RU2742976C1 - Method of treating allergic diseases - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine and concerns a method of treating allergic diseases based on using autologous serum, where the autologous serum is obtained from the patient's venous blood by holding at a temperature of +4°C for 20 minutes for retraction and clot formation and subsequent centrifugation for 40 minutes at rate of 3000 rpm, obtained autologous serum is introduced subcutaneously into the lower third of the shoulder daily or every second day, first in dilution of 1:100 sequentially in doses of 0.4 ml, 0.8 ml, 1.2 ml and 1.6 ml, then serially administered in the same doses in dilution 1:10 and further in the same sequence and in the same doses.

EFFECT: invention provides relief of an aggravated allergic disease in the process of treatment, normalization or a tendency to it of laboratory, functional and immunological indicators, disappearance of fast fatigue, improved psychoemotional status and patient's quality of life, prolonged remission periods between therapeutic courses.

4 cl, 3 dwg, 2 ex

Description

Scope of the invention

The invention relates to medicine, namely, allergology and can be used by allergists in the conditions of allergological offices of clinics, hospitals, medical centers.

State of the art

Against the background of the development of civilization and progress, there is a steady increase in the number of allergic diseases, which is due to the increasing pollution of the biosphere, the abuse of pharmacological agents, pronounced chemicalization at work and in everyday life, as well as a decrease in contact with nature at an early age.

Currently, for the treatment of allergic diseases, along with drug therapy, non-specific immunotherapy and drugs obtained from the patient's own blood are increasingly used.

The known "Method for the treatment of chronic recurrent inflammatory diseases of the nasal mucosa and paranasal sinuses by the method of endonasal autolymphocytotherapy", including recurrent polyposis rhinosinusitis (patent RU 2403071, IPC: A61M31 / 00, publ. 10.11.2010).

The method includes preliminary obtaining autologous lymphocytes from the patient's venous blood, culturing the obtained lymphocytes together with an immunomodulator, preferably immunophan, and subsequent introduction of 0.1 to 3.0 ml of a suspension of lymphocytes containing 10 ⁶ -10 ⁷ cells / ml into the paranasal sinuses with an interval between injections from 2 to 7 days.

The disadvantages of this method are: the need to take the patient's blood before each administration procedure throughout the course, the stage of cell cultivation for 1-6 hours, involving the use of immunomodulators, the need to use additional consumables when carrying out an invasive procedure for the introduction of a suspension of lymphocytes into the sinuses ...

A known method for the treatment of allergic diseases by autolymphocytotherapy (patent RU 2395305, IPC: A61M31 / 38, publ. 27.02.2010).

The method includes preliminary obtaining autologous lymphocytes from the patient's venous blood and subsequent subcutaneous administration of a suspension of autologous lymphocytes in saline in doses from 0.1 to 1.0 ml of suspension at a concentration of autologous lymphocytes of 10 ⁵ -10 ⁷ cells / ml. The introduction is carried out subcutaneously 4 to 10 times with an interval of 2 to 6 days, mainly in the lateral surface of the shoulder.

The disadvantages of this method are: the complexity and duration of preparation of the drug from blood, strict requirements of sterile conditions in the preparation of the drug, which limits the possibility of using the method.

The closest in technical essence to the proposed method is a method for the treatment of allergic diseases, including the preliminary receipt of autologous (autoimmune) serum from the patient's venous blood, which is injected intradermally every other day into the area of the inner surface of the forearm, starting with 0.05 ml and further increasing the dose of each subsequent injections per 0.025 ml, until a dosage of 0.2 ml is reached, the general course is 6-7 injections (Art. E. S. Brusilovsky, R. N. Polyak, A. N. Kharzhevskaya. Interdepartmental collection "Allergy", publishing house "Health ", Kiev, 1974, pp. 139 - 141).

The disadvantages of this method include the painfulness of intradermal serum administration, exacerbation of an allergic disease during treatment, which occurred in almost all patients, the maximum strength on the 4th day of treatment, as well as a positive treatment result delayed by 2-3 months. Improvement of the patient's condition, namely a decrease in the frequency, weakening or disappearance of asthma attacks in patients with bronchial asthma, a decrease or disappearance of edema with urticaria and Quincke's edema, occurred after the course of treatment only after 2-3 months.

