RU2675234C1 - Hydrogel for the periodont treatment - Google Patents

Abstract

FIELD: medicine.SUBSTANCE: invention relates to medicine, namely to dentistry, and can be used for the treatment of inflammatory periodontal diseases at any stage of development. Hydrogel for the treatment of inflammatory periodontal diseases is proposed, which includes: 70 % alcohol extract of thyme, methylcellulose in the form of a microcrystalline powder, 6 % solution of acyzol, aerosil and highly purified water in the following ratio per 100 g: alcohol extract of thyme – 6.0 ml, methylcellulose – 5.0 g, acyzol – 2.0 ml, aerosil – 1.2 g, highly purified water – 85.8 ml. Drug is well kept on the mucous membrane of the oral cavity for a long time, which allows for optimal contact of medicinal substances with the mucous membrane of the gums.EFFECT: use of the gel provides a pronounced anti-inflammatory effect, prolonged remission, acceleration of the regeneration processes.1 cl, 1 tbl, 2 ex

Description

The present invention relates to medicine, namely to dentistry, and can be used to treat inflammatory periodontal diseases at any stage of development.

Inflammatory periodontal diseases lead to aesthetic and functional disorders of the dentition, tooth loss, bleeding when cleaning and eating hard foods, and due to their prevalence and the adverse effects of foci of periodontal infection on the body, they represent both the medical and social significance of this problem (N.F. Danilevsky et al., 2000, T.M. Dunyazina et al., 2001, E.E., Ridgeway, 2000, LJ Brownetal., 2002). Recently, more and more studies have appeared on the role of stress on the involution of periodontal tissues. Stress activates the processes of lipid peroxidation, the deterioration of hemomicrocirculation, inhibition of the synthesis of the organic matrix and increased bone resorption. (Dmitrieva L.A., 2004; Yasnetsov V.V., 2004; Yanushevich O.O., 2005). In this regard, it is relevant to use drugs with antioxidant, antihypoxic properties, especially in people under high stress, as well as the need to develop dosage forms that provide the maximum exposure time of a drug substance on the mucous membrane.

Known methods of treating periodontal diseases with the inclusion of antioxidants, which in combination therapy provide stable remission, normalize microcirculation in the gums and free radical oxidation of peripheral blood (T.I. Lemetskaya, 1998).

In particular, a method for the treatment of periodontitis (Patent SU 1789214), comprising the use of the drug "Olifena" in the form of a 7% aqueous solution as an antioxidant. The drug has antihypoxic, antioxidant properties, normalizes purulent-destructive processes, accelerates regeneration. The method consists in the fact that after hygienic treatment of periodontal pockets, drug therapy is carried out. For this purpose, cotton turundas, impregnated with a 7% aqueous solution of olifene, which are covered with protective paraffin dressings, are introduced into periodontal pockets, the treatment course lasts 5 days.

The disadvantage of this method is its difficulty in application, poor adhesion to the gingival mucosa, which makes it necessary to keep the bandage with the drug under paraffin, and it does not provide a stable remission.

Also known is a method of treating chronic periodontitis (Patent RU 2174230) using a solution of antioxidant Mexidol 5% in the form of rinses and dressings on the gums, together with intramuscular injection of Mexidol 2 ml daily for 12 days. Mexidol is a powerful antioxidant with a pronounced anti-inflammatory effect, it has practically no side effects and can be used in patients with allergies, however, its use in this way is ineffective in the treatment of severe generalized periodontitis. The use of this method of treatment leads only to some improvement in the state of the tissues of the oral cavity, in some cases the state of the tissues remains unchanged. The method does not provide stable remission, and the depth of periodontal pockets decreases slightly. Due to complexity and invasiveness, poor adhesion to the mucosa, this technique does not give persistent positive results.

The closest analogue of the invention is (Patent RU 2453300 C2) a method for the treatment of chronic inflammation of periodontal tissues using toothpaste based on zinc metal complex with 1-alkenylimidazole derivatives. The dental composition proposed in the method is presented in the form of a toothpaste containing acizole, sodium carboxymethyl cellulose, glycerin, sorbitol (70% solution), methyl paraben sodium salt, titanium dioxide, sodium saccharin, sodium lauryl sulfate (33% solution), anti-inflammatory and antimicrobial agents of plant origin, flavors, silicon dioxide and water. It is recommended to use paste 2-4 times a day for 2-5 minutes, the course of treatment is 14 days. The use of acizole-based paste to a greater extent than analogues improves oral hygiene, reduces gum inflammation and thereby improves periodontal conditions. Acyzole-based toothpaste has a more hygienic effect than a therapeutic one.

