RU2611370C1 - Application of preparation laennek for reduction or elimination of manifestation of menopausal symptoms (versions) - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to field of medicine and gynaecology, namely to novel regimens of menopause therapy in women. Claimed are three versions of the method for reduction or elimination of manifestation of menopausal symptoms by intravenous drop introduction of preparation Laennek in combination with different preparations, belonging to group of substitutive hormonal therapy.

EFFECT: increase of efficiency, improvement of tolerance to hormonal therapy in adaptation period and reduction of course of its administration.

3 cl, 1 ex

Description

The invention relates to the field of medicine and gynecology, namely to new modes of menopausal therapy in women.

The age group of Russian women in peri- and postmenopausal women is more than 21 million. Menopause is a biological condition in which involuntary processes in the reproductive system dominate against the background of age-related changes. The frequency of menopausal symptoms is 40-60%.

In the menopause, against the background of age-related restructuring of the body, symptoms dominate, indicating a deficiency of sex hormones and reducing the quality of life.

In early postmenopausal women, symptoms of estrogen deficiency dominate, which can begin in perimenopause and continue in postmenopausal women. The list of early symptoms includes vasomotor symptoms - flushing, excessive sweating; psychological - depressive symptoms, irritability, irritability, sleep disturbance, weakness, decreased memory and concentration of attention; general physical - asthenization, headaches, muscular-joint pains, "crawling" goose bumps on the skin; urogenital and sexual - itching, burning, dryness, dyspareunia, impaired urination (urgent, frequent).

Late possible disorders can be metabolic, cardiovascular, musculoskeletal, urogenital symptoms, such as atrophic vulvovaginitis, rapid urination, cystitis, urgent urinary incontinence, dysuria.

The main treatment for menopausal symptoms is currently hormone replacement therapy (MHT). MHT includes a wide range of hormonal preparations for oral and parenteral administration in various doses, taking into account personal and family history, motivation of women, the results of relevant studies and women's health. MHT may include monotherapy with estrogens or progestogens; with an intact uterus, combined therapy (estrogens with progestogens) in a cyclic mode in the phase of menopausal transition and perimenopause, in postmenopausal women - monophasic combination therapy (estrogens with progestogens) in a continuous mode. However, the use of hormone therapy has many side effects, including addiction, the need to increase doses, etc. (Smetnik V.P. et al. MENOPAUSAL HORMONOTHERAPY AND PRESERVATION OF HEALTH OF WOMEN OF MATURE AGE Clinical recommendations, Moscow, 2014).

Most often, the choice of a woman is in favor of taking herbal remedies and biologically active additives (BAA), which have a positive, albeit significantly inferior to hormonal, therapeutic effect in the absence of risks inherent to hormonal therapy (I.V. Kuznetsova, Yu.B. Uspenskaya. phytoestrogens in women during the menopausal transition and postmenopause. "Effective pharmacotherapy", No. 55, 2013, p. 18-25). The active substances of herbal preparations and dietary supplements used in the menopause, phytoestrogens, are close in structure to endogenous estrogens and are non-steroidal substances of the class of polyphenolic compounds. Such phytotherapeutic methods include the use of Inoclim® dietary supplements containing genistein and daidzein in a dose of 40 mg (daily dose - 80 mg). However, there is evidence of a negative effect of phytoestrogens on the liver.

Contraindications to the appointment of hormone therapy in peri- and postmenopausal women, the refusal of women to use hormones determine the relevance of the search for alternative methods of alleviating menopausal disorders.

Currently, one of the promising drugs for inclusion in the arsenal of funds for menopausal disorders is the drug Laennec.

In the Russian Federation, Laennec is registered as a hepatoprotector and immunomodulator (Japan Bioproducts Industry Co., Japan). The basis of the drug is a human placenta hydrolyzate containing peptide components with a molecular weight of 2 to 100 kDa. The composition of laennec contains growth factors (GF): insulin-like (IGF), hepatocytes (HGF), fibroblasts (FGF), epidermal (EGF), nerve growth factor (NGF), granulocyte colony growth factor (G-CSF) and macrophages (M -GSF), transforming cell growth factor B1 (TGF B1), growth factors PDGF-BB, VEGF, tumor necrosis factor (TNF-α), as well as interleukins IL-1, -2, -3, -4, -5, -6, -8, -10, -12, erythropoietin, interferon-γ (INF-γ), leptin, dehydroepiandrosterone, low molecular weight peptides, nucleic acids, organic acids, nucleosides, 18 amino acids, glycosaminoglycans (glucuronic and hyaluronic acid, chondroitin sulfate), vitamins PP, C, D and group B. The cytokines that make up the laennec activate the metabolism of healthy cells, stimulate metabolic processes, enhance the mitogenic activity of lymphocytes (T, B and NK cells), provide resorption of excess connective tissue (an effect established in relation to the liver) and thus prevent the development of fibrosis. Nucleic and organic acids, nucleosides enhance protein synthesis. Vitamins contained in the placental extract provide the antioxidant and regenerative effect of the drug. Epidermal growth factor (EGF) stimulates the renewal and reproduction of epithelial cells, normalizes the function of melanocytes; fibroblast growth factor (FGF), activates the production of collagen and elastin. Insulin-like growth factor (IGF) helps normalize growth hormone levels. Hepatocyte growth factor (HGF) plays a large role in the restoration of liver cells by stimulating regeneration using cell proliferation mechanisms and hepatocyte DNA synthesis, reducing the cytolytic activity of enzymes.

