Cosmetic composition for lose weight comprising substance inducing il-6
FIELD: cosmetics, pharmaceutical chemistry.
SUBSTANCE: invention relates to cosmetic composition used for loss weight comprising at least one compound that induces producing IL-6 by adipocytes in form of mixture with NPY antagonist and/or α2 antagonist and with an excipient for the cosmetic variant. Invention provides effectiveness of fatty acids efflux from adipocytes and inhibitory effect on fatty acids incorporation into cells that results to the loss weight effect. The composition shows good stability in storage being without reducing its activity. The composition has no adverse effects.
EFFECT: valuable properties of composition.
11 cl, 3 dwg, 5 ex
This invention relates to cosmetic compositions containing the active substance for weight loss.
The active ingredients in this cosmetic composition selected from the receptor antagonist of neuropeptide Y, hereinafter referred to as NPY antagonist α2 receptors and inductor production of interleukin-6, hereinafter referred to IL-6.
The NPY antagonist, antagonist α2 or inducer of the production of IL-6 may represent ones connection, peptide, cellular or tissue extract of animal or vegetable origin or the product obtained by the fermentation carried out by a microorganism such as a bacterium or fungus.
Patent application EP 838217 describes a cosmetic composition for slimming, which contains the NPY antagonist and antagonist α2. The active substance in the composition is obtained when the fermentation is carried out in two microorganisms, deposited in the National collection of cultures of microorganisms (C.N.C.M.) of the Pasteur Institute, where they were registered under the numbers I 1332 and I 1778 respectively. In the present description of the invention, these active substances identified as the substance a and the substance B, respectively. Cosmetic composition for slimming containing them, referred to as composition Am1.
This composition slimming Am1 dei is there in subcutaneous adipose tissue and regulates the release of fat, stored in the adipocytes.
Composition Am1 by blocking α2 - and NPY-receptors allows you to clean hypertrophied adipocytes and avoid any new excess accumulation in adipocytes, allowing expression βreceptors, whose polifonicheskaja activity in normal masked antilipolytic α2 - and NPY-receptors, which are found in considerable abundance in subcutaneous adipose tissue. Composition Am1, thus, can effectively influence the outflow of the fatty acids accumulated in adipocytes.
The compositions of the present invention support this activity, but complement it with one hand, acts of the action in respect of the receipt of fatty acids, which manifests itself by the effect of reducing the production of LPL (lipoproteinlipase), the enzyme responsible for the intake of fatty acids in the cell and, on the other hand, the hyperplasia of adipocytes. This unexpected additional action receive from substances capable of inducing the production of IL-6 by adipocytes. This substance is produced by the microorganism deposited in the C.N.C.M. the Pasteur Institute and registered under number I, 1844. This active substance later identified as a substance of the Century
Considered for a long time exclusively as an energy reserve,adipocytes over the last few years have demonstrated the functions of the endocrine and secretory cells (Ailhaund G. et al., Medecine/Science 1998, 14, 858-864). Leptin fully illustrates this new secretory function adipocyte. This protein is produced by exactly a Mature adipocyte. He is involved in the regulation of saturation; it is believed that he is also involved in the regulation of fat. Thus, adipocyte responsible for producing factors with autocrine and paracrine activity, which should regulate the physiology of adipose tissue.
In particular, recently it was demonstrated that the endocrine function of adipocyte affected by two specific mediator:
- lysophosphatidic acid (LPA), a lipid factor, the production of which is mediated by activation α2-receptor and function of which is the recruitment of new adipocytes (Valet P., et al., J. Clin. Invest. 1998, 101(7), 1431-1438);
IL-6, which is a multifunctional cytokine.
The substance is known as an inducer of the production of IL-6 by keratinocytes. The method thereof is described in international patent application WO 99/40896. It has an effect on aging skin.
Nothing could indicate that this substance (produced by microorganism 1844 I) will, in addition, to provide a double action on adipocytes.
Recently studies have shown that fat cells can produce IL-6, whose function at the level of adipocytes is to suppression of the synthesis of LPL, an enzyme responsible for the intake of fatty acids in fat cells (Greenberg A. S. et al. Cancer Research, 1992, 52, 4113-4116).
The production of IL-6 by cells in subcutaneous adipose tissue was positively correlated with increasing body mass index (Mohamed Ali V. et al. J. Clin. Endocrinol. Metab. 1997, 82, 4196-4200), but also varies depending on the origin of adipose tissue.
So, in subjects suffering from obesity, basal adipocytes collected from the stuffing area, free 2-3 times more IL-6 than subcutaneous adipocytes (Fried, S. K. et al. J. Clin. Endocrinol. Metab. 1998, 83, 847-860).
Finally, in addition to the ability of IL-6 to reduce the production of LPL by adipocytes, IL-6 may also act through inhibition, differentiation of progenitor cells adipocytes (Hauner H. et al., 8th International Congress on Obesity 1999, 47-53).
IL-6, therefore, acts as a cytokine, which exerts autocrine effect (LPL) and paracrine action (preadipocyte) to slow the development of subcutaneous adipose tissue.
However, as with all the cytokines, IL-6 is a pleiotropic glycoprotein, in other words, he takes different actions depending on the cells that it produces. Thus, at the level of adipocyte IL-6 will provide the actions of a completely different type than those that are already known to keratinocytes.
