WO2022265537A1

WO2022265537A1 - Method of treating erectile dysfunction

Info

Publication number: WO2022265537A1
Application number: PCT/RU2022/050187
Authority: WO
Inventors: Армаис Альбертович КАМАЛОВ; Михаил Евгеньевич ЧАЛЫЙ; Александр Владимирович ПОТАПОВ; Сергей Владимирович ПОТАПОВ
Original assignee: Общество с ограниченной ответственностью "ИнертГаз Медикал"
Priority date: 2021-06-18
Filing date: 2022-06-15
Publication date: 2022-12-22

Abstract

The invention relates to medicine, and more particularly to urology, and can be used for treating erectile dysfunction (ED). The technical result of the invention for which a patent is sought consists in stimulating microcirculation in erectile tissue, as well as providing improved functioning of the endothelium in the penile arteries. A method of treating erectile dysfunction includes steps in which, once a day or once every two days, a patient undergoes from 5 to 15 inhalation procedures, during which a breathing mixture consisting of 20-50% oxygen and 80-50% helium, heated to 45-95°С, is fed to the patient via an inhalation apparatus with a heating device, the patient alternating between inhaling and exhaling for 1-5 minutes and holding their breath for 20-60 seconds, wherein as the patient is holding their breath, pulse oximetry is performed to monitor the drop in blood oxygen saturation, after the end of the breath holding period or after a decrease in the saturation parameters to 93%, the cycle of inhalation and exhalation and breath holding is repeated, the duration of the procedure being 5-10 minutes, with a volume of 30-200 litres of helium-oxygen mixture being consumed during the procedure.

Description

Method for treating erectile dysfunction

The invention relates to medicine, namely to urology, and can be used for the treatment of erectile dysfunction (hereinafter referred to as ED).

ED is an extremely common disorder, affecting 40% of men aged 40-50, 50% of men aged 50-60, and 70% of men over 60 regardless of country or ethnicity (Massachusetts Older Men Study, MMAS). ). Allocate psychogenic, organic and mixed ED. If earlier various psychological problems were considered the main cause of ED, it is now believed that ED in 80% of cases is of an organic nature and occurs as a complication of various somatic diseases. At the same time, almost all epidemiological studies on ED have revealed a relationship between its occurrence and arterial hypertension (AH), diabetes mellitus, coronary heart disease, and atherosclerosis. Moreover, according to some authors, the detection of ED may indicate that the patient has one of these diseases in a latent form.

Due to atherosclerotic lesions of the vessels of the penis, not only a mechanical disturbance of blood flow occurs, but also the production of neurotransmitters is disturbed, the elasticity of the vessels decreases.

Hypertension can cause ED regardless of whether a person suffers from atherosclerosis or not. If hypertension is not treated for a long time, the walls of the vessels, constantly exposed to increased blood pressure, become dense and inelastic, and the vessels are unable to supply the organs with the necessary amount of blood. In diabetes mellitus, ED develops three times more often and 10-15 years earlier than in a healthy population, it occurs, according to A. Guay et al. (1998) in 50-75% of diabetic men.

According to A. Guay (2002), the main causes of organic ED in DM are diabetic polyneuropathy, macro- and microangiopathies.

The development of ED is often associated with the intake of various drugs, including antihypertensive drugs.

Currently, ED is treated by various methods that improve microcirculation and increase the production of neurotransmitters: surgical (RF patent N° 24385595, publication date 01/10/2012), physiotherapy (RF patent N° 2323018, publication date 04/28/2008), pharmacological, including, including the introduction of NO inductors (RF patent N° 2421211, publication date 06/20/2011).

The most recommended treatment for both psychogenic and organic ED, which we have chosen as a prototype, is the use of phosphodiesterase type 5 inhibitors (PDE5). (D.Yu. Pushkar Erectile dysfunction - modern methods of diagnosis and treatment. Journal "Directory of a polyclinic doctor", 2004, JV ° 2). During sexual stimulation, due to the activation of the nervous system and the release of nitric oxide (NO), cyclic guanosine monophosphate (cGMP) accumulates in vascular smooth muscle cells. It is cGMP that triggers a cascade of biochemical reactions leading to the onset and maintenance of an erection. Normally, its concentration decreases with the cessation of sexual stimulation due to the destruction of PDE5. In ED, cGMP deficiency is noted due to various pathogenetic factors, and its destruction of PDE5 leads to insufficient or no erection. PDE5 inhibitors do not have a direct relaxing effect on the cavernous bodies, but enhance the relaxing effect of nitric oxide by inhibiting PDE5 and increasing the concentration of cGMP during sexual arousal.

