RU2373968C1 - Method for treating patients suffering from allergic rhinitis - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to otorhinolaryngology and physiotherapy. The method involves endonasal introduction of bromide ipratropium by positive-pole endonasal electrophoresis of the solution 1 ml containing bromide ipratropium 0.25 mg/ml. Electrophoresis is performed at current strength not exceeding 2 mA during 10 - 20 minutes. Therapeutic course is 5 daily procedures.

EFFECT: higher clinical effectiveness with decreased number of daily procedures, excludes intillate ingress into gastrointestinal tract.

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Description

The invention relates to medicine, namely to otorhinolaryngology and physiotherapy, and can be used in the treatment of patients with allergic rhinitis (AR).

Known methods for treating patients with allergic rhinitis:

with the help of medicines: antihistamines, glucocorticosteroids, mast cell stabilizers, vasoconstrictors, M-anticholinergics (Clinical recommendations for the diagnosis and treatment of allergic rhinitis: A manual for doctors. / Ed. by A.S. Lopatin. St. Petersburg: RIA-AMI LLC ". 2003. - P.21-22 .; Mitrofanov VV, Shiman AG, Maksimov AV, Bezrukova EV Physical methods of treatment of vasomotor rhinitis: A training manual. - St. Petersburg: St. Petersburg State Medical Academy. I.I. Mechnikova, 2001 .-- 42 p., Pp.17-19.);

- using endonasal drug electrophoresis (LEF) of calcium chloride, diphenhydramine, ε-aminocaproic acid, intal, hydrocortisone hemisuccinate, histamine (Sosin I.N., Tondiy L. D., Sergieni E.V. et al. Clinical physiotherapy: Reference manual for a practical doctor. / Under the editorship of I.N.Sosin. - Kiev: "Health." - 1996. - 622 p., P.495 .; Mitrofanov V.V., Shiman A.G., Maksimov A .V., Bezrukova EV Physical methods for the treatment of vasomotor rhinitis: Textbook. - St. Petersburg: St. Petersburg State Medical Academy named after II Mechnikov, 2001. - 2 pp., P.38);

- using intramucosal exposure to radiation from a holmium laser (Zenger V.G .; Nasedkin A.N .; Deryugina O.V .; Kokoreva S.A. Method for the treatment of chronic hypertrophic, vasomotor and allergic rhinitis. Application: 97116980/14. Published: 2000.01.20).

These methods are not sufficiently effective due to the fact that to achieve a pharmacological effect, antihistamines must be administered in high doses several times a day, a number of first-generation drugs have side hypnotic effects, and second-generation drugs are effective for minor, mild clinical manifestations of the disease.

The maximum effect of topical glucocorticosteroids develops within a few days, they cause dryness of the mucous membrane of the nasal cavity, leading to atrophy, bleeding. There is only a small number of scientific studies substantiating the systemic use of systemic glucocorticosteroids; the optimal dosages, routes of administration and the dependence of the result on the dose of the drug have not been adequately studied.

Mast cell stabilizers in some cases have a sedative effect and require 4-6 times a day.

Vasoconstrictor drugs are used at the beginning of the course of treatment with severe swelling of the nasal cavity, when the use of other aerosol preparations is difficult. Short-term courses of treatment with vasoconstrictor drugs do not lead to functional and morphological changes in the mucous membrane. Long-term (over 10 days) use of these drugs can cause severe swelling in the nasal cavity, nasal hyperreactivity, changes in the histological structure (remodeling) of the mucous membrane, that is, the development of drug rhinitis.

The disadvantages of the known methods of physiotherapy are:

- application during the period of relative remission, a long exposure duration and a long course of electrotherapy (up to 20 procedures), sometimes it is necessary to conduct a preparatory course (5-7 procedures) of electrophoresis on the nose, which does not allow to obtain a pronounced therapeutic effect due to the relief of the main symptom of the disease and improve the condition of the patient in the short term of treatment;

- destruction of biological tissues and the need for local anesthesia (superficial and infiltration).

According to the closest technical essence, as a prototype, we have chosen a method of treating patients with allergic rhinitis, which consists in using the drug ipratropium bromide (IB). Used are nasal IB instillations of 20-25 μg (2 drops) in each half of the nose 3-4 times a day (Kaiser HB. Findlay SR, Georgitis JW Long-term treatment of perennial allergic rhinitis with ipratropium bromide nasal spray 0.06%, II J Allergy Clin. Immunol. - 1995. - Yol. 95. - P.1128-1132).

