The way photodynamic treatment of acute and chronic purulent sinusitis

 

(57) Abstract:

The invention relates to medicine, and is intended for the treatment of acute and chronic sinusitis. Maxillary sinus exempt from the content, give it the photosensitizer (PS). At the same time as FS using chlorophyll-type porphyrins. Carry out the irradiation of the walls of the sinus laser radiation with a wavelength matching the wavelength of peak absorption used FS for 10-60 min and with a capacity of 0.10-0.35 watts. Irradiation is carried out by laser radiation wavelength 654-670 nm and the dose of 10-1000 j/cm2. Irradiation of the walls of the sinus spend 2 hours after the introduction of the FS. The set dose is conducted in stages, with intervals of 20-30 s, during which the sinus blow, freeing from accumulation of mucus. Maxillary sinus before and 2 h after injection in her FS was washed with saline solution. Subsequently, after treatment 3-5 days shall lavage of the maxillary sinus saline solution. The method provides a complete reorganization of the maxillary sinus, shortens treatment and prevent relapse. 5 C.p. f-crystals, 5 PL.

The invention relates to medicine and can be used in otorhinolaryngology for treatment the of belongs to the so-called “photodynamic therapy” (PDT). Photosensitizers (PS) are used in photodynamic therapy as therapeutic agents.

Known methods of treatment of acute exacerbation of chronic purulent sinusitis when to release sinus from pus make a special puncture needle (needle Kulikovskii) and a sinus wash off pus from sterile saline solution or any antiseptic (furatsilin), followed by the introduction (instillation) in her antibacterial drugs or other pharmaceutical products, contributing to the elimination of the inflammatory process [1]. However, this method of treatment after a single and sometimes multiple rinsing the sinuses with subsequent instillation of drug substances quite often does not give the desired positive effect, i.e. does not cure the disease (purulent sinusitis), which forces the doctor again and again to resort to the puncture of the maxillary sinus and massive antibiotic treatment.

Also known is a method of surgical treatment (hamartoma) purulent sinusitis, especially frequently used in the chronic form of this disease, when conservative treatment with repeated Cycling is edenia this method of treatment is based on the fact, by opening the maxillary sinus from it remove the possibility of the entire mucous membrane, which should facilitate the termination of purulent inflammatory process [2]. However, this method does not guarantee a cure, because there are known cases of recurrent suppurative inflammation and after radical surgery of the maxillary sinus (according to different authors, up to 30%).

To the above must be added that at present, all known methods of treatment of purulent inflammation of the maxillary sinus (sinusitis) carried out with the obligatory use of antibiotics, which affect not only strictly locally in inflammation, but also on the whole body, often leading to the development of allergic reactions. If antibiotics are used without regard to the sensitivity to the microflora of inflammation, it leads to the development of addiction and the increasing resistance of pathogenic microbes, which in turn contributes to the chronicity of the inflammatory process.

The disadvantages of the above methods of treatment of a genyantritis has led to the need to formulate and solve the problem of searching an efficient, safe and rapid therapeutic way to influence changed the about and chronic purulent sinusitis by affecting the inflammation of the photodynamic reaction, in which for the full rehabilitation of the maxillary sinus, reduction of terms of treatment and prevention of recurrence of the disease in the maxillary (maxillary) sinus injected photosensitizer and spend processing of the mucous membrane of the photosensitizer (incubation) followed by radiation to the walls of the sinus laser radiation. As photosensitizer using chlorophyll-type porphyrins and lead exposure laser radiation wavelength 654-670 nm, power 0,10-0,35 W within 10-60 min before reaching the dose 10-1000 j/cm2.

The present invention fundamentally differs from all known as by way of impact on the home purulent inflammation, and the final result from the treatment. The basis of the proposed method is the principle of interaction between two components, each of which in isolation is ineffective or not effective at all. In this case, the effect of the treatment comes as a result of photochemical reactions initiated by the interaction of FS entered into the inflammatory focus, with laser radiation with a wavelength matching the wavelength of peak absorption of this FS. This method is successfully applied for the treatment of neoplastic diseases, however, in mo [5, 6]. However, it is not known use of the method of PDT for the treatment of purulent maxillary sinusitis.

Used in the present invention lasers have a wavelength in the range 654-670 nm (in each case coincides with the maximum absorption of the drug is 3 nm, which is important for efficient generation of active particles), characterized by the presence of semiconductor components and generation of radiation (increased reliability and stability of the emission wavelength), small weight and overall dimensions (ease of use).

As a photosensitizer can be used FS “Radachlorin” [3] or FS “Potohari II [4], the incubation time may be 2 hours, and the quality of the laser radiation can be used radiation wavelength 654-670 nm, power 0,10-0,35 W within 10-60 min once.

FS “Radachlorin” is characterized by the fact that it includes alkaline Sol-13-carboxy-17[2-carboxyethyl]-15-carboxymethyl-17,18-TRANS-dihydro-3-vinyl-8-ethyl-2,7,12,18-tetramethylpiperidine (chlorin e6) formula

in the amount of 80-90%; alkaline salt 13-carboxy-17-[2-carboxyethyl]-15-formyl-17,18-TRANS-dihydro-3-vinyl-8-ethyl-2,7,12,18-tetramethylpiperidine (purpurine 5) formula

6) formula

in the number - rest.

