Objective:The cross-linked production,which was prepared by HA and cross-linking agent STMP,EDC,GP through cross-linking reaction,might be used in drug delivery system(DDS).To ensure the security of clinical applicati...Objective:The cross-linked production,which was prepared by HA and cross-linking agent STMP,EDC,GP through cross-linking reaction,might be used in drug delivery system(DDS).To ensure the security of clinical application,the excellent properties such as none cell toxicity,nonirritant,none general toxicity,none immunological rejection are necessary.Methods:In accordance with the request of GB/T 16886.1 on security evaluation of medical biomaterials,cell toxicity test,hemolysis test,intracutaneous stimulation test,acute toxicity test,and hypersensitive test were required.Results:Cell toxicity of HA-STMP,HA-EDC,HA-GP were all less than 1.All hypersensitive tests were eligible.But HA-EDC,HA-GP produced different degrees of slight thrill,slight toxicity,hemolysis rate,which were larger than the standard value.Conclusion:HA-STMP possesses favourable biocompatibility,which is a kind of ideal biomaterials and drug carriers.展开更多
Acute and repeat-dose toxic effects ofHOC （7-hydroxycoumarin）, ethanol and their mixture were studied in rats. Single oral administration of HOC （5,000 mg/kg） caused transitional glycosuria associated with lowered...Acute and repeat-dose toxic effects ofHOC （7-hydroxycoumarin）, ethanol and their mixture were studied in rats. Single oral administration of HOC （5,000 mg/kg） caused transitional glycosuria associated with lowered serum glucose levels, decreased urea clearance. HOC given orally during 28 days （200 mg/kg） decreased serum glucose, and increased serum triglyceride concentrations. No enhancement of acute toxic effect of HOC （5,000 mg/kg） and ethanol （6,000 mg/kg） mixture was found in the acute toxicity study phase. Effect of HOC （200 mg/kg） and ethanol （750 mg/kg） during 28 days of exposure was less pronounced in comparison with HOC effect only, as far as neither decrease of glucose, nor increase oftriglyceride serum concentrations were found.展开更多
Heavy metals pose a potential threat to aquatic organisms. In this study, a static-renewal acute toxicity test was conducted to investigate the effects of cadmium on the antioxidant defense systems （both enzymatic an...Heavy metals pose a potential threat to aquatic organisms. In this study, a static-renewal acute toxicity test was conducted to investigate the effects of cadmium on the antioxidant defense systems （both enzymatic and non-enzymatic） and lipid peroxidaton in liver and gill tissues of juvenile GIFT tilapia Oreochromis niloticus. After 8 days of exposure to Cd （0, 0.016, 0.08, 0.4 and 2 mg/L）, livers accumulated significantly more Cd than gills. Catalase （CAT）, superoxide dismutase （SOD） and glutathione S-transferase （GST） activities were stimulated only at the highest concentration tested （2 mg/L）. Glutathione peroxidase （GPx） activity was stimulated in the gill while inhibited in the liver, these alternations in gill and liver showed a strong relationship with Cd levels in these tissues. This may indicate either a tissue-specific response of GPx to Cd or, most probably, a hormetic effect of Cd on GPx. Cd increased GSH levels and decreased the ratio GSSG/GSH in fish livers at 2 mg/L. Cd exposure resulted in an elevated level of MDA in the livers of fish at 2 mg/L, indicating that Cd caused lipid peroxidation. Taken together, the results demonstrated that Cd altered the enzymatic and non-enzymatic defensive systems and caused lipid peroxidation in O. niloticus at relatively high concentrations （compared to environmentally relevant concentrations）. In addition, the results implied that O. niloticus could tolerate high level of Cd in sites polluted by Cd.展开更多
Objective:In the medium of ethanol(non-polar),STMP and ADH as crosslinkers to HA,to prepare drug delivery microspheres by getting stable cross-linked products without a gel phase,and to study biocompatibility and biod...Objective:In the medium of ethanol(non-polar),STMP and ADH as crosslinkers to HA,to prepare drug delivery microspheres by getting stable cross-linked products without a gel phase,and to study biocompatibility and biodegradability of cross-linked products.Methods:ISO10993.1-Safety Evaluation of Biomedical materials as a reference,to make hemolysis test,percutaneous stimulation test,acute toxicity test,and analyze in vitro degradation test,and degradation products.Results:HA-STMP cross-linked product had no hemolysis,no irritation,no acute systemic toxicity,but HA-ADH had a mild skin irritation and adverse acute systemic toxicity.HA-STMP cross-linked product had lower sensitivity on HAse and the curve is flatting.With the increase of degradation time HA-STMP results were changed by the structure analysis,degradation products of these cells were no toxicity.Conclusion:HA-STMP cross-linked products with better biocompatibility and better resistance to hydrolysis could delay the degradation time,which is suitable for the preparation of biodegradable drug carriers.展开更多
