The solubilities of the lower testosterone esters

The solubilities of the formate to valerate esters of testosterone have been determined in water and several organic solvents. The aqueous solubilities decrease logarithmically as the homologous series is ascended, but the acetate is less soluble than anticipated in the organic solvents. The variation in solubility from ester to ester can be predicted in the organic solvents from thermodynamic data, and is a reflection of the differences in melting point. The melting point differences are explained from the space group dimensions and the area of α to α face contact in the crystals.     

Solubilities of testosterone propionate in non-polar solvents at 100°

THE solubilities of the formate to valerate esters of testosterone in non-polar solvents at 25° were determined by James & Roberts (1968) who also compared them with ideal mole fraction solubilities (X₂), calculated from the equation, (Hildebrand & Scott 1962). ΔH^F is the heat of fusion of the solute and T_M the melting point. Changes in solubility as the homologous series is ascended were predicted by equation (1), but the individual experimental results did not agree with the calculated values. ΔH^F was calculated from the heat of fusion at the melting point, ΔH^F_M, by correcting for the differences in heat capacity of the solid and the supercooled liquid between T_M and T. The correction was estimated with a differential scanning calorimeter by extrapolating the liquid enthalpy line back to 25° and measuring the area between the extrapolation and the enthalpy line of the solid. The method was considered questionable, however, because it assumed that the enthalpy line of the supercooled liquid decreased linearly over the whole range of temperature. This theory is tested below by comparing the measured and calculated solubilities of testosterone propionate at a temperature just below its melting point, where the heat capacity correction is small and ΔH^F_M can be used for ΔH^F. The solvents examined by James & Roberts (1968) had smaller molar volumes than the testosterone esters, and it was suggested that the difference in molar volume between solute and solvent could prevent the random distribution assumed by regular solution theory. Prediction of solubility would thus improve as the molar volume of the solvent approached that of the solute. The test is applied below by determining the solubility of testosterone propionate in a range of solvents.     

高效液相色谱法测定复方丙睾凝胶剂中丙酸睾酮的含量

目的:测定复方丙睾凝胶剂中丙酸睾酮的含量。方法:用高效液相色谱法,采用Kromasil C18柱,以甲醇-水(85∶15)为流动相,流速为0.8 ml/min,检测波长为254 nm,柱温为25℃。结果:丙酸睾酮在0.030 3~0.161 6 mg/ml内呈现良好的线性关系(r=0.999 9)。结论:本法可灵敏、快速、准确测定复方丙睾凝胶剂中丙酸睾酮的含量。     

The effect of testosterone propionate supplement on testicular toxicity with thiamphenicol in male Sprague-Dawley rats

Testosterone propionate (TP) was supplemented to male rats for assessment of its ameliorating effect on testicular toxicity with thiamphenicol (TAP). A total of 20 male Sprague-Dawley rats were treated orally with TAP at 200 mg/kg/day for up to 4 weeks. In addition, 5 male rats were allotted to the control group receiving vehicle only. Ten of the 20 treated rats had a Silastic capsule (containing about 80 mg of TP) implanted in the dorsal skin at Week 2 and assigned to the TAP-TP group, while the other 10 treated rats were in the TAP group. After Weeks 3 and 4, five of both treated groups were examined for weight and histology of the testis and accessory genital glands, and for staging analysis of the seminiferous tubules. The same parameters were also assessed in the control group after Week 4. Weights and morphology of the seminal vesicle and prostate recovered remarkably from the TAP toxicity after TP supplement. However, no ameliorating effects of TP were obtained for the testis in either weight, morphology, or staging analysis of the seminiferous tubules.     

The effect of testosterone propionate on energy metabolism indices and the catecholamine content of the vascular wall

The effect of testosterone propionate (1 mg/kg) on the specific activity of lactate dehydrogenase, malate dehydrogenase, contents of pyruvic and lactic acids, levels of catecholamines in target tissues and non-target tissues of rats was studied. Deficit of androgens and their single compensation by administering testosterone propionate lead to an inhibition of energy formation, a decrease of enzyme activity and contents of metabolites in tissues of the seminal vesicles. The course administration of testosterone propionate increases the activity of malate dehydrogenase in the aorta and myocardium. Acetylsalicylic acid (40 mg/kg) induces an increase of noradrenaline levels in the heart and aorta along with an increase of androgen level in the organism.     