In particular, in the adipocyte IL-6 synthesized by this cell, on the basis of feedback regulates the content and, consequently, activity f is rment, responsible for intake of fats.
Thus, compositions according to the invention provide the ability to adjust the appearance of the inflow and outflow of fatty acids, including the accumulation and hypertrophy of adipocytes. It also allows you to influence the hyperplasia of adipocytes.
It is known that the formation of new adipocytes in humans occurs throughout the life of individuals. So, the "sleeping" fat cells were isolated older people, regardless of their gender (G. Ailhaud et al. Int. J. Obes. Relat. Metab. Disord. 1992, 16(2), 517-521; Spielgelman In et al. Cell 1996, 87, 377-389; Hauner et al. J. Clin. Invest. 1989; 84, 1663-1670).
The development of adipose tissue occurs as a result of the increase in the size of adipocytes is associated with excessive accumulation of fatty acids, as well as in the recruitment of new fat cells, resulting in the proliferation and differentiation of progenitor cells of the adipocyte - preadipocytes (Valet P. et al. J. Clin. Invest. 1998, 101 (7), 1431-1438).
This recruitment of new adipocytes is mediated by soluble factors produced by hypertrophic adipocytes: in particular LPA - through stimulation α2-receptor, and IL-6 - due to its ability to regulate differentiation of preadipocytes.
Therefore, blocking α2-receptor is such as to enable, in parallel with its positive effects on lipolysis, inhibiting the liberation of LPA, advantage is the result from the inhibition of the recruitment of new adipocytes.
IL-6 limits the maturation of preadipocytes to differentiated adipocytes. Stimulation of adipocyte production of this cytokine inducer of IL-6 enhances this property.
The combination of substances B, an inhibitor of the receptor, and substances In, inductor IL-6, therefore, is such that provides enhanced and innovative effectiveness against hyperplasia of fat cells. Adding substance And to this combination allows to obtain a composition for weight loss that works on multiple mechanisms of action, namely hypertrophy and hyperplasia.
Studies have been conducted to demonstrate the effect of the active substances obtained from a microorganism 11844, or substance In, on Mature adipocytes and differentiation of adipocytes.
Prepared a cosmetic composition for slimming according to the invention, which contains substances a, B and C and is further referred to as AM2.
The slimming effect from AM2 has been the subject of clinical studies.
Biological effects of substances In in vitro was studied on mouse line 3T3-L1. This line of preadipocytes, usually cultivated in DMEM medium (minimum essential medium, Dulbecco), enriched with 10% fetal calf serum, has the property to differentiate into Mature adipocytes in the presence of inducers, such as insulin and indomethacin (Slcker L. J. Biochem. Biophys. Res. Com. 1998, 251, 225-229). After eight to ten days after the induction of differentiation of cells 3T3-L1 showed properties of Mature adipocytes. This transition from the stage of immature cells to the stage of functional adipocyte can be assessed morphologically by the appearance of intracytoplasmic vesicles accumulation of lipids, which are visible under the microscope or which can be detected biochemically by measuring the production of leptin, a hormone saturation produced exclusively Mature adipocytes.
The influence of the substances on the activity of adipocytes was evaluated on two levels. On the one hand, by measuring the ability of the active agent to change the production of IL-6 by adipocytes and, on the other hand, evaluating its effect on differentiation into Mature adipocytes.
1 - the Effect of substances on the production of IL-6 Mature adipocytes 3T3-L1
Mature adipocytes 3T3-L1 (collected after 10 days of differentiation, induced by a combination of insulin (5 μg/ml) and indomethacin (125 ámol), stimulating substance in quantities of 1% (vol./about.) within 24 hours.
Then, culture is taken of the supernatant, and the content of IL-6 is determined by using ELISA (enzyme linked immunosorbent assay) according to the instructions of the supplier (R&D System, Abingdon, GB). The amount of secreted IL-6 compared with the amount of secreted IL-6 control cult is s, treated only with solvent substance (a mixture of ethanol/water (50/50), diluted 1/100 in culture medium), or culture, stimulated the reference inducer of IL-6, TNF-α (tumor necrosis factor), 50 ng/ml (Fried, S. K., J. Clin. Endocrinol. Metab. 1998, 83, 847-860). Figure 1 shows that the substance stimulates the production of IL-6 by adipocytes 3T3-L1 with a factor of about five compared to the control culture with solvent (43 PG/mg vs. 9 PG/ml, respectively), representing 83% of the action obtained with the reference inductor (52 PG/ml).
The results show that, on the one hand, recognizes substance In adipocytes as target for induction and that, on the other hand, under the action of substances In the basal production of IL-6 by adipocytes magnified by a factor of 5, which is 83% of the maximum action obtained with the positive control.
This increase makes it possible, taking into account the known properties of IL-6, to provide, first, the reduction of synthesis of the enzyme responsible for the intake of fatty acids, LPL, and then, as a consequence, the decline in fatty acids.
2 - the Action of a substance In the differentiation of adipocytes
The purpose of this second study was to determine the action of a substance In the formation of new adipocytes.
The influence of the substances on the differentiation of pre is depozitul 3T3-L1 Mature adipocytes explore, on the one hand, by assessing the synthesis of the hormone leptin, a marker of differentiation of adipocytes and, on the other hand, observing under the microscope for education vnutriredaktsionnyh lipid vesicles, other indicators of functional transformation in Mature adipocytes. In all cases, a substance is injected into the culture in the amount of 1% (vol./about.) in the beginning of the process of differentiation and induced as described above) and incubated until the end of the process. Synthesis of leptin appreciate every two days using ELISA (R&D System, Abingdon, GB).
