RU2301062C2 - Method for treating patients for periodontium diseases - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: method involves administering Acizol (bis1-vinyl imidazole zinc diacetate).

EFFECT: stable remission; improved bone tissue resorption in postoperative period; accelerated periodontium tissue recovery.

3 dwg, 3 tbl

Description

The invention relates to medicine, in particular to the treatment of periodontal diseases.

According to the WHO, the prevalence of periodontal diseases in people over 40 years old exceeds 98%, and in patients with diabetes mellitus periodontal diseases are noted in 100% of cases, and the diseases proceed aggressively and practically cannot be treated. Periodontitis, gingivitis and stomatitis predominate in the structure of periodontal diseases (NNLoginova, A.I. Volozhin. Pathophysiology of periodontal disease. M., 1995).

The classic treatment for periodontal disease is as follows: oral hygiene, dental plaque removal, curettage of periodontal pockets, local anti-inflammatory therapy, antiseptics, antibiotics, gum massage, oral sanitation, antioxidants (sodium hydroxybutyrate, oliphene, mexidol, etc.) [Kuryakina N.V., Kutepova T.F. Periodontal disease. M., Medical Book, 2003, p.96-97].

However, practice shows the low efficiency of the existing method of treatment of this pathology.

The objective of the present invention is the creation of a new tool for the treatment of periodontal disease, including in persons suffering from type II diabetes.

The problem is solved by the use of Zinc diacetate, formerly known as carbon monoxide antidote (Patent No. 2038079), an agent for treating psoriasis and other inflammatory skin diseases (Patent No. 2204392, Patent No. 2275758) for the treatment of periodontal diseases with the drug Acyzole - bis (1-vinylimidazole). .

The given examples of experimental and clinical studies show quite high efficacy of Atsizol; clinical examples also show the use of Atsizol in patients with periodontal diseases suffering from type II diabetes mellitus.

Example 1. An experimental study of the effectiveness of Acizole in models of periodontal disease

1.1. Creating a rat paradontosis model using a peroxidized diet

A.I. Evdokimov (Evdokimov A.I., Parodontosis, M., 1967, pp. 4-10) showed that in rats with a diet containing atherogenic factors, it is possible to cause periodontal disease, which in morphological manifestations resembles periodontal disease in humans .

Studies were performed on rats of males of the Wistar strain weighing 160-180 g. Animals received a standard diet such as a feed mixture. To intensify lipid peroxidation (LPO), peroxidized sunflower oil (10% of the ration weight, approximately 2 ml per rat) was added to the feed mixture of experimental animals. Animals of the control group received the same amount of ordinary refined sunflower oil.

Animals were observed for 45 days. After this, animals with a peroxidized diet were divided into 2 groups: 1 - control; 1 - treatment with Acyzolum.

The treatment was carried out by irrigation of the mucous membranes of the gums with a solution of the studied drug using a pipette at a dose of 50 mg / kg daily for 14 days. In this case, both local and resorptive effects of the drug were taken into account. Then under ether anesthesia they were killed with total bloodletting. 2 days earlier, rats received pilocarpine-stimulated saliva in which protein content was determined [Lowry O.N., Rosebrough T.L., Farr A.L., Ran-dell R.J. biol. Chem., 1951, vol. 193, pp. 265-275], alkaline phosphatase (ALP) [Handbook. Laboratory research methods in the clinic. Ed. V.V. Menshikova. M., Medicine, 1987, 58-60 pp.], Malondialdehyde (MDA) and catalase [Vladimirov Yu.A., Archakov A.I. Lipid peroxidation in biological membranes. M., 1972, 220 pp., Research methods in occupational pathology. Ed. O.G. Arkhipova. M., 1988, p. 156-170]. After slaughtering animals, tissues were taken for histological examination, and the degree of atrophy of the alveolar ridge of the jaw of rats was also determined [Danilevsky N.F. Pathogenesis, clinic and treatment of periodontal disease. Abstract. diss. Doct. honey. sciences. Kiev, 1968, 50 pp.]. Protein content was evaluated in gum tissue [Handbook. Laboratory research methods in the clinic. Ed. V.V. Menshikova. M., Medicine, 1987, 58-60 pp.] And hydroxyproline [Rybakov A.I. Periodontal disease. M., 1967, p.10-12].

1.2. Creating a model of stomatitis and periodontitis in rats by applying a chemical burn with acid

The mucous membrane of the oral cavity and gums is injured by applying two to three drops of concentrated sulfuric acid. During the day, erosion or ulcer with perifocal inflammation is formed.

