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1.
BACKGROUND: ACIDFORM is a microbicidal and contraceptive candidate with strong buffering capacity. METHODS: This was a Phase I blinded, randomized and crossover clinical study on two products, ACIDFORM and a commercial nonoxynol-9 (N-9) product (2%), evaluating their vaginal safety in 20 couples aged between 19 and 45 years. The women had regular menses, underwent previous tubal ligation, were not breast-feeding, had no vaginal sign and symptom and were in a stable partnership; both partners had no previous STI. Colposcopy, vaginal microbiology, inflammation markers and subject complaints were studied after coitus. Women were randomly assigned sequentially to receive ACIDFORM 0-30 min (0-30 min before intercourse), ACIDFORM 8-10 h (8-10 h before intercourse) or N-9 0-30 min after a control cycle. RESULTS: Mild/moderate vulvar irritation was observed in five postcoital test colposcopies, burning and pruritus were reported in six treated cycles and non-irritation-related symptoms were found in five cycles with different treatments. No difference in vaginal pH, Nugent scores, H2O2-producing lactobacillus or leukocytes and interleukin 6 in the cervicovaginal lavage was found between the treatment and control cycles. CONCLUSIONS: ACIDFORM appears to be safe for clinical use once a day. There is a potential spermicidal-microbicidal role for ACIDFORM as a vaginal flora helper or as a vehicle for products, except N-9.  相似文献   

2.

Objective

ACIDFORM is a candidate microbicide with spermicidal properties. A large Phase 3 trial is underway, and it is anticipated that this product will be approved for contraceptive use and marketed soon in the United States. The goal of this article is to critically review the evidence supporting the properties, safety profile and different uses of ACIDFORM gel.

Study design

We searched PubMed and Medline for any published literature on ACIDFORM.

Results

ACIDFORM is an acidifying agent that works by lowering the vaginal pH to enhance the normal vaginal defenses. In addition to strong acid-buffering properties, ACIDFORM has high bioadhesive and viscosity-retaining properties. Several Phase 1 clinical trials have demonstrated the vaginal safety of ACIDFORM used alone or in combination with a diaphragm, although dose-dependent side effects appear to be present. Studies investigating the efficacy of ACIDFORM against sexually transmitted infections (STIs) are promising, but further trials are needed.

Conclusions

The properties of ACIDFORM offer many advantages for use, either alone or in combination with another active ingredient, such as Tenofovir. Potential applications for ACIDFORM include use as a personal lubricant, a vaginal contraceptive (alone or with a barrier method) and a microbicidal product or as a formulation vehicle for an active ingredient.

Implications

ACIDFORM is a candidate female-controlled vaginal preparation with microbicidal and spermicidal properties. A dual protection method could prevent unwanted pregnancies and reduce the risk of STI acquisition.  相似文献   

3.
BACKGROUND: This study was conducted to compare the effectiveness of a new, single-size silicone contraceptive diaphragm used with either spermicide [2% nonoxynol-9 (N-9)] or lubricant in preventing sperm from penetrating midcycle cervical mucus. STUDY DESIGN: A crossover postcoital test (PCT) in healthy, sexually active women not at risk for pregnancy due to tubal occlusion was conducted. Couples had a baseline PCT without a device to verify normal fertility parameters. Qualified couples underwent up to two test cycles using the SILCS diaphragm with a metal spring. A subgroup of couples underwent a third test cycle with the SILCS polymer spring diaphragm used with N-9 gel. RESULTS: Fifteen couples completed a baseline cycle and were randomized to order of study gel. Of these, 14 couples completed a baseline cycle and at least one test cycle, 12 couples completed a baseline cycle and two test cycles and 8 couples completed a third test cycle with the polymer spring prototype. Sperm was detected in the vaginal pool in all completed test cycles. The SILCS metal spring diaphragms used with N-9 gel reduced the average number of progressively motile sperm per high power field in the cervical mucus from a baseline of 12.5 to 0, while use of this device with lubricant reduced the number to 0.5. The SILCS polymer spring diaphragm used with N-9 performed the same as the metal spring used with N-9. CONCLUSION: The SILCS diaphragm used with N-9 gel performed well. It is likely that the SILCS diaphragm will give acceptable results in a contraceptive effectiveness study but that adjunctive use of a chemical barrier such as N-9 gel will be necessary for it to be most effective.  相似文献   