The disadvantage of this tool is the small exposure on the surface of the mucosa, the high frequency of procedures throughout the day, the duration of treatment and the complexity of the release of drugs. Acyzole-based toothpaste fights only superficial inflammation without affecting regeneration processes. The effectiveness of toothpaste in relation to gingivitis has been proven, but in the case of chronic generalized periodontitis, this method of treatment is ineffective.

The objectives of the invention were to ensure the speed and completeness of the release of the drug, enhance the anti-inflammatory effect, ensure long-term remission, accelerate the regeneration processes, and also increase the retention time of the drug on the gingival mucosa.

The essence of the invention is that it is proposed a visco-plastic structure for use in individual mouthguards. The composition of the product includes 70% alcohol extract of thyme - creeping thyme, methyl cellulose in the form of microcrystalline powder, 6% aqueous solution of acizole, aerosil in the form of a dry powder, highly purified water in the following ratio per 100 grams:

Thyme Alcohol Extract - Creeping Thyme - 6.0 ml

Cellulose - 5.0 g

Acizole 6% - 2.0 ml

Aerosil - 1.2 g

Highly purified water - 85.8 ml

The technical result of the claimed invention is the creation of a hydrogel with a tight viscous-plastic consistency. This allows you to keep the gel on the gum in an individual mouthguard, prevents it from being washed off by saliva, and provides the optimal exposure time of medicinal substances on the gingival mucosa. Methyl cellulose, which is taken as the basis, provides high speed and complete release of drug components. The therapeutic effect is achieved by the inclusion of acyzole 6% (bis-1 vinylimidazole zinc diacetate) and thyme phytocomposition (creeping thyme - Tymusserpyllum) in the gel. Thyme water extract is enriched with antioxidants; in the gel it serves to neutralize and eliminate the effects of free radicals and enhance the anti-inflammatory effect. Acyzole (bis-1 vinylimidazole zinc diacetate) is a powerful antioxidant; by increasing hydroxyproline in the gum, it provides stable remission, stabilizes bone resorption processes and accelerates regeneration processes with a shorter treatment time.

Gel production technology: microcrystalline methylcellulose in the amount of 5.0 grams per 100 grams of gel was chosen as the gel base. Methyl cellulose is added to highly purified water 85.8 ml. After swelling and obtaining a viscous liquid, the obtained gel base is homogenized using a laboratory stirrer, gradually adding 6% aqueous solution of acisole (2.0 ml), 70% alcoholic thyme extract (6.0 ml), then, in order to give the corresponding structural and mechanical properties, aerosil 1.2 grams per 100 grams of gel is added as a plasticizer, until a viscous-plastic mass is obtained. Store in a refrigerator at a temperature of 5 ° C for 60 days. The finished gel is placed in a dark glass jar with a ground lid, and subsequently injected into the oral cavity in a soft disposable mouthguard.

The choice of the optimal composition of excipients was carried out according to the results of determining the intensity of release of biologically active substances from gel samples. During testing, it was found that the degree of release of the active complex is higher from the composition based on methylcellulose.

A hydrogel for the treatment of inflammatory periodontal diseases was tested in 126 patients with chronic generalized periodontitis of various degrees of severity.

Patients were divided into 3 groups, each of which received a different local drug therapy. The first group received acizole 6% in the form of applications for the gums for 15 minutes daily, 10 days course. The second - used toothpaste with acizole 2 times a day for 3-4 minutes, a course of 10 days, the third group - developed hydrogel with thyme and acyzole in soft individual mouthguards for 15-20 minutes, a course of 10 days. Before treatment, all patients underwent complete rehabilitation of the oral cavity. Then, according to the classical scheme, treatment was carried out, including: professional hygiene, if necessary, closed curettage and local drug therapy.

The examples of clinical trials show the effectiveness of the hydrogel according to the main clinical indicators of periodontal health. The gel can be recommended as a therapeutic and prophylactic agent for inflammatory diseases of the gums. Provides a high anti-inflammatory effect, increases regeneration processes and provides a stable remission of the disease.

For a comparative assessment of the therapeutic efficacy of acizole in different dosage forms, we used the results of an index assessment of the hygiene index (hygiene index - GI), bleeding index (gingival groove bleeding index (SBI) - IR) and periodontal tissue health index (periodontal Russell index - PI) . The data are listed in table 1.

Note: * the level of statistical reliability was calculated when comparing with the indicators for the period "before treatment" and corresponded to p <0.05, which indicates a significant difference in the values of the indicator.

