Вирулицидная эффективность таблеток для рассасывания с фиксированной комбинацией цетилпиридиния хлорида и бензидамина гидрохлорида против вируса гриппа А

1. Беляков Н.А., Боева Е.В., Симакина О.Е., и др. Пандемия COVID-19 и ее влияние на течение других инфекций на Северо-Западе России. ВИЧ-инфекция и иммуносупрессии. 2022;14(1):7-24 [Belyakov NA, Boeva EV, Simakina OE, et al. COVID-19 pandemic and its impact on other infections in Northwest Russia. HIV Infection and Immunosuppressive Disorders. 2022;14(1):7-24 (in Russian)]. DOI:10.22328/2077-9828-2022-14-1-7-24
2. Merced-Morales A, Daly P, Abd Elal AI, et al. Influenza Activity and Composition of the 2022-23 Influenza Vaccine – United States, 2021–22 Season. MMWR Morb Mortal Wkly Rep. 2022;71(29):913-9. DOI:10.15585/mmwr.mm7129a1
3. Осидак Л.В., Смородинцева Е.А., Афанасьева О.И., и др. Грипп на пороге. Осельтамивир при лечении детей в возрасте 1 года и старше. Фарматека. 2022;29(1):44-50 [Osidak LV, Smorodintseva EA, Afanasieva OI, et al. Influenza on the threshold. Oseltamivir in the treatment of children aged 1 year or older. Farmateka. 2022;29(1):44-50 (in Russian)]. DOI:10.18565/pharmateca.2022.1.44-50
4. Еженедельный национальный бюллетень по гриппу и ОРВИ за 24 неделю 2022 года (13.06.22–19.06.22). Режим доступа: https://www.influenza.spb.ru/system/epidemic_situation/laboratory_diagnostics. Ссылка активна на 01.09.2022 [Weekly national bulletin on influenza and SARS for the 24th week of 2022 (13.06.22–19.06.22). Available at: https://www.influenza.spb.ru/system/epidemic_situation/laboratory_diagnostics. Accessed: 01.09.2022 (in Russian)].
5. Грипп у взрослых: клинические рекомендации. М., 2021 [Gripp u vzroslykh: klinicheskie rekomendatsii. Moscow, 2021 (in Russian)].
6. Uyeki TM, Bernstein HH, Bradley JS, et al. Clinical Practice Guidelines by the Infectious Diseases Society of America: 2018 Update on Diagnosis, Treatment, Chemoprophylaxis, and Institutional Outbreak Management of Seasonal Influenza. Clin Infect Dis. 2019;68(10):1790. DOI:10.1093/cid/ciz044
7. (WHO) WHO. Influenza (Seasonal) 2018. Available at: https://www.who.int/en/news-room/fact-sheets/detail/influenza-(seasonal). Accessed: 01.09.2022.
8. Popkin DL, Zilka S, Dimaano M, et al. Cetylpyridinium chloride (CPC) exhibits potent, rapid activity against influenza viruses in vitro and in vivo. Pathog Immun. 2017;2(2):253-69. DOI:10.20411/pai.v2i2.200
9. Guarner J, Paddock CD, Shieh WJ, et al. Histopathologic and immunohistochemical features of fatal influenza virus infection in children during the 2003–2004 season. Clin Infect Dis. 2006;43:132-40.
10. Nagao T, Morishima T, Kimura H, et al. Prognostic factors in influenza-associated encephalopathy. Pediatr Infect Dis J. 2008;27:384-9.
11. Sellers SA, Hagan RS, Hayden FG, Fischer WA2nd. The hidden burden of influenza: a review of the extra-pulmonary complications of influenza infection. Influenza Other Respir Viruses. 2017;11:372-93.
12. Barnes M, Heywood AE, Mahimbo A, et al. Acute myocardial infarction and influenza: a meta-analysis of case-control studies. Heart. 2015;101:1738-47.
13. Dawood FS, Kamimoto L, D’Mello TA, et al. Children with asthma hospitalized with seasonal or pandemic influenza, 2003–2009. Pediatrics. 2011;128:e27-32.