Figure 2 shows that in the presence of substances In the production of leptin remains extremely low for all 10 days of the experiment, and it is significantly lower (≤200 PG/ml)than the production observed in the control culture, which, as expected, increasing the level of leptin on the second day after the induction of differentiation and increase to a maximum plateau 1200-1400 PG/ml starting from the sixth day. Inhibition of the synthesis of leptin substance is the first indicator of a blocked process of differentiation of adipocytes.
The second is given in the experiment, reflected in figure 3, which shows that after 10 days of differentiation control cells detect the morphology of Mature adipocytes containing large lipid vesicles, which occupy almost all cyto is plazmaticheskoi space (A), while the same cells treated with the substance To remain at a very immature stage with a few rare vesicles, which are much smaller in size (B).
Using the model 3T3-L1 commonly used in the literature to study functions of adipocytes, it was shown that the substance has a dual property: stimulation, in Mature adipocytes, the production of IL-6 and inhibition of progenitor cells, transformation into Mature adipocytes. The substance, therefore, operates in the forward direction, preventing the maturation of adipocytes, and in the opposite direction, stimulating, at the level of Mature adipocytes, the production of the cytokine, which is involved in limiting the accumulation of fatty acids.
These results confirm the unique property of this substance to induce the production of IL-6 by adipocytes, whose autocrine function (in relation to producing cells) and paracrine function (in the cells near these producing cells) is shown in relation to the receipt of fatty acids in Mature adipocytes, and in the recruitment of new adipocytes by terminating differentiation preadipocytes.
Conducted preliminary clinical studies with compositions slimming according to the invention, which contain 3 active substances (hereinafter - AM2).
Composition AM2 were PR is conducted two clinical studies.
The first relates to the measurement of the thickness of subcutaneous adipose tissue, and used in the second dimension by inches.
1) measure the thickness of subcutaneous adipose tissue.
The aim of this study is to evaluate the clinical performance of a new composition AM2 containing 3 active substances.
Used the Protocol described below.
Number of subjects: 61 healthy female volunteers, divided into 2 groups (31 subject using the composition for slimming AM2 containing 3 active ingredients, 30 subjects - composition for slimming Am1).
The products twice a day put on thigh entirely with a circular massage, which stopped after complete penetration of the product.
Evaluating the effectiveness of doing over a period of time of 2 months by measuring the thickness of subcutaneous adipose tissue at time T0T28 days, T56 days. Used the method of ultrasound.
Place to measure identified by markings in the skin or in height, on which is mounted a probe.
To facilitate vertical identification and to avoid any movement or compression of the tissue during the measurement, the ultrasound probe is placed on a stable device that can be adjusted in height and regardless of the operator.
Consistently get three images at the level of identification labels. the and each image produce 3 thickness measurement. All 6 measurements thus allow to obtain accurate ± 1 mm
These measurements are supplemented by the weight control subjects included in the test, and analysis of self-assessment.
The significance of the results was evaluated using student test for paired groups. The criterion applied to both the raw values and the variations of these parameters during the test (the value is expressed on T0).
Regardless of the considered group average weight remained stable throughout the duration of the study and, therefore, unlikely to be responsible for variations in the thickness measurement of subcutaneous adipose tissue of the thighs.
Selected conditions of the study do not allow to confirm a significant slimming effect for the composition Am1: after 1 month of use, a decrease in subcutaneous adipose tissue by 0.8% and after 2 months, a decrease of 2.6%.
Composition AM2 provides the ability to get very significant slimming effect with 28 days of application (p<10-5): reduction of subcutaneous adipose tissue observed with composition AM2 is -2,2% after 1 month and -4,3% after 2 months of use.
2) Measurement of a centimeter.
Used the Protocol below.
Number of subjects: 39 female volunteers, divided into 2 groups: 20 got the song and Am 19 - composition AM2.
The products were applied twice a day for 2 months.
Evaluation of the effectiveness of weight loss were carried out by the cm at time T0T28daysand T56daysat hip level (3 cm below the crease of the buttocks) to the right and to the left.
Regardless of the considered group average weight remains essentially constant throughout the study and, therefore, unlikely to be responsible for fluctuations in the measurements of the thickness of the subcutaneous adipose tissue of different regions.
Table 1 presents the significant results obtained when measuring a centimeter.
The results obtained when measuring a centimeter.
|% of subjects||Interval reduction|
|TRACK||1 month||2 months||1 month||2 months|
|Composition Am1||30||45||1-0,2 cm||1-2,0 cm|
|Composition AM2||72||73||1-3,5 cm||1-2,5 cm|
Composition Am2 has the best activity slimming against T0than the composition Am1, after one month of use.
With Auntie results received after these two studies, allows you to set a marked superiority of the composition Am2 before its placebo, but also reveals the best action of the composition Am2 compared with the composition Am1.
Thus, despite the General part of the way through substances A+B and their effectiveness in relation to lipolysis, the beneficial action obtained with the new formula AM2, increased by the action of a substance In the intake of fatty acids in adipocytes.
