Orally soluble and/or effervescent compositions, containing at least one s-adenosylmethyonine (sam)

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to a pharmaceutical, dietary, nutritional orally soluble composition for peroral intake, which contains at least one S-adenosylmethyonine (SAMe) salt in a combination with physiologically acceptable excipients and optionally other active ingredients. The physiologically acceptable excipients include light magnesium oxide.

EFFECT: compositions of the claimed invention have high taste qualities, which provides easier peroral introduction The compositions by the invention are characterised by the higher systemic bioavailability of S-adenosylmethyonine.

15 cl, 2 dwg, 13 ex

 

S-adenosylmethionine (SAM) is a physiologically important molecule, opened in 1952, which is formed in the body when combining essential amino acid methionine with adenosine triphosphate (ATP) in the high-energy reactions, such as enzymatic reactions, controlled SAM-synthase.

The main source of SAM for humans is food with high protein content considering the fact that methionine is its predecessor. It is estimated that people in normal proteincalorie diet consumes on average per day to about 1 g of methionine, which is converted to SAM.

The half-life of SAM from the liver is very short (about 5 minutes), which indicates that the avidity of the body for a given molecule.

Quality and balanced nutrition is a key factor that allows you to provide your body with the required daily amount of bioavailable SAM, which is about 500 mg, whereas plasma levels of approximately 20 to 50 mg/ml (Bottiglieri T.:SAMe: from the bench to the beside-molecular basis of a pleiotropic molecule. Am. J. Clin. Nutr., 2002, 76:1151S-1157S).

The most famous of the corresponding deficit of the condition include, for example, the aging process, when there is a decline SAM more than 50%, neurological diseases that involve the emotional sphere (on pressigny syndromes in General) and the cognitive sphere (dementia), acute and chronic disorders of the liver (alcoholic fatty liver, acute and chronic hepatitis, alcoholic and postoronny cirrhosis, intrahepatic cholestasis), and degenerative musculoskeletal diseases musculoskeletal disorders (osteoarthritis) (Grazi, S., Costa, M.: SAMe: The safe and natural way to combat depression and relieve the pain of osteoarthiritis. Prima Health, Rocklin, CA, 1999).

Supplementation with exogenous SAM metabolized the same way that natural molecule, derived from methionine, received from food.

The idea about the possibility of introducing exogenous SAMe patients has emerged since the discovery of this molecule in the fifties, but only after the second half of the seventies, it has become feasible for admission to the pharmaceutical market the first drugs injected parenterally (endovenous and intramuscularly) or oral (swallow pills, protected from degradation in the stomach or resistant to gastric environment) SAMe salts (such as, for example, tosylate, butanedisulfonate or phytate), stable at room temperature.

In particular, in U.S. patent US3 954726 and US4057672 described relatively stable salts of S-adenosylmethionine, in particular, at a temperature of 25°C and 45°C respectively. Furthermore, in U.S. patent US4465672 described stable salts of S-adenosylmethionine with 5 moles of sulfonic acid is you, with the index pK is lower than 2.5.

In General, it should be noted that the SAMe in mesolevel form is very unstable at temperatures above 0°C. the Second important factor in the degradation of the molecule together with its thermolability is a hygroscopic molecule, which can be circumvented by obtaining thermally stable salts of SAMe in a special protective membranes or by drying by freezing of such salt in vacuum with subsequent introduction into the vial.

The availability of a stable pharmaceutical preparations on the basis of the SAMe salts allowed to conduct multiple clinical trials to evaluate various options for their therapeutic use, such as in the case of depressive syndromes, dementia, liver pathologies, osteoarthritis, fibromyalgia, and the results confirmed the clinical efficacy in combination with a high tolerance to a given molecule (Friedel HA, Goa KL, Benfield P.: SAMe: A review of its therapeutic potential in liver dysfunction and affective disorders in relation to its physiological role in cell metabolism. Drugs, 1989, 38:389-416).

After the first application in Italy using the SAMe in the pharmaceutical industry began to spread quickly to other countries, such as Spain, Germany, Russia and China already in the 80s-90s

Recently, since 1999, SAMe in salt form, in combination with tosylate or butanedisulfonate was approved for use in the United States as a dietary Supplement, the rich are still protected from decomposition in the environment of the stomach swallow the tablets with a dose of 200 and 400 mg of the active ingredient.

When parenteral (for example, endovenous or intramuscularly) exogenous SAMe guaranteed high levels of bioavailable compounds in plasma (equivalent to approximately 90-100% of the injected dose), and when ingested by swallowing protected from decomposition in the environment of the stomach swallow tablets SAMe was achieved only low plasma levels of unmodified molecules, namely <5-10% of the administered dose.

