三波长分光光度法测定复方甲基炔诺酮片中有效成分的含量

复方甲基炔诺酮片为含甲基炔诺酮(0.3mg/片)和炔雌醇(0.03mg/片)的糖衣片,对其有效成分含量的测定已有比色法、高效液相色谱法、导数分光光度法、荧光法及正交函数法。本文用三波长分光光度法消除组分间的相互干扰,对甲基炔诺酮和炔雌醇的含量进行测定,操作简便。     

3,5-甾二烯化合物的合成及抗早孕活性

以18-甲基-17β-羟基-17α-乙炔基-雌甾-4-烯-3-酮(18-甲基炔诺酮),17β-羟基-17α-乙缺基-雌甾-4-烯-3-酮(炔诺酮),17β-羟基-17α-乙炔基-雄甾-4-烯-3-酮(妊娠素)和17a-羟基孕甾-4-烯-3,20二酮(17α-羟基黄体酮)为原料,经NaBH,还原、脱水、双键转位和酯化等反应合成一系列3,5-甾二烯化合物,用¹HNMR和MS证明了它们的结构。动物筛选结果表明,17β-丙酰氧基-17α-乙炔基-雌甾-3,5-二烯(IV_b2有明显的抗早孕活性。中断早期妊娠的作用似与其雌激素活性有关。     

复方18甲女用长效口服避孕药对恒河猴的远期安全性研究

选用40例成年健康雌性恒河猴(Macaca mulatta)为实验对象,随机将猴均分为两组。服药猴每月定日喂复方18甲1次,剂量按体重计算,约为妇女月用量的两倍。连续给药6年,停药观察4年。对照猴不给药,在相同条件下饲养观察10年。10年内先后进行了药物与肿瘤学、细胞遗传学和生殖内分泌学等方面的观察。结果表明:该药未能诱发猴的恶性肿瘤;没有造成猴子宫内膜超微结构的明显变化和损伤;不引起猴淋巴细胞染色体的畸变率和SCE 频率发生有统计学意义的改变;服药期间猴的排卵被抑制,停药一段时间后,排卵恢复,并能生育,说明恒河猴长期用该药是安全的。     

Clinical trial with a new low oestrogen combined oral contraceptive

Summary

An oral contraceptive combination of 30 μg. ethinyl oestradiol and 150 μg. D-norgestrel was studied in 98 patients over 1216 cycles. No pregnancies were reported during the trial period. Cycle control was good: 96.7% of cycles were 28 ± 3 days with a mean duration of menstrual bleeding of 4.3 days. Bleeding irregularities were not marked; amenorrhoea occurred in 1.7% of cycles, spotting in 5.4% and breakthrough bleeding in 5.8 %. The incidence of side-effects commonly associated with combined oral contraceptives was also low.

The author concludes, therefore, that this new lower-dose combination is an effective and relatively trouble-free ovulation inhibitor.     

18-甲基炔诺酮抗家兔排卵作用机理的初步分析

本实验使用家兔诱导排卵动物模型,分别观察了消旋18-甲基炔诺酮和左旋18-甲基炔诺酮对于用铜盐、由PMSG和hCG以及由LH-RH诱导的家兔排卵的影响。实验分三组:一组于实验第1～3天皮下注射雌二醇(每只100μg/天),第4天经耳缘静脉注射1%醋酸酮(0.4ml/kg),24小时后处死并检查排卵点。二组于实验第1～2天皮下注射雌二醇,第4天皮下注射一次LH-RH(12.5μg/只),48小时后处死并观察和记数排卵点。三组于实验第2天皮下注射PMSG(12.5u),第4天经耳缘静脉注射50iuhCG,48小时后处死并检查排卵点。各组中的实验组于第1～4天肌肉注射消旋18-甲基炔诺酮或左旋18-甲基炔诺酮(每只8mg/天)对照组给予等量溶媒。结果表明,两种18-甲基炔诺酮皆明显抑制由铜盐诱导的家兔排卵,抗排卵率分别为83.3%和66.7%。然而,两者对于由LH-RH和由PMSG与hCG诱导的家兔排卵皆无明显影响。以上结果提示,消旋18-甲基炔诺酮和左旋18-甲基炔诺酮的抗排卵作用可能是通过干扰下丘脑LH-RH的释放而实现的,并非由于在垂体水平拮抗LH-RH的作用或在性腺水平上拮抗促性腺激素作用的结果。     

