RU2139035C1 - Dentifrice water - Google Patents

Abstract

FIELD: stomatology. SUBSTANCE: dentifrice water contains 2.0 % of water-soluble propolis form, 0.02% of menthol, 31.0% of ethanol, and water (the rest) and has deodorant, disinfecting, and anti-inflammatory properties. EFFECT: excluded allergy and oral cavity mucous membrane irritation.

Description

 The invention relates to dentistry, and in particular to means for caring for the oral cavity.

 Dental elixirs are adjuvants (in addition to pastes and tooth powders) for oral care. They are designed to rinse your mouth after brushing your teeth and eating. Some of them have not only hygienic, but also therapeutic and prophylactic properties - they strengthen the gums, reduce their bleeding, and disinfect the oral cavity.

 As a rule, the composition of elixirs includes compositions of plant extracts with anti-inflammatory effect [1], antiseptics [2, 3], enzyme preparations that destroy plaque [5, 6].

 Known dental elixir containing an aqueous extract of the pomegranate peel, an aqueous extract of licorice root, glycerin, lemon wormwood essential oil and water (ed. St. USSR 1674844, MKI 5 A 61 K 7/16). It has anti-inflammatory, cleansing, refreshing properties. The disadvantage of this hygiene product is the instability during storage.

 Known dental elixir containing, wt.%: Ethyl alcohol 50-60, polyhydric alcohol 5-15, menthol 1-2, allantoin 0.04-0.2, procaine derivatives 0.1-0.5, citric acid 0, 1-0.3, solubilizer 1-2, citron juice 0.4-1.0, carbon dioxide extract or clove oil 0.2-1.0, carbon dioxide extract or eucalyptus oil 0.05-0.5, oak bark extract 3-5, extract of chamomile, calendula, St. John's wort or sage 3-6, extract of rose hips, mountain ash or dill seeds 4-8, extract of calamus rhizome, coriander seeds or caraway seeds 3-8, flavoring 0.05-0, 3, perfume 1-2, water - the rest (pa RF tent 2011376, MKI 5 A 61 K 7/16, 1994).

 The analysis of this elixir showed that with obvious redundancy of the components, the elixir has an insufficient cleaning effect. It contains a lot of alcohol and therefore has some tanning effect, which is poorly perceived by consumers. This is further exacerbated by the presence of a procaine antiseptic.

The invention consists in the fact that the claimed dental elixir contains, wt.%:
Water-soluble form of propolis - 2.0
Menthol - 0.02
Rectified ethyl alcohol - 31.0
Distilled Water - Else
The essential features of the proposal should be considered the qualitative and quantitative composition of the elixir, which has antiseptic, deodorizing, anti-inflammatory, wound healing properties, increases periodontal resistance to various influences.

 The claimed elixir is a homogeneous clear liquid of light brown color with a pleasant mint-bitter smell.

 The elixir has a pH close to that of the oral cavity.

Apply the elixir in the following way: 5-10 drops of the elixir are dissolved in 100 ml of boiled water with a temperature not exceeding 40 ^o C. Mix well and get an opalescent solution, which rinse the oral cavity. Swallowing the balm is safe.

 The following is a description of the components that make up the elixir.

 The water-soluble form of propolis is obtained in the following way.

The raw material for obtaining water-soluble propolis is propolis, collected in apiaries. This is a solid brown-brown mass with a greenish tint, heterogeneous structure with traces of impurities. Propolis is crushed and extracted with 96% ethanol, with a ratio of propolis-alcohol-1: 2, 3, process temperature 40 ^o C, exposure time 48 hours. Next, the target product is filtered, the filtered alcoholic extract is sent to the reactor and then served through the reactor jacket brine with a temperature of minus 4 ^o C. The process time is 6 hours with constant stirring, the cooled extract is filtered under vacuum on a suction filter. Next, the extract is heated by supplying water or steam with a temperature of 75-80 ^o C and carry out the distillation under vacuum of 0.06-0.08 MPa. Vacuum evaporation and moderate heating ensure the preservation of valuable biologically active substances of propolis in conditions of rapid concentration. Alcohol vapor passes from the reactor to a shell-and-tube water-cooled shell-and-tube heat exchanger. Condensate is collected in a container. Concentration is carried out until the smell of alcohol is removed. Propolis thus purified is mixed with tween-80 in a ratio of 1: 5. The process is carried out with continuous stirring with a rotation speed of a revolution of the mixer of 60 rpm, at a temperature of 45 ^o C for 3-5 hours

 The resulting water-soluble propolis extract is a viscous liquid from light yellow to brown in color with a bitter propolis taste and smell of poplar buds, honey, and vanillin. It is soluble in water, water-alcohol solutions and alcohol without restrictions. The mass fraction of the sum of phenolic compounds is at least 5%, the qualitative reaction to polyphenols is positive.

