RU2790528C1 - Method of local treatment of erosive and ulcerative form of flat lichen of the mucous membranes of the mouth - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to therapeutic dentistry and physiotherapy, and can be used for the local treatment of erosive and ulcerative form of flat lichen of the mucous membranes of the mouth. For this purpose, on the 1st, 2nd, 3rd, 4th, 5th, 7th days of therapy the treatment of affected erosive and ulcerative sections is carried out by applying 0.2% hyaluronic acid gel on them for 60 s. Then ozone therapy is performed using a Prozone device with a duration of exposure of 6 seconds at a distance of 1-2 mm from the mucosa. After that, the surface of the mucosa is dried and closed with a self-adhesive Ora-Aid patch until it completely dissolves. On the same days of treatment, 0.5% prednisolone ointment is applied 3 times a day for 5-10 minutes. Then the surface of the mucosa is dried and closed with a self-adhesive Ora-Aid patch until it completely dissolves. On 8, 9, 10, 11, 12, 13 days of local treatment 3 times a day, cover the surface with a self-adhesive Ora-Aid patch until it completely dissolves.

EFFECT: improving the therapeutic effect by increasing the intake of biological substances into the lesion, relieving pain, leveling microbial contamination, reducing the degree of inflammation, enhancing the process of epithelialization and regeneration of the oral mucosa, as well as preventing relapses of the disease.

1 cl, 2 ex

Description

The invention relates to medicine, namely to therapeutic dentistry and physiotherapy, and can be used for local treatment of erosive and ulcerative lichen planus (PL) of the oral mucosa.

PL is a chronic polyetiological inflammatory-destructive disease with an unspecified etiopathogenesis, characterized by a chronic course with relapses. In the development of dermatosis, several theories are considered - neurogenic (stress, chronic nervous strain), hereditary, infectious-toxic, traumatic, viral, autoimmune. Identification of the microbial factor in the form of an increased content of yeast-like fungi of the genus Candida, enterobacteria, Stafylococcus aureus, Leptotrichia spp, enterobacteria. The main etiologically significant microorganisms in patients with erosive-ulcerative form of PL are associations consisting of yeast-like fungi of the genus Candida, Staphylococcus aureus and opportunistic enterobacteria.

Morphological elements on the oral mucosa (MOR) are "mother-of-pearl" papules merging with each other, against which erosions and ulcers are located, their most frequent localization on the distal parts of the buccal mucosa, the lateral surface of the tongue.

Treatment of this disease consists of an integrated approach. The use of general therapy alone leads to an increase in the duration of the disease, frequent relapses, and possible progression of the process to the SOR. Despite the wide choice of modern drugs used in local treatment, and various methods of their application, the selection of optimal local therapy for the erosive-ulcerative form of PL of the oral mucosa continues at the present time.

The pathogenetic basis of the erosive-ulcerative form (EIF) of lichen planus is a violation of the integrity of the epithelium, the presence of inflammatory exudate in the proper mucous layer, inflammatory mediators, toxins, microcirculation disorder with the phenomenon of hypoxia, pronounced morphological, microbiological and immunological changes. The leading mechanism of its occurrence is associated with metabolic disorders in tissues and its individual cells. We have established the relationship between the formation of inflammatory changes in the oral mucosa, nonspecific factors of local immunity, antioxidant protection in unstimulated oral fluid [Method for the differential diagnosis of keratotic processes of the oral mucosa related to "white manifestations" Usmanova I.N., Gerasimova L.P., Kabirova M.F., Khusnarizanova R.F., Usmanov I.R., Minyakina G.F. Patent for invention RU 2544173, 10.03.2015]. Therefore, to influence all the pathological links of the erosive-ulcerative form of PL, local treatment and general therapy (local antiseptics, enzymes, corticosteroid, antihistamines and epithelial drugs) are usually prescribed, complementing each other. This usually increases the risk of developing allergic and adverse reactions, since in the aggregate the pharmacodynamics of all drugs change significantly with their longer circulation in the body and slow elimination.

A known method for the treatment of PL SOR using biologically active substances (BAS) for the normalization of metabolic processes in the body and the epithelium of the oral mucosa, both for general treatment (vitamins A, E, C multivitamins), and for local application of oil solutions of vitamins A, E, carotolina, rose hip oil, sea buckthorn oil, etc. ["Diseases of the oral mucosa: Study guide / Edited by L.M. Lukinykh. - Nizhny Novgorod: NGMI, 1993, p. 73-77]. The disadvantages of this method are the low effectiveness of treatment, long periods of epithelization of erosions and elimination of inflammatory phenomena in complicated forms of PL, short periods of remission of the disease.