4.
Vaginal prophylactic methodology may prevent heterosexual transmission of the HIV and other sexually transmitted disease-causing organisms as well as unplanned pregnancies. A new delivery system (ACIDFORM) was designed with acid-buffering, bioadhesive, and viscosity-retaining properties to (1) maintain the acidic vaginal milieu (the low pH inactivates many pathogens and spermatozoa), (2) form a protective layer over the vaginal/cervical epithelium (minimizing contact with pathogenic organisms), and (3) provide long-term vaginal retention. A Phase I clinical study with ACIDFORM provided initial information about its safety and showed the formation of a layer over the vaginal/cervical epithelium [1; Amaral et al., Contraception 1999;60:361-6]. To study the properties of the gel (without active ingredient) in more detail, ACIDFORM's acid-buffering, bioadhesive, viscosity-retaining, and spermicidal properties were compared in vitro to marketed formulations, and its long-term stability was assessed. ACIDFORM, either when titrated with NaOH or when mixed directly with semen, is highly acid buffering and much more effective than Aci-Jel, a commercial acid-buffering vaginal product. ACIDFORM adheres well to two model membranes (excised sheep vagina and cellophane) and is more bioadhesive than Conceptrol, Advantage S, Replens, Aci-Jel, and K-Y jelly. On dilution, ACIDFORM also retains its viscosity better than these marketed products. ACIDFORM is spermicidal and is stable for at least 2 years. These results suggest that ACIDFORM has advantages over presently marketed vaginal delivery systems. The gel may either be useful by itself as an antimicrobial contraceptive product or as a formulation vehicle for an active ingredient with antimicrobial and/or contraceptive properties.  相似文献   

5.
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).  相似文献   

6.
Several studies have shown that users of vaginal preparations containing nonoxynol-9 (N-9) are at a high risk for sexually transmitted diseases, including HIV. Therefore, there is a great interest in identifying compounds that can specifically inhibit sperm without damaging the vaginal lining, possess a powerful spermicide activity, and can be used in contraceptive vaginal preparations to replace N-9. In this work, we studied the spermostatic and/or spermicidal activity of five non-detergent, disulfide compounds on human sperm, HeLa cells, and Lactobacillus acidophilus. The motility and viability of human sperm in semen and culture medium was evaluated after treatment with different concentrations of the disulfide compounds (2.5 - 100 μM). In addition, we evaluated the cytotoxic effect on HeLa cells and L. acidophilus. We identified compound 101, N,N'-dithiobisphthalimide (No. CAS 7764-30-9), as the most effective molecule. It has a half maximal effective concentration (EC(50)) of 8 μM and a minimum effective concentration (defined as the concentration that immobilizes 100 percent of the sperm in 20 sec) of 24 μM. At these concentrations, compound 101 does not affect the viability of the sperm, HeLa cells, or L. acidophilus. Our results indicate that dithiobisphthalimide has a potent spermostatic, irreversible effect with no toxic effects on HeLa cells and L. acidophilus.  相似文献   

7.
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.  相似文献   

8.
Vaginal tolerance tests were performed with a new potential microbicidal and spermicidal product, an acid-buffering vaginal gel (Acidform) without or with nonoxynol-9 (N-9). The potential advantages over other vaginal products include keeping a low pH, decrease of the irritating effect of N-9 on the cervix or vaginal mucosa associated with greater retention of the product after application, and decreasing “messiness” as compared to other vaginal products. Three groups of six women were admitted and randomly assigned to use Acidform with 0%, 2.5%, and 5% N-9. Colposcopic evaluation for vulvar, vaginal, and cervical signs of irritation was performed and photographs were taken, following a specific World Health Organization protocol, at time 0, and after 24 h and 6 days of application of the gel. No irritation or symptom was reported by users of Acidform without N-9. A generalized and intense erythema in cervix was observed in 10 of 12 Acidform/N-9 users and abrasion occurred in nine of them. Vulvar irritation was seen in seven of these 10 volunteers. N-9 concentration in the gel (2.5% or 5.0%) was not related to the findings. No ulcer, exulceration, or de-epithelialization was observed. Acidform without N-9 was well tolerated by volunteers, but it was unable to protect the cervix, vagina, and vulva from the N-9 effects.  相似文献   