According to the source of information M.N. Kong, E.J. Lee, S.Y. Lee, S.J. Cho, Y.S. Hong, and S.B. Park, "Effect of human placental extract on menopausal symptoms, fatigue, and risk factors for cardiovascular disease in middle-aged Korean women," Menopause, vol. 15, no. 2, pp. 296-303, 2008, the effects of laennec placenta hydrolyzate on menopausal symptoms, fatigue, and cardiovascular risk factors in Korean women in randomized controlled trials were studied. Korean women aged 40 to 64 years, with menopausal symptoms and fatigue syndrome, who received subcutaneous injections of the drug in the abdominal cavity for 8 weeks, were subject to the study.

Also, the article Investigator Initiated Clinical Study to Explore the Efficacy and Safety of Human Placenta Hydrolysate in the Chronic Fatigue Patients (http://clinicaltrials.gov/ct2/show/NCT01742013?term=laennec&rank=1) discloses the use of Laennec injection, 4 ml ( 2 ml × 2) / day, 3 times a week, for 6 weeks. The article deals mainly with chronic fatigue, but it is also noted that the drug was prescribed for many diseases, such as menopausal disorders.

As the closest analogue, the source of KUZNETSOV I.V. et al. HUMAN PLACENTA HYDROLYSIS EFFICIENCY IN TREATING MENOPAUSAL SYMPTOMS IN WOMEN IN THE MENOPAUSAL TRANSITION. GYNECOLOGY. Volume 15, No. 6, 2013, pp. 24-27, MediaMedica, Moscow, which discloses an analysis of a comparative study on the results of treatment of menopausal women with Laennec® with a course of 10 intravenous drip infusions of 8 ml of the drug in 250 ml of saline 1 time per a week. In the control group, tablet preparations of phytoestrogens were prescribed according to the schemes indicated by the manufacturers for 22 weeks.

The present invention is the development of an improved method of reducing or eliminating the manifestation of menopausal symptoms in women (options).

The problem is solved in that patients with menopausal symptoms in combination with hormone therapy are prescribed intravenous drip of 6.0-10.0 ml laennec per 250 ml of 0.9% saline or 5% glucose solution (procedure time 1 h 30 min) 1 time per week (10 treatments). At the same time, a Klimar patch and hormone replacement therapy drug selected from Divigel, Estrozhel, Estreva (cream) are prescribed (drugs are prescribed in doses according to the manufacturers instructions).

Subsequently, Laennec is prescribed intravenously dropwise 6.0 ml per 250 ml of 0.9% saline or 5% glucose solution 1-2 times a month, the general course is 4-6 months in the form of monotherapy.

In peri- and postmenopausal women, it is advisable to repeat courses with an individually selected frequency once every 6-12 months.

The problem is also solved by the fact that patients with menopausal symptoms are prescribed Laennec according to the scheme.

The treatment begins with the introduction of the drug Laennec IV 6.0-10.0 ml per 250 ml of 0.9% saline or 5% glucose solution in the form of a dropper, for 1 h 30 min, 2 times a week, for correction lipid metabolism No. 5. Then they add 6.0-10.0 ml intravenously drip in the same dilution on the 6th dropper 6 times a day, 2 times a week, drugs of choice: Klimonorm (for hormone replacement therapy), Trisequens, Kliogest, IUD "Mirena" (drugs are prescribed in doses according to manufacturers instructions).

Total laennec iv drip 6.0 ml-10.0 ml per 250 ml of 0.9% saline or 5% glucose solution, No. 10 (5 droppers initially without hormone replacement therapy and then 5 droppers with HRT).

Subsequently, laennec is prescribed intravenously 1-2 times a month, 6.0 ml per 250 ml of 0.9% saline or 5% glucose solution in the form of a dropper for 3-4 months with a control of biochemistry or laennec v / m 6.0 ml to 4 -6 months 1-2 times a week with biochemistry control.

The problem is also solved by a method with a continuous regimen of administration using low-dose drugs.

Simultaneous complex therapy is carried out with the prescription of preparations Angelik, Femoston 1/5, Indiva with a minimum dose of estrogen 25 μg - 1 mg / day and Laennec 6.0 ml per 250 ml of 0.9% saline or 5% glucose solution in the form of an intravenous dropper or / m from the beginning of taking hormonal preparations No. 10, subsequently 1-2 times a month for 3-4 months.

Effect: increase efficiency, improve tolerance to hormone therapy during adaptation and reduce the course of its appointment.

