Biologically active substances composition with geroprotective activity and method for complex correction of age-related changes of hormonal balance, epiphysis functions and antioxidant status involving said composition administration

FIELD: food industry.

SUBSTANCE: invention relates to a biologically active composition and may be used as a remedy with geroprotective activity. The composition contains a concentrate of vegetal saponins - 0.5-5.0 weight parts, Ala-Glu-Asp-Gly / Ala-His peptides composition - 0.001-0.01 weight parts, a complex of acetyl-L-carnitine and alpha lipoic acid - 10.0-25.0 weight parts. The composition with preventive and corrective action is orally administered in an amount of 140-300 mg per day during 28-30 days.

EFFECT: biologically active substances composition stimulates production of dehydroepiandrosterone, reconditions epiphysis functions and increases melatonin level, protects against oxidation with mitochondrion free radicals.

8 cl, 6 ex

 

The invention relates to biotechnology, medicine, pharmaceuticals and nutraceuticals in the creation of biologically active compositions on the basis of biologically active substances for the prevention and correction of age-related changes in hormonal balance, function epiphysis and antioxidant status and can be used as a means of having geroprotective activity.

The concept of "geroprotective activity" means a biologically active, slow aging and prolong life by preventing premature aging and improve its quality, and by reducing the number, extent and intensity of pathologies that are compatible with life, characteristic of elderly and senile age. The increased life expectancy of the person is one of the most important tasks of gerontology and, in General, modern preventive medicine and nutraceuticals. There is every reason to believe that effective prevention of premature aging is the most adequate and most importantly, promising, in the sense of achieving the result that direction.

Currently there are several dozen substances in respect of which shows the ability to increase life expectancy and called geroprotectors. Unlike geriatric funds DL the treatment of diseases in the elderly, geroprotectors can and should be applied not only in adulthood to improve the quality of life, but in the middle and even a young age to prevent premature aging.

According to modern concepts there are a number of theories of aging: genetic, cellular, molecular, hormonal, free radical, and in accordance with these theories is the search for methods of influence to address the causes of aging. It should be noted that proposed on the basis of various theories of aging geroprotectors have different mechanism of action.

On the free radical theory of aging is based antioxidants as geroprotectors. According to this theory, free radicals endogenous and exogenous nature have multiple damaging effects on macromolecules (nucleic acids and proteins), causing their degradation and aging. Antioxidants - compounds that can interact with reactive oxygen species and thereby protect the body from damaging free radicals, slowing the aging process.

Known antioxidant activity of ascorbic acid, tocopherol, beta-carotene, retinol, biogenic amines - serotonin, histamine, as well as polyphenols and phospholipids. Beta-carotene and retinol, as antioxi what ants, at the same time possess the properties of geroprotectors. Active antioxidants geroprotective action are acetyl-L-carnitine and alpha-lipoic acid, which are natural metabolites of mitochondria - the energy of the substances of the cells that are most susceptible to oxidative stress. Known cholinergic, antihypoxic and neurotrophic effects of drug Carnitin based on acetyl-L-carnitine. Anti-oxidant and neurodegenerative properties of plain products alpha lipoic acid described in the patent RU 2357722, publ. 10.06.2009; EN 2372904, publ. 30.11.2009. The manifestation of a synergistic antioxidant effect when combined acetyl-L-carnitine and alpha lipoic acid are reflected in the application No. 2001108586, publ. 20.02.2003, patent RU 2407513, publ. 27.12.2010.

With reduced levels of melatonin produced by the pineal gland (epiphysis) and the body needs for coordination of jet lag, increase antioxidant activity, protection of the genome from damage and regulation of metabolism connected with another of the major theories of aging. Melatonin also has muscle relaxant activity, sedative, hypnotic and anxiolytic action. The lack of melatonin causes depression, the time offset most healthy, sleep disorders, sexual disorders, impaired the functions of the immune and neuroendocrine systems.

To normalize the level of melatonin synthesis which fades with age, and his lack of further accelerating the aging process, from modern prior art it is known to use a mono - or complex preparations containing the substance melatonin EN 2336890, publ. 20.01.2009; EN 2205646, publ. 10.06.2003; EN 2203053, publ. 27.04.2003. However, the constant use of melatonin is a contentious issue, there is an opinion that in this case the probability of side effects (RU 2162076, publ. 20.01.2001).

In addition, it is known that many physiological functions epiphysis associated with produced in him peptides, peptide drug epiphysis epithalamin and synthetic tetrapeptide epiphysis of epitalon (EN 2157233, publ. 10.10.2000) have geroprotective and anti-oxidant effect.

The hormonal theory of aging is based on the fact that the level of hormones determines the biological age of a person. Indeed, hormones are chemical messengers secreted by endocrine glands and affecting virtually all body functions.

The most widely used in this area is hormone replacement therapy - substitution in the body of the missing hormones, for example, reception of a thyroxine in the thyroid gland (EN 2205003, publ. 27.05.2003; EN 2407533, publ. 27.12.2010), or estrogen at estrog the new failure and dysfunction female sexual sphere (EN 2403046, publ. 10.11.2010; EN 2377984, publ. 10.01.2010), or testosterone with impaired spermatogenesis (application No. 2009120990, publ. 10.12.2010; EN 2303981, publ. 10.08.2007).

To prevent premature aging of the body are also encouraged to use various means of natural origin. It is known the use of the drug Vita-plant, consisting of a mixture of dry extracts of the skin of dark grapes, olive leaves, rosemary leaves, grape seeds, and gum Arabic and Aerosil (EN 2274469, publ. 20.04.2006) and designed to provide anti-aging effects on the human body. The drug increases the body's resistance to adverse external factors, slows the aging process and stimulates the regenerative processes of the body.