9.
Several studies have shown that users of vaginal preparations containing nonoxynol-9 (N-9) are at a high risk for sexually transmitted diseases, including HIV. Therefore, there is a great interest in identifying compounds that can specifically inhibit sperm without damaging the vaginal lining, possess a powerful spermicide activity, and can be used in contraceptive vaginal preparations to replace N-9. In this work, we studied the spermostatic and/or spermicidal activity of five non-detergent, disulfide compounds on human sperm, HeLa cells, and Lactobacillus acidophilus. The motility and viability of human sperm in semen and culture medium was evaluated after treatment with different concentrations of the disulfide compounds (2.5 – 100 µM). In addition, we evaluated the cytotoxic effect on HeLa cells and L. acidophilus. We identified compound 101, N,N'-dithiobisphthalimide (No. CAS 7764-30-9), as the most effective molecule. It has a half maximal effective concentration (EC50) of 8 µM and a minimum effective concentration (defined as the concentration that immobilizes 100 percent of the sperm in 20 sec) of 24 µM. At these concentrations, compound 101 does not affect the viability of the sperm, HeLa cells, or L. acidophilus. Our results indicate that dithiobisphthalimide has a potent spermostatic, irreversible effect with no toxic effects on HeLa cells and L. acidophilus.  相似文献   

10.
目的:观察中药复方药液洁泽1号(Jieze NO.1,JZ1)对外用杀精剂壬苯醇醚(N-9)的杀精增效作用及洁泽2号(Jieze NO.2,JZ2,JZ1与N-9混合制剂)凝胶大鼠阴道内用药的避孕(抗生育)效果。方法:采用改良的Sander-cramer方法观察JZ2中N-9的最低杀精浓度对正常人精子前向运动率、活动率和存活率的影响;大鼠阴道内给予JZ2药物凝胶后雌雄合笼,分别于交配后1 min、3 min、5 min、10 min观察阴道内精子活动情况,并观察各组避孕率。结果:N-9 20 s、3 min最低杀精浓度均为0.25 mg/ml,与洁泽1号混合(即JZ2)后,N-9最低杀精浓度分别为0.125 mg/ml、0.062 5 mg/ml。交配后1 min,各单纯N-9及JZ2凝胶组大鼠阴道内均未见活动精子。N-9(12%及以上浓度)、JZ2(含10%及以上浓度N-9)各组均有较高的避孕率,与自然对照组及空白凝胶组之间的差异均有极显著统计学意义(P<0.01)。JZ2(含14%、12%N-9)药物凝胶组抗生育率均可达100%,与14%N-9作用相当。JZ2(含10%N-9及8%N-9)抗生育率分别为90%、40%,与自然对照组之间有统计学差异。JZ2(含12%N-9和10%N-9)凝胶组对大鼠的避孕作用强于相同浓度的N-9组,且比较差异有统计学意义(P<0.05)。结论:由剂量-反应关系曲线可以看出JZ1对N-9的杀精作用具有协同作用,两药混合后(即JZ2)可以减少N-9的剂量;JZ2凝胶大鼠阴道内用药具有较好的抗生育作用,在相同避孕效果下可减少N-9的用量。  相似文献   

11.
目的研究鹿藿正丁醇提取物(n-Butanol extract of Rhynchosia volubilis Lour,BERVL)的体外杀精子作用及机制。同时观察该提取物体外对嗜酸乳酸杆菌的影响,初步评估BERVL作为杀精子剂的可行性和安全性。方法体外杀精子实验以生理盐水为阴性对照,壬苯醇醚(nonoxynolum-9,N-9)为阳性对照,显微镜下观察浓度为250mg/ml,125mg/ml,100mg/ml,90mg/ml,62.5mg/ml的BERVL对人精子活力的影响;体外抑菌实验用试管稀释法和琼脂稀释法;体外杀精子机制探讨:用伊红Y水试验和Hoechst 33342/PI荧光双染,显微镜下检测精子膜功能和精子凋亡。结果 BERVL在90mg/ml浓度组:体外杀精实验,原地活动精子百分率为(4.730±3.231)%;体外抑菌试验,对嗜酸乳酸杆菌抑制率为32.96%35.70%;伊红Y水溶液染色,精子头部未着色百分率为(7.846±4.706)%。Hoechst 33342/PI荧光双染,凋亡精子百分率为(4.977±2.267)%,死精子百分率为(90.111±4.509)%。结论90mg/ml为BERVL较安全理想的体外杀精浓度。BERVL有显著的体外杀精子作用,可能与破坏精子膜和加速精子凋亡及死亡有关。  相似文献   

12.
Foote RH 《Contraception》2002,66(3):193-197
Vaginal contraceptives have potential for controlling reproduction as well as sexually transmitted diseases. Two extensively used fungicides, amphotericin B and nystatin, were found to be highly spermicidal to bull and rabbit sperm even in the presence of organic material found in milk and egg yolk, both excellent components of media designed to preserve sperm. In repeated tests with many samples of bull and rabbit sperm, as little as 0.5 micro g/mL of amphotericin B completely immobilized sperm after prolonged exposure, and 1000 micro g/mL immobiled sperm in less than 1 min. Treatment of rabbit sperm with 1000 micro g of solubilized amphotericin B in 0.4 ml of a glucose-semen mixture before insemination resulted in a total of 2 young born from 9 inseminated Dutch does, compared with 55 young from 9 control does. As this inhibition was achieved without the use of enhancing foams or gels, these results provide promising leads for contraceptive research.  相似文献   

