RU2558827C2 - Method of treating dermatosis and detoxication agent for implementing it - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to dermatology, and describes a method of treating dermatosis based on patient's detoxication by binding toxins with using enterosorbents and discharge them. The method involves dissolving toxins and stimulating diuresis with using an infusion therapy, administering normal saline, administering a diuretic which is presented by lasix, stimulating the blood microcirculation, including at the level of small vessels with using Fraxiparine, low-molecular heparin, with the agent nadroparin calcium; the enterosorbent is Polysorb.

EFFECT: method enables increasing the clinical effectiveness for dermatosis by the smooth effect of the homeostasis system and detoxification, reducing the body intoxication, dehydration and hypercoagulation, improving the small microcirculation and can be used in treating severe forms of chronic dermatosis and psoriasis.

6 cl, 1 tbl, 1 dwg, 2 ex

Description

The invention relates to medicine, namely to dermatology, and can be used in the treatment of patients with severe forms of chronic dermatoses, including psoriasis.

It is known that dermatoses, like psoriasis, are multifactorial diseases, due to the malfunction of various functional systems of the patient’s body for various reasons, therefore, the methods of treating diseases are diverse, aimed at restoring, normalizing the functions of the affected systems and treating the consequences of the failure. The most common methods of treatment are complex, which combine various methods of treatment used with their own schemes for carrying out procedures and using pharmacological agents.

Known methods of treating psoriasis, which include various methods of treatment. The latter include medication, immunocorrecting, immunomodulating, immunostimulating, detoxifying, hyposensitizing, physiotherapeutic, photochemotherapeutic and others (see Russian patents No. 2190406 "Method for the treatment of psoriasis", A61K 31/505, published on 10/10/2003; No. 207; 2077; , A61K 35/28, published October 27, 2012; No. 2412684, “A method for treating patients with exudative psoriasis,” A61H 33/02, published February 2, 2011; No. 2135184, “Method for the treatment of psoriasis,” A61K 31/59, published August 27, 1999; 2154458 "A method for the treatment of psoriasis", A61G 10/02, published but 08/20/2000; No. 2290926 "A method for the treatment of psoriasis", A61P 17/00, published January 10, 2007).

Each method includes its own actions (operations), is accompanied by its own treatments, which are most often selected individually within the framework of generally accepted schemes, have their own restrictions on the use by age of patients, on concomitant diseases, on compatibility with other pharmacological drugs, their effectiveness for each case of the disease . The components of complex treatment can reduce the effect of each other's actions and can even harm the patient when prescribing a large number of drugs, since when they are used, the detoxification organs are stressed.

The disadvantages of the known methods of treatment are the wide spread in the methods of treatment used, the randomness and subjectivity of the choice of both of them, and the selection of their combination, which are associated with the elimination of individual symptoms of the disease. Another disadvantage is their low efficiency, the absence of a tangible result, and therefore long treatment periods, with a short period of remission.

The closest chosen complex method of treatment of psoriasis, which declares a reduction in treatment time and an increase in the period of remission. This method includes desensitization (anti-allergic) therapy, detoxification therapy using enterosorbent, the use of external ointment agents, photochemotherapy with ultraviolet irradiation of the patient with ammifurin, the appointment of vitamins and sedative collection (RF Patent No. 2290926 "Method for the treatment of psoriasis", A61P 17/00, published on January 10, 2007). The treatment is complex, each component of its method pathogenetically affects different zones of the body’s damage and affects the course of the disease.

The disadvantage of the closest analogue is its limited use due to the presence of restrictions and contraindications for the use of ammifurin, which can lead to side effects of such treatment. For the use of ammifurin, there is an impressive list of contraindications, namely:

- hypersensitivity;

- acute gastritis;

- peptic ulcer of the stomach and duodenum;

- pancreatitis;

- hepatitis;

- cirrhosis of the liver;

- jade;

- diabetes;

- cachexia;

- arterial hypertension;

- decompensated endocrine diseases;

- thyrotoxicosis;

- tuberculosis;

- blood diseases;

- chronic heart failure;

- malignant and benign tumors;

- pregnancy;

- lactation period;

- cataract;

- multiple pigmented nevus.