However, the drugs are based, mainly, on the antioxidant activity of the composition of ingredients in the stated proportions. The antioxidant activity of the drug determines the effect of protecting cells from damage by free radicals, increases resistance to adverse external factors and due to this slows down the aging process.

Known drug to slow the aging (EN 2169575, publ. 27.06.2001), including tumeric, Nigella damascena, myrobalan, ginger,garlic, cardamom, pepper cubeb, long pepper, cinnamon and sugar. The drug has antioxidant activity, restores the trace element balance in the body, stimulates the immune and hormonal system.

The disadvantage of the drug is that its action is mainly aimed at the treatment of diseases associated with aging: vegetative-vascular dystonia, desapariciones syndrome, immunodeficiencies various etiologies, kidney stone and gallstone diseases, etc. That is slow aging while using this drug occurs indirectly through a positive impact on the course of disease due to elderly and senile age.

Also available biologically active compound tetrapeptide L-alanyl-L-glutamyl-L-aspergillosis General formula L-Ala-L-Glu-L-Asp-Gly (EN 2157233, publ. 10.10.2000) for the preparation means having a geroprotective activity. Methods of prevention of premature aging involves preventive and/or therapeutic introduction to a patient in doses of 0.01-100 μg/kg of body weight at least once during the period required to achieve a therapeutic effect.

The disadvantage of this drug is moneyproblems his actions, namely the manifestation of geroprotective activity by stimulating about the ECCA synthesis of melatonin, as the leading mechanism of aging in the paper the disorders in the physiological functions of the pineal gland responsible for the production of melatonin.

Known biologically active food Supplement (EN 2345571, publ. 10.02.2009), representing a balanced antioxidant complex, including water - and fat-soluble antioxidant vitamins a, C and E, cisternasii compounds (amino acid methionine and lipoic acid), selenium-containing compound (sodium Selenite) and technological filler. The invention allows for efficient quenching of free radicals in aqueous and lipid environments of the body, increases the activity of antioxidant enzymes accelerates tracklemovania oxidized forms of antioxidants and blocks the initiation of free radical processes.

The disadvantage of the proposed BAD is that it only regulates the processes of free radical oxidation, eliminating the imbalance between oxidative and antioxidative processes in the body. There has only an antioxidant effect, but does not affect other mechanisms causing age-related changes in the body.

Known anti-stress and nootropic agent with antiviral and immunostimulating action (EN 2211703, publ. 10.09.2009)containing the nonapeptide DSIP from posledovatelnostyakh Trp-Ala-Gly-Asp-Ala-Ser-Gly-Glu and genetically engineered alpha-interferon (IFN). The tool may further comprise a glycine or glycine and dipeptide carnosine or glycine dipeptide carnosine and melatonin.

A disadvantage of the proposed tools is focused on reducing risk and preventing viral diseases of the stress associated not so much with the aging process, but with the characteristics of the ecological and social environment. In addition, this tool is offered for use in intranasal form.

Renowned pharmaceutical composition for the treatment and prevention of cerebral cardiovascular disease (RU 2349337, publ. 20.03.2009)containing steroidal saponins, including 5-25 wt. parts furastanol saponin, 1-10 wt. parts spirostanol saponin or sapogenin, these steroid saponins obtained from extracts of dioskoreya Dioscorea family Dioscoreaceae.

However, this pharmaceutical composition refers to products intended for treatment of diseases of the cardiovascular system: angina, ischemia, myocardial infarction, arrhythmia and other cerebrovascular disorders caused by various pathogenic factors and not just the aging process.

Known neuroprotective dietary Supplement (EN 2389500, publ. 20.05.2010), which contains a peptide composition comprising two peptide with the sequence is almostly 1: NMVPFPR or sequence 2: ASAFQGIGSTHWVYDGVGNS. Mixed additive may further comprise additional peptides with molecular weight less than 10 kDa. It can optionally contain amino acids. The proposed dietary Supplement can prevent or reduce age-related neurodegeneration, age-related decline in cognitive function and age-related memory impairment. It serves as a tool to improve memory, attention and vigilante in humans, preferably in the elderly.

The disadvantage of this food additive is that it is aimed solely at maintaining mental functions in the aging process and does not affect the impact on other functional systems that determine the aging process.

Famous syrup (EN 2152744, publ. 20.07.2000)containing vitamins, Hematogen liquid multi-vitamin "Decemeber", and the hormone melatonin, dehydroepiandrosterone, testosterone and aqueous-alcoholic liquid. The drug helps to increase the duration of life with consistent use.

The use of this syrup, which has in its composition hormones such as melatonin, dehydroepiandrosterone, and testosterone, assumes exogenous introduction of hormones, that is a direct analogue of the conduct of hormone replacement therapy. Hormone replacement therapy does not belong to the category of curative procedures, and is Leche is of pathological conditions, therefore, can and should be done only by a doctor and always under the supervision of a physician. In addition, the presence of the male hormone (testosterone) significantly limits the consumer segment.

Known composition for the correction of age-related changes in the endocrine system of humans (EN 2275930, publ. 10.05.2006)containing substances with hormonal (VG) or hormone-like (GP) activity, selected from the group of C21 - or C19-steroids, pregnenolone, 17-hydroxypregnenolone, DHEA, progesterone, testosterone, or hormone-like substance of vegetable origin (BP), and dry methanol root extract of nettle in the following ratio of components, wt. part: VG, VP, or BP is 0.0001-25,0 root extract nettle - 0,05-50,0. The composition contains BP in the form of phytochemical compounds, such as diosgenin and protodioscin. Anti-aging composition may also contain a dry alcoholic extract of the antlers of deer or dry extract of ginseng root. This composition allows to correct hormonal changes in the body.