A known method for the treatment of lichen planus, which consists in the introduction of desensitizing agents, local application of a hormonal agent to the oral mucosa, as well as a keratoplastic agent in the form of a 4% water-insoluble colloidal solution of chitosan with a deacetylation degree of 0.95, a molecular weight of 100-120 kD. This drug is applied in a thin layer to the affected areas of the oral mucosa for 30 days, which are pre-treated with a 1% hydrogen peroxide solution and dried. 30 days [patent RU 2258516, 2005].

A known method of local treatment of lichen planus of the oral mucosa of a typical form, which consists in the fact that two layers of a medicinal composition of tizol with lidase are evenly applied to the lesion twice a day with an exposure of 15 seconds, not more than 0.01 mm thick, in the ratio: tizol 10 g, lidase 128 UE. The course of treatment is 14 days [patent RU 2540493, 2015].

A known method for the treatment of patients with complicated forms of lichen planus of the oral mucosa, characterized by the fact that a solution of photoditazine is administered, prepared at the rate of 1.4 mg/kg of the patient's body weight and dissolved in 200 ml of 0.9% sodium chloride solution, which is administered by intravenous drip for 30 minutes in a darkened room, then 2 hours after the introduction of the photosensitizer, a session of laser irradiation of pathologically altered tissues of the oral mucosa is carried out with a laser medical device with a wavelength of 661-668 nm, a power of 350-400 mW for 10-15 minutes, with this course is 2-3 procedures with an interval of 4 to 7 days [patent RU 2681528, 2019].

A known method for the treatment of patients with erosive and ulcerative elements of the lesion, which is characterized by the fact that before the start of treatment, a study of local immunity of the oral cavity is carried out, determining the values of immunoglobulin G, immunoglobulin A, lysozyme, the coefficient of balance of factors of local immunity of the oral cavity (Kcb) is calculated, an overlay is prescribed applications with Celestoderm-B ointment 2 times a day on a sterile gauze napkin, holding with a finger, for 20 minutes with an interval of 12 hours, a course of 5 days, then with Keb values \u200b\u200bmore than 1.5, they are carried out 1 time per week, a course of 3 procedures injections of platelet autoplasma at 0.1-0.3 ml per mm2 under morphological elements and along the transitional fold in their projection, with each procedure completed by application with platelet autoplasma on a sterile gauze napkin for 15 minutes, and with Keb values equal to 1 5 and less, are limited to standard therapy, including applications with rosehip oil, oral baths with infusions and herbs and antiseptics [patent RU 2692108, 2019].

A known method for the treatment of erosive form of PL using applications of hyaluronic acid for 28 days, which contributed to a decrease in pain sensitivity within 4 hours, a decrease in the size of the pathological focus [Nolan A., Badminton J., Maguire J., Seymour R.A. The efficacy of topical hyaluronic acid in the management of oral lichen planus. J Oral Pathol Med. 2009;38:299-303].

The closest analogue of the invention is a method of local treatment of the erosive-ulcerative form of PL using ozone therapy on the Prozone apparatus with a nozzle developed by the author for an exposure time of 6 seconds at a distance of 1-2 mm from the area of the treated mucosa, the course of treatment is 10 daily procedures [The use of gaseous ozone in a complex treatment of erosive-ulcerative form of lichen planus of the oral mucosa. Serikova O.V., Kordenko A.N., Kosheleva S.V., Duev R.M. Bulletin of new medical technologies. 2016;23(2):201-205]. The disadvantage of the prototype is the lack of efficiency due to the use of only gaseous ozone.

The objective of the invention is to develop a method for local treatment of EP PL, which ensures the prevention of recurrence of the disease.

The technical result when using the invention is an increase in the therapeutic effect by increasing the supply of biological substances to the lesion, relieving pain, leveling microbial contamination, reducing the degree of inflammation, enhancing the process of epithelialization and regeneration of the COR.

The proposed method of local treatment of erosive-ulcerative forms of PL is carried out as follows. On the 1st, 2nd, 3rd, 4th, 5th, 6th, 7th days of local treatment, erosive and ulcerative lesions localized on the oral mucosa are first treated by applying 0.2% hyaluronic acid gel on them for 60 seconds. Then, erosive and ulcerative lesions of the SOR are treated by ozone therapy on the Prozone apparatus, the duration of exposure is 6 seconds, the distance from the mucous membrane is 1-2 mm. Dry the surface with a swab and cover with a self-adhesive Ora-Aid patch until it is completely dissolved.

During the period of 1, 2, 3, 4, 5, 6, 7 days of local treatment every 6 hours (3 times a day) at home, the patient performs applications of 0.5% prednisolone ointment for 5-10 minutes, drying the surface and closure with self-adhesive Ora-Aid plaster until it is completely dissolved.

