RU2622757C1 - Method for erectile dysfunction treatment - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: fat tissue is taken from a patient under local anesthesia or intravenous anesthesia by liposuction in a volume of up to 250 ml. The fat tissue is processed on the Celution 800/CRS hardware complex for 1.5 hours and 4.0 ml of stromal-vascular fraction (SVF) is obtained. At that, the SWF contains 50 million or more cells. The SWF is then intracavernously administered to the patient at 6 points along the lateral surface of the penis bilaterally. 1.0 ml are administered proximally, 0.5 ml - medially and distally, total 2.0 ml per cavernous body. Then, a tightening garrot is put on the penis base for 15 minutes.

EFFECT: increased effectiveness of treatment due to the absence of complications and side effects in patients with erectile dysfunction.

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Description

The invention relates to medicine, namely to urology, and can be used to treat erectile dysfunction.

et al., 2003). По статистике 20% мужчин старше 40 лет страдают эректильной дисфункцией, при этом с возрастом распространенность данной патологии увеличивается (Е.О. Laumann, et al., 2007). Так, мужчины в возрасте от 61-70 лет в 2 раза чаще страдают ЭД в сравнении с мужчинами в возрасте 51-60 лет. В РФ по данным эпидемиологического исследования, при анкетировании 1225 мужчин, признаки эректильной дисфункции отсутствовали только у 10,1% опрошенных, симптомы ЭД присутствовали у 1101 респондентов (Пушкарь Д.Ю. и соавт., 2012).Erectile dysfunction (ED) refers to an important men's health problem, leading to a significant deterioration in the quality of life and a breakdown in relationships with a partner (

et al., 2003). According to statistics, 20% of men over 40 suffer from erectile dysfunction, while the prevalence of this pathology increases with age (E.O. Laumann, et al., 2007). So, men aged 61-70 years are 2 times more likely to suffer from ED compared with men aged 51-60. In the Russian Federation, according to an epidemiological study, when questioning 1225 men, only 10.1% of the respondents did not show signs of erectile dysfunction, 1101 respondents had symptoms of ED (Pushkar D.Yu. et al., 2012).

Allocate psychogenic, organic and mixed ED. If earlier the main cause of ED was considered various psychological problems, now it is believed that ED in 80% of cases is organic in nature and arises as a complication of various somatic diseases.

The main causes, according to A. Guay (2002), of organic ED in diabetes are diabetic polyneuropathy, macro- and microangiopathies. With atherosclerotic lesions of the vessels of the penis, not only mechanical impairment of blood flow occurs, but the production of neurotransmitters (nitric oxide) is also disturbed, and the elasticity of the vessels decreases.

Currently, ED treatment is carried out by various methods that improve microcirculation and increase the production of neurotransmitters: surgical (RU 24385595, 01/10/2012), physiotherapeutic (RU 2323018, 04/28/2008), pharmacological, including the introduction of NO inducers (RU 2421211 06/20/2011).

There is a method of treating organic ED using type 5 phosphodiesterase inhibitors (PDE-5), as the most recommended treatment for psychogenic and organic ED.

During sexual stimulation due to activation of the nervous system and the release of nitric oxide (N0), cyclic guanosine monophosphate (cGMP) accumulates in the smooth muscle cells of blood vessels. It is cGMP that triggers a cascade of biochemical reactions leading to the emergence and maintenance of an erection. Normally, its concentration decreases with the termination of sexual stimulation due to the destruction of PDE-5. With ED there is a deficiency in cGMP due to various pathogenetic factors, and its destruction of PDE-5 leads to insufficient erection or lack thereof. PDE-5 inhibitors do not have a direct relaxing effect on cavernous bodies, but enhance the relaxing effect of nitric oxide by inhibiting PDE-5 and increasing the concentration of cGMP during sexual arousal.

However, the use of PDE-5 inhibitors has a number of contraindications. These include the simultaneous administration of nitrates or alpha-adrenergic receptor 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 an extended Q-T interval because of the possibility of heart rhythm disturbances.