To further assess hyperoside as a potential new anti-hepatitis B virus （HBV） drug, the safety of hyperoside extracted from Abelmoschus manihot （L.） Medic was evaluated by testing its acute toxicity and mutagenic r...To further assess hyperoside as a potential new anti-hepatitis B virus （HBV） drug, the safety of hyperoside extracted from Abelmoschus manihot （L.） Medic was evaluated by testing its acute toxicity and mutagenic risk. To test the acute toxicity of hyperoside, we determined the median lethal dose （LD 50 ） in mice. Forty healthy BALB/c mice （20 per sex） were administered a single oral dose of 5000 mg/kg hyperoside via the intragastrical route. The number of animals poisoned and died was noted daily for 14 consecutive days. All animals survived and appeared active and normal, indicating that the LD 50 of hyperoside was more than 5000 mg/kg. Potential genotoxicity of hyperoside was investigated using a bacterial reverse mutation assay （Ames test）, a chromosome aberration test in Chinese hamster lung （CHL） fibroblasts, and an in vivo micronucleus test in rat bone marrow cells. In the bacterial reverse mutation assay, we observed no increases in the number of revertant colonies at any concentrations of hyperoside regardless of metabolic activation （S9） in all tester strains （TA97, TA98, TA100 and TA102） compared to the vehicle control （P0.05）. Hyperoside did not cause significant structural aberration in CHL cells in the presence or absence of S9 （P0.05）. The micronuclei rates of mice bone marrow cell in all groups showed no significant difference when compared with the negative control （P0.05）. In summary, hyperoside showed no genotoxicity in our experimental conditions.展开更多
OBJECTIVE： To design a combined dynamic inhalation device for testing the toxicity induced by moxa smoking. METHODS： The new apparatus （Patent No. 201120101911.5） includes air renewal and recycling systems, a gas ...OBJECTIVE： To design a combined dynamic inhalation device for testing the toxicity induced by moxa smoking. METHODS： The new apparatus （Patent No. 201120101911.5） includes air renewal and recycling systems, a gas generating device, a gas control unit, and a device to measure and control tem- perature and humidity. Sprague-dawley rats were tested for acute and sub-chronic toxicity after exposure to moxa-burning smoke.METHODS： The new apparatus （Patent No. 201120101911.5） includes air renewal and recycling systems, a gas generating device, a gas control unit, and a device to measure and control tem- perature and humidity. Sprague-dawley rats were tested for acute and sub-chronic toxicity after exposure to moxa-burning smoke.RESULTS： We found an LQ0 of 1.2× 10^4 mg/m^3 in the acute toxicity assays. In sub-chronic toxicity tests the organ coefficients studied showed no sig-nificant differences within rats groups of the same gender after treatment with moxa smoke or a month of recovery. However, mean gray degree of lung 70 heat shock protein （HSP70） was significantly elevated in the high dose group in comparison with the low dose group （P 〈 0.05）, mean gray degree, mean optical density, gross area of HSP70 in other organs and caspase-9 parameters showed no significant differences between groups.CONCLUSION： These results suggest that moxa smoke had no overt toxicity in rats. This work pro- vides evidence and reference for the design of dy- namic inhalation exposure systems.展开更多
OBJECTIVE: To assess the safety and effectiveness of Dengzhanxixin injection(DZI) extracted from Dengzhanxixin(Herba Erigerontis Breviscapi) and identify its potential risks.METHODS: A series of studies were conducted...OBJECTIVE: To assess the safety and effectiveness of Dengzhanxixin injection(DZI) extracted from Dengzhanxixin(Herba Erigerontis Breviscapi) and identify its potential risks.METHODS: A series of studies were conducted on the production process, quality standards, and pharmacology. Postmarketing clinical studies and literature reviews including adverse reactions(ADR),adverse events(ADE), case analysis and systematic reviews were also conducted. Data from the hospital information system and spontaneous reporting system were analyzed.RESULTS: The acute toxicity test indicated that the Lethal Dose 50 test( LD 50) dosage was 250 times more than the clinical maximum daily dosage(6mg/kg). In long-term toxicity tests, rats experi-enced renal tubular damage at 480 mg/kg. However, the dose of 120 mg/kg is safe and non-toxic,which is 40 times above the clinical daily maximum. Beagles had increased serum creatinine at160 mg/kg. In a prospective study, 15 962 cases experienced 16 ADR/ADE. The rate of ADR/ADE was0.1002%. ADR symptoms included rash(16.00%),chills(16.00%), and fever(16.00%).CONCLUSION: There is significant evidence that DZI is safe and effective in a clinical setting.展开更多
文摘Objective:The cross-linked production,which was prepared by HA and cross-linking agent STMP,EDC,GP through cross-linking reaction,might be used in drug delivery system(DDS).To ensure the security of clinical application,the excellent properties such as none cell toxicity,nonirritant,none general toxicity,none immunological rejection are necessary.Methods:In accordance with the request of GB/T 16886.1 on security evaluation of medical biomaterials,cell toxicity test,hemolysis test,intracutaneous stimulation test,acute toxicity test,and hypersensitive test were required.Results:Cell toxicity of HA-STMP,HA-EDC,HA-GP were all less than 1.All hypersensitive tests were eligible.But HA-EDC,HA-GP produced different degrees of slight thrill,slight toxicity,hemolysis rate,which were larger than the standard value.Conclusion:HA-STMP possesses favourable biocompatibility,which is a kind of ideal biomaterials and drug carriers.
