AIM： To investigate the effect of release behavior of sustained-release dosage forms of sinomenine hydrochloride （SM·HCl） on its pharmacokinetics in beagle dogs. METHODS： The in vitro release behavior of two ...AIM： To investigate the effect of release behavior of sustained-release dosage forms of sinomenine hydrochloride （SM·HCl） on its pharmacokinetics in beagle dogs. METHODS： The in vitro release behavior of two SM·HCl dosage forms, including commercial 12-h sustained-release tablets and 24-h sustained-release pellets prepared in our laboratory, was examined. The two dosage forms were orally administrated to beagle dogs, and then the in vivo SM.HCI pharmacokinetics was investigated and compared. RESULTS： The optimal SM·HCl sustained-release formulation was achieved by mixing slow- and rapidrelease pellets （9：1, w/w）. The SM·HCl release profiles of the sustained-release pellets were scarcely influenced by the pH of the dissolution medium. Release from the 12-h sustained-release tablets was markedly quicker than that from the 24-h sustained-release pellets, the cumulative release up to 12-h was 99.9% vs68.7%. From a pharmacokinetic standpoint, the 24-h SM.HCI sustainedrelease pellets had longer tmax and lower Cmax compared to the 12-h sustained-release tablets, the tmax being 2.67±0.52 h vs 9.83±0.98 h and the Cmax being 1334.45±368.76 ng/mL vs 893.12±292.55 ng/mL, respectively. However, the AUC0-tn of two SM·HCl dosage forms was comparable and both preparations were statistically bioequivalent. Furthermore, the two preparations had good correlations between SM·HCl percentage absorption in vivoand the cumulative percentage release in vitro. CONCLUSION： The in vitro release properties of the dosage forms strongly affect their pharmacokinetic behavior in vivo. Therefore, managing the in vitro release behavior of dosage forms is a promising strategy for obtaining the optimal in vivo pharmacokinetic characteristics and safe therapeutic drug concentration-time curves.展开更多
In order to investigate the mechanisms of acute cerebral ischemia, and to look for effective drugs on cerebral resuscitation, we made a model of acute complete global brain ischemia, reperfusion and resuscitation on r...In order to investigate the mechanisms of acute cerebral ischemia, and to look for effective drugs on cerebral resuscitation, we made a model of acute complete global brain ischemia, reperfusion and resuscitation on rats according to Garavilla's method.Our results showed that the event of cerebral ischemia and reperfusion injury could resuh in the increase of total brain calcium content, and anisodamine has the same reducing brain calcium contents as diltiazem's, while improving neurological outcome and alleviating injury to neurons.展开更多
Objective.To investigate the protective effects of melatonin(MT )on cardiomyocytes against the ox-idative injury induced by H 2 O 2 .Methods.Ventricular myocytes were isolated from neonatal rats and cultured for3～5da...Objective.To investigate the protective effects of melatonin(MT )on cardiomyocytes against the ox-idative injury induced by H 2 O 2 .Methods.Ventricular myocytes were isolated from neonatal rats and cultured for3～5days.Cells were divided into4groups:control group,H 2 O 2 (100μmol/L H 2 O 2 )group,MT group(100μmol/L MT )and MT preconditioning group(100μmol/L MT+100μmol/L H 2 O 2 ).The fluorescent probe,DCFH?DA,was used to detect intracellular levels of reactive oxygen species(ROS)and another fluorescent probe,Fluo-3?AM,was used to detect[Ca 2+ ] i by using a laser scanning confocal microscopy(LSCM).The malondi-aldehyde(MDA)content in cardiomyocytes was determined by measuring thiobarbituric acid?reactive sub-stances to monitor lipid peroxidation.The activity of cytoplasmic enzyme lactate dehydrogenase(LDH)that was released into the culture media was assayed to indicate alternation in the integrity of the cellular membrane.Trypan blue exclusion was used to detect the cell viability.Results.Compared with the control group,intracellular ROS,[Ca 2+ ] i ,MDA content ,LDH leakage and cell death were significantly elevated when cells were treated by100μmol/L H 2 O 2 for60minutes(P<0.01).However,those changes were significantly attenuated in MT preconditioning group.Conclusion.MT has very good antioxidant effect and can protect the cardiomyocytes against H 2 O 2 -in-duced injury.展开更多