In the experiment, studies were conducted on the use of stem cells for the treatment of erectile dysfunction. Bochinski was the first to confirm the effect of stem cells in restoring erectile function in mice with erectile dysfunction in case of damage to the cavernous nerve [BochinskiD, LinGT, NunesL, CarrionR, RahmanN, LinCS, etal. (2004) The effect of neural embryonic stem cell therapy in a rat model of cavernosal nerve injury. BjuInt 94: 904-09]. Also You D [You D et al. Comparative study of autologous stromal vascular fraction and adipose-derived stem cells for erectile function recovery in a rat model of cavernous nerve injury. StemCellsTranslMed. 2015 Apr; 4 (4): 351-8. doi: 10.5966 / sctm.2014-0161] showed that an autologous stromal-vascular fraction is able to improve erectile function in rats, with induced erectile dysfunction in cases of damage to the cavernous nerve. In a randomized study in 40 rats, the parameters of erectile function (intracavernous pressure and histochemical analysis of cavernous tissue) were evaluated 4 weeks after injection. As a result, it turned out that in the experimental group, which was administered the stromal-vascular fraction, the indicators were significantly higher. The smooth muscle / collagen ratio, smooth muscle content, the number of neuronal and endothelial nitric oxide synthase and von Willebrand factor expression were high.

A known method of treating erectile dysfunction (RF patent No. 2514639, 04/27/2014) by introducing platelet-rich autoplasma (AOT), which includes three stages: at the first stage, using an insulin syringe, an injection of platelet-rich plasma is injected on the lateral surface of the penis bilaterally: proximal, medially and distally injected with 1.0 ml of autoplasma, a total of 3.0 ml of autoplasma in each cavernous body; at the second stage, 2.0 ml of autoplasm is administered under the protein membrane of the penis; at the third stage, autoplasma is injected into the sciatic-cavernous muscles of 1.0 ml each, followed by a light massage of the penis to distribute the autoplasma; the procedure is repeated three times with an interval of 1 week.

The disadvantage of this method is the fact that AOT activates only the first phase of the regenerative cycle - alteration (90 + days), which reduces the severity of the clinical effect and requires periodic repetition of AOT therapy.

The objective of the present invention is to increase the effectiveness of the method of treatment of ED.

The technical result consists in the implementation of pathogenetically substantiated effects on the pathological chain in the development of erectile dysfunction.

The problem is solved by the method of treatment of erectile dysfunction, which consists in the fact that the patient under local anesthesia or intravenous anesthesia is taken adipose tissue by liposuction in a volume of up to 250 ml, the resulting adipose tissue is processed on a Celution 800 / CRS hardware complex for 1.5 hours until a 4.0 ml stromal-vascular fraction (SVF) is obtained containing 50 million or more cells, then SVF is intracavernously administered to the patient at 6 points along the lateral surface of the penis bilaterally: proximal to 1.0 ml, medially and distally of 0.5 ml, a total of 2.0 ml in each cavernous body, after which a tightening tourniquet is applied to the base of the penis for 15 minutes.

The stromal-vascular fraction of adipose tissue cells is stromal and vascular vascular cells, pericytes, leukocytes, fibroblast-like multipotent cells and hematopoietic stem cells. The content of stem cells is from 1 to 5%. The advantages of the proposed method is its pathogenetic orientation, based on the regenerative effect of the stromal-vascular fraction of the patient’s own adipose tissue cells on the processes of neovascularization, strengthening of the protein coat and regeneration.

The method is as follows. On the day of the operation, the patient in the operating room, under local anesthesia or intravenous anesthesia, takes adipose tissue by liposuction in a volume of 80 to 250 ml to isolate the stromal-vascular fraction of the patient’s own adipose tissue cells on a Celution 800 / CRS apparatus. Then, the resulting stromal-vascular fraction of 4.0 ml intrinsic adipose tissue cells is intracavernously administered to the patient at 6 points. The total number of introduced cells is 50 million or more. At the end of the injection, a tightening tourniquet is applied to the base of the penis for 15 minutes.

The inventive method of intracavernous treatment of erectile dysfunction has been tested experimentally and clinically. At the experimental stage, more than 40 preclinical studies were conducted on rats, mice and rabbits, which reproduced ED in various ways (diabetes mellitus, cavernous nerve damage, hyperlipidemia).

We present clinical examples of the method.