14. Kwong JC, Schwartz KL, Campitelli MA, et al. Acute myocardial infarction after laboratory-confirmed influenza infection. N Engl J Med. 2018;378:345-53.
15. Thompson WW, Weintraub E, Dhankhar P, et al. Estimates of US influenza-associated deaths made using four different methods. Influenza Other Respi Viruses. 2009;3:37-49.
16. Nair H, Abdullah Brooks W, Katz M, et al. Global burden of respiratory infections due to seasonal influenza in young children: a systematic review and meta-analysis. Lancet. 2011;378:1917-3.
17. Molinari NA, Ortega-Sanchez IR, Messonnier ML, et al. The annual impact of seasonal influenza in the US: measuring disease burden and costs. Vaccine. 2007;25(27):5086-96. 
DOI:10.1016/j.vaccine.2007.03.046
18. Centers for Disease Control and Prevention Influenza antiviral medications: summary for clinicians. Available at: https://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm. Accessed: 01.09.2022.
19. Villani L, D'Ambrosio F, Ricciardi R, et al. Seasonal influenza in children: Costs for the health system and society in Europe. Influenza Other Respir Viruses. 202;16(5):820-31. DOI:10.1111/irv.12991
20. European Centre for Disease Prevention and Control. Factsheet about seasonal influenza. Available at: https://www.ecdc.europa.eu/en/seasonal-influenza/facts/factsheet. Accessed: 01.09.2022.
21. Uyeki TM, Hui DS, Zambon M, et al. Influenza. Lancet. 2022;400(10353):693-706. DOI:10.1016/S0140-6736(22)00982-5
22. Pan M, Gao R, Lv Q, et al. Human infection with a novel, highly pathogenic avian influenza A (H5N6) virus: Virological and clinical findings. J Infect. 2016;72:52-9. DOI:10.1016/j.jinf.2015.06.009
23. Zhu W, Li X, Dong J, et al. Epidemiologic, clinical, and genetic characteristics of human infections with influenza A(H5N6) viruses, China. Emerg Infect Dis. 2022;28(7):1332-44. DOI:10.3201/eid2807.212482
24. Lu PJ, Santibanez TA, Williams WW, et al. Surveillance of influenza vaccination coverage–United States, 2007-08 through 2011-12 influenza seasons. MMWR Surveill Summ. 2013;62(4):1-28. 
25. Grohskopf LA, Sokolow LZ, Broder KR, et al. Prevention and Control of Seasonal Influenza with Vaccines. MMWR Recomm Rep. 2016;65(5):1-54. DOI:10.15585/mmwr.rr6505a1
26. Lakdawala SS, Jayaraman A, Halpin RA, et al. The soft palate is an important site of adaptation for transmissible influenza viruses. Nature. 2015;526:122-5. DOI:10.1038/nature15379
27. Свистушкин В.М., Никифорова Г.Н., Шевчик Е.А., Топоркова Л.А. Эффективность топических препаратов в лечении больных острыми воспалительными заболеваниями глотки. Вестник оториноларингологии. 2019;84(6):112-7 [Svistushkin VM, Nikiforova GN, Shevchik EA, Toporkova LA. Efficacy of topical drugs in the treatment of patients with acute inflammatory diseases of the pharynx. Vestnik Oto-Rino-Laringologii. 2019;84(6):112-7 [(in Russian)]. DOI:10.17116/otorino201984061112
28. Morokutti-Kurz M, Graf C, Prieschl-Grassauer E. Amylmetacresol/2,4-dichlorobenzyl alcohol, hexylresorcinol, or carrageenan lozenges as active treatments for sore throat. Int J Gen Med. 2017;10:53-60.
