The effects of solvent and impurity on the crystal habit of 11α-hydroxy-16α,17α-epoxyprogesterone (HEP)grown from solution were studied by scanning electron microscope.Long prismatic crystals were produced when HEP...The effects of solvent and impurity on the crystal habit of 11α-hydroxy-16α,17α-epoxyprogesterone (HEP)grown from solution were studied by scanning electron microscope.Long prismatic crystals were produced when HEP was crystallized from pure acetone and N,N-dimethylformamide,while blocky crystals were produced from pure chloroform by cooling crystallization.One kind of isomorphic impurity,16α,17α-epoxyprogesterone(EP) was selected to examine its effect on the HEP crystal habit.When the content of EP in the mother liquor is very high(55.45%,solvent free basis),the habit of produced HEP crystals was greatly modified from prismatic to octa-hedral.The differential scanning calorimetry and X-ray powder diffraction analyses showed that the change of crystal habit was originated from the crystal structure modification.展开更多
背景与目的:由小鼠全身动态PET显像数据获得药物在小鼠体内的生物分布,利用器官内剂量评估/指数模型分析软件(organ level inter dose assessment/exponential model,OLINDA/EXM)估算18F-fluoroestradiol,^(18)F-FES)在人体内的吸收剂...背景与目的:由小鼠全身动态PET显像数据获得药物在小鼠体内的生物分布,利用器官内剂量评估/指数模型分析软件(organ level inter dose assessment/exponential model,OLINDA/EXM)估算18F-fluoroestradiol,^(18)F-FES)在人体内的吸收剂量、全身有效剂量和有效剂量当量。方法:健康雌性KM小鼠尾静脉注射^(18)F-FES后行160 min动态PET采集,经3D-OSEM/MAP算法重建获得PET图像。再行高分辨率CT显像,在PET/CT融合图像上,选取各脏器勾画感兴趣体积(volume of interest,VOI),获得相应时间-活度曲线和其曲线下面积、滞留时间、成年女性体模对应各器官的滞留时间。依据美国核医学会医用内照射剂量学委员会提出的内照射剂量计算方法(MIRD体系),利用OLINDA/EXM软件计算^(18)F-FES在人体内的吸收剂量、全身有效剂量和有效剂量当量。最后所得数据与已公开发表计算^(18)F-FES内照射剂量的文献数据行配对t检验,验证本文方法的有效性。结果:人体内胆囊壁、膀胱壁、小肠、上部大肠和肝脏的吸收剂量最高,分别为0.072 5、0.044 5、0.043 0、0.031 5和0.028 2 m Gy/MBq。大脑、皮肤、乳腺、心脏壁和甲状腺吸收剂量最低,分别为0.005 2、0.001 1、0.001 2、0.001 2和0.001 3 m Gy/MBq。对放射性敏感的器官如骨原细胞、胸腺和红骨髓的吸收剂量均较低,范围为0.001 4~0.021 8 m Gy/MBq。全身平均吸收剂量为0.014 7 m Gy/MBq,全身有效剂量当量为0.025 0 m Gy/MBq,全身有效剂量为0.019 0 m Sv/MBq。对于常规注射185 MBq ^(18)F-FES,人体有效剂量为3.515 0 m Sv。与直接测量^(18)F-FES在健康人体各主要脏器内吸收剂量的文献行配对t检验,差异无统计学意义(t=1.478,P=0.153)。结论:利用OLINDA/EXM软件根据小鼠全身动态PET/CT数据可有效估算^(18)F-FES在人体内的吸收剂量和有效剂量。^(18)F-FES可安全地用于人体,其有效剂量低于允许范围上限。该研究可为临床放心使用^(18)F-FES提供依据。展开更多
Hydroxy-16α,17α,21-trimethyl-5-en-20-one was synthesized from 3α-acetoxypregna-5,16-dien-20-one and characterized by elemental analysis, 1H NMR, MS and IR. 16α,17α-Dimethyl steroid was formed by treatment of 3β-...Hydroxy-16α,17α,21-trimethyl-5-en-20-one was synthesized from 3α-acetoxypregna-5,16-dien-20-one and characterized by elemental analysis, 1H NMR, MS and IR. 16α,17α-Dimethyl steroid was formed by treatment of 3β-acetoxypregna-5,16-dien-20-one with methylmagnesium bromide, followed by reaction of the resulting 17(20)-enolate with methyl iodide. The main by- products were 3β-hydroxy-16α,17α-dimethyl-5-en-20-one. LHDMS([(CH 3) 3Si] 2NLi) and LDA([(CH 3) 2CH] 2NLi) were chosen as proper reagents for 21-position alkylation. The almost quantitative conversion of 16α,17α-dimethyl corticosteroid was achieved and the highest yield of the 16α,17α,21-trimethyl corticosteroid was 78%. The optimum reaction temperature was -20 ℃ for 16α,17α- dialkylation and was -50 ℃ for 21- position alkylation.展开更多
文摘The effects of solvent and impurity on the crystal habit of 11α-hydroxy-16α,17α-epoxyprogesterone (HEP)grown from solution were studied by scanning electron microscope.Long prismatic crystals were produced when HEP was crystallized from pure acetone and N,N-dimethylformamide,while blocky crystals were produced from pure chloroform by cooling crystallization.One kind of isomorphic impurity,16α,17α-epoxyprogesterone(EP) was selected to examine its effect on the HEP crystal habit.When the content of EP in the mother liquor is very high(55.45%,solvent free basis),the habit of produced HEP crystals was greatly modified from prismatic to octa-hedral.The differential scanning calorimetry and X-ray powder diffraction analyses showed that the change of crystal habit was originated from the crystal structure modification.