The proposed invention is aimed at eliminating the aforementioned disadvantages and increasing the effectiveness of the treatment carried out with the use of autologous serum.

Disclosure of the essence of the invention

The technical results achieved with the use of the invention: relief of the exacerbation of the corresponding disease during treatment, normalization or tendency towards it of laboratory, functional and immunological indicators, disappearance of rapid fatigue, improvement of the patient's psycho-emotional status and quality of life, lengthening periods of remission between courses of treatment.

The essence of the proposed method for the treatment of allergic diseases based on the use of autologous serum is as follows. Autologous serum is obtained from the patient's venous blood by holding it at a temperature of + 4 ° C for 20 minutes for retraction and formation of a clot and subsequent centrifugation for 40 minutes at a speed of 3000 rpm. The autologous serum obtained in this way is injected subcutaneously into the lower third of the shoulder daily or every other day, first at a dilution of 1: 100 sequentially in doses of 0.4 ml, 0.8 ml, 1.2 ml and 1.6 ml, then sequentially in the same doses at a dilution of 1:10, and then undiluted serum is injected in the same sequence and in the same doses.

A preservative is added to the serum taken into a sterile test tube after centrifugation.

A 1:10 dilution is obtained by adding 4.5 ml of sterile 0.9% sodium chloride solution to 0.5 ml of undiluted autologous serum.

A dilution of 1: 100 is obtained by adding 4.5 ml of sterile 0.9% sodium chloride solution to 0.5 ml of diluted 1:10 autologous serum.

Each part, namely diluted 1: 100, diluted 1:10 and undiluted autologous serum, is divided into doses: 0.4 ml, 0.8 ml, 1.2 ml and 1.6 ml. Each dose is placed in a separate sterile vacuum tube, labeled and stored until use.

The proposed method of treatment with autologous serum can be used to treat patients with bronchial asthma, atopic dermatitis, allergic conjunctivitis, rhinitis and rhinosinusitis, angioedema Quincke, mild and moderate severity of Lyell's syndrome, frequent recurrent diseases of the upper and lower respiratory tract, etc.

As shown by the use of the proposed method for the treatment of patients with the aforementioned diseases, in the course of treatment, relief of the exacerbation of the corresponding disease, normalization or tendency towards it of laboratory, functional and immunological parameters, disappearance of rapid fatigue, improvement of the psycho-emotional status and quality of life of the patient, as well as lengthening periods of remission between courses of treatment.

Autologous serum prepared from the patient's own blood is known to be the safest preparation for the patient. With subcutaneous injections of autologous serum at a dilution of 1: 100, which has a low concentration of antibodies, the patient's body practically does not feel the reaction of binding of the antibody to the allergen, and at the same time gradually adapts to the drug. Due to this, during the transition to the second stage of treatment with autologous serum diluted 1:10, the human body, which has already adapted, also clinically does not feel the reactions of binding of serum antibodies to allergens. As a result of such a gradual preparation of the body, during the transition to treatment with undiluted autologous serum, exacerbation of the disease does not occur (which occurs in known methods), while the positive therapeutic effect remains and the body's immune defense increases.

The results achieved have made it possible to expand the possibilities of using the method for different age groups, namely, for the elderly and young children.

Treatment of children from 1 year to 12 years old is carried out using the above scheme, but with half doses: 0.2 ml, 0.4 ml, 0.6 ml and 0.8 ml.

Suggested dosages for each dilution: 0.4 ml, 0.8 ml, 1.2 ml, 1.6 ml - for adults; and 0.2 ml, 0.4 ml, 0.6 ml and 0.8 ml for children are the most optimal for achieving the above results.

At the same time, the method is simple to implement and is available for use in any allergy room.

Figure 1 shows an autologous serum treatment regimen for adult patients (Table 1).

FIG. 2 - treatment regimen for children from 1 year to 12 years old (Table 2).

FIG. 3 - a table with the results of treatment of patients with various diseases (Table 3).

Implementation of the invention

The preparation of autologous serum for the treatment of allergic diseases is carried out as follows.

