RU2549498C1 - Therapeutic agent for treating exudative hyperemic and erosive ulcerative forms of oral lichen planus - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, more specifically to clinical dentistry. The invention represents a composition for treating erosive ulcerative and exudative hyperaemic forms of oral lichen planus.

EFFECT: implementing the invention provides high oral adhesion of the preparation, increases the therapeutic concentration of the preparation in the area of involvement (inflammation), accelerates the length of treatment (reduces the size of erosion, the length of epithelisation of erosions).

2 dwg

Description

The invention relates to medicine, specifically to clinical dentistry, to preparations for treating diseases of the oral mucosa, namely, lichen planus of the oral mucosa of exudative-hyperemic, erosive-ulcerative forms.

Lichen planus - a chronic polyetiological disease with rashes of papules on the mucous membranes and skin, is found in all age groups, but women from 30 to 60 years old are more likely to get sick. The clinical picture and the course of lichen planus on the oral mucosa significantly differ from its manifestations on the skin, which is due to structural features of the oral mucosa, as well as the specificity of biological and physicochemical processes in the oral cavity associated with the presence of focal infection foci, fillings and prostheses from various metals, the composition and properties of saliva, the processes of initial cleavage of food products [1].

According to the classification proposed by A. Mashkillayson. and Borovsky E.V. (1984) identified the following clinical forms of lichen planus of the oral mucosa: typical, exudative-hyperemic, erosive-ulcerative, bullous, hyperkeratotic, atypical [2]. In the oral cavity, the favorite place for localization is the mucous membrane of the cheeks, lateral and dorsal surfaces of the tongue, less often the mucous membrane of transitional folds, lips and the bottom of the oral cavity.

To date, the problem of treatment of lichen planus (CPL), especially of the erosive-ulcer form, which has the highest potential malignancy, is one of the most important and unresolved tasks of clinical dentistry [3, 4, 5].

The most significant of the primary stages of complex therapy for CPL, in addition to etiotropic and pathogenetic therapy, is local conservative treatment.

The arsenal of drugs used in the local therapy of erosive and ulcerative lesions of SOPR in CPL has expanded significantly in recent years - these are antiseptic solutions, enzymes, hydrocortisone ointment, 0.5% prednisolone ointment, various combined biomaterials containing solcoseryl, proteolytic enzymes, emoxipin, parmidin, dalargin, tocopherol and retinol acetate based on collagen [6, 7, 8, 9].

The complex treatment of patients with an erosive-ulcerative form of CPL MOP includes the collagen-based emparkol preparation, which includes dimexide, parmidin and emoxipin. The drug has an antimicrobial and wound healing effect and is applied to the dried affected surface on gauze napkins 4-5 times a day for 2-3 minutes for 7 days [10].

In case of erosive-ulcerative and bullous forms, hydrocortisone or prednisolone ointment is used to stop the process in the form of applications for problem areas of the mucous membrane for 15-20 minutes 3-4 times a day, as well as hydrocortisone injections for lesion elements [11].

In this case, the choice of a drug is based on determining the therapeutic coefficient of the ratio of effectiveness / safety (benefit / risk). However, these drugs have a number of drawbacks: poor adhesion to the affected area, high solubility in the oral fluid, and are inconvenient to use (ointment forms in the form of applications on gauze napkins).

The most optimal option for local drug therapy of exudative-hyperemic, erosive-ulcerative forms of CPL is the use of a medicinal composition: Tizol gel preparation with triamcinolone.