Psoriasis is known to be associated with pathology of the cardiovascular system (arterial hypertension, chronic cardiovascular failure) and others (diabetes mellitus), i.e. just with the main disorders that accompany psoriasis and for which the drug ammifurin has contraindications. The drug does not directly affect the hemostatic system. This is a photosensitizing agent to enhance the production of melanin in the skin under the influence of ultraviolet radiation.

With caution, it can be used in children (up to 5 years) and in old age (over 60 years).

Another disadvantage of the closest analogue is its lack of effectiveness, a long treatment period, a long stay of patients in a hospital until their condition improves.

A known method of treatment, hard acting on the body systems, can cause its imbalance and lead to a deterioration of the patient's condition.

The objective of the invention is to increase the effectiveness of the method of treatment, reducing its duration, increasing the period of remission and thereby improving the quality of life of patients. The technical result is a mild effect on the hemostatic system and detoxification, reduction of intoxication, dehydration and hypercoagulation of the body, improvement of microcirculation in small vessels.

The problem is solved and the technical result is achieved in a method for the treatment of dermatoses, in particular psoriasis, which, as in the prototype, is based on the detoxification of the patient's body by binding toxins using enterosorbent and their removal, and also includes local treatment with external agents.

The difference from the prototype is the treatment according to the following scheme:

- carry out “dilution of toxins” and stimulation of diuresis using infusion therapy by the introduction of crystalloids - isotonic physiological solutions of a concentration of about 0.9%, for example, sodium chloride solution, in an amount of 1000-1600 ml per day by intravenous drip - depending on body weight and pathology diseases

- enter a diuretic, which is used as the drug Lasix, with a dose of a single injection of 10-20 mg per day intramuscularly;

- they stimulate blood microcirculation, including at the level of small vessels, using low molecular weight heparins, for example, fraxiparin with the active principle of calcium nadroparin 0.3-0.6 U / day - subcutaneously;

- Polysorb is used as an enterosorbent in the form of an aqueous suspension in 3-4 doses during the day;

- enter the digestive enzyme, which is used as Creon, Pancytrate.

Known drugs that have antitoxic effects that reduce the intoxication of the body due to the adsorption of toxins from the intestine. These drugs include the Polysorb enterosorbent (www.polisorb.ru). However, its action is not enough to completely cleanse the entire body. In a slagged body, toxins can be concentrated in the blood, causing coagulation and hypercoagulation processes, which is typical for dermatitis, in particular, for various forms of psoriasis. Therefore, know-sorbents are not effective enough in the treatment of dermatitis.

The objective of the invention is also to increase the effectiveness of the treatment of dermatoses using disintegration agents by improving microcirculation in small vessels.

The problem is solved by the use of calcium nadroparin as a detoxification agent. Calcium nadroparin, the trade name Fraxiparin, acting on the microcirculation system from the smallest vessels, reduces hypercoagulation in patients with chronic dermatoses, thereby contributing to the removal of toxins from the microcirculation system, reducing the level of intoxication of the body.

Thus, infusion therapy and stimulation of diuresis are first carried out and enterosorbent, fraxiparin and, at the same time, creon are used at the same time. The toxin dilution procedure is known per se, but in pathology with severe forms of psoriasis (psoriatic erythroderma with joint damage - psoriatic arthritis) and in conjunction with fraxiparin and enterosorbent, the dilution procedure was not used. In such a ligament, several pathogenetic mechanisms are immediately affected - the enterosorbent adsorbs toxins from the intestines (thus reducing intoxication), and fraxiparin has an “antitoxic effect” due to the effect on the microcirculation system - the smallest vessels - arterioles, etc., reduces hypercoagulation in patients with chronic dermatoses, in particular psoriasis. The use of fraxiparin with this pathology will lead to an expansion in the indications of its use. Currently, indications for the use of fraxiparin are only the prevention of thrombosis during surgical interventions and blood coagulation in the extracorporeal circulation system during hemodialysis or hemofiltration, thromboembolic complications in patients with a high risk of thrombosis (in acute respiratory and / or heart failure under intensive care) .

The use of heparin for the treatment of thrombosis and thromboembolism is known, the effect of which is associated with a decrease in thrombosis. However, in the proposed method, low molecular weight heparin, namely fraxiparin with the active principle of calcium nadroparin, has a detoxifying effect, which is its unknown property.