The combination of these actions, supported by activity in terms of recruitment of new adipocytes, allows to reduce the importance of fatty tissue and prevent its development.
In the preparation of compositions of the present invention, designed extracts mixed with an aqueous or non-aqueous solvents and with suitable diluents, which are compatible with the local application, as well as with the active components of this composition. Suitable solvents and/or diluents should be selected on their ability to transport the active component of the extract according to the invention in the subcutaneous fat layer.
These compositions usually contain excipients or additives, chosen from ingredients commonly used in intended for local use compositions, depending on the requirements of a particular question is of the courthouse square.
They may contain, for example, thickeners, agents, reducing irritation, softening agents, stabilizers, preservatives, agents for preventing foaming, surfactants, antioxidants, dyes and/or pigments and perfumes.
They can also contain other active ingredients, which either may have an action of the same type, such as products that contribute to the regulation of lipolysis/lipogenesis, or products that are useful in compositions for topical application such as stimulators of collagen synthesis, inhibitors of collagenase or elastase and soudanaise agents.
Cosmetic compositions according to the present invention contain substances a, B or C in amounts from 0.00001% to 5% relative to the total weight of the composition, in the form of a mixture with excipients normally used for the preparation of cosmetic preparations that need to be applied to the skin.
These amounts can vary within the limits specified above, depending on the activity, characteristic included in the composition components. Preferably, the components a, B and C are present in amounts of from 0.0001% to 2%.
The preferred form of the compositions according to the invention is a liquid that is applied topically using adhesive carrier, hereinafter referred to as "the patch", and this patch gives moznosti controlled diffusion of the active components.
The compositions of the present invention have good stability and can be stored for a period required for use at temperatures between 0°s and 60°without precipitation of components or phase separation or a reduction in activity that may jeopardize their application.
These songs are very well tolerated; they have no phototoxicity, and applying them on the skin for extended periods does not entail any adverse effect.
After the first applications, the skin relief is smooth, the skin becomes more toned and tight. After using for one month, has a slimming effect, the appearance of "orange peel" is visually reduced, and the shape becomes more thin.
1. Cosmetic composition for slimming, containing at least one component, inducing the production of IL-6 by adipocytes, antagonist α2 and antagonist of NPY in the form of a mixture with excipients for cosmetic preparations.
2. The composition according to claim 1, characterized in that the component inducing the production of IL-6 by adipocytes, selected from the ones synthesized compounds, peptide, is gunning or tissue extracts of animal or vegetable origin and product obtained through fermentation carried out by the organism.
3. The composition according to claim 2, characterized in that the component inducing the production of IL-6 by adipocytes, is a product obtained by the fermentation carried out by a microorganism selected from bacteria and fungi.
4. The composition according to claim 3, characterized in that the component inducing the production of IL-6 by adipocytes, may be obtained by fermentation, carried out by the strain of Rhodotorula sp.
5. The composition according to claim 4, characterized in that the component inducing the production of IL-6 by adipocytes, may be obtained by fermentation, carried out by the strain of Rhodotorula sp., deposited in the National collection of cultures of microorganisms (C.N.C.M.) of the Pasteur Institute under the number I of 1844, or one of its mutants-producers.
6. The composition according to claim 1, characterized in that the specified components antagonist α2 or a NPY antagonist selected from the ones synthesized products, cell or tissue extracts of animal or vegetable origin, and products obtained by fermentation carried out by microorganisms.
7. The composition according to claim 6, characterized in that the components antagonist α2 or antagonist of NPY can be obtained when the fermentation is carried out by microorganisms selected from bacteria and fungi.
8. The composition according to claim 7, characterized in that mponent antagonist α 2, can be obtained by fermentation, carried out by the strain Bacillus licheniformis deposited in the C.N.C.M. the Pasteur Institute under the number I 1778, or one of its mutants-producers.
9. The composition according to claim 7, characterized in that the antagonist of NPY can be obtained when the fermentation is carried out by the strain Streptomyces sp., deposited in the C.N.C.M. the Pasteur Institute under the number I 1132, or one of its mutants-producers.
10. The composition according to claim 1, characterized in that the NPY antagonist, antagonist α2 and the inductor production of IL-6 was obtained through fermentation, carried out respectively by the strains I 1132, I 1778 and I 1844 deposited in the C.N.C.M. the Pasteur Institute.
11. The composition according to claim 1 for the regulation of lipolysis/lipogenesis in the skin.
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to new derivatives of tetrahydroisoquinoline of the formula [I] wherein R1 represents hydrogen atom or lower alkyl; R2 represents alkyl having optionally a substitute taken among alkoxycarbonyl and carboxy-group, cycloalkyl, cycloalkylalkyl, aryl having optionally a substitute taken among lower alkyl, arylalkyl having optionally a substitute taken among lower alkyl, lower alkoxy-group, halogen atom and acyl, alkenyl, alkynyl, or monocyclic heterocyclylalkyl wherein indicated heterocycle comprises 5- or 6-membered ring comprising nitrogen atom and having optionally a substitute taken among lower alkyl; R3 represents hydrogen atom or lower alkoxy-group; A represents a direct bond or >N-R5 wherein R5 represents lower alkyl; B represents lower alkylene; Y represents aryl or monocyclic or condensed heterocyclyl comprising at least one heteroatom taken among oxygen atom and nitrogen atom and having optionally a substitute taken among lower alkyl, carboxy-group, aryl, alkenyl, cycloalkyl and thienyl, or to its pharmaceutically acceptable salt. Also, invention relates to pharmaceutical composition eliciting hypoglycaemic and hypolipidemic effect based on these derivatives. Invention provides preparing new compounds and pharmaceutical agents based on thereof, namely, hypoglycaemic agent, hypolipidemic agent, an agent enhancing resistance to insulin, therapeutic agent used for treatment of diabetes mellitus, therapeutic agent against diabetic complication, agent enhancing the tolerance to glucose, agent against atherosclerosis, agent against obesity, an anti-inflammatory agent, agent for prophylaxis and treatment of PPAR-mediated diseases and agent used for prophylaxis and treatment of X-syndrome.
