RU2460528C2 - Method for local immune therapy of chronic odontogenic maxillitis - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely dentistry, and may be used for local immune therapy of chronic odontogenic maxillitis. That is ensured by the intraoperative introduction into a sinus of a tampon impregnated with 6.25% cyclopheron prepared of 12.5% cyclopheron dissolved in Octenisept antiseptic solution. On the second, third, forth, seventh and eighth postoperative days, 5% ointment is applied in the sinus directly.

EFFECT: invention provides preventing recurrent sinus contamination by nosocomial flora, reduces a risk of inflammation of the postoperative wound.

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Description

The invention relates to medicine, more specifically to surgical dentistry, and is intended for the treatment of chronic odontogenic maxillary sinusitis by local immunotherapy with cycloferon against the background of complex drug treatment.

Currently, for local treatment of chronic odontogenic maxillary sinusitis, antiseptic treatment is carried out [G. Piskunov. Problems of general and local conservative treatment of acute and chronic sinusitis / G.Z. Piskunov, S.Z. Piskunov, I.V. Elkov and others // Russian rhinology. - No. 1. - 1994. - S.5-15]. A known method of local treatment of chronic odontogenic maxillary sinusitis by antiseptic treatment of the maxillary sinus in combination with low-frequency ultrasound [application 5063762/14, 09/30/1992, A method for the treatment of chronic odontogenic perforated sinusitis, published: 05.27.1995].

The introduction of an antiseptic in the maxillary sinus is a traditional method and is actively used in medical practice, this method is chosen for the prototype. It has a significant drawback - it is a one-pointed action, which excludes the universality of use, and damage to factors of local immunity of the maxillary sinus is not taken into account.

Also for local treatment of maxillary sinusitis antibacterial drugs are used [Ovchinnikov Yu.M. Possibilities of using the aerosol antibiotic Bioprox in the treatment of patients with diseases of the upper respiratory tract / Yu.M. Ovchinnikov, V.M. Svistushkin // Russian rhinology. - No. 5. - 1996. - 43 p .; Ryazantsev S.V. Otof, isofra and Polydex - new drugs for the treatment of otitis media and rhinosinusitis / S.V. Ryazantsev // News of otorhinolaryngology and logopathology. - St. Petersburg - 2001 - C.115-116]. This method is not always effective, since there is an effect only on the pathogenic sinus microflora, while it does not take into account that among the main reasons for the complicated postoperative course in patients with chronic odontogenic maxillary sinusitis, most researchers call a decrease in immunological and innate protective factors of the body, and also an increase in the number of antibiotic-resistant forms of pathogens of purulent dental processes and their periodic change [T. Robustova Factors of nonspecific protection and immune reactivity of patients with inflammatory diseases of the maxillofacial region and neck / TG Robustova // Inflammatory diseases of the maxillofacial region and neck / Ed. A.G. Shargorodsky. - M., 1985 .-- Ch. 3. - S. 46-66].

A known method of local immunocorrection of rhinosinusitis with betaleikin [application 2000106080/14, 03/13/2000, a method for the treatment of chronic purulent rhinosinusitis, published: 01/20/2001]. This method is not used in the treatment of chronic odontogenic maxillary sinusitis due to the nature of the clinical course of the disease (the presence of oroantral anastomosis). The presence of anastomosis between the oral cavity and the maxillary sinus leads to continuous contamination of the sinus with microflora of the oral cavity and its derivatives, which, in turn, affects the parameters of local mucosal immunity of the sinus and oral cavity, creating adverse conditions for surgical treatment and healing of the postoperative wound [Korolinsky S.A. Changes in the factors of local immunity in odontogenic purulent-inflammatory diseases and their correction / S.A. Korolinsky, R.A. Belovolova, S.V.Novgorodsky // Med. immunology. - 2003. - T.5, No. 3-4].

Cycloferon (meglumine acridone acetate, registration No. 001049 / 01-2002, NTFF Polisan, St. Petersburg) - a domestic drug from the group of inducers for the synthesis of interferon, is among the low molecular weight peptides that induces the synthesis of IF-α. The mechanism of action of cycloferon continues to be studied, however, the direct and indirect immunotropic effects of the drug are currently well described. Cycloferon increases the formation of reactive oxygen species by phagocytes, contributing to complete phagocytosis with the elimination of captured pathogen forms.

Local use of cycloferon solution led to positive clinical results in the treatment of ENT pathology, 5% liniment of the drug is widely used in the complex treatment of acute rhinitis, generalized periodontitis, chronic periodontitis, sialadenitis, chronic red border rupture of the lips, chronic herpetic stomatitis [Aznabaeva L.F. . Cycloferon in the treatment of rhinitis and sinusitis / L.F. Aznabaeva, N.A. Arefieva, A.P. Kovalenko - St. Petersburg. - 2000. - 40 s .; Arefieva N.A. The mechanisms for the implementation of the immune response in patients with recurrent rhinosinusitis during treatment with cycloferon / N.A. Arefieva, L.F. Aznabaeva, P.N. Mashko, F.A. Kilsenbaeva // Ros. rhinology. - 1999. - No. 1. - S. 49-52].

