Method of treating spontaneous tumours in domestic animals and therapeutic device

FIELD: medicine.

SUBSTANCE: group of inventions refers to medicine and veterinary science. A method involves sequential intravenous introduction of a binary catalytic system (BCS): an oxidation catalyst - a metal complex and an oxidation substratum - ascorbic acid (AA). The oxidation catalyst is introduced in a maximally tolerable or lower doses, and AA - in doses related to molar ratio of the metal complex: AK=1:10. The method also involves local hyperthermia of the tumour with using near infra-red laser emission. The tumour temperature is maintained within the range of 43-45°C by adjusting laser power density. The emission is terminated after achieving the minimum power density maintaining the tumour temperature within the preset temperature range. The declared device comprises a near infra-red laser with emissive power switch-on, switch-off and adjustment systems, and optical system of laser beam formation, a tumour temperature control system with its output connected both with an input of a laser negative feedback system, a laser power density control system. The device comprises an additionally adjustable power density discriminator. An input of the laser power density discriminator is connected with an output of the laser power density control system. The output of the discriminator is connected to an input of the laser switch-off system.

EFFECT: invention provides higher clinical effectiveness.

5 cl, 1 dwg, 1 ex

 

The present invention relates to medicine and veterinary medicine and can be used in the treatment of malignant tumors.

There is a method of inhibiting the growth of tumors by applying a binary catalytic system (BCS), which is consistent injecting laboratory animals with transplantable tumor metal complex - oxidation catalyst substrate, and ascorbic acid (AA), substrate oxidation. The oxidation catalyst accumulate in tumor tissue, leads to catalytic oxidation of the substrate, resulting in the formation of highly reactive reactive oxygen species, including gidroperekisi and free radicals with high cytotoxic potential. As the oxidation catalyst used salt OCTA-4,5-carboxylic acid phthalocyanine cobalt Terephthal (TF) [RF patent 2106146, 10.03.98 g] or their esters (Afiter) [RF patent 2172319, 20.08.01 g]. Studies have shown that this method allows to achieve inhibition of tumor growth and increase the lifespan of mice.

The disadvantage of this method is the low antitumor activity of these BCS when alone, which is the lack of regression of the tumor.

To enhance the anticancer activity of BCS in the treatment of laboratory animal is (mice with transplantable tumors, a method for suppressing tumor growth, combining the use of BCS "metal complex + AK and laser hyperthermia, in which the animal is injected metal complex catalyst of the oxidation of the substrate in most portable or lower doses. Then intravenously injected AK in doses corresponding to the molar ratio of metal complex:AK 1:5-1:30, followed by heating of the tumor by laser radiation with a wavelength of 800 nm at temperatures below 41°C in a period of time not less than 5 min [RF patent 2376999, 27.12.2009, - prototype].

However, the authors experimentally it was found that this method of suppressing tumor growth, when these characteristics of the laser radiation is selected for the treatment of transplantable tumors in mice, no significant antitumor effect in the treatment of spontaneous tumors of natural origin. Spontaneous tumors are diverse histological types (skin cancer, basal cell carcinoma, mastocytoma, melanoma, histiocytoma, fibrosarcoma etc.), localized in areas of the body with different microenvironment (blood flow, angiographic and vasculogenic, lymph and the like), have a fairly extensive area of invasion into the surrounding tissue and therefore recur capable of metastasis. These characteristics also determine and sensitivity to treatment. In connection with the foregoing selection of the best n the parameters of laser irradiation, acting on the tumor should be performed under conditions adequate or as close as possible to the real cancer of the situation, i.e. spontaneous malignant tumors. Selected parameters of laser irradiation (intensity and duration) to ensure maximum impact on the tumor and the achievement of complete remission of the tumor process without irreversible damage to the surrounding normal tissues.