EFFECT: valuable medicinal properties of compounds and composition.
13 cl, 7 tbl, 75 ex
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to new derivatives of glucopyranosyloxybenzylbenzene represented by the formula (I): wherein R1 represents hydrogen atom or hydroxy(lower)alkyl; R2 represents lower alkyl group, lower alkoxy-group and lower alkylthio-group being each group is substituted optionally with hydroxy- or (lower)alkoxy-group, or to its pharmaceutically acceptable salts. Also, invention relates to pharmaceutical composition eliciting hypoglycemic activity and to a method for treatment and prophylaxis of hyperglycemia-associated diseases, such as diabetes mellitus, obesity and others, and to their intermediate compounds. Invention provides preparing new derivatives of glucopyranosyloxybenzylbenzene that elicit the excellent inhibitory activity with respect to human SGLT2.
EFFECT: valuable medicinal properties of compounds.
13 cl, 2 tbl, 2 ex
FIELD: organic chemistry, pharmacology.
SUBSTANCE: invention relates to polycyclic dihydrothiazoles of formula I , containing in substituted alkyl residues in 2-posiiton, as well as physiologically accepted salts thereos, having anorexia action. In formula Y is direct bond; X is CH2; R1 and R1' are independently H, Cl; R2 and R3 are H; R4 is (C8-C16-cycloalkyl, (CH2)n-A-R8, wherein n = 1-6, excepted group of formula -CH2-O-CH2-phenyl with unsubstituted phenyl; A is O, S; R8 is methyl or (CH2)m-aryl, where in m = 0-6; and aryl may represent phenyl, wherein aryl group may be optionally substituted with one or two substituents, selected from Cl, O-(C1-C6)-alkyl or (C1-C6)-alkyl. Also disclosed is method for production thereof.
EFFECT: new anorexia pharmaceuticals.
5 cl, 4 ex, 2 tbl
FIELD: organic chemistry, medicine.
SUBSTANCE: invention represents ligands MC-4 and/or MC-3 of the formula (I): , wherein X means hydrogen atom, -OR1, -NR1R1' and -CHR1R1' wherein R1 and R1' are taken among the group: hydrogen atom, (C1-C6)-alkyl and acyl; (1) each R2 is taken independently among the group: hydrogen atom, (C1-C6)-alkyl; or (2) (a) R2 bound with carbon atom that is bound with X and Z1 and substitute R5 can be optionally bound to form carbocyclic or heterocyclic ring that is condensed with phenyl ring J; or (b) R2 bound with carbon atom that is bound with ring Ar can be bound with R7 to form ring condensed with ring Ar; each among Z1, Z2 and Z3 is taken independently from the following groups: -N(R3e)C(R3)(R3a)-, -C(R3)(R3a)N(R3e)-, -C(O)N(R3d)-, -N(R3d)C(O)-, -C(R3)(R3a)C(R3b)(R3c)-, -SO2N(R3d)- and -N(R3d)SO2- wherein each among R3, R3a, R3b and R3c, R3d, R3e when presents is taken independently among hydrogen atom and (C1-C6)-alkyl; p is a whole number from 0 to 5 wherein when p above 0 then R4 and R4' are taken among hydrogen atom, (C1-C6)-alkyl and aryl; R5 represents 5 substitutes in phenyl ring J wherein each R5 is taken among hydrogen atom, hydroxy-, halogen atom, thiol, -OR12, -N(R12)(R12'), (C1-C6)-alkyl, nitro-, aryl wherein R12 and R12' are taken among hydrogen atom and (C1-C6)-alkyl; or two substitutes R5 can be bound optionally to form carbocyclic or heterocyclic ring that is condensed with phenyl ring J; q = 0, 1, 2, 3, 4 or 5 wherein when q above 0 then R6 and R6' are taken among hydrogen atom and (C1-C6)-alkyl; Ar is taken among the group consisting of phenyl, thiophene, furan, oxazole, thiazole, pyrrole and pyridine; R7 are substitutes at ring Ar wherein each R7 is taken among hydrogen, halogen atom, -NR13R13', (C1-C6)-alkyl and nitro- wherein R13 and R13' are taken among hydrogen atom and (C1-C6)-alkyl; r is a whole number from 0 to 7 wherein when r is above 0 then R8 and R8' are taken among hydrogen atom and (C1-C6)-alkyl; B is taken among -N(R14)C(=NR15)NR16R17, -NR20R21, heteroaryl ring and heterocycloalkyl ring wherein R14-R17, R20 and R21 are taken independently among hydrogen atom and (C1-C6)-alkyl; s = 0, 1, 2, 3, 4 or 5 wherein when s is above 0 then R and R9' are taken among hydrogen atom and (C1-C6)-alkyl; R10 is taken among the group consisting of optionally substituted bicyclic aryl ring and optionally substituted bicyclic heteroaryl ring; D is taken among hydrogen atom, amino- and -C(O)R11 wherein R11 is taken among the following group: hydroxy-, alkoxy-, amino-, alkylamino-, -N(R19)CH2C(O)NH2 wherein R19 represents (C1-C6)-alkyl, -NHCH2CH2OH and -N(CH3)CH2CH2OH, or its isomers, salts, hydrates or biohydrolysable ester, amide or imide.