For the first time, a technique has been proposed for the local use of cycloferon (solution and liniment) in the complex treatment of patients with chronic odontogenic maxillary sinusitis.

A comparable analysis of the claimed and known technical solutions showed that the proposed method meets the criterion of "novelty."

The basis of the invention is the task of optimizing the integrated treatment of patients with chronic odontogenic maxillary sinusitis by local immunocorrection in the postoperative period.

The problem is solved by the fact that the cycloferon immunotherapy is applied topically, introducing it into the sinus during the operation and on the second, third, fourth, seventh, eighth days after the operation.

The inventive method is as follows:

1. During the operation, a tampon soaked in a 6.25% cycloferon solution is introduced into the sinus (in the course of preliminary studies, the concentration of the active substance of cycloferon (6.25%) was determined, which had the most pronounced clinical and immunological effectiveness). The solution is prepared immediately before administration. Two ampoules of 2 ml of a 12.5% cycloferon solution are diluted with 8 ml of the Octenisept antiseptic solution (Octenidine dihydrochloride registration No. 013953/01 - 2002, Schülke and Mayr GmbH, Germany), the tampon in the maxillary sinus lasts a day.

2. On the second, third, fourth, seventh, eighth day after the operation, 5% cycloferon liniment is introduced in a volume of 2 ml with a sterile syringe with a blunt needle through the anastomosis in the lower nasal passage.

In order to justify the proposed method, a comprehensive treatment was performed for 30 people aged 23 to 54 years (18 women, 12 men) with a diagnosis of chronic odontogenic maxillary sinusitis, oro-antral fistula. The average age of patients was 34 [28; 52; 75] years. Patients were admitted to hospital treatment at 53 [28.5; 66] days from the onset of the disease. All patients underwent surgical treatment - sinusotomy with plastic closure of the oroantral communication.

The complex of medical measures included preoperative antibacterial prophylaxis; in the postoperative period, patients received therapy with non-steroidal anti-inflammatory drugs and vasoconstrictor drugs in the nasal cavity.

To assess the effectiveness of local immunocorrection with cycloferon, a short-term, prospective, comparative, “simple blind” randomized study was conducted — 30 patients were randomly selected into two groups. In the comparison group (n = 15) in the postoperative period, patients underwent traditional local treatment - a daily toilet and antiseptic treatment of the postoperative wound. In the main group (n = 15), against the background of traditional treatment, an immunomodulator cycloferon was used according to the patented scheme. All patients were comparable by sex, age.

In the course of treatment, a number of clinical signs were studied in all patients, which made it possible to assess the dynamics of the postoperative course of chronic odontogenic sinusitis and the general condition of patients — the duration (in days) of disappearance of soft tissue edema of the infraorbital region, disappearance of marginal hyperemia and wound edema, and termination of exudation from the nasal cavity.

In addition, for an objective assessment of the postoperative course and the nature of immunobiological changes in the maxillary sinus, a study was made of the local immunity of the maxillary sinus - the functional activity of neutrophils and macrophages was studied on the 5th and 11th days of treatment (lysomal according to the method of Freidlin I.C. 1986, phagocytic on the absorption model particles of latex and HCT-reducing according to the method of Mayansky A.N., Vicksman M.K., 1979), in addition, the number and change in the dynamics of neutrophilic extracellular traps (NVL) were studied [Dolushushi n I.I. Neutrophilic traps and methods for assessing the functional status of neutrophils / I.I. Dolgushin, Yu.S. Andreeva, A.Yu. Savochkina // Moscow: RAMS. - 2009. - 208 p.].

The data processed by the methods of variation statistics were expressed as the median and percentiles (M [Q1; Q2]), n is the number of observations in the sample. The significance of differences was judged using nonparametric Wilcoxon, Mann-Whitney criteria. The results of the study were processed on a PC using the software package "Statistica 6.0". Data were considered statistically significant at p≤0.05.

In patients who underwent local immunocorrection with cycloferon, at significantly earlier dates than in patients with traditional local treatment, the disappearance of soft tissue edema of the face was observed (on 3 [2; 3.25] days in patients of the main group, by 5 [4; 5, 5] days in the comparison group), hyperemia and edema of the mucous membrane in the area of the postoperative wound (on the 4th [3; 4] and on the fifth [5th, 6th] day, respectively), exudation from the nasal cavity (on the 3rd [2; 3.25 ] day during treatment with Cycloferon and at 6 [5; 7.5] days with local traditional treatment).

As a result of a study of local immunity of the nasal cavity and maxillary sinus, it was revealed that the initial indices in patients of the comparison group and the main group did not have significant differences. However, during treatment, patients in the comparison group showed a decrease in the intensity of the lysosomal apparatus of neutrophils, a decrease in the activity and intensity of phagocytosis of the studied cells, a decrease in the number of extracellular neutrophil traps.

