RU2787970C1 - Method for treatment of patients with rosacea - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to dermatology, and can be used in the treatment of patients with rosacea. The method includes taking doxycycline 100 mg per day orally and applying azelaic acid - 15% gel - 2 times a day to all affected areas of the skin. As a drug, ethoxidol is additionally prescribed orally at 100 mg 3 times a day for a course of 30 days.

EFFECT: method provides a more pronounced therapeutic effect, long-term remission, does not cause side effects, allergic reactions, has a noticeable antioxidant effect and leads to the normalization of the clinical picture of the disease due to the additional intake of ethoxidol in the specified dosage.

1 cl, 3 ex

Description

The invention relates to medicine, namely to dermatology, and can be used in the treatment of patients with rosacea.

Rosacea is one of the most common chronic inflammatory dermatoses of the face, characterized by erythema, telangiectasias, inflammatory papules, pustules with periodic episodes of exacerbation and remission. Inflammation plays a central role in the pathophysiology of rosacea, which is associated with processes acting through various mechanisms, including vascular changes, ultraviolet and oxidative tissue damage. Oxidative stress is the basis for many inflammatory skin diseases and is very important in the pathophysiology of rosacea. Oxidative stress occurs as a result of an imbalance between the body's pro-oxidant and antioxidant defenses. Rosacea patients show imbalances in the oxidative and antioxidant systems. In this regard, the search for drugs that affect the antioxidant mechanisms of the pathogenesis of rosacea is very important and appropriate.

There is a known method "Method for the treatment of patients with rosacea" (RU 2321399 C1, 10.04.2008), which is carried out by intravenous administration of sodium thiosulfate, metronidazole and external treatment with 1% metronidazole gel, characterized in that it is additionally subcutaneously injected into the lesions on the skin of the face ozone-oxygen mixture with a concentration of 3000 mcg / l, 1-2 ml with a total volume of 15 ml 3 times a week for 4 weeks.

The disadvantage of this method is its limited use due to the presence of restrictions and contraindications for use. Contraindications to ozone therapy are all blood clotting disorders, including thrombocytopenia, hemophilia, hyperthyroidism, a tendency to convulsions, an allergic reaction to ozone, acute alcohol intoxication, hypoglycemia, acute pancreatitis, menstruation, deficiency of the enzyme glucose-6-phosphate dehydrogenase, the use of drugs, leading to decreased blood clotting.

A known method of oral treatment of patients with rosacea metronidazole, which has an antioxidant effect and is used in a daily dose of 1.0-1.5 g for 4-6 to 8 weeks (Adaskevich V.P., Kozin V.M. Skin and sexually transmitted diseases. Textbook. - M.: Med. lit.. -2006. - S. 350. https://www.studmed.ru/adaskevich-v-p-kozin-v-m-kozhnye-i-venericheskie-bolezni_782cc4843b6.html; Pinson I Ya., Verkhoglyad I.V., Semochkin A.V. Modern methods of treatment of rosacea. 2012. - No. 10. - P.12-26. https://www.lvrach.ru/2012/10/15435544;

Miyachi, Y. Potential antioxidant mechanism of action of metronidazole: implications for the treatment of rosacea. Adv Therapy 18, 237-243 (2001). https://doi.org/10.1007/BF02850193;

Narayanan S., Hunerbein A., Getie M. et al. Purging properties of metronidazole on oxygen free radicals in the model system of skin lipids. JPP. - 2007. - No. 59. P.1125-1130. https://onlinelibrary.wiley.com/doi/epdf/10.121l/jpp.59.8.0010).