The effect of applying this composition is intended only for the correction of hormonal changes in the body with age and not for other aging mechanisms.

The disadvantage of these technical solutions is moneyproblems action visapur the numerical tools. That is, each proposed solution has a specific mechanism of action in accordance with one theory of aging.

Each theory, which determines the mechanism of human aging, uses its own set of physiological parameters for the initial assessment of biological age of a person, as well as to assess changes after the correction procedure. The nature of age-related changes of some physiological parameters used for the assessment of biological age of a person, shows that only some of them objectively correlate with age. These indicators are referred to as biological markers of aging. Directional effects on these markers allows correction of the biological age of a person, preventing, including premature aging.

Technical problem on which the invention is directed, is the creation of a new composition of biologically active substances with a geroprotective effect, and how complex impact on three biological marker of aging, aimed at the correction of age-related changes in accordance with the three theories of aging.

The technical result of the invention is to provide a composition having a geroprotective effect, which stimulates PR the production of DHEA (dehydroepiandrosterone) - natural metabolite of the adrenal glands, the level of which determines the biological age of a person, restores the functional activity of the pineal gland and, consequently, increases the production and secretion of melatonin protects macromolecules cells from damage by free radicals by increasing the antioxidant status of the organism.

To solve the problem and achieve the technical result of the proposed composition of biologically active substances with a geroprotective effect, characterized in that it contains a synergistically active ingredients - concentrate plant saponins, and composition of the peptides (Ala-Glu-Asp-Gly/Ala-His) and a complex of acetyl-L-carnitine/alpha lipoic acid in the following proportions herbal " lift", parts by weight: concentrate plant saponins - 0,5-5,0; the composition of the peptides (Ala-Glu-Asp-Gly/Ala-His) - 0,001-0,01; complex acetyl-L-carnitine/alpha lipoic acid - 10,0-25,0.

When the above composition is a biologically active food Supplement and contains the composition of the peptide Ala-Glu-Asp-Gly/Ala-His ratio, parts by weight: 5,5-9,0:1,0, complex acetyl-L-carnitine/alpha lipoic acid in the ratio of 2.5-3.0:1.0 in.

The above composition also optionally contains additional components selected from the group of: silicon dioxide (Aerosil), calcium stearate (or the Agnes stearate), starch, gelatin, microcrystalline cellulose.

The composition of biologically active substances with a geroprotective effect, is also characterized in that the composition of peptides previously placed in starch or gelatin matrix method microfilaraemia and complex acetyl-L-carnitine/alpha lipoic acid pre-audren a mixture of highly disperse silicon dioxide (Aerosil) and stearate of calcium (or magnesium).

The composition of biologically active substances with a geroprotective effect, also characterized by the fact that the complex acetyl-L-carnitine/alpha lipoic acid and concentrate plant saponins pre Audrey a mixture of highly disperse silicon dioxide (Aerosil) and stearate of calcium (or magnesium).

The composition is a bulk homogeneous powdery mass. Using the composition of the peptides in the form of microspheres allowed in homogeneous powdery mass inclusion of microspheres. The proposed tool can be used independently or in the form of one of the components of the pharmaceutical or nutraceutical compositions, which may be encapsulated or tableted.

The essence of this invention lies in the fact that the composition consists of substances previously not used together, but possessing the x in such a combination of synergistic effect. The components used are selected in such a way as to provide a multi-functional action to prevent the aging process, especially premature. The cumulative impact of its components on the body allows to obtain a composition having high geroprotective activity by stimulating the production of DHEA, restore the functional state of the epiphysis and increase the production of melatonin, as well as the active antioxidant protection of mitochondria.

Included in the composition of biologically active components are not antagonists, and their ratio in the composition are selected in such a way that they complement each other. The combination of biologically active concentrate of plant saponins, and composition of the peptides (Ala-Glu-Asp-Gly/Ala-His) and complex acetyl-L-carnitine and alpha-lipoic acid creates sverhsummarny the effect of their actions.

The mechanism of geroprotective properties of the claimed composition is based on the cumulative impact of three biological marker of aging: the level of DHEA, which determines mainly hormonal aging process; the level of melatonin, which defines the functional aging epiphysis; antioxidant status, defines the process of damage to cell structures (primarily mitochondria) free radicals. The ability to simultaneously impact is painted on three biological marker of aging allows for a comprehensive approach to the correction of age-related changes and prevent premature aging.

So, biologically active substances belonging to the class of steroidal saponins, characteristic of plants of the family Liliaceae, amaryllises, figwort, dioscoreaceae. Steroidal saponins are a class of important bioactive substances in plants. The content of saponins in these plants varies widely depending on the facilities to the family, growing region, but also from a number of other subjective factors. Therefore, as a source of saponins was used standardized concentrate of saponins obtained by multi-stage processing of raw materials of plant origin containing saponins (mainly Dioscoreae). Steroidal saponins are similar in their structure to the hormones and possess high biological activity in relation to the mobilization of domestic hormonally reserves. Steroid saponins, getting into the body, stimulate the production of its own hormones more DHEA, which "marked" biological age of a person.

In the process of studying the mechanisms of aging pineal gland (epiphysis) found that age-related decline in the ability of cells to induction of protein synthesis is a consequence of the accumulation of damage to macromolecules due to the action of endogenous free the radicals. While reliable data were obtained, which indicate that changes with age in the epiphysis, are more functional than organic in nature, which makes possible the correction of age-related changes of this neuroendocrine cancer. Peptides in the proposed composition Ala-Glu-Asp-Gly/Ala-His previously for the normalization of the functions of the pineal gland was not used. The innovation proposed composition of the peptides is that it acts simultaneously on all fronts needed to restore the physiological functions of the epiphysis. The proposed peptide composition Ala-Glu-Asp-Gly/Ala-His restores the function of the epiphysis associated not only with produced in him peptides, but also neutralizes free radicals endogenous and exogenous origin, provoking a reduction in the ability of cells to synthesize proteins and peptides. That is, at the same time affects the cause and eliminate the consequences.

