ОРИГИНАЛЬНАЯ СТАТЬЯ Эндодонтические силеры как профилактика биопленки: факты и гипотезы М. Соломонов, отделение эндодонтии госпиталь Шиба, Тель0Хашомер, Израиль Резюме Äàííàÿ ñòàòüÿ ïîñâÿùåíà âîïðîñó âëèÿíèÿ ñîñòàâà êîðíåâîãî ñèëåðà íà áèîïëåíêó êîðíåâîãî êàíàëà.  ðàáîòå ïðèâåäåíû ïîñëåäíèå äàííûå, êàñàþùèåñÿ ïðèìåíåíèÿ íåðàñòâîðèìûõ ìàêðîìîëåêóë, à òàêæå íàíî÷àñòèö â êà÷åñòâå àíòèáàêòåðèàëüíûõ àãåíòîâ, âõîäÿùèõ â ñîñòàâ êîðíåâûõ ñèëåðîâ. Êðàòêî èçëîæåíû ìåõàíèçìû èõ âîçäåéñòâèÿ íà ýíäîäîíòè÷åñêóþ èíôåêöèþ, ðàññìîòðåíû äîñòîèíñòâà ýòèõ àãåíòîâ, à òàêæå ïîòåíöèàëüíûå ðèñêè èõ ïðèìåíåíèÿ. Ключевые слова: корневой силер, пломбирование корневого канала, биопленка, дезинфекция, наноча6 стицы. Èñòîðè÷åñêè êîíöåïöèè èñïîëüçîâàíèÿ ñèëåðîâ â ýíäîäîíòèè â Àìåðèêàíñêîé è Åâðîïåéñêîé øêîëàõ áûëè ïîëÿðíûìè. Åâðîïåéñêèé ïîäõîä ïðåäïîëàãàë íàëè÷èå ó ñèëåðà âûðàæåííûõ àíòèáàêòåðèàëüíûõ ñâîéñòâ. Àìåðèêàíñêàÿ íàó÷íàÿ ýíäîäîíòè÷åñêàÿ øêîëà ïðåäïî÷èòàëà ðåêîìåíäîâàòü äëÿ îáòóðàöèè êàíàëîâ èíåðòíûå ñèëåðû. Ïðè÷èíà çàêëþ÷àåòñÿ â òîì, ÷òî àíòèáàêòåðèàëüíûå èíãðåäèåíòû, ÿâëÿÿñü àêòèâíûìè âåùåñòâàìè, âûäåëÿþòñÿ èç îñíîâíîãî ìàòåðèàëà (ñèëåðà) è ïîýòîìó ñî âðåìåíåì èñ÷åçàþò [1] - â ýòîò ìîìåíò ìàòåðèàë òåðÿåò àíòèáàêòåðèàëüíûå ñâîéñòâà, à çàîäíî ñâîé îáú¸ì è, ñëåäîâàòåëüíî, ãåðìåòè÷íîñòü. Ïðîöåññ ïîòåðè àêòèâíîãî ðàñòâîðèìîãî èíãðåäèåíòà óñêîðÿåòñÿ àïèêàëüíîé ïåðêîëÿöèåé - äâèæåíèåì ïåðèàïèêàëüíîé æèäêîñòè â àïèêàëüíóþ ÷àñòü êîðíåâîãî êàíàëà âî âðåìÿ æåâàíèÿ. Ñîâðåìåííûå ìåòîäèêè äåçèíôåêöèè íå ñïîñîáíû ñòåðèëèçîâàòü êîðíåâûå êàíàëû [2], ïîýòîìó èññëåäîâàòåëè ïîëàãàþò, ÷òî êà÷åñòâåííàÿ îáòóðàöèÿ âûïîëíèò ôóíêöèþ çàìóðîâûâàíèÿ îñòàâøèõñÿ â êàíàëå ìèêðîîðãàíèçìîâ è òåì ñàìûì íàðóøèò èõ æèçíåäåÿòåëüíîñòü [3]. Âàæíàÿ ðîëü ïðè ýòîì ïðèíàäëåæèò òåì ñèëåðàì, êîòîðûå íà ýòàïå òâåðäåíèÿ îáëàäàþò âûðàæåííûìè àíòèáàêòåðèàëüíûìè ñâîéñòâàìè, ñòàíîâÿñü èíåðòíûìè ïîñëå çàòâåðäåâàíèÿ [4]. Îäíà èç íàèáîëåå ðåêîìåíäóåìûõ ãðóïï êîðíåâûõ ãåðìåòèêîâ - ýïîêñèäíûå ñèëåðû, êîòîðûå ïðè