A device for the treatment of tumors of domestic animals using laser hyperthermia, including laser with a wavelength in the near-infrared range of 800 nm, containing system enable, disable and power control of laser radiation, an optical system for shaping the laser beam, ensuring the specified density distribution of the radiation power on the surface of the irradiated tumor; a temperature control system tissues irradiated tumor, the output of which is connected to the input of the system is negative feedback laser, and the control system power density of laser radiation [RF patent 2196623, 20.01.2003, - prototype].

A disadvantage of the known device is that the duration of exposure is set manually by the operator or automatically by a timer with a preset exposure time without monitoring the adequacy of impact for the achievement is in effect. Due to these features of the known device does not provide the opportunity to optimize the exposure time and achieve maximum therapeutic efficacy of treatment with minimal damage to surrounding tissues.

In the invention solves the problem of increasing the effectiveness of anticancer therapy.

This task is solved in that a method of treatment of tumors of domestic animals characterized by sequential intravenous binary catalytic system (BCS): oxidation catalyst (metal complex) and substrate oxidation (ascorbic acid) (AK), the oxidation catalyst is injected at the maximum tolerated or lower doses, and AK in doses corresponding to the molar ratio of metal complex:AK = 1:10, and local hyperthermia of the tumor by laser radiation in the near-infrared wavelength range, the temperature of the tumor support in the range of 43-45°C by adjusting the power density of laser radiation and terminate the irradiation after reaching the minimum power density providing the temperature of the tumor in the specified temperature range.

This task is solved by the fact that the irradiation start at power density of the laser radiation at least 3 W/cm2.

This task is solved in that the irradiation of termination is jut after reaching a power density of 0.8 W/cm 2.

This task is solved in that the device for the treatment of tumors of domestic animals contains the laser radiation in the near-infrared wavelength range systems enable, disable and power control of laser radiation, an optical system for shaping the laser beam, the temperature control system of the tumor tissue, the output of which is connected to the input of the system is negative feedback laser, and the control system power density of laser radiation, the device additionally contains an adjustable discriminator power density of laser radiation, the input of the discriminator connected to the output of the control system power density of laser radiation, and the output connected to the input of the system off of the laser radiation.

This task is solved in that the device for the treatment of tumors of domestic animals includes the additional adjustable timer of laser radiation, through which the output of the discriminator power density laser radiation is connected to the input of the system off of the laser radiation.

The invention is illustrated Figure 1.

The following notation is used:

1 - laser;

2 - the system including the laser radiation;

3 - disconnect system of the laser radiation;

4 - system power control laser irradiation is s;

5 - optical system for shaping the laser beam;

6 - irradiated tumor;

7 - temperature control system of the tumor tissue;

8 - system negative feedback laser;

9 - control system power density of laser radiation;

10 - adjustable discriminator power density of laser radiation;

11 - adjustable timer of laser radiation.

Device for the treatment of tumors of domestic animals contains the laser 1 with the system include 2, shutdown system 3, the control system 4 power laser radiation, the optical system of the formation 5 of the laser beam, the temperature control system 7 of the tumor tissue, the output of which is connected to the input of the system is negative feedback 8 laser control system power density 9 laser radiation, adjustable discriminator 10 power density of laser radiation, adjustable timer 11 turn off the laser, the input of the discriminator 10 power density of laser radiation coupled to the output of the control system 9 power density of laser radiation, the output to the input of an adjustable timer 11 disable laser the radiation output of the timer 11 is connected to the input of the system off 2 laser radiation.

