RU2720815C1 - Method of endothelial dysfunction correction in patients with secondary lymphedema of lower extremities - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to a method of endothelial dysfunction correction in patients with secondary lymphedema of lower extremities. Method comprises wearing compression jersey of compression class III and using endothelioprotector for 3 months, wherein the endothelioprotector used is a purified micronised flavonoid fraction, in terms of dry substance, 1000.00 mg, consisting of 900 mg of diosmine and 100 mg of flavonoids in terms of hesperidin orally once a day.

EFFECT: above described method provides correction of endothelial dysfunction in patients with secondary lymphedema of lower extremities.

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Description

The invention relates to medicine, namely to lymphology and cardiovascular surgery and can be used to increase the effectiveness of pathogenetic conservative treatment of patients with secondary lymphedema of the lower extremities.

According to epidemiological data, in the general structure of vascular pathology, lymphedema occupies about 12% of patients [1,2]. According to WHO, around 300 million people in the world suffer from various forms of lymphedema. 96% of all patients are people under 65 years of age engaged in labor activities [1,2].

From the point of view of today's data from Russian and foreign scientists, in recent years, the role of endothelial dysfunction, as the leading pathophysiological mechanism for the development and progression of many diseases of the vascular system, including lymphedema, has been increasingly emphasized [1,3,4]. Violation of the lymphatic outflow is closely associated not only with structural changes in the lymphatic system, but also with its functional state. The mechanisms of development of endothelial dysfunction with lymphedema include damage to lymphatic vessels endothelial cells under conditions of oxidative stress and ischemic damage, the formation of pro-inflammatory status, impaired vasoconstriction and vasodilation due to the formation of free radicals and lipid peroxidation products (LPO) [1,5]. Assessment of the severity of endothelial dysfunction with lymphedema, as well as the effectiveness of the therapy, is carried out using a number of biochemical markers of the functional state of the endothelium. Such markers include the end-product of lipid peroxidation - malondialdehyde (MDA) and indicators of the enzymatic link of the antioxidant system - superoxide dismutase (SOD), glutathione peroxidase (GPO) and catalase (CAT) [6,7].

Flavonoids - a group of natural medicines, which include the chromatan nucleus of tocopherols. The endotheliotropic effect of flavonoids is determined by the presence of OH substituents. The main pharmacological properties of the group are: inhibition of lipid peroxidation, destruction of superoxide and hydroxyl radicals, increased resistance of capillary walls. The literature describes the use of a purified, micronized flavonoid fraction, calculated on the dry matter, 1000.00 mg, consisting of 900 mg of diosmin and 100 mg of flavonoids in terms of hesperidine in terms of hesperidin in lymphedema. At the same time, lymphatic drainage improves, which is due to an increase in the flow rate of lymph and a decrease in lymphangions, a decrease in the concentration of protein in tissue and fibroblasts [1,6,8].

The literature describes studies confirming the endotheliotropic effect of the purified, micronized flavonoid fraction, calculated on the dry matter, 1000.00 mg, consisting of 900 mg of diosmin and 100 mg of flavonoids in terms of hesperedin on the endothelium of the venous channel with venous pathology [6,8, 9.10].

We have proposed a method for the correction of endothelial dysfunction of lymphatic vessels in patients with secondary lymphedema of the lower extremities.

The technical result of the invention: correction of endothelial dysfunction in patients with secondary lymphedema of the lower extremities.

The method consists in the following: in the study, a group of patients of 30 people suffering from secondary lymphedema of the lower limbs of stage II was studied. Not less than 2 months before inclusion in the study, all patients were wearing compression hosiery of compression class III. Patients excluded diseases of the venous and arterial systems. All subjects were assigned to wear compression compression jersey class III and an endothelium protector, which was used as a purified, micronized flavonoid fraction, calculated on the dry matter, 1000.00 mg, consisting of 900 mg of diosmin and 100 mg of flavonoids in terms of hesperine orally 1 time per day. The period of conservative therapy was 3 months; surgical treatment was not carried out. All patients underwent whole venous blood sampling in the morning on an empty stomach in an amount of 12 ml. Blood was incubated for 40 minutes at room temperature. Then it was centrifuged at a temperature of + 4 ° C for 15 minutes to obtain blood serum. All serum samples were stored at -80 ° C until laboratory testing. Determination of biochemical parameters of the functional state of the endothelium was carried out before treatment, then after 1 and 3 months from the start of therapy. The levels of CAT, MDA, GPO, SOD were determined. Since arterial and venous pathology in patients was excluded, changes in these biochemical parameters indicated precisely dysfunction of the endothelium of the lymphatic vessels. The concentration of MDA was determined using a competitive enzyme-linked immunosorbent assay (ELISA), which was performed using a kit to assess the overall level of MDA (manufacturer: USCN Life Science Inc. US-CEA597GE). CAT concentration was determined using a competitive enzyme-linked immunosorbent assay (ELISA), which was performed using a kit for quantitative in vitro determination of catalase (manufacturer: USCN Life Science Inc. US-SEC418Hu). GLP was determined using a competitive enzyme-linked immunosorbent assay (ELISA), which was performed using a kit for the quantification of glutathione peroxidase (supplier Abfrontier, Republic of Korea - LF-EK0110). The concentration of SOD was determined using a competitive enzyme-linked immunosorbent assay (ELISA), which was performed using a kit for determination of total superoxide dismutase (supplier Cayman Chemical Company, US - 706002).

The concentration of MDA, CAT, GPO was expressed in nanograms per milliliter (ng / ml). SOD concentration is expressed in units of action per milliliter (U / ml).