The ratio of the composition of the peptide Ala-Glu-Asp-Gly/Ala-His 5,5-9,0:1,0 determined experimentally and is due to the fact that the use of such a ratio is the maximum increase in nocturnal peaks of secretion of melatonin and regulation of circadian rhythms.

High antioxidant activity of complex acetyl-L-carnitine and alpha-lipoic acid appears to improve the ability mitochon the s to produce ATP the main fuel cells to enhance cell energy systems and, simultaneously, to reduce the level of lipid peroxidation of cell membranes. This effect is achieved thanks to the joint use of acetyl-L-carnitine and alpha-lipoic acid is a natural metabolite of mitochondria, which in addition to antioxidant activity, as shown in experiments in vitro (in test tube)and in vivo (in a living organism), ensure the absence of toxicity when injected into the cell. It distinguishes complex acetyl-L-carnitine and alpha-lipoic acid from a variety of synthetic antioxidants for use in a living organism is often accompanied by toxic effect.

The ratio of acetyl-L-carnitine and alpha-lipoic acid as 2,5-3,0:1,0 determined experimentally and is due to the fact that when you share in that value acetyl-L-carnitine and alpha-lipoic acid exhibited antioxidant activity, ten times the antioxidant activity of each of the components separately.

Suggested accessories: silicon dioxide (Aerosil), calcium stearate or magnesium stearate, talc, starch, microcrystalline cellulose (MCC) perform technological functions to ensure the release forms suitable for use.

Thus, the action included in the inventive composition of biologically active components is carried out by different biological mechanisms, so their total (combined) therapeutic effect is more pronounced than the effect of biologically active substances separately.

Experimentally it was determined the optimal ratio in the composition concentrate of plant saponins, and composition of the peptides (Ala-Glu-Asp-Gly/Ala-His) and complex acetyl-L-carnitine and alpha-lipoic acid, which is from 0.5:0,01:25 to 5:0,001:10. Mainly on 1 Mac. part concentrate plant saponins take 0,005 parts of the composition of the peptides (Ala-Glu-Asp-Gly/Ala-His) in the ratio (9:1) and 13 wt. parts of the complex acetyl-L-carnitine and alpha-lipoic acid in the ratio (3:1). At this ratio, the composition contains the optimal number of biologically active substances to stimulate the production of its own hormones, mainly DHEA, normalization of the functions of the pineal gland and the production of melatonin and provide antioxidant protection of mitochondria from aggressive free radicals endogenous and exogenous origin.

Introduction to composition components in a quantity lower than the specified values, reduces efficiency, and the increase of the content is inappropriate.

Thus, the claimed composition of biologically active substances with geroprotective properties:

- restores the level of DHEA to 25-30 years due to the fact that stimulates production of hormones in the body (unlike hormone replacement therapy);

- restores the function of the pineal gland and helps to normalize production of melatonin, raising its level to "young", by introducing the composition of peptides with high tissue specificity in relation to the epiphysis, and neutralizing factors causing the reduction in the ability of cells to their own synthesis of proteins and peptides;

prevents age-related degradation of mitochondria by displaying a high antioxidant activity against cellular structures.

The composition of biologically active substances prepared as follows.

Example 1.

Components for the manufacture of the composition concentrate of plant saponins: the composition of the peptides (Ala-Glu-Asp-Gly/Ala-His): a complex of acetyl-L-carnitine and alpha-lipoic acid (3:1) is used in the following ratio: 0,8:0,01:10.

75 g of acetyl-L-carnitine and 25 g of alpha-lipoic acid separately optivault a mixture of highly dispersed silica (Aerosil) and calcium stearate. This procedure is carried out with the aim of achieving clean is necessary technological characteristics. Powdered acetyl-L-carnitine and alpha lipoic acid are mixed in the mixer cone type and is passed through the mill with the size of the sieve of 0.5, resulting in making the necessary homogeneity of mixing and workability of intermediate composition (A). 8 g of the concentrate of plant saponins also optivault a mixture of highly dispersed silica (Aerosil) and calcium stearate, and then pass through a sieve with a mesh size of 0.5 and get the following intermediate composition (In). Preliminary preparation of the composition of the peptides (Ala-Glu-Asp-Gly/Ala-His) does not hold.

For uniform distribution of the composition of peptides and ensure the homogeneity of the proposed composition prepared by mixing components is carried out stepwise. 0.1 g of the composition of the peptides are mixed with the composition, then in five stages add is divided into five parts part A. After adding each portion of the structure And carry out the mixing in the mixer cone type for 5-15 minutes. After stirring 108, 1 g of the finished composition is passed through a sieve with mesh size of 0.5.

The resulting composition has the following characteristics:

1. Appearance and colorPowder from white to beige to yellowish color.
2. The content of L-carnitine, %, not less than43
3. Alpha-lipoic acid, %, not less than17
4. The content of saponins, %, not less than8

The content of acetyl-L-carnitine and alpha-lipoic acid in the composition, as well as the identification of peptides and saponins were determined by high performance liquid chromatography; the content of saponins were identified by means of UV-spectroscopy.

Example 2.

Components for the manufacture of the composition concentrate of plant saponins: the composition of the peptides (Ala-Glu-Asp-Gly/Ala-His): a complex of acetyl-L-carnitine and alpha-lipoic acid (3:1) is used in the following ratio 5:0,001:24.

