Composition for treatment and prevention of oral diseases and method for its use

Abstract

FIELD: pharmaceutical industry.SUBSTANCE: use of the composition in the treatment of inflammatory diseases of the oral cavity. The use of a composition in the form of a chewing marmalade, including components in the following ratio, wt.%: stevioside 2.0 to 10.0, gum arabic 2.0 to 20.0, ginger 0.5 to 5.0, Siberian fir extract 1.0 to 10.0, quercetin 0.01 to 0.5, pine extract 0.01 to 0.5, green chlorophyll 0.01 to 0.5, pine chlorophyll 0.01 to 0.5, pine paste 0.01 to 0.5, kelp extract 0.01 to 0.5, citric acid 0.1 to 0.7, flavoring 0.01 to 0.1, preservative 0.1 to 0.5, drinking water - up to 100.0, in the treatment of inflammatory diseases of the oral cavity.EFFECT: above-described composition is effective in the treatment of inflammatory diseases of the oral cavity.2 cl, 6 dwg, 1 tbl, 3 ex

Description

[0001] The invention relates to medicine, directly to therapeutic dentistry, and is intended for use as an oral care product that ensures the prevention of dental diseases.

[0002] The most common oral diseases today are dental caries and inflammatory periodontal diseases - gingivitis and periodontitis [Kuzmina E.M., Yanushevich, O.O. Preventive Dentistry: Textbook / E.M. Kuzmina, O.O. Yanushevich. - M .: Practical Medicine, 2016. - 544 p.].

[0003] What these diseases have in common is that dental plaque and the microbial biofilm (dental plaque) formed from it play an important role in their occurrence. [Therapeutic dentistry. Part I: study guide / edited by V.V. Nikitenko, A.M. Kovalevsky, E.G. Borisova. - St. Petersburg: Military Medical Academy, 2021. - 306 p.; Grudyanov A.I. Periodontal diseases / A.I. Grudyanov. - Moscow: Medical Information Agency Publishing House, 2009. - 336 p.; Yanushevich O.O. Periodontal diseases. A modern view of clinical, diagnostic and therapeutic aspects: study guide / O.O. Yanushevich [et al.]. - Moscow: GEOTAR-Media, 2010. - 160 p.].

[0004] It should be taken into account that gingivitis is an inflammation of the gums caused by the adverse effects of local and systemic factors and occurring without compromising the integrity of the gingival attachment, while periodontitis is an inflammation of the periodontal tissues, characterized by progressive destruction of the periodontium and the bone of the alveolar arch of the jaw. In this regard, periodontitis, along with periodontitis, which is a complication of dental caries, are the most common causes of tooth loss in patients [Integrative Periodontology: A Guide for Dentists / edited by A.M. Kovalevsky, V.A. Nikitenko. - M .: SIMK, 2019. - 252 p.].

[0005] In the pathogenesis of chronic generalized periodontitis, along with other factors, an important role is played by increased production of free radicals and suppression of the body's natural antioxidant system, as well as immune disorders [Periodontium diseases / edited by prof. L.Yu. Orekhova. - M .: Poli Media Press, 2004. - 432 p.].

[0006] A method is known for influencing the processes of lipid peroxidation in the oral cavity by local application of antioxidants, in particular, the drug Mexidol [Krasnova, V.V. Clinical and experimental substantiation of the use of the drug Mexidol in the complex treatment of periodontitis in flight personnel of the Air Force: author's abstract. diss. ... candidate of medical sciences: 14.00.21 / V.V. Krasnova. - M., 2005. - 26 p.].

[0007] The disadvantages are the lack of anticaries effect and the logical limitation of the time of use for a medicinal product.

[0008] In the prevention of dental caries, the most important value is given to the saturation of hard dental tissues with fluoride ions; a distinction is made between local and general fluoride prophylaxis of dental caries [Kuzmina E.M., Yanushevich, O.O. Preventive Dentistry: Textbook / E.M. Kuzmina, O.O. Yanushevich. - M .: Practical Medicine, 2016. - 544 p.].