Objective: To investigate the effects of Lycium barbarum polysaccharide (LBP) on experimental gastric ulcers in rats.Methods: The ulcers were induced by water-immersion restraint stress, acetic acid and pylorus-ligati...Objective: To investigate the effects of Lycium barbarum polysaccharide (LBP) on experimental gastric ulcers in rats.Methods: The ulcers were induced by water-immersion restraint stress, acetic acid and pylorus-ligation in rats. In each model, animals were divided randomly into 4 groups and administrated with LBP of 100 mg/kg and 300 mg/kg, ranitidine 100 mg/kg (as a reference standard) and saline respectively. Mucosal lesions were scored as ulcer index. In the pylorus-ligation model, we also compared the gastric juice volume, total acidity, acid output and pepsin activity among groups.Results: Oral administration of LBP inhibited the formation of the acute gastric lesions induced by physical stress such as water-immersion restraint (P<0.05), and accelerated the healing of chronic gastric ulcer model induced by acetic acid (P<0.05 to P<0.01). In the pylorus-ligated rats, significant decrease was also seen in ulcer index (P<0.05 to P<0.01), total acidity (P<0.05), acid output (P<0.05 to P<0.01). LBP 300 mg/kg even showed marked reduction of the volume (P<0.05) and pepsin activity (P<0.05) in the gastric juice. These effects were in a dose-dependent manner. Conclusion: LBP has protective effects on treating gastric ulcer and this action may relate to the reduction of acid output and pepsin activity in the gastric juice.展开更多
Objectives.To study the expression of TNF α mRNA and the effect of somatostatin on the expression of TNF α mRNA in multiorgans of rats with acute hemorrhagic necrotic pancreatitis(AHNP). Methods.AHNP in the rat was ...Objectives.To study the expression of TNF α mRNA and the effect of somatostatin on the expression of TNF α mRNA in multiorgans of rats with acute hemorrhagic necrotic pancreatitis(AHNP). Methods.AHNP in the rat was induced by retrograde injection of 5% sodium taurocholate into the bile-pancreatic duct. Somatostatin octapeptide (SS-OP) (2μg/kg)was injected into the femoral vein imme- diately in rats of the treatment group after inductive AHNP. Rats of the sham operative group received in- jection of saline. Sixty animals of the AHNP and sham operative groups at the designated time(0. 2h, 0. 5 h, 2h, 4h, 8h, after the operation,six animals at each time point)and tweleve animals of treatment group at 4h after the operation were sacrificed for samples of pancreas, liver and lung. The expressions of TNF α mRNA within the pancreas, liver and lung were established by RT－PCR. Results. TNF α mRNA became detectable in the pancreas as early as 0. 2h after inductive AHNP, while it was undetectable in other organs until 0. 5h. Expression of TNF α mRNA in each tissue increased continuously and reached a peak at 4h,demonstrating a significant difference compared with that at 0. 5h and 8h. Expressions of TNF α mRNA from pancreas, liver and lung were decreased 50-80% in the treat- ment group, the pancreatic necrosis was also attenuated dramatically. Conclusion. TNF α mRNA was detectable in pancreas,liver and lung tissues at the early stage of AH- NP.SS-OP can significantly inhibit the expression of TNF α mRNA and attenuate the pancreatic necrosis. We feel that this may be an important mechanism of SS-OP in the treatment of AHNP.展开更多
Objective: To detect the inhibition of urogenitalchlamydia trachomatis (CT) by 12 traditional Chinesemedicines in vitro.Methods: The inhibition of CT isolates by these medicineswas detected by micro-culture technique ...Objective: To detect the inhibition of urogenitalchlamydia trachomatis (CT) by 12 traditional Chinesemedicines in vitro.Methods: The inhibition of CT isolates by these medicineswas detected by micro-culture technique with McCoy cellsin vitro. Results: All the diuretic traditional Chinese medicinesinhibited urogenital CT The minimum inhibitoryconcentrations (MICs) ranged from 0.122 mg ml^(-1) to 62.5mg ml^(-1). Diathus superbus L., Poria cocos (Shew.) Woft,Polyporus umbellatus (Pers.) Fries, and Artemisia capillariesThunb showed stronger inhibition than the other eighttraditional Chinese medicines. The numbers and sizes ofinclusions bodies reduced gradually and disappeared finallywith the increase of the concentrations. Conclusion: All the 12 diuretic traditional Chinesemedicines inhibited urogenital CT.展开更多