睾酮对大鼠睾丸形态学的影响

本文研究了丙酸睾酮对大鼠睾丸形态超微结构的影响,结果发现：大剂量外源性丙酸睾酮可使睾丸出现抑制性超微结构的形态学改变。     

Avermectin在不同溶剂中溶解度的测定与关联

本文用动态法测定avermectin在甲醇、乙醇、正丙醇、正丁醇和正戊醇中的溶解度曲线，并分别用理想溶液模型、Apelblat溶解度模型和多项式经验方程对实验测定溶解度数据进行关联。结果显示理想溶液模型的误差较大，多项式经验方程的误差最小。实验得到的溶解度曲线及关联结果对avermectin结晶工艺的研究具有较大的指导意义。     

丙酸睾丸酮及催产素配伍米非司酮及米索前列醇抗早孕研究

目的　研究丙酸睾丸酮及催产素配伍米非司酮及米索前列醇抗早孕的临床效果。方法　将停药天数≤ 49d的早孕妇女 2 0 0例随机分为两组 ,对照组 :10 0例 ,米非司酮 2 5mg ,每日 3次 ,连服 2d ,于第 3天晨空腹 1次口服米索前列醇 60 0 μg。试验组 :服药剂量及方法同对照组 ,服药第 1、2天上午加肌肉注射丙酸睾丸酮各 10 0mg ,孕囊排出后立即肌肉注射催产素 2 0IU。结果　试验组完全流产率96% ,对照组 85 % ,差异显著 (P <0 .0 5 ) ;试验组孕囊排出时间、阴道出血量明显少于对照组 ,差异显著(P <0 .0 5 )。结论　加用丙酸睾丸酮可加强早孕绒毛组织的损伤作用 ,丙酸睾丸酮及催产素可明显促进绒毛球更完整 ,更快排出 ,减少流产后出血量 ,缩短出血时间。     

丙酸睾丸酮和神经节苷脂对交感神经化学损毁的影响

正常成年早小鼠♀经6-羟多巴胺(6—OHDA)15mg·kg~(-1)ip后24h颌下腺内去甲肾上腺素(NE)和多巴胺(DA)含量均下降95％以上,2wk时分别恢复到59和33％,丙酸睾丸酮(TP)给药后颌下腺内NE的含量提高63％,TP处理后再给6-OHDA,24 h和2 wk时腺体内的NE和DA含量仍在正常水平,但都低于正常动物TP处理后的水平;6-OHDA损伤早期给神经节苷脂(GM),24h颌下腺内NE和DA含量没有下降,而在2wk时有明显下降;TP处理后的动物在损伤早期再给GM,在2wk时NE和DA含量与正常动物TP处理后的水平相当,TP和GM在抗6-OHDA损伤中可能有协同作用。     

Promoting effect of testosterone propionate on experimental exocrine pancreatic tumors by 4-hydroxyaminoquinoline 1-oxide in rats

A single intravenous injection of 4-hydroxyaminoquinoline 1-oxide in a dose of 9 mg/kg induced exocrine adenomas of the pancreas in a significantly higher rate in male than in female rats. Castration following HAQO administration diminished the incidence of the pancreatic tumors in male rats. A combined treatment with castration and weekly injections of testosterone propionate in a dose of 1 mg/rat after HAQO administration resulted in high incidence of the pancreatic tumors in both sexes. From these findings, it is concluded that testosterone can promote the induction of the pancreatic tumors in rats by HAQO.     

丙酸睾酮对去势beagle犬前列腺上皮细胞的影响

目的　探讨丙酸睾酮与犬前列腺上皮细胞生长的关系。方法　去势beagle犬经丙酸睾酮处理后 ,获取前列腺组织 ,利用放射免疫分析法 (RIA)测定前列腺组织中双氢睾酮 (DHT)含量。组织经石蜡包埋切片 ,HE染色 ,显微镜下观察前列腺的组织学变化 ,并借助显微图像分析技术测定前列腺腺腔大小及腺上皮细胞高度。免疫组织化学技术检测前列腺上皮细胞前列腺特异抗原 (PSA)及酸性磷酸酶(PAP)的表达。结果　去势犬经丙酸睾酮处理后 ,前列腺中DHT水平明显升高。光镜下前列腺腺腔增大 ,腺上皮细胞增高。图像分析结果显示前列腺腺腔面积明显增大 (P <0 .0 1) ,增大后面积分别为对照组的 4 .5～ 7倍 ,腺上皮细胞高度明显增高(P <0 .0 1) ,细胞增高幅度分别为对照组的 4～ 8倍。免疫组化结果显示丙酸睾酮处理组前列腺上皮细胞PSA表达高于对照组 (P <0 .0 5 ) ,PAP的表达也高于对照组 (P <0 .0 5 )。结论　去势犬前列腺上皮细胞生长及功能正常发挥依赖于雄激素 ,剥夺雄激素导致前列腺上皮细胞萎缩     

