RU2731904C1 - Composition for modification of root canal irrigation agent - Google Patents

Abstract

FIELD: medicine; chemistry.

SUBSTANCE: invention refers to dentistry, namely to a composition for modifying an irrigant based on sodium hypochlorite, which is used for endodontic treatment and disinfection of root canals. Proposed composition is intended for introduction in 3 % sodium hypochlorite solution at ratio of 1:1. Composition contains, wt. %: surfactant in form of amine oxide - 0.2–1.2; disinfectant, used as alkyldimethylbenzalkonium chloride or myramistin - 0.05–0.3; disodium EDTA - 0.1–0.3; distilled water is balance.

EFFECT: technical result with introduction of said composition in ratio 1:1 in 3 % sodium hypochlorite solution: reducing coefficient of surface tension of irrigant to 34–39 mN/m, reduced toxic properties of the irrigant based on sodium hypochlorite due to the fact that in the composition with the disclosed composition its concentration is not more than 1_5 %; maintaining high virucidal and bactericidal activity of the irrigant based on sodium hypochlorite, along with the expansion of its antimicrobial spectrum even with concentration of sodium hypochlorite in the finished composition of not more than 1_5 % due to the synergetic effect of combining sodium hypochlorite and the disclosed composition, which provides higher effectiveness of medicamentous treatment of root canals and provides the safety of patients.

1 cl, 4 dwg, 2 tbl, 4 ex

Description

The invention relates to dentistry, namely to a composition for modifying an irrigant based on sodium hypochlorite, which is used for endodontic treatment and disinfection of root canals, due to its antiseptic and dissolving properties. Effective irrigation in chemical-instrumented root canal treatment is critical to the future success of endodontic treatment.

Improving the quality of endodontic treatment is still an urgent task, because it is at this stage of treatment that the largest number of complications arise. Analyzing the causes of endodontic failures, it is necessary to overestimate the significance of its individual stages: instrumental cleaning, drug treatment and filling of a complex root canal system.

The purpose of instrumental treatment of the root canal is to completely remove the remnants of the pulp or products of its decay from it, to remove incompletely mineralized infected tissues from the walls of the canal, to expand the canal and give it the appropriate shape and taper necessary for a complete filling of the root canal.

Today, endodontic science has extensive knowledge of the structure of the root canal system. It is known that the internal morphology of a tooth is extremely complex and varied. Perfectly round in cross section, a tapered root canal with one apical foramen is perhaps the rare exception rather than the rule. In the overwhelming majority of cases, the canals have an irregular shape, different diameters in the buccolingual and mesiodistal directions, numerous undercuts, the so-called "fins". Oval or C-shaped canals are common. In addition, many lateral tubules depart from the main canal at different levels. Lateral tubules are also found in the area of bifurcations and trifurcations of multi-rooted teeth. There are numerous anastomoses and isthmuses between the root canals, which are especially common, for example, between the mesial canals of the mandibular molars. The morphology of the apical third of the root is very complex. It is known that the main canal in the apical part forms a delta and opens at the root apex not with one but with several apical foramen. Based on the foregoing, it becomes obvious that such a complex system cannot be cleaned only mechanically - instrumentally.

During the preparation of hard tooth tissues with hand or machine tools, a microscopic layer is formed on the surface of the dentin, consisting of a mixture of destroyed dentin and dentin - a lubricated layer. It closes the openings of the dentinal tubules; serves as a source and by way of periodontal infection; impairs the adaptation of the sealers to the wall of the root canal, i.e. it is an obstacle to the penetration of the sealers into the dentinal tubules; reduces apical and orifice permeability. In connection with the above, the smeared layer of the root canal must be completely removed.

The complexity of the internal morphology of the tooth, as well as the presence of a smeared layer, force us to search for new solutions to increase the efficiency of root canal cleaning, as a guarantee of successful endodontics.

Irrigation solutions used in root canal preparation have a number of functions. First of all, they flush decay and dentin filings from the canal. This eliminates the blockage of the root canal. Secondly, in most cases they have an antiseptic effect, removing the smeared layer consisting of organic and inorganic components that are formed during the preparation of the canal. Finally, flushing solutions are a kind of lubricant between the instrument and the canal wall.

