RU2572159C1 - Method of treating otorhinolaryngological inflammatory disorders - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: area of inflammation is treated with 3% N-acetylcystein solution in 0.9% sodium chloride. A solution exposure length is 30-60 minutes. That is followed by an antimicrobial photodynamic therapy of the area of inflammation.

EFFECT: higher therapeutic effectiveness ensured by the effective destruction of the bacterial film, which is followed by transformation of a pathogenic flora of the area of inflammation into a planktonic form and become available for the laser exposure as a microflora free from an exopolymeric matrix.

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Description

The invention relates to medicine, namely to otolaryngology, and is intended for the treatment of inflammatory diseases of ENT organs.

One of the important aspects of the treatment of inflammatory diseases of the ENT organs caused by infections is the provision of a long-term therapeutic effect and the prevention of relapse. During treatment, it is necessary to take into account the ability of bacterial populations (more than 99%) to form specifically organized biofilms attached to substrates, consisting of microbial cells enclosed in a matrix of extracellular polymeric substances synthesized by them, their phenotype is changed compared to plankton cells. The ability to form biofilms is an integral part of the life cycle of most microorganisms and a successful strategy for protecting bacteria from adverse environmental factors (Khmel I.A. Bacterial biofilms and the associated difficulties of medical practice, IMG RAS, 2014). Virtually all antibacterial drugs are effective against fast-growing cells, while bacteria living in biofilms are in a stationary phase of growth according to their physiological state and metabolic activity; in addition, the exopolymer biofilm matrix limits the diffusion of substances and binds antimicrobial agents. Thus, the treatment of infectious and inflammatory diseases of the ENT organs by traditional methods aimed at the planktonic form of bacteria can be ineffective and contribute to the chronicity of the process.

One of the progressive methods of treating this group of diseases is laser exposure, in particular antimicrobial photodynamic therapy (AFDT). The prior art method known as AFDT for acute inflammatory diseases of the larynx and pharynx or their acute complications (RU 2511545 C1, 02/07/2014). The method consists in introducing a photosensitizer in the form of a powder based on starch or sorbitol with a photosensitizer content of 0.5-1.0% by insufflation followed by laser irradiation with a wavelength of 0.685 μm, a power of 18-20 mW and an energy density of 21.0-28 , 8 J / cm ² , while 2-5 sessions of AFDT are performed.

The disadvantage of this method is the impossibility of complete degradation of the biofilm, especially mature. Laser irradiation allows you to get holes (perforations) in biofilms, these holes can facilitate access to biofilms of medicinal compounds inside, but this effect is far less effective than on the planktonic form of pathogenic flora. In addition, this method is aimed only at the treatment of diseases of the larynx and pharynx and does not cover the entire spectrum of ENT diseases.

As you know, silver preparations have high antiseptic activity and have a wide spectrum of antibacterial action, therefore they are quite common in the treatment of inflammatory diseases of the otolaryngological profile. A known method of treating inflammatory diseases of the ENT organs (patent RU 2307657 C2, January 27, 2007, selected as a prototype), consisting in local treatment using 0.5-2% aqueous solutions of colloidal silver in the form of a complex of silver and polyvinylpyrrolidone (PVP ), in which silver is 7-85, PVP 92-93%, or the use of these solutions in water-soluble polymer gels.

The disadvantage of this method is the lack of a long therapeutic effect. Due to the small size (10-15 Å), colloidal silver complexes stabilized by PVP are able to penetrate into the biofilm and affect some microorganisms, but this effect is temporary.

Thus, there is a need for a method of treating inflammatory diseases of the ENT organs, which consists in effectively destroying the bacterial biofilm, after which the pathogenic flora of the focus of inflammation becomes planktonic and becomes available for exposure. To solve this problem, a real method has been developed. The method consists in carrying out local treatment of the inflammatory focus, namely, that the inflammatory focus is treated with 3% N-acetylcysteine solution in 0.9% sodium chloride solution, the exposure time of the solution is 30-60 minutes, after which antimicrobial photodynamic therapy of the inflammatory focus is performed .

The method is as follows.