The disadvantage of this method is the possible appearance of the digestive system: diarrhea, anorexia, nausea, vomiting, intestinal colic, constipation, metallic taste and dry mouth, glossitis, stomatitis, pancreatitis; on the part of the nervous system, there may be dizziness, impaired coordination of movements, ataxia, confusion, irritability, depression, irritability, weakness, insomnia, headache, convulsions, hallucinations, peripheral neuropathy. Possible allergic reactions such as urticaria, skin rash, skin flushing, nasal congestion, fever, arthralgia. On the part of the genitourinary system, dysuria, cystitis, polyuria, urinary incontinence, candidiasis, urine staining in red-brown color are possible. Also, during treatment, neutropenia, leukopenia, flattening of the T wave on the ECG may appear. Contraindications for metronidazole are leukopenia (including history), organic lesions of the central nervous system, liver failure (in the case of high doses), pregnancy (first trimester), lactation, hypersensitivity. Contraindicated in liver failure (in case of high doses). With caution prescribed for violations of liver function, liver failure, renal failure, with severe violations of kidney function (CC less than 10 ml / min), the daily dose should be halved. During the treatment period, ethanol is contraindicated (possible development of a disulfiram-like reaction: spastic abdominal pain, nausea, vomiting, headache, sudden rush of blood to the face). With prolonged therapy, it is necessary to control the blood picture. With leukopenia, the possibility of continuing treatment depends on the risk of developing an infectious process. The appearance of ataxia, dizziness and any other deterioration in the neurological status of patients requires discontinuation of treatment. May immobilize treponema and lead to a false positive Nelson test. Colors urine dark. Enhances the effect of indirect anticoagulants, which leads to an increase in the time of formation of prothrombin. Similar to disulfiram, it causes ethanol intolerance. Simultaneous use with disulfiram can lead to the development of various neurological symptoms (the interval between administration is at least 2 weeks). Cimetidine inhibits the metabolism of metronidazole, which can lead to an increase in its concentration in the blood serum and an increase in the risk of side effects. The simultaneous administration of drugs that stimulate microsomal oxidation enzymes in the liver (phenobarbital, phenytoin) can accelerate the elimination of metronidazole, resulting in a decrease in its plasma concentration.

A known method for correcting lipid peroxidation and the antioxidant system in the complex treatment of patients with erythematoeno-telangiectatic, papulopustular and pustular-nodular forms of rosacea using the drug phosphogliv inside 2 capsules 3 times a day (1 capsule contains phosphatidylcholine 0.065 g and trisodium salt of glycyrrhizic acid 0.035 g) within four weeks against the background of standard treatment (Kobtseva O.V. Influence of essential phospholipid phosphogliv on the nature of the course and the effectiveness of complex therapy in patients with rosacea. Abstract of the thesis. candidate of medical sciences. Kursk. -2012. - 21 p. https:// new-disser.ru/_avtoreferats/01005092179.pdf).

The disadvantage of this method is the presence of restrictions and contraindications for use. Contraindications are antiphospholipid syndrome, hypersensitivity to glycyrrhizic acid, phosphatidylcholine or other components of the drug. With caution, the drug should be prescribed to patients with portal hypertension, arterial hypertension. If you have these diseases, you should consult your doctor before starting the drug.

There is a known method "Method of treating rosacea" (RF patent No. 2640447), which is carried out by exposure to a physical factor, characterized in that the treatment of pathological foci of the facial skin is performed on a Dualis SP Spectro Nd:YAG laser with a wavelength of 1064 nm, using a scanning handpiece S -11.40 J / cm2, frequency 3 Hz, pulse length 30-50 ms, while the number of treatments per procedure is from 1 to 3 times, then the oxygen-ozone mixture obtained at the Medozons BM installation is immediately sequentially injected into concentrations of 1300-1600 mcg / l both directly under the lesions and over the entire surface of the face, maintaining a distance between injections of 2.5 cm, while 6 procedures are carried out with an interval of 2 times a week, then 3 procedures with an interval of 1 time per week and 3 procedures with an interval of 1 time per month, repeat the course of treatment after 1.5-3 months (Gerasimenko M.Yu., Konovka E.P., Vasilyeva E.S. and others. Method for the treatment of rosacea. Patent of the Russian Federation No. 2640447. https ://patenton.ru/patent/RU26404 47C1.pdf)

The disadvantage of this method is the contraindications of ozone therapy in the form of blood clotting disorders, an allergic reaction to ozone, hypoglycemia, acute pancreatitis, bleeding of a different nature, increased thyroid function, thrombocytopenia, the use of drugs leading to a decrease in blood clotting, acute cerebrovascular accident. Contraindications to the use of the Nd:YAG laser are blood diseases, thyroid pathologies, defects on the surface of the skin that should be exposed to the laser, purulent pathologies of an acute or chronic nature, poor blood clotting, and mental disorders.