Prediction of the solubility of griseofulvin in glycerides and other solvents of relatively low polarity from simple regular solution theory

Regular solution theory is applied to literature values of the solubility of griseofulvin in hydrocarbons and in other solvents of relatively low polarity. The solubility parameter of griseofulvin is calculated as $\text{10.2 ± 0.2}\text{cal}{}^{\mathrm{<mtext>1</mtext><mtext>2</mtext>}}\text{·}\text{cm}{}^{\mathrm{<mtext>?</mtext><mtext>3</mtext><mtext>2</mtext>}}\text{at 25 °}\text{C}$. The relatively high solubilities of griseofulvin in polar, non-hydrogen-bonded solvents are interpreted in terms of dipolar or hydrogen-bonding interactions between solute and solvent, whereas the sub-ideal solubilities in alcohols and water are attributed to solvent self-association. The solubilities of griseofulvin in the glycerides are predicted from regular solution theory in its simplest form, assuming that London dispersion forces are the most important interactions in solution. The solubility parameter of each solvent is calculated from its refractive index. The predicted values agree well with the experimental values of solubility in the triglycerides and diglycerides, except when the hydrocarbon component is so high that the solvent is behaving effectively as a hydrocarbon. The solubilities of griseofulvin in the monoglycerides are about one-fifth of the predicted values, and this is attributed to appreciable solvent self-association by hydrogen-bonding.     

Comparison of the biological effectiveness of injected testosterone propionate and testosterone released from silastic capsules

The in vitro release and biological effectiveness of silicone rubber implants containing testosterone in orchidectomized male rats was investigated over a period of 20 weeks. A marked reduction in release in 0.9% saline solution could be observed in vitro relative to the incubation time in the medium. The reduction in release was greatest during the first few weeks of the experiment. Rat seminal vesicles and prostates, which were greatly stimulated at the start of the experiment, lost weight corresponding to the release rate in vitro. The implants containing testosterone used here were 4 to 26 times more effective than testosterone propionate injected s.c.     

The effect of allopurinol on testosterone metabolism

Plasma testosterone, dehydroepiandrosterone, 17-hydroxy-progesterone and estrogens were diminished in male renal stone patients under treatment with allopurinol, whereas urinary testosterone glucuronide was elevated. Since plasma LH (luteinizing hormone) was diminished it is concluded that allopurinol decreases the plasma testosterone level via an inhibition of LH secretion. Also in male rats treated with allopurinol, plasma testosterone and LH concentrations were diminished. The activities of NADPH-5 alpha-reductase and the testosterone hydroxylases in rat liver microsomes were decreased, UDP-glucuronyl transferase activity was elevated. delta 5-3 beta-Hydroxysteroid dehydrogenase/delta 4,5-isomerase and 17 beta-hydroxysteroid dehydrogenase in rat testes were unchanged.     

The effect of solvents on drug metabolism in vitro

Nine water-miscible organic solvents, methanol, ethanol, acetone, ethoxyethanol, tetrahydrofuran, dioxane, dimethylformamide, acetonitrile, and dimethyl sulfoxide were each used with five commonly employed substrates of in vitro microsomal mixed-function oxidase assays containing liver 9,000g supernatant fractions from rats treated with phenobarbital or Aroclor 1254. When the metabolism of aminopyrine, aniline, 7-ethoxycoumarin, p-nitroanisole, and benzo[a]pyrene was determined in the presence of these solvents, varying degrees of stimulation and inhibition were observed. These effects were dependent on the substrate studied, the particular solvent incorporated into the assay, and the rat liver 9000g supernatant fraction used. These differential effects were also observed when 2-aminoanthracene was metabolically activated in the Ames Salmonella/mammalian-microsome mutagenicity test, but were not as dramatic when benzo[a]pyrene was tested.     

An infrared study of solute-solvent interactions of testosterone propionate

Interactions between testosterone propionate and 10 different organic solvents have been investigated by observing the shifts of the stretching frequencies of the ketone and ester carbonyl groups. The shifts are shown to be approximately proportional to the degree of deviation from regular solution behaviour. The solvents are classified into three groups and the possible interactions in each discussed.