FS “Potohari II is characterized by the fact that it includes alkaline salt 13-carboxy-17-[2-carboxyethyl]-15-carboxymethyl-17,18-TRANS-dihydro-3-[1-ethoxyethyl]-8-ethyl-2,7,12,18-tetramethylpiperidine (2-devinyl-2-[1-ethoxyethyl]chlorin e6) formula

These FS can be used in the form of an aqueous solution.

As the alkali metal may be sodium or potassium.

Physico-chemical properties of FS described in examples 1, 2. Biological activity of photosystem evaluate in vitro and in vivo (examples 3-7).

FS “Radachlorin” and “Potohari II” from the point of view of physical chemistry have the ability to absorb light in the visible region, resulting in their photo-activation and subsequent relaxation of the excited state by energy transfer to dissolved in the tissues of molecular oxygen and organic substrates. The latter leads to oxidative and free-radical processes in biological tissues, facilitating their release from pathogenic microorganisms. The most preferred band excitation is the long wavelength band, because with increasing wavelength grows penetrating the JV is to destroy microorganisms and aseptically to act on the biological tissue after excitation with light of wavelength 654-670 nm at a depth of 10 mm (see tab.1).

The balance of the Federal Assembly of amphiphiles confirm the standard experiment in vitro [7] (table 2, Example 2). The distribution coefficient FS in 1-octanol/phosphate buffer, pH 7.4 (Kp), equal to 1.40 for the “Radachlorin” and 2,40 for Photochlorin II. This means that the proposed FS equally well soluble both in aqueous and the lipid phase, and proves the lipophilicity of the Federal Assembly, which allows them to be transferred from the water in the cytoplasmic membrane of bacterial cells rapidly enter cells and to accumulate in cytoplasmic intracellular membranes and microsomes, or you can enter cells by diffusion through the plasma membrane of these cells.

Thus, FS “Radachlorin” and “Potohari II” have the ability to selectively accumulate in infected pockets, along with a strong photodynamic activity.

For research dasavasebeli cytopathologically (after laser exposure and biological "dark" activity FS using the MTT-test, which allows to accurately determine the number of living cells after they are processed FS and irradiation with a laser to calculate the cytotoxic and cytopathological indexes [8]. With long-term action “Radachlorin” at a concentration of 5 M on the cells in the dark survived 96,5-86.2% of PC-12. In these conditions, the DNA synthesis in the cells of the PC-12 was almost unchanged. In General, for FS in the absence of irradiation more typical manifestation of the cytotoxic activity than the induction of proliferative. After laser irradiation, cells treated with FS, there is their death. Found a dose-dependent cytopathological effect of the drug that allows you to calculate EC50, i.e., to determine the concentration of FS that will kill 50% of cells. These data are shown in table 2. It should be noted that FS, at which the EU50less than 20 M, it is considered effective to suppress bacterial cultures. The investigated cell line highly sensitive to the action of laser irradiation after they are processed FS (data MTT-test). When determining generatesecret after treatment of cells with 5 M FS and exposure to get laser sharp decrease in DNA synthesis (96,5% compared to irradiated control) cells.

Thus, the FS are vysokotekhnologichnye drugs. In high concentrations (>5 M) they are moderate inhibitors of cell growth and without irradiation. High generatesecret FS optimum activity of photosystem confirmed by the results obtained in in vitro experiments.

The causative agents of acute and chronic sinusitis are gram-positive (Streptococcus, Staphylococcus, pneumococcus) and gram (Hemophilus influenzae, Moraxella catarrhalis) bacteria and yeast fungi of the genus Candida.

Because gram-negative bacteria and yeast are much more resistant to photodynamic effects compared to gram-positive bacteria [12-14] to determine the effectiveness of the photosensitizer and failover modes photodynamic treatment was carried out on test systems for gram-negative bacteria (Example 3) and Candida (Example 4).

In vivo study of the toxic properties of FS [8] (Example 5). LD50on average, taking into account the weighting factor for the “Radachlorin”, 147 mg/kg, and the dose causing the death of 10% of the test animals (LD10) is 119 mg/kg of the Carried out researches allow to classify both FS as “Toxic substances”.

To activate FS used laser diode module for photodynamic therapy ML500-SP (“LAHTA”), developed by ZAO "MILON LASER" (, St. Petersburg) [11]. This module has a capacity of 2.5 W in the fiber of 250 μm by photodynamic and laser therapy “Sunny 662/810”, developed by OOO "SIGMA PLUS", Moscow). The module has up to three channels (capacity of 1.2 or 2.5 watts each, in the fiber 250 µm aperture is 0.22) and the maximum wavelength 6563 nm, 6623 nm, 8083 nm. In General, activation of FS can use any lasers with a capacity of not less than 0.1 watts maximum wavelength 654-670 nm and equipped with a connector for connecting a fiber-optic waveguide, which may be at the end as a straight edge, and a cylindrical diffuser of different lengths.

The value supplied energy range from 60 to 1260 j (0,10-0,35 W within 10-60 min). When the laser power below 0.10 W procedure PDT becomes excessively long. At light doses of more than 1250 joules significant damage to healthy tissue, leading to an increase of the period of regeneration.