EFFECT: valuable medicinal properties of compounds.
18 cl, 107 ex
FIELD: improved method for oil production.
SUBSTANCE: target oil, enriched in HODE, or esters thereof is obtained by controlled oxidation of linoleic acid and/or linolenic acid or esters thereof in presence of oxidation catalyst. Oxidation is stopped when total HODE or ester content is more than 5 %, and/or content of isomeric 9-hydroxy-10,12-octadecadienic acid (9-HODE) or esters thereof is more than 1,5 %; and hydroperoxides formed in oxidation process are reduced with reducing agent in presence of antioxidant. Invention is also relates to oil enriched in 9-HODE or esters or salts thereof having an lipolytic action; to drug or food additive for obesity treatment; cosmetic for local treatment of cellulite. Compound for controlling of adipocyte lipolytic activity and hydrolysis of triglycerides accumulated in adipocytes is also disclosed.
EFFECT: novel pharmaceutical composition for obesity treatment.
11 cl, 1 ex
FIELD: organic chemistry, biochemistry, medicine.
SUBSTANCE: invention describes a method for prophylaxis or treatment of states that involves inhibition of activity of enzyme that catalyzes hydrolysis of ester functional groups and wherein indicated state represents obesity or accompanying disorder, and wherein compound of the formula (1):
is prescribed, or its pharmaceutically acceptable salt, ester, amide or a precursor. Also, invention relates to a method for manufacturing the medicinal preparation used for prophylaxis or treatment of states wherein inhibition of activity of enzyme is required wherein indicated enzyme catalyzes hydrolysis of ester functional groups. In the formula (1) A means a 6-membered aromatic or heteroaromatic ring; R1 means a branched or unbranched alkyl (its carbon chain can be broken by one or more oxygen atoms), alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, reduced arylalkyl, arylalkenyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, reduced aryl, reduced heteroaryl, reduced heteroarylalkyl or their substituted derivative wherein a substitute is taken independently among the following group: halogen atom, alkyl, alkyl substituted with halogen atom, aryl, arylalkyl, heteroaryl, reduced heteroaryl, reduced heteroarylalkyl, arylalkoxy-, cyano-, nitro-group, -C(O)R4, -CO2R4, -SOR4, -SO2R4, -NR6R7, -OR6, -SR6, -C(O)CX1X2NR6R7, -C(O)NR4R5, -C(O)N(OR5)R6, -NR6C(O)R4, -CR6(NH2)CO2R6, -NCX1X2CO2R6, -N(OH)C(O)NR6R7, -N(OH)C(O)R4, -NHC(O)NR6R7, -C(O)NHNR6R7, -C(O)N(OR5)R6 or lipid, or steroid (natural or synthetic) under condition that any substituting heteroatom in R1 or R2 must be separated from exocyclic nitrogen atom by at least two carbon atoms (preferably, saturated atoms), and wherein R4 represents hydrogen atom, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, reduced heteroaryl or reduced heteroarylalkyl, OR6, NHCX1X2CO2R6 or NR6R7; R5 represents hydrogen atom, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, reduced heteroaryl or reduced heteroarylalkyl; R6 and R7 are taken independently among hydrogen atom, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, heteroaryl, reduced heteroaryl, heteroarylalkyl, reduced heteroarylalkyl or -(CH2)n(OR5)m wherein n = from 1 to 12, preferably, from 2 to 10; m = from 1 to 3; R5 means preferably (C2-C10)-alkyl; X1 and X2 represent independently hydrogen atom, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, heteroaryl, reduced heteroaryl, heteroarylalkyl or reduced heteroarylalkyl. Also, invention describes compound of formulae (II), (IIa) and (IIb) given in the description and a method for preparing compound of formulae (II), (IIa) and (IIb), pharmaceutical composition used for prophylaxis or treatment of obesity and/or accompanying disorder, nutrition product, a method for prophylaxis or treatment of obesity or accompanying disorders, a method for inhibition of activity of enzymes, a method for reducing fat content in animals, a cosmetic method for maintaining this weight and a new intermediate compound of the formula (IV) indicated in the description. Invention discloses the possibility for prophylaxis or treatment of obesity or accompanying disorders.
EFFECT: valuable medicinal properties of compounds.
33 cl, 1 dwg, 2 tbl, 5 ex
FIELD: organic chemistry, biochemistry, medicine.