Objective: To study the therapeutic effect of nimodipine on experimental brain injury. Methods: Experimental and control rabbits were subjected to a closed head injury. In one group nimodipine was given intravenously ...Objective: To study the therapeutic effect of nimodipine on experimental brain injury. Methods: Experimental and control rabbits were subjected to a closed head injury. In one group nimodipine was given intravenously and the effect evaluated by electron microscopy, brain water content, calcium levels, transcranial Doppler, and intracranial pressure monitoring. Results: In rabbits treated with nimodipine the level of neuronal cytosolic free calcium was markedly decreased. There were less cellular damage and less spasm of the middle cerebral artery seen on electron microscopy. No difference regarding intracranial pressure changes between the two groups was noted. Conclusions: Nimodipine has a protective action on brain injury by blocking a series of pathological reactions induced by neuronal calcium overload, and by reducing the spasm of brain vessels and improving cerebral blood flow.展开更多
文摘AIM： To investigate the effect of release behavior of sustained-release dosage forms of sinomenine hydrochloride （SM·HCl） on its pharmacokinetics in beagle dogs. METHODS： The in vitro release behavior of two SM·HCl dosage forms, including commercial 12-h sustained-release tablets and 24-h sustained-release pellets prepared in our laboratory, was examined. The two dosage forms were orally administrated to beagle dogs, and then the in vivo SM.HCI pharmacokinetics was investigated and compared. RESULTS： The optimal SM·HCl sustained-release formulation was achieved by mixing slow- and rapidrelease pellets （9：1, w/w）. The SM·HCl release profiles of the sustained-release pellets were scarcely influenced by the pH of the dissolution medium. Release from the 12-h sustained-release tablets was markedly quicker than that from the 24-h sustained-release pellets, the cumulative release up to 12-h was 99.9% vs68.7%. From a pharmacokinetic standpoint, the 24-h SM.HCI sustainedrelease pellets had longer tmax and lower Cmax compared to the 12-h sustained-release tablets, the tmax being 2.67±0.52 h vs 9.83±0.98 h and the Cmax being 1334.45±368.76 ng/mL vs 893.12±292.55 ng/mL, respectively. However, the AUC0-tn of two SM·HCl dosage forms was comparable and both preparations were statistically bioequivalent. Furthermore, the two preparations had good correlations between SM·HCl percentage absorption in vivoand the cumulative percentage release in vitro. CONCLUSION： The in vitro release properties of the dosage forms strongly affect their pharmacokinetic behavior in vivo. Therefore, managing the in vitro release behavior of dosage forms is a promising strategy for obtaining the optimal in vivo pharmacokinetic characteristics and safe therapeutic drug concentration-time curves.
文摘In order to investigate the mechanisms of acute cerebral ischemia, and to look for effective drugs on cerebral resuscitation, we made a model of acute complete global brain ischemia, reperfusion and resuscitation on rats according to Garavilla's method.Our results showed that the event of cerebral ischemia and reperfusion injury could resuh in the increase of total brain calcium content, and anisodamine has the same reducing brain calcium contents as diltiazem's, while improving neurological outcome and alleviating injury to neurons.
文摘Objective.To investigate the protective effects of melatonin(MT )on cardiomyocytes against the ox-idative injury induced by H 2 O 2 .Methods.Ventricular myocytes were isolated from neonatal rats and cultured for3～5days.Cells were divided into4groups:control group,H 2 O 2 (100μmol/L H 2 O 2 )group,MT group(100μmol/L MT )and MT preconditioning group(100μmol/L MT+100μmol/L H 2 O 2 ).The fluorescent probe,DCFH?DA,was used to detect intracellular levels of reactive oxygen species(ROS)and another fluorescent probe,Fluo-3?AM,was used to detect[Ca 2+ ] i by using a laser scanning confocal microscopy(LSCM).The malondi-aldehyde(MDA)content in cardiomyocytes was determined by measuring thiobarbituric acid?reactive sub-stances to monitor lipid peroxidation.The activity of cytoplasmic enzyme lactate dehydrogenase(LDH)that was released into the culture media was assayed to indicate alternation in the integrity of the cellular membrane.Trypan blue exclusion was used to detect the cell viability.Results.Compared with the control group,intracellular ROS,[Ca 2+ ] i ,MDA content ,LDH leakage and cell death were significantly elevated when cells were treated by100μmol/L H 2 O 2 for60minutes(P<0.01).However,those changes were significantly attenuated in MT preconditioning group.Conclusion.MT has very good antioxidant effect and can protect the cardiomyocytes against H 2 O 2 -in-duced injury.