The proposed method of treatment is as follows. In the presence of a purulent process (acute or chronic) in the maxillary (maxillary) sinus, the latest release from contents (mucus and pus) by puncture standard method followed by washing sinus sterile saline. After rinsing fluid is clean (eye - ad oculus),the Kulikovsky extracted from punctional sinus and a cotton pad tightly plugging the common nasal passage in order to prevent leakage of mortar FS, then the patient is placed on the same side in the bed. Thus, while in a horizontal position the patient spends two hours, alternately changing the position (on the side on the back), but not standing up and not lying down on his stomach and the opposite side. After two hours, when FS maximum penetrates into the superficial layers of the epithelium and the rest in the bosom of the microbes, the patient again the dotted line, but in the bosom on the needle Kulikovskii enter the drainage system through which your bosom again thoroughly washed with saline solution and rinsed. At the final stage of the procedure in the sinus through the drainage impose quartz-polymer fiber (light guide), which transmit the laser light and is irradiated sinus mucosa during the time required to achieve the required dose, which goes photochemical reaction (10-1000 j/cm2). A set of radiation dose in time can be phased with a small (20-30 sec) intervals, during which the sinus blow, freeing the latter from accumulation of mucus. After the laser irradiation, the fiber is extracted, leaving the sinus drainage tube. Through this drain tube in the next 3-5 days after photodynamic therapy daily exercise rinse the region is abundant sleeveline. If your bosom to leave without drainage and not to puncturevine in these days, the patient may develop aseptic inflammation with severe hypertensive syndrome (swelling and pain in the sinuses). During the last rinse sinus carry out bacteriological control.

Example 1. Description of physico-chemical properties of FS.

FS is a liquid, black in color, thin layer of acquiring a green tint, with a characteristic odor.

Solution “Radachlorin” ethanol has a yellow-green color, and “Photochlorin II” - bright green. When passing through the solution layer of the light rays from the lamp medical blue marks MDS 220-75 (TU 16.535.376-79) in the dark place, the solution becomes a ruby-red color.

To authenticate to 10 ml of FCS was added diluted hydrochloric acid and the precipitate discarded FS, which is filtered off, dried in vacuum over pjatiokisi phosphorus within 12 h and remove PMR, mass spectra and absorption spectrum in the wavelength range 360-720 nm.

Range PMR FS “Radachlorin”: (DMSO-D6, conc. the solution): 9,64, 9, 55, 9,52, 9,39, 8,90, 8,79 (s, meso - chlorin e6and purpurine 5), 8,09, 8,04, 7,97, 7,92 (2D, C=CH/SUB>COOH), 4,60 (m, 7-), of 4.45 (m, 8-), 3.80, 3,56 (CH, 4-C2CH3), 3.75, 3,64, 3,51, 3,46, 3,29, 3,23 (C, nuclear3chlorin e6and purpurine 5), 2,38, 2,32 (2m, 7-C2CH2COOH), 2,71, 2,20 (2m, 7-C2CH2COOH), of 1.76 (d, 8-C3), 1,72 (t, 4-CH2WITH3), - 1,63, is 1.91 (2c, 2N) M. D.

The mass spectrum of the “Radachlorin”: e.i., M+(%), 596 (16,0), 566 (9,4), 508 (100,0), 494 (7,3), 447 (9,4), 435 (50,6), 421 (12,8), 405 (6,9), 254 (7,4).

Absorption spectrum “Radachlorin” visible: () (ethanol), 386 (22310), 406 (113040), 506 (14870), 536 (8925), 608 (7437), 662 (34220).

According to PMR spectrum, the substance contains 80% of chlorin e6, 15% of purpurine 5 and 5% of chlorin p6(minor signals at 9,25, 9,10, 8,71, 7,84, 3,55, 3,32, 3,04 memorial plaques), which corresponds to a patentable composition. According to the mass spectrum contains peaks of molecular ions 596 from chlorin e6and 566 from purpurine 5. In the absorption spectrum has a band at 662 nm with the magnitude of the absorption, is well correlated with the molecular extinction pattern FS (34230).

Therefore, the studied sample is the “Radachlorin”.

Example 2. The distribution coefficient n-octanol/phosphate buffer, pH 7.4. Shake for 20 with 300 ml of n-octanol and 300 ml of phosphate buffer solution, pH 7.4, and for stratifying centrifuged 10 min pryamo 0.1 ml with a concentration of FS 5 mg/ml and determine the absorption maximum at a wavelength of 406 nm. Get the values of Dtoand DbKwhere o - n-octanol, b - phosphate buffer to control. Equilibrium distributions of the n-octanol/phosphate buffer to achieve, shaking at 20 ° C with 2 ml of phosphate buffer and 8 ml of n-octanol with 0.1 ml of FCS for 20 s, followed by centrifugation for 10 min at 10000 rpm by Measuring the optical density of each phase at 406 nm, gain values D and Dbwhere o - n-octanol, b - phosphate buffer.

TOpdetermined by the formula:

TOp= (D V DtoVto)/(DbVbDbtoVbto), where V is the volume of octanol taken to determine the equilibrium distribution (8 ml), Vbto- the volume of octanol saturated with water, taken to control for absorbance of aliquots (8 ml), Vb- the volume of the buffer is taken to determine the equilibrium distribution (2 ml), Vbto- volume of buffer saturated with octanol taken to control for absorbance of aliquots (2 ml). The experiment is carried out 3 times and the obtained values TOpaverage.