18-甲基炔诺酮中间体的拆分

D-及L-18-甲基炔诺酮是以消旋19-去甲基13β-乙基-3β,17β-双羟基17α-乙炔基-4-雄甾烯(Ⅲ)为原料,经Ⅲ的丁二酸单醋与(+)α-甲基苯乙胺成盐,然后分离,分别水解,氧化即得D-左旋18-甲基炔诺酮(Ⅶa)和L-右旋18-甲基炔诺酮(Ⅶb)。如用(—)α-甲基苯乙胺,首先得L-构型的右旋18-甲基炔诺酮(Ⅶb),而母液中的D-左旋体未进行分离。     

二阶导数分光光度法和紫外分光光度法测定炔诺孕酮炔雌醚片中炔雌醚和炔诺孕酮的含量

采用二阶导数分光光度法对炔诺孕酮炔雌醚片中炔雌醚的含量进行了测定；采用紫外分光光度法测定炔诺孕酮的含量。该方法不需预先分离，简单、快速，其精密度及准确度均较好。同时，采用一般分光光度计进行手动式二阶导数分光光度法对比实验，也获得了满意的结果。     

Clinical and biochemical investigations of an ultra low-dose combined type oral contraceptive

Summary

A combination of 150 μg. d-norgestrel plus 30 μ.g. ethinyl oestradiol daily was administered by the usual 21-day treatment cycle regimen to 75 young healthy women for a total of 840 cycles. There were no pregnancies, nor any serious side-effects. Cycle control was good with a mean length of 28.5 ± 3.2 days. Breakthrough bleeding occurred in 6.1 % of cycles, spotting in 7.3 % and amenorrhoea in 1.5 %. Fasting early morning blood specimens were collected from some of the women who had received 6 treatment cycles or more, and a large series of biochemical tests was conducted on plasma or serum. The results were contrasted with similar biochemical tests conducted on other women under treatment with other oral contraceptive products, each of which contained 50 μg. daily of synthetic oestrogen. Of 70 biochemical parameters examined, 33 were closer to the normal reference range in women taking the 150/30 d-norgestrelethinyl oestradiol combination than in women using the higher dose products.     

Effects of conjugated equine oestrogens with and without the addition of cyclical norgestrel on serum and urine electrolytes, and the biochemical indices of bone metabolism and liver function

Serum and urine electrolytes, and biochemical indices of bone metabolism and liver function were measured in 51 post-menopausal women treated with two hormone replacement therapy regimens for 24 wk. Twenty-six of the women were treated continuously with conjugated equine oestrogens (0.625 mg/day) and the remainder were treated as above with the addition of norgestrel (0.15 mg/day) during the last 12 days of each 28-day cycle.

Both treatment regimens affected electrolytes in a similar manner. The most consistent effect was a reduction in serum sodium levels and a reduction in urinary sodium/creatinine ratios. The combined regimen appeared to have a greater effect on sodium reabsorption.

Both regimens decreased all the biochemical indices of bone metabolism measured, viz serum calcium (corrected for albumin), phosphate and alkaline phosphatase and urinary calcium/creatinine and hydroxyproline/creatinine ratios. The preparations used decreased the parameters by similar amounts over the 24 wk indicating that both were equally effective in reducing bone turnover. The data suggested, however, that the combined regimen had a more profound effect on bone metabolism during the early phase of treatment.

The two treatment regimens had broadly the same effects on the biochemical indices of liver function, reducing albumin levels and all the liver enzymes. Judging by these indices neither regimen had a deleterious effect on liver function.

We conclude that the two hormone replacement regimens have similar effects on the biochemical indices measured, but there are subtle differences between the two treatments which merit further research.