 Menthol.

 Colorless crystals with a strong smell of peppermint and a cooling taste. Very soluble in water, easily soluble in alcohol, ether, acetic acid, oils. Obtained from peppermint oil or synthetically. When applied to the mucous membranes, it gives a pleasant feeling of cold, has a mild, painful analgesic effect, and also has weak antiseptic properties.

 Alcohol.

 In medical practice, ethyl alcohol is used primarily as an external antiseptic and irritant. In addition, they are used in various dilutions for the manufacture of tinctures, extracts, and dosage forms for external use.

 Obtaining a dental elixir is as follows.

 At the first stage, mixtures of water-soluble propolis and menthol and, in parallel, a water-alcohol solution are prepared. The components are mixed. Then carry out the lining, filtering in vacuum on a suction filter, packaging and labeling.

 Mixing the water-soluble form of propolis and menthol is carried out in a water bath at a certain temperature. Standing is carried out in hermetically sealed containers for 24-48 hours.

To disclose the invention below are the results of an experimental clinical study of the claimed elixir
1. The study of the safety and biological activity of the dental elixir.

 In animal studies, acute and subacute toxicity with morphological control of the structure of periodontal, skin and internal organs, allergizing, irritating effects, as well as anti-inflammatory and proliferative properties, antimicrobial activity, and mucosal regeneration dynamics were studied.

 1.1. Research Methods.

 1.1.1. Acute and subacute toxicity.

 Acute toxicity experiments were performed on nonlinear white mice of both sexes weighing 20-22 g. Samples of the dental elixir were injected once through a probe into the stomach in volumes from 0.1 to 1 ml. Each dose was studied in 10 animals, the observation of which was carried out for 30 days.

 Experiments on the study of subacute toxicity were performed on non-linear white male rats with an initial weight of 120-140 g. Elixir samples were administered to animals daily for 1 month in a volume of 1 ml / 150 g.

 Throughout the experiment, visual control of body weight was conducted. At the end of the experiment, the animals were killed and examined internally histologically.

 1.1.2. Anti-inflammatory and epithelizing effect.

 Conducted by the method of A.F. Nessina. Rabbits weighing 2.5 ± 0.5 kg under ether anesthesia suffered thermal injury for 20 seconds with a red hot plug with a diameter of 3.0 • 3.0 mm in the area of the transitional fold at the upper incisors on the left and right. 24 hours after the application of the defect necessary for the development of a typical inflammation pattern resulting from the penetration of pathogenic microflora into the wound, the animals were divided into two groups - experimental and control. In the experimental group, the elixir began to be applied to the wound surface one day after mucosal damage, twice a day, after feeding the animals.

 The nature of the inflammatory reaction and the dynamics of wound healing were judged visually during a daily examination of animals. In addition to visual observation, planimetry of foci of inflammation was performed before and after treatment with the claimed elixir, as well as a Pisarev-Schiller test / staining of tissues around the wound surface with Lugol's solution / and the study of microflora from foci of inflammation during treatment.

 1.1.3. The study of irritating and allergenic effects.

 It was studied in guinea pigs according to the method of E.A. Ievleva with the study of the morphological structure of the skin, periodontal mucosa and internal organs (hematoxylin staining with eosin and Sudan-3).

 The locally irritating effect of the elixir is studied in 30 rats by application to the oral mucosa for 30 days. The irritating effect of the elixir on the conjunctiva of the rabbit eye was also studied. The elixir was administered at a dilution of 1: 10, 1: 20 and 1: 5. Distilled water was used as a control. The introduction was carried out for 3 days 10 times a day at intervals of 30 minutes between instillations.

 1.1.4. Clinical researches.

Clinical trials of the elixir were performed in 38 patients aged 25-50 years male and female, suffering from periodontal disease. Elixir was used in patients with the following types of oral pathology:
- periodontal disease - gingivitis, periodontitis;
- diseases of the oral mucosa of an inflammatory nature (ulcerative and ulcerative necrotic stomatitis).

 After removing dental deposits and brushing, the elixir was applied to the gingival margin and gingival pockets. Then the elixir was given to patients at home and was used to rinse 1-2 times a day after meals. The course of use of the elixir was 1 month.