Get the value 1,40,3 for “Radachlorin” and 2,40,4 for Photochlorin II”, which means that the proposed FS - amphiphilic substances.

Example 3

To rehydration samples of bacteria (1 ml) E. coli TG1 (rhap) was added to 0.35% aqueous solution of Radachlorin to the final concentration in the assay of 10 μm and after 10-60 min incubation was irradiated with laser light 662 nm with 100 mW (irradiation dose of 150 j/cm2). The intensity of the luminescence of the bacteria was detected using a luminometer "Biotox-6". The results of the experiment are shown in table 3.

Thus, the full repayment of bioluminescence and, consequently, loss of colony forming ability (KOS) preincubating with Radachlorin 662 nm and irradiated cultures of bacteria E. coli TG1 (rhep) shows high antibacterial activity of this FS. Maximum photodynamic effect was achieved at the time of inactivated 60 minutes

Example 4. For selection of effective photosensibilisation (1 ml) Candida guilliermondi added 0,35% aqueous solution of Radachlorin to the final concentration in the sample of 10-20 μm, and after 10 min incubation was irradiated with laser light 662 nm with 100 mW. The results of the experiment are shown in table 4.

The data show that complete loss of colony forming ability preincubating 10 min with Radachlorin 662 nm and irradiated cultures of yeast fungi Candida guilliermondi is achieved when the concentration of the FC 10 μm and the dose of 150 j/cm2or 20 μm and the dose of 75 j/cm2.

Thus, a complete inactivation of yeast fungi occurs when the parameters influences the concentration of FC and radiation dose), less than or equal to those for gram-negative bacteria.

Example 5. The study of the toxic properties of FS in vivo.

Toxicity study with intravenous FS laboratory white mice weighing 19-21 g (kennel Russian Academy of medical Sciences, Department of Kryukovo). Animals are contained in standard vivarium conditions and feeding is carried out in accordance with the Order of Ministry of health of the USSR No. 1179 from 10.10.83 of the year “On approval of regulations of the cost of feed for laboratory animals in health care facilities”.

Toxicity is determined by the deaths of animals, after calculating sredneseriynoe dose - LD50. The calculation carried out by statistical methods, recommended by the State Pharmacopoeia XI edition (1, 3). On the basis of Sterner. They also hold into account the reactions of intoxication during the experiment.

In the experience of selected mice of 12 individuals (6 males and 6 females) for each tested dose FS. To determine LD50FS examine the following doses: 5, 10, 15, 20, 30, 40, 50, 75, 100, 125, 150, 175, 200, 225, 250, 275 mg/kg of solution with a concentration of 5 mg/ml FS administered to mice intravenously, by varying the dose-volume filesystem.

Get the value LD50“Radachlorin” equal to 147 mg/kg LD50equal to 119 mg/kg, and for “Photochlorin II”, respectively, 153 mg/kg and 92 mg/kg, which means that the proposed FS are low-toxic compounds (table.5).

Example 6. Patient K., 1957 R. (I. B. No. 6809/01), was admitted in the ENT clinic MONICA complaining purulent discharge from the right half of the nose, congestion and difficulty breathing nose to the right, headache, localized predominantly in the frontal area.

From the anamnesis: ill for 7 months prior to admission. Was treated at the place of residence antibacterial drugs, physiotherapy, in the last 2 months was made about 30 punctures the right maxillary sinus. Every time you flush the sinuses got purulent discharge.

Admission: General condition abolishe through the right half of the nose, the nasal septum in the midline, mucous membrane and lower swollen nasal turbinates, on average, the forward course right after anemizatsii - Muco-purulent discharge. Clinical blood and urine in normal limits. Radiographically: total darkening of the right maxillary sinus. When the puncture received around 4.0 ml of purulent discharge with an unpleasant odor. Microbiological study detachable selected bacteria of the genus Haemophilus<103.9/l). Other values were within normal limits. When the control seeding wash water right maxillary sinus with its puncture on the 11th day after the session of PDT - growth no. According to the results of diagnostic microhaematuria on day 12 after photodynamic therapy histologically determined that the mucous membrane of the sinuses are covered with respiratory epithelium, subepithelial based on edema, hyperemia of the vessels, polymorphic cell inflammatory infiltration with a high content of eosinophils.

The patient was discharged on the 20th day after photodynamic therapy in satisfactory condition, clinical blood and urine in normal breathing through the nose is not difficult, in the nasal passages detachable no.

In the follow-up after 3 and 6 months after discharge from the hospital breathing through the nose at this sick free, discharge, pain complaints were not filed.

Example 7. Patient D., 1957 R. (I. B. No. 19058), was admitted in the ENT clinic MONICA complaining purulent discharge from the right half of the nose, frequent headaches.

Considers herself a patient in the last 2 years. Was treated at the place of residence by puncture of the right maxillary sinus, antibacterial and phyto-ven, made 12 sinus punctures, each time I got a purulent discharge.