Example 1

Patient A., 60 years old, was treated from 04/22/2015 to 10/28/2015 with a diagnosis of erectile dysfunction of arteriogenic and venogenic origin. Upon receipt, he complained of a decrease in the quality of an erection. From the anamnesis it is known that these complaints are noted since 2010. Over the past year, the severity of complaints has intensified, and there are no morning erections. He does not abuse alcohol, he does not smoke systematically, 1-2 cigarettes a day. Married. The total score on the ICEF-5 scale is 13 points; on the SEP (sexual relations profile), 2 points. In the biochemical analysis of blood: total cholesterol 7.1 mmol / L, LDL cholesterol 3.64 mmol / L, HDL cholesterol 3.10 mmol / L. A general blood count, a coagulogram and a general urinalysis within normal values. PSA total 0.8 ng / ml. Testosterone total 12.3 ng / ml. Pharmacodopplerography of the penile vessels (FDG IF) with an intracavernous administration of 10 μg prostaglandin E1 (PGE1) shows a slight increase in peak systolic blood flow velocity and a decrease in the resistance index in both cavernous arteries. During the pharmacological test with 10 μg PGE1, an erection of the ER3 degree according to the Unem scale was achieved, with rapid detumescence. When evaluating the endothelial function on the AngioScan-01 hardware complex, a pronounced dysfunction of the endothelium in small resistive arteries (microcirculation), as well as impaired endothelial function in large muscle arteries, were noted.

The diagnosis was established on the basis of complaints, medical history, clinical, laboratory research methods, FDH IF with PGE1 and evaluation of endothelial function on the AngioScan-01 hardware complex.

Treatment: 05/13/15, a minimally invasive intervention was performed, intracavernous injection of the stromal-vascular fraction from the autologous adipose tissue into the penis by the proposed method.

In the operating room, the patient was pre-labeled with local infiltration anesthesia in the area of the anterior abdominal wall and flanks in a volume of (100, 150 ml, respectively). Adipose tissue was collected by lipoaspiration from these areas with a total volume of 185 ml. Then, the resulting adipose tissue was processed on a Celution 800 / CRS apparatus for 1.5 hours. At the end, a 4.0 ml stromal-vascular fraction (SVF) was obtained containing 308 × 10 ⁶ cells, which were intracavernously administered to the patient at 6 points bilaterally on the lateral surface of the penis: proximally 1.0 ml, medially and distally 0, 5 ml, a total of 2.0 ml in each cavernous body. After injections, a tightening tourniquet is applied to the base of the penis for 15 minutes. Adverse events were noted.

Examination of the patient included 10 visits (1, 3, 7 days, 1, 2, 3, 4 weeks, 2, 6 months).

Complaints decreased, notes the improvement in the quality of erections, the resumption of morning and night erections. He adheres to a diet, quit smoking, is actively involved in sports. The sum of points on the ICEF-5 scale is 19 points, on SEP - 4 points. In the biochemical analysis of blood: total cholesterol 6.2 mmol / L, LDL cholesterol 2.48 mmol / L, HDL cholesterol 1.82 mmol / L. A general blood count, a coagulogram and a general urinalysis within normal values. Testosterone total 13.1 ng / ml.

During the control pharmacodopplerography of the vessels of the penis with intracavernous administration of 10 μg PGE1: a significant increase in the peak systolic blood flow velocity and an insignificant index of resistance in both cavernous arteries compared with the baseline. During the pharmacological test with 10 μg PGE1 an erection of ER4 degree on the Unem scale was achieved. Evaluation of endothelial function: Preserved endothelial function in small resistive arteries (microcirculation). Endothelial function in the large muscle arteries is impaired.

After a course of treatment for patients with vasculogenic erectile dysfunction of arteriogenic and venogenic origin, a distinct positive dynamics was noted. This technique allows to obtain a clinical effect already in the early stages of treatment with preservation of the patients during the entire observation period, which is confirmed by the data obtained.

Example 2

Patient D., 33 years old, was treated from 04/13/2015 to 10/05/2015 with a diagnosis of erectile dysfunction of arteriogenesis. He went to the urology clinic with complaints of erectile dysfunction, lack of morning erections. The above complaints are noted over the past three years. Took PDE-5 inhibitors on demand with a variable effect. He rarely drinks alcohol. Smokes from 18 years old, 16-18 cigarettes a day, single. Previously, I did not apply for urological help.