An isotonic aqueous solution of sodium chloride 0.9% was used as a physiological solution.

As a diuretic, Lazix (furosemide) was used, a solution for intravenous and intramuscular administration of 20 mg / 2 ml: ampoules, registration number P No 14865/02, 05.16.2008, owner of the registration certificate Aventis Pharma, Ltd.

Fraxiparin Forte manufactured by GLAXO WELLCOME PRODUCTION was used as low molecular weight heparins, the direct anticoagulant was low molecular weight heparin, injection solution with active principle calcium nadroparin 11400, 15200, 19000 ME anti-Xa / 0.6; 0.8; 1.0 ml, transparent or slightly opalescent, colorless or slightly colored, registration number: P No. 12486/01, 06/07/2010, Owner of registration certificate GlaxoSmithKline Trading, CJSC. As low molecular weight heparins, fragmentin, clexane with a similar mechanism of action can be used.

Polysorb MP, colloidal silicon dioxide, powder for oral administration of white or white with a bluish tint, odorless, with the formation of a suspension upon stirring with water, reg. number Р No. 1140/01, 09/10/2008, Owner of the registration certificate Polisorb, CJSC.

As a digestive enzyme, Creon, the active principle of pancreatin, enteric-soluble capsules size 0 and 00, with a colorless transparent body and an orange-opaque cap, containing light brown microspheres, reg. numbers P No. 15582/01, 05/13/2009, LSR-000832/08, 02/18/2008. Owner of registration certificate ABBOTT PRODUCTS, GmbH.

A treatment method based on a comprehensive detoxification of the patient’s body is as follows.

First, dilution of toxins accumulated in the patient’s body is carried out, for their best subsequent excretion by the excretory system. Dilution of toxins is carried out by introducing an isotonic saline solution with a concentration of 0.9% in a volume of 1000-1600 ml per day, drip intravenously, which also stimulates diuresis, removing the toxin solution from the body. The calculation of the dose of physiological saline is based on the physiological needs. The physiological need of a normal body for fluid is 30 ml per 1 kg of body weight. With various pathologies, the need increases. For example, for every degree C above 37, the need for fluid increases by another 10 ml per 1 kg of body weight. Use of physical 0.9% solution due to several reasons. It is safe, does not cause allergic reactions and is rapidly excreted through the kidneys.

Then they carry out the binding of toxins in the intestinal tract without dissolving them using an enterosorbent. As an enterosorbent use the drug Polysorb in a daily dose in the form of an aqueous suspension of 100-200 mg / kg body weight, with a multiplicity of intake 3-4 times a day. When administered orally in the form of a suspension, the Polysorb preparation captures toxins and their removal in the undissolved form through the gastrointestinal tract. Polysorb in the lumen of the gastrointestinal tract binds and removes endogenous and exogenous toxic substances of various nature, pathogenic bacteria, bacterial toxins, antigens, food allergens, drugs, poisons, salts of heavy metals, radionuclides, alcohol, some metabolic products of the body (excess bilirubin, urea, cholesterol, lipid complexes, metabolites responsible for the development of endogenous toxicosis). To obtain an aqueous suspension of the drug, its required amount is thoroughly mixed in 1 / 4-1 / 2 cups of water (50-100 ml). A suspension is prepared before each dose and is taken 1 hour before meals or 1 hour before other medications. The average daily dose for adults is 8-12 grams. The maximum daily dose in adults is 0.33 g / kg body weight. The dose for children is calculated depending on body weight. The table shows the results of calculating the daily dose of Polysorb MP depending on the patient’s body weight.

The use of this enterosorbent is due to its higher sorption capacity of 300 square meters. g / m compared with other enterosorbents, as can be seen in the graph.

Further stimulate the removal of toxins in the urine. The removal of toxins in the urine is stimulated by the administration of a diuretic in the form of the drug Lasix in a dose of 10-20 mg, which is administered intramuscularly once after the infusion of saline. Lasix accelerates diuresis and the removal of toxins from the body. Despite the prominence of physical stimulation. with a diuresis solution, in patients with a high degree of disease, the removal of toxins from the urine will be delayed due to dehydration (moderate dehydration) due to the severity of the disease. With a diuretic, the process proceeds faster and more efficiently not only from the vascular bed, but also from tissues and cells of the body systems.