Admission: General condition is satisfactory, internal organs: chronic salpingo-oophoritis. Status localis: breathing is not difficult, the columella moderately curved to the right, the mucous membrane of the nasal cavity edematous, cyanotic tint, discharge in the nasal passages no. When the rear rinoskopii: in nasopharynx to the right is determined by Muco-purulent discharge. Clinical blood and urine within normal limits. Radiographically: right maxillary sinus intensively homogeneous dark, veiled cells of the ethmoid labyrinth on the right. When the puncture received scant purulent discharge with no smell. Microbiological study detachable selected E. coli 106.

The patient was carried out washing the right maxillary sinus through the established drainage with the introduction of antiseptic solutions on a background of antibacterial and anti-inflammatory therapies, washing the sinuses method move with no apparent positive effect. On day 10 of treatment, the patient performed a session of PDT in the mode of 0.10 W, exposure time 60 min (FS “Potohari II solution for HV the functions of the right maxillary sinus, slight pain in her eyes, pain in the right eye socket and discomfort in the area of projection of the right frontal sinus. In the following PDT 5 days daily through drainage of the sinus was rinsed with sterile saline. On day 7 after photodynamic therapy in clinical blood and urine dynamics were observed. Control seeding wash water right maxillary sinus with its puncture 10 days after photodynamic therapy the growth of microorganisms is not given. The patient was discharged 14 days after photodynamic therapy in satisfactory condition, clinical blood and urine in normal breathing through the nose is not difficult, in the nasal passages detachable no, when the rear rinoskopii determined mucous discharge in the nasopharynx to the right.

According to the follow-up monitoring after 3 and 5 months after discharge from the hospital breathing through the nose, the patient is free, the nasal cavity is a small amount of mucus, pain complaints there.

Sources of information

1. A. I. Feldman, S. I. Wolfson “diseases of the ear and upper respiratory tract in children”. M - “Midges”. - 1950. - S. 264-265.

2. B. C. Pogosov “Atlas of operative otorhinolaryngology. M - “Medicine”. - 1983. - S. 227.

3. Reshetnikov A. C., Seow C. A., A. Lappa Century, Novels Century A. the Photosensitizer and the method of its production. // Patent RF №2183956, issued June 27, 2002, a Positive decision of 21 December 2001 on the application number 2001108397 dated March 30, 2001

4. A. C. Reshetnikov, A. C. Ivanov, O. S. Abakumov, A. T. Gridyushko, I. D. Zalewski, A. Century Of Carmean, C. P. Laptev, N. P. Neugodova. Evaluation of biological properties of new chlorin photosensitizers series. In Proc. of “the Use of lasers for the diagnosis and treatment of diseases. Research and information collection (application for Bulletin “Laser-inform”), vol.3, 34-40 (2001).

5. P. I. Tolstykh et al. “Photodynamic therapy in the complex treatment of purulent wounds in patients with diabetes mellitus” in proceedings of international. proc. “Laser and information technologies in medicine of the XXI century”. SPb, 2001. - S. 449-450.

6. A. B. Schechter et al. “Experimental rationale for the use of photodynamic therapy for the treatment of purulent wounds”. Ibid - S. 457-458.

7. Kessel D. Biochemistry. 1977. V. 16. R. 3443-3449.

8. A. V. Reshetnickov, et. al. In Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy IX. - T. J. Dougherty, ed., 2000, Vol. 3909, p.124-129.

9. A. E. Medvedev et al., Biomed. Science, 1990, V. 1, p.261.

10. O. Yu. Abakumova, et. al., J. Neural. Transm. Suppl. 3, 1998, V. 52, p.87.

11. Certificate of Ministry of health of the Russian Federation.N. Photodamage of gram-positive and gram-negative bacterial cells in the presence of derivatives of chlorin e6. Microbiology, 1991, T. 60, vol.3, 507-511.

1. A method of treating acute and chronic sinusitis, characterized in that the maxillary sinus is released from the content, give it the photosensitizer (PS), the FS using chlorophyll-type porphyrins and carry out the irradiation of the walls of the sinus laser radiation with a wavelength matching the wavelength of peak absorption used FS for 10-60 min and with a capacity of 0.10-0.35 watts.

2. The method according to p. 1, characterized in that the irradiation is carried out by laser radiation wavelength 654-670 nm and the dose of 10-1000 j/cm2.

3. The method according to PP.1 and 2, characterized in that the irradiation of the walls of the sinus spend 2 hours after the introduction of the FS.

4. The method according to PP.1-3, characterized in that the set dose of the irradiation is conducted in stages, with intervals of 20-30 s, during which the sinus blow, freeing from accumulation of mucus.

5. The method according to PP.1-4, characterized in that the maxillary sinus before and 2 h after injection in her FS was washed with saline solution.

6. The method according to PP.1-5, x is ideological solution.

 

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FIELD: medicine.

SUBSTANCE: method involves introducing 0.1-0.3 ml of photosensitizing gel preliminarily activated with laser radiation, after having removed neovascular membrane. The photosensitizing gel is based on a viscoelastic of hyaluronic acid containing khlorin, selected from group containing photolon, radachlorine or photoditazine in the amount of 0.1-2% by mass. The photosensitizing gel is in vitro activated with laser radiation having wavelength of 661-666 nm during 3-10 min with total radiation dose being equal to 100-600 J/cm2. The gel is introduced immediately after being activated. To compress the retina, vitreous cavity is filled with perfluororganic compound or air to be further substituted with silicon oil. The operation is ended with placing sutures on sclerotomy and conjunctiva areas. Compounds like chealon, viscoate or hyatulon are used as viscoelastic based on hyaluronic acid. Perfluormetylcyclohexylperidin, perfluortributylamine or perfluorpolyester or like are used as the perfluororganic compound for filling vitreous cavity.