The proposed device operates as follows. After intravenous injection the animal Metallica the Lex and AK include laser 1 and enable 2 laser radiation, then, using the optical system 5 to form the laser beam on the tumor 6. Pre-set power level by using the system of regulation 4 of the laser power so that with regard to the size of the tumor 6 power density laser radiation has reached or exceeded 3 W/cm2. The power density of the laser radiation is controlled by the system control 9 power density, the temperature of the tumor tissue in the area of exposure - using system temperature control 7 of the tumor tissue. Since the temperature control system 7 of the tumor tissue is connected to the system 8 negative feedback laser, the power density of laser radiation enters the level that provides the desired temperature in the range of 43-45°C. Exposure leads to disruption of blood flow in the tumor, the abstraction of heat is reduced, which causes a temperature rise in the heating zone above the specified limits. With a system output temperature control 7 of the tumor tissue to the input system 8 negative feedback laser signal to reduce power density laser radiation required to achieve the specified temperature. With continued exposure occurs deterioration of tumor blood flow and reducing the heat sink, which leads to a further decrease in the density powerfully the ti laser radiation, necessary to ensure a predetermined temperature. Due to exposure to a tumor's blood supply is stopped, thermal conductivity is stabilized and the desired temperature is achieved when the density level of the laser power, lying, usually near 0.8 W/cm2. Further irradiation does not lead to more damaging effects on the tumor, so after the time specified adjustable timer 11 disable laser radiation and is usually not more than 5 min, from the output of the timer signal to the input of the system 3 turn off the laser radiation and the irradiation is terminated.

The tests were carried out on 13 Pets (dogs and cats) with spontaneous superficial tumours. As a result of preliminary tests in animals were identified malignant epithelial tumors (carcinoma of the mucosa of the right nasal passage, non-squamous squamous cell skin cancer and Diavolo edge of the upper jaw), mesenchymal (fibrosarcoma, lymphoma, mastocytoma), histiocytoma (histiocytoma sarcoma, malignant fibrous histiocytoma skin and melanocytic (melanoma) origin.

The animal was intravenously injected binary catalytic system (BCS): Terephthal (TF)+AK - standard doses, then held laser hyperthermia (LHT) tumor ezlucenesearch semiconductor laser "LFD-01/800-BIOSPEC" with a wavelength of 797 nm within 15-30 minutes. The temperature of the irradiated tumor was 43-45°C. temperature Control irradiated tumors was carried out non-contact infrared thermometer (AZ Instrument, USA) on the surface of the node.

Schema therapy: 1 hour 45 minutes to LGT have introduced the symbol AK intravenously in doses of 90 and 220 mg/m2accordingly, the interval between injections 15 minutes, then 45 minutes irradiation was performed using the proposed device.

Tumor size was measured before and after treatment. Additionally performed a full clinical examination to detect metastasis and possible side effects. Observation of the animals was carried out within 4 months after exposure. To assess the antitumor effect used the who-recommended indicators:

complete remission, regression of tumor;

- partial remission, reduction of tumor size not less than 50%;

- stabilization of tumor growth, reducing tumor size of less than 50% or no negative dynamics;

- the objective effect (complete remission + partial remission);

control of tumor growth (complete remission + partial remission + stabilization).

Examples of the proposed method of treatment of tumors using the inventive laser device.

Example 1

Dog, male, 8 years old, nicknamed "Altai". Diagnosis: carcinoma of clinicolaboratory right nasal passage. Education has a rounded shape with dimensions of 8.0×5,0×5.0 mm3with a smooth uniform surface.

Intravenously injected sequentially TF at a dose of 90 mg/m2and AK at a dose of 220 mg/m2once daily , with an interval of 15 minutes between injections. Then there was LGT tumors with the use of the proposed device at a temperature of 43-45°C, the initial power density of 3 W/cm power density at the termination of 0.8 W/cm2. The exposure time was 15 minutes.

The results of treatment 12 days after treatment the survey. Achieved complete regression of the tumor. After 96 days after treatment signs of the tumor was not detected.

Example 2

Dog, male, 10 years old, nicknamed "gosh". Diagnosis: squamous non-squamous cancer Diavolo edge of the upper jaw. Education has ellipsoidal form sizes 55,0×21,0×8.0 mm3with a pitted surface.

Intravenously injected sequentially TF at a dose of 90 mg/m2and AK at a dose of 220 mg/m2once daily , with an interval of 15 minutes between injections. Then there was LGT tumors with the use of the proposed device at a temperature of 43-45°C, the initial power density of 3 W/cm2, power density at the termination of 0.8 W/cm2. The exposure time was 20 minutes.

