutaneous ; Animals ; Chemistry, Pharmaceutical ; Gels ; In Vitro Techniques ; Male ; Permeability ; Pyrazines ; administration & dosage ; chemistry ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Boronic Acids ; administration & dosage ; Bortezomib ; Humans ; Multiple Myeloma ; diagnosis ; drug therapy ; Pyrazines ; administration & dosage

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Boronic Acids ; administration & dosage ; Bortezomib ; Humans ; Multiple Myeloma ; drug therapy ; Pyrazines ; administration & dosage

OBJECTIVETo explore the efficacy and safety of subcutaneous injection of bortezomib in the treatment of de novo multiple myeloma (MM) patients.

METHODSA total of 36 MM patients treated with bortezomib, adriamycin and dexamethasone (PAD) from January 2012 to April 2013 were analyzed. Among them, 18 received improved PAD (improved PAD group) with the subcutaneous injection of bortezomib, another 18 received conventional PAD (PAD group). The efficacy and safety of two groups were analyzed.

RESULTSExcept 4 cases can not be assessed, 32 patients were evaluated. Of 32 cases, 19(59.4%) achieved complete remission (CR) or very good partial remission (VGPR) after induction therapy, which were 61.1% and 57.1% for PAD group and improved PAD group, respectively (P=1.000). No significant difference between the time to achieve maximum effectiveness in two groups was detected. In the PAD group, one patient (5.6%) died of serious lung infection and eight (44.4%) experienced grade 3 or higher adverse events, while only one (5.6%) discontinued treatment in improved PAD group due to similar toxicity. Compared to PAD group, grade 3 or worse adverse events was significantly reduced in improved PAD group, the most common symptoms were leucopenia (33.3% vs 61.1%, P=0.086), thrombocytopenia (50.0% vs 61.1%), anaemia (27.8% vs 16.7%), infection (16.7% vs 50.0%, P=0.075), diarrhea (5.6% vs 33.3%, P=0.088), peripheral neuropathy(0 vs 27.8%, P=0.045).

CONCLUSIONThe improved PAD regimen by changing bortezomib from intravenous administration to subcutaneous injection significantly reduced adverse events, improved the safety of clinical application of bortezomib without affecting curative effect, and had great progress.

Boronic Acids ; administration & dosage ; Bortezomib ; Dexamethasone ; administration & dosage ; Doxorubicin ; administration & dosage ; Humans ; Injections, Subcutaneous ; Multiple Myeloma ; drug therapy ; Pyrazines ; administration & dosage ; Remission Induction

OBJECTIVETo observe the effect of inhalation of aerosolized perfluorocarbon combined with tetramethylpyrazine on the hemodynamics and histopathology in a porcine model of acute lung injury.

METHODSNormal adult pigs were subjected to saline lavage of the bilateral lungs to induce acute lung injury and randomized subsequently into 3 groups for treatment with inhalation of perfluorocarbon, combined inhalation of perfluorocarbon and tetramethylpyrazine, or inhalation of tetramethylpyrazine. The changes of mean arterial pressure (MAP), PetCO(2), mPAP, CVP and PAWP were recorded at different time points following the lung injury, and the lung tissues were sampled for histological observations.

RESULTSThe MAP, mPAP, CVP and PAWP all increased significantly in the 3 groups after acute lung injury. Interventions with combined tetramethylpyrazine and perfluorocarbon inhalation significantly improved these indices as compared with inhalation of tetramethylpyrazine or perfluorocarbon alone (P<0.05). The pulmonary pathology was the mildest in the combined inhalation group, and the most severe in tetramethylpyrazine group.

CONCLUSIONCombined inhalation of perfluorocarbon and tetramethylpyrazine can effectively improve the oxygenation, reduce pulmonary arterial pressure?and ameliorate lung pathology in pigs with acute lung injury.

