Star-Shaped Poly(furfuryl glycidyl ether)-Block-Poly(glyceryl glycerol ether) as an Efficient Agent for the Enhancement of Nifuratel Solubility and for the Formation of Injectable and Self-Healable Hydrogel Platforms for the Gynaecological Therapies.

In this paper, we present novel well-defined unimolecular micelles constructed a on poly(furfuryl glycidyl ether) core and highly hydrophilic poly(glyceryl glycerol ether) shell, PFGE-b-PGGE. The copolymer was synthesized via anionic ring-opening polymerization of furfuryl glycidyl ether and (1,2-isopropylidene glyceryl) glycidyl ether, respectively. MTT assay revealed that the copolymer is non-cytotoxic against human cervical cancer endothelial (HeLa) cells. The copolymer thanks to furan moieties in its core is capable of encapsulation of nifuratel, a hydrophobic nitrofuran derivative, which is a drug applied in the gynaecology therapies that shows a broad antimicroorganism spectrum. The study shows high loading capacity of the copolymer, i.e., 146 mg of nifuratel per 1 g of copolymer. The load unimolecular micelles were characterized using DLS and TEM microscopy and compared with the reference glyceryl glycerol ether homopolymer sample. The presence of numerous 1,2-diol moieties in the shell of PFGE-b-PGG macromolecules enabled the formation of reversible cross-links with 2-acrylamidephenylboronic acid-based polyacrylamide. The obtained hydrogels were both injectable and self-healable, which was confirmed with a rheological study.

High-dose nifuratel for simple and mixed aerobic vaginitis: A single-center prospective open-label cohort study.

AIM: The efficacy and safety of two nifuratel dosages for the treatment of aerobic vaginitis (AV) were compared. METHODS: This was a prospective open-label cohort study of patients diagnosed and treated at the Tianjin Third Central Hospital between January 2012 and December 2013. The co-presence of bacterial vaginosis (BV), vulvovaginal candidiasis (VVC), or/and trichomonal vaginitis (TV; mixed AV) was determined. Patients were randomized to nifuratel-500 (500 mg nifuratel, intravaginal, 10 days) or nifuratel-250 (250 mg nifuratel, intravaginal, 10 days), and followed-up for three to seven days after treatment completion. Primary and secondary outcomes were recovery rate and adverse events, respectively. RESULTS: The study included 142 patients with AV. Age was not significantly different between the groups (n = 71 each), and disease distribution was identical: 29 (40.85%) simple AV and 42 (59.15%) mixed AV (AV + BV, 42.86 %; AV + VVC, 30.95%; AV + TV, 26.19%). In patients with simple AV, the recovery rate did not differ significantly between the nifuratel-500 (26/29, 89.66%) and nifuratel-250 (22/29, 75.86%) groups. In patients with mixed AV, recovery rates were significantly higher in the nifuratel-500 than in the nifuratel-250 group (AV + BV, 88.89% vs 50.00 %; AV + VVC, 76.92 % vs 30.77 %; AV + TV, 90.91 % vs 36.36%; all P < 0.05). Only one patient (nifuratel-500) reported an adverse event (mild anaphylactic reaction). CONCLUSION: Nifuratel 500 mg showed good clinical efficacy for the treatment of AV, particularly mixed AV, and is superior to the 250 mg dosage in the treatment of mixed AV.

Bacterial vaginosis, Atopobium vaginae and nifuratel.

As bacterial vaginosis (BV) is a potential cause of obstetric complications and gynecological disorders, there is substantial interest in establishing the most effective treatment. Standard treatment - metronidazole or clindamycin, by either vaginal or oral route � is followed by relapses in about 30% of cases, within a month from treatment completion. This inability to prevent recurrences reflects our lack of knowledge on the origins of BV. Atopobium vaginae has been recently reported to be associated with BV in around 80% of the cases and might be involved in the therapeutic failures. This review looks at the potential benefits of nifuratel against A. vaginae compared to the standard treatments with metronidazole and clindamycin. In vitro, nifuratel is able to inhibit the growth of A. vaginae, with a MIC range of 0.125-1 µg/mL; it is active against G. vaginalis and does not affect lactobacilli. Metronidazole is active against A. vaginae only at very high concentrations (8-256 µg/mL); it is partially active against G. vaginalis and also has no effect on lactobacilli. Clindamycin acts against A. vaginae with an MIC lower than 0.125 µg/mL and is active on G. vaginalis but it also affects lactobacilli, altering the vaginal environment. These observations suggest that nifuratel is probably the most valid therapeutic agent for BV treatment.

[Local combined therapy of vaginal infections by nifuratel-nistatin]. / Lokalno lijecenje vaginalne infekcije s kombinacijom nifuratela i nistatina.

A test included 40 women in the reproductive age with clinical symptoms of vaginitis and microbiological examination. They were treated by combined therapy of vaginal tablets of nifuratel, 500 mg and nistatin 200 000 i. u. during six days, after which they underwent gynaecological reexamination and repeated microbiological examination of vaginal and cervical smears. An analiysis of vaginal secretion found bacterial flora in 34 smears (65%), fungus (Candida albicans) in 15 (24%) and Trichomonas vaginalis in 7 (11%). Local vaginal therapy in vaginitis caused by Trichomonas vaginalis was successfull in all 7 patients, vaginitis caused by Candida albicans was successly treated in 14 (93%) patients. Bacterial vaginitis was cured in 29 (71%) patients during this tharapy. Local vaginal combined therapy of nifuratel and nistatin is eficient in patients with vaginitis caused by fungi and Trichomonas vaginalis too.