In a sterile room, venous blood is taken from a patient on an empty stomach: the patient sits on a chair, frees the upper limb from clothes, the hand rests on a pillow, on the back of a chair or on a table for blood sampling. The place of blood sampling is treated with an alcohol napkin and the required amount of blood, mainly 5-7 ml of venous blood, is collected with a sterile syringe into a sterile vacuum tube with a rubber stopper. This test tube with blood is placed in a refrigerator at a temperature of + 4 ° C for 20 minutes for the formation and retraction of a clot.

After this time, the tube is placed in a centrifuge and centrifuged for 40 minutes at a speed of 3000 rpm. Then the obtained serum is collected with a sterile disposable syringe with a long needle, a blood preservative is added to it (for example, 0.8 ml of the preservative "Glugitsir" or other preservative is added to the amount of serum at least 3 ml), shake gently and injected into a sterile vacuum tube with rubber stopper.

The thus obtained autologous serum (otherwise: autoserum) is used as follows.

From a vacuum tube with a rubber stopper with undiluted autoserum, 0.5 ml is collected with a sterile syringe, and 4.5 ml of a sterile 0.9% sodium chloride solution is collected with the same syringe. Received in a syringe diluted 1:10 autoserum is introduced into the next sterile vacuum tube.

Similarly, 0.5 ml of a 1:10 diluted autoserum is collected and 4.5 ml of sterile 0.9% sodium chloride solution is added to it, thus obtaining a 1: 100 dilution of autologous serum.

Then carry out the preparation of single doses for subsequent use.

From a test tube with undiluted autoserum, take 0.4 ml with a sterile disposable syringe, inject it into a separate sterile vacuum tube and label this dose. Also, 0.8 ml, 1.2 ml and 1.6 ml doses are taken into separate sterile disposable tubes, which are also labeled.

Similarly, single dosages are prepared from autoserum diluted 1:10 and autoserum diluted 1: 100.

The same principle is used to prepare single doses for children.

Autologous serum treatment regimens for adults and children from 1 to 12 years of age are shown in Figures 1 and 2, respectively.

Treatment is carried out in three stages, gradually increasing the concentration of autoserum from stage to stage; at each stage, four procedures are performed.

Treatment begins with a diluted 1: 100 autoserum, performing a daily or every other day injecting a dose subcutaneously into the lower lateral third of the shoulder, and gradually increasing the dose from procedure to procedure: 0.4 ml, 0.8 ml, 1.2 ml, 1, 6 ml - for adults and 0.2 ml, 0.4 ml, 0.6 ml and 0.8 ml - for children.

Further, treatment is carried out with a diluted 1:10 autoserum using the same scheme with a gradual increase in dose. And then with undiluted autologous serum. In total, 12 injections.

Examples of clinical application of the method.

Clinical example No. 1. Patient Sh. V. A., Orenburg, 16 years old.

Came with a diagnosis: bronchial asthma, atopic form, moderate course, exacerbation, severe frequent attacks of suffocation. The seizures were removed by inhalation of Pulmicort 50 mg in the morning and evening and after inhalation of Berodual, after which bronchospasm still persisted. In the general blood test: erythrocytes 4.7 × 10 ¹² / l, hemoglobin 126 g / l, platelets 276 × 10 ⁹ / l, leukopenia 3.8 × 10 ⁹ / l, in the leukocyte formula: basophils - 0%, eosinophils -1 %, stab neutrophils - 1%, segmented neutrophils - 63%, lymphocytes - 30%, monocytes - 5%, ESR - 5 mm / hour. IgG - 5.0 g / l, IgM - 2.8 g / l, IgA - 2.1 g / l, total IgE - 250 IU / ml. Peak expiratory flow rate 100 l / min (below normal).

Objectively: a state of moderate severity. The skin is pale, clean. The physique is normosthenic. The conjunctiva of both eyes is pale pink. The mucous membrane of the lower nasal passages is pale, the swelling in the nose is moderate. The pharynx is pale pink, the tonsils are clean, not enlarged, the arches are pale pink, the tongue is slightly coated with a white coating, the imprints of teeth on the mucous membrane of the cheeks, along the edge of the tongue. The chest is cylindrical in shape, the shoulders are raised, shortness of breath is of an expiratory nature. Breathing is shallow, in the lungs - weakened, harsh vesicular breathing, high and low tonal wheezing over all fields of the lungs during normal breathing. BH 36 / min. Heart rate 116 beats per minute. The abdomen is soft, painless, the liver does not protrude from the costal margin, the spleen is not palpable. The tapping symptom is negative on both sides. Physiological functions, according to the patient, are normal.