文摘背景与目的:由小鼠全身动态PET显像数据获得药物在小鼠体内的生物分布,利用器官内剂量评估/指数模型分析软件(organ level inter dose assessment/exponential model,OLINDA/EXM)估算18F-fluoroestradiol,^(18)F-FES)在人体内的吸收剂量、全身有效剂量和有效剂量当量。方法:健康雌性KM小鼠尾静脉注射^(18)F-FES后行160 min动态PET采集,经3D-OSEM/MAP算法重建获得PET图像。再行高分辨率CT显像,在PET/CT融合图像上,选取各脏器勾画感兴趣体积(volume of interest,VOI),获得相应时间-活度曲线和其曲线下面积、滞留时间、成年女性体模对应各器官的滞留时间。依据美国核医学会医用内照射剂量学委员会提出的内照射剂量计算方法(MIRD体系),利用OLINDA/EXM软件计算^(18)F-FES在人体内的吸收剂量、全身有效剂量和有效剂量当量。最后所得数据与已公开发表计算^(18)F-FES内照射剂量的文献数据行配对t检验,验证本文方法的有效性。结果:人体内胆囊壁、膀胱壁、小肠、上部大肠和肝脏的吸收剂量最高,分别为0.072 5、0.044 5、0.043 0、0.031 5和0.028 2 m Gy/MBq。大脑、皮肤、乳腺、心脏壁和甲状腺吸收剂量最低,分别为0.005 2、0.001 1、0.001 2、0.001 2和0.001 3 m Gy/MBq。对放射性敏感的器官如骨原细胞、胸腺和红骨髓的吸收剂量均较低,范围为0.001 4~0.021 8 m Gy/MBq。全身平均吸收剂量为0.014 7 m Gy/MBq,全身有效剂量当量为0.025 0 m Gy/MBq,全身有效剂量为0.019 0 m Sv/MBq。对于常规注射185 MBq ^(18)F-FES,人体有效剂量为3.515 0 m Sv。与直接测量^(18)F-FES在健康人体各主要脏器内吸收剂量的文献行配对t检验,差异无统计学意义(t=1.478,P=0.153)。结论:利用OLINDA/EXM软件根据小鼠全身动态PET/CT数据可有效估算^(18)F-FES在人体内的吸收剂量和有效剂量。^(18)F-FES可安全地用于人体,其有效剂量低于允许范围上限。该研究可为临床放心使用^(18)F-FES提供依据。
文摘Hydroxy-16α,17α,21-trimethyl-5-en-20-one was synthesized from 3α-acetoxypregna-5,16-dien-20-one and characterized by elemental analysis, 1H NMR, MS and IR. 16α,17α-Dimethyl steroid was formed by treatment of 3β-acetoxypregna-5,16-dien-20-one with methylmagnesium bromide, followed by reaction of the resulting 17(20)-enolate with methyl iodide. The main by- products were 3β-hydroxy-16α,17α-dimethyl-5-en-20-one. LHDMS([(CH 3) 3Si] 2NLi) and LDA([(CH 3) 2CH] 2NLi) were chosen as proper reagents for 21-position alkylation. The almost quantitative conversion of 16α,17α-dimethyl corticosteroid was achieved and the highest yield of the 16α,17α,21-trimethyl corticosteroid was 78%. The optimum reaction temperature was -20 ℃ for 16α,17α- dialkylation and was -50 ℃ for 21- position alkylation.