180 g of acetyl-L-carnitine and 60 g of alpha-lipoic acid separately optivault a mixture of highly dispersed silica (Aerosil) and calcium stearate. This procedure is carried out in order to achieve the necessary technological characteristics. Powdered acetyl-L-carnitine and alpha lipoic acid are mixed in the mixer cone type and is passed through the mill with the size of the sieve of 0.5, resulting in making the necessary homogeneity of mixing and workability of intermediate composition (C). 0.1 g of the composition of the peptides (Ala-Glu-sp-Gly/Ala-His) placed in starch or gelatin matrix method microfilaraemia (D). Microencapsulation composition of peptides is carried out for the conservation of biological activity in the manufacturing process, and further use as a pharmaceutical or nutraceutical supplements. The concentrate of plant saponins prior training is not required.

For uniform distribution of the composition of peptides and ensure the homogeneity of the proposed composition mixing of the components is carried out stepwise. Composition D is stirred with 50 g of a concentrate of plant saponins, then in five stages add is divided into five parts part C. After the addition of each portion of the composition To carry out the mixing in the mixer cone type for 5-15 minutes. After stirring 290, 1 g of the finished composition is passed through a sieve with mesh size of 0.5.

The resulting composition has the following characteristics:

1. Appearance and colorPowder from white to beige with a yellowish tint, allowed blotches microspheres.
2. The content of L-carnitine, %, not less than43
3. Alpha-lipoic acid, %, not less than17
4. With the actual content of saponins, per cent, not less than8

The content of acetyl-L-carnitine and alpha-lipoic acid in the composition, as well as the identification of peptides and saponins were determined by high performance liquid chromatography; the content of saponins were identified by means of UV-spectroscopy.

The technical result is also achieved by the fact that offers comprehensive correction of age-related changes in hormonal balance, function epiphysis and antioxidant status, including oral administration to a patient the composition of biologically active substances according to any one of items 1 to 7 on 140-300 mg per day for 28 to 30 days.

The possibility of objective manifestations of the technical result of the use of the claimed composition is confirmed by reliable data, containing details of the experimental nature obtained in the course of the research methodologies adopted in this area. Clinical studies on patients, volunteers showed the following. The experiment involved 20 people: 10 men and 10 women aged 35 to 55 years without somatic pathology. The results showed that the proposed composition in 97% of cases (P≤0,05) leads to a correction of age changes due to the stimulation of production of DHEA and improving the overall hormonal levels, improve functional the state of epiphysis and normalization phases of sleep and wakefulness, as well as due to the activation of cell energy systems and the normalization of the energy balance of the organism.

To achieve the required result of the proposed composition (in pill, capsule or other form) is recommended for the following dosages.

For persons under the age of 45 years, the recommended intake is between 70 to 150 mg of the composition daily rate of 28-30 days. The course of treatment should be repeated 3-4 times a year. In the intervals between courses effective procedure supports reception number from 17 to 35 mg every day.

After the age of 45 years is recommended a higher dosage of from 140 to 300 mg daily for 28 to 30 days with a repetition rate of 3-4 times per year. In the intervals between courses that supports the reception in the amount of from 35 to 70 mg every day.

The invention is illustrated by examples of specific implementation that should not be a reason to limit the claims of the applicant, but should be regarded only as examples, confirming the possibility of carrying out the invention with the achievement of the technical result.

Example 1. The patient Y.A., age 42 years, looks older than his age, complaints of difficulty falling asleep, interrupted sleep, fatigue. Within 28 days the patient has claimed the comp is the position of 70 mg twice daily. A comparative analysis of the hormonal profile before and after administration within four weeks of the claimed composition showed significant positive changes. If the initial level of DHEA was to 5.1 µg/ml, which is about 50% of the physiological norm for this age, after the course the level of this hormone was 10.6 µg/ml, which is close to 100% of the physiological norm for this age. While testosterone levels within the physiological norm and to receive the proposed composition remained in the same range and after a four-week course of treatment, which confirms the corrective properties of the claimed composition, when the change of one parameter correlated with the physiological value of the other. Objective indicators are supplemented by the following positive changes observed subjective: there are no difficulties with falling asleep, increased duration of the phases of deep sleep, decreased fatigue.

Example 2. The patient A.G., 54 years old, according to the main indicators healthy for his age, expressed complaints about the weakening of potency and desire to look younger. The patient is offered a four-week course of treatment at a dosage of 140 mg twice a day. Upon completion of the course assessed changes in hormonal profile. The level of DHEA shows virtually DVWK atoe increase compared with the initial result, the corresponding average value for a given age. The level of testosterone increased by 30%, while the patient has no complaints about the weakening of potency. In addition, upon completion of the course the patient felt more active mentally and physically, improved performance, increased elasticity of the muscles and skin turgor.

Example 3. The patient BE, 52 years old, has age-related changes of the level of DHEA and female sex hormones, accompanied by symptoms of menopause such as hot flashes, increased nervousness and irritability, sleep disorders. The original had low levels of DHEA - 1.5 mcg/ml and progesterone - 1.4 nmol/l After 28-day course of treatment with the inventive compositions in a dosage of 150 mg twice a day the level of DHEA increased more than three times and began to meet to 4.7 µg/ml, which is slightly higher than the average rate for this age group. Also about three times higher levels of progesterone (4.2 nmol/l). Subjective indicators, the patient was noted normalization of the correlation of the phases of sleep and wakefulness, as well as expressed the normalization of emotional balance. This is largely due to improved functional status of the epiphysis and the normalization of the production of melatonin.