文摘Acute and repeat-dose toxic effects ofHOC （7-hydroxycoumarin）, ethanol and their mixture were studied in rats. Single oral administration of HOC （5,000 mg/kg） caused transitional glycosuria associated with lowered serum glucose levels, decreased urea clearance. HOC given orally during 28 days （200 mg/kg） decreased serum glucose, and increased serum triglyceride concentrations. No enhancement of acute toxic effect of HOC （5,000 mg/kg） and ethanol （6,000 mg/kg） mixture was found in the acute toxicity study phase. Effect of HOC （200 mg/kg） and ethanol （750 mg/kg） during 28 days of exposure was less pronounced in comparison with HOC effect only, as far as neither decrease of glucose, nor increase oftriglyceride serum concentrations were found.
文摘Heavy metals pose a potential threat to aquatic organisms. In this study, a static-renewal acute toxicity test was conducted to investigate the effects of cadmium on the antioxidant defense systems （both enzymatic and non-enzymatic） and lipid peroxidaton in liver and gill tissues of juvenile GIFT tilapia Oreochromis niloticus. After 8 days of exposure to Cd （0, 0.016, 0.08, 0.4 and 2 mg/L）, livers accumulated significantly more Cd than gills. Catalase （CAT）, superoxide dismutase （SOD） and glutathione S-transferase （GST） activities were stimulated only at the highest concentration tested （2 mg/L）. Glutathione peroxidase （GPx） activity was stimulated in the gill while inhibited in the liver, these alternations in gill and liver showed a strong relationship with Cd levels in these tissues. This may indicate either a tissue-specific response of GPx to Cd or, most probably, a hormetic effect of Cd on GPx. Cd increased GSH levels and decreased the ratio GSSG/GSH in fish livers at 2 mg/L. Cd exposure resulted in an elevated level of MDA in the livers of fish at 2 mg/L, indicating that Cd caused lipid peroxidation. Taken together, the results demonstrated that Cd altered the enzymatic and non-enzymatic defensive systems and caused lipid peroxidation in O. niloticus at relatively high concentrations （compared to environmentally relevant concentrations）. In addition, the results implied that O. niloticus could tolerate high level of Cd in sites polluted by Cd.
文摘Objective:In the medium of ethanol(non-polar),STMP and ADH as crosslinkers to HA,to prepare drug delivery microspheres by getting stable cross-linked products without a gel phase,and to study biocompatibility and biodegradability of cross-linked products.Methods:ISO10993.1-Safety Evaluation of Biomedical materials as a reference,to make hemolysis test,percutaneous stimulation test,acute toxicity test,and analyze in vitro degradation test,and degradation products.Results:HA-STMP cross-linked product had no hemolysis,no irritation,no acute systemic toxicity,but HA-ADH had a mild skin irritation and adverse acute systemic toxicity.HA-STMP cross-linked product had lower sensitivity on HAse and the curve is flatting.With the increase of degradation time HA-STMP results were changed by the structure analysis,degradation products of these cells were no toxicity.Conclusion:HA-STMP cross-linked products with better biocompatibility and better resistance to hydrolysis could delay the degradation time,which is suitable for the preparation of biodegradable drug carriers.