Compliance with the irrigation protocol (sodium hypochlorite 5.25% - distilled water - EDTA 17% - distilled water - chlorhexidine) allows you to clean the root canal system due to the chemical dissolution of organic and inorganic residues, as well as their mechanical washing out with a stream of liquid; disinfect it - remove barriers to 3D obturation and hope for successful long-term results in root canal therapy. [Zehnder M. Root Canal Irrigants. J Endod. 2006; 32: 389-98. [PubMed] [Google Scholar]

It is not yet possible to achieve all the goals of irrigation using only one irrigant, since none of the known irrigants fulfills all the requirements for root canal irrigants at the same time:

• have a wide spectrum of antimicrobial activity and high efficiency against anaerobic and facultative microorganisms in the biofilm structure;

• provide root canal disinfection;

• ensure endotoxin deactivation;

• dissolve diseased tissues and bacterial debris;

• remove the smeared layer;

• have sufficient lubricating properties;

• have a low surface tension;

• have low toxicity;

• be systemically non-toxic, do not provoke damage to the periodontal tissues;

• have a low cost, be readily available, and have a sufficient shelf life.

[Internet link: https://stomatologclub.ru/stati/terapiya-10/specifika-irrigacii-gipohloritom-natriya-1996/]

Most of these requirements are met by sodium hypochlorite (NaOCl), which is called the "gold standard" of endodontics. Sodium hypochlorite solution was proposed for use as a wound flushing agent as early as 1915, and as an irrigation solution for endodontics began to be used in the United States around 1920. [J Conserv Dent. October-December 2010; 13 (4): 256-264. // Root canal irrigants]

Sodium hypochlorite has a number of properties that make it popular in endodontics. Many studies have demonstrated its antiseptic properties. The exact mechanism of the antimicrobial activity of sodium hypochlorite is not completely clear, but it can be determined by the formation of hypochlorous acid and the release of active chlorine, which leads to the oxidation of sulfhydryl groups of bacterial enzymes. [Esterla C, Cyntia RA, Esterla, Barbin EL. The mechanism of action of sodium hypochlorite. Braz Dent J. 2002; 13: 113-7. [PubMed] [Google Scholar]

The unique ability to dissolve the organic contents of root canals: necrotic tissues, decay products, scraps of extirpated pulp - distinguishes it from other irrigants.

Despite all the advantages, sodium hypochlorite has disadvantages, for example, high surface tension, which prevents it from completely cleaning and disinfecting the root canal system. At a concentration of 1%, the surface tension is 75 dynes / cm (which corresponds to 75 mN / m) (Carlos EstrelaI; Cyntia RA EstrelaI; Eduardo Luis BarbinII; Júlio César E. SpanóII; Melissa A. MarchesanII; Jesus D. PécoraII, Mechanism of action of sodium hypochlorite, Braz. Dent. J. vol. 13 no. 2 Ribeirão Preto 2002, internet link: https://www.researchgate.net/publication/11151657_Mechanism_of_Action_of_Sodium_Hypochlorite).

Another disadvantage is its cytotoxic properties, which are directly proportional to its concentration. Irrigation with sodium hypochlorite removes biofilm and eliminates most pathogenic microorganisms due to the oxidizing, hydrolytic and osmotic properties of hypochlorite. However, the accidental extrusion of a high concentration hypochlorite solution beyond the apex of the tooth root can cause a serious complication due to the specific cytotoxic properties of the antiseptic solution. The complication was called "hypochlorite accident" due to the sudden onset of symptoms and rapid development. The literature describes severe cases of NaOCl excretion into the periapical tissues, as well as cases of hypochlorite excretion into the maxillary sinus, as well as cases of the development of allergic reactions upon contact with the oral mucosa.