After identifying the patient’s complaints, collecting a medical history, ENT organ endoscopy data, clinical and laboratory data, and before AFDT, the inflammation site is washed with 0.9% sodium chloride solution (saline), a smear is taken to determine the microflora. Then the area of inflammation is treated with a 3% solution of N-acetylcysteine in a 0.9% solution of sodium chloride. The exposure time is 30-60 minutes (min). In time, the focus of inflammation is stained with a photosensitizer (PS), with the use of porphyrins of the chlorin series as PS, the exposure time is also 30-60 minutes. At the end of the exposure time, the focus of inflammation is washed off, in order to avoid the effect of screening. The site of inflammation is irradiated with a wavelength that matches the wavelength of the absorption peak of the used PS for 10-60 minutes and with a power of 100 mW to 1 W. At the end of the procedure, take a control smear on the flora. The proposed method allows to increase the effectiveness of treatment due to local effects of the drug, which can destroy bacterial biofilms, as a result of which the fight against the planktonic form of pathogenic flora becomes quite feasible. It is a combination of direct, local effects on bacterial biofilms of a solution of N-acetylcysteine of the indicated concentration and subsequent AFDT of the focus that has the desired effect.

Clinical example 1.

Patient D., born in 1988, turned to the ENT clinic with complaints of difficulty in nasal breathing, mucopurulent discharge from the nose, snoring in a dream, and a rise in body temperature to 37.8 ° C. The above complaints worry about 2 weeks. Suffers from chronic adenoiditis for 20 years, exacerbation 1 time in 3-6 months.

AD-adenoids are hypertrophied, hyperemia and swelling of the nasal mucosa.

For the other ENT organs at the time of examination, evidence of acute pathology was not detected.

Diagnosis: hypertrophy of adenoids of the II-III degree, chronic adenoiditis, OIVDP (acute infection of the upper respiratory tract).

Before the patient, AFDT performed nose washing with 0.9% saline by the method of moving the liquid along the Proetz, a nasopharyngeal swab to determine the microbiological landscape. After the patient was placed lying down, with his head thrown back. In both halves of the nose, an instillation of a 3% solution of N-acetylcysteine (a solution of the “ACC-long” 600 mg drug diluted in 20 ml of a 0.9% sodium chloride solution) with an exposure of 30 minutes was performed, after which the adenoid tissue was stained with the preparation “Radachlorin” (0.35% solution for administration), 2 ml in each half of the nose, for 30 minutes. At the end of half an hour, the patient was again washed with a nose by the method of moving the liquid along the Proetz. The silicone cone of the fiber through one of the halves of the nose was lowered to the level of the nasopharynx. A laser effect on adenoid tissue with a wavelength of laser radiation of 662 nm and a power of 100-200 mW for 10-15 minutes was performed. At the time of exposure, the patient had a sensation of burning and tingling in the area of exposure. At the end of AFDT, a smear was taken from the nasopharynx to determine microflora.

In the next 3-5 days, the patient experienced reactive manifestations, manifested by nasal congestion and nasal mucosa.

Control smears were taken on 3,7,12 days (see Table 1).

By the 12th day, the patient's nasal breathing returned to normal and the nasal mucosa was stopped.

As a result of observation in this patient for 8 months. relapse did not occur.

Clinical example 2.

A patient K., born in 1978, came to the ENT clinic complaining of a feeling of fullness and pain in the maxillary sinus, a sensation of dripping along the back of the pharynx, a headache in the facial skeleton when the head was tilted down, and the nose was nasal, mucous purulent discharge from the nose, a rise in body temperature to 37.8 ° C. The above complaints worry for 1 week. Previously, she did not suffer from maxillary sinusitis, punctures of the maxillary sinuses were not performed.

On the presented x-ray - fluid levels in both maxillary sinuses.

Diagnosis: Acute bilateral maxillary sinusitis.

With anterior rhinoscopy: the mucous membrane of the nasal cavity is hyperemic, the nasal septum is slightly curved to the left, the lower nasal turbinates are edematous, contract well after anemia, and the middle nasal passage on both sides shows a pathological discharge.

According to the standard method, the patient was punctured by the maxillary sinuses, smears were taken to determine the type of microflora, titer and sensitivity to antibacterial drugs. Both sinuses were repeatedly washed repeatedly until a clean wash liquid was obtained, they introduced a 3% solution of N-acetylcysteine (600 ml diluted in 20 ml of 0.9% sodium chloride solution) in 10 ml of sinus, with an exposure of 60 minutes for each sinus in the supine position on the same side. At the end of the exposure time of the N-acetylcysteine solution, each sinus was washed with 0.9% saline, then 10 ml of the Radachlorin photosensitizer (0.35% solution for intravenous administration) was instilled into it with an exposure of 60 minutes. Then, a sinus puncture was performed again, it was thoroughly washed and a quartz-polymer fiber was introduced through a Kulikovsky needle through which laser radiation with a wavelength of 662 nm was transmitted. The AFDT session, when the laser radiation power was 200-400 mW at the exit from the fiber, lasted 40 minutes.