The closest in essence, the prototype method for the treatment of patients with rosacea, according to the totality of matching signs and the achieved technical result, is "A method for correcting the antioxidant status in the treatment of patients with erythematous-telangiectatic and papulopustular forms of mild to moderate rosacea" (RU 2741988 C1, 02/01/2021), which is carried out by daily oral administration of an antioxidant drug against the background of external use of azelaic acid, cream 20% or gel 15%, 2 times a day in the morning and evening, characterized in that patients take as an antioxidant drug Cytoflavin 2 tablets 2 times a day, morning and evening 30 minutes before meals, for 21 days. Long-term observations have shown that along with a positive therapeutic effect when using this method, in a significant percentage of cases, the development of undesirable side effects is observed.

The disadvantage of this method is its limited use due to the fact that cytoflavin should be administered with caution to patients with diseases of the digestive system (erosion, gastric and / or duodenal ulcers, gastritis, duodenitis) in the acute phase, with arterial hypotension, with nephrolithiasis, concomitant gout, hyperuricemia.

In addition, during treatment, riboflavin in the composition of the drug reduces the activity of some antibiotics (tetracyclines, erythromycin, lincomycin), and is incompatible with streptomycin. Ethanol, tricyclic antidepressants, blockers of tubular secretion reduce the absorption of riboflavin, and thyroid hormones accelerate its metabolism. In case of impaired renal function, the drug should be used with caution in nephrolithiasis. With arterial hypertension, dose adjustment of antihypertensive drugs may be required. In patients with diabetes mellitus, treatment should be carried out under the control of blood glucose concentration. During the treatment period, intense staining of urine in yellow is possible.

The objective of the invention is to increase the therapeutic efficacy of the method for the treatment of patients with rosacea, improve the clinical dermatological status of patients, reduce the duration of therapy, increase the period of remission and thereby improve the quality of life of patients.

The solution to this problem and the technical result is achieved in a method for the treatment of patients with rosacea, which, as in the prototype, is based on the antioxidant activity of the drug, by improving the antioxidant status of the patient by treating according to the following scheme: 100 mg of ethoxydol with the active ingredient ethylmethylhydroxypyridine malate orally 3 times a day for a course of 30 days.

The claimed method is carried out as follows. Patients on the background of standard therapy (doxycycline 100 mg per day orally, externally: azelaic acid 15% gel) were prescribed ethoxidol - an inhibitor of free radical processes, has a membrane-protective, antitoxic, nootropic, anticonvulsant, anxiolytic effect, increases the body's resistance to stress in the form of tablets of 100 mg with the active ingredient ethylmethylhydroxypyridine malate containing acetylglutamic acid (N-acetyl L-glutamic acid), deanol (2-dimethylaminoethanol), glycine, microcrystalline cellulose, povidone (collidone 90F), lactose monohydrate (milk sugar), pregelatinized starch (starch 1500 ), colloidal silicon dioxide (aerosil), magnesium stearate, sodium croscarmellose (primellose), sodium cyclamate, orange flavor, used as excipients, were prescribed to patients with rosacea in addition to standard therapy 3 times a day for 30 days. The use of ethoxidol showed that the drug reduces the duration of treatment, contributes to the normalization of the antioxidant system, and provides an increase in the body's resistance to the effects of various damaging factors. Ethoxydol was administered to patients with rosacea in addition to standard therapy at 100 mg 3 times a day for 30 days.

The examples given, reflecting the results of the study and the clinical assessment of the use of ethoxidol in comparison with conventional methods of treatment, reveal the essence of the invention and demonstrate the effectiveness of the proposed method.