To reduce the risk of complications, it is recommended to accurately determine the working length of endodontic instruments, use stoppers on lateral-perforated endodontic needles for irrigation needles, use low pressure during irrigation, and use low concentrations of sodium hypochlorite solution during treatment. [Accidental trans-apical extrusion of sodium hypochlorite, diagnosed by tomographic examination Authors: Elif Delve BaGer Can, Meric KarapJnar KazandaL, Rabia Figen Kaptan, Internet link: https://stomatologclub.ru/stati/terapiya-10/sluchajnaya-zaapikalnaya-ekstruziya -natriya-gipohlorita-diagnostirovannaya-pri-pomoshi-tomograficheskogo-issledovaniya-1243]

A decrease in the surface tension coefficient of a sodium hypochlorite solution is achieved by introducing surfactants into the solution. This increases the wettability of dentin, improves the penetration of the material into hard-to-reach areas of the root canal system, and ensures effective destruction of bacteria located in them.

Known foreign irrigants based on sodium hypochlorite, which have a reduced coefficient of surface tension.

For example, Clor Xtra is a one-component material containing 6% NaOCl with surface modifiers (Chlor-Xtra®, Vista Dental Products) with a surface tension of 33.14 mN / m. (internet link: https://vistadental.com/products/chlor-xtra/).

The disadvantage of Clor Xtra is the insufficient preservation of the properties of sodium hypochlorite during long-term storage.

Also known is a two-component material Hypoclean based on 5% NaOCl (component 1, in an amount of 45 ml) in combination with surface tension modifiers (component 2, in an amount of 1.8 ml). The combination of sodium hypochlorite with surface tension modifiers improves the penetration of the solution into hard-to-reach areas of the root canal system. [Gatina E. N., Egorova G.R., Fazylova Yu.V. Modern possibilities of root canal irrigation // Young scientist №11 (91) June-1 2015]

Before using the material, it is necessary to mix components 1 and 2. In this case, a mixture of two different surfactants is used as a surface tension modifier: cetrimide (cationic surfactant) and polypropylene glycol (nSAS - nonionic surfactant). The surface tension of the Hypoclean material is, according to the literature, 29.13 mN / m (Internet link: https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2591.2011.01952.x).

When mixing the components in the specified ratio, the concentration of sodium hypochlorite decreases slightly from 5% to 4.8%, i.e. the toxic properties of sodium hypochlorite and the risk of complications when working in the apical third of the canal remain.

Thus, despite the presence of foreign irrigants based on sodium hypochlorite in combination with surface tension modifiers, the problem of developing highly effective domestic compositions for modifying an irrigant based on sodium hypochlorite remains relevant.

The objective of the invention is the development of a composition for modifying the irrigant of root canals of teeth based on sodium hypochlorite, which reduces the surface tension coefficient and toxic properties of the initial solution while maintaining its high virucidal and antimicrobial activity.

The technical result with the introduction of the claimed composition in a 3% sodium hypochlorite solution in a 1: 1 ratio is:

- lowering the coefficient of surface tension of the irrigant by almost two times, due to the introduction of a surface-active compound;

- reducing the toxic properties of the irrigant based on sodium hypochlorite due to the fact that in the composition with the proposed composition its concentration is no more than 1.5%;

- preservation of high virucidal and bactericidal activity of the irrigant based on sodium hypochlorite, along with the expansion of its antimicrobial spectrum even when the concentration of sodium hypochlorite in the finished composition does not exceed 1.5% due to the synergistic effect of combining sodium hypochlorite and the proposed composition, which ensures an increase in the efficiency of drug treatment root canals, and ensures patient safety.

The problem is solved by the proposed composition for modifying the irrigant of root canals of teeth based on sodium hypochlorite, introduced into a 3% sodium hypochlorite solution in a 1: 1 ratio, including (wt%):

- a surface-active compound characterized by stability in oxidant solutions and moderate toxicity - from 0.2 to 1.2;

- a disinfectant belonging to the group of quaternary ammonium compounds (hereinafter QAC) - 0.05-0.3;

- disodium salt of EDTA, as a stabilizing agent - 0.1-0.3;

- distilled water - the rest.