Triamcinolone is a topical glucocorticosteroid. External use is based on anti-inflammatory, immunosuppressive, anti-allergic, antipruritic effect, which is due to the following pharmacological effects:

- inhibition of migration of neutrophils, monocytes and eosinophils into the focus of inflammation;

- activation of histaminase and the associated decrease in histamine levels in the focus of inflammation;

- a decrease in the sensitivity of nerve endings to histamine;

- increased production of lipocortin protein, inhibiting the activity of phospholipase A, which in turn leads to a decrease in the synthesis of mediators of allergic inflammation (arachidonates);

- a decrease in the activity of hyaluronidase and lysosomal enzymes, which reduces the permeability of the vascular wall and the severity of edema;

- a decrease in the formation of free oxygen radicals;

- inhibition of the synthesis of mucopolysaccharides;

- a decrease in the number of antigen presenting and mast cells;

- inhibition of nucleic acid synthesis.

According to the data of American and European researchers, seven classes of topical glucocorticosteroid drugs are distinguished, depending on the degree of their anti-inflammatory activity: from 1st (drugs of maximum potency) to 7th (drugs of minimum potency) [12].

In recent years, predominantly preferred topical glucocorticosteroids of maximum strength, characterized by high efficiency, minimal side effects, as well as prolonged action [13].

Triamcinol is positioned as a strong topical glucocorticosteroid of the 2nd class, it is not only highly effective, but also has a low absorption when applied topically, i.e. less likely to develop systemic side effects. Often used in the treatment of exacerbations of chronic, persistent inflammatory diseases of the skin and mucous membranes, when it is necessary to quickly stop pronounced island-inflammatory phenomena.

The closest analogue of triamcinolone is hydrocortisone, a topical corticosteroid of minimal potency. With external and local application, the therapeutic activity of hydrocortisone is due to anti-inflammatory, anti-allergic and antiexudative (due to the vasoconstrictor effect) effect. Compared with triamcinolone, the anti-inflammatory activity of hydrocortisone is 5 times lower, which is expressed by low clinical efficacy.

The choice of dosage forms is an important part of the treatment strategy for lichen planus, as the drug base has a significant effect on the absorption of the drug.

Tizol is used as a medicine and as a basis for the preparation of medicines (P No. 001667 / 01-010807). The drug Tizol according to the Instructions for medical use is used in surgery, rheumatology, dermatology, oncology (as a local radioprotector for radiation therapy), and also as a conductor of drugs. Tizol-gel - titanium glycerol solvate aquacomplex - has anti-inflammatory, antimicrobial, protective, dehydrating, decongestant, local analgesic effects. A unique property of Tizol is its conductivity through the skin, mucous membranes and bone tissue. Tizol is well combined with various drugs, does not destroy, but increases their therapeutic activity and helps to lead them to the pathological focus, completely releasing the substance. Not cumulated in the body. It does not cause allergic reactions, is not toxic, is easily applied to the skin, mucous membrane, very economical, convenient for use. The element of titanium contained in the preparation is a vital element, given its content in the body and the functions it performs. Titanium is present in blood plasma, liver, endocrine glands: breast milk contains 0.0136 mcg%; whole blood contains 0.53 μg% titanium; up to 1% contains it in the gamma-globulin fraction of blood proteins. Titanium has a positive effect on erythropoiesis, increases the number of red blood cells, and catalyzes the synthesis of hemoglobin. He participates in the processes of hematopoiesis, immunogenesis, does not have cumulative properties. Titanium preparations are low toxic and are strong biostimulants. Their effect on cell membranes is a zero-order chemical process, they provide a high ingredient in potassium and calcium concentrations, and neutralize the "harmful" effects of adverse environmental factors.

Toliz form - gel. It does not accumulate fluid in tissues, protects tissues from drying out and swelling, enhances their oxygenation. Tizol has a high transcutaneous and transmucoid conductivity.

The closest analogue of Thysol is DMSO (dimethyl sulfoxide), the drawback of which is that it has an unpleasant “garlic” smell and often causes “itchy” dermatitis. DMSO is contraindicated in cases of impaired liver antitoxic function, renal excretory function, angina pectoris, severe atherosclerosis, pregnancy, glaucoma, and cataracts. DMSO can enhance not only the activity, but also the toxicity of drugs. Caution should be exercised when prescribing DMSO simultaneously with other drugs. Quite often, individual intolerance to DMSO is found, therefore, it is necessary to conduct a drug test for tolerance to it, and allergic reactions are possible during the treatment of DMSO.

