History of the creation of the drug Likopid®

Proponents of a healthy lifestyle recommend eating red fruits and vegetables more often. They are useful, in particular, thanks to the pigment that gives the fruits their pleasant red color - lycopene. It is rich in fruits with juicy red pulp - watermelons, tomatoes, blood oranges, grapefruits, guavas.

Lycopene is part of the group of carotenoid compounds, but vitamin A is not formed from it in the body. Lycopene has its own special role in the body.

Biological role of lycopene

Lycopene is an antioxidant. Antioxidants neutralize free radicals, large quantities of which cause undesirable changes in the body: premature aging, decreased vascular elasticity, endocrine problems, tissue growth and degradation, neoplasms, etc.

And although the mechanism of neutralizing free radicals is the same for different antioxidants, they are not interchangeable. Each antioxidant has its own “area of ​​responsibility” – the organs or tissues where it acts most effectively.

Lycopene protects the gastrointestinal tract, reducing the risk of inflammation and degeneration of stomach and intestinal cells into cancer, and also “works” well in blood vessels, preventing the formation of “bad” cholesterol and protecting “good” cholesterol.

Like all carotenoids, lycopene also has a positive effect on vision. But if the zone of influence of most carotenoids extends to the retina, then lycopene protects the lens, protecting it from exposure to ultraviolet radiation and other destructive radiation. So if you are a big fan of sunbathing, live or vacation in the tropics or equatorial zone, or are in the Arctic Circle, go skiing, lycopene should definitely become part of your daily diet. Taking lycopene in periodic courses is also recommended for older people to prevent age-related changes in the lens.

Lycopene helps protect not only the eyes, but also the skin from harmful radiation: regular use reduces the negative effects of ultraviolet radiation and reduces the risk of skin tumors.

But lycopene plays a key role in the reproductive organs of men and women.

KOZLOV Ivan Genrikhovich

Doctor of Medical Sciences, Professor, Moscow.

• Kozlov I.G., Andronova T.M. "Drug effects through innate immune receptors."
• Guryanova S.V., Kozlov I.G. "HMDP normalizes the Th1/Th2 balance in atopic bronchial asImmunopathogenesis of dermatological diseases."
• Kozlov I.G. "Licopid in tumor immunotherapy (review)."
• Kozlov I.G. "New direction in pathogenetic therapy of allergic diseases."
• Revyakina V.A., Kozlov I.G. "Possibilities of GMDP in the treatment of atopic diseases in children."

Lycopene for men

Lycopene reduces the harmful effects of free radicals on the reproductive system and sperm. The main role of lycopene in the male body is to protect the prostate gland from destruction and degeneration.

Consumption of lycopene prevents and slows down the development of benign prostate hyperplasia, and also significantly reduces the risk of prostate cancer. Eating 10 medium-sized tomatoes weekly will help reduce the likelihood of this disease by 40%, but in order to get enough lycopene, it is more advisable for men to take lycopene in a precise dosage - in the form of supplements or as part of antioxidant complexes. Lycopene is a lipophilic compound, that is, fat-soluble. Therefore, lycopene is absorbed much better if taken simultaneously with food, since almost all foods contain at least a small proportion of fat.

In addition, lycopene is used for certain types of male infertility associated with a violation of the structure of sperm and their insufficient quantity.

IVANOV Vadim Tikhonovich

Academician of the Russian Academy of Sciences, director of the Institute of Bioorganic Chemistry named after. Academicians M.M. Shemyakin and Yu.A. Ovchinnikov of the Russian Academy of Sciences, head of the laboratory of peptide chemistry.