This significant difference in bioavailability is associated with a high presystemic metabolism at the level of the liver SAMe, taken orally in the form of being protected from decomposition in the environment of the stomach forms (such as resistant to the environment of the stomach, capable of passing unaltered through the medium of the stomach and dissolves only in the intestines, the branches of the portal vein).

In fact, it is well known that oral administration of SAMe, labeled with a radioactive label on the carbon of the methyl group leads to intensive metabolism in the liver, estimated at about 60% of the administered radioactive label (Giulidori P. et al.-Metabolism of exogenous SAMe in humans and its significance in therapeutic use of the drug. Proceedings of the Workshop"Methionine Metabolism: Molecular Mechanisms and Clinical Implications".Madrid, Spain, Jarpyo Editores, 1998:159-163).

This high presystemic metabolism in the liver depends on the selective absorption of the SAMe in the intestine, which is determined by taking the th is protected from degradation in the stomach forms, aimed at facilitating its direct transition to the liver through the dominant intestinal-hepatic part of the system of the portal vein.

The levels of systemic bioavailability of the SAMe molecule are greatly reduced due to its metabolic avidity for the liver.

While presystemic metabolism SAMe insignificant for subjects suffering from liver disease, it is very worsens the condition of those individuals who accept this molecule oral, in order to obtain a clinically significant effect in other diseases, in particular, this occurs in subjects with depressive syndromes or with osteoarthritis, where important molecular tropism extrahepatic SAMe molecule.

In the case of subjects with depression have shown that low plasma of the SAMe number, which goes from absorption by the liver is still able to cross the blood brain barrier and accumulate in cephalorachidian fluid. In the case of patients with osteoarthritis shown that SAMe can also be concentrated in the synovial fluid of the joints.

Thus it is seen that in the situation of large-scale capture of the SAMe liver when it is received in the form that is protected from degradation in the stomach oral drug, it reaches the selected therapeutic sites in very small amounts.

In this regard, there is a need to increase systemic bioavailability of the SAMe and/is whether its salts when they are orally administered, in order to make it more suitable for the treatment of vnepechenochnykh diseases, such as diseases affecting the nervous system or bone-joint system.

The authors of the present invention unexpectedly discovered that it is possible to solve the problem of presystemic metabolism in the liver salts of SAMe, with respect to the currently applied swallow and resistant to the environment of the stomach oral drugs, by creating a product in the form of specific not resistant to the environment of the stomach soluble in the mouth and/or effervescent compositions.

Preferably, these are soluble in the mouth and/or effervescent compositions are characterized by a very good taste, which guarantees the comfort of their admission through the mouth.

When using soluble in the mouth and/or effervescent compositions of salts of SAMe are entered and are absorbed directly in the mouth, which leads to more rapid absorption and higher bioavailability compared with practiced currently by way of introduction through the use of resistant environment of the stomach tablets at the same dose of the active ingredient.

This technical effect can also be attributed to the fact that the circulatory system of the oral cavity extends into the upper Vena cava, bypassing the system of the portal vein, responsible for well-known about the effect of the first is of an unforgettable, which increases systemic bioavailability.

Thus, the present invention relates to soluble in the mouth and/or effervescent compositions for oral administration containing at least one salt of SAMe in combination with physiologically acceptable excipients.

These are soluble in the mouth and/or effervescent compositions of the present invention preferably are characterized by the fact that they have good taste, which guarantees the comfort of their oral intake.

These high taste qualities also determine the subject of the treatment of the subject (human or animal) over a longer period of stay of the composition in the oral cavity, and also reduced the need to immediately swallow it, which contributes to the absorption and improves the bioavailability of the active ingredient.

In the context of the present description, the term "SAMe" is used to identify both the racemic mixture and the individual diastereoisomers (RS)-(+)-S-adenosyl-L-methionine [(RS)-(+)-SAMe)] and (SS)-(+)-S-adenosyl-L-methionine [(SS)-(+)-SAMe)] even in mixtures, non-racemic.

According to the present invention of the SAMe salt is preferably selected from tosilata (para-toluensulfonate), butanedisulfonate, phytate, or a mixture thereof. The specified at least one salt of SAMe is included in the composition of the present invention in an amount of 5 to 70 wt.%, pre is respectfully from 7 to 50 wt.% relative to the weight of the entire composition.

According to the present invention ranges specified percentages relate to the total number of SAMe salt or common SAMe amount of salts in the mixture contained in the composition.

Soluble in the mouth and/or effervescent compositions of the present invention can be manufactured in the form of tablets, capsules and/or pellets, preferably in soluble form in the mouth and/or effervescent tablets. The compositions of the present invention can be also manufactured in the form of sublingual tablets.

According to the present invention, the term "sublingual" refers to compositions that are to be placed under the tongue to dissolve and release the active ingredient.