The advantages of the claimed medicinal product are as follows:

1. Due to the high adhesion of the drug to the mucous membrane of the oral cavity, the therapeutic concentration of the drug in the lesion (inflammation) increases;

2. The treatment time is accelerated (the size of the erosive lesion is reduced, the time of epithelization of erosive sites is reduced);

3. The drug consumption is reduced several times and its dosage is achieved;

4. Stop pain in the oral mucosa;

5. There are no systemic side effects;

6. Convenient and easy to use;

7. There are no negative reactions in patients.

The drug is claimed to treat erosive-ulcerative and exudative-hyperemic forms of lichen planus, which is prepared by mechanical stirring in the following ratios of components, g:

Tizol  - 10.0 Triamcinolone  - 0.004

A thin layer of the drug, whose thickness is 0.1 mm, is applied to the lesion of the mucous membrane of the oral cavity. The drug is applied with a small glass spatula. To improve the therapeutic effect, it is recommended not to eat food for one hour, use it twice a day, the course of treatment is 14 days.

Figure 1 shows the condition of the oral mucosa with an erosive-ulcerative form of lichen planus before treatment.

Figure 2 shows the state of the oral mucosa after treatment with the claimed drug.

The inventive drug was used to treat 30 patients with red lichen planus of the oral mucosa, of which: 14 - erosive-ulcerative form, 16 - exudative-hyperemic form. The effectiveness of treatment was evaluated in dynamics according to subjective signs and the clinical picture.

Clinical examples:

Example No. 1. Patient O. turned to the therapeutic dentistry clinic of the Ural State Medical University with complaints of a burning sensation and soreness of the oral mucosa, aggravated by the intake of hot, spicy and spicy food.

Objectively: on the mucous membrane of the cheeks there are multiple papular elements, grayish-white in color, merging to form a net pattern, the mucous membrane is hyperiminated, slightly swollen, painful on palpation.

Diagnosis: lichen planus - exudative-hyperemic form.

The diagnosis was made on the basis of complaints, medical history, objective data, histological examination.

The patient was prescribed the claimed drug 2 times a day for 14 days as a local treatment.

After the first day of using the drug, the pain in the oral cavity significantly decreased, on the 2nd day the pain disappeared, on the 3rd day of treatment there was a change in the clinical picture in the direction of reducing inflammatory phenomena (hyperemia, edema decreased). After treatment, the patient has no complaints, the mucous membrane of the oral cavity is pale pink, moist, isolated papules without signs of inflammation are preserved.

Example No. 2. Patient I. turned to the clinic of therapeutic dentistry of the Ural State Medical University with complaints of erosion under the tongue, pain when eating.

Objectively: the mucous membrane of the hyoid region to the left, closer to the frenum of the tongue, is hyperemic, swollen with multiple papular elements, grayish-white in color, which, merging, form a mesh pattern, there is a violation of the integrity of the mucous membrane, erosion is covered with plaque, painful on palpation.

Diagnosis: lichen planus - erosive-ulcerative form (Figure 1).

The diagnosis was made on the basis of complaints, medical history, objective data, histological examination.

Together with the general treatment, the claimed drug was prescribed as a local treatment 2 times a day for 14 days.

As a result of treatment, after the first day of using the drug, pain during eating was significantly reduced, the pain disappeared on day 3, and erosion cleared of plaque. On the 4th day of treatment, there was a decrease in hyperemia, edema, erosion had no plaque, epithelization of the peripheral part of erosion began. On the 12th day, epithelization of erosion was observed, the mucous membrane of the oral cavity was pale pink, moist, isolated papules without signs of inflammation, flattened (Figure 2).