As the surface active compound of the present invention, it is preferable to use amine oxides. Amine oxides belong to a special class of surfactants classified as amphoteric surfactants. Amine oxides have a low coefficient of biological accumulation, are easily removed by standard purification methods, and are biodegradable under the action of aerobic and anaerobic bacteria. Amine oxides have low to moderate toxicity and are stable in oxidizing solutions (sodium hypochlorite or hydrogen peroxide). [https://nobel-group.by/2017/12/11/oksidy-amina-nekotorye-informatsiya/].

As a disinfecting agent, the composition contains QAS, which are classified as cationic surfactants, are used in medicine and veterinary medicine both as independent preparations and as active components in mixed antiseptic agents. (Vashkov V.I. Sterilization means used in medicine.-M.-1973, p. 296; Afinogenov G.E., Elinov P.N. Antiseptics in surgery, 1987, p. 75-90; Krasilnikov A.P. Handbook of antiseptics. Minsk. 1995, p. 67, 294).

Disodium EDTA salt was used as a stabilizing agent to eliminate a possible negative effect on the activity of the used QAS hardness salts, which can be in a solution of an irrigant based on sodium hypochlorite, as well as to prevent the formation of deposits of mineral salts during storage of the composition.

As a result of clinical and laboratory research and evaluation of the effectiveness of each ingredient of the proposed composition, and combinations of ingredients of the composition within the stated limits, it was unexpectedly found that due to the manifestation of synergism of the components of the composition and sodium hypochlorite, the claimed composition when introduced into

A 3% sodium hypochlorite solution in a 1: 1 ratio not only lowers the surface tension while maintaining a high virucidal and bactericidal activity of an irrigant based on sodium hypochlorite, but also expands its antimicrobial spectrum.

An analysis of known technical solutions in this field of technology showed that the proposed technical solution does not follow for a specialist explicitly from the state of the art, since no solutions have been identified that have features that coincide with the distinctive features of the invention and the knowledge of the influence of distinctive features on the technical result. Those. the claimed solution has features that are absent in known technical solutions, and the use of these features in the claimed set of essential features makes it possible to obtain a new technical result, therefore, the proposed technical solution could only be obtained by a creative approach and is not obvious for an average specialist in this area, i.e. .e. has an inventive step in comparison with the state of the art.

The presented invention is characterized by the following graphic materials:

FIG. 1. Image of a fragment of a mixed biofilm with a pronounced mantle and free-lying bacterial cells, obtained as a result of ex vivo modeling on extracted teeth: SEM Magnification 12000x.

FIG. 2. Image of the result of exposure of 3% sodium hypochlorite to biofilm in Fig. 1 ex vivo: SEM Magnification 12000x.

FIG. 3. Image of the effect of the composition of 3% sodium hypochlorite with the claimed composition for modifying the irrigant of root canals of teeth in a 1: 1 ratio, containing alkyldimethylbenzalkonium chloride as QAC, on the biofilm in Fig. 1: SEM Magnification 6000x.

FIG. 4. Image of the result of the effect of the composition of 3% sodium hypochlorite with the composition for modifying the irrigant of the root canals of the teeth, containing miramistin as HR, on the biofilm in figure 1: SEM Magnification 6000x

Experimental and clinical laboratory assessment of the antimicrobial activity of surfactants - amine oxide, QAS - alkyldimethylbenzalkonium chloride and miramistin, their combinations in the composition, 3% sodium hypochlorite and a composition of 3% sodium hypochlorite with the proposed composition in a ratio of 1: 1, carried out on the basis of NIMSI MGMSU them. A.I. Evdokimova.

Example 1

A method of obtaining a composition for modifying an irrigant for root canals of teeth based on sodium hypochlorite.

Water is poured into a container equipped with a stirrer, with the stirrer turned on, the disodium salt of EDTA is loaded, the mixture is heated to 45-50 ^° C, stirred until the components are completely dissolved. Then load the amine oxide and QC. Stir for 15-20 minutes. After preparation, the composition is cooled to room temperature. Measure the surface tension of an aqueous solution of amine oxide, disodium salt of EDTA, CHAS (samples 1-3), compositions with different amounts of these ingredients in the stated ratios (samples 4-10), as well as the surface tension of their mixture with 3% sodium hypochlorite solution in the ratio 1: 1.