After examination, polyvalent food, household epidermal, and drug allergies were revealed. Preventive measures have already somewhat reduced the frequency of asthma attacks from household, epidermal and drug allergies. A correctly formulated, individually selected hypoallergenic diet reduced the frequency of asthma attacks.

Began to carry out treatment with autologous serum daily according to the scheme (figure 1), starting with a dilution of 1: 100 in doses: 0.4 ml, 0.8 ml, 1.2 ml, 1.6 ml, then at a dilution of 1:10, in the same doses, and then - undiluted autologous serum.

On the sixth day from the start of treatment, the attacks of suffocation disappeared. The patient became cheerful, became more active, gained weight, lethargy, sweating, and fatigue disappeared.

At the end of treatment, repeated examinations were performed. Complete blood count erythrocytes 4.6 × 10 ¹² / l, hemoglobin 134 g / l, platelets 290 × 10 ⁹ / l, leukocytes 5.4 × 10 ⁹ / l, in the leukocyte formula basophils –0%, eosinophils –4%, stab neutrophils -1%, segmented neutrophils -53%, lymphocytes-36%, monocytes-6%, ESR-8mm / hour. PSV on the 7th day of treatment is 145 l / min (increase-28%), on the 19 day of treatment -164 l / min (increase-38%). IgG-14.0 g / l, IgM-0.6 g / l, IgA-0.8 g / l, total IgE-80 IU / ml.

Breathing in the lungs was vesicular, it was carried out in all parts of the lungs, no wheezing was heard during calm and forced breathing. Breathing through the nose is free, the swelling of the mucous membranes of the nose and mouth disappeared, the small uvula returned to normal size. After the end of treatment and the patient returned home, seizures appeared only with the use of an allergenic product. I stopped suffering from colds and viral infections. Repeated treatment, carried out a year later, made it possible to consolidate the results and exclude the occurrence of seizures.

Clinical example No. 2. Patient K. V., 4 years old, Donetsk.

On consultation with an allergist with a diagnosis of atopic dermatitis, allergic rhinoconjunctivitis, sensitization to household, food, pollen allergens.

Complaints at the reception: dry skin, itching, rashes, redness. Objectively: the condition is satisfactory. The skin in the face, neck, elbow and popliteal folds is hyperemic, infiltrated. The skin of the trunk, lower extremities - xerosis, on the scalp - crusts, peeling. The conjunctiva of both eyes is hyperemic. The nasal passages are edematous, pale pink, moderate edema, nasal breathing is difficult on the right. The pharynx is pale pink, the tonsils are clean, the tongue is coated with a white coating, "geographical", the imprints of teeth on the mucous membrane of the cheeks and along the edge of the tongue, edema of the small uvula. The rib cage is cylindrical, the right and left halves are evenly involved in the act of breathing. Breathing in the lungs was vesicular, it was carried out in all parts of the lungs, wheezing was not heard during calm and forced breathing, percussion - pulmonary sound. BH 27 / min. Heart rate 118 / min. The abdomen is soft, painless, the liver does not protrude from the costal margin, the spleen is not palpable. The tapping symptom is negative on both sides.

In a general blood test: erythrocytes 4.7 × 10 ¹² / l, hemoglobin 132 g / l, platelets 265 × 10 ⁹ / l, leukocytes 8.4 × 10 ⁹ / l, in the leukocyte formula basophils -0%, eosinophils - 2% , stab neutrophils - 4%, segmented neutrophils - 32%, lymphocytes - 53%, monocytes - 9%, ESR - 10 mm / hour. IgG-17.2 (above normal) g / l, IgM-0.35 (below normal) g / l, IgA-2.4 (above normal) g / l, total IgE -145 IU / ml.

The girl underwent allergological testing; not only polyvalent food and household allergies, but also pollen and epidermal (cat hair) allergies were revealed. The child's age and polyvalent sensitization did not allow ASIT to be carried out by allergens “guilty” of the disease.

Treatment with autologous serum was carried out according to the children's scheme (see figure 2), in addition, a hypoallergenic diet was individually selected, preventive measures were taken for household and pollen allergies.