EFFECT: excluded recurrences of surgically removed neovascular membrane and development of proliferative retinopathy and retina detachment; retained vision function.

3 cl, 5 dwg

FIELD: medicine.

SUBSTANCE: method involves making incision in conjunctiva and Tenon's capsule of 3-4 mm in size in choroid hemangioma projection to sclera 3-4 mm far from limb. Tunnel is built between sclera and Tenon's capsule to extrasclerally introduce flexible polymer magnetolaser implant through the tunnel to the place, the choroid hemangioma is localized, after performing transscleral diaphanoscopic adjustment of choroid hemangioma localization and size, under visual control using guidance beam. The implant has permanent ring-shaped magnet in the center of which a short focus scattering lens of laser radiator is fixed. The lens is connected to light guide in soft flexible envelope. The permanent implant magnet is axially magnetized and produces permanent magnetic field of 2-3 mTesla units intensity. It is arranged with its north pole turned towards the choroid hemangioma so that extrascleral implant laser radiator disposition. The other end of the implant is sutured to sclera 5-6 mm far from the limb with two interrupted sutures through prefabricated openings. The implant is covered with conjunctiva and relaxation sutures are placed over it. Light guide outlet is attached to temple using any known method. 0.1-1% khlorin solution is injected in intravenous bolus dose of 0.8-1.1 mg/kg as photosensitizer and visual control of choroid hemangioma cells fluorescence and fluorescent diagnosis methods are applied. After saturating choroid hemangioma with the photosensitizer to maximum level, transscleral choroid hemangioma laser radiation treatment is carried out via laser light guide and implant lens using divergent laser radiation at wavelength of 661-666 nm with total radiation dose being equal to 30-120 J/cm2. The flexible polymer magnetolaser implant is removed and sutures are placed on conjunctiva. Permanent magnet of the flexible polymer magnetolaser implant is manufactured from samarium-cobalt, samarium-iron-nitrogen or neodymium-iron-boron system material. The photosensitizer is repeatedly intravenously introduced at the same dose in 2-3 days after the first laser radiation treatment. Visual intraocular neoplasm cells fluorescence control is carried out using fluorescent diagnosis techniques. Maximum level of saturation with the photosensitizer being achieved in the intraocular neoplasm, repeated laser irradiation of the choroid hemangioma is carried out with radiation dose of 30-60 J/cm2.

EFFECT: enhanced effectiveness of treatment.

4 cl

FIELD: medicine.

SUBSTANCE: method involves creating tunnel between sclera and Tenon's capsule in intraocular neoplasm projection. Intraocular neoplasm localization and size is adjusted by applying transscleral diaphanoscopic examination method. 0.1-0.3 ml of photosensitizing gel based on viscoelastic of hyaluronic acid, selected from group containing chealon, viscoate or hyatulon, is transsclerally introduced into intraocular neoplasm structure using special purpose needle in dosed manner. The photosensitizing gel contains khlorin, selected from group containing photolon, radachlorine or photoditazine in the amount of 0.1-1% by mass. Flexible polymer magnetolaser implant is extrasclerally introduced into the built tunnel in intraocular neoplasm projection zone under visual control using guidance beam. The implant has permanent ring-shaped magnet axially magnetized and producing permanent magnetic field of 3-4 mTesla units intensity, in the center of which a short focus scattering lens of laser radiator is fixed. The lens is connected to light guide in soft flexible envelope. The implant is arranged with its north pole turned towards the intraocular neoplasm so that implant laser radiator lens is extrasclerally arranged in intraocular neoplasm projection zone. The implant light guide is sutured to sclera 5-6 mm far from the limb with single interrupted suture. The implant is covered with conjunctiva and relaxation sutures are placed over it. Light guide outlet is attached to temple using any known method. Visual control of intraocular neoplasm cells is carried out by applying fluorescence and fluorescent diagnosis methods. After saturating the intraocular neoplasm with the photosensitizer to maximum saturation level, transscleral intraocular neoplasm laser radiation treatment is carried out via laser light guide and implant lens using divergent laser radiation at wavelength of 661-666 nm. The treatment course being over, the flexible polymer magnetolaser implant is removed and sutures are placed on conjunctiva. Permanent magnet of the flexible polymer magnetolaser implant is manufactured from samarium-cobalt, neodymium-iron-boron or samarium-iron-nitrogen. 0.1-1% khlorin solution as photosensitizer, selected from group containing photolon, radachlorine or photoditazine, is additionally intravenously introduced in 2-3 days at a dose of 0.8-1.1 mg/kg and repeated laser irradiation of the intraocular neoplasm is carried out with radiation dose of 30-45 J/cm2 15-20 min later during 30-90 s.

EFFECT: complete destruction of neoplasm; excluded its further growth.

4 cl

FIELD: medicine.