13.
14.
目的分析影响宫腔内人工授精(intrauterine insemination,IUI)成功率的相关因素。方法回顾性分析2013~2014年北京市海淀区妇幼保健院生殖中心1 659个IUI周期的患者年龄、不孕年限、不孕类型、自然周期或促排卵周期、子宫内膜厚度、排卵数、IUI的时机、洗精前后前向运动精子数、IUI的周期数与妊娠结局的关系。结果 IUI治疗妊娠率与患者年龄、子宫内膜厚度、IUI治疗周期数、排卵数及洗精前前向运动精子数有关(P0.05);与不孕类型、自然周期或促排卵周期、IUI时机、洗涤后前向运动精子数无关(P0.05)。结论影响IUI结局的主要因素是:子宫内膜厚度、患者年龄、IUI治疗周期数、排卵数及洗涤前前向运动精子数。  相似文献   

15.
Control of sexually transmitted infections (STIs) is feasible, leads to improved sexual and reproductive health and contributes to preventing HIV transmission. The most advanced HIV epidemics have developed under conditions of poor STI control, particularly where ulcerative STIs were prevalent. Several countries that have successfully controlled STIs have documented stabilization or reversal of their HIV epidemics.STI control is a public health outcome measured by reduced incidence and prevalence. The means to achieve this include: (i) targeting and outreach to populations at greatest risk; (ii) promoting and providing condoms and other means of prevention; (iii) effective clinical interventions; (iv) an enabling environment; and (v) reliable data.Clinical services include STI case management, screening and management of STIs in sex partners. Syndromic case management is effective for most symptomatic curable STIs and screening strategies exist to detect some asymptomatic infections. Presumptive epidemiologic treatment of sex partners and sex workers complement efforts to interrupt transmission and reduce prevalence. Clinical services alone are insufficient for control since many people with STIs do not attend clinics. Outreach and peer education have been effectively used to reach such populations.STI control requires effective interventions with core populations whose rates of partner change are high enough to sustain transmission. Effective, appropriate targeting is thus necessary and often sufficient to reduce prevalence in the general population. Such efforts are most effective when combined with structural interventions to ensure an enabling environment for prevention. Reliable surveillance and related data are critical for designing and evaluating interventions and for assessing control efforts.  相似文献   

16.
中药远志提取物体外杀精子效果与机制研究   总被引:1,自引:0,他引:1  
目的:通过精子低渗肿胀(HOS)实验结合改良伊红染色法观察中草药远志粗提物体外杀精活性及机制。方法:HOS实验结合伊红-姬姆萨(EG)染色(HOS-EG)判断精子膜完整性,将精子分为A(HOS+-EG-)、B(HOS-EG-)、C(HOS+-EG+)、D(HOS-EG+)4型。精子染色质扩散实验(SCD)检测精子DNA碎片。制备远志粗提物,并判断其体外杀精子活性。壬苯醇醚-9(N-9)作为标准参照物,生理盐水为对照组。结果:远志粗提物浓度为50.0mg/ml和20.0mg/ml时体外20s内即可完全杀灭精子(与精液1:1混合)。对照组、远志粗提物组及N-9组精子DNA碎片比例各组比较无差异。对照组A、B、C和D型精子百分比分别为(69.0±8.3)%、(3.4±0.5)%、(10.2±1.7)%和(17.4±2.1)%。远志粗提物组及N-9组精子膜完整性全部被破坏,无A型和B型精子,C型精子较对照组明显减少,D型精子比对照组明显增加(P<0.001)。精子复活实验显示远志粗提物组和N-9组均无活动精子恢复。结论:HOS-EG实验可以同时判断一条精子头膜或尾膜损伤。远志粗提物在体外通过破坏精子膜使精子快速失活。  相似文献   