At the same time, blood microcirculation in the distal parts of the body at the level of arterioles is improved by the administration of subcutaneously low molecular weight heparins, in particular, the drug Fraxiparin. Fraxiparin, when administered subcutaneously at a dose of 0.3-0.6 U / day, as a direct-acting anticoagulant, is characterized by high activity against blood coagulation factor Xa due to its high ability to bind to antithrombin III (AT III), it stimulates microcirculation blood in the microvasculature at the level of small and tiny vessels, dissolving blood clots. Improving blood microcirculation based on changes in the anti-Xa factor activity of plasma, fraxiparin also helps to dilute toxins in small vessels and remove them through the excretory system, also exhibiting a pronounced antitoxic effect. Low molecular weight heparins improve the course of the disease, affect not only microcirculation, but also reduce hypercoagulation.

Patients with psoriasis, especially in its severe form, suffer from various diseases of the gastrointestinal tract, which leads to stagnation of food. A large amount of undigested food accumulates in the intestine, which accumulate in the form of toxins, and the waste products of gram-negative bacteria that inhabit the intestine enter the bloodstream. This exacerbates the course of the disease. To eliminate these phenomena, it is necessary to increase the efficiency of the gastrointestinal tract. Increasing the efficiency of the digestive tract is carried out using an enzyme to improve the digestion of food, which results in a decrease in the total number of unprocessed products, and hence a decrease in the formation of toxins, which, in general, also helps to cleanse the body and improve the patient's condition. According to normal clinical practice, the patient should receive at least 20000-50000 ED Ph. Eur. lipases. When treated with Creon ^® (Creon ^® 10000, Creon ^® 25000, Creon ^® 40000), the average initial dose of lipase is 10000-25000 PIECES of Ph. Eur. Reception of creon is carried out together with each meal in a dose from 20,000 to 75,000 PIECES Ph Eur./kg. However, higher doses may be required in order to minimize steatorrhea and maintain a good nutritional status. When taking an enzyme-containing drug, normalization of the gastrointestinal function is carried out, the absorption process of toxins, including endotoxins, is reduced.

The proposed treatment regimen is used as part of traditional (complex) therapy for patients with severe forms of psoriasis (common forms, including primarily psoriatic erythroderma with joint damage (psoriatic arthritis), as an extreme manifestation of psoriasis. These patients have a significant violation of the hemostasis system, blood is in a state of increased coagulability - hypercoagulation, and the proposed scheme greatly facilitates the course of the disease. The effect on the hemostatic system is carried out gently, without significant fluctuations in the coagulation and anticoagulation systems.The authors associate this pathology with the violation of hemostasis and hypercoagulation, since the blood flow suffers in the small and, especially, in the smallest vessels, which causes a violation in microcirculation system Low molecular weight heparins (fraxiparin), among other things, have a pronounced detoxification property due to the effect on microcirculation, enterosorbent (polysorb) binds current ins, and infusion therapy (Phys. solution) with a diuretic (lasix) contribute to the stimulation of diuresis, the active elimination of toxins in the regime of forced diuresis. In addition, physical. the solution reduces dehydration. Moderate dehydration, manifested by complaints of patients with dry mouth or even thirst, enhances hypercoagulation and, as a result, exacerbates the course of the disease.

The table shows the results of calculating the daily dose of Polysorb MP.

The graph shows the sorption capacity of the main sorbents.

The following are examples of the implementation of the proposed invention.

EXAMPLE No. 1. Patient N., 52 years old. The diagnosis upon admission to the hospital is psoriatic erythroderma. Complaints on admission of "redness of the skin, chills (fever up to 39 ° C), dry mouth, a feeling of" tightness of the skin ", decreased appetite, severe itching, pain in the joints." With an objective examination, the pathological process is generalized in nature, localized throughout the skin in the form of erythroderma. The condition is serious, the severity of the condition is due to intoxication, moderate dehydration, hypercoagulation. Against the background of traditional therapy - a condition without significant improvement, after a clinical expert commission (KEK, after 21 days) a decision was made to extend hospitalization in the inpatient unit.

The patient was assigned:

- Saline solution of 0.9% 1400 ml iv drip No. 6,

- Lasix 20 mg / m (after infusion) No. 4,

- Fraxiparin 0.3 subcutaneously - 2 times a day No. 3 and further 0.3 - 1 time per day No. 3.