Clinical example 1.

Patient M., aged 36, complained of rashes in the face, located mainly in the central part, burning sensation. Tides are not noted. Over the past year, she applied for medical help for a skin disease 4 times, was treated by a therapist without a successful effect. Objectively: on examination, the skin process was localized in the face, characterized by mild erythema and telangiectasias, in the cheeks, hemispherical foci, red in color, 0.1-0.3 cm in diameter, papular elements tend to merge, peeling.

Subjectively: there is no pain, a slight burning sensation, itching, notes the chronic course of the disease with a pronounced staging of clinical manifestations.

Dz: Rosacea, erythematous-papular form.

Concomitant diseases: arterial hypertension, gastritis, hepatic steatosis, history of coronary artery disease.

The patient received systemic treatment: doxycycline 100 mg per day orally, externally: azelaic acid 15% gel was applied to all affected areas of the skin, gently rubbing 2 times a day (morning and evening). Additionally included etoksidol 100 mg 3 times a day daily for 30 days. After 4 weeks of therapy, erythematous foci regressed, papular inflammatory elements decreased sharply, peeling and itching of the skin of the face disappeared, which indicates a significant clinical improvement.

Before and after therapy with the inclusion of ethoxidol, studies of the antioxidant status were carried out. Before treatment, dysfunction of superoxide dismutase, lipid peroxidation was revealed. After therapy with the inclusion of ethoxidol, the studied parameters of the antioxidant status and the clinical picture were normalized.

Clinical example 2.

Patient F., aged 48, complained of rashes on the skin of the face, hot flashes, intense skin itching. Over the past year, she applied for medical help for a skin disease 5 times, but the complete resolution of the skin process was not observed. There was no effect against the background of standard therapies.

Objectively: On examination, the skin process is localized in the forehead, chin, cheeks on both sides in the form of papules reaching a size of approximately 3-4 mm, erythema of a stagnant pink color without clear boundaries, slight finely lamellar peeling.

Subjectively: intense itching, burning sensation of the skin.

Dz: Rosacea, erythematous-papular form.

Concomitant diseases: chronic gastritis, chronic bronchitis, hypertension, frequent SARS, atherosclerosis.

The patient received treatment: doxycycline 100 mg per day orally, externally: azelaic acid 15% gel was applied to all affected areas of the skin 2 times a day (morning and evening). Additionally included etoksidol 100 mg 3 times a day daily for 30 days. After 4 weeks of therapy, erythematous foci completely regressed, perifollicular papules leveled out, single elements of pale color remained, and she did not present subjective complaints.

Before and after therapy with the inclusion of ethoxidol, studies of the antioxidant status were carried out. Before treatment, dysfunction of superoxide dismutase, lipid peroxidation was revealed. After therapy with the inclusion of ethoxidol, the studied parameters of the antioxidant status and the clinical picture were normalized.

Clinical example 3.

Patient V., aged 54, complained of changes in the face, burning, itching. Despite the therapy, relapses of the disease occurred with a frequency of 4-5 times a year. Standard methods without positive dynamics.

Objectively: on examination, the skin process was localized on the cheeks and lateral surfaces of the nose in the form of centrofacial erythema of moderate severity of bluish-reddish color, perifollicular papules of a rounded shape with clear boundaries, up to 0.2-0.5 cm in diameter.

Subjectively: peeling, itching.

Dz: Rosacea, erythematous-papular form.

Concomitant diseases: chronic tonsillitis, iron deficiency anemia, ischemic heart disease, chronic doudenitis, a history of appendectomy.

Treatment was carried out according to the above method. The patient tolerated the treatment very well. After 5 weeks, the patient did not notice a deterioration in the condition of the skin of the face, the appearance of new rashes, peeling or itching. Skin process with significant improvement, single papular elements are noted.

Before and after therapy with the inclusion of ethoxidol, studies of the antioxidant status were carried out. Before treatment, dysfunction of superoxide dismutase, lipid peroxidation was revealed. After therapy with the inclusion of ethoxidol, the studied parameters of the antioxidant status and the clinical picture were normalized.