The disadvantages of this method are the insufficiently high efficiency of treatment, as well as the need for frequent use of the drug and getting the instillate in the digestive tract when swallowed.

The technical result of the invention is to increase the effectiveness of treatment by improving clinical and laboratory parameters, a single daily use and the exclusion of instillate in the digestive tract.

The technical result is achieved by the fact that the drug ipratropium bromide is administered endonasally by the method of drug electrophoresis, the course of treatment is 5 procedures performed daily, the duration of the procedure is 10-20 minutes.

Iprotropium bromide belongs to the group of M-cholinoblockers, blocking the muscarinic receptors of the glands of the mucous membrane, interrupts parasympathetic stimulation mediated by the classical mediator acetylcholine, and reduces the amount of watery secretion intensely produced in the early phase of an allergic reaction. Ipratropium bromide is available in several countries as a nasal spray (a sealed aerosol that can be replaced with a water spray). In Russia, ipratropium bromide (trade name "Atrovent", the active substance is ipratropium bromide at a concentration of 0.25 mg / ml) is widely used only in the treatment of bronchial asthma, since it is available only in the form of oral inhalation. There are no data on the use of ipratropium bromide for the treatment of AR in Russia.

The staff of St. Petersburg State Medical Academy. I.I. Mechnikov, on the basis of the Central Research Laboratory of St. Petersburg State Medical Academy. I.I. Mechnikov, the electrophoreticity of information security was investigated. The possibility of its introduction into the tissues of the body using galvanic current.

The method is as follows: conduct electrophoresis ipratropium bromide using the apparatus "Potok-1". The technique is endonasal. The ends of the duplicated electrode are wrapped with gauze napkins, forming turundas. They are moistened with an IB solution in a volume of 1 ml, injected into the common nasal passages and connected to the positive pole of the device. The second electrode with an area of 80-100 cm ² is located on the back of the neck and connected to the negative pole of the apparatus. The current must not exceed 2 mA. The duration of the procedure is 10-20 minutes. The course of treatment consists of 5 procedures conducted daily.

Distinctive essential features of the proposed method are:

1) iprotropium bromide is administered endonasally by drug electrophoresis;

2) the duration of the treatment 5 procedures conducted daily, the duration of the procedure is 10-20 minutes.

A causal relationship between the distinctive essential features and the achieved result:

1) iprotropium bromide is administered endonasally by the method of drug electrophoresis, which allows to increase the duration of the therapeutic effect by creating a depot of the drug substance in the nasal mucosa and the prolonged action of the drug, using it once a day;

2) the duration of the procedure is 10-20 minutes and the duration of the treatment course of 5 procedures is sufficient for the development of therapeutic effects.

For the first time, we have proved that the drug ipratropium bromide has electrophoreticity and can be introduced into biological tissues using galvanic current.

The set of distinctive essential features is new and allows to increase the effectiveness of treatment by improving clinical and laboratory parameters, as well as a single daily use and eliminating the ingress of instillate into the digestive tract.

Case Studies

Example 1

Patient Z., 47, IS No. 2732, was admitted to the ENT clinic of St. Petersburg State Medical Academy. I.I. Mechnikova with complaints of a nasal discharge of a foamy nature, difficulty in nasal breathing, sneezing, itching in the nose, decreased smell. From the medical history of the disease, it is known that the patient is sick for 10 years. It is allergic to house dust. It was treated on an outpatient basis: antihistamines, vasoconstrictor drops in the nose, novocaine blockade, FTL: UHF, electrophoresis with calcium chloride endonasally. As a result of treatment, a slight short-term improvement arose. Objective upon admission: the mucous membrane of the nose is swollen, the nasal passages are sharply narrowed, in the nasal passages copious discharge, in the middle nasal passages mucous polyps of small size. The intensity of the symptoms upon admission according to the standard scale: nasal congestion - 3, nasal discharge - 2, sneezing - 1, decreased sense of smell - 3.

Clinical diagnosis: allergic rhinitis.

The treatment was carried out according to the claimed method: drug electrophoresis of the drug "Atrovent" (solution for inhalation 0.25 mg / ml) according to the endonasal technique for five days.

Result: there was a positive dynamics of subjective sensations, nasal breathing improved from the first day of treatment and recovered by day 5; nasal discharge decreased significantly by day 2 and stopped by day 5, sneezing from day 2 and itching in the nose from day 4 of treatment stopped.

Objectively: the nasal mucosa is pink, somewhat swollen, the discharge is insignificant, transparent, the nasal passages are free.