However, the use of PDE5 inhibitors has a number of contraindications. These include the simultaneous use of nitrates or alpha-adrenergic blockers, since combined use with these drugs can lead to a sharp decrease in blood pressure and collapse. The drug is not used in patients with a prolonged Q-T interval due to the possibility of cardiac arrhythmias.

The technical problem of the present study is to develop a method for effective treatment of ED, devoid of the above side effects, and aimed at eliminating the cause of ED.

This problem is solved by using a breathing gas mixture of helium and oxygen (heliox) in a ratio of 20-50% oxygen and 80-50% helium, respectively. At the same time, the gas mixture is heated to a temperature exceeding the thermoneutral range from 45 to 95 °C, using a specialized device for supplying the gas mixture and heating it.

The technical result of the patented invention is to stimulate the microcirculation of the cavernous tissue, as well as to improve the functionality of the endothelium in the penile arteries. The use of thermal heliox has been proven to increase the vital capacity of the lungs after 100 minutes of breathing by an average of 20% compared to the initial value. Due to increased gas exchange and blood saturation with oxygen, the delivery of the latter through the microvasculature of the cavernous tissue is enhanced. Thus, increased oxygenation of the cavernous tissue provides an increase in the regularity of the occurrence of spontaneous erections during sleep, improves morning erections, increasing the sexual activity of patients.

The claimed technical result is achieved through the implementation of a method for the treatment of erectile dysfunction, including stages in which the patient is given 5 to 15 inhalations once a day or once every two days, during which the patient is supplied with a respiratory mixture consisting of 20-50% oxygen and 80-50% helium, respectively, in a heated state up to 45-95 ° C through an inhalation apparatus with a heating device, in the mode alternating breaths and exhalations for 1-5 minutes and holding the breath for 20-60 seconds, while holding the breath, the patient is subjected to pulse oximetry to control the degree of drop in oxygen saturation in the blood, after the expiration of the time of holding the breath or reducing the saturation parameters to 93%, the cycle is repeated from inhalations and exhalations with breath holding, while the duration of the procedure is 5-10 minutes with a flow rate of helium-oxygen mixture in the amount of 30-200 liters per procedure.

Activation of the microcirculatory bed of the cavernous tissue due to an increase in oxygen supply upon resumption of heliox inhalation immediately after holding the breath leads to an increase in the reflex of spontaneous nocturnal tumescences that occur against the background of the predominance of parasympathetic innervation of the pelvic organs. In this case, there is an increase in the multiplicity and amplitude of spontaneous tumescences during the paradoxical phase of sleep. A thermal mixture of helium and oxygen is used to improve blood circulation. The stimulating effect of thermal heliox is achieved due to the following biophysical properties:

• decrease in airway resistance;

• reduction of pulmonary hyperinflation,

• uniformity of ventilation of the upper, middle and lower parts of the lungs;

• decrease in intrathoracic pressure;

• increase in respiratory volume;

• increase in diffusion capacity

• improvement of the ventilation-perfusion ratio through the alveolar-capillary membrane of the lungs;

• normalization of acid-base balance;

• increased oxygen delivery;

• increased oxygen consumption by tissues;

• reduction of hypoxemia;

• elimination of CCL;

• correction of hemodynamic disturbances due to a decrease in the resistance of the vessels of the small and large circulation;

• reduction of load on the right ventricle;

• improvement of vascular microcirculation and vascular tone;

• thermal dilatation of blood vessels;

• has a neuroprotective and cardioprotective effect;

• normalization of lactate;

• increased activity of enzymatic systems, • stimulation of metabolism, improvement of metabolic processes

• increased exposure in the distal bronchi of drugs inhaled through a nebulizer;

• thermal effect on the body (optimizes the temperature regime of the body, evenly warms the parenchyma of the organs of the chest cavity, quickly relieves hypothermia of the body);

• reduction of partial atrophy of the optic nerve, improvement of the retina, increased visual acuity and expansion of the field of view;

• reduction of manifestation of ischemic neuropathy;

• strengthening of redox processes in various tissues;

• activation of detoxification, metabolism and excretion of metabolic products;

• quick recovery from supercooling of the body;

• normalization of acid-base balance;

• increasing the resistance of organs and tissues to hypoxia;

• elimination of clinical manifestations of overtraining;

• restoration of the initially reduced level of working capacity;

• optimization of vegetative regulation;

• improvement of psychological status.