çàòâåðäåâàíèè îáëàäàþò àíòèáàêòåðèàëüíûì ýôôåêòîì, à ïîñëå çàòâåðäåâàíèÿ ñòàíîâÿòñÿ ïîëíîñòüþ èíåðòíûìè [4]. Ïðîáëåìà ñîâðåìåííûõ îáòóðàöèîííûõ ìàòåðèàëîâ â òîì, ÷òî îíè íå â ñèëàõ íà äëèòåëüíûé ñðîê ñïðàâèòüñÿ ñ ïðîíèêíîâåíèåì íîâûõ ìèêðîîðãàíèçìîâ èç ðîòîâîé ïîëîñòè ïðè íàðóøåííîì êîðîíêîâîì ãåðìåòèçìå [5]. Êàê ïðàâèëî, ÷åðåç 3 ìåñÿöà êîíòàêòà ñ ðîòîâîé ïîëîñòüþ îáòóðèðîâàííûé êîðíåâîé êàíàë èíôèöèðóåòñÿ è ïîäëåæèò ïåðåëå÷èâàíèþ [6]. І Том VII, № 102, 2014 Ñ ìîìåíòà îáíàðóæåíèÿ è îñîçíàíèÿ òîãî ôàêòà, ÷òî áàêòåðèàëüíàÿ èíôåêöèÿ â íàøåì îðãàíèçìå, è â ÷àñòíîñòè â êîðíåâîì êàíàëå çóáà, ñóùåñòâóåò â áîëüøèíñòâå ñëó÷àåâ â ôîðìå áèîïëåíêè [7], íà÷àëñÿ ïîèñê íîâûõ ìåòîäîâ áîðüáû ñ íåé. Îäíî èç íîâåéøèõ íàïðàâëåíèé - ýòî ïðèìåíåíèå íåðàñòâîðèìûõ äåçèíôèöèðóþùèõ ìàêðîìîëåêóë, êîòîðûå óíè÷òîæàþò áàêòåðèè ïðè ïðÿìîì êîíòàêòå, íè÷åãî íå âûäåëÿÿ è íå ðàñòâîðÿÿñü. Ìåõàíèçì èõ äåéñòâèÿ ñëåäóþùèé: ìàêðîìîëåêóëû îáëàäàþò ïîëîæèòåëüíûì (+) ýëåêòðè÷åñêèì çàðÿäîì, à ìèêðîáû - îòðèöàòåëüíûì (-) ýëåêòðè÷åñêèì çàðÿäîì, â òî âðåìÿ êàê êëåòêè ÷åëîâå÷åñêîãî îðãàíèçìà ýëåêòðè÷åñêèì çàðÿäîì íå îáëàäàþò. Ïðè êîíòàêòå ìàêðîìîëåêóëû ñ áàêòåðèåé íàðóøàåòñÿ ïðîíèöàåìîñòü ìåìáðàíû ìèêðîáà ñ ïîñëåäóþùåé åãî ãèáåëüþ [8]. Âàæíåéøèì ñâîéñòâîì ìàêðîìîëåêóëû ÿâëÿåòñÿ òî, ÷òî, äåéñòâóÿ, îíà íå èñ÷åçàåò, íå ðàñòâîðÿåòñÿ è íå òåðÿåò ñâîèõ ñâîéñòâ [8] â îòëè÷èå îò êëàññè÷åñêèõ àíòèáàêòåðèàëüíûõ âåùåñòâ: ãèïîõëîðèòà íàòðèÿ (NaOCl), õëîðãåêñèäèíà áèãëþêîíàòà (CHX), ãèäðîêñèäà êàëüöèÿ (Ca(OH)2) è éîäîôîðìà. Ñóùåñòâóåò íåñêîëüêî íîâûõ íàïðàâëåíèé â èñïîëüçîâàíèè äåçèíôèöèðóþùèõ ìàêðîìîëåêóë â ýíäîäîíòèè. Îäíî èç íèõ - ýòî èñïîëüçîâàíèå íàíî÷àñòèö âåëè÷èíîé îò 1 íì äî 100 íì. Íàïðèìåð, ïðèðîäíàÿ íàíî÷àñòèöà Õèòîçàí äîáûâàåòñÿ èç õèòèíîâîãî ïîêðîâà ìåëêèõ ðàêîîáðàçíûõ [9]. Èññëåäîâàòåëè ãðóïïà Øðåñòû è Êèøåíà ïîïûòàëèñü ïðèìåíèòü åå äëÿ ëèêâèäàöèè áèîïëåíêè [10]. Îäíàêî îíè íå ïîëó÷èëè çíà÷èìîãî óëó÷øåíèÿ ðåçóëüòàòà ïî ñðàâíåíèþ ñ êëàññè÷åñêèìè ìåòîäàìè ñ ïðèìåíåíèåì Ca(OH)2 è ôîòîàêòèâèðóåìîé