壬苯醇醚_(-9)(NP_9)栓避孕效果的研究

津NP_9栓经多中心临床342例3963个月经周期的观察避孕有效率99.07％/百妇年,对照组美国Intercent栓116例,1296个月经周期有效率98.17/百妇年,两组比较无显著性差异(x=0.58,P>0.05)。副反应除外阴搔痒外,分泌物增多、阴道烧灼感和男方局部不适两组有显著性差异(P<0.01)。提出:津NP_9栓副反应少于Intercept栓。使用不当是失败的主要原因,78.3％的失败致孕者发生在用药头4个月,因此指导正确使用方法是提高避孕效率的不可缺少的因素。     

复方壬苯醇醚-9栓对家兔抗生育作用和阴道刺激性实验研究

目的:观察复方壬苯醇醚-9栓对家兔的抗生育作用和阴道刺激性。方法:采用改良Eckstein方法,对性成熟雌性家兔进行阴道刺激性研究。结果:家兔抗生育实验结果表明,高、中、低剂量实验药物组的避孕率分别为 100％、80％和60％;阴道刺激炎症总分值分别为4．3、3．5、3．0。结论:在实验应用剂量下壬苯醇醚-9抗生育作用及对阴道刺激性在可接受范围内。     

长效避孕栓溶出度试验研究

本文对长效避孕栓进行体外溶出度测定。溶出度试验条件选择在溶出度5分钟达到35％以上,3小时达到60％～80％以上,6小时达到90％以上。用高效液相色谱法测定溶出样品液的浓度。结果表明:测定的三批样品溶出度均符合要求。认为本方法可满足该栓剂体外溶出度测定要求,可用于控制该产品制剂工艺,以保证产品质量。     

外用阴道杀微生物避孕凝胶剂稳定性研究

目的:评价外用阴道杀微生物避孕凝胶剂的稳定性.方法:对凝胶剂中两种主药成分辛苯聚醇和聚甲酚磺醛的理化性质和含量进行测定.分别将其在(30±2)℃、相对湿度(65±5)%条件下进行加速3个月,在室温条件下放置1年和在照度(4 000±500)LX(勒克斯)下放置1,3,5,7和10 d做稳定性考察试验.结果:在上述试验条件下,3批样品中辛苯聚醇的标示量均在90%～110%,聚甲酚磺醛的标示量均在85%～115%.结论:该制剂具有较好的稳定性.     

外用阴道杀微生物避孕凝胶剂稳定性研究

目的:评价外用阴道杀微生物避孕凝胶剂的稳定性。方法:对凝胶剂中两种主药成分辛苯聚醇和聚甲酚磺醛的理化性质和含量进行测定。分别将其在(30±2)℃、相对湿度(65±5)%条件下进行加速3个月,在室温条件下放置1年和在照度(4000±500)LX(勒克斯)下放置1,3,5,7和10d做稳定性考察试验。结果:在上述试验条件下,3批样品中辛苯聚醇的标示量均在90%～110%,聚甲酚磺醛的标示量均在85%～115%。结论:该制剂具有较好的稳定性。     

形形色色的杀精剂

屏障避孕法中的“化学屏障”俗称“外用杀精剂”。外用杀精剂是房事前置入女性阴道、对精子有灭活作用的一类化学避孕制剂。目前常用的外用杀精剂，其活性成份大多是一种化学名叫“壬苯醇醚”的表面活性剂。壬苯醇醚主要是通过破坏精子的生物膜系统发挥避孕作用，如质膜脱失、顶体膜受损或顶体脱失、线粒体肿胀或空泡变性等。大多数微生物，特别是病毒的结构上，表面均有一层脂质包膜。杀精剂同样能破坏其包膜使之失去感染性。     

释药吸液避孕膜稳定性与体外释放度研究

目的:考察新研制释药吸液避孕膜的稳定性,体外释放度和体、内外溶化时限。方法:稳定性试验在40℃±1℃、相对湿度75%±5%的恒温恒湿培养箱内和室温自然条件下放置样品,使用高效液相色谱法(HPLC),在设定的时间测定样品中壬苯醇醚-9(NP-9)含量;分别将释药吸液避孕膜放入37℃±0.5℃水浴中及女性阴道内测定体外释放度并观察体内外溶化时限,在不同的时间点采样,采用HPLC测定释放介质中NP-9累积释放量。结果:在设定的时间内,样品中NP-9含量无明显变化,稳定性良好。药膜中NP-9累积释放量随着时间的延长而增加,0min及80min时累积释放率分别为28.93%、98.10%。释药吸液避孕膜在妇女阴道内溶化时限为8～12h,在体外溶化时限平均为61.48±0.16min。结论:释药吸液避孕膜具有良好的稳定性,可在室温条件下存放24个月。释药吸液避孕膜中N-9体外释放量随着时间的延长而增加。体内、外溶化时间不一致的特性,表明释药吸液避孕膜溶化速度可能与液体量有关,这一特点可使药膜在遇到精液时迅速释放出N-9,以提高杀精效果。     