The measurement is carried out in accordance with GOST R 50003-92 Surface active substances. Determination of surface tension by pulling liquid films by the ring-peel method (Dew Nui method) and the Instrument manual for the Tensiometer K6.

The results of measurements of the surface tension of the ingredients of the composition (samples No. 1-3) and the composition of 3% sodium hypochlorite with various variants of the proposed composition in the stated ranges (samples No. 4-10) are shown in Table 1.

As can be seen from Table 1, the proposed composition allows to reduce the coefficient of surface tension of water from 72 to 33-38 mN / m, and when used as an irrigant modifier based on 3% sodium hypochlorite, in a 1: 1 ratio, from 75 to 34- 39 mN / m.

The best results were shown by a composition containing:

- alkyldimethylamine oxide fraction C10-C16 in an amount (wt%) from 0.6 to 0.8;

- HOUR calculated as a pure substance in an amount (wt%) from 0.05 to 0.3, namely:

alkyldimethylbenzalkonium chloride (C12-C14) in the form of a 50% aqueous solution

miramistin, which is a colorless crystalline substance, readily soluble in water.

Example 2.

A three-component microbial biofilm was formed on the extracted teeth. After 7 days of cultivation in a preparation prepared by a microtome cut, using scanning electron microscopy (SEM) revealed abundant formation of the biofilm mantle, located in the form of multi-layer layers, with ejections of accumulations of planktonic forms of coccal and bacteroid morphology (Fig. 1.)

Example 3.

An ex vivo study was devoted to assessing the activity of the irrigant - 3% sodium hypochlorite and the activity of the composition obtained by mixing the specified irrigant with the proposed composition in a 1: 1 ratio by treating the microbial biofilm obtained in example 1.

When 3% sodium hypochlorite is used as an irrigant in scanning electron microscopy, complete eradication of biofilm elements and free bacteria is observed. There were no signs of the presence of microorganisms in the orifices of the dentinal tubules, the surface of the dentin appears to have a pronounced pattern, although the orifices of the dentinal tubules are partially obturated with detritus or formed salt sediment (Fig. 2)

When using 3% sodium hypochlorite as an irrigant in combination with the proposed composition for modifying the irrigant of dental root canals, containing alkyldimethylbenzalkonium chloride as QAC in an amount of 0.2 wt%, no signs of the presence of microorganisms in the mouths of the dentinal tubules were also detected, the surface dentin appears with a clearly pronounced pattern, practically without extraneous artifacts. Noteworthy is the absence of any obturation of the mouths of the dentinal tubules (Fig 3.)

When using 3% sodium hypochlorite as an irrigant in combination with the proposed composition for modifying the irrigant of root canals of teeth, containing Miramistin as an HRC in an amount of 0.2 wt%, no signs of the presence of microorganisms in the mouths of the dentinal tubules were detected, the dentin surface appears with a pronounced pattern, practically without extraneous artifacts, obturation of the mouths of the dentinal tubules is absent (Fig. 4.).

Thus, the results of comparative experimental studies allow us to conclude that the use of 3% sodium hypochlorite as an irrigant with a composition for modifying the irrigant of root canals of teeth in a 1: 1 ratio, containing CHAS as a disinfecting agent, significantly affects the effectiveness of antiseptic tooth treatment. and root canals and promotes better cleansing of the mouths of the dentinal tubules from detritus and sediment formed as a result of the action of antiseptics in bactericidal concentrations.

The examples given above, using alkyldimethylbenzalkonium chloride or miramistin as QAC, does not limit the use of other known QAC for a person skilled in the art.

Example 4.

On the basis of NIMSI MGMSU them. A.I. Evdokimov conducted a clinical and microbological study of the effectiveness of using the proposed composition for modifying the irrigant of root canals of teeth in the traditional scheme of chemo-mechanical treatment of root canals.

Examined 28 people with a diagnosis of chronic apical periodontitis, apical granuloma (K04.5 ICD-10).

The age of patients is from 21 to 48 years, men and women - 11 and 17 people, respectively.