äåçèíôåêöèè [10]. Áûëà òàêæå ïîïûòêà èñïîëüçîâàòü íàíî÷àñòèöû ñåðåáðà äëÿ óíè÷òîæåíèÿ áèîïëåíêè, îäíàêî ðåçóëüòàò íå áûë çíà÷èìûì [11]. Íà ìîé âçãëÿä, ïðîáëåìà êðîåòñÿ â ýëåêòðè÷åñêîì çàðÿäå. Áèîïëåíêà èìååò (-) çàðÿä, è ïîýòîìó íàíî÷àñòèöû áóäóò ïðèòÿãèâàòüñÿ 63 ОРИГИНАЛЬНАЯ СТАТЬЯ ê ïîâåðõíîñòè áèîïëåíêè, íå ïðîíèêàÿ â åå âíóòðåííèå ñëîè. Áåçóñëîâíî, ýòî ïðåäïîëîæåíèå òðåáóåò íàó÷íîãî ïîäòâåðæäåíèÿ. Ïàðàëëåëüíî âîçíèêëî íàïðàâëåíèå, ñâÿçàííîå ñ èñïîëüçîâàíèåì íàíî÷àñòèö äëÿ ïðåäîòâðàùåíèÿ âîçíèêíîâåíèÿ áèîïëåíêè.  Èåðóñàëèìñêîì Óíèâåðñèòåòå áûëà ñîçäàíà ñèíòåòè÷åñêàÿ íàíî÷àñòèöà Quaternary ammonium polyethyleneimine (QA-PEI), íàçûâàåìàÿ òàêæå I-ABN (Insoluble Anti-Bacterial Nanoparticles, Íåðàñòâîðèìûe Àíòè-Áàêòåðèàëüíûe Íàíî÷àñòèöû) [12].  ñåðèè ýêñïåðèìåíòîâ äàííóþ ÷àñòèöó äîáàâëÿëè â ðàçëè÷íûå ñòîìàòîëîãè÷åñêèå ìàòåðèàëû [12, 14, 15, 18, 19]. Êàê ðåçóëüòàò, â òå÷åíèå 1-3 ìåñÿöåâ (äëèòåëüíîñòü ýêñïåðèìåíòoâ) ïîëíîñòüþ ïðåäîòâðàùàëîñü îáðàçîâàíèå áèîïëåíêè íà ïîâåðõíîñòè ìàòåðèàëîâ.  ãðóïïå ìàòåðèàëîâ, íàïðèìåð êîìïîçèòîâ, áåç äîáàâëåíèÿ íàíî÷àñòèö óæå ÷åðåç 24 ÷àñà ïîâåðõíîñòü áûëà ïîêðûòà áèîïëåíêîé [13, 14, 15].  ýíäîäîíòèè âîçíèêëà èäåÿ ñîçäàíèÿ ñèëåðà ñ äîáàâëåíèåì íàíî÷àñòèö. Áûë ñîçäàí íîâûé ýïîêñèäíûé ñèëåð BJM Root Canal Sealer. Äàííûé ñèëåð ñ äîáàâëåíèåì íàíî÷àñòèöû êàê ìèíèìóì 3 ìåñÿöà ïðåäîòâðàùàåò îáðàçîâàíèå áèîïëåíêè ïðè ïðÿìîì êîíòàêòå ñ èíôåêöèåé [19]. Èäåÿ äîáàâëåíèÿ íàíî÷àñòèöû â ñèëåð áûëà ïðîâåðåíà è äðóãîé ãðóïïîé èññëåäîâàòåëåé. Íàíî÷àñòèöà áûëà äîáàâëåíà â òàêèå ñèëåðû, êàê AH Plus è Root Canal Såaler; ðåçóëüòàòû ïîêàçàëè âûðàæåííîå äåéñòâèå ïðîòèâ áèîïëåíêè [20]. Îäíàêî ñ èñïîëüçîâàíèåì íàíî÷àñòèö âîçíèêëà îïðåäåëåííàÿ ïðîáëåìà: íàíî÷àñòèöû ìîãóò ïðîõîäèòü ÷åðåç ëþáûå áàðüåðû â ÷åëîâå÷åñêîì îðãàíèçìå, âêëþ÷àÿ ïëàöåíòàðíûé è ãåìàòîýíöåôàëè÷åñêèé [21, 22], è èññëåäîâàòåëè íå çíàþò, ê êàêèì áèîëîãè÷åñêèì ïîñëåäñòâèÿì ýòî ìîæåò ïðèâåñòè.  