RU2511545C1 - Method for antimicrobial photodynamic therapy of acute inflammatory diseases of laryngeal pharynx and suppurative complications - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: starch or sorbite photosensitiser powder is administered into a laryngeal pharynx that is further exposed to laser light. The laser light exposure is performed at wave length 0.685 mcm, powder 18-20 mWt, energy density 18-28.8 J/cm².

EFFECT: implementing the method provides the reliable laryngeal fixation of the photosensitiser, maintains the constant concentration of the photosensitiser for the whole therapeutic session, and thereby faster reduction of the inflammatory process.

2 cl, 4 ex

Description

The invention relates to medicine, namely to otorhinolaryngology, and can be used for antimicrobial photodynamic therapy of acute inflammatory diseases of the laryngopharynx or their purulent complications.

Currently, antibiotic therapy is widely used to treat purulent-inflammatory diseases of the larynx and pharynx (Kozlov S.N. Antibacterial therapy: A practical guide. - M. 2000. - P.190). Often, a combination of two or more antibacterial agents is prescribed to maximize the range of potential pathogens. Despite the continuous improvement of the methods for diagnosing and treating acute inflammatory diseases of the ENT organs and their purulent complications, a steady increase in the incidence among the able-bodied population has been noted over the past few years. This is primarily due to the uncontrolled administration and use of antimicrobial agents. It was the unreasonable use of antibacterial drugs that led to the emergence of complex problems of antibiotic resistance by the beginning of the 70s. The species composition of microflora has significantly changed in the direction of the predominance of staphylococcal and opportunistic flora. The problem of antibiotic resistance, which arose sharply in that era, forced practitioners to increase dosages of antimicrobial chemotherapy drugs, often change drugs, and scientists look for more and more groups of antibacterial agents.

Due to the decrease in the effectiveness of antibiotic therapy, the formation of strains resistant to most known antibiotic strains, the increase in the number of postoperative infectious complications, the low efficiency of most conventional methods of therapy, the length of treatment, the exceptional high cost of the use of antimicrobial therapy, the search for new ways to treat purulent-inflammatory processes of ENT organs on all stages of medical science is relevant.

One of the progressive methods of treating acute inflammatory diseases of the larynx and pharynx and their purulent complications is laser and magnetic laser therapy, extracorporeal laser or ultraviolet irradiation of blood (V.T. Palchun, A.S. Lapchenko, D.L. Muratov. "Inflammatory diseases of the larynx and their complications ”, M., 2010. P.163). In addition, the progress of laser medicine has led to the emergence of a fundamentally new way of influencing biological objects, associated with the interaction of focused laser radiation and a new class of pharmacological drugs - photosensitizers. A method of treating inflammatory and proliferative diseases, malignant neoplasms, based on the use of photodynamic effects on pathological objects (tissues, organs), is called photodynamic therapy (PDT).

The targets of antimicrobial photodynamic therapy are viruses, bacteria, fungi and protozoa. The selectivity of the method is due to the local delivery of the photosensitizer and light to the infected area and a greater sensitivity to photodynamic effects in microorganisms, depending on the species, in comparison with animal cells. In this case, their selective destruction occurs as a result of the combined effect of the photosensitizer and coherent or incoherent radiation.

A known method of antimicrobial photodynamic therapy of severe purulent complications of inflammatory diseases of the ENT organs using cationic phthalocyanines ZnPcPym ₈ and ZnPcChol ₈ (RF Patent 2282647, C09B 47/32 from 08/27/2006). In this method, photodynamic therapy was started immediately after the surgical opening of purulent foci and emergency and resuscitation measures. The light source used was the radiation of the Mustang semiconductor laser therapeutic device with a wavelength of 0.67 microns and a power of 24 mW.

The treatment technique was that gauze napkins impregnated with a photosensitizer solution were placed in the cavity of the surgically opened abscess for a period of 10 minutes to 24 hours. Then, a purulent wound was exposed with an exposure of 7 minutes. The procedure was carried out daily until the wound was completely cleansed of purulent discharge and wound detritus, from 5 to 10 procedures per treatment course, depending on the severity and prevalence of the purulent process. At the end of the PDT course and the disappearance of signs of suppuration of the wound, the latter were sutured again with delayed sutures.