[0009] It is known that a large amount of fluoride salts is found in kelp (seaweed), as a result of which the introduction of kelp into the diet is a measure of endogenous prevention of dental caries [Organization of the work of a dentist in a military unit (ship): guidelines. - M .: 2013. - 104 p.].

[0010] A disadvantage is the inconvenience of using kelp, which is only suitable for use in catering establishments. Its distinctive taste and smell often cause aversion, which reduces adherence to its regular consumption.

[0011] The drug Urolesan, which contains fir oil in combination with other plant components, is known to have anticalculous, antiseptic, antioxidant and peripheral circulation-improving effects [Urolesan use in the complex treatment of periodontal diseases in children with diabetes mellitus / R.V. Kazakova, M.A. Luchinsky, L.V. Godovanets et al. / / Dentistry of the new millennium: Collection of abstracts. - Moscow: Aviaizdat, 2002. - P. 24-25; Zuzuk B.M. Urolesan - 30 years of success / B.M. Zuzuk / / Pharmacist. - 2004. - No. 21. - P. 18-19.] and others.

[0012] A disadvantage is the fact that the instructions for the drug state that it must be taken by dissolving it under the tongue along with sugar, which contributes to an increase in the amount of aerobic coccal microbiota of the oral cavity, for which sucrose is a nutrient medium, and, accordingly, an increase in the risk of developing dental caries.

[0013] A chewing gum composition is known, including a chewing base and fillers, characterized in that it contains synthetic and / or natural gum bases as a chewing base, and resin of coniferous trees as fillers with the following content of components, in wt.%: synthetic and / or natural gum bases 40-60 resin of coniferous trees 40-60, including resin of Siberian larch or Siberian cedar [Chewing gum 2 392 023 C1 RU, IPC A23G 4 / 06 (2006.01) / I.A. Sitnikov; 2009108580 / 13, 2009.03.10; declared 2009.03.10; publ. [2010.06.10].

[0014] The disadvantage is the absence of an active anti-caries component in the chewing gum.

[0015] An oral care product and chewing gum are known, which contains a calcium salt, sodium phosphate and potassium phosphate, wherein the phosphate salts are encapsulated, and the molar ratio of the sodium salt to the potassium salt is in the range from about 3 to about 4. The invention provides for the creation of a favorable environment for the mineralization / remineralization of teeth [Oral care product and chewing gum 2 455 974 C2 RU, IPC A61K 8 / 24, A61Q 11 / 00(2006.01) / Haas Michael (US); 2009131493 / 15, 2008.02.18; declared 2008.02.18; published 2012.07.20].

[0016] The disadvantage is the lack of anti-film-forming and antioxidant action of the product.

[0017] The prototype is an oral care composition for preventing dental plaque, containing magnolia extract. The composition comprises the active compound Cortex from magnolia extract and an anticalculus system comprising tetrasodium pyrophosphate and sodium tripolyphosphate in various ratios. The composition can be used in a form selected from the group consisting of a mouthwash, a confectionery product, a toothpaste, and a dissolving tablet.

[0018] In one embodiment, the invention provides a method of treating plaque and tartar on an oral surface of a mammalian subject, the method comprising preparing an oral care composition, contacting the oral care composition with an oral surface to thereby reduce both plaque formation and tartar formation [Oral care composition for preventing plaque formation containing magnolia extract 2 385 709 C2 RU, IPC A61 K 8 / 97, A61K 8 / 24, A61Q 11 / 00 (2006.01) / Xu Tao (US), Herles Susan M. (US), Brown James R. (US), Barnes Virginia (US), Richter Rose (US), Prencipe Michael (US); 2007121731 / 15.2005.11.10; [declared 2005.11.10; published 2010.04.10].

[0019] The disadvantages include the lack of an active anticaries component, as well as the effect on lipid peroxidation, which is an important pathogenetic factor in the development of chronic generalized periodontitis.

[0020] The purpose of the invention: to create a composition for the prevention and treatment of oral diseases, which has a complex effect on the tissues of the gums and teeth, the body as a whole, and is highly effective.

[0021] Improves mechanical cleaning of the tooth surface from plaque, prevents bacterial adhesion to the tooth surface and the formation of microbial biofilm, normalizes the oral microbiota, increases caries resistance of hard dental tissues and local protective factors of the oral cavity through the use of a complex of plant-based components.