• low density (7 times lower than that of nitrogen);

• high thermal conductivity (5.8 times higher than that of nitrogen);

• superfluidity;

• high diffusion capacity through the alveolar-capillary membrane (1.8 times higher than that of oxygen);

• as an inert gas, helium does not enter into biochemical reactions;

• insoluble in water and biological fluids.

Due to the low density of helium, the flow of gases through the respiratory tract becomes less turbulent, especially in the distal regions. The proportion of laminar flow increases and the total airway resistance decreases. The use of heliox, heated to a temperature of 45-95 ° C, which exceeds the thermoneutral range, leads to an increase in the speed of the gas mixture, to the excitation of thermoreceptors, followed by a pronounced dilatation of the smooth muscles of the bronchi and an improvement in the blood supply to the lungs. Heliox inhalation improves the ventilation-perfusion ratio within the physiological norm. A decrease in airway resistance leads to a decrease in intrathoracic pressure drops and to the correction of hemodynamic disorders.

The high diffusion capacity of helium is of great importance. Therefore, when heliox is used, the gas exchange function of the lungs improves, which is manifested by an increase in the partial pressure of oxygen in the arterial blood (PaCl), an increase in saturation (SaCb). increased elimination of carbon dioxide from arterial blood. The decrease in arterial blood oxygen partial tension (PaCL) against the background of inhalation of thermal heliox occurs quickly, which makes it possible to recommend it for hypercapnic respiratory failure.

The concentration of lactate is normalized, which indicates a decrease in the anaerobic phase of metabolism.

In addition, heliox does not have general and specific toxicity, mutagenicity, embryotoxicity, teratogenicity, carcinogenicity, does not cause allergies, does not impair reproductive function, which allows it to be used in various diseases and conditions.

As you know, with age, the risk of a number of diseases increases, such as arterial hypertension, coronary heart disease, cerebrovascular diseases, each of which is directly related to atherosclerotic lesions of vessels of various localization. The severity of the clinical manifestations of each of these diseases directly depends on the degree of damage to the vascular plexuses that provide blood supply to the relevant organs. It is believed that the most significant hemodynamic changes occur in vessels with the smallest diameter, while larger vessels are capable of long-term compensation. According to Montorsi R. et al. (2003) the diameter of penile arteries is 1-2 mm, coronary arteries - 3-4 mm, carotid arteries - 5-7 mm. Thus, the presence of ED and concomitant cardiovascular diseases in patients indicates a pronounced and long-term (at least 3–3.5 years) damage to the penile arteries. In this regard, it becomes clear that the presence of ED is a risk factor for cardiovascular disease.

It is advisable to treat patients with ED with thermal heliox on the basis that an increase in oxygenation of the cavernous tissue helps to restore or improve the spontaneous tumescence reflex during sleep, and also helps to reduce the functional, morphological and oxidative consequences of chronic ischemia in the human body.

At the same time, there is an increase in the compensatory capabilities of the microvasculature due to an increase in the total area of the capillary network, which is achieved by improving the trophism of the cavernous tissue due to a greater supply of oxygen to the tissues. An increase in spontaneous erections of the penis during sleep is achieved. To improve blood circulation in the cavernous tissue, a heated mixture of helium and oxygen (45-95 ° C) is used.

The method is carried out as follows. The duration of one procedure is 5-10 minutes, the Stange and Soobre tests are initially measured, the data of which are recorded before and after the course of treatment, and serve as one of the criteria for the objectivity of the evaluation of the therapy. Breathing is performed in the usual mode of average inhalation and exhalation. After 5-30 breaths and exhalations (1-5 minutes of inhalation), the patient makes a maximum exhalation and holds his breath for 20-60 seconds, forming hypoxia. Then the patient takes the maximum possible breath and continues to hold his breath on inspiration for the maximum possible time. The number of such procedures ranges from 5 to 15 daily or every other day.

