Ethinyl estradiol（EE） as a contraceptive,（17α）-19-nopregna-1,3,5-（10）-trien-20-yne-3,17-diol（formula： C（20）H（24）O2, molecular weight： 296.4, CAS number： 57-63-6）, is known to have different pseudo-poly...Ethinyl estradiol（EE） as a contraceptive,（17α）-19-nopregna-1,3,5-（10）-trien-20-yne-3,17-diol（formula： C（20）H（24）O2, molecular weight： 296.4, CAS number： 57-63-6）, is known to have different pseudo-polymorphic forms. Some EE polymorphs have been synthesized by means of physical or chemical methods, characterized by X-ray powder diffraction（XRPD）, thermogravimetric（TG）, differential scanning calorimetry（DSC） and IR spectra. Dissolution profile was tested by high performance liquid chromatography（HPLC）. Meanwhile, the crystal structure of the new EE solvate（formamide） was characterized by single-crystal X-ray structure analysis（SXRD）. The results confirmed that EE existed polymorphism. Five crystal forms of EE were presented and two of them were reported firstly. Furthermore, five polymorphs＇ dissolution curves were drawn and they could be identified by several analysis methods. Our study on polymorphs of EE could provide a variety of crystal material composition, preparation methods and solubility.展开更多
A sensitive and simultaneous liquid chromatography-tandem mass spectrometry method was developed and validated for quantification of ethinyl estradiol and levonorgestrel. The analytes were extracted with methyl-tert-b...A sensitive and simultaneous liquid chromatography-tandem mass spectrometry method was developed and validated for quantification of ethinyl estradiol and levonorgestrel. The analytes were extracted with methyl-tert-butyl ether： n-hexane （50：50, v/v） solvent mixture, followed by dansyl derivatization. The chromatographic separation was performed on a Kinetex Cla （50 mm × 4.6 mm, 2.6 μm） column with a mobile phase of 0.1% （v/v） formic acid in water and acetonitrile in gradient composition. The mass transitions were monitored in electrospray positive ionization mode. The assay exhibited a linear range of 0.100-20.0 ng/mL for levonorgestrel and 4.00-500 pg/mL for ethinyl estradiol in human plasma. A run time of 9.0 min for each sample made it possible to analyze a throughput of more than 100 samples per day. The validated method has been successfully used to analyze human plasma samples for application in pharmacokinetic and bioequivalence studies.展开更多
Objective:To assess the effect of plumbagin-free alcohol extract（PFAE） of Plumbago zeylanica Linn.（Plumbaginaceae）（P.zeylanica） root,on female reproductive system and ferlility of adult Female wislar rats.Method...Objective:To assess the effect of plumbagin-free alcohol extract（PFAE） of Plumbago zeylanica Linn.（Plumbaginaceae）（P.zeylanica） root,on female reproductive system and ferlility of adult Female wislar rats.Methods:After the oral acute toxicity study,the PFAE was administered at two dose levels to perform the estrous cycle study,anti-implantation and ahortifacient activity and hormonal analysis.However,the estrogenic/antiestrogenic activity was evaluated at only one most effective dose.Results:LD<sub>50</sub> cut-off was 5 000 mg/kg body weight.The extract exhibited significant anti-implantation and ahortifacient activity at the tested dose levels（300 and 500 mg/ kg.p.o.）（P【0.01）.The extract dose-dependency decreased the levels of serum progesterone, follicle stimulating hormone and luteinizing hormone,while a dose-dependent increase was observed in the concentration of serum prolactin.The extract did not show any significant changes in structure and function of Uterus when given alone,hut when given along with ethinyl estradiol,it exhibited significant antiestrogenic activity in immature overieclonzed female rats（P【0.001） Biochemical parameters in the serun/blood and haematological parameters did not show appreciable changes throughout and after the course of investigation.However,all the altered parameters returned to normalcy within 30 days following withdrawal of treatment. Conclusions:All findings suggest that the anlifcrtility activity of extract could possibly he through the changes in the implantation site,altered hormonal levels,prolonged estrous cycle and anti-estrogenic activity.Hence,the extract possesses reversible antifcrtility activity without adverse toxicity in female rats.展开更多