Example 4. The patient TI, 38 years old, has a premature age-related changes in levels of the female is elovich hormones, the level of DHEA corresponds to the lower rate. These changes are accompanied by reduced libido, aging skin, fatigue and the inability to restore power during sleep due to the emergence of sleep. Within four weeks the patient was taken twice a day 100 mg of the inventive composition. Already in the process of receiving the composition, the patient returned to normal sleep, allowing the body to recover at night and to reduce the fatigue during the day. Analysis of hormone levels in the blood confirmed the correction of age-related changes: progesterone levels increased three times and began to conform to the norm, and the level of DHEA increased to the average for this age norms. Upon completion of the course receive a marked improvement in the density and elasticity of the skin, improving the overall emotional background and increased libido.

Thus, the compositions can be recommended as a geroprotective means for the prevention of premature aging. A study of the safety characteristics showed that this composition has no contraindications except for the individual intolerances, as well as women during pregnancy and lactation.

An advantage of the claimed composition is useful reinforcement of the pharmacological properties of each the incoming ingredient, its compliance with polivalentes Genesis of aging, the impact in General on the human body as a corrective system.

Considering the combined effect of the inventive composition can be used in addition to fatigue, short-term and prolonged stress conditions, during convalescence after illness.

The effectiveness of the composition caused by the action of substances in components of this composition. While each component has its impact on the achievement of the stated result. And its absence does not allow you to fully solve tasks, which gives grounds to consider this essential component.

The advantage of the drug lies in the fact that he not only restores lost body functions and slows down the aging process, but also prevents the occurrence of many age-related diseases, the development of which in the body would contribute to premature aging.

An additional advantage of the inventive compositions is the lack of toxicity that allows you to use it long courses as a standalone tool geroprotective action, and as an aid, for example, in the period of convalescence after illness.

1. the song of biologically active substances, with geroprotective effect, characterized in that it contains synergistically acting components of the concentrate plant saponins, and composition of the peptides Ala-Glu-Asp-Gly/Ala-His and complex acetyl-L-carnitine and alpha-lipoic acid in the following ratio of components, parts by weight:

the concentrate of plant saponins0,5-5,0
the composition of the peptide Ala-Glu-Asp-Gly/Ala-His0,001-0,01
complex acetyl-L-carnitine and alpha-lipoic
acid10,0-25,0

2. The composition of biologically active substances with a geroprotective effect according to claim 1, characterized in that it contains the composition of the peptide Ala-Glu-Asp-Gly/Ala-His in the ratio of parts by weight of 5,5-9,0:1,0.

3. The composition of biologically active substances with a geroprotective effect according to claim 1, characterized in that it contains a complex of acetyl-L-carnitine and alpha-lipoic acid in the ratio of 2.5-3.0:1.0 to

4. The composition of biologically active substances with a geroprotective effect according to claim 1, characterized in that it further comprises an excipient selected from the group: d is silicon oxide (Aerosil), stearate of calcium (or magnesium), starch, gelatin, microcrystalline cellulose.

5. The composition of biologically active substances with a geroprotective effect according to claim 1, characterized in that it is a biologically active food Supplement.

6. The composition of biologically active substances with a geroprotective effect according to claim 1, characterized in that the composition of the peptide Ala-Glu-Asp-Gly/Ala-His previously placed in starch or gelatin matrix method microfilaraemia and complex acetyl-L-carnitine and alpha-lipoic acid pre-audren a mixture of highly disperse silicon dioxide (Aerosil) and stearate of calcium (or magnesium).

7. The composition of biologically active substances with a geroprotective effect according to claim 1, characterized in that the complex of acetyl-L-carnitine and alpha-lipoic acid and concentrate plant saponins pre Audrey a mixture of highly disperse silicon dioxide (Aerosil) and stearate of calcium (or magnesium).

8. The method of complex correction of age-related changes in hormonal balance, function epiphysis and antioxidant status, including oral administration of the composition of biologically active substances according to any one of claims 1 to 7 140-300 mg per day for 28-30 days.



 

Same patents:

FIELD: medicine.

SUBSTANCE: method of individual recovery of functional activity of adrenal cortex in patients with somatic diseases with long history of glucocorticosteroid (GCS) therapy includes detection of iatrogenic adrenal insufficiency by value of indices of cortisol in blood, urine and on the basis of indices of functional test, which consists of intramuscular introduction of 1 mg synacthen-depot, synacthen-depot being introduced in the morning and determined in day urine: free, conjugated and general cortisol, in blood, obtained in the morning hours: ACTH, dehydroepiandrosteron-sulfate (DHEA-s), aldosteron, glucose, potassium, sodium, stimulation of synacthen-depot is carried out step-by-step with simultaneous reduction of taken doses of glucocorticosteroids; if indices of hormones in blood and urine decrease on the 3-rd or 5-th day by more than 50% from the lower norm boundary, further stages of medication injections are carried out after different time intervals from 6 to 5 months depending on the content of said indices in blood and urine without injection of synacthen-depot during dynamic examination of patient, further stages are realised with additional determination of cortisol content in blood 1 hour after synacthen-depot injection, if level of cortisol in vblood is higher than 500 nmol/l an hour after the injection, with normal excretion of free cortisol on the 3-rd or 5-th day, normal content of electrolytes, glucose in blood with satisfactory patient's condition, intake of glucocorticosteroids is cancelled.

EFFECT: invention makes it possible to avoid clinical manifestations of cessation syndrome and exacerbation of main and accompanying diseases in patients.

3 tbl, 3 ex, 2 dwg

FIELD: medicine.

SUBSTANCE: invention relates to medicine and application of hexapeptide of structural formula arginyl-alpha-aspartyl-lisyl-valyl-tirozyl-arginine in steroid therapy.

EFFECT: invention provides for development of new efficient agent for coping with steroid resistance.