• E.Meshcheryakova, E.Makarov, D.Philpott, T.Andronova, V.Ivanov. "Evidence for correlation between the intensities of adjuvant effects and NOD2 activation by monomeric, dimeric and lipophylic derivatives of N-acetylglucosaminyl-N-acetylmuramyl peptides."
• Elena A. Meshcheryakova, Konstantin S. Mineev, Pavel E. Volynski, Tatiana M. Andronova and Vadim T. Ivanov. GMDP: unusual physico-chemical and biological properties of the anomeric forms. J Pept Sci. 2015 Sep;21(9):717-22. doi: 10.1002/psc.2796.
• Laman AG, Lathe R, Shepelyakovskaya AO, Gartseva A, Brovko FA, Guryanova S, Alekseeva L, Meshcheryakova EA, Ivanov VT. Muramyl peptides activate innate immunity conjointly via YB1 and NOD2. Innate Immun. 2021 Nov;22(8):666-673. doi: 10.1177/1753425916668982.

Lycopene for women

In the female body, lycopene is actively involved in the antioxidant protection of breast tissue. Mastopathy is a very serious disease. And some women are at risk for it, for example, if they have breast injuries, genetic predisposition, or termination of pregnancy. Taking lycopene reduces the likelihood of developing mastopathy for women at risk and reduces the likelihood of neoplasms degenerating into malignant ones for those affected.

Lycopene also reduces the likelihood of developing another serious disease - cervical cancer.

For pregnant women over 30 years of age, lycopene helps reduce the risk of developing preeclampsia and prevents fetal damage and hypoxia.

Lycopene is especially necessary for women after the age of 45, when the body's protective antioxidant system begins to deplete.

ANDRONOVA Tatyana Mikhailovna

President of Peptek JSC

• Kozlov I.G., Andronova T.M. Drug effects through innate immune receptors. "Allergology and Immunology", 2013, volume 14, number 4, pp. 254-259.
• Andronova T.M., Chumakova M.M. "Immunomodulator Lykopid® in the treatment of chronic recurrent furunculosis."
• E.Meshcheryakova, E.Makarov, D.Philpott, T.Andronova, V.Ivanov. "Evidence for correlation between the intensities of adjuvant effects and NOD2 activation by monomeric, dimeric and lipophylic derivatives of N-acetylglucosaminyl-N-acetylmuramyl peptides."

Synergin – a source of lycopene

In order to get enough lycopene, it is most convenient to take it additionally - individually or in combination with other antioxidants. An effective source of lycopene is the Synergin complex.

Synergin contains 5 mg of lycopene (in two capsules of the drug), this is the daily requirement for disease prevention. In addition, the complex includes other antioxidants, selected in such a way as to enhance each other’s effects. This is how beta-carotene works well with lycopene. Together they protect the eyes, skin, and also prevent inflammatory processes in the prostate and breast tissue. Synergin also contains coenzyme Q10, rutin, vitamins C and E.

Literature

1. Gupta NP Kumar R. Lycopene therapy in idiopathic male infertility – a preliminary report. Int Urol Nephrol. 2002;34(3): 369-72.
2. Durairajanayagam D., Agarwal A., Ong C., Prashast P. Lycopene and male infertility. Asian J Androl. 2014 May-Jun;16(3): 420-5.
3. Schwarz S, Obermüller-Jevic UC, Hellmis E. Et al. Lycopene inhibits disease progression in patients with benign prostate hyperplasia. J Nutr. 2008 Jan;138(1): 49-53.
4. Sharma JB, Kumar A, Malhotra M et al. Effect of lycopene on pre-eclampsia and intra-uterine growth retardation in primigravidas. Int J Gynaecol Obstet. 2003 Jun;81(3):257-62.
5. Ilic D., Misso M. Lycopene for the prevention and treatment of benign prostatic hyperplasia and prostate cancer: a systematic review. Maturitas. 2012 Aug;72(4): 269-76.

THIS IS NOT AN ADVERTISING. THE MATERIAL WAS PREPARED WITH THE PARTICIPATION OF EXPERTS.