29. Mukherjee PK, Esper F, Buchheit K, et al. Randomized, double-blind, placebo-controlled clinical trial to assess the safety and effectiveness of a novel dual-action oral topical formulation against upper respiratory infections. BMC Infect Dis. 2017;17(1):74. DOI:10.1186/s12879-016-2177-8
30. Eduardo FP, Corrêa L, Heller D, et al. Salivary SARS-CoV-2 load reduction with mouthwash use: A randomized pilot clinical trial. Heliyon. 2021;7(6):e07346. DOI:10.1016/j.heliyon.2021.e07346
31. Seneviratne C, Balan P, Kwan KK, Udawatte NS. Efficacy of commercial mouth-rinses on SARS-CoV-2 viral load in saliva: randomized control trial in Singapore Chaminda. Infection. 2020;1-7. DOI:10.1007/s15010-020-01563-9
32. Carrouel F, Gonçalves LS, Conte MP, et al. J Antiviral Activity of Reagents in Mouth Rinses against SARS-CoV-2. Dent Res. 2021;100(2):124-32. DOI:10.1177/0022034520967933
33. Baker N, Williams AJ, Tropsha A, Ekins S. Repurposing Quaternary Ammonium Compounds as Potential Treatments for COVID-19. Pharm Res. 2020;37(6):104.
DOI:10.1007/s11095-020-02842-8
34. Steyer A, Marušić M, Kolenc M, Triglav T. A Throat Lozenge with Fixed Combination of Cetylpyridinium Chloride and Benzydamine Hydrochloride Has Direct Virucidal Effect on SARS-CoV-2. COVID. 2021;1(2):435-46.
35. Association BIBR. Toxicity Profile for Cetylpyridinium chloride 2005. Available at: http://www.bibra-information.co.uk/downloads/toxicity-profile-for-cetylpyridinium-chloride-2005/ Accessed: 01.09.2022.
36. Pitten FA, Kramer A. Efficacy of cetylpyridinium chloride used as oropharyngeal antiseptic. Arzneimittelforschung. 2001;51(7):588-95. DOI:10.1055/s-0031-1300084
37. Russell AD. Bacterial spores and chemical sporicidal agents. Clin Microbiol Rev. 1990;3:99-119.
38. Mao X, Auer DL, Buchalla W, et al. Cetylpyridinium Chloride: Mechanism of Action, Antimicrobial Efficacy in Biofilms, and Potential Risks of Resistance. Antimicrob Agents Chemother. 2020;64(8):e00576-20. DOI:10.1128/AAC.00576-20
39. Serrano J, Escribano M, Roldan S, et al. Efficacy of adjunctive anti-plaque chemical agents in managing gingivitis: a systematic review and meta-analysis. J Clin Periodontol. 2015;42(Suppl. 16):S106-38. DOI:10.1111/jcpe.12331
40. Raut P, Weller SR, Obeng B, et al. Hess Cetylpyridinium chloride (CPC) reduces zebrafish mortality from influenza infection: Super-resolution microscopy reveals CPC interference with multiple protein interactions with phosphatidylinositol 4,5-bisphosphate in immune function. Toxicol Appl Pharmacol. 2022;440:115913. DOI:10.1016/j.taap.2022.115913 
41. Seo HW, Seo JP, Cho Y, et al. Cetylpyridinium chloride interaction with the hepatitis B virus core protein inhibits capsid assembly. Virus Res. 2019;263:102-11.
42. Koch-Heier J, Hoffmann H, Schindler M, et al. Inactivation of SARS-CoV-2 through Treatment with the Mouth Rinsing Solutions ViruProX® and BacterX® Pro. Microorganisms. 2021;9(3):521.
43. Gilbert P, Moore LE. Cationic antiseptics: diversity of action under a common epithet. J Appl Microbiol. 2005;99(4):703-15. DOI:10.1111/j.1365-2672.2005.02664.x
44. Muñoz-Basagoiti J, Perez-Zsolt D, León R, et al. Mouthwashes with CPC reduce the infectivity of SARS-CoV-2 variants in vitro. J Dent Res. 2021;100(11):1265-72. DOI:10.1177/00220345211029269
45. Alvarez DM, Duarte LF, Corrales N, et al. Cetylpyridinium chloride blocks herpes simplex virus replication in gingival fibroblasts. Antivir Res. 2020;179:104818.
46. Славский А.Н., Мейтель И.Ю. Боль в горле: обоснование оптимального выбора препарата. Медицинский совет. 2016;18:128-32 [Slavsky AN, Meytel IY. Sore throat: justification of the optimal drug selection. Meditsinskiy sovet. 2016;18:128-32 (in Russian)].