 The state of the gums was determined using the PMA index (papillary-alveolar), which characterizes the severity of inflammation and its extent. The surface of the gums in the area of all teeth was treated with Pisarev-Schiller solution and the presence of inflammation was judged by a change in the color of the gums.

Criteria for evaluation:
0 points - absence of inflammation;
1 point - inflammation of the interdental canal (gap);
2 points - inflammation of the marginal gums;
3 points - inflammation of the alveolar gum.

При сохранении целостности зубного ряда количество зубов принимается равным 30. Степень воспаления десны оценивали также по степени кровоточивости, которую определяли по индексу ВОЗ путем зондирования карманов пуговчатым зондом. Зондирование проводили в области 6 зубов.The calculation of the PMA index was carried out according to the formula

While maintaining the integrity of the dentition, the number of teeth is taken equal to 30. The degree of inflammation of the gums was also evaluated by the degree of bleeding, which was determined by the WHO index by probing pockets with a button probe. Probing was performed in the area of 6 teeth.

Criteria for evaluation:
0 - lack of bleeding;
1 - bleeding is determined.

 To assess the degree of healing of wounds and erosion, planimetry of the foci of mucosal lesions was used. In addition, we studied the microbial landscape of lesions before and after applying the elixir.

 In the treatment of all diseases, the clinical picture of foci of lesion of the periodontal mucosa in dynamics and the assessment of their condition by patients were taken into account.

 The cleaning effect of the test elixir was studied by changing the hygiene index.

To determine the hygiene index, the vestibular and oral surfaces of the teeth were stained with Pisarev-Schiller solution (or fuchsin solution). Then carried out a quantitative assessment of the hygienic condition of the oral cavity:
0 - no plaque;
1 - plaque covering not more than 1/3 of the surface of the tooth crown;
2 - plaque covers from 1/3 to 2/3 of the surface of the tooth crown;
3 - plaque covers more than 2/3 of the surface of the tooth crown.

 1.2. Research results.

 1.2.1. Acute and subacute toxicity.

 Studies have shown that all the studied samples of the dental elixir in terms of effects on animals do not have a visible effect on the behavior and general condition of mice. The results obtained suggest that the toxicity of the elixir is low, because LD 50 = 1 ml / mouse or 50 ml / kg.

 When studying subacute toxicity, it was also found that the elixir is a non-toxic drug.

 Throughout the experiment, the behavior and general condition of the experimental animals did not differ from the control. The dynamics of body weight is positive. According to the increase in body weight, experimental rats did not differ from the control.

 On visual inspection: the appearance of the animals - the coat is smooth, shiny, no hair loss.

 Functional changes were not identified. Breathing is free, not difficult. No changes in heart rate during visual observation were noted. Increased salivation is not detected. Urination and excretion are not impaired.

 1.2.2. Anti-inflammatory and epithelizing effect.

 The presence of a pronounced anti-inflammatory and epithelizing effect was noted.

 In the experimental group, when using the elixir, already on the 2nd day, hyperemia of the inflammatory roller around the mucosal defect is less pronounced, cleaning of the wound bottom from necrotic plaque begins. On the 3rd day in the experimental group, the wound surface decreased by 0.2-0.4 mm.

 In the control group, an increase in puffiness was observed up to 6 days, and only by 11 days a decrease in puffiness and hyperemia of adjacent tissues was noted.

In general, the healing time was:
in the experimental group in which the claimed elixir was used - 6.9 ± 0.5 days, and in the control group (without using the elixir) - 22.1 ± 0.4 days.

 A simultaneous study of microbiological contamination of the wound showed that in the control group on the 4th day of the experiment the highest levels of staphylococcus, streptococcus, E. coli, protea, yeast-like fungi were revealed in the wound, and the number of lactobacilli was reduced, which indicates the development of dysbacteriosis processes in the wound. In the experimental group, this phenomenon was not observed, where already on the 7th day normalization of the microflora state was noted.

 Thus, the use of a dental elixir contributes to the normalization of autoflora of the oral cavity of rabbits in the focus of inflammation at an earlier date in the experimental group compared to the control group. Normalization of autoflora in the focus of inflammation at an earlier date significantly reduces the overall healing time of the inflamed mucosa.

 1.2.3. Irritant and allergenic effect.

 The study of locally irritating and allergenic effects using various methods showed the absence of such when using the claimed elixir. The intensity of the color of the mucous membrane of the experimental and control eyes of rabbits was the same, which indicates the absence of a locally irritating effect in the elixir.