SUBSTANCE: invention describes a method for prophylaxis or treatment of states wherein inhibition of enzyme activity is required wherein this enzyme catalyzes hydrolysis reaction of ester functional groups and wherein indicated disorder represents obesity or accompanying disease. Method involves prescribing compound of the formula (1):
or its pharmaceutically acceptable salt, ester, amide or precursor wherein in the formula (1) a means six-membered aromatic or heteroaromatic ring; R1 means a branched or unbranched alkyl (its carbon chain can be broken possibly by one or more oxygen atoms), alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, reduced arylalkyl, arylalkenyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, reduced aryl, reduced heteroaryl, reduced heteroarylalkyl or their substituted derivative wherein a substitute represents one or more group taken independently among the following group: halogen atom, alkyl, halogen-substituted alkyl, aryl, arylalkyl, heteroaryl, reduced heteroaryl, reduced heteroarylalkyl, arylalkoxy-, cyano-, -C(O)R4, -CO2R4, -SOR4, -SO2R4, -NR6R7, -OR6, -SR6, -C(O)CX1X2NR6R7, -C(O)NR4R5, -C(O)N(OR5)R6, -NR6C(O)R4, -CR6(NH2)CO2R6, -NCX1X2CO2R6, -N(OH)C(O)NR6R7, -N(OH)C(O)R4, -NHC(O)NR6R7, -C(O)NHNR6R7, -C(O)N(OR5)R6, or lipid or steroid (natural or synthetic one) under condition that any substituting heteroatom in R1 or R2 must be segregated from nitrogen exocyclic atom by at least two carbon atoms (preferably, saturated ones); R2 means hydrogen atom or group, such as determined for R1 and wherein R4 represents hydrogen atom, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, reduced heteroaryl or reduced heteroarylalkyl, OR6, NHCX1X2CO2R6 or NR6R7; R5 represents hydrogen atom, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, reduced heteroaryl or reduced heteroarylalkyl; R6 and R7 are taken independently among hydrogen atom, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, heteroaryl, reduced heteroaryl, heteroarylakyl, reduced heteroarylalkyl or -(CH2)n(OR5)m wherein n = from 1 to 12 but preferably from 2 to 10; m = from 1 to 3; for R5 (C2-C10)-alkyl is preferable; X1 and X2 represent independently hydrogen atom, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, heteroaryl, reduced heteroaryl, heteroarylalkyl or reduced heteroarylalkyl. Also, invention describes compounds of formulas (II), (IIa), (IIb) given in the invention description, method for preparing compound of the formula (II), pharmaceutical composition used for prophylaxis or treatment of obesity or accompanying disorder, the nutrition foodstuff, method for prophylaxis or treatment of obesity or accompanying disorders, method for inhibition of enzymes activity, method for reducing the fat content in animals, cosmetic method for maintaining this weight of animals. Invention discloses the possibility for prophylaxis or treatment of obesity or accompanying disorders.
EFFECT: valuable medicinal properties of compounds.
30 cl, 1 dwg, 2 tbl, 5 ex
SUBSTANCE: invention relates to cosmetic production. Cosmetic composition comprises ultradispersed diamonds or nanodiamonds with hydrophilic or hydrophobized surface of particles or their mixture and taken in the concentration 10-8 - 10-10 g/kg in cosmetic agents on aqueous, fatty, ointment, jelly, emulsion or liposomal base. The composition provides improving viscoelastic properties of integument tissues.
EFFECT: valuable cosmetic properties of composition.
FIELD: medicine, cosmetics.
SUBSTANCE: invention relates to composites used in face skin care. The cosmetic composition concentrate involves biologically active substances of natural origin, glycerol, inorganic salts and a base as polyethylene oxide gel and the composition comprises additionally nutrient medium for animal cells culture. Biologically active substances of natural origin comprise whole male and/or female gonads of sea animals taken in the definite quantitative ratios. The concentrate comprises additionally vegetable oil and essential oils of vegetable origin. As inorganic salt the concentrate comprises potassium chloride and sodium chloride, and nutrient medium comprises the Eagle's medium. The concentrate provides the balanced cleansing, nutrient and regenerative effect on keratinocytes.
EFFECT: improved and valuable properties of concentrate.
2 cl, 1 tbl, 4 ex
FIELD: sanitary science, cosmetology, skin care.
SUBSTANCE: claimed formulation contains water, mineral salts and dissolved in water oxygen, additionally it contains at least one irreplaceable proteinogenic amino acid with isoelectric point at pH 3.0-6.0 and has hardness not more than 0.5 mg-eqv/dm3. Optionally formulation may contain ascorbic acid, provitamin B5 and mixture of bacteria belonging to human skin normal microflora.
EFFECT: non-toxic stable formulation for correction of adverse alteration of skin surface layers, maintaining of normal chemical and biological skin state, and prevention of skin cell metabolism suppression.
4 cl, 3 ex, 5 tbl
FIELD: pharmaceutical industry, in particular production of moor preparation.
SUBSTANCE: claimed method includes extraction of moor raw material such as peaty piloids with decomposition rate of 50 % or more, decontamination, homogenization by agitation in mortar-mixer with addition of mineral sodium hydrocarbonate water under specific conditions followed by pulping through screen to produce product with shearing resistance of 1500-4000 din/cm3 and conserving agent addition. As conserving agent hydantoin in specific ratio is used. Then product is pre-packed in sealed containers and conditioned in stock for ageing.
EFFECT: peaty moor dough with increased biological value, high penetrability, improved nutrient and healing effects.
FIELD: pharmaceutical industry, in particular topical composition for skin healthcare.
