RU2707098C1 - Dental lollipops for treatment of mucous membrane damages of oral cavity - Google Patents

Abstract

FIELD: pharmaceutics.

SUBSTANCE: present invention refers to pharmaceutical industry, namely to an agent for treating mucous membrane lesions of the oral cavity. An agent for treating oral mucosal lesions is presented in the form of candies containing essential oil of peppermint, sorbitol, purified water, additionally contains a liquid monk extract produced by percolation taken in certain amounts.

EFFECT: disclosed agent is effective for treating mucous membrane lesions of the oral cavity.

1 cl, 3 tbl, 4 ex

Description

The invention relates to medicine, namely to pharmacy, and can be used to treat lesions of the oral mucosa, including aphthous stomatitis, ulcerative necrotic gingivostomatitis, fungal lesions of the mucous membrane (acute and chronic) and other pathological lesions of the oral mucosa .

Damage to the mucous membrane of the oral cavity is an urgent problem of dentistry, since it begins in childhood, in the future the disease acquires a chronic course. Severe forms of damage dramatically reduce the patient’s quality of life and form a state of physical and psychological discomfort, and in some cases cause psychosomatic disorders. [Chernysheva ND, Ron G.I. Determination of local immunological status in patients with chronic recurrent aphthous stomatitis // Problems of Dentistry. - 2009. - No. 1.]. All this suggests the need for the development of new drugs and forms for the treatment of lesions of the oral mucosa.

Currently, various drugs that exhibit antibacterial properties are widely used to treat lesions of the oral mucosa, for example, from the group of antibiotics, such as gramicidin, doxacycline, azithromycin, bactericidal and antiseptic drugs - metrogil, chlorhexidine, miramistin, which are available in in the form of tablets, solutions, powders, and also means for direct application to the affected area of the mucous membrane - these are ointments, gels, pastes, etc. [Breus, V.E. Trends in modern dentistry // Act. questions dentistry. - 2001. - No. 5. - S. 13-14]. However, many of these drugs have side effects and restrictions on their use, so the urgent task is to develop new, effective and safe medicines based on medicinal plant materials. In this regard, it is interesting to create a rational sustained-release dosage form in the form of lozenges containing plant components that practically do not cause unwanted side effects, allergic reactions and provide ease of use, dosing accuracy, and maintaining the necessary concentration of biologically active substances in the oral cavity [Gorbatova E. A., Lometskaya T.N., Manuylov B.M. Domestic preparations from plant materials in the complex treatment of periodontal diseases // Institute of Dentistry. 2000 .-- 1 (6). - S. 32-33].

Lollipops are a solid dosage form for resorption containing invert sugar or sorbitol, which is obtained by pouring. The lollipop may contain one or more active substances and is intended for local exposure to the mucous membrane of the oral cavity and gums. The introduction of plant-based components with anti-inflammatory, antibacterial and antioxidant activity into the lollipops composition is promising, since it is oxidative stress that underlies the inflammation process [Dmitrieva L.A., Prosvirova E.P. Clinical and laboratory assessment of the effectiveness of Mexidol in the complex treatment of chronic generalized periodontitis. // Periodontology. - 2004. - No. 4. - S. 12-15.].

A known tool for the treatment and prevention of inflammatory diseases of the oral cavity, which is an aqueous extract of the herb St. John's wort perforated, rhizomes of the hemorrhagic medicinal, fruits of juniper and leaves of coltsfoot taken in equal proportions. The tool has anti-inflammatory, antibacterial and saliva-thinning action while maintaining the natural microflora of the oral cavity [RF Patent No. 2295967, A61K 36/739, 11/14/2005]. The disadvantage of this drug is that an aqueous extract is recommended, but aqueous extracts have a limited shelf life.

Dentos candies are known for the treatment and prevention of infectious and inflammatory diseases of the oral cavity, which include the herbal medicine Dentos, which is an alcohol-water extract based on 70% ethanol from several types of raw materials: eucalyptus leaves (Eucaliptus viminalis), echinacea herb purplish (Echinaceae purpurea), calendula flowers (Calendula officinalis), oak bark (Quercus robur), clove oil (Caryophyllos aromaticus [patent RU 2428171, 2011].

The closest analogue of the invention is a biologically active food supplement in the form of absorbable candies, which contains sorbitol, citric acid, essential oil of eucalyptus or peppermint, water, and also as a biologically active substance Lamifaren powder in the following ratio of starting components, wt. %: Lamifaren powdery - 2.3, sorbitol - 81, citric acid - 0.6, essential oil of eucalyptus or peppermint - 0.1 and purified water - 16 [patent RU 2642639, 2018]. The disadvantage of these candies is their low therapeutic activity.

The objective of the invention is to expand the arsenal of funds for the treatment of lesions of the oral mucosa.

The technical result is an increase in the therapeutic activity of candies, the production of a new drug of domestic production in the form of candies for the treatment of lesions of the oral mucosa, which has a prolonged antimicrobial, anti-inflammatory, antiseptic, wound healing and antioxidant effects, convenient and hygienic to use.