Objective To investigate the feasibility and optimal regimen of orally administration of low dose gossypol acetic acid （GA） combined with methyltestosterone （MT） plus ethinyl estradiol （EE） for contraception in ...Objective To investigate the feasibility and optimal regimen of orally administration of low dose gossypol acetic acid （GA） combined with methyltestosterone （MT） plus ethinyl estradiol （EE） for contraception in males.Methods Wistar male rats were randomly assigned into four groups, 20 in each group. Animals in group A or B were administered daily with 1% methyl cellulose or GA （12 mg/kg） suspended in 1% methyl cellulose, respectively. Rats in group C or D took firstly GA 12 mg/kg＋MT 20 mg/kg＋EE 0.1 mg/kg or MT 20 mg/kg＋EE 0.1 mg/kg, in asuspension with 1% methyl cellulose, via gastric intubation. After the infertilities were initiated（6 weeks for group C, 8 weeks for group D）, GA was served alone while MT＋EE were withdrawn in rats of groups C and D. The treatment was ceased after 18 weeks and some males from group C were permitted to recover. Fertility testing, 10 males per group, was served for determining infertility or restoration of fertility in treated rats. Examinations of histology and biochemistry in treated rats were used to examine the morphologic influences on sperm, testis, epididymides and viscera, and biochemical changes in blood. The growth and development of F1 generation of the rats would also be tested in a series of behavioral tests.Results Ten rats from group C were infertile at week 6 after treatment, and the fulfilled infertility was maintained with low-dose GA （12 mg/kg） only daily. Six weeks after cessation of treatment, all of treated males recovered their fertility. However, 8 of 10 rats from group D were in sterility at 6th week of treatment and all at 8th week of treatment, but the infertility could not be kept with the similar dose GA alone later on. Moreover, no adverse effects were found in our present experiments.Conclusion Administration of oral low dose GA combined with MT and EE as loading dose could successfully induce infertility in short term, whereafter the efficacy could completely be maintained by similar low dose of GA alone for long term. 展开更多
Objective:To study the endocrinologic and metabolic effects of metformin in combi-nation with compound cyproterone acetate (CPA) on patients with polycystic ovariansyndrome (PCOS).Methods: A prospective study involved...Objective:To study the endocrinologic and metabolic effects of metformin in combi-nation with compound cyproterone acetate (CPA) on patients with polycystic ovariansyndrome (PCOS).Methods: A prospective study involved total 65 patients, 45 PCOS patients as group Aand 20 non-PCOS infertility patients as control (group B). Complete baseline work-up inclu-ding body mass index (BMI), waist/hip ratio(WHR), Ferriman-Gallwey score(FGS), gona-dotrophin, testosterone(T), sex hormone-binding globulin (SHBG), dehydroepiandrosteronesulfate (DHEAS), and fasting lipid, glucose (FG) , insulin (FI) and oral glucose tolerancetest (OGTT), were performed in all patients. Patients in group A were treated with CPA a-lone (group A1), metformin alone (group A2) or combination of CPA with metformin (groupA3) , respectively by randomizatior. At the end of the 12-week therapy, subjects were re-evaluated and above parameters were measured.Results: Women in group A had significant increases in BMI, WHR, FGS, LH, T,FI, insulin resistance (IR), triglycerides(TG), and significant decrease in HDL-C com-paring with the control group (P＜0.01). No significant difference among A1, A2 andA3 were found at baseline. LH, T, FT (free testosterone) were significant decreasedfrom (13.9±5.9)IU/L, (2. 1±0. 8)nmol/L and (2.8±2.3)nmol/L respectively to(5.8±2.2)IU/L, (1.2±0. 4)nmol/L and (0. 8±0.5)nmol/L respectively and SHBGwas significant increased from (99 ± 42) nmol/L to (187±64)nmol/L in group A3,when compared with LH,T and FT from (13.8±7.6)IU/L, (2.2±1.1) nmol/L and(2. 5±1.9) nmol/L respectively to (11.8±6.5)IU/L, (1.8±0.8) nmol/L and (1.7±1.0) nmol/L respectively and SHBG from (99±40) nmol/L to (120±51) nmol/L ingroup A2 (P＜0.05,P＜0. 001). HDL-C was significant increased from (1.5±0.3)mmol/L to (1.8±0.3) mmol/L in group A3 comparing with HDL-C from (1.5±0.4)mmol/L to (1.6±0.4) mmol/L in groupA1(P＜0.001).Conclusions: The PCOS patients treated with metformin in combination with compoundcyproterone acetate may be more effective展开更多