The disadvantages of this method are that its use is possible only when conducting a percutaneous surgical opening of the abscess, as well as the inability to maintain the necessary stable concentration of the photosensitizer during the entire session of photodynamic therapy.

Another method for the treatment of purulent diseases of the larynx is also known using cationic phthalocyanines ZnPcPym ₈ and ZnPcChol ₈ (RF Patent 2361633, dated 20.07.2009 - prototype). The method consisted of spraying a photosensitizer through an inhaler into the larynx, introducing through the general nasal passage of the fiber and further irradiating the inflamed sections of the larynx. The method includes the use of a phototherapeutic LED apparatus APS “Solaris” with a wavelength of 0.675 μm, a radiation power of 40 mW at the output, in continuous mode, using an optical fiber nozzle for an ENT with a diffuser to the AFS apparatus, a diffuser diameter of 1.5 cm, a diffuser length ( with side radiation) 2 cm, the radiation power at the output of the fiber is 15-24 mW. For delivery of the sensitizer use an ultrasonic inhaler "Monsoon + 1" for the delivery of the photosensitizer. As a photosensitizer, the mentioned cationic phthalocyanines were used in a concentration of 1.5-6.5 microns.

The treatment method is as follows: a patient through the freer half of the nose, after preliminary adrenalization, is introduced a polyvinyl chloride catheter with an inner diameter of 2 mm, through which a nozzle-guide for the ENT with a diffuser is connected, connected to the AFS “Solaris” phototherapeutic LED device, and it is carried out through the general nasal passage, nasopharynx and further on the eve of the larynx.

The ultrasonic inhaler "Monsoon + 1" is filled with 20 ml of a solution of a photosensitizer in a concentration of 1.5-6.5 microns and included in the network. When vaporization occurs, the patient inhales the mixture with his mouth for 2 minutes. Then, without stopping the inhalation of the mixture, they begin to conduct photodynamic therapy using the previously introduced fiber, for 10 minutes, then the fiber is removed and the photosensitizer is not inhaled.

The course of treatment is 3-10 sessions conducted daily, once a day.

The disadvantages of this method is that its use is possible only after the introduction of the fiber through the free half of the nose, which is extremely negatively tolerated by many patients. Also, the use of an inhaled photosensitizer does not allow reliable fixation of the photosensitizer in the laryngeal cavity, does not allow for a stable concentration of the photosensitizer throughout the entire photodynamic therapy session, and extends the course of PDT treatment to 10 sessions.

The objective of the invention is the development of a method for the treatment of acute inflammatory diseases of the larynx and pharynx or their purulent complications by the method of photodynamic exposure to ensure that a constant concentration of the photosensitizer is maintained throughout the treatment session.

The problem is solved in that a photosensitizer (PS) in the form of a powder based on sorbitol or starch with a PS concentration of 0.5% -1.0% is injected into the larynx or pharynx using a special nebulizer, then an optical fiber is inserted into the larynx from a therapeutic laser and irradiated areas of the larynx or abscess cavity are irradiated with a laser with a wavelength of 0.685 μm, the output radiation power. 18-20 mW with an energy density of 21-28.8 J / cm ² .

The method includes the use of a therapeutic LED laser device "Grenade" ALOD-01, in continuous mode, using a nozzle-fiber with a diffuser of 2 cm. For insufflation use a nebulizer for a powder photosensitizer in the laryngeal cavity of a special design, which is a double-lumen laryngeal nozzle, a pear with a valve for air injection and a flask for powder. The following drugs were used as a photosensitizer: Photosens, Holosens, methylene blue at a concentration of 0.5% and 1.0%. In all cases, the exposure of the photosensitizer was at least 10 minutes, and the irradiation of inflamed tissues in the larynx cavity was at least 1.5 minutes. Carrying out antimicrobial photodynamic therapy with an irradiation power of less than 18 mW is not effective, and with a value above 20 mW, the effectiveness of therapy does not increase. The concentration of photosensitizers should also be not lower than 0.5% (lower - ineffective) and not higher than 1.0% when the efficiency does not increase.