47. Steyer A, Mikuletič T, Cerar Kišek T, Triglav T. Virucidal Efficacy of Lozenges with a Fixed-dose Combination of Cetylpyridinium Chloride and Benzydamine Hydrochloride Against Influenza A Virus. Med Razgl. 2022;61(1):121-30.

________________________________________________

1. Belyakov NA, Boeva EV, Simakina OE, et al. COVID-19 pandemic and its impact on other infections in Northwest Russia. HIV Infection and Immunosuppressive Disorders. 2022;14(1):7-24 (in Russian). DOI:10.22328/2077-9828-2022-14-1-7-24
2. Merced-Morales A, Daly P, Abd Elal AI, et al. Influenza Activity and Composition of the 2022-23 Influenza Vaccine – United States, 2021–22 Season. MMWR Morb Mortal Wkly Rep. 2022;71(29):913-9. DOI:10.15585/mmwr.mm7129a1
3. Osidak LV, Smorodintseva EA, Afanasieva OI, et al. Influenza on the threshold. Oseltamivir in the treatment of children aged 1 year or older. Farmateka. 2022;29(1):44-50 (in Russian). DOI:10.18565/pharmateca.2022.1.44-50
4. Weekly national bulletin on influenza and SARS for the 24th week of 2022 (13.06.22–19.06.22). Available at: https://www.influenza.spb.ru/system/epidemic_situation/laboratory_diagnostics. Accessed: 01.09.2022 (in Russian).
5. Gripp u vzroslykh: klinicheskie rekomendatsii. Moscow, 2021 (in Russian).
6. Uyeki TM, Bernstein HH, Bradley JS, et al. Clinical Practice Guidelines by the Infectious Diseases Society of America: 2018 Update on Diagnosis, Treatment, Chemoprophylaxis, and Institutional Outbreak Management of Seasonal Influenza. Clin Infect Dis. 2019;68(10):1790. DOI:10.1093/cid/ciz044
7. (WHO) WHO. Influenza (Seasonal) 2018. Available at: https://www.who.int/en/news-room/fact-sheets/detail/influenza-(seasonal). Accessed: 01.09.2022.
8. Popkin DL, Zilka S, Dimaano M, et al. Cetylpyridinium chloride (CPC) exhibits potent, rapid activity against influenza viruses in vitro and in vivo. Pathog Immun. 2017;2(2):253-69. DOI:10.20411/pai.v2i2.200
9. Guarner J, Paddock CD, Shieh WJ, et al. Histopathologic and immunohistochemical features of fatal influenza virus infection in children during the 2003–2004 season. Clin Infect Dis. 2006;43:132-40.
10. Nagao T, Morishima T, Kimura H, et al. Prognostic factors in influenza-associated encephalopathy. Pediatr Infect Dis J. 2008;27:384-9.
11. Sellers SA, Hagan RS, Hayden FG, Fischer WA2nd. The hidden burden of influenza: a review of the extra-pulmonary complications of influenza infection. Influenza Other Respir Viruses. 2017;11:372-93.
12. Barnes M, Heywood AE, Mahimbo A, et al. Acute myocardial infarction and influenza: a meta-analysis of case-control studies. Heart. 2015;101:1738-47.
13. Dawood FS, Kamimoto L, D’Mello TA, et al. Children with asthma hospitalized with seasonal or pandemic influenza, 2003–2009. Pediatrics. 2011;128:e27-32.
14. Kwong JC, Schwartz KL, Campitelli MA, et al. Acute myocardial infarction after laboratory-confirmed influenza infection. N Engl J Med. 2018;378:345-53.
15. Thompson WW, Weintraub E, Dhankhar P, et al. Estimates of US influenza-associated deaths made using four different methods. Influenza Other Respi Viruses. 2009;3:37-49.
16. Nair H, Abdullah Brooks W, Katz M, et al. Global burden of respiratory infections due to seasonal influenza in young children: a systematic review and meta-analysis. Lancet. 2011;378:1917-3.