An example embodiment of the invention

The study included women of menopausal age from 45 to 52 years. Patients were randomized into 4 groups (15 women in each treatment group and 15 in the control group). In the 1st treatment group, 8.0 ml of laennec per 250 ml of 0.9% physiological saline was administered intravenously dropwise 1 h 30 min 1 time 10 procedures. At the same time, Klimar and Estrogel patch were prescribed in 5 patients, Klimar patch and Divigel patch in 5 patients, Klimar patch and Estrev cream for the remaining patients. Subsequently, laennec is prescribed intravenously dropwise 6.0 ml per 250 ml of 5% glucose solution 1-2 times a month, the general course is 4-6 months in the form of monotherapy.

In the second group, all patients were injected with Laennec IV 6.0 ml 2 times a week to correct lipid metabolism No. 5. Next, they added HRT preparations on a 6th dropper laennec (6.0 ml iv twice a week), randomly selected by each patient Klimonorm, Trisekvens, Kliogest, IUD "Mirena".

Total laennec iv drip No. 10 (5 droppers at first without HRT and then 5 droppers with HRT). In the subsequent part of the group, laennec is prescribed once a month 6.0 ml intravenously drip for 4 months with a control of biochemistry and another part of the laennec IM group 6.0 ml up to 4 months 2 times a week with a control of biochemistry.

The third treatment group was administered Laennec 6.0 ml IM at the same time as taking Femoston 1/5, 1 mg / day. Subsequently, 6.0 ml of laennec was administered intravenously drop by drop 1-2 times a month.

In the control group, 10 patients were prescribed tablet preparations of hormones according to the schemes specified by the manufacturers, and 5 patients were only given Laennec drug 8 ml iv 10 droppers. All subjects were questioned using the Kapperman menopausal index. To assess the severity of menopausal syndrome, 11 symptoms were considered:

Vasomotor complaints

Paresthesia

Sleep disorders

Nervousness

Depression

Dizziness

Weakness

Arthralgia, myalgia

Headache

Heartbeat

Crawling sensation

Score on a scale of 0 to 3 points in each individual case. The severity of the disease was evaluated by the total score according to the following criteria: 0-14 points - no menopausal syndrome; 15-20 points - mild; 21-35 - moderate severity; above 35 - severe menopause.

The effectiveness of therapy was evaluated immediately after the end of the course.

The decrease in the index in the group taking only laennec averaged from 24.6 ± 5.2 to 15.6 ± 2.2, in the group taking only hormones - from 25.2 ± 6.1 to 17.3 ± 6 , 8, in the first treatment group - from 24.2 ± 5.9 to 13.1 ± 2.0, in the second treatment group - from 25.0 ± 5.2 to 123.1 ± 1.9, in the third treatment group - from 24.3 ± 6.2 to 13.4 ± 1.8.

Moreover, in the treatment groups, the percentage of side effects, such as headaches, dizziness, nausea, increased pressure and tachycardia, according to the survey results were observed only in 4% of cases, while in the group taking hormones - 12%.

Thus, all three variants of the method of reducing or eliminating the manifestation of menopausal symptoms in women can achieve greater effectiveness in therapy and can be recommended for implementation in clinical practice.

Claims (3)

1. A method of reducing or eliminating the manifestation of menopausal symptoms, characterized in that a patient with menopausal symptoms is injected intravenously with 6.0-10.0 ml of laennec per 250 ml of 0.9% saline or 5% glucose solution in the form of a dropper, during 1 h 30 min, 1 time per week, a total of 10 procedures, with the simultaneous administration of a Klimar patch and hormone replacement therapy selected from the group including Divigel, Estrozhel, Estreva (cream), subsequently, 6.0 ml 250 ml of 0.9% saline or 5% glucose solution 1-2 times a month, the general course of 4-6 months in the form of monotherapy. 2. A method of reducing or eliminating the manifestation of menopausal symptoms, characterized in that the patient with menopausal symptoms is prescribed Laennec, starting the course of treatment with intravenous administration of 6.0-10.0 ml of Laennec per 250 ml of 0.9% saline or 5% solution glucose in the form of a dropper, for 1 h 30 min, 2 times a week for the correction of lipid metabolism, 5 procedures, then, starting from the 6th procedure, intravenously drip laennec in the amount of 6.0-10.0 ml per 250 ml 0.9% saline or 5% glucose solution, over 1 h 30 min, 2 times a week, and at the same time a hormone replacement therapy drug selected from the group including: Klimonorm, Trisekvens, Kliogest, IUD "Mirena", and carry out 5 such procedures, subsequently prescribed 6.0 ml of laennec intravenously 1-2 times a month, 3-4 months with a biochemistry control or laennec IM 6.0 ml up to 4-6 months 1-2 times a week with a biochemistry control. 3. A method of reducing or eliminating the manifestation of menopausal symptoms, characterized in that a patient with menopausal symptoms is prescribed an intravenous drop of 6.0 ml of laennec per 250 ml of 0.9% saline or 5% glucose solution, for 1 hour 30 minutes or 6, 0 ml laennecum oil, 10 procedures, and at the same time, a drug selected from the group of Angelik, Femoston 1/5, Indivina, with a minimum dose of estrogen of 25 μg - 1 mg / day is prescribed, then 6 ml of laennec are administered intravenously dropwise to 250 ml 0.9% saline or 5% solution g lucose or 6 ml laennec intramuscularly 1-2 times a month, 3-4 months.