Introduction In recent years, there has been a tendency to increase the number of long-term and frequently ill children (CHI). This group includes both children with an episodic increase in morbidity, in particular, acute respiratory infections throughout the year, and children suffering from repeated respiratory diseases over a long period of life. In the etiology of acute respiratory diseases in FBD, adenoviral infection, rhinosyncytial infection, influenza and parainfluenza viruses, which contribute to the formation of repeated infections of the nasopharynx and respiratory tract, occupy a large place (5). The development of repeated infections of the nasopharynx and respiratory tract in children is also facilitated by factors affecting the immune system, including environmental disturbances observed in the world and in Russia, a delay in the development of the immune system, in particular disorders in the local immune system, sensitization to bacterial allergens and an increase in the frequency of allergic diseases (1, 2, 4, 6). The use of modern clinical and immunological methods makes it possible to study in more depth the disorders of the immune system that contribute to the development of repeated infections of the nasopharynx and respiratory tract and to develop adequate methods of treatment for this category of patients. Materials and methods of research The study included 90 children who were treated in the children's department of the clinic of the Institute of Immunology or on an outpatient basis with repeated infections of the upper respiratory tract and ENT organs at the age of 2 to 15 years; of which 38 are boys and 52 are girls. Criteria for inclusion of patients in the study: disease duration > 1 year; frequency of acute respiratory infections > 6 times a year; frequency of exacerbations of concomitant diseases over the past 6 months – 4 or more times; number of days with disease symptoms of 30 or more in the last 6 months; Criteria for excluding patients from the study: children suffering from autoimmune diseases; children who have received immunomodulatory drugs within the previous 6 months. Most children were diagnosed with combined pathology of the upper respiratory tract: the frequency of acute respiratory infections is more than 6 times a year in all children, adenoids (28 children), tracheobronchitis (20 children), rhinosinusitis (48 children), chronic tonsillitis (18 children), otitis ( 18 children). To objectify the assessment of the patients’ condition, we introduced the concept of “exacerbation severity index,” which was calculated using the following formula (8): “exacerbation severity index” = number of days of illness + number of days of antibacterial therapy per month for one patient (in the case of hospitalization of a child in a hospital, the number sick days doubled). The study of immunological parameters included: determination of the relative and absolute number of CD3+, CD4+, CD8+, CD16+, CD19+ cells, serum immunoglobulins G, A, M classes, IgA level in saliva, spontaneous chemiluminescence, induced chemiluminescence, stimulation index. Assessment of CD markers was performed by direct immunofluorescence using monoclonal antibodies (7). Samples were analyzed on an Epics PROFILE-II flow cytometer (Cultronics). During the study, the viability of lymphocytes was monitored by staining dead cells with a 0.1% trypan blue solution; cell death did not exceed 5–7%. Chemiluminescence indices were studied using a standard method using a chemiluminometer. The concentration of serum immunoglobulins (A, M, G) was determined by the method of radial immunodiffusion in a gel according to Mancini (7). The level of IgA in saliva was determined by enzyme immunoassay. 60 children received licopid (30 children - 1st regimen; 30 people - 2nd regimen) and 30 children constituted a control group that did not receive immunomodulators. The groups were identical in gender, age, nature of concomitant diseases and treatment program. Likopid (Russia) was prescribed orally, 1 mg (1 tablet) at a time, in the morning, on an empty stomach, for 10 days (1st regimen). The effectiveness of the 1st regimen of licopid has been studied previously (9). 30 patients received licopid according to the 2nd regimen: 1 mg (1 tablet) in one dose, in the morning on an empty stomach, for 10 days a month, each of three months. Immunological examination was carried out before and after the end of the course of treatment, after 3 months (1st regimen) and after 6 months (2nd regimen). During the prescription of licopid, the children did not receive antibacterial therapy. Subsequently, in all groups, including the control, antibiotics were prescribed according to indications: culture from the throat, nose or tonsils (hemolytic streptococcus, hemolytic staphylococcus against the background of an exacerbation or purulent otitis, when diagnosing infection with Mycoplasma pneumonia and Chlamydia pneumonia. Children were observed for 6 months before the appointment and for 6 months after the appointment of immunomodulators.Licopid was prescribed outside the period of exacerbation, so the effectiveness of treatment was assessed by the number of episodes of acute respiratory infections and exacerbations of concomitant diseases (preventive effect of the drug): negative effect (increase in the number of acute respiratory infections and exacerbations of concomitant diseases by more than 25% ); no effect (change in the number of acute respiratory infections and exacerbations of concomitant diseases by 0–25%); satisfactory effect (reduction in the number of acute respiratory infections and exacerbations of concomitant diseases by 25–50%); good effect (reduction in the number of acute respiratory infections and exacerbations of concomitant diseases by more than 50 %). Results and discussion The results of the effect of licopid (when prescribed according to the 1st regimen) on hematological parameters in the BBD group are presented in table. 1. A separate group of children (14 people) with an initially reduced number of CD4+ cells was identified. As can be seen from the data presented in the table in the general group of patients and in the group of children with a decrease in T-cells, there are no significant significant changes in hematological parameters when licopid is prescribed. In table Figure 2 demonstrates the effect of lycopid (1st scheme) on immunological parameters. In the general group of patients, there was an increase in the rate of induced chemiluminescence after a course of licopid (p <0.05), other indicators did not undergo significant changes (CD3+-, CD4+-, CD8+-, CD19+-cells, IRI, spontaneous chemiluminescence indicators, stimulation index).