文摘Objective: To investigate the effects of Lycium barbarum polysaccharide (LBP) on experimental gastric ulcers in rats.Methods: The ulcers were induced by water-immersion restraint stress, acetic acid and pylorus-ligation in rats. In each model, animals were divided randomly into 4 groups and administrated with LBP of 100 mg/kg and 300 mg/kg, ranitidine 100 mg/kg (as a reference standard) and saline respectively. Mucosal lesions were scored as ulcer index. In the pylorus-ligation model, we also compared the gastric juice volume, total acidity, acid output and pepsin activity among groups.Results: Oral administration of LBP inhibited the formation of the acute gastric lesions induced by physical stress such as water-immersion restraint (P<0.05), and accelerated the healing of chronic gastric ulcer model induced by acetic acid (P<0.05 to P<0.01). In the pylorus-ligated rats, significant decrease was also seen in ulcer index (P<0.05 to P<0.01), total acidity (P<0.05), acid output (P<0.05 to P<0.01). LBP 300 mg/kg even showed marked reduction of the volume (P<0.05) and pepsin activity (P<0.05) in the gastric juice. These effects were in a dose-dependent manner. Conclusion: LBP has protective effects on treating gastric ulcer and this action may relate to the reduction of acid output and pepsin activity in the gastric juice.
文摘Objectives.To study the expression of TNF α mRNA and the effect of somatostatin on the expression of TNF α mRNA in multiorgans of rats with acute hemorrhagic necrotic pancreatitis(AHNP). Methods.AHNP in the rat was induced by retrograde injection of 5% sodium taurocholate into the bile-pancreatic duct. Somatostatin octapeptide (SS-OP) (2μg/kg)was injected into the femoral vein imme- diately in rats of the treatment group after inductive AHNP. Rats of the sham operative group received in- jection of saline. Sixty animals of the AHNP and sham operative groups at the designated time(0. 2h, 0. 5 h, 2h, 4h, 8h, after the operation,six animals at each time point)and tweleve animals of treatment group at 4h after the operation were sacrificed for samples of pancreas, liver and lung. The expressions of TNF α mRNA within the pancreas, liver and lung were established by RT－PCR. Results. TNF α mRNA became detectable in the pancreas as early as 0. 2h after inductive AHNP, while it was undetectable in other organs until 0. 5h. Expression of TNF α mRNA in each tissue increased continuously and reached a peak at 4h,demonstrating a significant difference compared with that at 0. 5h and 8h. Expressions of TNF α mRNA from pancreas, liver and lung were decreased 50-80% in the treat- ment group, the pancreatic necrosis was also attenuated dramatically. Conclusion. TNF α mRNA was detectable in pancreas,liver and lung tissues at the early stage of AH- NP.SS-OP can significantly inhibit the expression of TNF α mRNA and attenuate the pancreatic necrosis. We feel that this may be an important mechanism of SS-OP in the treatment of AHNP.
文摘Objective: To detect the inhibition of urogenitalchlamydia trachomatis (CT) by 12 traditional Chinesemedicines in vitro.Methods: The inhibition of CT isolates by these medicineswas detected by micro-culture technique with McCoy cellsin vitro. Results: All the diuretic traditional Chinese medicinesinhibited urogenital CT The minimum inhibitoryconcentrations (MICs) ranged from 0.122 mg ml^(-1) to 62.5mg ml^(-1). Diathus superbus L., Poria cocos (Shew.) Woft,Polyporus umbellatus (Pers.) Fries, and Artemisia capillariesThunb showed stronger inhibition than the other eighttraditional Chinese medicines. The numbers and sizes ofinclusions bodies reduced gradually and disappeared finallywith the increase of the concentrations. Conclusion: All the 12 diuretic traditional Chinesemedicines inhibited urogenital CT.
文摘Objective: To study the therapeutic effect of nimodipine on experimental brain injury. Methods: Experimental and control rabbits were subjected to a closed head injury. In one group nimodipine was given intravenously and the effect evaluated by electron microscopy, brain water content, calcium levels, transcranial Doppler, and intracranial pressure monitoring. Results: In rabbits treated with nimodipine the level of neuronal cytosolic free calcium was markedly decreased. There were less cellular damage and less spasm of the middle cerebral artery seen on electron microscopy. No difference regarding intracranial pressure changes between the two groups was noted. Conclusions: Nimodipine has a protective action on brain injury by blocking a series of pathological reactions induced by neuronal calcium overload, and by reducing the spasm of brain vessels and improving cerebral blood flow.