The specified technical result is achieved in that the agent for treating lesions of the oral mucosa, made in the form of lozenges containing peppermint essential oil as a biologically active substance, sorbitol in the amount of 80 masses as a caramel mass. % and purified water to 10.0, in contrast to the prototype, as a biologically active substance additionally contains monarda liquid extract obtained by percolation at a ratio of raw materials: extractant 1: 1, and sea buckthorn oil in the following ratio of initial components, mass. %:

percolation monarda liquid extract with the ratio of raw materials: extractant 1: 1 9.6 sea buckthorn oil 0.3 peppermint essential oil 0.1 sorbitol 80.0 purified water 10.0

Characteristics of the components that make up the lollipops:

- Monarda liquid extract is obtained by the method of percolation, from monarda herb, which has anti-inflammatory, antibacterial, antiseptic and antioxidant effects. Production method: 20.0 g of monarda grass is poured with an equal volume of 40% ethyl alcohol and left for 24 hours to wet the raw material, then the raw material is loaded into the percolator, filled with 40% ethyl alcohol to a “mirror” and left for extraction for 48 hours. What follows is percolation, i.e. direct absorption by the extractant of biologically active substances of the monarda raw material. Percolation is carried out at a rate of 1/48 part of the working volume (the volume occupied by the raw material) per hour until the raw material is completely depleted, until the effluent becomes colorless. The resulting liquid extract is a dark brown liquid with a specific odor. The finished extract is placed in tightly corked dark glass bottles.

- Sea-buckthorn oil (FS 42-1730-95) - a fatty oil obtained from dried beet pulp of the fruits of wild-growing or cultivated buckthorn buckthorn bush, by extraction with sunflower oil at a ratio of raw material and extractant 1: 2. It is an oily liquid of orange-red color with a characteristic odor; a slight precipitate is allowed, which dissolves when heated to 40 C. It is practically insoluble in water, easily soluble in chloroform.

- Peppermint oil (FS 2.4.0001.18, State Pharmacopoeia XIV, v. 4, p. 5826) - an essential oil obtained by distillation with water vapor from leaves and other aboveground parts of peppermint, purified by secondary distillation with water vapor: main components: 1 -mentol, 2-menthol and menthol esters with acetic, valerianic and other acids. Easily mobile, transparent liquid, colorless or painted in a slightly yellowish color with a characteristic mint smell and a burning cooling taste, without bitterness, easily soluble in 95% alcohol; 1 ml of oil should dissolve in 4 ml of 70% alcohol to form a clear solution.

Sorbitol (TU 64-5-17-86) is a transparent crystal, white or slightly yellowish, odorless, has a sweet cooling tongue taste with a touch of iron (soluble in water, hot and cold alcohol, almost insoluble in fatty solvents .

- Purified water (GF XIV, FS 2.2.0020.18, GF XIV t. 3, p. 3602). The composition of dental lozenges should provide convenience and hygiene in use, prolonged action with high therapeutic activity, dosing accuracy, constant concentration of the drug over a long time, good adhesive ability to the mucous membrane of the cavity. Monarda liquid extract provides antimicrobial, anti-inflammatory, antiseptic, antioxidant properties, sea buckthorn oil has a pronounced wound healing and anti-inflammatory activity, which is important to ensure the effectiveness of the dosage form. Peppermint oil is introduced into the composition of candies as a flavoring agent to improve taste sensations and, in addition, in itself it has anti-inflammatory, antispasmodic, antiseptic and distracting effect due to the cooling effect. Since lozenges are a solid dosage form, no preservatives are needed.

The following examples were studied to select the optimal composition of the dosage form:

Example 1. The composition of the candies, mass. %: liquid monarda extract - 9.6; sea buckthorn oil - 0.3; peppermint essential oil - 0.1; sorbitol - 80.0; purified water 10.0.

Production technology: 10.0 ml of purified water is added to 80.0 g of sorbitol and stirred by heating on a tile until a clear solution (caramel mass) is obtained. 9.6 g of liquid monarda extract, 0.1 g of peppermint essential oil, 0.3 g of sea buckthorn oil are added to the cooling caramel mass, mixed well and poured into molds. The obtained candies are placed in a refrigerator at a temperature of 5-8 ° C and left for 24 hours. Then the candies are removed from the molds and left for a day at room temperature. Ready-made candies are wrapped in wrapping paper. The mass of one candy is on average about 3.0 g.

The obtained lozenges for absorption are yellowish-brown caramel, with a faint smell of mint, caramel and a pleasant sweet, mint-carvacrol taste.

Example 2. The composition of the candies, mass. %: liquid monarda extract - 9.6; sea buckthorn oil - 0.3; sorbitol - 80.0; purified water 10.0.

Lollipops are made in the same manner as in Example 1.

The lollipops obtained are a tan caramel, sugary-sweet taste, turning into a bitter-carvacrol, astringent taste of the extract.