基金supported by the Key National Research and Development Programs(No.2016YFC1000900)
文摘Ethinyl estradiol（EE） as a contraceptive,（17α）-19-nopregna-1,3,5-（10）-trien-20-yne-3,17-diol（formula： C（20）H（24）O2, molecular weight： 296.4, CAS number： 57-63-6）, is known to have different pseudo-polymorphic forms. Some EE polymorphs have been synthesized by means of physical or chemical methods, characterized by X-ray powder diffraction（XRPD）, thermogravimetric（TG）, differential scanning calorimetry（DSC） and IR spectra. Dissolution profile was tested by high performance liquid chromatography（HPLC）. Meanwhile, the crystal structure of the new EE solvate（formamide） was characterized by single-crystal X-ray structure analysis（SXRD）. The results confirmed that EE existed polymorphism. Five crystal forms of EE were presented and two of them were reported firstly. Furthermore, five polymorphs＇ dissolution curves were drawn and they could be identified by several analysis methods. Our study on polymorphs of EE could provide a variety of crystal material composition, preparation methods and solubility.
文摘A sensitive and simultaneous liquid chromatography-tandem mass spectrometry method was developed and validated for quantification of ethinyl estradiol and levonorgestrel. The analytes were extracted with methyl-tert-butyl ether： n-hexane （50：50, v/v） solvent mixture, followed by dansyl derivatization. The chromatographic separation was performed on a Kinetex Cla （50 mm × 4.6 mm, 2.6 μm） column with a mobile phase of 0.1% （v/v） formic acid in water and acetonitrile in gradient composition. The mass transitions were monitored in electrospray positive ionization mode. The assay exhibited a linear range of 0.100-20.0 ng/mL for levonorgestrel and 4.00-500 pg/mL for ethinyl estradiol in human plasma. A run time of 9.0 min for each sample made it possible to analyze a throughput of more than 100 samples per day. The validated method has been successfully used to analyze human plasma samples for application in pharmacokinetic and bioequivalence studies.
文摘Objective:To assess the effect of plumbagin-free alcohol extract（PFAE） of Plumbago zeylanica Linn.（Plumbaginaceae）（P.zeylanica） root,on female reproductive system and ferlility of adult Female wislar rats.Methods:After the oral acute toxicity study,the PFAE was administered at two dose levels to perform the estrous cycle study,anti-implantation and ahortifacient activity and hormonal analysis.However,the estrogenic/antiestrogenic activity was evaluated at only one most effective dose.Results:LD<sub>50</sub> cut-off was 5 000 mg/kg body weight.The extract exhibited significant anti-implantation and ahortifacient activity at the tested dose levels（300 and 500 mg/ kg.p.o.）（P【0.01）.The extract dose-dependency decreased the levels of serum progesterone, follicle stimulating hormone and luteinizing hormone,while a dose-dependent increase was observed in the concentration of serum prolactin.The extract did not show any significant changes in structure and function of Uterus when given alone,hut when given along with ethinyl estradiol,it exhibited significant antiestrogenic activity in immature overieclonzed female rats（P【0.001） Biochemical parameters in the serun/blood and haematological parameters did not show appreciable changes throughout and after the course of investigation.However,all the altered parameters returned to normalcy within 30 days following withdrawal of treatment. Conclusions:All findings suggest that the anlifcrtility activity of extract could possibly he through the changes in the implantation site,altered hormonal levels,prolonged estrous cycle and anti-estrogenic activity.Hence,the extract possesses reversible antifcrtility activity without adverse toxicity in female rats.