íàñòîÿùåå âðåìÿ ðàçðàáàòûâàþòñÿ íîâûå ìåòîäèêè ïðîâåðîê, è ïîêà ìèíèñòåðñòâà çäðàâîîõðàíåíèé ìíîãèõ ñòðàí íå äàþò ðàçðåøåíèå íà èñïîëüçîâàíèå ìàòåðèàëîâ, ñîäåðæàùèõ íàíî÷àñòèöû [23, 24].  êà÷åñòâå ðåøåíèÿ ýòîé ïðîáëåìû âîçíèêëî íàïðàâëåíèå èñïîëüçîâàíèÿ äåçèíôèöèðóþùèõ ìàêðîìîëåêóë, íå ÿâëÿþùèõñÿ íàíî÷àñòèöàìè. Îäíîé èç íàèáîëåå øèðîêî èñïîëüçóåìûõ òàêèõ ìàêðîìîëåêóë â îáùåé ìåäèöèíå ÿâëÿåòñÿ ìàòåðèàë BioSafe, êîòîðûé øèðîêî ïðèìåíÿåòñÿ â êà÷åñòâå äîáàâêè ê ïëàñòèêàì, èç êîòîðûõ äåëàþòñÿ êàòåòåðû è ïîêðûòèÿ êëàâèàòóðû [25]. Äîáàâêå BioSafe â ýíäîäîíòèè áûëî ïðèñâîåíî ìàðêåòèíãîâîå îáîçíà÷åíèå Immobilized Antibacterial Technology (IABT). BJM Root Canal Sealer âûïóñêàåòñÿ ñåãîäíÿ ñ ýòîé äîáàâêîé. Òàê êàê BJM Root Canal Sealer - íîâûé ñèëåð, âàæíî ïðîâåðèòü, ñîîòâåòñòâóþò ëè åãî ñâîéñòâà ñòàíäàðòàì ISO, íå èçìåíÿòñÿ ëè åãî ôèçè÷åñêèå ñâîéñòâà ïðè äîáàâëåíèè BioSafe è, êîíå÷íî, êà- 64 êîâ óðîâåíü åãî áèîñîâìåñòèìîñòè. Òàêîå èññëåäîâàíèå áûëî ïðîâåäåíî è ñåé÷àñ ãîòîâèòñÿ ê ïóáëèêàöèè [26]. Ñâîéñòâà ìàòåðèàëa áûëè ïðîâåðåíû â ñðàâíåíèè ñ êëàññè÷åñêèìè ýïîêñèäíûìè ñèëåðàìè AH Plus è MMSeal. BJM Root Canal Sealer ñîîòâåòñòâóåò ñòàíäàðòàì ISO è äåìîíñòðèðóåò âûñîêóþ áèîñîâìåñòèìîñòü. Ñóùåñòâóåò íåîáõîäèìîñòü â äîïîëíèòåëüíûõ èññëåäîâàíèÿõ, êîòîðûå ìîãëè áû ïðîâåðèòü äëèòåëüíîñòü äåéñòâèÿ ìàêðîìîëåêóë â êîíòàêòå ñ áèîïëåíêîé â ìàêñèìàëüíî ïðèáëèæåííûõ ê ðîòîâîé ïîëîñòè óñëîâèÿõ. Åñëè áóäåò äîêàçàíà íåîãðàíè÷åííàÿ äëèòåëüíîñòü äåéñòâèÿ, êàê íàì îáåùàþò õèìèêè, òî ìû ìîæåì îêàçàòüñÿ â êà÷åñòâåííî íîâîé ñèòóàöèè - ïðîãíîç ýíäîäîíòè÷åñêîãî ëå÷åíèÿ ïðàêòè÷åñêè íå áóäåò çàâèñåòü îò êà÷åñòâà êîðîíàëüíîé ãåðìåòèçàöèè! Áåçóñëîâíî, ýòî ãèïîòåçà, è ìû áóäåì æäàòü ðåçóëüòàòîâ èññëåäîâàíèé. 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Quintessence international 44, no. 3 (2012): 209-216. 19. D. Kesler Shvero, N. Zaltsman, E. Weiss, N. Beyth Antibacterial mechanism of novel endodontic sealer. Manuscript in preparation. 