Example No. 3. Patient M. turned to the therapeutic dentistry clinic of the Ural State Medical University with complaints of a burning sensation and soreness of the oral mucosa, aggravated by the intake of hot, spicy and spicy food.

Objectively: the mucous membrane of the cheeks, the lateral surface of the tongue is hyperemic, edematous, on the background of which typical papules are located, the mucous membrane is painful on palpation.

Diagnosis: lichen planus - exudative-hyperemic form.

The diagnosis was made on the basis of complaints, medical history, objective data, cytological examination.

The patient was prescribed the claimed drug 2 times a day for 14 days as a local treatment.

After the first day of using the drug, pain in the oral cavity decreased, the pain disappeared on the 2nd day, and the inflammatory foci decreased on the 3rd day of treatment (hyperemia, edema decreased). After treatment, the patient does not complain, the mucous membrane of the oral cavity is pale pink, moist, isolated papules remain without signs of inflammation.

Bibliography:

1. Dovzhansky S.I. Clinic, immunopathogenesis and therapy of lichen planus / S.I. Dovzhansky, N.A. Slesarenko // Ross. honey. Journal. - 1998. - No. 6. - S. 348-352.

2. Mashkillayson A.L. Lichen planus. In the book: Diseases of the mucous membrane of the mouth and lips. - M. - 1984. - S.190-204.

3. Litvinov S.L. Local treatment of lichen planus of the oral mucosa // Russian Journal of Skin and Sexually Transmitted Diseases. - 2003. - No. 3. - S. 4444.

4. Petrova L.V., Kushlinsky N.E., Makarov Ya.L. Treatment of patients with leukoplakia of the oral mucosa with spironolactone // Vestn. dermatology and venereology. - 2004. - No. 4. - S.68-69.

5. Rabinovich O. F., Grigoryan A. S., Epeldimova E. L. The use of the drug мп Emparkol ’in the treatment of erosive and ulcerative forms of lichen planus of the oral mucosa // Institute of Dentistry. - 2003. - No. 4. - S. 39.

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7. Samoilova O.P., Molokov V.D., Noskov S.I. et al. Evaluation of the effectiveness of local treatment of sick women with erosive and ulcerative form of lichen planus associated with iodine deficiency // Sib. honey. journal (Irkutsk). - 2007. - No. 5. - S. 44-46.

8. Epeldimova E.L., Rabinovich O.F. Methods of diagnosis and local treatment of diseases of the oral mucosa (lichen planus, recurrent aphthous stomatitis, decubital ulcers) // Dentistry. - 2005. - No. 3. - S. 58-63.

9. Papageorgiou V.P., Assimopoulou A.N., Ballis A.C. Alkannins and shikonins: a new class of wound healing agents // Current Medicinal Chemistry. - 2008 .-- Vol.15. - P.3248-3267.

10. Rabinovich O.F. The use of the drug "Emparkol" in the treatment of erosive and ulcerative forms of lichen planus of the oral mucosa / O.F. Rabinovich, A.L. Grigoryan, E.L .: Epeldimova // Institute of Dentistry - 2003. - No. 4. - S. 39.

11. Systemic and topical corticosteroid treatment of oral lichen planus: a comparative study with long-term follow-up / M. Carbone [et al.] // J. Oral Pathol. Med. - 2003. - Vol.32, No. 6. - P.323-329.

12. Toropova N.P., Sorokina K.N., Levchik H.K. Atopic dermatitis in children - modern clinicopathogenetic aspects of the disease and approaches to external therapy. Pediatrics. 2009; 8 (5): 40-47.

13. Ulrich R. Hengge, Thomas Ruzicka, Robert A. Schwartz, Michael J. Cork. Adverse effects of topical glucocorticosteroids. J Am Acad Dermatol 2006; 54: 1-15.

Claims (1)

A drug for the treatment of erosive-ulcerative and exudative-hyperemic forms of lichen planus in the following ratios of components, g:
Tizol 10.0 Triamcinolone 0.004

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