In the group of patients with an initial decrease in CD4+ cells (normally, the relative number of CD4+ cells is 30-60%, the absolute number is 0.6-1.0 x 109/l), after a course of licopid there is an increase in the relative and absolute number of CD4+ cells , IRI, induced chemiluminescence index (p<0.05). In the general group of patients, after therapy with lycopid, an increase in the level of IgA in saliva was observed (p <0.05); no significant dynamics in the level of IgM, G, A in the blood was observed. When assessing the immunomodulatory effect of lycopid in patients with an initial decrease in CD4+ cells, a significant increase in the level of serum IgG is observed in patients who had an initially reduced level (normally, the level of serum IgG ranges from 800 to 2000 mg%). The drug Likopid was well tolerated. None of the patients refused to take the drug during the entire course. During the course of treatment, the following side effects were noted: dyspeptic symptoms in the form of liquefied stools were observed in one patient on the second day of taking the drug, which went away on their own. A more detailed examination of the anamnesis revealed that they arose after errors in the diet. During treatment, one patient’s temperature rose to 38.5°C on days 2–3 of taking licopid. The temperature remained for 3 days. The child's condition was controlled by prescribing antipyretic drugs. The effectiveness of treatment was assessed based on the frequency and duration of episodes of acute respiratory infections and concomitant diseases (the drug was prescribed outside the period of exacerbation) for 6 months after the end of the course of immunomodulatory therapy. Results of assessing the effectiveness of treatment with lycopid: good treatment effectiveness was noted in 3 patients (10%); satisfactory – in 15 patients (50%); no effect – in 12 patients (40%); onegative – not marked. Thus, when licopid was prescribed according to the 1st regimen, 50% of patients had a satisfactory effect, and 10% had a good effect. In 40% of patients, the frequency of acute respiratory infections and exacerbations of concomitant diseases within 6 months after the course of licopid remained unchanged. In terms of immunological indicators, after the administration of licopid, activation of the macrophage unit (induced chemiluminescence) is noted. In patients with an initially reduced number of CD4+ cells against the background of lycopid, an increase in the relative and absolute number of CD4+ cells, IRI, induced chemiluminescence, and IgG levels in the blood was noted. All patients had an increase in IgA levels in saliva. The data obtained indicate that lycopid affects the immunological parameters of the blood (systemic effect) and parameters of local immunity (IgA level in saliva). An assessment of the dynamics of immunological parameters, the frequency of acute respiratory infections and exacerbations of concomitant diseases allows us to recommend an interval between courses of lycopid of 3 months (1st scheme). For the first time, we proposed and tested the 2nd regimen for taking licopid. In table Figure 3 demonstrates the effect of lycopid (2nd scheme) on hematological parameters in patients with acute respiratory syndrome. The indicators in the general group are presented and children with a decrease in CD4+ cells (13 people) are highlighted separately. The data in the table indicate that in both groups of patients there were no significant changes in hematological parameters when licopid was prescribed according to the 2nd regimen. In table Table 4 presents data on the effect of lycopid (2nd scheme) on immunological parameters. In the general group of patients, there was an increase in the rate of spontaneous and induced chemiluminescence after the course (p <0.05), other indicators did not undergo significant changes (CD3+-, CD4+-, CD8+-, CD19+-cells, IRI, stimulation index). In the group of patients with a decrease in T cells against the background of lycopid, there was an increase in the relative number of CD4+ cells, IRI, spontaneous and induced chemiluminescence indicators (p <0.05), the dynamics of other indicators were not significant.