基金National Nature Science Foundation of China (Grant No.30572350)New Drug Foundation of State Administration of Traditional Chinese Medicine (Grant No.DIX005A)
文摘To further assess hyperoside as a potential new anti-hepatitis B virus （HBV） drug, the safety of hyperoside extracted from Abelmoschus manihot （L.） Medic was evaluated by testing its acute toxicity and mutagenic risk. To test the acute toxicity of hyperoside, we determined the median lethal dose （LD 50 ） in mice. Forty healthy BALB/c mice （20 per sex） were administered a single oral dose of 5000 mg/kg hyperoside via the intragastrical route. The number of animals poisoned and died was noted daily for 14 consecutive days. All animals survived and appeared active and normal, indicating that the LD 50 of hyperoside was more than 5000 mg/kg. Potential genotoxicity of hyperoside was investigated using a bacterial reverse mutation assay （Ames test）, a chromosome aberration test in Chinese hamster lung （CHL） fibroblasts, and an in vivo micronucleus test in rat bone marrow cells. In the bacterial reverse mutation assay, we observed no increases in the number of revertant colonies at any concentrations of hyperoside regardless of metabolic activation （S9） in all tester strains （TA97, TA98, TA100 and TA102） compared to the vehicle control （P0.05）. Hyperoside did not cause significant structural aberration in CHL cells in the presence or absence of S9 （P0.05）. The micronuclei rates of mice bone marrow cell in all groups showed no significant difference when compared with the negative control （P0.05）. In summary, hyperoside showed no genotoxicity in our experimental conditions.
基金Supported by the Study of Warming Effect of Moxibustion and its Principle(the Major National Basic Research Program of China,No.2009CB522904)the Study of Safety of Moxibustion Products Based on High Performance Liquid Chromatography-Mass Spectrometry in Metabonomics Technology(Hunan Graduate Student Innovation Fund,No.CX2010B342)
文摘OBJECTIVE： To design a combined dynamic inhalation device for testing the toxicity induced by moxa smoking. METHODS： The new apparatus （Patent No. 201120101911.5） includes air renewal and recycling systems, a gas generating device, a gas control unit, and a device to measure and control tem- perature and humidity. Sprague-dawley rats were tested for acute and sub-chronic toxicity after exposure to moxa-burning smoke.METHODS： The new apparatus （Patent No. 201120101911.5） includes air renewal and recycling systems, a gas generating device, a gas control unit, and a device to measure and control tem- perature and humidity. Sprague-dawley rats were tested for acute and sub-chronic toxicity after exposure to moxa-burning smoke.RESULTS： We found an LQ0 of 1.2× 10^4 mg/m^3 in the acute toxicity assays. In sub-chronic toxicity tests the organ coefficients studied showed no sig-nificant differences within rats groups of the same gender after treatment with moxa smoke or a month of recovery. However, mean gray degree of lung 70 heat shock protein （HSP70） was significantly elevated in the high dose group in comparison with the low dose group （P 〈 0.05）, mean gray degree, mean optical density, gross area of HSP70 in other organs and caspase-9 parameters showed no significant differences between groups.CONCLUSION： These results suggest that moxa smoke had no overt toxicity in rats. This work pro- vides evidence and reference for the design of dy- namic inhalation exposure systems.
基金Supported by National Science and Technology Major Projects for"Major New Drugs Innovation and Development":Study on Key Technologies of Postmarketing Evaluation for Chinese Medicine(No.2009ZX09502-030)
文摘OBJECTIVE: To assess the safety and effectiveness of Dengzhanxixin injection(DZI) extracted from Dengzhanxixin(Herba Erigerontis Breviscapi) and identify its potential risks.METHODS: A series of studies were conducted on the production process, quality standards, and pharmacology. Postmarketing clinical studies and literature reviews including adverse reactions(ADR),adverse events(ADE), case analysis and systematic reviews were also conducted. Data from the hospital information system and spontaneous reporting system were analyzed.RESULTS: The acute toxicity test indicated that the Lethal Dose 50 test( LD 50) dosage was 250 times more than the clinical maximum daily dosage(6mg/kg). In long-term toxicity tests, rats experi-enced renal tubular damage at 480 mg/kg. However, the dose of 120 mg/kg is safe and non-toxic,which is 40 times above the clinical daily maximum. Beagles had increased serum creatinine at160 mg/kg. In a prospective study, 15 962 cases experienced 16 ADR/ADE. The rate of ADR/ADE was0.1002%. ADR symptoms included rash(16.00%),chills(16.00%), and fever(16.00%).CONCLUSION: There is significant evidence that DZI is safe and effective in a clinical setting.