[0022] To achieve the intended goal, the developed composition in the form of a marmalade of highly elastic consistency is used, which provides a combination of local action in the oral cavity upon contact with teeth and the oral mucosa and a general effect on the body when absorbed through the oral mucosa and swallowed.

[0023] The composition, unlike the prototype, includes kelp extract (TU 10.39.30-025-41669896-2019), rich in macro- and microelements, including fluoride ions, which have an anti-caries effect, forming fluorapatites in the hard tissues of teeth, resistant to the effects of acids arising during the metabolism of cariogenic microorganisms, and also hinder the adhesion of bacteria to the surface of the tooth.

[0024] Ginger (GOST ISO 1003-2016) helps to activate local immunity of the oral cavity and general immunity, and also, having a local effect as a spice, activates local blood circulation in the periodontal tissues and the oral mucosa as a whole.

[0025] Fir juice (for example, 100% carbon dioxide extract of Siberian fir (water fraction)) has an antiseptic, local and general antioxidant, immunocorrective and peripheral circulation-improving effect, helping to prevent inflammatory periodontal diseases.

[0026] Coniferous extract (e.g. fir extract 50%, cedar extract 50%), green chlorophyll (e.g. manufacturer Biotvin) and coniferous chlorophyll (e.g. manufacturer EVKlab) have additional local cleansing, antiseptic, anti-inflammatory and anti-halitosis effects.

[0027] Pine chlorophyll-carotene paste (GOST 21802-84) due to the contained phytosterol (provitamin D), beta-carotene, lutein and other carotenoids, tocopherol and tocotrienols, other vitamins, phytoncides, polyprenols, squalene, polyunsaturated fatty acids has a general antioxidant, immunomodulatory and hypolipidemic effect on the body, helps to increase non-specific resistance, normalize intestinal microbiota and carbohydrate metabolism.

[0028] Quercetin (GOST R 57990-2017) has a pronounced local and systemic antioxidant effect. Gum arabic (GOST 33310-2015) is a prebiotic that helps normalize intestinal microbiota, has antioxidant and lipid-lowering effects, and improves calcium absorption in the gastrointestinal tract.

[0029] Stevioside (GOST R 53904-2010) is a sweetener of the composition, and also has immunomodulatory, hypolipidemic and hypoglycemic effects.

[0030] Gelatin (GOST 11293-2017) promotes additional cleaning of teeth from plaque by achieving a highly elastic consistency of the composition in the form of marmalade.

[0031] Auxiliary components of the composition: food citric acid (GOST 908-2004), flavoring agent (for example, food flavoring agent “Lemon”), sodium benzoate (preservative) (GOST 32777-2014).

[0032] The content of ingredients of the composition for the prevention of oral diseases is shown in Table 1.

[0033] Table 1.

[0034] Content of ingredients of the composition for the prevention of oral diseases, g per 100 g

[0035] Stevioside from 2.0 to 10.0 Gummiaribik from 2.0 to 20.0 Ginger from 0.5 to 5.0 Siberian fir extract from 1.0 to 10.0 Quercetin from 0.01 to 0.5 Pine extract from 0.01 to 0.5 Chlorophyll green from 0.01 to 0.5 Coniferous chlorophyll from 0.01 to 0.5 Pine paste from 0.01 to 0.5 Laminaria extract from 0.01 to 0.5 Citric acid from 0.1 to 0.7 Flavoring agent from 0.01 to 0.1 Preservative from 0.1 to 0.5 Drinking water up to 100.0

[0036] The proposed composition combines plant-based ingredients whose combined action creates a synergistic effect aimed at the comprehensive prevention of oral diseases. The mechanism of this synergistic effect can presumably be described as follows.

[0037] Laminaria extract (TU 10.39.30-025-41669896-2019), containing fluoride ions, strengthens enamel by forming fluorapatites, reducing the risk of acid damage. Its effectiveness is enhanced when combined with ginger and fir sap: the latter activate local blood circulation and the immune response, improving the delivery of micronutrients to dental and periodontal tissues. This combination not only prevents bacterial adhesion but also creates an environment unfavorable for biofilm formation.