The proposed method of influencing the antioxidant system of the body in rosacea, which is manifested by a change in antioxidant parameters, was tested on an outpatient basis. The results of treatment were evaluated by the clinical method and the method of laboratory diagnostics.

When using ethoxidol, there is a significantly more pronounced therapeutic effect compared to traditionally accepted methods of treatment and a beneficial effect on the course of the disease.

One month after the start of the study, the therapeutic effect index (TE) was assessed. Evaluation of ITE treatment was performed by the percentage of reduction in the severity of rosacea, expressed in points, one month after the therapy. For this we used the formula:

where A1 is the initial severity of rosacea, A2 is the severity of rosacea after treatment.

The use of ethoxidol in the complex therapy of patients with rosacea increases the effectiveness of therapeutic measures, which makes it possible to achieve a clinical improvement in the dermatological status of patients with rosacea by 88.1% compared with the group receiving standard treatment.

The drug does not have a toxic effect, does not cause side effects, allergic reactions, has a positive effect on lipid peroxidation, increases the activity of superoxide oxidase, in addition, ethoxidol has a noticeable antioxidant effect, has a membrane-protective effect.

The application of the claimed method by the end of therapy with ethoxidol against the background of standard treatment contributed to the improvement in the following indicators, which turned out to be the most informative.

Compared with the control group of standard treatment, patients noted:

- faster transition to the stabilization stage;

- earlier terms of resorption of papules, cessation of the appearance of new rashes, disappearance of itching, regression of rashes, disappearance of erythema;

- a positive clinical result, all patients tolerated the prescribed treatment well, in no case was there any exacerbation of the skin process;

- there was a normalization of the main parameters of the antioxidant system: the signs of violations of superoxide dismutase, catalase, glutathione reductase, glutathioperoxidase were eliminated, which underlies the therapeutic effect.

After carrying out the specified course of treatment, the course of the disease was significantly facilitated and remission was prolonged. In some cases, already after the first weeks of taking ethoxidol, a significant effect was observed, the state of health improved in all patients, and the symptoms of the disease were reduced.

The proposed method for the treatment of patients with rosacea with the use of ethoxidol satisfies the criteria for novelty, since when determining the level of technology, no agent was found that has characteristics that coincide with the use of a drug in the complex therapy of patients with rosacea, which is an inhibitor of free radical processes that has a membrane-protective, antitoxic, nootropic, anticonvulsant, anxiolytic an action that increases the body's resistance to stress, which was prescribed in addition to standard therapy, 100 mg of ethoxidol with the active ingredient ethylmethylhydroxypyridine malate orally 3 times a day for 30 days. The use of ethoxidol showed that the drug leads to a significant improvement in the clinical picture, reduces the duration of treatment, and contributes to the normalization of the antioxidant system.

The method for treating patients with rosacea using ethoxidol has an inventive step, since no technical solutions have been identified that have features that coincide with the distinctive features of this invention, and the influence of the distinctive features on the specified technical result has not been established.

Treatment with ethoxydol can be used in patients of various age groups with comorbidities, regardless of the seasonality of dermatosis. Long-term use of antioxidant correction and repeated courses are possible.

The method of treating patients with rosacea with the use of ethoxidol showed its high efficiency, no side effects, stable remission, accompanied by the normalization of the antioxidant system and a reduction in the duration of treatment. Therefore, the claimed technical solution can be implemented in the activities of healthcare organizations, through the use of ethoxidol in the complex therapy of patients with rosacea, which meets the criteria for inventions. The invention provides high efficiency in the treatment of patients with rosacea.

Claims (1)

A method for treating patients with rosacea, including systemic treatment: taking doxycycline 100 mg per day orally and applying azelaic acid - 15% gel - 2 times a day to all affected areas of the skin, characterized in that ethoxidol is additionally administered orally as a drug 100 mg 3 times a day for 30 days.