洁泽2号对兔体内杀精及抗生育作用的实验研究

目的:观察洁泽2号(JZ2)对家兔体内杀精及抗生育的作用效果。方法:将82只雌性家兔随机分为JZ2高、中、低剂量组、JZ1组、N-9高、中、低剂量组、空白凝胶组和生理盐水对照组。雌兔阴道给药后与雄兔交配,交配后吸出阴道深部黏液观察不同时间精子的活动率、死亡率及精子全部死亡的时间;在交配后的第20天剖腹观察雌兔黄体数、胚泡数,计算受精率及妊娠率。结果:同一时间下,JZ2高、中、低剂量组精子活动率和死亡率与生理盐水对照组比较差异均有极显著统计学意义(P<0.01),与JZ1比较,在1min差异有极显著统计学意义(P<0.01),低剂量组与同浓度的N-9组比较差异在1min有统计学意义(P<0.05);JZ2高、中、低剂量组精子全部死亡时间分别为(0.00±0.00)min,(4.00±1.25)min,(4.50±1.06)min,3组与生理盐水对照组比较差异均有极显著统计学意义(P<0.01),JZ2低剂量组与同浓度的N-9组比较差异有极显著统计学意义(P<0.05),JZ2高剂量组与JZ1组比较差异有极显著统计学意义(P<0.01);交配后家兔黄体数在各组间差异均无统计学意义(P>0.05);JZ2组家兔胚泡数量、受精率及妊娠率低于生理盐水组和JZ1组(P<0.01),JZ2低剂量组与同浓度的N-9组比较差异有极显著统计学意义(P<0.05)。结论:JZ2对雌兔有较好的体内杀精及抗生育作用,其作用优于单用JZ1或N-9。     

Spermicide use and Down's syndrome.

A connection has been suggested between use of vaginal spermicides and the occurrence of Down's syndrome among offspring born to women who used these contraceptive agents. This hypothesis was evaluated with data from a case-control study of congenital heart disease, which included among the subjects 16 infants with Down's syndrome. The estimated ratio of the proportion of Down's syndrome births among spermicide users to the proportion in non-users was 3.6, with a 90 per cent confidence interval of 1.2 to 9.0, thus providing a tentative confirmation of the hypothesis.     

Spermicide use and pregnancy outcome.

The relation between periconceptional vaginal spermicide use and sex ratio at birth, birthweight, and the frequency of congenital anomalies was examined in a cohort of 2,712 New York City obstetric patients, 149 of whom (5.5 per cent) became pregnant while using spermicides or had used spermicides before and after conception. Periconceptional spermicide use was not associated with any important variation in the expected sex ratio at birth, nor with major or minor congenital anomalies. Exposure to spermicides in the periconceptional period, defined dichotomously as present or absent, was not associated with decreased birthweight in male or female infants. There was a slight decrease in birthweight among female infants with increasing duration of postconceptional spermicide use; an estimated 7.4 grams decrease with each day of use. The size of the effect and its selectivity by sex suggest a chance finding.     

Synergistic effect of gramicidin and EDTA in inhibiting sperm motility and cervical mucus penetration in vitro

Gramicidin, a linear polypeptide with antiviral and antimicrobial properties, was compared in vitro with a commonly used spermicidal detergent—nonoxynol-9 (N9). The inhibition of sperm functions was evaluated by computer-assisted semen analysis (CASA) for sperm motility, in cervical mucus penetration assay, and by colorimetric tetrazolium salt and lactate dehydrogenase release assays routinely employed for testing the toxicity of drugs. The effective 100% inhibitory concentration (IC₁₀₀) of gramicidin in a 2-min sperm immobilization assay by CASA was equal to 4 μg/ml, whereas IC₁₀₀ of N9 was equal to 200 μg/ml. The presence of 0.1% of chelating agent, EDTA, reduced IC₁₀₀ of gramicidin to 10 ng/ml, while less than a twofold enhancement in N9 activity was observed upon combination with EDTA. Likewise, the gramicidin/EDTA combination was 100,000 times more potent than N9/EDTA in the sperm penetration assay. Quantitative toxicity tests confirmed that gramicidin is a potent spermostatic rather than spermicidal agent. Further development of a gramicidin/EDTA formulation is warranted as a nontoxic topical contraceptive with activity against viral and microbial sexually transmitted diseases (STDs).     