The technique consisted of the following: after opening an abscess in the larynx (abscess of the lingual surface of the epiglottis) or opening a paratonsillar abscess (or abscessesiltsillectomy) and evacuating the purulent contents in the abscess cavity and laryngeal cavity, a powder based on starch or sorbitol containing an photosensitizer was applied by insufflation; exposure was 10 minutes. Then, a fiber with a diffuser was installed in the abscess cavity and laser irradiation of the inflamed sections of the larynx was performed.

The following examples illustrate the invention.

Example 1

Patient I., 56 years old, complained of sore throat when swallowing, difficulty swallowing, fever up to 38 ° C after hypothermia. I did not receive specialized treatment. The patient had a history of a year ago - an abscess of the lingual surface of the epiglottis. It was treated stationary, an autopsy of the epiglottis was performed. As a result of the studies, the diagnosis was established: “Phlegmonous laryngitis. Abscess of the lingual surface of the epiglottis. "

Upon admission, an abscess of the lingual surface of the epiglottis was opened under local anesthesia. Received 3 ml of purulent discharge. Rinsed with an antiseptic solution. Half an hour after opening the abscess, an starch-based powder was applied to the abscess cavity using starch containing a Holosens photosensitizer in a concentration of 0.5% for 10 minutes. Then the ball was started with a PDT session with the Granat therapeutic semiconductor laser endolaryngially (2 minutes, 20 mW, energy density 21.0 J / cm ² ).

The next day, the patient noted a significant improvement, the temperature returned to normal. Indirect laryngoscopy revealed an improvement: the entrance to the larynx is free. The epiglottis is somewhat hyperemic, mobile, on its lingual surface on the left - linear incisio, the edges of the wound with plaque of fibrin. Hemorrhagic discharge was found in the abscess cavity. Then, a second PDT session was carried out according to the method described above.

On the third day after admission to the ENT hospital, the patient had no complaints. An improvement was noted. Indirect laryngoscopy showed moderate pastorality of the epiglottis. The phenomena of inflammation in the larynx have almost completely subsided. Held another PDT session.

On the fourth day after the onset of inflammation in the larynx completely subsided, in the clinical analysis of blood normalization of laboratory parameters occurred. The patient was prepared for discharge from the ENT hospital for outpatient monitoring.

Example 2

Patient G., 24 years old. Received complaints of sore throat when swallowing, difficulty opening the mouth, fever up to 38.0 ° C. According to the patient, the above complaints worry 2 days after hypothermia; I did not receive specific treatment. According to the results of the examination, the diagnosis was made: “Right-sided paratonsillar abscess. Chronic tonsillitis, TAF I ". Upon admission to the ENT department, an operation was performed - "opening the paratonsillar abscess on the right", an abundant purulent discharge was obtained. On the same day, a course of antimicrobial and anti-inflammatory photodynamic therapy was started, consisting of the following: starch-based powder was applied to the abscess cavity and right palatine tonsil containing 0.5% methylene blue photosensitizer by insufflation. The exposure was 10 minutes. Next, a fiber with a diffuser from an IR laser ALOD-01 "Granat" with a wavelength of 0.685 μm was installed in the abscess cavity. A session of antimicrobial photodynamic therapy was performed: 4 minutes, energy density 25.2 J / cm ² , power 18 mW.

The next day, the patient noted improvement. The temperature returned to normal. When examining the pharynx, an improvement was also noted: the soft palate is slightly asymmetric, the right palatine tonsil extends beyond the palatine arches, is hyperemic, there are no raids. Then a second session of antimicrobial PDT was carried out according to the specified method.

On the third day after the start of treatment, the patient had complaints of discomfort in the field of surgical intervention, weakness, an improvement in the general condition was noted. When examining the pharynx of a purulent discharge from the cavity, an abscess was not received. The opening of the mouth was free, the right palatine tonsil was slightly pasty. Then a third session of antimicrobial PDT was performed.

On the fourth day, the patient showed no complaints. On examination, the soft palate was symmetrical. No purulent discharge was obtained from the abscess cavity. In a clinical blood test, normalization of clinical and laboratory data. The patient was discharged for outpatient observation at the clinic at the place of residence.