SUBSTANCE: invention relates to composition for therapy of various skin conditions (e.g., wrinkles, whipping, light-damaged skin, sensitive skin, dry skin, scaled skin, irritated skin, itchy skin and age-dependent spots). Claimed composition contains a) conjugated linolic acid and/or derivatives thereof, comprising molecular parts of conjugated linolic acid wherein at least 50 mass % of conjugated linolic acid and/or molecular parts are present in cis-9,trans-11-isomer; and b) dermatologically acceptable carrier.
EFFECT: useful skin healthcare effects such as wrinkle-smoothing effect and reducing of light-damaged skin.
4 cl, 8 tbl, 7 ex
FIELD: cosmetology, dermatology.
SUBSTANCE: the present innovation deals with applying preparations affecting the values of blood microcirculation in skin. The suggested preparation is the emulsion of perfluorocarbons that increases skin resistance to negative impacts and favorably affects microcirculation by steadily increasing its total level that enables to improve the state of microcirculatory canal of skin.
EFFECT: higher efficiency.
FIELD: cosmetology, in particular methods and composition for face, neck and decollete zone skin healthcare.
SUBSTANCE: claimed method includes subsequent skin treatment with cosmetic preparations. Primarily make-up is removed with cleaning milk containing fruit acids; then skin is cleaned with non-alcoholic tonic containing fruit acids; eyelids, lips and nose are creamed with fat cream; then skin is creamed with foamed scrub for deep cleaning and keratoid layer exfoliation; further glycol pilling is carried out for 2-5 min; neutralizing mask is applied and hold until absorption; relaxing mask is applied for 10-15 min to remove excitation; then skin is cleaned with non-alcoholic tonic containing fruit acids and creamed with light protective cream SPF-50.
EFFECT: method, which provides skin deep cleaning, increases skin tonus and elasticity, and sufficiently improves skin appearance.
FIELD: cosmetic industry.
SUBSTANCE: the present innovation deals with cosmetic preparations for nourishing and protecting one's skin. The suggested cosmetic preparation contains vegetable oil and extracts of plant raw material, additionally, it contains carbon dioxide extracts out of propolis and bee wax and, also, it may contain ramson juice, aqueous extract out of fir's woody greens or its bark and, also, honey, chalk and fatty foundation, moreover, components should be taken at a certain quantitative ratio. Method to obtain this cosmetic preparation deals with mixing fatty foundation with biologically active substances to obtain homogeneous mass, moreover, biologically active substances should be added into the fatty foundation at 18-22 C. The suggested cosmetic preparation enables to heal small scratches, excoriations, pustules and acne due to its antiphlogistic action. It should be, also, applied during body massage being of antioxidizing action, as well.
EFFECT: higher efficiency of application.
6 cl, 2 ex, 2 tbl
SUBSTANCE: skin of one's face, neck and decollete line should be successively treated with cosmetic preparations, moreover, it is necessary to perform demake-up of skin with purifying milk, apply pearl cream-peeling along with vaporization. Then on should apply phytocomplex to the skin of face, neck and decollete line to be kept till its complete absorption followed by massage due to applying a cream, ten one should repeatedly apply phytocomplex followed by pearl mask, then - cream with active oxygen or balsam for dry skin, moreover, after applying purifying milk, creams and masks one should rinse the residues of the suggested preparation with warm water and apply skin tonic. The present innovation restores the structure of collagen fibers, stimulates the process for the development of new cells, strengthens capillary walls, decreases tissue intumescence, removes irritation and smoothes out wrinkles.
EFFECT: higher efficiency.
SUBSTANCE: the present innovation deals with preparations that improve the state of patient's skin. The suggested preparation for biological skin rejuvenation contains emulsion of perfluorocarbons and organosilicon compound, at their ratio being (30:70) to (70:30) vol.%, moreover, one should, also, apply the mixture of organosilicon compounds. The suggested preparation enables to affect deep and surface layers of skin for persons of any age groups and it shifts metabolic processes in cutaneous tissues towards the predominance of those processes that are peculiar for juvenile tissues.
EFFECT: higher efficiency of rejuvenation.
2 cl, 10 ex
FIELD: medicine, in particular healthful and dietary products.
SUBSTANCE: claimed product contains dry biomass of living bacteria Lactobacillus rhamnosus odi 83 and Lactococcus lastic ssp lactis odi 83, and filler. Filler represents dry fermented milk product obtained by fermentation of milk and honey mixture with strains Lactobacillus rhamnosus odi 83, Lactococcus lastic ssp lactis odi 83, Saccharomyces cerevisae odi 83, and contains biomass of inactivated microorganisms mentioned above. To obtain healthful and dietary product pasteurized milk is cooled to 20-25°C, honey is added, ferment containing strains Lactobacillus rhamnosus odi 83, Lactococcus lastic ssp lactis odi 83, and Saccharomyces cerevisae odi 83 is introduced, fermentation is carried out; then obtained mixture is blended and sterilized; cooled again to 20-25°C, two strains: Lactobacillus rhamnosus odi 83 and Lactococcus lastic ssp lactis odi 83 is introduced, and fermentation is carried out again up to acidity of 85±15°T. After process finishing mixture is thoroughly agitated and dried at 35-40°C up to residue humidity. For treatment of infective and non-infective disorders claimed product in therapeutically effective amount is administered to patient in need of such treatment.
EFFECT: agent for treatment of wide range of diseases without contraindications.
4 cl, 5 tbl, 20 ex, 1 dwg