[0038] Pine extract, chlorophyll, and fir sap mutually enhance their antiseptic and anti-inflammatory effects. Chlorophyll neutralizes volatile compounds that cause halitosis, while pine phytoncides inhibit the growth of pathogenic microflora. Together, they reduce the bacterial load, complementing the mechanical cleansing provided by the elastic texture of the marmalade.

[0039] Pine toothpaste and gum arabic act as prebiotics to maintain the balance of the oral microbiota. Antioxidants—quercetin and tocopherols—from the pine toothpaste neutralize free radicals, protecting periodontal tissue from oxidative stress, which exacerbates inflammation.

[0040] Stevioside, in addition to its hypoglycemic effect, reduces the risk of growth of sugar-dependent cariogenic bacteria.

[0041] The immunomodulatory properties of ginger and provitamin D from pine paste complement each other: the former stimulates the production of protective factors in saliva, while the latter supports the body's overall resistance. This ensures long-term prevention, as resistance to infections depends on both local and systemic mechanisms.

[0042] Also, during the development of the composition, achieving systemic effects, which are manifested through the cumulative overall effect of the composition's components on the body, was not obvious. Importantly, systemic effects are also associated with oral health and contribute to the increased effectiveness of the composition's active components on dental tissue and gums. The mechanism of systemic effects can presumably be described as follows.

[0043] Pine phytosterol, by competing with cholesterol, reduces its absorption, exerting a hypolipidemic effect. This is especially important for patients with hyperlipidemia, as it reduces the risk of atherosclerosis of periodontal capillaries and improves blood flow. Stevia improves cellular sensitivity to insulin, reducing circulating glucose levels—a key factor in protein glycation, which increases inflammation in periodontal tissues. Thus, normalizing the lipid and carbohydrate profile creates an environment less favorable for the progression of periodontitis.

[0044] Gum arabic, acting as a prebiotic, stimulates the growth of Bifidobacterium and Lactobacillus in the intestine. Intestinal dysbiosis often correlates with the overgrowth of pathogenic microflora in the oral cavity (e.g., Porphyromonas gingivalis). By strengthening the intestinal microflora, the product reduces the systemic bacterial load, which indirectly reduces the risk of gingivitis and caries.

[0045] Kelp extract, rich in iodine, normalizes thyroid function, dysfunction of which is associated with impaired calcium-phosphorus metabolism and osteoporosis of the jaw bones.

[0046] The ratio of components in the proposed composition is selected to minimize the risk of irritation of the oral mucosa (for example, citric acid is balanced by kelp extracts and chlorophyll, which soften the mucosa), but to maximize the therapeutic effect, including with long-term use.

[0047] During development, the composition also demonstrated an anti-cold effect, presumably due to the inhalation of pine needle terpenes (facilitating breathing), as well as the anti-inflammatory, antioxidant, and immunomodulatory properties of ginger, quercetin, pine extracts, and chlorophylls when absorbed systemically. Its calming effect is also presumably due to the aromatherapeutic (inhalation) effect of pine needle terpenes (fir sap, pine extract). The anti-inflammatory effects of other components may indirectly help reduce stress on the body.

[0048] Clinical examples.

[0049] Example No. 1.

[0050] Patient M., 47 years old. Complains of bleeding gums. He considers himself ill for at least 9 years and mentions type 2 diabetes. He is being monitored by an endocrinologist and follows the recommended diet. He receives oral hypoglycemic medication.

[0051] Average laboratory parameters over the 6 months prior to seeing a doctor: total cholesterol - 7.8 mmol / l, fasting glucose - 8.3 mmol / l, glycated hemoglobin (HbA1c) - 7.2%.

[0052] Physical examination data: General condition is satisfactory, face is symmetrical. Facial skin is pale pink. The mouth opens freely to a width of 4 cm. The bite is orthognathic. The cervical areas of the teeth are covered with a large amount of soft plaque. The mucous membrane of the gingival papillae is edematous, hyperemic, and bleeds upon probing. Percussion of the teeth is painless.

