RU2760275C1 - Dental gel with probiotic for the treatment of inflammatory diseases of periodontal tissues and oral dysbiosis - Google Patents

Abstract

FIELD: pharmacy and medicine.SUBSTANCE: invention relates to pharmacy and medicine, namely to dentistry, can be used to treat inflammatory periodontal diseases and dysbiotic phenomena in the oral cavity. The offered dental gel includes Asept gel with propolis and probiotic Bifilis. In this case, Bifilis in the form of a powder for the preparation of suspensions for oral administration is combined with boiled water at room temperature, left to swell for 2-3 minutes, until a homogeneous cloudy suspension of beige color is formed, mixed with Asept gel with propolis in the following ratios: water - 5 ml; Bifilis - 2.5 doses; Asept gel with propolis - 2 g.EFFECT: use of the gel provides a pronounced anti-inflammatory effect, elimination of bleeding gums, reduction of pain and itching of the oral mucosa.1 cl, 2 ex

Description

The invention relates to pharmacy and medicine, namely to dentistry, can be used to treat inflammatory periodontal diseases and dysbiotic phenomena in the oral cavity.

Treatment of periodontal tissue diseases is one of the most difficult and important problems of modern dentistry, the relevance of which is due to the high frequency of inflammatory periodontal diseases among the population in all age groups - up to 90% in the population. Despite the progressive development of medical science and practice, the incidence of this pathology remains at a high level not only in middle-aged and elderly population groups, but at the same time there is a tendency to its spread at a young age [Assessment of the effectiveness of complex treatment and compliance of patients with periodontal tissue diseases / Chirkova N.V., Plutakhina A.A., Petrosyan A.E., Andreeva E.A., Bobeshko M.N.// System analysis and control in biomedical systems. - T. 19, No. 4. 2020. - S. 42-55].

Studies conducted by WHO in more than 30 countries have revealed a high prevalence of periodontal tissue diseases among patients from 18 to 30 years old. Irregular prophylaxis and untimely access to a periodontist for the prevention and treatment of periodontitis tissue diseases aggravate the course of the disease, which progresses in the absence of treatment. It is known that the development of periodontitis is the result of an imbalance between the microflora of the oral cavity and the immune defense of the body [Prevention of dental diseases: a tutorial / S.I. Borodovitsin, N.A. Savelyeva, E.S. Tabolin; FGBOU VO RyazGMU, 2019. - 264 p.].

Immunological changes are associated with a violation of the interaction of factors of nonspecific resistance of the organism and suppression of the local immunity system. Therefore, use immunocorrectors and antibacterial agents (antiseptics, antibiotics), which in turn can worsen the quantitative and qualitative indicators of oral microbiocinosis [Biktimerova O.O. Improving the quality of treatment and compliance of patients with chronic generalized periodontitis based on the inclusion of a synbiotic with live cultures of lactobacilli in the treatment complex: dissertation ... candidate of medical sciences, 14.01.14 - dentistry. Izhevsk, 2016]. Recently, forms of periodontitis have appeared, caused by atypical infectious agents, viruses, fungi resistant to antibiotic therapy.

An alternative to antibiotic therapy for periodontal tissue diseases are methods of biotherapeutic action, involving the local and systemic use of probiotics, phage preparations and other agents.

This class of remedies includes the Parodontal Asepta gel for applications has a light yellow color, completely opaque, viscous consistency and is well fixed on the mucous membrane, is not washed off with saliva [found on the Internet https://vertex.spb.ru/products/series/ asepta-parodontal /, date of access 01.21.2021].

Active ingredient: propolis extract - 10%. Excipients: water, propylene glycol, carbomer, PEG-40 hydrogenated castor oil, triethanolamine, disodium edetate, sodium saccharinate, methylparaben. It has anti-inflammatory, antimicrobial action against gram-positive bacteria, as well as antipruritic and analgesic effects (reduces pain in the affected tissues), accelerates the process of regeneration and epithelialization of wound surfaces, and stimulates metabolic processes.

However, the results of clinical observations indicate an insufficient severity of the effect of Asept gel. The action after application is short-lived, the gel is more of a prophylactic than a remedy. Clinical data, including the assessment of the antimicrobial effect, show its limited severity. The problem of the complete elimination of certain types of periodontal pathogenic bacteria, which play a key role in the occurrence of inflammatory processes and the violation of microbiocinosis in the oral cavity when using Asept gel, remains unresolved. Efficiency was established against gram-positive bacteria, and its absence against gram-negative and anaerobic bacteria. When studying the analgesic effect, its minimal and short-term effect is noted.