[Rifaksimin in complex treatment of Helicobacter pylori infection in children (a pilot study)].

AIM: To provide a pilot study of empiric rifaximin, bismuth subcitrate, furazolidone/nifuratel triple therapy for H. pylori gastritis in childhood. MATERIALS AND METHODS: Forty one pediatric outpatients (27 females, mean age 14.5+/-1.4 ys) with H. pylori-associated chronic gastritis who underwent endoscopy for dyspeptic symptoms received the combination of bismuth subcitrate (8 mg/kg/day, q. d. s.) for 14 days, rifaximin (800 mg/day) for 10 days and furazolidone (10 mg/kg/day, q. d. s.) or nifuratel (15 mg/kg/two times daily) for 10 days. H. pylori status was determined before the treatment by modified Giemsa staining/urease test and after the treatment (in 4-6 weeks) by ammonia breath test. RESULTS: H. pylori was eradicated in 35 children (85.4%; 95%CI: 75.4-96.4 ITT and PP tests). There were no serious adverse reactions and were no withdrawals due to any side effects. CONCLUSION: The combination of rifaximin, bismuth subcitrate and furazolidone/nifuratel was an effective and tolerable regimen for initial H. pylori eradication.

Clinical effects of nifuratel in vulvovaginal infections. A meta-analysis of metronidazole-controlled trials.

Nifuratel (CAS 4936-47-4) displays a strong antiprotozoarian and antibacterial activity and is provided with certain fungicidal effect, but it is not active against the physiologic flora. Its therapeutic effectiveness has been evaluated in more than 12,000 patients. The wide clinical experience with nifuratel confirms that the drug is safe and effective for the treatment of trichomoniasis, bacterial vaginosis, candidosis, and, particularly, in patients suffering from mixed vaginal infection. A meta-analysis of clinical trials comparing nifuratel and metronidazole (CAS 443-48-1) in vulvovaginal infections was performed. All parallel-group metronidazole-controlled trials carried out in patients with vulvovaginal infections have been included, complying with the following criteria: 1) cure assessed both as disappearance of symptoms and signs, and negative microbiological findings; 2) microbiological tests performed with valid methods still used in current practice. Seven clinical trials have been selected, including overall 1767 patients, 832 out of whom were treated with nifuratel and 935 with metronidazole. The results of the meta-analysis confirmed the equivalence between nifuratel and metronidazole: overall proportion of cured patients in the two groups were 88.5% and 90.0%, respectively, in the presence of homogeneity among studies (p = 0.342). In the fixed and random effect analyses, the confidence interval of Odds ratio included 1 and the p values for testing the hypothesis of no difference between treatments were 0.656-1.266, p = 0.582 (fixed effects) and 0.643-1.290, p = 0.599 (random effects), respectively, indicating equivalence. Furthermore, some controlled studies and the wide clinical experience showed that the cure rate of nifuratel in patients with mixed infections due to Trichomonas vaginalis + Candida or Trichomonas vaginalis + bacteria or with bacterial vaginosis and mixed bacterial flora is higher than that of metronidazole, due to the wide spectrum of action of nifuratel.

Microbiological and pharmaco-toxicological profile of nifuratel and its favourable risk/benefit ratio for the treatment of vulvo-vaginal infections. A review.

Nifuratel (CAS 4936-47-4) is a furane-derivative provided with a strong trichomonicidal activity equivalent to that of metronidazole (CAS 443-48-1); it has a broad antibacterial spectrum of action, including both Gram-negative and Gram-positive organisms. It is active against Chlamydia trachomatis and Mycoplasma spp. and has also some degree of activity against Candida spp. and mycetes. Its broad spectrum of action, confirmed by in vitro and in vivo studies, covers virtually all the micro-organisms responsible for the infections of the genito-urinary tract. Nifuratel has a very safe toxicological profile. It is practically non-toxic in acute tests in mice and rats and is also well tolerated after repeated oral and intravaginal administrations. Nifuratel is devoid of teratogenic effects. The comparison among past and recent clinical studies confirms that, in contrast to metronidazole, no resistance phenomena to the treatment with nifuratel are reported. The drug can be used during pregnancy due to the absence of teratogenic effects. In conclusion, nifuratel shows a very favourable risk/benefit ratio for the treatment of patients with vulvo-vaginal infections.

Treatment of candidal urinary tract infection with nifuratel.

Three patients with candidal urinary tract infections were successfully treated with oral nifuratel, a nitrofuran antimicrobial agent active against yeast and Trichomonas as well as urinary bacterial pathogens. The recommended dose is 400 mg thrice daily for a week. No side effects that could be attributed to the treatment were noted. Minimum ibhibitory concentration determinations for nifuratel against Candida strains of five species showed that 48 out of 59 organisms were inhibited by 50 mg/1 or less, the three strains of Candida species eliminated from our treated patients having MICs of nifuratel in the range of 10-50 mg/1.