When viewed 2 weeks after the end of treatment: complaints only of periodic sneezing.

The dynamics of clinical and laboratory parameters are presented in table 1.

Example 2

Patient O., 22 years old, IS No. 14940, was admitted to the ENT clinic of St. Petersburg State Medical Academy. I.I. Mechnikova with complaints of a nasal discharge of a foamy nature, difficulty in nasal breathing, sneezing, itching in the nose, decreased smell. It is allergic to house dust.

From the medical history of the disease, it is known that the patient is sick for 3 years. It is allergic to house dust. Treated by an allergist: antihistamines - no effect.

Objective upon admission: the mucous membrane of the nose is swollen, the nasal passages are sharply narrowed, in the nasal passages there is a plentiful discharge. The intensity of symptoms upon admission according to the standard scale: nasal congestion - 3, nasal discharge - 1, sneezing - 1, decrease in sense of smell - 0.

Clinical diagnosis: allergic rhinitis.

The treatment was carried out according to the claimed method: drug electrophoresis of the drug "Atrovent" (solution for inhalation 0.25 mg / ml) according to the endonasal technique for five days.

Result: there was a positive dynamics of subjective sensations, the absence of all symptoms by the 5th day of treatment.

Objectively: the nasal mucosa is pink, somewhat swollen, the discharge is insignificant, transparent, the nasal passages are free.

On examination, 2 weeks after the end of treatment, slight discharge from the nose and nasal congestion are noted. There is no sneezing.

The dynamics of clinical and laboratory parameters are presented in table 2.

Example 3 (prototype)

Patient I., 76 years old, I / B No. 2433, was admitted to the ENT clinic of St. Petersburg State Medical Academy. I.I. Mechnikova with complaints of a nasal discharge of a foamy nature, difficulty in nasal breathing, sneezing, itching in the nose, decreased smell. From the medical history of the disease, it is known that the patient is sick for 30 years. Repeatedly treated on an outpatient and inpatient basis with an allergist and ENT doctor. Received antihistamines, vasoconstrictor drops in the nose, FTL: electrophoresis with calcium chloride endonasally. As a result of the treatment, a slight improvement arose, after the cessation of taking the drugs, the above symptoms reappeared.

Objective upon admission: the condition is satisfactory, the mucous membrane of the nose is swollen, the nasal passages are sharply narrowed, in the nasal passages copious discharge. An allergy to house dust has been identified.

The intensity of symptoms at admission was maximum.

Clinical diagnosis: allergic rhinitis.

The treatment was carried out according to the prototype method: “Atrovent” (solution for inhalation 0.25 mg / ml), 2 drops in both halves of the nose 3 times a day for five days.

Result: the positive dynamics of subjective sensations was noted, nasal breathing recovered on the 2nd day of treatment, nasal discharge stopped on the 4th day, sneezing on 2, the sense of smell was restored on the 5th day of the drug.

Objectively: the nasal mucosa is pink, somewhat swollen, the discharge is insignificant, transparent, the nasal passages are free.

Upon examination, 2 weeks after the end of treatment, symptoms of allergic rhinitis increased again: abundant discharge from the nose, severe nasal congestion, moderate sneezing, and a slight decrease in smell. The dynamics of clinical and laboratory indicators are presented in table 3.

Materials and methods: under observation, there were 50 patients (14 men and 36 women) aged 18 to 76 years suffering from year-round allergic rhinitis (CAR). The duration of the disease in the examined patients ranged from 1 year to 30 years.

All patients underwent a study to determine the sensitivity to household allergens. Sensitization to house dust was detected in the majority of the examined - 45 people. (90.0%), to the pollen of plants in 23 (46.0%), to the hair of animals in 14 (28.0%), to house mites in 3 (6.0%), to feather cushions - in 2 people (4.0%).

For treatment, the drug Atrovent was used in the form of a solution for inhalation. The active substance is ipratropium bromide at a concentration of 0.25 mg / ml.

At the first stage of work, on the basis of the Central Scientific Research Laboratory of St. Petersburg State Medical Academy. I.I. Mechnikov, the electrophoreticity of ipratropium bromide was investigated. The possibility of its introduction into the body tissue using galvanic current from the positive pole has been established.