- Polysorb 6 g per day in the form of a suspension, divided into 3 doses until clinical improvement,

- Creon 25000 - 3 times a day after meals until clinical improvement,

- local treatment until clinical improvement.

After 10 days, a significant improvement was noted - a decrease in itching, the disappearance of chills (body temperature 36.9 ° C) and thirst, normalization of appetite, improved sleep, decreased pain in the joints, dry skin. There was a regression (reverse development) of the clinical manifestations of psoriatic erythroderma.

EXAMPLE No. 2. Patient I., 37 years old. The diagnosis upon admission to the hospital is psoriatic erythroderma, psoriatic arthritis. Complaints on admission of "redness of the skin, chills (fever up to 38.5 ° C), thirst, a feeling of" tightness of the skin ", lack of appetite, severe itching, deformation and pain in the joints." An objective examination revealed that the pathological process is generalized in nature, localized throughout the skin in the form of erythroderma; there is a restriction of movements and deformation of all joints. The condition is serious. Against the background of traditional therapy - a condition without improvement.

The patient was assigned:

- Saline solution of 0.9% 1200 ml in / drip No. 8,

- Lasix 10 mg / m (after infusion) No. 6,

- Fraxiparin 0.3 subcutaneous - 2 times a day No. 7,

- Polysorb 6 g per day in the form of a suspension, divided into 3 doses until clinical improvement,

- Creon 25000 - 3 times a day after meals until clinical improvement,

- local treatment until clinical improvement.

After 8 days, a significant improvement was noted - a decrease in itching, the disappearance of chills (body temperature 36.9 ° C) and thirst, improved appetite, a decrease in soreness in the joints, dry skin. There was also a regression of the clinical manifestations of psoriatic erythroderma.

The treatment regimen in accordance with the invention was applied to 45 patients with severe forms of psoriasis - with psoriatic erythroderma (including in combination with psoriatic arthritis), common forms of psoriasis (i.e., with significant skin damage, primarily with severe manifestations of intoxication, dehydration and the presence of concomitant pathology). It was possible to reduce the symptoms of the disease, to achieve remission within 10-12 days with a hospitalization period of known methods of treatment at 21 days. After the indicated course of treatment, the course of the disease was significantly facilitated and the remission was prolonged. In some cases, after the first infusion, nat. a solution, the use of a diuretic, enterosorbent and the administration of fraxiparin showed a significant effect, the well-being of all patients improved, and the symptoms of the disease were reduced. Patients with severe forms of psoriasis, as a rule, are referred for treatment up to 3-4 times a year. In some patients treated with the proposed method, the hospitalization period decreased to 1-2 times, which already indicates the effectiveness of the proposed method of treatment compared with the known ones.

Table of calculation of the daily dose of Polysorb MP Patient body weight in kg The average dose per day up to 5 0.3-0.7 g 5-10 0.7-1.5 g 10-20 1.5-3 g 20-40 3-6 g 40-60 6-9 g more than 60 9-12 g

Claims (6)

1. A method of treating dermatoses, based on the detoxification of the patient’s body by binding toxins using enterosorbent and their removal, characterized in that the toxins are diluted and diuresis stimulated using infusion therapy with physiological saline, a diuretic is used, which is used as the drug Lasix, carried out stimulation of blood microcirculation, including at the level of small vessels, using low molecular weight heparin - fraxiparin with the active principle of nadroparin calcium, Polysorb is used as an enterosorbent in the form of an aqueous suspension, a digestive enzyme is introduced, and the proposed treatment regimen is used as part of traditional therapy, which includes local therapy, carried out before clinical improvement. 2. The method according to claim 1, characterized in that as a physiological solution, a sodium chloride solution of 0.9% is administered in an amount of 1000-1600 ml per day intravenously. 3. The method according to claim 1, characterized in that Lasix is administered intramuscularly with a single dose of 10-20 mg per day. 4. The method according to claim 1, characterized in that fraxiparin is administered at a dose of 0.3-0.6 U / day subcutaneously. 5. The method according to claim 1, characterized in that Polysorb is used as an aqueous suspension in 3-4 doses during the day. 6. The method according to claim 1, characterized in that as a digestive enzyme use Creon or Pancytrate.

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