The sum of points on the ICEF-5 scale is 15 points, on SEP - 3 points. In the biochemical analysis of blood: total cholesterol 5.8 mmol / L, LDL cholesterol 3.7 mmol / L. A general blood count, a coagulogram and a general urinalysis within normal values. Testosterone total 13.5 ng / ml. With pharmacodopplerography of the vessels of the penis with an intracavernous injection of 10 μg PGE1, a slight increase in the peak systolic blood flow velocity in both cavernous arteries is noted. In the projection of the right and left cavernous arteries, the resistance index is within the normal range. During the pharmacological test with 10 μg PGE1, an erection of degree ER3 on the Unem scale was achieved. When evaluating the endothelial function on the AngioScan-01 hardware complex, a pronounced dysfunction of the endothelium in small resistive arteries (microcirculation), as well as impaired endothelial function in large muscle arteries, were noted.

The diagnosis was established on the basis of complaints, medical history, clinical, laboratory research methods, FDH IF with PGE1 and evaluation of endothelial function on the AngioScan-01 hardware complex.

Treatment: 04/20/15, performed minimally invasive intervention, intracavernous introduction into the penis of the stromal-vascular fraction from autologous adipose tissue by the proposed method.

In the operating room, the patient was taken under an intravenous anesthesia for adipose tissue by liposuction by preliminary marking in the area of the anterior abdominal wall and flanks with a total volume of 168 ml. Then, the resulting adipose tissue was processed on a Celution 800 / CRS apparatus for 1.5 hours. At the end, a 4.0 ml stromal-vascular fraction (SVF) was obtained containing 162 × 10 ⁶ cells, which were intracavernously administered to the patient at 6 points bilaterally on the lateral surface of the penis: proximally 1.0 ml, medially and distally 0.5 ml , a total of 2.0 ml in each cavernous body. After injections, a tightening tourniquet is applied to the base of the penis for 15 minutes. Adverse events were noted.

Examination of the patient included 10 visits (1, 3, 7 days, 1, 2, 3, 4 weeks, 2, 6 months).

Complaints decreased, notes the improvement in the quality of erections, the resumption of morning and night erections. He adheres to a diet, reduced the number of cigarettes to 8 per day, spends a lot of time in the fresh air. The sum of points on the ICEF-5 scale is 23 points, on SEP - 5 points. Laboratory indicators within normal values. Testosterone total 13.4 ng / ml.

During the control pharmacodopplerography of the vessels of the penis with intracavernous administration of 10 μg of PGET: a significant increase in the peak systolic blood flow velocity and resistance index in both cavernous arteries compared with the baseline. During the pharmacological test with 10 μg PGE1, an erection of degree ER5 on the Unem scale was achieved. Evaluation of endothelial function: an occlusal test did not reveal impaired endothelial function.

After a course of treatment of patients with vasculogenic erectile dysfunction of arteriogenesis, a distinct positive dynamics was noted.

In this way, 12 patients with an established diagnosis were treated when signing informed consent: vasculogenous erectile dysfunction with the achievement of a positive clinical effect in all patients.

The advantage of this method is its high efficiency, which is due to the effect of the components of the SVF on all phases of the regenerative cycle for a long period (365 days or more). The absence of complications and side effects allows you to successfully apply this method of treatment in urological practice.

Claims (1)

A method for the treatment of erectile dysfunction, which consists in the fact that the patient under local anesthesia or intravenous anesthesia takes adipose tissue by liposuction in a volume of up to 250 ml, the resulting adipose tissue is processed on a Celution 800 / CRS hardware complex for 1.5 hours to obtain stromal -vascular fraction (SVF) with a volume of 4.0 ml, containing 50 million or more cells, then intracavernously administered to the patient SVF at 6 points on the lateral surface of the penis bilaterally: proximally 1.0 ml, medially and distally at 0, 5 ml, a total of 2.0 ml in each cavernous body, after which a tightening tourniquet is applied to the base of the penis for 15 minutes.