It is known to use the Asept gel with additives to its basic composition, which makes it possible to enhance the anti-inflammatory effect [US Pat. RU 2740450. Dental gel with adaptogen for the treatment of inflammatory periodontal diseases]. In the composition of the gel, the authors proposed to additionally introduce finely dispersed pantohematogen as an active substance, and vaseline oil as an auxiliary substance, with the following ratio of components: Asept gel with propolis - 10g, finely dispersed pantogematogen - 0.05-0.1 g, vaseline oil 0.025- 0.05g. The modified composition allows to reduce the degree of local oxidative stress in the oral cavity, has an immunostimulating and antioxidant effect, and has an increased regenerative effect.

The disadvantage of such a composition is the lack of an antibacterial effect, which is necessary in the treatment of inflammatory periodontal diseases, which are usually caused by high bathial contamination.

Known drug Bifiliz, manufacturer: Firm FERMENT Russia [found on the Internet https://www.rlsnet.ru/tn_index_id_36381.htm, date of treatment 01/15/2021] is approved for medical use, contains a lyophilized microbial mass of live, antagonistically active bifidobacteria strain Bifidobacterium No. 1 and lysozyme (Liysocim). Designed for the preparation of a suspension for oral administration, used for the treatment and prevention of dysbacteriosis and intestinal infections.

The combination of two unique components, bifidobacteria and lysozyme, improves the biological properties of a living culture of bifidobacteria and the enzyme. If lysozyme destroys mainly the causative agents of purulent-inflammatory diseases, then bifidobacteria suppress the activity of opportunistic microflora. Available in 5-dose vials. It is a porous or crystalline mass of beige or whitish-gray color. One dose contains: Bifidobacterium bifidum at least 10 million CFU, lysozyme 10 mg.

For therapeutic purposes, it is recommended to take 5 doses of the medicine 2-3 times per knock. In order to prevent intestinal infections and dysbiosis, it is recommended to take the drug 2 times a day for 10 days.

There is no release form that allows the use of the drug for the treatment of periodontal diseases; there is no information on the variants of the manifestation of the drug's properties in an environment with a temperature and acid regime typical for the oral cavity in the available literature.

The objective of the invention is to create a modified gingival paste-dressing with a probiotic in a gel form with an extended spectrum of therapeutic effect, prolonged action, easy to use, allowing it to be evenly distributed on the periodontal tissues and the oral mucosa to improve the quality of complex treatment of patients with inflammatory and dysbiotic symptoms. character.

The result is achieved by introducing into the gel Asept additionally, as an active substance, the probiotic "Bifiliz"

Gel for gums with propolis Asepta - TU 9158-008-52164484-06, in our case is the basis of a new drug.

The component additionally introduced into the gel is Bifiliz.

To prepare the modified gel, divide the contents of the Bifiliz bottle, 5 doses, into two equal parts, pour one part of the drug into a container with 5 ml of boiled water at room temperature, leave to swell for 2-3 minutes, until a homogeneous cloudy suspension of beige color is formed.

A prepared suspension of Bifiliz mixed with 2 g of Asept gel is applied to the dentogingival tray for the upper and lower jaw, made of silicone material. The mixture is placed in the projection of the mucous membrane of the alveolar process of the upper jaw or the alveolar part of the lower jaw in a recess in the mouthguard. The exposure of the modified gel is carried out once a day for 30 minutes. The duration of the course of treatment is 14 days.

We examined 60 patients aged 18 - 20 years suffering from chronic generalized catarrhal gingivitis of mild and moderate severity. The surveyed showed a low level of oral hygiene, diseases of the digestive system with characteristic signs of oral dysbiosis. All patients underwent standard treatment for chronic generalized catarrhal gingivitis, according to the ICD 10: K05.1 classification.

Removal of dental plaque using an ultrasonic scaler, debridement of the oral cavity, removal of defects in fillings and removal of non-removable non-removable structures were performed. Conducted a conversation with the subjects in order to improve compliance with treatment and adherence to oral hygiene

The patients were divided into 3 groups: group 1 (20 patients), who were prescribed the application of butadion ointment once a day for 14 days; Group 2 (20 patients), who were prescribed the application of the official gel Asept with propolis daily for 14 days. In the 3rd group, 20 patients, were prescribed applications of Asept gel with propolis, modified with the probiotic Bifilis, according to our proposed preparation scheme, daily in a silicone mouthguard for 30 minutes, for 14 days.

In patients of each group, the values of the indices were assessed: papillary-marginal-alveolar (PMA), Müllemann and Fedorov-Volodkina.