SUBSTANCE: method involves applying transscleral diaphanoscopic examination method for adjusting intraocular neoplasm localization and size. Rectangular scleral pocket is built 2/3 times as large as sclera thickness which base is turned from the limb. Several electrodes manufactured from a metal of platinum group are introduced into intraocular neoplasm structure via the built scleral pocket. Next to it, intraocular neoplasm electrochemical destruction is carried out in changing electrodes polarity with current intensity of 100 mA during 1-10 min, and the electrodes are removed. Superficial scleral flap is returned to its place and fixed with interrupted sutures. 0.1-2% aqueous solution of khlorin as photosensitizer, selected from group containing photolon, radachlorine or photoditazine, is intravenously introduced at a dose of 0.8-1.1 mg/kg. Visual control of intraocular neoplasm cells is carried out by applying fluorescence and fluorescent diagnosis methods. After saturating the intraocular neoplasm with the photosensitizer to maximum saturation level, transpupillary laser radiation of 661-666 nm large wavelength is applied at a dose of 30-120 J/cm2. the operation is ended with placing sutures on conjunctiva. Platinum, iridium or rhodium are used as the metals of platinum group. The number of electrodes is equal to 4-8. 0.1-1% khlorin solution, selected from group containing photolon, radachlorine or photoditazine, is additionally repeatedly intravenously introduced in 2-3 days at a dose of 0.8-1.1 mg/kg. Visual control of intraocular neoplasm cells is carried out by applying fluorescence and fluorescent diagnosis methods. After saturating the intraocular neoplasm with the photosensitizer to maximum saturation level, repeated laser irradiation of the intraocular neoplasm is carried out with radiation dose of 30-45 J/cm2.

EFFECT: complete destruction of neoplasm; excluded tumor recurrence; reduced risk of tumor cells dissemination.

3 cl, 3 dwg

FIELD: medicine.

SUBSTANCE: the present innovation deals with treating vascular cutaneous neoplasms, such as nevus flammeus and gemangiomas. Light-thermal impact at energy ranged 39-47 J/sq. cm should be performed in two stages, and between them, 2-3 wk after the onset of vascular resistance at the first stage one should perform beta-therapy daily for 2-3 d at single dosage being 20 g. Then, 3 wk later it is necessary to conduct the second stage of light-thermal impact by starting at energy value being 42 J/sq. cm, not less. The method enables to shorten therapy terms due to applying combined method to affect vascular cutaneous neoplasms.

EFFECT: higher therapeutic and cosmetic effect.

1 ex

FIELD: medicine.

SUBSTANCE: method involves intravitreously introducing two electrodes into intraocular neoplasm after carrying out vitrectomy and retinotomy to expose the intraocular neoplasm. The electrodes are manufactured from platinum group metal. Electrochemical destruction is carried out with current intensity of 100 mA during 1-10 min or 10 mA during 10 min in changing electrodes polarity and their position in the intraocular neoplasm space, and the electrodes are removed. 0.1-1% aqueous solution of khlorin as photosensitizer, selected from group containing photolon, radachlorine or photoditazine, is intravenously introduced at a dose of 0.8-1.1 mg/kg. Visual control of intraocular neoplasm cells fluorescence is carried out by applying fluorescent diagnosis methods. After saturating the intraocular neoplasm with the photosensitizer to maximum saturation level, intravitreous laser radiation is carried out in parallel light beam of wavelength equal to 661-666 nm is applied at a dose of 30-120 J/cm2.The transformed retina and tumor destruction products are intravitreally removed. Boundary-making endolasercoagulation of retinotomy area is carried out after having smoothed and compressed retina with perfluororganic compound. The operation is finished with placing sutures on sclerotomy and conjunctiva. Platinum, iridium or rhodium are used as the platinum group metals. Another embodiment of the invention involves adjusting position and size of the intraocular neoplasm in trans-scleral diaphanoscopic way. Rectangular scleral pocket is built above the intraocular neoplasm to 2/3 of sclera thickness with its base turned away from limb. Several electrodes are introduced into intraocular neoplasm structure via the built bed. The electrodes are manufactured from platinum group metal. Electrochemical destruction is carried out with the same current intensity in changing electrodes polarity and their position in the intraocular neoplasm space, and the electrodes are removed. Superficial scleral flat is returned to its place and fixed with interrupted sutures. 0.1-1% aqueous solution of khlorin as photosensitizer, selected from group containing photolon, radachlorine or photoditazine, is intravenously introduced at a dose of 0.8-1.1 mg/kg after having carried out vitrectomy and retinotomy. Visual control of intraocular neoplasm cells fluorescence is carried out by applying fluorescent diagnosis methods. After saturating the intraocular neoplasm with the photosensitizer to maximum saturation level, intravitreous laser radiation is carried out in parallel light beam of wavelength equal to 661-666 nm is applied at a dose of 30-120 J/cm2. The transformed retina and tumor destruction products are intravitreally removed using vitreotome. Boundary-making endolasercoagulation of retinotomy area is carried out after having smoothed and compressed retina with perfluororganic compound. The operation is finished with placing sutures on sclerotomy and conjunctiva. Platinum, iridium or rhodium are used as the platinum group metals. The number of electrodes is equal to 4-8.

EFFECT: reduced risk of metastasizing.

4 cl, 13 dwg

FIELD: medicine.

