RU2607931C2 - Therapeutic composition for oral care for hematology-oncology patients - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to dentistry, and specifically to compositions for oral care for preventing and treating consequences of high–dose chemotherapy. Therapeutic composition (TC) comprises, at the ratio of components, wt%: leucovorin – 0.1–1.0; allantoin – 0.1–0.5; biosol – 0.05–0.15; D-panthenol–75% – 1.0–5.0; potassium sorbate – 0.1–0.3; Cosphaderm® Magnolia Extract 98 0,1–0,3; citric acid – 0.05–0.15; menthol – 0.1–0.25; sodium benzoate – 0.1–0.3; sodium lauryl sulphate – 0.1–0.5; sodium methylparaben – 0.05–0.15; sodium saccharinate – 0.05–0.15; sodium citrate – 0.05–0.15; propylene glycol – 1.0–3.0; PEG–40 – 1.0–3.0; rosemary extract – 0.5–1.0; sorbitol – 5.0–10.0; trilon B – 0.05–0.15; thick propolis extract – 0.5–2.5; water – up to 100. TC is recommended as an effective agent for oral care for hematology–oncology patients, receiving high–dose chemotherapy.

EFFECT: invention provides a set of technical results: a wider range of TC users, high stability of its properties, high efficiency of action on the oral cavity, including dental tissue.

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Description

The invention relates to the field of dentistry, more specifically to compositions for caring for the oral cavity, specifically for the prevention and treatment of the effects of high-dose chemotherapy.

Known therapeutic and prophylactic composition for caring for the oral cavity of blood-oncological patients, containing active medicinal agents and auxiliary ingredients, including sodium lauryl sulfate, sodium saccharin and water: see patent application WO 2009/106963.

This well-known therapeutic and prophylactic composition (LPC) is an analogue and prototype of the invention. LPK prototype has a number of significant disadvantages. They are explained, first of all, by the active drug agents, which include myrrh extract, zinc chloride, chlorhexidine bigluconate. Mirra is contraindicated for use by women during pregnancy, is contraindicated in patients with diseases of the heart, liver and kidneys, with diabetes, as well as with intestinal inflammation and diarrhea. That is, the well-known forest industry has limited application in relation to the contingent of users. Further, the aforementioned antiseptic chlorhexidine bigluconate is prone to inactivation in the presence of sodium lauryl sulfate contained in the LPC prototype. That is, the properties of this timber complex are not kept stable. Another significant drawback of the known LPC is its consistency: paste or gel, so when using the LPC, you need a toothbrush, which irritates the damaged tissue of the oral cavity. After using the LPC, it is necessary to rinse the mouth from its residues, which limits the duration of contact of the LPC with the oral cavity, reducing the effectiveness of the therapeutic and prophylactic effect of the LPC prototype.

The claimed invention is aimed at solving the technical problem of complex improvement of the LPC for the care of the oral cavity of blood-oncological patients, namely: to expand the contingent of users of the LPC, to increase the stability of properties, to increase the effectiveness of the action of the LPC.

The stated technical problem is solved in that the therapeutic composition for the care of the oral cavity of blood-oncological patients, containing active medicinal agents and auxiliary ingredients, including sodium lauryl sulfate, sodium saccharin and water, according to the invention, contains active medicinal agents: leucovorin, allantoin, biosol, D-panthenol-75%, Cosphaderm® Magnolia Extract 98, rosemary extract, thick propolis extract; contains additional auxiliary ingredients: potassium sorbate, citric acid, menthol, sodium benzoate, sodium methyl araben, sodium citrate, propylene glycol, PEG-40, sorbitol, Trilon B - in the following proportions, wt. %:

leucovorin 0.1-1.0

allantoin 0.1-0.5

biosol 0.05-0.15

D-panthenol-75% 1.0-5.0

potassium sorbate 0.1-0.3

Cosphaderm® Magnolia Extract 98 0.1-0.3

citric acid 0.05-0.15

menthol 0.1-0.25

sodium benzoate 0.1-0.3

sodium lauryl sulfate 0.1-0.5

sodium methylparaben 0.05-0.15

sodium saccharin 0.05-0.15

sodium citrate 0.05-0.15

propylene glycol 1.0-3.0

PEG-40 1.0-3.0

rosemary extract 0.5-1.0

sorbitol 5.0-10.0

Trilon B 0.05-0.15

thick propolis extract 0.5-2.5

water - up to 100.

A technical result (s) is expected from the invention, which coincides with the essence of the problem being solved.

The composition of the proposed LPK for the care of the oral cavity of blood-oncological patients includes both some components of the LPK prototype, as well as a number of new components; all of them, in the proposed quantitative proportions, give the timber industry properties that solve the technical task.

The primary active drug agent of the proposed LPC is, in accordance with its intended use, leucovorin (calcium folinate). Blood-oncological patients taking high-dose chemotherapy with methotrexate are at risk of ulcerative stomatitis in the oral cavity. Leucovorin successfully prevents this, it prevents the toxic effect of methotrexate on healthy cells, restores the disturbed biosynthesis of DNA, RNA and proteins in them.