By the level of the main enzymes of the antioxidant system of the body, limiting the process of lipid peroxidation at different stages, one can judge the activity of the antioxidant defense of the body.

According to the results of the study, there was a statistically significant increase (p = 0,00026) in the level of GPO after 1 month from the start of the drug (73.14 ± 8.36 ng / ml) compared with the initial (45.34 ± 16.86 ng / ml )

When evaluating CAT, a significant increase (p = 0.007) was observed between the initial indicator (0.369 ± 0.047 ng / ml) and the indicator after 1 month (0.492 ± 0.128 ng / ml), there was also a significant increase (p = 0.064) between the initial indicator and catalase after 3 months (0.470 ± 0.052 ng / ml).

There was a significant increase (p = 0.036) in the level of SOD after 1 month from the start of the study (0.04 ± 0.009 U / ml) compared with the initial level (0.034 ± 0.007 U / ml).

MDA is the final product of lipid peroxidation, and LPO activity is judged by its content. A decrease in MDA was observed after 1 month (365.1 ± 10.7 ng / ml) compared with the initial (368.56 ± 1.88 ng / ml), while there were no significant differences between the groups during the observation period between these visits.

          Table 1

Index Before treatment After 1 month In 3 months MDA (ng / ml) 368.56 ± 1.88 365.1 ± 10.7 368.2 ± 2.72 GPO (ng / ml) 45.34 ± 16.86 73.14 ± 8.36 * 69.85 ± 7.21 CAT (ng / ml) 0.369 ± 0.047 0.492 ± 0.128 * 0.470 ± 0.052 * SOD (ED / ml) 0.034 ± 0.007 0.04 ± 0.009 * 0.035 ± 0.002

* - a significant change in the level of the indicator compared with the value before treatment (p≤0.05)

Thus, against the background of conservative therapy of secondary lymphedema of the lower extremities, there is a change in the level of the main biochemical indicators of the functional state of the endothelium - an increase in the level of superoxide dismutase, catalase, glutathione peroxidase and a decrease in the level of malondialdehyde. The study revealed that wearing compression hosiery of compression class III and oral administration of a purified, micronized flavonoid fraction, calculated on the dry matter, 1000.00 mg, consisting of 900 mg of diosmin and 100 mg of flavonoids in terms of hesperine 1 time per day during 3 months with secondary lymphedema of the lower extremities, leads to a decrease in the activity of lipid peroxidation processes, and, consequently, to the correction of endothelial dysfunction.

Sources of information:

1. Kalinin R.E., Suchkov I.A., Maksaev D.A. Endothelial dysfunction in patients with secondary lymphedema and methods for its correction (literature review) // Young Science (Eruditio Juvenium). 2019.Vol. 7, No. 2. S. 283-293. doi: 10.23888 / HMJ201972283-293]

2. Maksaev D.A., Arkhipkina N.A., Kiseleva E.V. et al. Pathogenetic aspects of the development and progression of lymphedema of the lower extremities. In: Materials of the IV All-Russian Scientific Conference of Young Specialists, Graduate Students, Residents with International Participation; October 11-12, 2018. Ryazan

3. Kalinin R.E., Suchkov I.A., Pshennikov A.S. Endothelial dysfunction and methods for its correction in obliterating atherosclerosis. M .: GEOTAR-Media; 2014.

4. Suchkov I.A. Correction of endothelial dysfunction: the current state of the problem (literature review) // Academician I.P. Russian Medical and Biological Bulletin Pavlova. 2012. No4. S. 151-157.

5. Siems W. G., Brenke R., Beier A., et al. Oxidative stress in chronic lymphoedema // Q J Med. 2002. No. 95. P. 803–809.

6. Kalinin RE, Suchkov IA, Mnikhovich MV, et al. Endotheliotropic effects of the micronized purified fraction of flavonoids in various experimental models of venous endothelial dysfunction // Phlebology. 2014. No4. S. 29-36.

7. Kalinin R.E. The state of pro- and antioxidant systems in patients with arteriosclerosis obliterans of the lower extremities before and after surgery // Russian Medical and Biological Bulletin named after academician I.P. Pavlov. 2005. No. 1-2. S. 78-83.

8. Kalinin RE, Suchkov IA, Pshennikov AS, et al. Effect of venotonic drugs on the functional state of the endothelium in the treatment of varicose veins of the lower extremities. In: Endothelial Dysfunction: Experimental and Clinical Studies. Materials of the X Anniversary International Scientific and Practical Conference; June 1, 2018. Vitebsk, Belarus. 2018.S. 218-221

9. Kalinin R.E., Suchkov I.A., Kamaev A.A. et al. Endotheliotropic effects of venotonic drugs in the treatment of patients with varicose veins // Angiology and Vascular Surgery. 2018.V. 24. No. 4. P. 72-75

10. Kalinin R.E., Suchkov I.A., Pshennikov A.S., Mzhavanadze N.D. The possibilities of pharmacotherapy of chronic venous insufficiency with diosmin preparations from the position of the functional state of the endothelium // Angiology and Vascular Surgery - 2015.21 (21). - S. 91-97.

Claims (1)

A method for the correction of endothelial dysfunction in patients with secondary lymphedema of the lower extremities, including wearing compression hosiery of compression class III and using an endothelioprotector for 3 months, characterized in that the purified micronized flavonoid fraction is used as an endothelium protector, based on the dry matter, 1000.00 mg, consisting of 900 mg of diosmin and 100 mg of flavonoids in terms of hesperidin orally 1 time per day.