Example 3

Patient S., 26 years old. He entered the ENT department with complaints of sore throat when swallowing, difficulty opening his mouth, an increase in body temperature to 38.5 ° C for about 3 days, was treated independently, without a lasting effect. Previously denied paratonsillar abscesses. The patient was previously bothered by frequent sore throats. As a result of the studies, the diagnosis was made: "Left-sided paratonsillar abscess, left-sided parapharyngitis." On the day of admission, an operation was performed - "Left-sided abscessesillectomy with revision of the parapharyngeal space, right-sided tonsillectomy." On the same day, the PDT course was started, which consisted of the following: a starch-based powder containing photosensitizer Photosens at a concentration of 1.0% was injected into the fistula into the parapharyngeal space using a photosensitizer, the photosensitizer was also applied to the right and left tonsils, the application was 10 minutes. Next, a fiber with a diffuser from the ALOD-01 Granat IR laser with a wavelength of 0.685 μm was introduced into the parapharyngeal fistula for 4 minutes with an energy density of 28.4 J / cm ² with a power of 20 mW.

On the next day after the onset of antimicrobial PDT, the patient noted an improvement, the temperature decreased to subfebrile values. When revising the parapharyngeal space, a slight purulent discharge was obtained. Then, a second session of antimicrobial PDT was carried out according to the above scheme.

On the third day, the temperature returned to normal. The patient noted complaints of discomfort in the field of surgical intervention, weakness. When revising the parapharyngeal space, a purulent discharge was not obtained. Next, a third session of antimicrobial PDT was carried out according to the method described above.

On the fourth day after surgery and the beginning of antimicrobial photodynamic therapy, the patient noted a significant improvement in general condition, complained of discomfort in the field of surgical intervention, weakness. On examination: the soft palate is symmetrical, the tonsil niches are free, covered with a touch of fibrin. Purulent discharge was not received. Then, a fourth session of antimicrobial PDT was performed according to the above scheme.

On the fifth day, the patient had no complaints. Clinical and laboratory data were within normal limits. The patient was prepared for discharge from the ENT hospital for outpatient monitoring of the ENT doctor in the clinic at the place of residence.

Example 4

Patient S., 24 years old. I went to the ENT department with complaints of severe sore throat radiating to the right ear, weakness, difficulty swallowing, and an increase in body temperature to 38.5 ° C. As a result of the conversation with the patient, it was found that the above complaints were disturbed for 2 days after cooling and eating cold drinks. The patient did not receive specific treatment. After examination, the patient was diagnosed with Follicular tonsillitis.

On the day of the examination, the patient began a course of antimicrobial photodynamic therapy, which consisted of the following: a sorbitol-based powder containing a 0.5% methylene blue photosensitizer was applied to the surface of the tonsils, a 10-minute exposure. Next, a fiber with a diffuser from the ALOD-01 Granat IR laser with a wavelength of 0.685 μm was introduced into the pharynx for 2 minutes with an energy density of 23.4 J / cm ² and a power of 18 mW. The next day, the patient noted a significant improvement, sore throat was almost completely absent, the temperature was 37.1 ° C. On examination, hyperemia and edema of the tonsils were significantly reduced. There were no raids on the tonsils. Then, a second session of antimicrobial photodynamic therapy was performed according to the above scheme.

On the third day after the start of treatment, the patient had no complaints. The sore throat subsided. Clinical and laboratory data returned to normal. Clinical manifestations of angina were absent.

Thus, the proposed method provides: the introduction of a photosensitizer without percutaneous surgical intervention, maintaining a constant concentration of the photosensitizer throughout the treatment session, eliminating more severe purulent complications, reducing the frequency and volume of surgical procedures, reducing the patient’s hospital stay due to the acceleration of the relief of the inflammatory process and rehabilitation, effective PDT of the specified area. Reliable fixation of the powder-based photosensitizer in the larynx was also noted for another hour after the completion of the antimicrobial photodynamic therapy session.

Claims (2)

1. A method of antimicrobial photodynamic therapy of acute inflammatory diseases of the larynx and pharynx or their purulent complications, which consists in introducing into the larynx of the pharynx a photosensitizer in the form of a powder based on starch or sorbitol with a photosensitizer content of 0.5-1.0% by insufflation and subsequent laser irradiation with a wavelength of 0.685 microns, with a capacity of 18-20 mW and an energy density of 21.0-28.8 J / cm ² . 2. The method according to claim 1, characterized in that spend 2-5 sessions of photodynamic therapy.