Example 3. The composition of the candies, mass. %: liquid monarda extract - 9.6; sea buckthorn oil - 0.1; peppermint essential oil - 0.3; sorbitol -80.0; purified water 10.0.

Lollipops are made in the same manner as in Example 1.

The resulting candies are yellowish brown caramel, with a strong mint smell and a cooling mint-menthol taste.

Example 4. The composition of the candies, mass. %: liquid monarda extract - 9.6; sea buckthorn oil - 0.2; peppermint essential oil - 0.2; sucrose - 80.0; purified water to 10.0.

Lollipops are made in the same manner as in Example 1.

The lollipops obtained are yellow caramel with a faint mint smell and a sugary-sweet, mint-carvacrol taste. During storage, the lollipop loses its shape and ease of use, as it becomes soft and malleable.

It should be noted that from the examples given by technological properties, organoleptic characteristics and from the point of view of ease of use, storage, the optimal composition of dental lozenges described in Example 1 is optimal. When lozenges are absorbed in the oral cavity, saliva production is stimulated and, accordingly, the oral cavity is moisturized, which provides a prolonged release of biologically active substances and an increase in the therapeutic effect.

In order to evaluate the dynamics of the release of biologically active substances from the dosage form in vitro experiments, we used the dialysis method through a semipermeable membrane: in a basket, the walls and bottom of which were lined with a sheet of cellophane grade MSAT-100 with a sheet thickness and an average area of at least 55 cm ² , lollipops were placed in 10 pieces and filled with purified water with a volume of 50 ml. The temperature of the aqueous medium was maintained with a thermostat in the range 34 ± 2 ° C. The rotation speed of the basket is 100 rpm. Samples of dialysate in a volume of 5 ml were taken after 15, 30, 45, 60 minutes, followed by replenishment of the dialysate. In the dialysate, the quantitative content of flavonoids was determined as the main group of biological active substances with various types of pharmacological activity. The determination was carried out by differential spectrophotometry at a wavelength of 389 nm, in a cell with a thickness of 10 mm The results of the study are presented in table 1. Analyzing the results, it can be noted that the most optimal composition of dental candies for the release of flavonoids is composition No. 1 (table. 1).

The determination of antimicrobial activity was carried out for the liquid extract of the monarda herb, as the main active component of the dosage form, and for the aqueous dialysate obtained from lozenges in determining the release of biologically active substances from the dosage form. To evaluate antimicrobial activity, the disk diffusion method was used. Sterile discs were impregnated with the studied drugs and placed in a Petri dish with nutrient medium and seeded microorganisms. After application of the discs, Petri dishes were placed in a thermostat at a temperature of 35 ° C and incubated for 18-24 hours. Then, zones of growth inhibition of microorganisms were evaluated. The results of the study are presented in table 2. It was found that both the liquid extract from the monarda herb and the aqueous dialysate obtained from the dosage form have antimicrobial activity against C. albicans, Ps. aeruginos, St. aureus, in comparison with gatifloxacin (table. 2).

For the monarda herb extract, anti-inflammatory activity was determined on a screening model of formalin paw edema in mice. The study was conducted on white outbred male mice weighing 18-24 g. The studied group of animals, the monarda herb extract was administered intragastrically at a dose of 0.08 ml using a special probe for 7 days. The control group received water. The comparison drug was a solution of diclofenac sodium at a dose of 10 mg / kg. On the last day, an hour after administration of the extract, phlogogen was administered. Subplanetary administration of 0.05 ml of a 1% formalin solution under the plantar aponeurosis of the right mouse paw introduced acute inflammation, resulting in the development of paw edema. After a day, the animals were euthanized under ether anesthesia and the anti-inflammatory effect was evaluated by reducing edema and expressed as a percentage of control. The results of the study are presented in table 3. Analyzing the results, it can be noted that the monarda herb extract, when administered intragastrically, exhibits anti-inflammatory activity, significantly reducing paw edema by 16.2% in comparison with the control (Table 3).

As a result of experimental studies, it was found that the claimed original composition of dental lozenges provides a drug with good technological properties, organoleptic characteristics, ease of use, providing a prolonged therapeutic effect, dosing accuracy, constant concentration of the drug over a long time, high adhesive ability to the mucous membrane the oral cavity. Thus, the obtained dosage form in the form of lozenges containing plant components can be recommended for use in dental practice in the treatment of lesions of the oral mucosa.

Claims (4)

The tool for the treatment of lesions of the oral mucosa, made in the form of lozenges containing peppermint essential oil as a biologically active substance, sorbitol in the amount of 80 wt.% And purified water 10.0, characterized in that as a biologically active substance active substances additionally contains a liquid extract from the monarda herb obtained by percolation at a ratio of raw materials: extractant 1: 1, and sea buckthorn oil in the following ratio of starting components, wt.%: monarda herb liquid extract, obtained by percolation with the ratio of raw materials: extractant 1: 1 9.6 sea buckthorn oil 0.3 peppermint essential oil 0.1 sorbitol 80.0 purified water 10.0