1 cl, 2 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to pharmaceutical compositions possessing inhibitory effect with respect to MC2R-receptors, for preparing medicinal preparations as tablets, granules, capsules, suspensions, solutions or injections placed into pharmaceutically acceptable package. As active substance the composition comprises azaheterocyclic compound of general formulas (1.1.1) , (1.2.1) or (1.3.1) , wherein R1 in the general formula (1.1.1) represents substituted alkyl, aryl, heteroaryl, heterocyclyl, or R1 in the general formula (1.2.1) represents a substitute of amino-group chosen from hydrogen atom or possibly substituted lower alkyl or lower acyl; each R2, R3 and R4 represents independently of one another a substitute of cyclic system chosen from hydrogen atom, azaheterocyclyl, possibly substituted lower alkyl, possibly substituted hydroxy-group, carboxy-group, cycloalkyl; or R3 and R4 in common with carbon atoms to which they are bound form azaheterocycle, or R1 in common with nitrogen atom to which it is bound, and R3 and R4 in common with carbon atoms to which they are bound form azaheterocycle through R1, R3 and R4; R18 and R19 represent independently of one another substitutes of amino-group chosen from hydrogen atom or lower alkyl substituted with azaheterocycle as their racemates, optically active isomers or their pharmaceutically acceptable salts and/or hydrates; R20 and R21 in common with nitrogen atom to which they are bound form possibly substituted azaheterocycle. Also, invention relates to a method for preparing a pharmaceutical composition and using compounds and compositions for preparing medicinal preparations and for treatment or prophylaxis of diseases associated with enhanced activation of adrenocorticotropic hormone for compounds of general formulas (1.1.1), (1.2.1) and (1.3.1), and for using compounds for experimental investigations of indicated processes in vitro or in vivo also.

EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions, improved preparing method.

15 cl, 1 dwg, 4 tbl, 5 ex

The invention relates to medicine
The invention relates to medicine

FIELD: chemistry.

SUBSTANCE: invention relates to a quinazoline derivative of general formula [1], or a pharmaceutically acceptable salt thereof [1], where R1-R6 assume values given claim 1, except compounds in which R5 is hydrogen and R6 is -NH2. The invention also relates to a pharmaceutical composition having the activity of an antipruritic agent, containing as an active ingredient said quinazoline derivative or pharmaceutically acceptable salt thereof.

EFFECT: obtaining a novel quinazoline derivative with low irritant action on skin and excellent action of significant suppression of scratching behaviour, as well as an antipruritic agent containing such a quinazoline derivative as an active ingredient.

9 cl, 250 ex, 7 tbl

FIELD: medicine.

SUBSTANCE: present invention refers to medicine and describes prolonged release therapeutic tablets for oral administration containing a first layer including a first active substance with the first layer arranged between the two adjoining controlled release layers with at least one of said adjoining layers containing at least one second active substance containing acetaminophen with the two adjoining layers enclosed in substantially integrally whole first layer around an external border wherein said tablet provides the applied serum concentration of acetaminophen Tmax from approximately 2 hours to approximately 8 hours after administered in a subject. What is also described is the therapeutic tablet wherein the first layer is provided between the two adjoining controlled release layers combined in one continuous layer. There are described methods for controlling drug release.

EFFECT: invention provides preparing the prolonged release composition of simple formulation and structure which can effectively integrate a number of active substances in a stable state and which can provide effective combination drug-induced treatment over a long periods of time.

44 cl, 10 dwg, 9 tbl, 7 ex

Chemical compounds // 2462472

FIELD: chemistry.

SUBSTANCE: invention relates to certain glucocorticoids derived by unsaturated fatty acids having anticancer therapeutic action and pharmaceutical compositions containing said compounds.

EFFECT: improved properties of the compound.

26 cl, 7 ex, 3 tbl

Compounds // 2461559

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new purine derivatives possessing the properties of an inhibitor of the enzyme CDK specified in CDK1, CDK2, CDK3, CDK4, CDK6, CDK7, CDK8 and CDK9. In formula (I): R1 and R2 each independently represents H, C1-6alkyl or C1-6halogenalkyl; R3 and R4 each independently represents H, C1-6-alkyl or C1-6-halogenalkyl; R5 represents C1-6-alkyl or C3-12-cycloalkyl, or C3-12-cycloalkyl-C1-6-alkyl each of which may be optionally substituted by one or more OH groups; R6 represents wherein Y represents N, X and Z represents CR9; R7, R8 and R9 optionally represent H, alkyl or C1-6-halogenalkyl; wherein at least one of R7 , R8 and R9 is other than H. The invention also refers to a pharmaceutical composition containing said compounds, using the compounds for treating alopecia, stroke, a proliferative disease, such as cancer, leukaemia, glomerulonephritis, rheumatoid arthritis, psoriasis, viral diseases, such as a disease caused by human cytomegalovirus, type 1 herpex simplex virus, type 1 human immunodeficiency virus, a neurodegenerative disease, a CNS disease, such as Alzheimer's disease.

EFFECT: preparing new purine derivatives possessing the properties of the inhibitor of the enzyme CDK.

30 cl, 8 tbl, 18 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely obstetrics and gynaecology, and may be used for treating early miscarriage in females with primary hyperprolactinemia. That is ensured by prescribing a sparing regimen combined with the administration of dufaston. It is added with prescribing the preparation dostinex 0.125 mg - 0.250 mg at bedtime to a pregnant woman 1-2 times a week to the 10-12th week of pregnancy.

EFFECT: method provides higher clinical effectiveness, reduced side effects and complications.

3 ex

FIELD: chemistry.