17. Molinari NA, Ortega-Sanchez IR, Messonnier ML, et al. The annual impact of seasonal influenza in the US: measuring disease burden and costs. Vaccine. 2007;25(27):5086-96. 
DOI:10.1016/j.vaccine.2007.03.046
18. Centers for Disease Control and Prevention Influenza antiviral medications: summary for clinicians. Available at: https://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm. Accessed: 01.09.2022.
19. Villani L, D'Ambrosio F, Ricciardi R, et al. Seasonal influenza in children: Costs for the health system and society in Europe. Influenza Other Respir Viruses. 202;16(5):820-31. DOI:10.1111/irv.12991
20. European Centre for Disease Prevention and Control. Factsheet about seasonal influenza. Available at: https://www.ecdc.europa.eu/en/seasonal-influenza/facts/factsheet. Accessed: 01.09.2022.
21. Uyeki TM, Hui DS, Zambon M, et al. Influenza. Lancet. 2022;400(10353):693-706. DOI:10.1016/S0140-6736(22)00982-5
22. Pan M, Gao R, Lv Q, et al. Human infection with a novel, highly pathogenic avian influenza A (H5N6) virus: Virological and clinical findings. J Infect. 2016;72:52-9. DOI:10.1016/j.jinf.2015.06.009
23. Zhu W, Li X, Dong J, et al. Epidemiologic, clinical, and genetic characteristics of human infections with influenza A(H5N6) viruses, China. Emerg Infect Dis. 2022;28(7):1332-44. DOI:10.3201/eid2807.212482
24. Lu PJ, Santibanez TA, Williams WW, et al. Surveillance of influenza vaccination coverage–United States, 2007-08 through 2011-12 influenza seasons. MMWR Surveill Summ. 2013;62(4):1-28. 
25. Grohskopf LA, Sokolow LZ, Broder KR, et al. Prevention and Control of Seasonal Influenza with Vaccines. MMWR Recomm Rep. 2016;65(5):1-54. DOI:10.15585/mmwr.rr6505a1
26. Lakdawala SS, Jayaraman A, Halpin RA, et al. The soft palate is an important site of adaptation for transmissible influenza viruses. Nature. 2015;526:122-5. DOI:10.1038/nature15379
27. Свистушкин В.М., Никифорова Г.Н., Шевчик Е.А., Топоркова Л.А. Эффективность топических препаратов в лечении больных острыми воспалительными заболеваниями глотки. Вестник оториноларингологии. 2019;84(6):112-7 [Svistushkin VM, Nikiforova GN, Shevchik EA, Toporkova LA. Efficacy of topical drugs in the treatment of patients with acute inflammatory diseases of the pharynx. Vestnik Oto-Rino-Laringologii. 2019;84(6):112-7 [(in Russian)]. DOI:10.17116/otorino201984061112
28. Morokutti-Kurz M, Graf C, Prieschl-Grassauer E. Amylmetacresol/2,4-dichlorobenzyl alcohol, hexylresorcinol, or carrageenan lozenges as active treatments for sore throat. Int J Gen Med. 2017;10:53-60.
29. Mukherjee PK, Esper F, Buchheit K, et al. Randomized, double-blind, placebo-controlled clinical trial to assess the safety and effectiveness of a novel dual-action oral topical formulation against upper respiratory infections. BMC Infect Dis. 2017;17(1):74. DOI:10.1186/s12879-016-2177-8
30. Eduardo FP, Corrêa L, Heller D, et al. Salivary SARS-CoV-2 load reduction with mouthwash use: A randomized pilot clinical trial. Heliyon. 2021;7(6):e07346. DOI:10.1016/j.heliyon.2021.e07346
31. Seneviratne C, Balan P, Kwan KK, Udawatte NS. Efficacy of commercial mouth-rinses on SARS-CoV-2 viral load in saliva: randomized control trial in Singapore Chaminda. Infection. 2020;1-7. DOI:10.1007/s15010-020-01563-9
32. Carrouel F, Gonçalves LS, Conte MP, et al. J Antiviral Activity of Reagents in Mouth Rinses against SARS-CoV-2. Dent Res. 2021;100(2):124-32. DOI:10.1177/0022034520967933
33. Baker N, Williams AJ, Tropsha A, Ekins S. Repurposing Quaternary Ammonium Compounds as Potential Treatments for COVID-19. Pharm Res. 2020;37(6):104.