17.
目的:研究中药桔梗的单体化学成分桔梗皂苷D(PD)对人精子的杀伤效果,初步探索其杀精机制。方法:将同一健康男性的精液均分为4份,分别用生理盐水、0.15mmol/LPD、0.20mmol/LPD及0.31mmol/L壬苯醇醚-9(N-9),阳性对照处理样本2min。用计算机辅助的精液分析系统(CASA)检测PD对人精子的杀伤效果,并通过AnnexinⅤ-FITC检测精子凋亡。结果:生理盐水对照组、0.15mmol/LPD组、0.20mmol/LPD组、N-9对照组的精子活率分别为67.97±21.76%,36.68±28.23%,24.18±7.72%,42.74±25.62%。各处理组与生理盐水对照组间差异有统计学意义(P<0.001),N-9与两个PD剂量组之间差异无统计学意义(P>0.05)。细胞凋亡检测结果显示,PD主要引起精子的晚期凋亡,0.15mmol/LPD、0.20mmol/LPD、0.25mmol/LPD组的晚期凋亡指数分别为181.7±46.0、246.0±52.8、272.8±57.3,PD各剂量组的晚期凋亡率与对照组之间差异有统计学意义(P<0.001)。结论:PD对人精子有显著的瞬间杀灭效应,它主要引起精子的晚期凋亡,可能与PD对精子膜的损伤有关。PD将来可能作为一种有潜力的临床杀精剂。  相似文献   

18.
OBJECTIVES: We report on the synthesis of a potential nitric oxide releasing derivative of nonoxynol-9 (N9). METHODS: This derivative was synthesised via AgNO3 mediated nitroxylation of a chloride derivative of a N9 which itself was synthesised by thionyl chloride mediated chlorination of N9. In an initial in vitro study the spermicidal efficacy of the nitric oxide derivative and the parent compound (N9) was examined using boar spermatozoa. Sperm motility and viability were examined. RESULTS: The data showed that nitroxylation of N9 did not disrupt spermicidal activity; both sperm motility and viability were comparable between N9 and its nitroxylated derivative. For both compounds, low doses (1-10 microg/mL) were sufficient to induce significant immobilization of sperm after 1 min, whereas concentrations of 10-100 microg/mL were required to achieve significant increase in membrane permeability. CONCLUSION: The results show that a nitric oxide-releasing derivative of N9 retains the spermicidal activity of the parent compound and may have other beneficial effects associated with the release of NO.  相似文献   

19.
Purpose: To determine whether sexually active adolescent males who report being the victim of forced sexual contact and engaging in health risk and problem behaviors are more likely to report getting someone pregnant.

Methods: In 1995, 4159 students in Grades 9–12 in 59 randomly selected public high schools in Massachusetts were anonymously surveyed using the Youth Risk Behavior Survey (YRBS). Data were analyzed for 824 sexually active males. Demographic variables and indicators of sexual behavior, pregnancy, violence, and suicide were assessed. Data were analyzed with multiple logistic regression.

Results: A total of 12.0% of sexually active males reported having been involved in a pregnancy. The proportion of males who reported getting a partner pregnant increased with age. Of the sample, 8.1% gave a history of having had sexual contact against their will. Of those who reported forced sexual contact, 36.4% reported having been involved in a pregnancy; of the males who did not report a history of forced sexual contact, 9.4% were involved in a pregnancy (CV = 0.23; p < 0.00001). Based on multiple logistic regression, forced sexual contact [odds ratio (OR) 3.56; 95% confidence interval (CI) 1.79–7.09], frequency of weapon carrying on school property (OR 1.39; 95% CI 1.18–1.64), number of cigarettes smoked per day (OR 1.22; 95% CI 1.08–1.38), number of sexual partners in the previous 3 months (OR 1.43; 95% CI 1.25–1.65), and condom nonuse at last intercourse (OR 1.80; 95% CI 1.06–3.02) correctly classified 89.9% of the males who were involved in a pregnancy.

Conclusion: This study highlights the association between health-risk and problem behaviors, forced sexual contact, and involvement in pregnancy among sexually active male high school students. In our analysis, a history of forced sexual contact was associated with a higher risk of high school males’ involvement in pregnancy. These results strongly suggest the importance of screening sexually active males for a history of forced sexual intercourse and health risk and problem behaviors in the effort to prevent teenage pregnancy and childbearing.  相似文献   


20.
Population-based, cross-sectional data from 3587 ever-married Ukrainian women aged 17-44 are used to examine the association between physical violence perpetrated by a sexual partner (defined as kicking, hitting, slapping, pushing, or attacking with a weapon) and sexual health knowledge, sexual behavior, and the likelihood of reporting a sexually transmitted infection (STI). Such violence, both past and recent, is found to be associated with increased lifetime risk of acquiring an STI. Women who have been abused by a sexual partner, whether in the past 12 months or less recently, are significantly less likely to use condoms currently, and are significantly more likely to report having had multiple sexual partners in the past year. Findings from the study indicate that physical violence perpetrated by a sexual partner is associated with risky sexual behaviors and increased risk of sexually transmitted infection in Ukraine, and may constitute a barrier to prevention of HIV/STI transmission.  相似文献   

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