At the second stage, the effectiveness of the drug was studied in year-round AR. The examined patients were divided into two groups, comparable in age, disease duration and severity of clinical manifestations. The first group consisted of 27 CAR patients (10 men and 17 women) who received ipratropium bromide as monotherapy at a dose of 25 mcg (2 drops) in each half of the nose 3 times a day. The second group consisted of 23 people (4 men and 19 women) suffering from CAR who underwent drug electrophoresis of ipratropium bromide.

The effectiveness of treatment was evaluated by changing the severity of symptoms on a 4-point standardized scale: 0 - no symptoms, 1 - mild, 2 - moderately expressed, 3 - intense.

For an objective assessment of the effectiveness of the proposed treatment methods, the following clinical and laboratory research methods were used: endoscopy and photographing of the nasal mucosa; anterior active rhinomanometry (PARM); quantitative measurement of nasal secretion; determination of motor activity of ciliated epithelium; pH measurement cytological examination of smears-prints of the nasal mucosa.

To quantify nasal secretion, we proposed an original technique based on the properties of a filter paper strip to absorb liquid. By the length of the wetted portion of the strip, one can judge the amount of nasal secretion (rationalization proposal of GOUVPO SPbGMA named after II Mechnikov No. 1765 dated 04/12/07 "Method for the quantitative determination of nasal secretion"). The survey indicators of a group of rhinologically healthy individuals (20 people) were taken as the norm.

Assessment of clinical and laboratory parameters was carried out before treatment and on the 5th day of the drug. Long-term results were evaluated 2 weeks after the end of treatment. The results are presented in tables No. 4, 5 and 6. As can be seen from the data in tables No. 4 (Severity of symptoms in patients of group 1 on a 4-point scale (number of patients)) and No. 5 (Severity of symptoms in patients of group 2 according to 4-point scale (number of patients)), during the initial examination, all patients had pronounced symptoms of CAR, and in the vast majority of them, these symptoms were intense or moderately severe. Positive dynamics of the main symptoms of the disease (nasal discharge, nasal congestion, sneezing, decreased sense of smell) was found in all patients with CAR in both groups.

After 5 days of using the drug, a significant decrease in the intensity of clinical manifestations of CAR was recorded. Most patients in both groups reported a lack of all four observed symptoms; in a significant proportion of patients, these symptoms were mild; several people noted moderate nasal congestion, sneezing, and a decrease in sense of smell, and only in 2 patients of the second group the sense of smell was significantly reduced.

Examination of patients after 2 weeks revealed that the first group of patients again experienced an increase in the clinical manifestations of CAR. Most patients noted a mild or intense character. In the second group, in most patients, the symptoms of CAR were either absent or mild.

The results of the clinical laboratory examination are presented in table No. 6. Analysis of PARM data did not reveal any significant changes in nasal breathing. The average total resistance (SS) as a result of treatment was 0.40 cm ³ / s compared to the initial 0.44 cm ³ / s in the first group and 0.32 cm ³ / s compared to the initial 0.35 cm ³ / s in the second group. The total volume flow (SOP) also did not change significantly and amounted to 411.6 Pa / cm ³ / s compared to 371 Pa / cm ³ / s before treatment in the first group and 496.9 Pa / cm ³ / s compared to 465 , 7 Pa / cm ³ / s in the second group.

The PARM study, performed after 2 weeks, also did not reveal significant changes: in the first group, SS was 0.43 cm ³ / s, SOP - 373.2 Pa / cm ³ / s, in the second group 0.34 cm ³ / s and 477.8 Pa / cm ³ / s, respectively.

Indicators of the amount of nasal secretion revealed a decrease in rhinorrhea as a result of treatment by almost 2 times - from 6.5 mm to 3.1 mm on average in both groups of patients. A study of rhinorrhea after 2 weeks showed that in the first group the quantitative indicators of nasal secretion returned to their previous values, and in the second group they remained low, although, compared with the indicators immediately after treatment, they increased slightly.

The pH results on the 5th day of treatment approached normal and amounted to 7.3 in both groups. After 2 weeks, the pH values in the first group almost returned to their previous values - 7.7; and in the second group, the pH was slightly, but still closer to normal - 7.5.

The study of the transport function of the ciliated epithelium also revealed that despite the fact that on the 5th day of treatment the saccharin test time decreased to normal values (15-16 min) in both groups, two weeks later the transport time increased again, but in the first group to 22 8 min compared to the initial 26.4 min; and in group 2 to a much lesser extent - up to 19.8 minutes compared to the initial 30.9 minutes.