The table shows that the use of the proposed hydrogel with the content of acizole and thyme is more effective in basic indicators of hygiene, bleeding and periodontal health compared with the use of acizole in the form of toothpaste or solution for applications.

Due to the tight-viscous-plastic consistency of the gel, it was possible to keep it on the mucous membrane of the gums for 15-20 minutes. Due to the speed and completeness of the release of drugs from the proposed gel, it was possible to achieve an increase in the anti-inflammatory effect compared to the effect after the use of acizole in the form of applications on the gums or when using toothpaste with acizole. When using the proposed hydrogel, the periodontal index remained quite low for a year after the treatment, with indices from 1.25-1.85 ± 0.3, while the index values, when using toothpaste with acizole, were from 1, 31-1.95 ± 0.3, and when using acizole in the form of a solution for applications on the gum - 1.45-2.05 ± 0.3. The bleeding index when using the proposed gel was also lower than in the compared options and was not more than 1.25 ± 0.3. The hygienic index, in the treatment with the proposed gel, was not higher than 0.95-1.25 ± 0.3, which also indicates a more stable result during the year, compared with the use of acizole in the form of solution applications on the gingival mucosa or toothpastes. This dosage form allows you to maintain a stable treatment outcome and achieve stable remission according to the main indicators of periodontal health throughout the year.

Example 1. Patient A., 46 years old. Diagnosis: Chronic generalized periodontitis of moderate severity, stage of exacerbation. The patient suffers from this pathology for 12 years, periodically undergoes maintenance therapy, but notes frequent exacerbations of the process, up to 3-4 times a year. The mucous membrane of the gums is hyperemic, swollen. There are gum recessions up to 3 mm and tooth mobility of the I-II degree. Bad breath, suppuration from periodontal pockets, pain and itching in the gums are noted. The patient complains of severe bleeding gums when brushing your teeth.

Treatment: After pre-treatment of periodontal pockets with an ultrasonic scaler, a closed curettage procedure, the patient was prescribed local therapy for 7 days. For this, the resulting hydrogel was placed in a soft mouthguard in a volume of 13 grams per procedure and held for 20 minutes on the mucosa.

Already on the 3rd day of treatment, significant gum improvement was noted. Slept edema, decreased hyperemia. Desna acquired a good turgor. The patient noted a sharp decrease in bleeding. By the 5th day of therapy, the gum tightly covered the neck of the teeth and completely restored its turgor. On the 7th day of treatment, pain and itching of the gums were completely absent, there was a significant decrease in the depth of periodontal pockets. During a preventive examination of the patient after 6, and then after 12 months, persistent remission was noted.

Example 2. Patient N., 48 years old. Diagnosis: Chronic generalized periodontitis of a severe degree, stage of exacerbation. The patient suffers from this pathology for 18 years. He began to engage in treatment 5 years ago, when he noted the appearance of tooth mobility. Undergoing maintenance treatment every 6 months, but complains of frequent exacerbations up to 4-5 times a year. The mucous membrane of the gum is loose with the phenomena of congestive hyperemia, marked mobility of teeth of the II-III degree, suppuration from periodontal pockets, gum recession up to 5 mm is noted. The patient complains of pain, itching, burning in the gums, bleeding when eating hard foods and brushing teeth, bad breath.

Treatment: After a professional hygiene procedure, open curettage of periodontal pockets, tooth extraction with bone resorption over 2/3 of the root length and the maximum degree of mobility, local therapy was prescribed for 10 days. For this, the resulting hydrogel was placed in a soft mouthguard in a volume of 13 grams per procedure and held for 20 minutes on the mucosa.

First improvements were noted on day 5 of treatment. The congestive hyperemia and cyanosis subsided, the gum turgor recovered. The patient noted a sharp decrease in bleeding. By the 10th day of therapy, the gum tightly covered the neck of the teeth, suppuration went completely, there was a tendency to close periodontal pockets. During a routine examination of the patient after 3, and then after 6 months, persistent remission was noted.

As a therapeutic agent, the hydrogel can be used in a course of 7-10 procedures, 1 time in 4-6 months, after the gum curettage procedure.

As a prophylactic, this hydrogel can be used in a course of 3 procedures once every 6 months, after preliminary professional hygiene.

Claims (2)

Hydrogel for the treatment of inflammatory periodontal diseases, which consists in the fact that the composition of the product as the target component includes 70% alcohol extract of thyme, microcrystalline powder methylcellulose, 6% solution of acizole, aerosil and water highly purified in the following ratio per 100 g: Thyme Alcohol Extract 6.0 ml Cellulose 5.0 g Acizole 2.0 ml Aerosil 1.2 g Highly purified water 85.8 ml