After AFDT, silicone drains were installed in both maxillary sinuses, control smears were taken.

On the first day, the patient noted an increase in nasal congestion, copious mucous discharge from the nose, and a feeling of fullness in the region of the maxillary sinuses.

With anterior rhinoscopy: the mucous membrane of the nasal cavity is pink, the nasal septum is in the same position, moderate swelling of the lower nasal concha, mucous discharge is noted.

Starting from the second day after the AFDT session, with the daily drainage of the irradiated sinuses, the local symptoms stopped.

Control smears were also taken on days 3, 7, 12 (see Table 2).

Microbiological examination after AFDT revealed a complete elimination of microflora.

By the tenth day after the AFDT, the patient's condition was considered satisfactory and all complaints made by the patient upon admission were stopped.

As a result of observation, this patient did not relapse within 12 months.

Clinical example 3.

Patient K., born in 1976, came to the ENT clinic with complaints of hearing loss and pain in the left ear, suppuration from the left ear, and a rise in body temperature to 38.0 ° С. The above complaints worry for 3-4 days. Ear suppuration was not noted.

On examination: AS - the ear region is not changed, the ear canal is filled with purulent discharge, after the toilet of the ear, the central perforation in the stretched part of the tympanic membrane is about 3 mm.

For other ENT organs at the time of examination, data for acute pathology were not detected.

Diagnosis: Acute left-sided purulent otitis media.

After the toilet of the external auditory meatus, the tympanic cavity is freed from its contents by washing it with a warm 0.9% saline solution. A smear on the microflora was taken from the tympanic cavity. Then, a warm 3% solution of N-acetylcysteine (600 ml of diluted in 20 ml 0.9 ml sodium chloride solution in 20 ml) was instilled into the tympanic cavity. The exposure time was 60 minutes. After the lapse of time, the focus of inflammation was washed with 0.9% saline and stained with preheated 1 ml of the radachlorin photosensitizer (0.35% solution for intravenous administration) for 60 minutes. During instillations and expositions of the patient, the patient was on the right side, alternately changing position - on the right side - on the back. At the end of the exposure time, the tympanic cavity was washed, in order to avoid the screening effect. Through the external auditory canal, under the control of a microscope, a light guide was inserted into the tympanum, which was installed at such a distance from the irradiated surface of the mucous membrane of the tympanum that the light spot covered the entire surface. Laser exposure to the focus of inflammation with a wavelength of laser radiation of 662 nm was carried out for 40 min with a power of 100 mW to 1 W. At the end of the procedure, a control smear on the flora was taken.

Control smears were also taken on days 3, 7, 12 (see Table 3).

In the next 3-5 days, the patient experienced reactive phenomena, manifested by stuffiness of the ear and separated from the ear of a different nature (from transparent mucous membranes to dark brown), odorless. With otoscopy:

AS - the ear canal is wide, free, moderate hyperemia of the tympanic membrane is noted, there is no pathological discharge.

By the 12th day there are no complaints, reactive phenomena are completely stopped, there is no pathological discharge.

In the next 6 months, suppuration from the left ear was not repeated.

The proposed method is simple and affordable, can increase the effectiveness of the treatment of inflammatory diseases of ENT organs due to local, direct exposure to a solution of N-acetylcysteine of a certain concentration, aimed at the destruction of bacterial biofilms; subsequent AFPCT of the focus of inflammation has a powerful therapeutic effect on the planktonic form of the pathogenic flora obtained as a result of the action of the N-acetylcysteine solution, devoid of the exopolymer matrix.

Claims (1)

A method of treating inflammatory diseases of the ENT organs, including local treatment, characterized in that the focus of inflammation is treated with 3% N-acetylcysteine solution in 0.9% sodium chloride solution, the exposure time of the solution is 30-60 minutes, after which antimicrobial photodynamic therapy is carried out foci of inflammation.