Studies on Nonoxynol-9. II. Intravaginal absorption, distribution, metabolism and excretion in rats and rabbits

Some pharmacological aspects of Igepal CO-630, used by some pharmaceutical companies as the source of nonylphenoxypoly (ethyleneoxy) ethanol (Nonoxynol-9, N-9) in various spermicidal formulations, were studied. It was found that Igepal CO-630 contains at least 13 components, 70% having molecular weights near that of N-9. After intravaginal administration, the detergent is rapidly and quantitatively absorbed through the vaginal wall into the systemic circulation. The rate of vaginal absorption of N-9 depends on the vehicle in which the detergent is carried. Once in the blood, N-9 is excreted by liver-bile-feces and the kidney-urine routes, the first being more effective in rats, the latter in rabbits. Following intravaginal or intraperitoneal injection of radioactive N-9, the highest content of radioactivity was found in the liver and kidney. The detergent was detected in the milk of lactating rats and the serum of their pups within two hours after the intravaginal dose.     

Nonoxynol-9 causes rapid exfoliation of sheets of rectal epithelium

Nonoxynol-9 (N-9) containing spermicides and other N-9 containing products are commonly used as lubricants during rectal intercourse. We have previously demonstrated that rectal application of N-9 products in mice can cause exfoliation of epithelial cells, increasing the probability of infection by HSV-2. To determine if N-9-containing products would have a similar effect on the rectal epithelium in humans, the application of K-Y Plus and ForPlay, both over-the-counter (OTC) N-9 products, were compared to the application of two formulations, carrageenan and methyl cellulose, that do not contain N-9. The effects of each formulation were evaluated in 4 human participants. Light and electron microscope examination of rectal lavage specimens collected 15 min post application of N-9 products revealed the presence of sheets of epithelium. Each sheet contained hundreds of epithelial cells that included columnar and goblet cells, varieties of cells typical of rectal epithelial morphology. Sheets of epithelium were not observed in rectal lavage specimens collected 8 to 12 hr post N-9 product use or in either of the timed lavages involving non-N-9 containing formulations. In addition, no sheets of epithelial cells were observed in the baseline lavage specimens. We conclude that the rectal use of N-9-containing products causes a rapid exfoliation of extensive areas of the rectal epithelium. Exfoliation of the epithelium is no longer observed at 8 hr. It is reasonable to assume that the loss of the protective epithelium would render a person more at risk for infection by HIV and other sexually transmitted pathogens. We, therefore, caution against the use of N-9-containing products during rectal intercourse.     

Sperm transport and survival post-application of a new spermicide contraceptive

The present study was undertaken to evaluate the effectiveness of Advantage 24^® to inhibit sperm transport and survival when applied at 24 hours, 12 hours, and 15–30 minutes prior to a single act of intercourse. Conceptrol^®, applied at 15–30 minutes before intercourse, was employed as the comparative spermicide. One-hundred-thirty-nine women, aged 22 to 45 years, were enrolled into the study and 111 completed the trial. The ability of the spermicides to immobilize sperm was assessed by postcoital testing (PCT) and by examining the proportion of sperm immobilization failure (SIF) rates. SIF was a postcoital test result with ≥10 sperm with progressive motility (either sluggish or rapid) per ×400 power field. Conceptrol and Advantage 24 used at 15–30 minutes were similar with respect to their ability to inactivate sperm (0% and 2% SIF, respectively, P = 0.5). At longer intervals between spermicidal application and intercourse, less inhibition of sperm motility was noted (9% and 14% SIF for 12 and 24 hours, respectively). The present study indicates that Advantage 24 is an effective agent to immobilize sperm. The action of Advantage 24 may decrease if it is applied earlier than 15–30 minutes before intercourse.     

安芳欣~(TM)生物粘附缓释避孕凝胶剂的可接受性初步研究

30对已婚夫妇、294次性生活(男性392次填表)使用安芳欣~(TM)生物粘附缓释避孕凝胶剂(简称安芳欣),以询问表的形式进行可接受性评估。结果显示:93.3％的女性和100.0％的男性认为安芳欣可以接受,100.0％的夫妇认为是一种好的避孕方法;100.0％夫妇认为使用安芳欣的性快感与平时一样或增强;与避孕栓、膜或阴茎套相比,83.3％的女性和86.7％的男性更喜欢安芳欣。研究结果提示,有一定比例的育龄夫妇能够选用安芳欣作为避孕方法。