Initially, spontaneous erections are monitored during sleep using the Androscan MIT apparatus. For objectivity, the study is conducted for at least two nights. After the therapy, the final monitoring of spontaneous erections is carried out.

With mild and moderate EF disorders, 5-10 procedures for 5-10 minutes are enough. In severe forms of ED, at least 15 procedures for 10 minutes. During the use of thermal heliox therapy, the following changes were observed in patients: an increase in the vital capacity of the lungs by 20-30%, an increase in the parameters of the Stange and Soobre tests by 18-20%, an improvement in the well-being of patients, an increase in stress resistance, an improvement in visual acuity, an increase in the depth of inspiration at maximum inhalation, copious sputum production, increased exercise tolerance, reduced fatigue, improved sleep quality.

Thus, heliox inhalation causes an increase in spontaneous erections during sleep, improves morning erections, improves the quality of sexual life of patients, increases the frequency and amplitude of spontaneous erections during sleep (monitoring is carried out using the Androscan MIT device).

There is a clear positive trend.

In this way, with informed consent, 60 patients with ED were treated with a positive effect achieved in 44 patients. The results of the clinical study indicate that the proposed method is highly effective in the treatment of ED.

The advantage of this method is its low cost, ease of implementation, high efficiency, no complications and side effects, which allows it to be successfully used in urology and andrology.

The following are clinical examples of the implementation of the method with reference to the figures, which show the following.

Fig. 1 - data of the patient from example 2 before treatment (extract from the medical history).

Fig. 2 - data of the patient from example 2 after treatment with heliox using the BreezeLite inhalation device (extract from the medical history). Fig. 3 - data of the patient from example 3 before treatment (extract from the medical history).

Fig. 4 - data of the patient from example 3 after therapy with PDE-5 inhibitors, 12 sessions of shock wave therapy on the Domier Aries apparatus, as well as intracavernous therapy with Prostaglandin E1 20 mg. (extract from the medical history).

Fig. 5 - data of the patient from example 3 after treatment with heliox using the Breeze Lite inhalation device (extract from the medical history).

Example 1

Patient M., 47 years old, i/b, was treated from 03/03/2020 to 03/25/2020 with a diagnosis of arteriogenic erectile dysfunction. Upon admission, he complained of erectile dysfunction, reduced quality of life. The total score on the IIEF scale is 5 - 17. From the anamnesis - the duration of the disease is 6-8 months, it arose abruptly. The diagnosis was established on the basis of complaints, anamnesis, clinical, ultrasound and laboratory research methods. With pharmacodopplerography with 5 μg IHE 1, an ER3 erection was achieved. There were signs of insufficient arterial inflow in both cavernous arteries (the difference between baseline and control values was less than 25 cm per second), there were no signs of venous leakage. (resistance index in 30 minutes of the study more than 0.8).

Initially, spontaneous erections are monitored during sleep using the Androscan MIT device. For objectivity, the study is conducted for at least two nights. A decrease in the amplitude of the increase in the diameter of the penis during nocturnal tumescence was found to be less than 40%, while maintaining the total duration of spontaneous tumescences, which indicates a mild degree of erectile dysfunction.

The total duration of tumescences is 145 minutes,

Treatment: from 03/05/2020 to 03/24/2020, 10 procedures of inhalation with heliox (40% oxygen and 60% helium, 100-120 liters per procedure) heated to 90°C using the BreezeLite inhalation device (manufactured by InertGazMedikal LLC) were performed daily. "") with a heating device.

The duration of one procedure was 10 minutes, initially the Stange test was measured 1 min 11 s, according to 34 sec, the vital capacity of the lungs was 3444 ml, the data were recorded. Breathing was performed in the usual mode of average inhalation and exhalation. After 30 breaths and exhalations, the patient made the maximum exhalation and held his breath, held it for the maximum possible time (up to 60 seconds), forming hypoxia. Then the patient took the maximum possible breath and continued to hold his breath on the breath for the maximum possible time (50-60 seconds). Then, in the normal breathing mode, the procedure continued until it was completed. The patient did not complain of any discomfort after the procedures. After the course of therapy, the final monitoring of spontaneous erections during sleep was carried out, the results of which show a significant improvement in spontaneous tumescence during sleep. The amplitude of the erectile response increased by 25%, the duration of spontaneous erections was 200 min (+37.931%), the Stange test was 1 min 31 sec (+28.169%), the Compliance test was 49 sec (+44.1176%), the vital capacity was 4459 ml ( +29.4715%.