All patients underwent instrumental and drug treatment of root canals, which included stages in accordance with the protocol of the European Society of Endodontists.

During the study, patients were randomly divided into 3 groups depending on the solution used to rinse the root canals:

1st group:

10 patients who were treated using a composition obtained by mixing in a 1: 1 ratio of sodium hypochlorite 3% and a composition for modifying an irrigant for root canals of teeth containing miramistin in an amount of 0.2 wt%;

Group 2:

10 patients who were treated using a composition obtained by mixing in a 1: 1 ratio of sodium hypochlorite 3% and a composition for modifying an irrigant for root canals of teeth containing alkyldimethylbenzalkonium chloride in an amount of 0.2 wt%;

Group 3:

8 patients who were traditionally treated with 3% sodium hypochlorite solution (control).

Microbiological study of the pathological contents of root canals was carried out using a bacteriological research method, by quantitative inoculations on a nutrient medium M144 (Himedia, India) with the addition of 5% blood (for the cultivation of gram-negative anaerobic and gram-positive microaerophilic bacteria) and M1297A (Himedia, India) for fungi of the genus Candida.

The inoculations were placed in a thermostat at 37 ° C for 48 hours (for anaerobic cultures, in an anaerostat for 7 days), after which an automatic system for counting the number of colonies "Scan 500" (Interscience, France) was used.

Statistical processing of the results was carried out using the nonparametric Mann-Whitney test (reliable result when comparing p≤0.05 values) and X2 based on the MS DOS Biostat 9.0 computer program.

The analysis of the species composition of the microbiota showed that the strains identified in this study belonged to nine main taxonomic groups (taxa) of the oral microbiome. The number of viable microbes released from the opened root canals was significant and ranged from 4 to 7 lg CFU.

According to the results of clinical and microbiological studies, after the use of endodontic treatment schemes in patient groups 1, 2 and 3, there was a positive trend towards a decrease in the number of microorganisms detected in the root canals (Table 2).

As evidenced by the data presented in Table 2, the use in group 1 and 2 of a combination of sodium hypochlorite with a composition for modifying an irrigant of root canals of teeth containing alkyldimethylbenzalkonium chloride and miramistin as QAS, respectively, turned out to be more effective than using a 3% sodium hypochlorite solution in the control group 3.

Moreover, in groups 1 and 2, in addition to a significant decrease in quantitative contamination, out of nine taxa of microorganisms isolated during the opening of the focus, only 5 were identified after treatment, and in the third group, representatives of 7 taxa were distinguished, i.e. the number of remaining microorganisms compared with the original has significantly decreased.

Results of a comparative microbiological study of the effectiveness of endodotic treatment of root canals in patients with chronic apical periodontitis (microbial count, lg CFU)

* Differences are significant compared to the background (p≤0.5)

+ Differences are significant compared with control group 3 (p≤0.5)

The study of the effectiveness of using the proposed composition for modifying the irrigant of root canals of teeth in a clinical setting allows us to recommend it for clinical use in endodontics.

Thus, the composition for modifying the tooth root canal irrigant when mixed with the tooth root canal irrigant based on a 3% sodium hypochlorite solution in a 1: 1 ratio allows:

- to reduce the surface tension of the latter to 34-39 mN / m;

- to reduce the concentration of sodium hypochlorite solution by half after mixing with the proposed composition, as a result of which its toxicity and the risk of complications in periapical tissues are significantly reduced;

- due to the manifestation of the synergism of sodium hypochlorite and QAC, which is part of the proposed composition, maintain high bactericidal activity and expand the antimicrobial spectrum of the irrigant based on 3% sodium hypochlorite.

Claims (2)

A composition for modifying the irrigant of root canals of teeth based on sodium hypochlorite, introduced into a 3% sodium hypochlorite solution in a 1: 1 ratio and containing, wt. %: surface active compound, which is used as amine oxide 0.2-1.2 disinfecting agent, which is used as alkyldimethylbenzalkonium chloride or miramistin 0.05-0.3 disodium EDTA 0.1-0.3 distilled water rest

Images