Improving the pH and transport function of the ciliated epithelium in the long term - after 2 weeks - in the second group of patients was not so pronounced compared with indicators of nasal secretion, but nevertheless indirectly confirmed the effectiveness of the proposed method compared to the prototype method. The improvement in pH in both groups and the reduction in the time of the saccharin test are, presumably, a consequence of the normalization of the amount of nasal secretion and more effective work of cilia of the ciliated epithelium.

The study of smears-prints of the nasal mucosa before and after treatment did not reveal any patterns in the change in the cellular composition of the nasal secretion.

It should be noted the good tolerability of the drug. Of the side effects, patients of the first group in 6 (22.0%) cases noted dry nose, in 2 (7.5%) patients there was a slight cough. In the second group, only 3 (13.0%) patients noted dryness of the nasal mucosa and 1 (4.3%) patient complained of coughing.

Thus, the claimed method of treating patients with allergic rhinitis in comparison with the prototype increases the effectiveness of treatment by improving clinical and laboratory parameters. The advantage of the proposed method is also a single daily use and the exclusion of ingress of instillate in the digestive tract.

Table 1 The dynamics of clinical and laboratory parameters of patient Z. (example 1) Test indicator Norm Study Dates Before treatment On day 5 of treatment 2 weeks after treatment PARM Total resistance Pa / cm ³ / s 0.22 ± 0.01 0.49 0.35 0.40 The total volumetric flow cm ³ / s 682.6 + 35.8 304 420 360 Nasal secretion, mm / min 1.5 + 0.4 four 2 2 pH 7.0 ± 0.04 7.8 7.4 7.5 The motor activity of the ciliated epithelium / minute / 12.5 + 5.33 thirty 16 eleven table 2 The dynamics of clinical and laboratory parameters of patient O. (example 2) Test indicator Norm Study Dates Before treatment On day 5 of treatment 2 weeks after treatment PARM Total resistance Pa / cm ³ / s The total volumetric flow cm ³ / s 0.22 ± 0.01 0.28 0.21 0.21 682.6 + 35.8 528 700 700 Nasal secretion, mm / min 1.5 + 0.4 5 one 2 pH 7.0 ± 0.04 8.1 7.4 7.8 The motor activity of the ciliated epithelium / minute / 12.5 + 5.33 eleven 8 10

Table 3 The dynamics of clinical and laboratory parameters of patient I. (example 3) Test indicator Norm Study Dates Before treatment On day 5 of treatment 2 weeks after treatment PARM Total resistance Pa / cm ³ / s 0.22 ± 0.01 0.46 0.46 0.46 The total volumetric flow cm ³ / s 682.6 + 35.8 320 320 320 Nasal secretion, mm / min 1.5 + 0.4 7 3 7 pH 7.0 ± 0.04 7.2 7.2 7.8 The motor activity of the ciliated epithelium / minute / 12.5 + 5.33 35 twenty 25

Table 6 Indicators of the functional state of the nasal mucosa in patients with CAR (M ± m) Test indicator Norm Study Dates 1 group 2 group Before treatment On day 5 In 2 weeks Before treatment On day 5 In 2 weeks PARM SS Pa / cm ³ / s 0.22 ± 0.01 0.44 ± 0.06 0.40 ± 0.06 0.43 ± 0.05 0.35 ± 0.05 0.32 ± 0.05 0.34 ± 0.05 SOP cm ³ / s 682.6 ± 35.8 371.0 ± 41.15 411.6 ± 49.15 373.2 ± 40.55 465.7 ± 52.91 496.9 ± 52.97 477.9 ± 54.91 Nasal secretion, mm / min 1.5 ± 0.40 6.5 ± 0.54 3.0 ± 0.20 6.3 ± 0.46 6.6 ± 0.85 3.1 ± 0.86 4.3 ± 0.91 pH 7.0 ± 0.040 7.8 ± 0.11 7.3 ± 0.05 7.7 ± 0.12 7.8 ± 0.10 7.3 ± 0.08 7.5 ± 0.07 Propulsion
activity
atrial
epithelium
/ min / 12.5 ± 5.33 26.4 ± 4.08 15.4 ± 0.10 22.8 ± 2.18 30.9 ± 5.30 16.5 ± 3.82 19.8 ± 4.01

Claims (1)

A method of treating patients with allergic rhinitis, including endonasal administration of ipratropium bromide, characterized in that this administration is carried out by endonasal electrophoresis from the positive pole of 1 ml of a solution containing 0.25 mg / ml ipratropium bromide, with a current strength of not more than 2 mA for 10- 20 minutes for a course of 5 procedures conducted daily.