On the 8th, 9th, 10th, 11th, 12th, 13th days of local treatment, the surface of the mucous membrane is dried 3 times a day with a swab and covered with a self-adhesive Ora-Aid patch 3 times a day until it is completely dissolved.

Individual hygiene is recommended using a soft toothbrush and hypoallergenic toothpaste (HZP) (with natural active additives, silver ions and lysozyme (HZP with PADIOL).

The proposed method of local treatment of erosive-ulcerative form of PL by treating the mucosa with 0.2% hyaluronic acid gel (Hy + Al Gel), using 7 courses of ozone therapy, every day in combination with applications on the mucosa of 0.5% prednisolone ointment, drying the mucosa and closing the treated surface with a self-adhesive Ora-Aid plaster 3 times a day (after each ozone therapy and applications) until it is completely dissolved, on days 8, 9, 10, 11, 12, 13 of local treatment 3 times a day, closing with a self-adhesive Ora-Aid plaster Aid, in combination, allows you to weaken the influence of secondary microflora, increase the regeneration of the mucosa due to the preservation of healing growth factors on the surface of the wound - leukocytes, macrophages, proteolytic cell enzymes, growth factors.

The use of hyaluronic acid gel (Hy+Al Gel) provides tissue healing by activating and slowing down inflammatory reactions, stimulating cell proliferation, migration and angiogenesis, promotes re-epithelialization through the proliferation of basal keratinocytes. This mechanism of local action on the state of the mucosa in erosive-ulcerative LP is generally of no small importance in local treatment.

The two main ingredients in 0.2% Hy+Al Gel are hyaluronic acid and aluminum in sucralfate. Hyaluronic acid (HA) is a linear polymer of glucuronic acid and the disaccharide N-acetylglucosamine. The main function of HA includes tissue healing, including the activation and slowing down of inflammatory responses, stimulation of cell proliferation, migration and angiogenesis. It also promotes re-epithelialization through the proliferation of basal keratinocytes. HA is a hygroscopic macromolecule, and its solutions are highly osmotic. In the oral mucosa, this property allows control of tissue hydration during periods of inflammation or response to tissue injury leading to ulceration. HA has a high molecular weight and acts as an anti-inflammatory molecule. Studies have proven that HA is effective in the treatment of gingivitis and periodontitis [Pistorius A, Martin M, Willershausen B, Rockmann P. The clinical application of hyaluronic acid in gingivitis therapy. Quintessence Int. 2005;36:531-8, Mendes RM, Silva GA, Lima MF, Calliari MV, Almeida AP, Alves JB, et al. Sodium hyaluronate accelerates the healing process in tooth sockets of rats. Arch Oral Biol. 2008;53:1155-62].

Sucralfate, which is part of the HA, forms a cross-linking viscous paste-like material that can seal the ulcer within 6-8 hours after a single dosing, which plays an important role in the treatment. In addition to this, the water-soluble hydrocolloid PVA 40-88, which is part of the Hy + Al Gel gel, acts, which, being a bioadhesive substance, contributes to additional fixation of the composition and retention of healing components on the surface of the ulcer. These compounds adhere to the surface of the ulcer with the formation of a protective layer [Nolan A., Badminton J., Maguire J., Seymour R.A. The efficacy of topical hyaluronic acid in the management of oral lichen planus. J Oral Pathol Med. 2009;38:299-303].

Cetylpyridinium chloride, which is part of 0.2% Hy + Al Gel, has antiseptic and antimicrobial activity against gram-positive and gram-negative bacteria, yeast-like fungi of the genus Candida and viruses.

Ora-Aid is a healing patch for the oral mucosa with vitamin E, consists of an attached and a protective layer. The adhesive layer (self-absorbable) has a strong adhesion when it is applied and moistened on the mucosa. It is a water-soluble polymer that reacts with moisture (water and saliva) in the mouth for 20-30 seconds and turns into a gel state, after which sticky physical properties appear, sticking to the mucosa. The protective layer for protecting the bonded layer consists of a water-insoluble polymer. It is insoluble in water and covers the wound to protect the relevant area from the environment (bacteria, saliva, food, etc.) in the oral cavity. Relieves pain, protects growth factors, protects the wound during the early stages of healing. Preservation of healing growth factors on the wound surface - leukocytes, macrophages, proteolytic cell enzymes, growth factors. Isolation promotes blood supply and circulation, and also creates conditions for increased cellular activity. Safe and easy to use, easy to cut into different shapes or sizes. Mint flavor reduces bad breath. Contains vitamin E. Attaches in the mouth - upper jaw: 6~12 hours, lower jaw: 4~6 hours.