In the general group of patients, there was an increase in the level of IgA in saliva and IgG in the blood (p <0.05); there were no significant changes in the level of IgM and A in the blood. When assessing the immunomodulatory effect of lycopid in patients with an initial decrease in CD4+ cells, a significant increase in the content of serum IgG and IgA, as well as IgA in saliva, is observed. The drug was well tolerated (scheme 2). None of the patients refused to take the drug during the entire course. During the course of treatment, the following side effects were noted: dyspeptic symptoms in the form of liquefied stools were observed in two patients on the second and third days of taking the drug, which went away on their own; During treatment with the drug, in three patients, on the 2nd–3rd day of taking licopid, the temperature rose to 37.6–38.5°C. The temperature lasted for 2–3 days. The children's condition was controlled by prescribing antipyretic drugs. The effectiveness of treatment was assessed based on the frequency and duration of episodes of acute respiratory infections and exacerbations of concomitant diseases (the drug was prescribed outside the period of exacerbation) within 6 months after the end of the course of immunomodulatory therapy. Results of assessing the effectiveness of treatment with lycopid: good treatment effectiveness was noted in 12 patients (40%); satisfactory – in 15 patients (50%); no effect – in 3 patients (10%); negative – not marked. Thus, 40% of patients had a good effect, and 50% had a satisfactory effect. In 10% of patients, the frequency of acute respiratory infections and exacerbations of concomitant diseases within 6 months after the course of licopid remained unchanged. In terms of immunological parameters in the general group, there was an increase in serum IgG and activation of the macrophage component (spontaneous and induced chemiluminescence). In patients with an initially reduced number of CD4+ cells while taking licopid according to the 2nd regimen, an increase in the relative and absolute number of CD4+ cells, serum IgG and IgA, and indicators of spontaneous and induced chemiluminescence was noted. All patients had an increase in the level of IgA in saliva. The 2nd regimen of taking licopid is more effective; an interval between courses of 6 months is recommended.

In table Figure 5 shows the clinical effectiveness of licopid (schemes 1 and 2) over 6 months of observation in comparison with the control group of PBD, similar in gender, age, concomitant diseases and not receiving immunomodulators. The effectiveness of taking licopid according to the 1st regimen is noted within 3 months after the end of the course. In the group of patients who received licopid according to the 2nd regimen for 6 months of observation, good treatment effectiveness prevails over the indicators of the control group and patients who received licopid according to the 1st regimen ((2 >3.8; p<0.05). Traditional treatment did not affect the frequency of acute respiratory infections in the control group in 14 people, which was significantly higher when compared with the group receiving licopid according to the 2nd regimen ((2 >3.8; p <0.05). The exacerbation severity index was significantly lower in the group received licopid according to regimen 2. The frequency of acute respiratory infections and exacerbations of chronic pharyngitis over 6 months of observation was 2–2.5 times lower in the group receiving licopid according to regimen 2, compared to the control group. There was no reduction in the frequency of exacerbations of chronic otitis The data obtained confirm the results of the immunological examination, safety in pediatric practice and allow us to recommend Lycopid for use in a group of long-term and frequently ill children.