The positive effect of leucovorin is supported by other active medicinal agents of the forest complex. It contains a significant amount of the product D-panthenol-75%, which is a 75% aqueous solution of dexpanthenol. Dexpanthenol has an anti-inflammatory, healing and moisturizing effect, stimulates metabolic processes in the tissues of the oral cavity, improves their regeneration.

These positive effects are enhanced by the introduction of an extract of thick propolis, EPG, into the forest complex. This active drug agent is characterized by a high content of extractive substances, has excellent bactericidal and antimicrobial properties, does not allow infections to develop, and inhibits inflammatory processes. EPG propolis is a powerful biostimulant. Thanks to its antioxidant effect, it promotes the formation of collagen and elastic periodontal fibers, reduces fragility of blood vessels, improves metabolic processes, and prevents gum inflammation. Propolis is a complex substance that contains, along with essential oils, many vitamins and minerals that contribute to the prevention of dental diseases.

Cosfaderm (trade name Cosphaderm® Magnolia Extract 98) is a very important medicinal agent for the forest industry. Magnolol and honokiol, the main polyphenolic compounds of the magnolia plant, present in its composition actively counteract gingivitis and periodontitis. Being an active agent of a wide spectrum: antibacterial, antifungal, anti-inflammatory, antioxidant, cosfaderm is effective in treating periodontal disease, ulcerative and aphthous stomatitis. Cosfaderm also has preservative properties and inhibit the formation of dental plaque causing tooth decay.

The biosol contained in the forestry complex (Biosol®, INCI code: O-CYMEN-5-OL) is an isomer of thymol, the main component of the essential oils of the plants of the Labiaceae family, used in folk medicine. Biosol effectively acts against various types of bacteria and certain strains of viruses, including those that cause inflammatory processes. Biosol prevents oxidation and prevents the breakdown of materials used with it. Due to this property, biosol is also an effective preservative that contributes to the stability of the prepared LPK.

As auxiliary ingredients, preservatives LPK contains potassium sorbate, sodium benzoate, sodium methyl paraben. They belong to the class of food additives. The first of these substances is a highly effective natural preservative, which is widely used in the food, cosmetic and pharmaceutical industries. The allergenicity of potassium sorbate is very small, and its quantitative content in the proposed complex does not cause harm (cause irritation of the oral mucosa) even to especially sensitive patients. The food additives mentioned also have antimicrobial properties; sodium methylparaben is an antiseptic. Sodium benzoate prevents the formation of dental plaque, protecting teeth from tooth decay.

Due to the fact that the consumers of the proposed LPC are persons suffering from damage to the tissues of the oral cavity, the LPC is designed for the possibility of effective and convenient use without a toothbrush, namely in the form of foam. By consistency, the proposed LPC is a liquid with high foaming properties, which are provided by the presence of an auxiliary ingredient in the form of sodium lauryl sulfate (EMAL® 10N). This well-known surface-active substance (surfactant) also has antibacterial properties, increases the permeability of the oral mucosa for biologically active substances contained in the LPC, and dissolves tooth plaque. As you know, sodium lauryl sulfate can irritate the gums, oral membranes and dry the mucous membrane of the mouth. In the proposed LPC, these negative phenomena are minimized by a decrease in the quantitative content of surfactants relative to the LPC prototype, in combination with the addition of allantoin.

Water-soluble crystalline allantoin is characterized by anti-inflammatory, antioxidant activity. This active agent has a softening and moisturizing effect on tissues, has a pronounced healing effect, stimulates the regeneration of gums and oral mucosa.

The effect of allantoin supplements the rosemary extract contained in the LPC - INCI: Rosmarinus officinalis (rosemary) leaf extract. This natural plant product has pronounced antioxidant, astringent and tonic properties. Rosemary extract is effective in the treatment of damaged, sensitive tissues. It is rich in vitamins B1, B3, C and minerals useful for dental tissue.

High moisturizing and emollient qualities of the proposed forestry complex are also provided with significant additives of propylene glycol and sorbitol. The latter is found as a natural component in fruits, berries, corn, algae. Sorbitol is present in the LPC in the largest amount (not counting water), being a solvent for a number of other components. Sorbitol increases the remineralizing strength of saliva, helping to neutralize plaque acid, which prevents gingivitis, periodontitis and tooth decay.

Sorbitol is a sugar free sweetener. It gives LPK a characteristic pleasant taste, along with other auxiliary ingredients. Among them, sodium saccharinate contained in the LPK prototype, as well as menthol and citric acid.

Citric acid has the properties of a sequestrant. It regulates acidity, as well as sodium citrate contained in the timber. This ingredient interacts with organic enamel substances, contributing to the creation of a protective barrier against tooth pain reactions to temperature and chemical stimuli (to a hot, cold, sweet, acidic environment).

To give the necessary viscosity, a water-soluble hydrogenated castor oil PEG-40 was introduced into the woodworking complex. Together with the used surfactant, it provides the LPC with solubilizing, dispersing, emulsifying and wetting properties for other components.