Treatment with the compared drugs was carried out for 14 days (the procedure is the same as in the previous section). At the same time, the dynamics of regeneration and the histological picture were noted. In addition, indicators of the severity of inflammatory processes in the peripheral blood were determined by conventional methods: the number of leukocytes, the content of lymphocytes and neutrophils, ESR, CRP and fibrinogen.

1.3. The effectiveness of Acizole in periodontal disease

Paradontosis

The results of the study are presented in tables 1 and 2.

When comparing the studied parameters, a significant increase in atrophy of the alveolar ridge was found, which clearly correlated with the severity of periodontal tissue damage in rats treated with peroxidized sunflower oil.

Direct evidence of the presence of a pronounced pathological process in periodontal tissues in the 2nd control group of animals was obtained on the basis of histological studies.

In all the studied animals of this group, the presence of a gingival pocket, tissue bone resorption with its granulation replacement were observed. Cellular infiltration was determined both under the preserved zones of the epithelial lining of the pocket, and in the deep layers of the periodontium (Fig. 1).

Inflammatory infiltrate was represented by lymphocytes, histiocytes, and plasma cells. In favor of the development of a severe stage of periodontal disease in animals treated with peroxidized sunflower oil, the severity of resorption of interdental septa testified. It reached 2/3 of its size, which was accompanied by the formation of deep periodontal pockets (PC).

An important indicator of the development of periodontal disease is a decrease in the level of oxyproline, a specific amino acid of the collagen fibrillar protein, which forms the basis of the intercellular substance of the connective tissue. A peroxidized diet significantly reduced the level of oxyproline, and the use of the drug increased the content of oxyproline in the gum to normal.

The appointment of Acizole normalized processes in the periodontium. This was confirmed by morphological and histological studies (figure 2).

Keeping animals on a diet with peroxidized sunflower oil caused a significant increase in the rate of lipid peroxidation in saliva: the content of MDA increased, the level of anti-radical protection - catalase decreased. The level of alkaline phosphatase increased, which can be considered as a result of cytolysis. The administration of Acyzol reduced the level of lipid peroxidation and cytolysis, which favorably affected the regeneration of periodontal tissues.

Stomatitis and periodontitis

A day after a chemical burn with acid in rats, the development of erosion with perifocal inflammation of the mucous membranes of the oral cavity was observed. Histologically, there was a focal defect in the mucosal epithelium with edema and infiltration by polymorphonuclear leukocytes of loose connective tissue at the site of the defect (Fig. 3).

Later, at the site of erosion, a ulcerative lesion could form. Without treatment, the pathological process proceeded for 10-15 days and ended in recovery. The use of Acyzol significantly accelerated the regeneration processes: recovery occurred within 5-7 days. The results of the dynamics of inflammation are presented in table 3. They indicate the relief of the inflammatory process in periodontal tissues under the influence of Acyzole.

Thus, the drug Atsizol accelerates the regeneration processes until the full recovery.

2. The results of clinical trials of complex treatment of periodontitis using Atsizol

We examined 14 patients with periodontal diseases of varying severity, including with concomitant disease - type II diabetes mellitus. The following methods were used to examine patients:

- clinical [determination of the periodontal index of PI (according to Russel), PMA (papillary-marginal-alveolar index of gum disease), Schiller-Pisarev test];

- functional (polarographic method for determining the partial pressure of oxygen, rheoparodontography, Doppler fluometry);

- radiological (orthopantomography, panoramic radiograph);

- laboratory (monitoring the level of sugar in the blood over time).

After the initial examination, two groups of patients were identified.

In the control group (4 women, 3 men aged 40-65 years), periodontal diseases were treated according to the classical scheme [Kuryakina N.V., Kutepova T.F., Periodontal disease, M., Medical book, 2003, p .96-97]:

1. Training in proper oral hygiene (using the dentition model and personal hygiene products) and monitoring.

2. Removal of dental plaque: mechanically and using the Pyezon-Master ultrasonic device.

3. Grinding teeth, eliminating traumatic occlusion.

4. Temporary (or permanent splinting of teeth).

5. Curettage of periodontal pockets (PC) with a depth of more than 3-5 mm (generalized periodontitis of moderate and severe degree).

6. Local anti-inflammatory therapy (rinsing the mouth with infusions of medicinal herbs), antiseptic treatment of PC with 3% hydrogen peroxide solution and 0.05% chlorhexidine solution, antibiotic therapy (applications with Dimexide / Trichopolum mixture for the gums), sclerotherapy (solution of vagotil in the form of an application in PC), the purpose of oral baths of 0.01% solution of miramitin, massage of the gums with Metragil-Denta gel.