SUBSTANCE: invention relates to peptidyl analogues of ghrelin having greater stability which are active with respect to the GHS receptor, having the formula given below: (R2)-A2-A3-A4-A5-A6-A7-A8-A9-A10-A11-A12-A13-A14-A15-A16-A17-A18-A19-A20-A21-A22-A23-A24-A25-A26-A27-A28-Rl, where values of A1-A28, R1 and R2 are given in the description, pharmaceutically acceptable salts thereof and pharmaceutical compositions containing an effective amount of said compound, as well as therapeutic and non-therapeutic applications thereof.

EFFECT: high stability.

22 cl, 3 tbl, 11 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to endocrinology and cardiology and deals with treatment of metabolic syndrome. For this purpose complex treatment, which includes antihypertensive diet, individually selected aerobic physical exercise, introduction of metformin in dose 500 mg two days per day and melaxen, is carried out. Melaxen is introduced before going to bed 30 minutes before sleeping in dose 1-2 mg during first two weeks, and then in dose 3 mg during the following ten weeks. Course of treatment constitutes 12 weeks.

EFFECT: complex of non-pharmacological and pharmacological therapy as well as empirically selected mode of melaxen introduction ensure efficient treatment due to essential reduction of body weight and reduction of insulin-resistance in said group of patients.

2 ex

FIELD: medicine.

SUBSTANCE: endothelial dysfunction is diagnosed if observing the twofold increase of a rat's blood glucose level. The technique involves determining antioxidant system values, a concentration of total NO metabolites, eNOS activity, a micro- and macrohaemodynamic status, a MDA concentration and Na+ K+ ATP-ase activity in myocardial and hepatic cell membranes. The values variations enables stating the presence of endothelial dysfunction in alloxan diabetes. Such dysfunction is corrected by the subcutaneous introduction of the preparation Ubiquinone (Coenzyme Q10) 0.11 mcl/100 g of animal's weight once a day for 30 days.

EFFECT: more accurate and reliable diagnosis of the vascular disorders accompanying said type of diabetes, and effective correction of such disorders also provides reproducibility, ease, availability, safety and low cost of performing the experiment.

2 cl, 2 tbl, 6 dwg, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a pharmaceutical composition showing stress-protective action which contains peptide R1-Lys1-Arg2-Pro3-R2 [SEQ ID NO:1] or R1-Lys1-Arg2-Arg3-Pro4-R2 [SEQ ID NO:2] wherein R1=NH2 or CH3CO and R2=OH or NH2 and a method for prevention and/or treatment functional or stress-induced disorders caused by extreme factors.

EFFECT: producing the pharmaceutical composition exhibiting stress-protective action.

3 cl, 9 tbl, 7 ex

FIELD: chemistry.

SUBSTANCE: invention relates to stable metastin derivatives, having excellent biological activity. The disclosed metastin derivatives improve stability, gelation tendency is reduced, pharmacokinetics are also improved, and an excellent cancer metastasis suppressing activity or a cancer growth suppressing activity is exhibited.

EFFECT: metastin derivatives of the present invention also have a gonadotropic hormone secretion suppressing activity and sex hormone secretion suppressing activity.

5 cl, 4 tbl, 18 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine and concerns the use of a non-immunosuppressive derivative of cyclosporine A for reducing mitochondrial dysfunction and a degree of apoptosis in patient's cells with diagnosed congenital Ullrich myopathy or Bethlem myopathy.

EFFECT: invention provides considerable reduction of a degree of apoptosis and mitochondrial dysfunction.

5 cl, 5 ex, 6 dwg, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to a method of purifying a cyclic or an acyclic peptide selected from a group comprising eptifibatide, exenatide, atosiban and nesiritide or combination thereof, from a mixture containing at least one impurity, involving contacting said mixture with a reverse phase HPLC matrix and an ion-exchange chromatography matrix and obtaining a purified peptide product with purity of at least 96% and, preferably, at least about 99%.

EFFECT: obtaining a purified peptide product.

11 cl, 4 tbl, 18 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, particularly neurotraumatology. A method involves using pharmacological preparations and physiotherapeutic procedures. As pharmacological preparations, neuromedin, vitamins B1 B12, trental are administered. The physiotherapeutic procedures involve trasspinal exposure of the spinal cord and cerebrospinal roots at a level of the occurrence of the roots involved in injured nerve formation to pulse magnetic field. The exposure includes rhythmed pulses at frequency 3 Hz at intensity 1.5-2 T. Duration of a session is 5-7 minutes. The therapeutic course is 10-15 procedures.

EFFECT: method provides reduced length of treatment and higher degree of body functional recovery ensured by the integrated treatment involving exposure on the injured region.

1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to cytotoxic compounds of directed action and methods for therapeutic use thereof in treating neoplasm and other diseases.

EFFECT: high treatment efficiency.

9 cl, 12 tbl, 31 ex, 3 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to octapeptides of formula (I), where X and Y=H or a chelating group, particularly DOTA, covalently bonded with α- or ε-amino groups of N-terminal lysine, which are octreotide derivatives, as well as radiotracers based thereon, used in tumour diagnosis. The octapeptide of formula (I) forms a chelate complex with radionuclides, for example in form of gallium isotopes 68Ga, 66Ga, 67Ga to obtain a radiopharmaceutical complex. The radiotracer is used for diagnosis of tumours expressing somatostatin receptors or metastases thereof.

EFFECT: improved method.

4 cl, 8 ex, 3 tbl, 1 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to stable metastin derivatives, having excellent biological activity. The disclosed metastin derivatives improve stability, gelation tendency is reduced, pharmacokinetics are also improved, and an excellent cancer metastasis suppressing activity or a cancer growth suppressing activity is exhibited.

EFFECT: metastin derivatives of the present invention also have a gonadotropic hormone secretion suppressing activity and sex hormone secretion suppressing activity.

5 cl, 4 tbl, 18 ex

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