Before the start of treatment in patients of the 1st group, the PMA index had a value of 30.3 ± 2.9, 2 weeks after the start of treatment, the value was 7.5 ± 1.8 (p <0.001). This indicated a decrease in the inflammation of the gingival mucosa. However, the complete elimination of inflammation in patients of this group did not occur. The bleeding index of the periodontal sulcus before treatment was 2.6 ± 0.3 points, after treatment - 0.91 ± 0.2 points. A decrease in the bleeding index by 65% was observed, but a significant number of the examined patients retained the phenomenon of bleeding of the periodontal sulcus during probing. The hygienic index of Fedorov-Volodkina before treatment was 2.6 ± 0.23 points, after treatment there was a decrease to 1.11 ± 0.19 points. Thus, there was an improvement in the hygienic state of the oral cavity in patients of the first group, but no clinically significant reduction in inflammation and bleeding of the gingival groove was observed in most patients in the group.

In group 2, the PMA index was 29.4 ± 1.8; after treatment, the value decreased to 5.8 ± 1.9 (p <0.001). This indicated a decrease in the inflammation of the gingival mucosa, but the complete elimination of inflammation after treatment in patients did not occur. The bleeding index of the periodontal sulcus before treatment in patients of group 2 was 2.5 ± 0.21 points, after treatment - 0.81 ± 0.16 points. It was noted that there was a decrease in the bleeding index by 66%, but the studied patients had manifestations of bleeding of the periodontal sulcus during probing. The hygienic index of Fedorov-Volodkina was 2.7 ± 0.09 points before treatment, after treatment there was a decrease to 1.09 ± 0.17 points. Thus, an improvement in the hygienic state of the oral cavity of the subjects was noted, but the complete elimination of the inflammatory process did not occur and the bleeding of the gingival groove remained during probing.

In group 3, the PMA index before treatment was 29.6 ± 1.2. After treatment, it decreased to 2.9 ± 1.4 (p <0.001), which indicated a more pronounced anti-inflammatory effect than in groups 1 and 2. The bleeding index of the periodontal sulcus before treatment in patients of group 3 was 2.4 ± 0.18 points, after treatment - 0.24 ± 0.06 points. The hygienic index of Fedorov-Volodkina before treatment was 2.6 ± 0.11 points, after treatment there was a decrease to 1.1 ± 0.14 points. There were no significant differences in the Fedorov-Volodkina hygienic index in the three groups. However, the data on the dynamics of the PMA and Müllemann index indicate that the proposed complex treatment of chronic generalized catarrhal gingivitis in patients who were prescribed the application of Asept gel with propolis modified with the probiotic Bifiliz daily in a silicone tray for 30 minutes led to a pronounced anti-inflammatory effect.

Also, in patients of the 3rd group, accelerated epithelization and elimination of bleeding gums were observed. Patients noted a decrease in pain and itching of the oral mucosa. The manifestations of halitosis were eliminated.

Examples of implementation of the method

Example 1. Patient V., 19 years old, diagnosed with chronic generalized catarrhal gingivitis of mild severity. Were carried out standard therapeutic measures with the additional appointment of the application of 30 minutes of Asept gel with propolis daily, for 14 days. After 2 weeks of the course of applications, a slight decrease in inflammation of the gingival mucosa was noted, edema and hyperemia decreased according to the results of assessing the value of the PMA index. There was no bleeding when brushing the teeth after treatment, but the phenomenon of bleeding of the periodontal sulcus was noted during probing at the control appointment. After 14 days of the therapeutic course, the patient complained of discomfort while eating and the presence of bad breath, indicating the presence of dysbiotic changes in the constant and unstable microflora.

Example 2. Patient N., 20 years old, diagnosed with chronic generalized catarrhal gingivitis of mild severity. After the standard therapeutic measures in the oral cavity, the application of the dental gel Asept with propolis, modified by the probiotic Bifiliz, was prescribed, daily for 30 minutes, for 14 days. At the control admission, the absence of an inflammatory reaction from the oral mucosa was noted, the PMA index decreased. The patient noted a significant decrease in bleeding of the gums when brushing teeth and discomfort in the form of dryness and itching after 8 days of the course of therapeutic and prophylactic measures and the complete elimination of these manifestations after the end of the course of therapy. The control method showed the absence of bleeding of the periodontal sulcus during probing and the elimination of halitosis of the oral cavity. Sowing scrapings of the oral mucosa for pathogenic microflora is negative.

Claims (4)

Dental gel with probiotic for the treatment of inflammatory diseases of periodontal tissues and dysbiosis of the oral cavity, including Asept gel with propolis and probiotic Bifiliz, characterized in that Bifiliz in the form of a powder for preparing suspensions for oral administration is combined with boiled water at room temperature, left to swell for 2 -3 minutes, until a homogeneous cloudy suspension of beige color is formed, mix it with Asept gel with propolis in the following ratios: water - 5 ml; Bifilis - 2.5 doses; Asept gel with propolis - 2 gr.