7. Oral sanitation (treatment of caries and its complications, restoration of the anatomical shape of teeth - filling, elimination of overhanging edges of fillings, traumatic crowns, prostheses).

8. Rational prosthetics (if necessary), taking into account the concomitant pathology - diabetes mellitus.

In the control group, all patients experienced long-term healing of the gum tissue, moderate gum inflammation (according to the PMA gingivitis index - 40-60%) decreased by 14-21 days (up to 30-40%) after PC curettage, tooth mobility remained, had place PC reduction by 0.5-1.0 mm. The lack of stable remission in the dynamics. Two patients showed a tendency to restore the growth of pathological granulation tissue.

In the main group (3 women, 4 men aged 40-65 years), in addition to the classical treatment regimen, Acyzole was administered orally at a dose of 100 mg / day for 25 days.

In the main group, the best results were observed in the postoperative period: reduction of inflammation by 7-10 days, decrease in PC depth by an average of 3-5 mm, decrease in tooth mobility, which indicates the formation of connective tissue attachment - one of the main goals of surgical treatment of secondary and severe degrees of chronic periodontitis. In patients with concomitant diabetes mellitus, a decrease in the concentration of glucose in the blood was noted.

Example 1. Patient A., 64 years old. Diagnosis: chronic generalized periodontitis. Concomitant diseases: chronic pancreatitis, glaucoma; a history of cholecystectomy (1995). The stagnant-hyperemic mucous membrane of the gums of the upper and lower jaws was objectively noted, bleeds easily when probed, PMA 60-70%, PC depth 5-6 mm, tooth mobility II-III degree, plentiful dental deposits, high located vestibule of the lower jaw. On the radiograph - a decrease in bone tissue by 1/2 the length of the roots of the teeth.

The patient received acizole 100 mg per day for 25 days.

During treatment, on the 5th day after the patch operation, the gingival mucosa is pale pink, tightly encompasses the neck of the teeth. After 4 weeks, no complaints of gum bleeding were noted (PMA 10%).

6 months after prosthetics at a preventive appointment, there was no inflammation of the gums, PC within 2 mm, the mobility of individual teeth of 1 degree. On the R-gram - restoration of the bone structure of vertical bone defects to 2/3 of the root length.

Example 2. Patient G., 52 years old. Diagnosis: chronic generalized periodontitis. Concomitant disease is chronic bronchitis.

During the examination it was noted: hyperemic mucous membrane, PMA 40-50%, PC depth in the region of the anterior teeth 5 mm, in the area of masticatory teeth 2.5-3 m, tooth mobility II degree, supra- and subgingival dental deposits. On the radiograph - a decrease in bone tissue in the anterior teeth by 1/3 of the length of the roots.

During treatment with Acizol 100 mg per day on the third day after curettage, there are no complaints of pain. After 7 days, the mucous membrane of the gingival margin is pale pink, PMA - 10%. After 3 months of follow-up, a routine examination noted the absence of complaints, there is no inflammation, the depth of the PC in the area of splinted teeth does not exceed 2 mm.

Example 3. Patient C., 48 years old. The diagnosis of severe generalized periodontitis (CGP) is severe. Concomitant diseases: hypertension of the II degree, diabetes mellitus (since 1999). Before treatment, the depth of the PC is 7-8 mm.

The concentration of glucose in the blood is 11.2 mmol / L.

After a course of treatment with Atsizol 100 mg each, inflammation of the gum tissue decreased already on the 7th day after curettage of the PC and corresponded to a mild degree (20%). The depth of the PC for 21 days was 3-5 mm, tooth mobility decreased, which indicates the formation of a connective attachment. In the orthopedic department, splint clasp prostheses were made. The course of treatment with Acizol is 25 days. The concentration of glucose in the blood is 8, 57 mmol / l.

Example 4. Patient B., 44 years old. Diagnosis: periodontal abscess in the tooth region 41, mild CGP. Concomitant disease: diabetes mellitus (since 1999), insulin injections during the year.

Prior to treatment, the blood glucose is 9.0 mmol / L.

From the first day of treatment, the patient was prescribed Acyzole 100 mg per day (treatment course - 25 days).

An autopsy of the periodontal abscess, removal of dental deposits, splinting of the front teeth of the lower jaw was performed. Tissue inflammation decreased on day 5 (10% - mild), on day 14 there was no inflammation. The depth of the PC on day 14 is 3 mm in the region of 41 teeth.