In patients receiving local immunocorrection with Cycloferon, lysosomal intensity increased on day 5 (172 [97.5; 333.75] cu in the comparison group and 265 [223; 326.5] cu in the main group), activity (40 [36.5; 53]% in the comparison group and 52 [37.5; 81]% in the main group) and the intensity of phagocytosis of neutrophilic granulocytes (1.35 [1.29; 1.53] cu comparison group and 2.34 [2.2; 2.75] cu in the main group), the number of extracellular neutrophilic traps increased (27.5 [22.5; 37]% in the comparison group and 32 [22.5 ; 44]% in the main group).

Examples of specific implementation.

Example 1. Patient Sh. M.E., 19 years old, was hospitalized in the Department of Maxillofacial Surgery of the Chelyabinsk Regional Clinical Hospital from 02/27/2010 to 03/12/2010 with a diagnosis of "Chronic odontogenic right-sided maxillary sinusitis . Oro-antral communication through the tooth hole 1.8., A foreign body in the right maxillary sinus. "

Upon admission to the hospital, the patient complained of swelling in the right buccal region, ingestion of water and liquid food from the oral cavity into the nose. From the collected medical history of the disease and life, it turned out that the patient was admitted to the hospital 2 days after the onset of the disease (from the time of the attempt to remove the retined tooth 1.8. In the clinic at the place of residence), she was treated at the otorhinolaryngologist at the place of residence for acute purulent right-sided maxillary two years ago sinusitis. A local examination determined the asymmetry of the face due to slight swelling of the right buccal region. When examining the oral cavity proper, the 1.8 hole of the tooth was found. The nasal-oral test of Valsalva is positive, the mucous membrane in the region of the hole is not hyperemic, moderately edematous. The dentitions on the upper and lower jaws were full, sanitized.

03/01/2010, under endotracheal anesthesia, the operation was performed: "Sinus rotomy, removal of a foreign body, closing the oroantral communication" by the generally accepted method. Local treatment was carried out according to the proposed method.

The data of clinical and immunological studies have shown significant effectiveness of the patented method of treatment. The patient had a favorable postoperative course, an increase in the immunological parameters of the maxillary sinus and nasal cavity.

Example 2. Patient G-s OA, 45 years old, was hospitalized in the Department of Maxillofacial Surgery of the Chelyabinsk Regional Clinical Hospital from January 11, 2010 to January 25, 2010 with a diagnosis of Chronic odontogenic right maxillary sinusitis . Oroantral communication through the socket of the tooth 1.6. ".

Upon admission to the hospital, the patient complained of water and liquid food from the oral cavity to the nose. From the collected history of the disease and life, it turned out that the patient was admitted to the hospital a month after the onset of the disease (from the moment of tooth extraction 1.6. In the dental clinic). When examining the oral cavity proper, a tooth hole 1.6 was found. The nasal-oral test of Valsalva is positive, the mucous membrane in the region of the hole is not hyperemic. The dentitions on the upper and lower jaws are sanitized.

01/12/2010, under intubation anesthesia, the operation was performed: "Squint, closure of the oroantral communication" by the generally accepted method. Local treatment was carried out according to the proposed method.

The postoperative period in the patient proceeded smoothly, clinical indicators improved in a shorter time, the results of a study of immunological parameters of the maxillary sinus and nasal cavity before and after surgery did not show statistically significant differences.

During a dynamic examination of these patients (one month after discharge from the hospital), there were no signs of maxillary sinusitis.

It was established that local immunocorrection with cycloferon had a significantly higher clinical and immunological efficacy in comparison with traditional local methods of treatment. In the process of researching the patented method, the positive effect of cycloferon on the dynamics of the postoperative course of chronic odontogenic maxillary sinusitis and the general condition of the patients was determined. Patients at an earlier date showed the disappearance of postoperative edema of the soft tissues of the infraorbital region, faster healing of the postoperative wound, and the number of relapses of the oroanthral message decreased.

According to the results of a study of local immunity of the maxillary sinus and nasal cavity, an increase in the lysosomal, phagocytic and HCT-reducing activity of neutrophils was established, the growth of the functional reserve of these cells was determined.

Tests of the proposed method have confirmed its advantages over the prototype method: in contrast to the prototype method, local factors of local immunity are restored in the process of local treatment with cycloferon - phagocyte activity is enhanced, thereby preventing re-contamination of the sinus with nosocomial flora, and the risk of inflammation of the postoperative wound is reduced, which may lead to divergence of sutures and relapse of the disease.

Thus, the proposed method of local immunotherapy optimizes the comprehensive treatment of patients with chronic odontogenic maxillary sinusitis by local immunocorrection.

The invention can be used in medicine, in particular in surgical dentistry in the treatment of chronic odontogenic maxillary sinusitis.

Claims (1)

A method of local immunotherapy of chronic odontogenic maxillary sinusitis, comprising administering cycloferon directly to the sinus, characterized in that a tampon soaked in a 6.25% cycloferon solution obtained by diluting a 12.5% cycloferon solution with an antiseptic octenisept solution is introduced into the sinus during surgery and on the second, third, fourth, seventh, eighth days after surgery, a 5% ointment form of the drug is used.