文摘Objective To investigate the feasibility and optimal regimen of orally administration of low dose gossypol acetic acid （GA） combined with methyltestosterone （MT） plus ethinyl estradiol （EE） for contraception in males.Methods Wistar male rats were randomly assigned into four groups, 20 in each group. Animals in group A or B were administered daily with 1% methyl cellulose or GA （12 mg/kg） suspended in 1% methyl cellulose, respectively. Rats in group C or D took firstly GA 12 mg/kg＋MT 20 mg/kg＋EE 0.1 mg/kg or MT 20 mg/kg＋EE 0.1 mg/kg, in asuspension with 1% methyl cellulose, via gastric intubation. After the infertilities were initiated（6 weeks for group C, 8 weeks for group D）, GA was served alone while MT＋EE were withdrawn in rats of groups C and D. The treatment was ceased after 18 weeks and some males from group C were permitted to recover. Fertility testing, 10 males per group, was served for determining infertility or restoration of fertility in treated rats. Examinations of histology and biochemistry in treated rats were used to examine the morphologic influences on sperm, testis, epididymides and viscera, and biochemical changes in blood. The growth and development of F1 generation of the rats would also be tested in a series of behavioral tests.Results Ten rats from group C were infertile at week 6 after treatment, and the fulfilled infertility was maintained with low-dose GA （12 mg/kg） only daily. Six weeks after cessation of treatment, all of treated males recovered their fertility. However, 8 of 10 rats from group D were in sterility at 6th week of treatment and all at 8th week of treatment, but the infertility could not be kept with the similar dose GA alone later on. Moreover, no adverse effects were found in our present experiments.Conclusion Administration of oral low dose GA combined with MT and EE as loading dose could successfully induce infertility in short term, whereafter the efficacy could completely be maintained by similar low dose of GA alone for long term.
文摘Objective:To study the endocrinologic and metabolic effects of metformin in combi-nation with compound cyproterone acetate (CPA) on patients with polycystic ovariansyndrome (PCOS).Methods: A prospective study involved total 65 patients, 45 PCOS patients as group Aand 20 non-PCOS infertility patients as control (group B). Complete baseline work-up inclu-ding body mass index (BMI), waist/hip ratio(WHR), Ferriman-Gallwey score(FGS), gona-dotrophin, testosterone(T), sex hormone-binding globulin (SHBG), dehydroepiandrosteronesulfate (DHEAS), and fasting lipid, glucose (FG) , insulin (FI) and oral glucose tolerancetest (OGTT), were performed in all patients. Patients in group A were treated with CPA a-lone (group A1), metformin alone (group A2) or combination of CPA with metformin (groupA3) , respectively by randomizatior. At the end of the 12-week therapy, subjects were re-evaluated and above parameters were measured.Results: Women in group A had significant increases in BMI, WHR, FGS, LH, T,FI, insulin resistance (IR), triglycerides(TG), and significant decrease in HDL-C com-paring with the control group (P＜0.01). No significant difference among A1, A2 andA3 were found at baseline. LH, T, FT (free testosterone) were significant decreasedfrom (13.9±5.9)IU/L, (2. 1±0. 8)nmol/L and (2.8±2.3)nmol/L respectively to(5.8±2.2)IU/L, (1.2±0. 4)nmol/L and (0. 8±0.5)nmol/L respectively and SHBGwas significant increased from (99 ± 42) nmol/L to (187±64)nmol/L in group A3,when compared with LH,T and FT from (13.8±7.6)IU/L, (2.2±1.1) nmol/L and(2. 5±1.9) nmol/L respectively to (11.8±6.5)IU/L, (1.8±0.8) nmol/L and (1.7±1.0) nmol/L respectively and SHBG from (99±40) nmol/L to (120±51) nmol/L ingroup A2 (P＜0.05,P＜0. 001). HDL-C was significant increased from (1.5±0.3)mmol/L to (1.8±0.3) mmol/L in group A3 comparing with HDL-C from (1.5±0.4)mmol/L to (1.6±0.4) mmol/L in groupA1(P＜0.001).Conclusions: The PCOS patients treated with metformin in combination with compoundcyproterone acetate may be more effective