The proposed method was used in 43 patients with EYaF PL SOR. It was found that pain relief occurs on day 4.5 ± 0.65, hyperemia and erosion surface decrease with partial epithelization on day 6.9 ± 0.90 of treatment, final epithelization and transition to the typical form of PL on day 14 ± 0.95. days of treatment.

The essence of the invention is illustrated by the following clinical examples.

Example 1

Patient 3. 48 years old. Complaints of pain when eating. Objectively: on the mucous membrane of the cheeks against the background of a typical pattern, erosive-ulcerative elements are observed, the mucous membrane around them is hyperimposed, edematous.

Diagnosis: Erosive and ulcerative form of lichen planus of the buccal mucosa, was made on the basis of complaints, anamnesis, objective data and biopsy data. The patient received a local course of treatment according to the proposed method.

On days 1, 2, 3, 4, 5, 6, 7, local treatment of the oral mucosa consisted of the treatment of erosive and ulcerative lesions localized on the oral mucosa by applications of 0.2% hyaluronic acid gel for 60 seconds, treatment of erosive and ulcerative lesions of the SOR by ozone therapy on the Prozone apparatus, the duration of exposure is 6 seconds, the distance from the mucous membrane is 1-2 mm. The surface was dried with a swab and covered with a self-adhesive Ora-Aid patch until it was completely dissolved.

At home, for 1, 2, 3, 4, 5, 6, 7 days of local treatment, 0.5% prednisolone ointment was applied 3 times a day for 5-10 minutes, the surface of the mucosa was dried, and the surface to be treated was covered with a self-adhesive plaster Ora- Aid until its complete dissolution.

On the 8th, 9th, 10th, 11th, 12th, 13th days of local treatment at home, the patients dried the mucosa 3 times a day and closed the mucosa with a self-adhesive Ora-Aid patch until it was completely dissolved.

Individual hygiene was carried out using a soft toothbrush and GZP with PADIOL.

When examined on the 4th day, pain relief is noted, on the 6th day - a decrease in hyperemia and an erosive-ulcerative surface on the mucous membrane in the area of the location of pathological elements, on the 14th day - complete epithelialization of the mucosa and the beginning of the transition to a typical form of PL. The mucous membrane on the 14th day is painless, slightly hyperemic, moderately moistened.

By the 14th day of local treatment, the patients did not complain, with an objective assessment, the oral mucosa is moist, moderately hyperemic with flattened papules against the background of a typical pattern.

Example 2 (treatment according to the prototype). Patient S., 52 years old. Complaints of pain when eating. Objectively: on the buccal mucosa, against the background of multiple papular elements, erosive and ulcerative elements are observed, the mucosa is hyperimposed, painful when taking hot food. Diagnosis: erosive and ulcerative form of lichen planus. The diagnosis was made on the basis of complaints, anamnesis, objective biopsy data. The patient received a traditional course of local therapy. Local treatment of the oral mucosa consisted of antiseptic treatment by oral baths, the use of enzymes, corticosteroid, epithelial therapy against the background of general treatment for 21 days.

On examination on the 6th day, the presence of inflammatory foci was noted, pain persists when taking hot and irritating food, taking medications, roughness of the mucous membrane, on the 8th day there was a decrease in inflammation in the area of erosive and ulcerative elements, on the 10th day partial epithelization, on the 14th day - epithelization and transition to the exudative-hyperemic form. The patient was assigned to continue treatment and preventive measures - the use of an oil solution of vitamin A 1 time per day after meals, 1 time at night for 30 days. A month after the end of treatment, the patient complains of discomfort in the oral cavity, the oral mucosa is partially hyperemic, rough, and there are many papules.

Claims (1)

A method for local treatment of erosive-ulcerative form of lichen planus of the oral mucosa, including the treatment of erosive-ulcerative lesions by ozone therapy on the Prozone apparatus with a duration of exposure of 6 s at a distance of 1-2 mm from the mucosa, characterized in that 1, 2, 3, 4, 5, 6, 7 days of treatment before ozone therapy, erosive and ulcerative lesions are treated by applying 0.2% hyaluronic acid gel on them for 60 s, after ozone therapy, the mucosal surface is dried and covered with a self-adhesive Ora-Aid patch until it is completely dissolved, in addition, 3 times a day, 0.5% prednisolone ointment is applied for 5-10 minutes, then the mucosal surface is dried and covered with a self-adhesive Ora-Aid patch until it is completely dissolved; on the 8th, 9th, 10th, 11th, 12th, 13th days of local treatment, cover the surface with a self-adhesive Ora-Aid plaster 3 times a day until it is completely dissolved.