Literature 1. Averbakh M.M. Immunological aspects of sensitivity and resistance to generalized staphylococcal infection. Author's abstract. diss. ...Dr. med. Sci. M., 1995. 2. Albitsky V.Yu., Baranov A.A. Frequently ill children. Clinical and social aspects, ways of recovery. Saratov, Medicine, 1986. 3. Andronova T.M., Rostovtseva L.I., Dobrushkina E.P. Bioorganic chemistry, 1980, No. 6, p. 1830–1841. 4. Bogomilsky M.R., Markova T.P., Garashchenko T.I., Chuvirov D.G., Yagolnikova O.V., Radtsig E.Yu., Strebkova O.A., Skvira I.E. Clinical and immunological rationale for the use of the topical bacterial immunocorrector IRS-19 for the prevention of upper respiratory tract diseases in children. Children's Doctor, 2000, No. 5, p. 4–7. 5. Egorova N.B., Efremova V.N., Kreinin L.S. Journal Microbiol., 1987, No. 3, p. 49–52. 6. Sizyakina L.P., Dudarev I.V., Dyuzhikov A.A. The effectiveness of immunocorrective therapy with polyoxidonium in children operated on for congenital heart defects of the blue type. Immunology, 2002, No. 6, p. 356–359. 7. Khaitov R.M., Pinegin B.V., Istamov Kh.I. Ecological immunology. M., VNIRO, 1995, p. 162–167. 8. Chuvirov D.G. Clinical and immunological effectiveness of the use of polyoxidonium, lycopid and biostim in children with repeated infections. Atoref. diss... cand. medical sciences M., 2004. 9. Chuvirov D.G., Yartsev M.N. Clinical and immunological effectiveness of licopid in children with repeated upper respiratory tract infections. Immunology, 2000, No. 2, p. 48–50.

magazine "Policlinic" No. 3 2006 pp. 35-39

MINAEV Sergey Viktorovich

Doctor of Medical Sciences, professor, doctor of the highest qualification category, head of the Department of Pediatric Surgery with a course of additional professional education at the Stavropol State Medical University (StSMU) of the Ministry of Health of the Russian Federation, Stavropol.

• Minaev S.V. "The use of immunomodulatory therapy in children with purulent-inflammatory diseases."
• Minaev S.V. "Complex treatment of acute hematogenous osteomyelitis in children."
• Minaev S.V. "Optimization of the treatment program for children with acute nonspecific lymphadenitis."

MAYCHUK Yuri Fedorovich

Doctor of Medical Sciences, Professor, Honored Scientist of the Russian Federation, Honored Doctor of the Russian Federation, Head of the Department of Infectious and Allergic Eye Diseases of the Moscow Research Institute of Eye Diseases named after. Helmholtz Ministry of Health of the Russian Federation.

• Maychuk Yu.F. “Ten years of experience in using the immunomodulator Lykopid in the complex therapy of inflammatory eye diseases.”
• Maychuk Yu.F. “Complex therapy of severe inflammatory eye diseases using immunomodulators and specific treatment agents.” Lykopid in ophthalmology.

DEGTYAREVA Marina Vasilievna

Doctor of Medical Sciences, Professor, Head of the Department of Neonatology, Federal Postgraduate Education, Russian National Research Medical University named after N.I. Pirogov of the Ministry of Health of the Russian Federation.

• Degtyareva M.V. “The immunity of newborns is normal and pathological. Immunotherapy with Lykopid.
• Degtyareva M.V. “Features of cytokine production, subpopulation composition of lymphocytes and functional state of neutrophils in neonatal pneumonia and methods of immunocorrection.”

IVANOV Andrey Mikhailovich

Professor, Head of the Department of Clinical Biochemistry and Laboratory Diagnostics of the Military Medical Academy named after. CM. Kirova., Military Medical Academy, St. Petersburg, Chief specialist in laboratory diagnostics of the Military Medical Academy named after S.M. Kirov and Chief Laboratory Assistant of the Ministry of Defense of the Russian Federation, St. Petersburg.

• Apchel A.V., Ivanov A.M. "Immunotherapy of chronic trichomoniasis in men."

KONOREV Marat Ruslanovich

Doctor of Medical Sciences, Professor, Head of the Department of General and Clinical Pharmacology with a course of FPK and PK at the Vitebsk State Order of Peoples' Friendship Medical University. Vitebsk, Republic of Belarus.

• Konorev M.R. “The use of the immunomodulator N-acetylglucosaminyl-N-acetylmuramyl dipeptide during three-component anti-Helicobacter therapy.”