SUBSTANCE: method involves building tunnel to posterior eyeball pole in inferoexterior and superexterior quadrants. The tunnel is used for implanting flexible polymer magnetolaser implant to the place, the subretinal neovascular membrane is localized. The implant has a permanent magnet shaped as a cut ring and is provided with drug delivery system and a short focus scattering lens of laser radiator connected to light guide. The permanent implant magnet is axially magnetized and produces permanent magnetic field of 5-7 mTesla units intensity. It is arranged with its north pole turned towards sclera at the place of the subretinal neovascular membrane projection with extrascleral arrangement of laser radiator lens membrane being provided in the subretinal neovascular membrane projection area. The other implant end is sutured to sclera 5-6 mm far from the limb via holes made in advance. The implant is covered with conjunctiva and retention sutures are placed thereon. Light guide and drug supply system lead is attached to temple with any known method applied. Drugs are supplied via the implant drug supply system in retrobulbary way in any order. Triombrast is given in the amount of 0,4-0,6 ml and dexamethasone or dexone in the amount of 0,4-0,6 ml during 3-4 days every 12 h. 0.1-1% aqueous solution of khlorin is intravenously introduced at the third-fourth day after setting the implant as photosensitizer, selected from group containing photolon, radachlorine or photoditazine, at a bolus dose of 0.8-1.1 mg/kg. Visual control of subretinal neovascular membrane cells fluorescence is carried out by applying fluorescent diagnosis methods. After saturating the subretinal neovascular membrane with the photosensitizer to maximum saturation level, intravitreous, transretinal laser radiation of 661-666 nm large wavelength is applied at general dose of 30-120 J/cm2. The flexible polymer magnetolaser implant is removed and sutures are placed on conjunctiva. Permanent magnet of the flexible polymer magnetolaser implant is manufactured from samarium-cobalt, samarium-iron-nitrogen or neodymium-iron-boron system material. The photosensitizer is repeatedly intravenously introduced at the same dose in 2-3 days after the first laser radiation treatment. Visual intraocular neoplasm cells fluorescence control is carried out using fluorescent diagnosis techniques. Maximum level of saturation with the photosensitizer being achieved in the subretinal neovascular membrane via laser light guide and implant lens, repeated laser irradiation of the subretinal neovascular membrane is carried out with radiation dose of 30-60 J/cm2.

EFFECT: accelerated subretinal edema and hemorrhages resorption; regression and obliteration of the subretinal neovascular membrane; prolonged vision function stabilization.

6 cl

FIELD: medicine.

SUBSTANCE: method involves filling vitreous cavity with perfluororganic compound. Two electrodes manufactured from platinum group metal are intravitreally, transretinally introduced into intraocular neoplasm. Electrochemical destruction is carried out with current intensity of 10-100 mA during 1-10 min in changing electrodes polarity and their position in the intraocular neoplasm space, and the electrodes are removed. 0.1-1% aqueous solution of khlorin as photosensitizer, selected from group containing photolon, radachlorine or photoditazine, is intravenously introduced at a dose of 0.8-1.1 mg/kg. Visual control of intraocular neoplasm cells fluorescence is carried out by applying fluorescent diagnosis methods. After saturating the intraocular neoplasm with the photosensitizer to maximum saturation level, intravitreous, transretinal laser radiation of 661-666 nm large wavelength is applied at a dose of 30-120 J/cm2 in perfluororganic compound medium. The transformed retina and tumor destruction products are intravitreally removed with perfluororganic compound volume being compensated with its additional introduction. Boundary-making endolasercoagulation of retinotomy area is carried out. The perfluororganic compound is substituted with silicon oil. The operation is ended in placing sutures over sclerotmy areas and over conjunctiva. Perfluormetylcyclohexylperidin, perfluortributylamine or perfluorpolyester or like are used as the perfluororganic compound for filling vitreous cavity. Platinum, iridium or rhodium are used as the platinum group metals.

EFFECT: complete destruction of neoplasm; reduced dissemination risk.

6 cl, 12 dwg

FIELD: medicine, applicable for stopping of pains of various nature.

SUBSTANCE: the device has a quantum-mechanical oscillator located in a casing, magnet, vessel for medicinal agent and a hollow cylinder. The magnet is installed between the oscillator and the vessel. Positioned in the vessel is a hollow cylinder having through holes on its surface.

EFFECT: quick and absolute anestesia.

2 ex, 1 dwg

FIELD: medicine.

SUBSTANCE: method involves administering laser radiation therapy once a day using low intensity pulsating radiation of wavelength equal to 890nmand power density of 0.03 mW/cm2. Injured organ projection to frontal abdominal wall is exposed to radiation at the first laser therapy stage in two fields acting upon each field for 2 min with radiation pulse succession frequency equal to 80 Hz in applying stable contact-type method. Total treatment dose on two fields is equal to 0.008 J/cm2. The second laser therapy stage begins immediately after having finished the first one in applying radiation along the large intestine path using labile contact-type method in a way that radiation pulse succession frequency equal to 80 Hz is applied first during 1 min and then frequencies of 600, 150 and 300 Hz are applied also during 1 min, respectively. Total treatment dose is equal to 0.032 J/cm2 at the second stage. Total treatment dose is equal to 0.04 J/cm2 at both stages.

EFFECT: enhanced effectiveness in inhibiting dysbacteriosis; reduced frequency of postoperative complications.

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