According to the ICEF scale 5-21. There is a clear positive trend.

As an example, data from clinical examples taken from the personal files of two patents is given below.

Example 2

Patient V., aged 47, complains of gradual worsening of ED, absence of morning erections. During the initial examination of the ICEF 15 - 20 points; history of hypertension 1 tbsp; lipid profile: total cholesterol 4.26 mmol/l; LDL 2.18 mmol/l; HDL 1.66 mmol/l; Atherogenic index: 1.10.

Monitoring data of spontaneous erections during sleep on the device "Androscan MIT" indicate a mild degree of erectile dysfunction (Figure 1).

The patient underwent 10 sessions of breathing with hyperoxic heliox - a mixture of 50% oxygen and 50% helium, heated to 60 ° C for 10 minutes in a volume of 150 liters per procedure, without the use of any pharmacological preparations using only the BreezeLite inhalation apparatus with a heating device in mode of alternating inhalations and exhalations and breath holding.

During the breath hold, the patient underwent pulse oximetry to control the degree of drop in blood oxygen saturation, after 60 seconds of breath holding or a decrease in saturation parameters to 93%, a cycle of inhalations and exhalations for 1-5 minutes (the cycle time of inhalations and exhalations also changes during the procedure ) with breath holding at the end of each cycle.

Control monitoring of spontaneous erections during sleep after 10 treatments is shown in Fig.2. There is an increase in the amplitude and duration of spontaneous erections during sleep, morning erections appeared.

Example 3

Patient A., aged 60, complains of gradual worsening of ED; the use of PDE-5 type inhibitors without the expected effect; during the initial examination of the ICEF 15 - 15 points; history: hypertension 2 tbsp; lipid profile: total cholesterol 6.71 mmol/l; LDL 5.28 mmol/l; HDL 1.26 mmol/l; atherogenic index: 4.33.

Spontaneous erections during sleep were monitored using the Androscan MIT device (Fig. 3). A decrease in the amplitude and duration of spontaneous erections was revealed, corresponding to an average degree of erectile dysfunction, indicating severe ischemia of the cavernous tissue. Patient therapy with PDE-5 inhibitors, 12 sessions of shock wave therapy on the Domier Aries apparatus, intracavernous therapy with Prostaglandin E1 20 mg was carried out.

Androscan data (Figure 4) indicate an increase in the activity of spontaneous erections during sleep and correspond to a mild degree of ischemia of the cavernous tissue.

While taking IF D-5, the patient underwent 15 inhalations with normoxic thermal heliox - a mixture of 20% oxygen and 80% helium, heated to 45 ° C for 10 minutes in a volume of 100 liters per procedure, using the BreezeLite inhalation apparatus with a heating device, in the mode of alternating inhalations and exhalations and holding the breath.

Androscan data of the patient during sleep after 15 procedures are shown in Fig. 5. The results obtained indicate the restoration of the rhythm of spontaneous erections during sleep and the absence of signs of ischemia of the cavernous tissue, regular morning erections appeared.

Thus, the results of a clinical study indicate that the proposed method is highly effective in the treatment of erectile dysfunction.

The advantage of this method is its low cost, ease of use, high efficiency, absence of complications and side effects, which allows it to be successfully used in urology and andrology.

Claims

CLAIM

A method for the treatment of erectile dysfunction, which includes stages in which the patient is given 5 to 15 inhalations once a day or once every two days, during which the patient is given a respiratory mixture consisting of 20-50% oxygen and 80-50% helium, respectively, in a heated state to 45-95 ° C through an inhalation apparatus with a heating device, in the mode of alternating inhalations and exhalations for 1-5 minutes and holding the breath for 20-60 seconds, while holding the breath, the patient undergoes pulse oximetry to control degree of decrease in blood oxygen saturation, after the expiration of the breath holding time or a decrease in saturation parameters to 93%, a cycle of inhalations and exhalations with a breath hold is repeated, while the duration of the procedure is 5-10 minutes with a flow rate of helium-oxygen mixture in a volume of 30-200 liters per procedure.