Foaming and penetration into the tissues of the components of the LPC is facilitated by Trilon B (EDTA) contained in it - a substance known as a complexing agent, pH regulator, emollient and chelating agent. Trilon B also has antioxidant preservative properties and acts synergistically with preservatives, increasing their effectiveness.

The aforementioned kosfaderm and menthol are also flavorings. They give the wood a characteristic pleasant, delicate smell.

The proposed forestry complex is prepared by mixing the components in the proportions corresponding to the invention. In this case, water is preliminarily subjected to multistage preparation, including the removal of mechanical particles, softening, and microbiological treatment. First, half the mass of the final water is poured into the reactor, heated to a temperature of 55-60 ° C and loaded, with continuous stirring, leucovorin, allantoin, biosol, potassium sorbate, sodium saccharinate, sodium citrate, propylene glycol, sorbitol, EPG. After obtaining a homogeneous mass, the remaining half of the water is added and the remaining components are loaded at a temperature of 35-40 ° C. Constantly mix the raw materials, achieving a homogeneous mass. She is allowed to stand and cool to room temperature. The process of preparing the timber industry takes about an hour.

The finished mass is distributed into small plastic cartridges for personal use (usually 50 ml of the composition) equipped with a device for foaming the refilled mass of the timber and feeding it through the consumable nozzle. Such a spray can be found, for example, in US Pat. No. 5,048,750. When using it, the nozzle, made at the same time with the lid, is brought to the mouth and pressed, introducing a dose of foamed woodworking compound into the mouth. For 20-30 seconds they hold the foam in the mouth, making rinsing movements. Then the foam is spit out without rinsing the mouth with water.

Tests for microbial purity in the forest industry according to the requirements of the State Sanitary and Epidemiological Supervision of the Russian Federation showed a complete absence of bacteria, yeast and molds. Toxicological tests of the LPC showed the absence of acute toxicity when administered orally, the absence of irritating effects on the mucous membrane of the oral cavity and gastrointestinal tract. Clinical trials of pulmonary arteries in hemato-oncological patients taking high-dose chemotherapy with methotrexate have shown that they are safe for health, do not irritate oral tissue, are effective and anti-inflammatory, heal microscopic wounds, effectively counteract ulcerative and all other types of stomatitis, and effectively cleanse and strengthen enamel. .

The described properties of the timber complex are provided in the entire claimed range of the quantitative content of the components. For example, according to the invention, it is possible to prepare a LPC of such a specific composition, wt. %:

leucovorin 0.5

allantoin 0.5

biosol 0.1

D-panthenol 75% 3.0

potassium sorbate 0.25

Cosphaderm® Magnolia Extract 98 0.2

citric acid 0.1

menthol 0.2

sodium benzoate 0.2

sodium lauryl sulfate 0.3

sodium methylparaben 0.1

sodium saccharinate 0.1

sodium citrate 0.1

propylene glycol 3.0

PEG-40 2.5

rosemary extract 0.75

sorbitol 7.5

Trilon B 0.1

thick propolis extract 1.5

water - 79.0.

So, by creating the above-described LPC, the technical task stated by the invention has been solved for the comprehensive improvement of the LPC for caring for the oral cavity of hemato-oncological patients with obtaining the expected technical result, more precisely, the totality of results, namely: expanding the contingent of the LPC users, increasing the stability of the properties of the LPC, increasing the effectiveness of the LPC . Along with this, an additional technical result was obtained, consisting in the positive effect of LPC on dental tissue.

All components of the proposed forestry complex are manufactured industrially and presented on the market, and the technological methods for obtaining the composition are well mastered.

The proposed LPC is recommended as an effective tool for caring for the oral cavity of hemato-oncological patients receiving high-dose chemotherapy. It is recommended to use LPK after each meal.

Claims (21)

A therapeutic and prophylactic composition for caring for the oral cavity of hematologic patients, containing active medicinal agents and auxiliary ingredients, including sodium lauryl sulfate, sodium saccharinate and water, characterized in that it contains active medicinal agents: leucovorin, allantoin, biosol, D-panthenol -75%, Cosphaderm® Magnolia Extract 98, rosemary extract, thick propolis extract; contains additional auxiliary ingredients: potassium sorbate, citric acid, menthol, sodium benzoate, sodium methylparaben, sodium citrate, propylene glycol, PEG-40, sorbitol, Trilon B - in the following proportions, wt. %: leucovorin 0.1-1.0 allantoin 0.1-0.5 biosol 0.05-0.15 D-panthenol-75% 1.0-5.0 potassium sorbate 0.1-0.3 Cosphaderm® Magnolia Extract 98 0.1-0.3 citric acid 0.05-0.15 menthol 0.1-0.25 sodium benzoate 0.1-0.3 sodium lauryl sulfate 0.1-0.5 sodium methylparaben 0.05-0.15 sodium saccharin 0.05-0.15 sodium citrate 0.05-0.15 propylene glycol 1.0-3.0 PEG-40 1.0-3.0 rosemary extract 0.5-1.0 sorbitol 5.0-10.0 Trilon B 0.05-0.15 thick propolis extract 0.5-2.5 water - up to 100.