 With the oral administration of the elixir, the presence of an irritating effect on the oral mucosa was not noted. Increased salivation or any other signs of irritation of the oral mucosa during visual observation was not observed. In pathomorphological studies of microscopic sections, no traces of an irritant effect were detected, the mucous membrane of the usual color, shiny. During histological examination, the multilayer, flat, non-keratinizing epithelium, the thin layer of the mucosal plate itself, consisting of fibro-elastic tissue and the submucosa, adjacent to muscle tissue, are clearly distinguished. Edema, hemorrhage, dystrophic changes or inflammatory infiltration were not detected.

 1.2.4. Blood test.

 A clinical blood test performed one month after the start of the drug did not reveal any pathological changes. In the content of hemoglobin, erythrocytes, leukocytes, platelets, and the composition of the leukocyte formula, the experimental animals did not differ from the control. All studied indicators were within normal limits.

 2. Clinical studies.

 The results of a clinical study of the dental elixir showed its pronounced therapeutic and prophylactic effect.

 The anti-inflammatory effect on periodontal tissues in the treatment of gingivitis and periodontitis of mild to moderate severity was expressed in the onset of a feeling of comfort in the gums, the disappearance of itching, hyperemia, edema, and bleeding of the gums.

 Objective studies have also shown a positive effect of the elixir on periodontal tissues - the PMA index is significantly reduced by 54.89%, and the bleeding index - by 72.38%. The planimetry of the lesions of the mucous membrane of the oral cavity showed their rapid epithelization - already by 2-3 days, they decreased by 2 times, and by 6-7 days almost their complete healing was observed.

 The microbial landscape from the lesions of the mucous membrane and the hole of the extracted teeth was normalized both in the number of microorganisms and in the qualitative structure - a decrease in pathogenic microorganisms was observed already 3-5 days after the use of the elixir.

 An experimental - clinical study of the claimed dental elixir showed that the elixir is non-toxic, does not have irritating and allergenic effects, is a good therapeutic and prophylactic agent for caring for the oral mucosa and teeth.

 It has a pronounced anti-inflammatory, wound healing and deodorizing effect, has a positive effect on the periodontal mucosa with gingivitis and periodontitis, while rinsing the mouth well cleans the surface of the teeth and the mucous membrane of the oral cavity. Clinical trials have shown a significant decrease in hygiene index, PMA index and gum bleeding.

Example. After analyzing the feedstock for compliance with quality indicators, weigh the components on a VLR-200 balance. Weigh 2 kg of water-soluble propolis and 0.02 kg of menthol. A container with a propolis sample is placed in a water bath at a temperature of 50 ^o C and heated for 10-15 minutes. Then slowly for 5-10 minutes a portion of menthol is transferred into it, thoroughly mixing with a glass rod. The mixture is cooled.

 The preparation of a water-alcohol solution in a special measuring device is carried out by mixing 31 kg of high-purity alcohol and 66.98 kg of distilled water. When preparing a water-alcohol solution, use "Tables for determining the alcohol content in water-alcohol solutions", take into account the amount of compression in liters that occurs when mixing. The solution is thoroughly mixed for 3-5 minutes. Then carry out the mixing of the components. In a container with a mixture of a water-soluble form of propolis and menthol, a water-alcohol solution is added portionwise with thorough mixing. After loading all the components, the elixir is mixed thoroughly with a mixer for 30-40 minutes. The aging is carried out in a hermetically sealed container for 24 hours. Next, the elixir under vacuum is fed to the suction filter. After filtration, the elixir is poured into vials of 10.25 and 15 ml and packaged.

 The resulting elixir is a homogeneous clear liquid of light brown color with a pleasant odor.

 Clinical and experimental studies of the obtained elixir revealed the presence of a disinfectant, deodorizing, anti-inflammatory effect. In this case, the elixir is non-toxic, does not cause an allergenic or irritating effect.

 Thus, the claimed dental elixir has pronounced therapeutic and prophylactic properties, does not have allergic or irritating properties. All this allows us to recommend it for widespread use in dental practice and oral hygiene.

Claims (1)

A dental elixir containing ethyl alcohol, menthol and water, characterized in that it additionally contains a soluble form of propolis in the following ratio of components, wt.%:
Water-soluble form of propolis - 2.0
Menthol - 0.02
Ethyl alcohol - 31.0
Water - Else