DOI:10.1007/s11095-020-02842-8
34. Steyer A, Marušić M, Kolenc M, Triglav T. A Throat Lozenge with Fixed Combination of Cetylpyridinium Chloride and Benzydamine Hydrochloride Has Direct Virucidal Effect on SARS-CoV-2. COVID. 2021;1(2):435-46.
35. Association BIBR. Toxicity Profile for Cetylpyridinium chloride 2005. Available at: http://www.bibra-information.co.uk/downloads/toxicity-profile-for-cetylpyridinium-chloride-2005/ Accessed: 01.09.2022.
36. Pitten FA, Kramer A. Efficacy of cetylpyridinium chloride used as oropharyngeal antiseptic. Arzneimittelforschung. 2001;51(7):588-95. DOI:10.1055/s-0031-1300084
37. Russell AD. Bacterial spores and chemical sporicidal agents. Clin Microbiol Rev. 1990;3:99-119.
38. Mao X, Auer DL, Buchalla W, et al. Cetylpyridinium Chloride: Mechanism of Action, Antimicrobial Efficacy in Biofilms, and Potential Risks of Resistance. Antimicrob Agents Chemother. 2020;64(8):e00576-20. DOI:10.1128/AAC.00576-20
39. Serrano J, Escribano M, Roldan S, et al. Efficacy of adjunctive anti-plaque chemical agents in managing gingivitis: a systematic review and meta-analysis. J Clin Periodontol. 2015;42(Suppl. 16):S106-38. DOI:10.1111/jcpe.12331
40. Raut P, Weller SR, Obeng B, et al. Hess Cetylpyridinium chloride (CPC) reduces zebrafish mortality from influenza infection: Super-resolution microscopy reveals CPC interference with multiple protein interactions with phosphatidylinositol 4,5-bisphosphate in immune function. Toxicol Appl Pharmacol. 2022;440:115913. DOI:10.1016/j.taap.2022.115913 
41. Seo HW, Seo JP, Cho Y, et al. Cetylpyridinium chloride interaction with the hepatitis B virus core protein inhibits capsid assembly. Virus Res. 2019;263:102-11.
42. Koch-Heier J, Hoffmann H, Schindler M, et al. Inactivation of SARS-CoV-2 through Treatment with the Mouth Rinsing Solutions ViruProX® and BacterX® Pro. Microorganisms. 2021;9(3):521.
43. Gilbert P, Moore LE. Cationic antiseptics: diversity of action under a common epithet. J Appl Microbiol. 2005;99(4):703-15. DOI:10.1111/j.1365-2672.2005.02664.x
44. Muñoz-Basagoiti J, Perez-Zsolt D, León R, et al. Mouthwashes with CPC reduce the infectivity of SARS-CoV-2 variants in vitro. J Dent Res. 2021;100(11):1265-72. DOI:10.1177/00220345211029269
45. Alvarez DM, Duarte LF, Corrales N, et al. Cetylpyridinium chloride blocks herpes simplex virus replication in gingival fibroblasts. Antivir Res. 2020;179:104818.
46. Славский А.Н., Мейтель И.Ю. Боль в горле: обоснование оптимального выбора препарата. Медицинский совет. 2016;18:128-32 [Slavsky AN, Meytel IY. Sore throat: justification of the optimal drug selection. Meditsinskiy sovet. 2016;18:128-32 (in Russian)].
47. Steyer A, Mikuletič T, Cerar Kišek T, Triglav T. Virucidal Efficacy of Lozenges with a Fixed-dose Combination of Cetylpyridinium Chloride and Benzydamine Hydrochloride Against Influenza A Virus. Med Razgl. 2022;61(1):121-30.

О.В. Филиппова*

ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет), Москва, Россия
*ffiona@mail.ru

________________________________________________

Olga V. Filippova*

Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
*ffiona@mail.ru