[0053] PMA index - 64.4%, OHI-S index Green J., Vermillion J. - 2.5 points, SBI bleeding index Muhleman HR, Son S. - 2.2 points.

[0054] Dental formula:

[0055]

[0056] Periodontal pocket depth (the largest value of all surfaces of each tooth in mm is indicated):

[0057]

[0058] Pathological mobility of grade I is noted 3.2, 3.1, 4.1, 4.2.

[0059] Orthopantomogram shows uneven bone resorption in the alveolar arches of the jaws (Fig. 1). At the apices of the roots of the 3.6 teeth, there are foci of bone rarefaction with unclear boundaries, measuring approximately 3x4 mm.

[0060] Diagnosis: exacerbation of severe chronic generalized periodontitis against the background of type 2 diabetes mellitus. Chronic granulating periodontitis 3.6.

[0061] Treatment performed: professional supervised oral hygiene, endodontic treatment of teeth 3.6, 3.2, 3.1, 4.1, 4.2, flap surgery on both jaws with implantation of porous granular hydroxyapatite. Sutures were removed 12 days after surgery.

[0062] The prescribed dosage is the developed composition in the form of marmalade, twice a day after hygiene procedures, in the morning and in the evening, for 12 months, consisting of:

[0063]

[0064] Laboratory parameters after 3 months of taking the composition: total cholesterol level - 7.4 mmol / l, fasting glucose - 7.8 mmol / l, glycated hemoglobin (HbA1c) - 7.1%.

[0065] Laboratory parameters after 6 months of taking the composition: total cholesterol level - 7.2 mmol / l, fasting glucose - 7.4 mmol / l, glycated hemoglobin (HbA1c) - 6.7%.

[0066] Laboratory parameters after 12 months of taking the composition: total cholesterol level - 6.3 mmol / l, fasting glucose - 5.9 mmol / l, glycated hemoglobin (HbA1c) - 6.2%.

[0067] At the one-year follow-up, the patient had no complaints. His general condition was satisfactory. Locally, the oral mucosa was pale pink, with periodontal pockets up to 3.5 mm deep. Probing revealed bleeding in the 1.4 area, where a periodontal pocket up to 6 mm deep persisted. Tooth mobility was normal.

[0068] PMA index - 19.4%, OHI-S index Green J., Vermillion J. - 1.2 points, SBI bleeding index Muhleman HR, Son S. - 1.0 point.

[0069] On the orthopantomogram (Fig. 2) there are signs of partial restoration of the bone tissue of the interalveolar septa in the area of ​​2.6, 2.7, the contours of the bone tissue of the jaws are clear.

[0070] Diagnosis: chronic generalized periodontitis of moderate severity in remission against the background of type 2 diabetes mellitus.

[0071] Thus, the use of the developed composition in the form of a marmalade contributed to the achievement of remission of chronic generalized periodontitis associated with type 2 diabetes mellitus. A reduction in total cholesterol and glycated hemoglobin levels was achieved.

[0072] Example No. 2.

[0073] Patient B., 54 years old, complains of bleeding gums. Previously treated by a periodontist, he underwent professional oral hygiene. A blood test showed a total cholesterol level of 7.1 mmol / L.

[0074] Average laboratory parameters over 6 months before visiting a doctor: total cholesterol - 7.1 mmol / l, fasting glucose - 6.1 mmol / l, glycated hemoglobin (HbA1c) - 6.9%.

[0075] Objectively: General condition is satisfactory, facial configuration is unchanged. Skin is pale pink. Mouth opening is approximately 4 cm. Orthognathic bite. Gingival papillae are swollen, hyperemic, and bleed easily. Percussion of teeth is painless.

[0076] Periodontoid tissue condition index scores: PMA - 54.2%, OHI-S - 2.3 points, SBI - 2.1 points.

[0077] Dental formula:

[0078]

[0079] Depth of periodontal pockets (according to the largest indicator of the tooth surface study, mm):

[0080]

[0081] Orthopantomogram: uneven resorption of bone tissue of the alveolar arches of the jaws (Fig. 3).