She tolerated the treatment well, since there was no pronounced painful moment. After the fourth injection from the start of treatment, skin rashes disappeared, after the seventh injection - symptoms of allergic rhinitis and conjunctivitis, after the ninth injection dry skin disappeared. The girl became sociable, cheerful, active.

Objectively: the condition is satisfactory. The skin in the area of the face, neck, elbow and popliteal folds - cleared, slightly tanned. On the lower extremities there was a slight xerosis, the scalp - crusts and peeling regressed. The conjunctiva of both eyes is pink. The nasal passages are pale pink, the swelling is insignificant, nasal breathing became free. The pharynx is pale pink, the tonsils are clean, the tongue is coated with a white coating, the "geographical" pattern has disappeared, the imprints of teeth on the mucous membrane of the cheeks and along the edge of the tongue have decreased, the swelling of the small uvula has disappeared. The rib cage is cylindrical, the right and left halves are evenly involved in the act of breathing. Breathing in the lungs was vesicular, it was carried out in all parts of the lungs, wheezing was not heard during calm and forced breathing, percussion-pulmonary sound. BH 26 / min, HR110 / min. The abdomen is soft, painless, the liver does not protrude from the edge of the costal arch, the spleen is not palpable. The tapping symptom is negative on both sides.

At the end of treatment in the general blood test erythrocytes 4.7 × 10 ¹² / l, hemoglobin 134 g / l, platelets 198 × 10 ⁹ / l, leukocytes 6.2 × 10 ⁹ / l, basophils in the leukocyte formula - 0%, eosinophils - 4%, stab neutrophils - 2%, segmented neutrophils - 48%, lymphocytes -41%, monocytes - 5%, ESR-6 mm / hour. OAM without pathology. IgG-12.8 (norm) g / l, IgM-1.3 (norm) g / l, IgA-1.4 (norm) g / l, total IgE - 62 IU / ml (slightly above the norm).

The proposed method of treatment was tested on 277 patients with various allergic diseases.

All patients had no pronounced painful moment during treatment. In most cases (see table, Fig. 3), as a result of treatment, the general condition, parameters of the parameters of FVD and blood normalized, normalization or a tendency towards it, laboratory, functional and immunological parameters were revealed. So, in patients with bronchial asthma, asthma attacks disappeared or became easier and shorter. In patients with allergic dermatoses, the skin cleared, edema, burning, itching disappeared. In patients with allergic rhinitis and rhinosinusitis, nasal congestion and discharge disappeared. In patients, itching, cramps in the eyes, lacrimation, sweating, fatigue disappeared, work and study activity increased, psychoemotional status and quality of life improved.

Claims (4)

1. A method of treating allergic diseases based on the use of autologous serum, characterized in that autologous serum is obtained from the patient's venous blood by keeping it at a temperature of + 4 ° C for 20 minutes for retraction and clot formation and subsequent centrifugation for 40 minutes at speed of 3000 rpm, the obtained autologous serum is injected subcutaneously into the lower third of the shoulder daily or every other day, first at a dilution of 1: 100 sequentially in doses of 0.4 ml, 0.8 ml, 1.2 ml and 1.6 ml, then sequentially in the same doses at a dilution of 1:10, and then undiluted serum is injected in the same sequence and in the same doses. 2. The method according to claim 1, characterized in that a preservative is added to the serum obtained by centrifugation collected in a sterile test tube. 3. The method according to claim 1, characterized in that the 1:10 dilution is carried out by adding 4.5 ml of sterile 0.9% sodium chloride solution to 0.5 ml of autologous serum, a 1: 100 dilution is obtained by adding to 0.5 ml of diluted 1:10 autologous serum 4.5 ml of sterile 0.9% sodium chloride solution, while diluted 1: 100, diluted 1:10 and undiluted autologous serum are divided into doses of 0.4 ml, 0.8 ml, 1, 2 ml and 1.6 ml, each of which is placed in a separate sterile vacuum tube, labeled and used according to the scheme described in item 1. 4. The method according to claim 1, characterized in that for the treatment of children, the treatment regimen described in claim 1 is used, but with half doses: 0.2 ml, 0.4 ml, 0.6 ml and 0.8 ml.

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