The results of treatment 12 days after treatment is examined. Achieved complete regression of the tumor. After 96 days after treatment signs of the tumor was not detected.

Test results of 13 animals following: complete remission was achieved in 31% of the animals, partial remission - 15% of animals, stabilization - 23% of the animals. The objective effect was 46%, the control of tumor growth 69%. In 31% of the animals were observed the progression of cancer.

The achieved efficiency of treatment in the application of the proposed method using the proposed laser device more efficient than known methods. The proposed method and the laser device can be widely used in oncovirinae.

1. The method of treatment of spontaneous tumors of domestic animals, characterized by sequential intravenous binary catalytic system (BCS): oxidation catalyst is a metal complex and substrate oxidation - ascorbic acid (AA), the oxidation catalyst is injected at the maximum tolerated or lower doses, and AK in doses corresponding to the molar ratio of metal complex: AK = 1:10, and local hyperthermia of the tumor by laser irradiation in the near-infrared wavelength range, the temperature of the tumor support in the range of 43-45°C by adjusting the power density of laser radiation, and stop the irradiation of th is the minimum power density, providing the temperature of the tumor in the specified temperature range.

2. The method of treatment according to claim 1, characterized in that the irradiation start when the power density is not lower than 3.0 W/cm2.

3. The method of treatment according to claim 1, characterized in that the irradiation stop no more than 5 min after reaching a power density of 0.8 W/see

4. Laser device for the treatment of spontaneous tumors of domestic animals, characterized in that it comprises the laser radiation in the near-infrared wavelength range systems enable, disable and power control of radiation, an optical system for shaping the laser beam, the temperature control system of the tumor tissue, the output of which is connected to the input of the system is negative feedback laser control system power density of laser radiation, the device additionally contains an adjustable discriminator power density of the radiation, the input of the discriminator power density of laser radiation coupled to the output of the control system power density of laser radiation, the output of the discriminator is connected to the input of the system off of the laser radiation.

5. Laser device according to claim 4, characterized in that it includes the additional adjustable timer of laser radiation, through which the output of the discrimination is ora power density laser radiation is connected to the input of the system off of the laser radiation.



 

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4 cl, 3 dwg

FIELD: medicine.

SUBSTANCE: invention refers to medicine, particularly gastoenterology, reflexotherapy, physiotherapy. It involves a conventional drug-induced therapy of chronic pancreatitis. It is added with the antidepressant azaphen 75 mg daily in clinically apparent affective disorders, 50 mg daily in subclinically apparent affective disorders for 30 days. Magnetic laser puncture is performed with considering a vegetative balance state. One biologically active point is exposed to modulated wave length 1.3 mcm, frequency 2.4 Hz, magnetic induction 50 mT for 10-30 seconds. Sympathicotonia requires sequential sedation of the point GI 4 and toning of the points. E 25, E 36, MC 6. Vagotonia requires toning of the point GI 4 and sedation of the points E 25, E 36, MC 6. It is accompanied with transcutaneous magnetic laser exposure at wave length 0.89 mcm with using a magnetic tip 150 mT. A solar plexus area, a projection of pancreas, a projection of gall bladder are covered for 2 minutes. In manifested pain syndrome, the exposure starts at the frequency of 820 Hz to be decreased to 80 Hz. In weak pain syndrome, the frequency of 360 Hz is gradually decreased to 80 Hz. In the absence of pain syndrome, the exposure is applied at the frequency of 80 Hz.

EFFECT: method normalises a psychoemotional sphere, daily chronobiorhythms, vegetative balance state, reduced length of treatment, prolongs a remission period.

2 ex, 2 tbl

FIELD: medicine.

SUBSTANCE: invention refers to pharmaceutics and medicine and concerns a pharmaceutical composition for treating and preventing preexcitation syndrome (WPW-syndrome) containing 9-diethylaminoethyl-2-tert-butyl-imidazo[1,2-a] benzimidazole dihydrochloride of formula I as an agent.

EFFECT: composition shows high efficacy.

6 cl, 6 tbl, 2 ex

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