[0082] Diagnosis: exacerbation of chronic generalized periodontitis of moderate severity against the background of hypercholesterolemia.

[0083] Treatment carried out: professional oral hygiene, rinsing the mouth with antiseptic solutions, taking the developed composition in the form of marmalade twice a day after hygiene procedures, in the morning and in the evening, for 3 months, consisting of:

[0084] Laboratory parameters after 3 months of taking the composition: the level of general

[0085]

[0086] cholesterol - 6.5 mmol / l, fasting glucose - 5.3 mmol / l, glycated hemoglobin (HbA1c) - 6.2%.

[0087] At the 12-month follow-up, the patient had no complaints. Blood tests revealed total cholesterol of 5.7 mmol / L and glycated hemoglobin (HbA1c) of 5.4%.

[0088] The general condition is satisfactory. In the oral cavity: the mucous membrane is pale pink, percussion of the teeth is painless, tooth mobility is physiological. The depth of the periodontal pockets is unchanged. The PMA index is 17.2%, the OHI-S index is 1.2 points, and the SBI bleeding index is 0.9 points.

[0089] The orthopantomogram (Fig. 4) shows clear contours of bone tissue.

[0090] Diagnosis: chronic generalized periodontitis of moderate severity in remission.

[0091] Thus, the use of the developed composition in the form of marmalade contributed to the achievement of remission of chronic generalized periodontitis against the background of hypercholesterolemia, as well as a decrease in the level of cholesterol in the blood according to laboratory research data.

[0092] Example #3.

[0093] Patient F., 34 years old. No complaints. Considers himself healthy. Arrived for a routine checkup before a long business trip to the Arctic.

[0094] Physical examination data: General condition is satisfactory. The face is symmetrical, the skin is pale pink. The submandibular lymph nodes are not palpable.

[0095] Oral examination: the mucous membrane is pale pink, periodontal pockets up to 3.5 mm deep, and a small amount of tartar deposits are present. Tooth percussion is painless, and mobility is normal. The PMA index is 18.1%, the OHI-S index is 1.1 points, and the SBI bleeding index is 0.7 points.

[0096] Dental formula:

[0097]

[0098] The orthopantomogram (Fig. 5) shows clear contours of the jaw bone tissue.

[0099] Diagnosis: chronic generalized periodontitis of mild severity in remission.

[0100] Treatment performed: professional oral hygiene, oral irrigation with 0.05% chlorhexidine bigluconate solution. Prophylactic use of the developed composition in the form of a gummy in the morning after hygiene procedures throughout the entire business trip is recommended.

[0101]

[0102] Follow-up examination after 6 months. The patient has no complaints.

[0103] Objectively: the general condition is satisfactory. The face is symmetrical. Mouth opening is normal. The oral mucosa is pale pink. The depth of periodontal pockets is unchanged. The PMA index is 18.2%, the OHI-S index is 1.2 points, and the SBI bleeding index is 0.8 points.

[0104] The orthopantomogram (Fig. 6) shows clear contours of the jaw bone tissue.

[0105] Diagnosis: chronic generalized periodontitis of mild severity in remission.

[0106] Thus, the use of the developed composition in the form of marmalade contributed to maintaining remission of chronic generalized periodontitis during a long-term business trip to the Arctic zone.

Claims

1. Use of a composition in the form of chewing marmalade, including components in the following ratio, wt.%: Stevioside from 2.0 to 10.0 Gum arabic from 2.0 to 20.0 Ginger from 0.5 to 5.0 Siberian fir extract from 1.0 to 10.0 Quercetin from 0.01 to 0.5 Pine extract from 0.01 to 0.5 Chlorophyll green from 0.01 to 0.5 Coniferous chlorophyll from 0.01 to 0.5 Pine paste from 0.01 to 0.5 Laminaria extract from 0.01 to 0.5 Citric acid from 0.1 to 0.7 Flavoring agent from 0.01 to 0.1 Preservative from 0.1 to 0.5 Drinking water up to 100.0 in the treatment of inflammatory diseases of the oral cavity.

2. The use according to paragraph 1, characterized in that the composition additionally includes gelatin in an amount of 10-25% by weight.

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