20. Barros J., Silva M.G., Rocas I.N., Goncalves L.S., Alves F.F., Lopes M.A. & Siqueira Jr, J.F. Antibiofilm effects of endodontic sealers containing quaternary ammonium polyethylenimine nanoparticles. Journal of Endodontics, 2014; Aug; 40(8):1167-71. 21. Lockman P.R. et al. Nanoparticle surface charges alter blood-brain barrier integrity and permeability. J Drug Target. 2004; 12(9-10): 635-641. 22. FDA, 2010. Center for Drug Evaluation and Research MAPP. Office of Pharmaceutical Science. Reporting Format for Nanotechnology. 23. Rocks S.S., Pollard R.D., Levy L., Harrison P., Handy R. Comparison of risk assessment approaches for manufactured nanomaterials. 2008; Defra, London. 24. Chaudhry Q., Bouwmeester H. and Hertel R.F. (2010) The Current Risk Assessment Paradigm in Relation to Regulation of Nanotechnologies, In. G.A. Hodge, D.M. Bowman and A.D. Maynard (eds), International Handbook on Regulating Nanotechnologies. Cheltenham: Edward Elgar, 124-143. 25. D'Antonio N.N., Rihs J.D., Stout J.E., Yu V.L. Computer keyboard covers impregnated with a novel antimicrobial polymer significantly reduce microbial contamination. Am J Infect Control. 2013 Apr; 41(4):337-9. 26. Shemesh A., À. Levin, Ben Itzhak, Â. Katzenell, Ì. Solomonov. Comparisons of the physical properties of 3 epoxy resin-based root canal sealers - a novel one and two old. Ìanuscript in preparation. Root Canal Sealers as Biofilm Prevention: Facts and Speculations M. Solomonov Abstract The present paper is dedicated to the influence of endodontic sealer composition on the microbial biofilm within the root canal. The data of the recent studies concerning the use of insoluble macromolecules and nanoparticles as antibacterial agents included in the root canal sealers are also cited. Furthermore this article summarizes the information about its mechanisms of action on the endodontic infection, advantages of these new disinfection agents and the potential risks of its use. Key words: root canal sealer, obturation of the root canal, biofilm, disinfection, nanoparticles. І Том VII, № 102, 2014 65