After the treatment cycle, the concentration of glucose in the blood is 7.1 mmol / L.

Example 5. Patient B., 64 years. Diagnosis: CGP of moderate severity. Concomitant disease - diabetes mellitus (since 1996).

At the initial inspection, the PC depth was 7 mm.

Prior to treatment, the blood glucose is 7.4 mmol / L.

The patient received Acizole 100 mg per day for 25 days.

Conducted curettage PC, sclerotherapy. Gum disease decreased on the 7th day (20% for the PMA index). On the 28th day after the completion of Acizol administration, inflammation was not noted. On the 21st day, the depth of the PC is 3-3.5 mm. Decreased tooth mobility. Splint plate prostheses are made in the orthopedic department.

After the treatment cycle, the concentration of glucose in the blood is 5.9 mmol / L.

After completion of the course of treatment, patients were observed for 6 months. It was noted that in the main group sustained remission and stabilization of bone resorption processes in the postoperative period was maintained, which until now has been a difficult task in patients with a similar concomitant pathology - diabetes mellitus. In the control group, such results could not be achieved.

Thus, the results of experimental and clinical studies show the high effectiveness of Acyzole as a tool for the treatment of periodontal diseases. In patients with diabetes mellitus, a decrease in blood glucose levels by an average of 20-25% was also noted.

Explanation of the drawings given in the description of the invention

In FIG. Figure 1 shows a picture of periodontal disease in a rat. The mucous membrane of the rat’s gum is changed compared to the norm: there is swelling of the epithelium, indistinguishability of the cell borders, fuzzy basement membrane, hyperchromatosis of the nuclei of the epithelium; plethora, edema, and infiltration of loose connective tissue by polymorphonuclear leukocytes. Hematoxylin-eosin. Magnification 40 × 7.

In FIG. Figure 2 shows changes in the mucous membrane of rat gums after treatment with Acyzole. Normal structure The rat gingival mucosa has a normal structure. The nuclei of the epithelium and the basement membrane are clear. Hematoxylin-eosin. Magnification 40 × 7.

In FIG. 3 shows a fragment of the mucous membrane of the rat oral cavity at the site of a chemical burn. There is an epithelial defect, infiltration of loose connective tissue by polymorphonuclear leukocytes. Hematoxylin-eosin. Magnification 40 × 7.

Table 1 The degree of atrophy of the alveolar bone, the protein content and hydroxyproline in the gums of rats, M ± m Group of animals The degree of atrophy of the alveolar bone The protein content in the gums, g / kg The level of oxyproline, g / kg Control 1 (refined sunflower oil) 30.5 ± 0.5 65.5 ± 2.5 4.4 ± 0.3 Control 2 (reoxidized sunflower oil) 47.3 ± 1.0 * 72.3 ± 0.8 * 3.2 ± 0.5 * Acizole 38.2 ± 0.8 69.1 ± 1.3 4.1 ± 0.4 * - significant differences from control 1 at P <0.05 table 2 Enzyme activity and rate of lipid peroxidation in rat saliva, M ± m Group of animals Alkaline phosphatase, mkkat / l MDA, nmol / mg protein Catalase, mg / ml / min The protein content, g / l one 2 3 four 5 Control 1 (refined sunflower oil) 0.54 ± 0.06 0.95 ± 0.03 160 ± 10 6.5 ± 0.5 Control 2 (reoxidized sunflower oil) 1.26 ± 0.07 * 2.35 ± 0.15 * 60 ± 15 * 7.3 ± 0.2 Acizole 0.60 ± 0.05 1.12 ± 0.18 130 ± 20 7.0 ± 0.3 * - significant differences from control 1 at P <0.05

Table 3 Indicators of the inflammatory process in the blood of rats with chemically determined periodontitis, M ± m Indicators Intact animals Control 2 (chemical periodontitis) Acizole White blood cells, 10 ⁹ / L 12.5 ± 0.5 16.3 ± 0.2 * 11.8 ± 0.6 Lymphocytes,% 72 ± 8 86 ± 11 74 ± 5 Neutrophils,% 12 ± 2 14 ± 3 12 ± 2 ESR, mm / hour 4.6 ± 0.3 10.3 ± 0.8 * 5.3 ± 0.4 CRP, mm precipitation 0 4.4 ± 0.6 * 0.8 ± 0.1 Fibrinogen, g / l. 2.5 ± 0.5 10.2 ± 0.3 * 3.1 ± 0.3 * - significant differences from intact animals at P <0.05

Claims (1)

The use of acizole as a treatment for periodontal disease.

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