Acute Lung Injury ; drug therapy ; etiology ; pathology ; Administration, Inhalation ; Animals ; Drug Therapy, Combination ; Fluorocarbons ; administration & dosage ; Hemodynamics ; drug effects ; Lung ; pathology ; Phytotherapy ; Pyrazines ; administration & dosage ; Swine

In this study, we administered a modified schedule of weekly intravenous Bortezomib at 1.6 mg/m(2) with dexamethasone (BD) and compared it to the standard 1.3 mg/m(2) twice-weekly BD regimen in Chinese patients with newly diagnosed multiple myeloma (MM). We assessed the difference in efficacy, safety profile and survival between the once-weekly and twice-weekly cohorts (13 vs. 24 patients). The over response rate was similar with both arms of the study, being 77% in the once-weekly schedule and 74.9% in the twice-weekly schedule (P=0.690). The median overall survival was not reached in either schedule. Also, the median progression-free survival and duration of response of the once-weekly schedule did not significantly differ from those of the twice-weekly schedule (8 months vs.10 months, P=0.545 and 6 months vs.7 months, P=0.467 respectively). Peripheral sensory neuropathy and grade 3/4 hematologic toxic effects were more frequently reported in the twice-weekly schedule than the once-weekly schedule, but there was no statistically significant difference. This preliminary experience in Chinese patients with newly diagnosed MM indicated that once-weekly infusion of Bortezomib plus dexamethasone may improve safety without affecting outcome.
Adult ; Aged ; Boronic Acids ; administration & dosage ; Bortezomib ; Dexamethasone ; administration & dosage ; Female ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; drug therapy ; Pyrazines ; administration & dosage

Artificial neural network (ANN) is a multi-objective optimization method that needs mathematic and statistic knowledge which restricts its application in the pharmaceutical research area. An artificial neural network parameters optimization software (ANNPOS) programmed by the Visual Basic language was developed to overcome this shortcoming. In the design of a sustained release formulation, the suitable parameters of ANN were estimated by the ANNPOS. And then the Matlab 5.0 Neural Network Toolbox was used to determine the optimal formulation. It showed that the ANNPOS reduced the complexity and difficulty in the ANN's application.
Chemistry, Pharmaceutical ; Delayed-Action Preparations ; Drug Design ; Ligusticum ; chemistry ; Neural Networks (Computer) ; Pyrazines ; administration & dosage ; isolation & purification ; Software ; Tablets

OBJECTIVETo prepare ligustrazine (TMPZ) ocular sustained-release implant, and investigate its in vitro drug release, pharmacokinetics in rabbit vitreum and in vitro correlation.

METHODLigustrazine ocular sustained-release implants were prepared by micro-twin conical screw mixers with hot-melting extrusion method, with polyactic-co-glycolic acid (PLGA) as the matrix. HPLC was adopted to determine the concentration in vitreum after ligustrazine was implanted in rabbit eyes, in order to examine its in vivo sustained-release behavior, and study the correlation between in vitro and in vivo.

RESULTLigustrazine implants were prepared with a drug-loading rate between 10% and 30%, which was in conformity to the pharmacopoeia in terms of the content uniformity. Its in vitro release was in conformity to the zero-order release model. With PLGA 5050, 2. 5A as a vector, ligustrazine implants with a drug-loading rate of 30% could slowly release drug for more than 3 weeks, indicating a good correlation between in vitro and in vivo release.

CONCLUSIONLigustrazine ocular implants prepared with hot-melting extrusion method is practicable. Ligustrazine ocular implants release drug smoothly in rabbit vitreous vitreums, suggesting good sustained-release effect.

Animals ; Biological Availability ; Drug Implants ; Eye ; Female ; Male ; Polyglycolic Acid ; chemistry ; Pyrazines ; administration & dosage ; chemistry ; pharmacokinetics ; Rabbits ; Vitreous Body

This study aims to investigate whether a self-made novel pulsatile drug delivery system--razine phosphate pulsincap capsule-will achieve a pulsatile drug release in vivo and to study the drug release sites. A gamma scintigraphic study was conducted to assess the in vivo transit and release behavior of the pulsincap capsule with a drug tablet containing 99mTc-labeled diethylenetriamine pentaacetic acid (DTPA) in the gastrointestinal (GI) tract of dog. The results revealed that after a time interval (lag time), the drug tablet began to disintegrate and then released at the pylorus of stomach or in the small intestine of dogs with a relatively rapid release rate, which was consistent with the expected pulsed release pattern. The in vivo lag time of the pulsincap capsule in dog was shortened with the decrease of erodible plugs(EP) weight. Thus we can achieve a desirable lag time to meet the chronotherapeutic requirements by adjusting the weight of EP.
Animals ; Capsules ; Delayed-Action Preparations ; Dogs ; Gastrointestinal Tract ; metabolism ; Gastrointestinal Transit ; Pyrazines ; administration & dosage ; pharmacokinetics ; Radionuclide Imaging