According to the present invention, the term "soluble in the mouth" refers to compositions that can quickly dissolve and release the contained active ingredient upon contact with the oral mucosa. And thus the active ingredient can be directly absorbed by the mucous membrane of the oral cavity, bypassing the liver.

In this regard, according to the present invention, the term "soluble in the mouth" is preferably used to refer to compositions introduced into the oral cavity.

To obtain soluble in the mouth form the compositions of the present invention preferably are fabricated using SL is blowing classes of excipients, thinners, aggregation additives or binders, oil, lubricants, additives that reduce the aggregation of solubilization, sweeteners, flavouring substances and/or means used for adjusting pH.

More preferably soluble in the mouth of the composition of the present invention are manufactured using a light magnesium oxide, magnesium hydroxide, alginic acid, stearic acid, hydrogenated vegetable oils (palm, oleic, BeginInvoke), cocoa butter, cocoa paste, xylitol, maldita, sorbitol, mannitol, Sucralose, Acesulfame K, cyclamate, aspartame, sucrose, neohesperidin, fructose, dextrose, maltose, dried by spray drying of malt, sodium aspartate, maltodextrins, Inositol, inulin, chitosan, yeast, or a mixture thereof.

In particular, to obtain soluble in the mouth to form these excipients must be present in the compositions of the present invention in an amount of from 20 wt.% to 95 wt.% relative to the weight of the entire composition.

According to the present invention, the term "effervescent" refers to compositions that can form carbon dioxide upon contact with water and/or environment of the oral cavity in the presence of saliva, and they are divided into:

A: subsepecies soluble in the mouth tablets. So, they way the s to create weak effervescent effect, what defines a high gustatory qualities associated with the period of dissolution within 10 minutes.

B: classic effervescent tablets to dissolve in the water and taking small SIPS.

To obtain sparkling form compositions of the present invention are produced preferably with di - and tricarboxylic acids, or mixtures thereof.

More preferably the effervescent compositions of the present invention are manufactured using dihydrate and monohydrate sodium citrate, sodium carbonate, disodium carbonate, potassium bicarbonate, citric acid, tartaric acid, adipic acid, phosphate monolatry, alginic acid, hydroxycarbonate magnesium or mixtures thereof.

In particular, to obtain soluble in the mouth to form these excipients must be present in the compositions of the present invention in an amount of from 20 wt.% to 95 wt.% relative to the weight of the entire composition.

Accordingly, compositions of the present invention can be produced in soluble form in the mouth sparkling form or combined forms, including solubility in the mouth, and the Fizz.

The term "good taste" in relation to the compositions of the present invention means that they have a very pleasant taste, so can easily be entered in the oral mode, regardless f the KTA, that contained active ingredients can have unpleasant bitter and/or sour taste.

Other useful excipients of the present invention are selected from sodium citrate, calcium, magnesium, potassium, sodium phosphate, calcium, magnesium, potassium, light magnesium oxide, magnesium hydroxide, hydroxycarbonate magnesium, magnesium citrate, sodium chloride, potassium carbonate, sodium bicarbonate, potassium bicarbonate, adipic acid, citric acid, tartaric acid, alginic acid, stearic acid and its salts, oleic acid, L-leucine, behenate glycerol hydroxypropylmethylcellulose, hydrogenated vegetable oils (such as, for example, palm oil), palm oil, cocoa butter, cocoa paste, cocoa powder, xylitol, maldita, sorbitol, mannitol, Sucralose, Acesulfame K, sodium cyclamate, aspartame, sucrose, eritria, extract from citrus fruits, fructose, dextrose, maltose, dried by spray drying of malt, sodium aspartate, neohesperidine, maltodextrins, Inositol, inulin, yeast, silica, vegetable fibers (such as, for example, pea fiber), chitosan, flavouring substances (essential oils, powders, etc.): mint flavoring (peppermint, spearmint, sweet mint), star anise, anethole, vanilla, sage, additive tastefully liver, monosodium glutamate, fish m is CA, Supplement with a taste of chicken, Supplement with grapefruit flavor, Supplement with a taste of peach, lime, or a mixture thereof.

The compositions of the present invention may also contain at least one other active ingredient in combination with the specified at least one salt of the SAMe while maintaining good taste in songs. Specified active ingredient is preferably selected from vitamins, amino acids, glycosaminoglycans, flavolignans, hormones, natural substances of animal or vegetable origin, enzymes, polysaccharides, copolymers or mixtures thereof.

In particular, the other active ingredient may be selected from vitamins, such as vitamin B6, vitamin B12, vitamin B9 (folic acid), methylfolate, vitamin C; salts of magnesium, taurine, tryptophan, restored glutathione, n-acetylcysteine, tyrosine; hyaluronic acid, silymarin, silybin, L-theanine, melatonin, bromeline, St. John's wort, lipoic acid, Liapunov, bioflavonoids, rutin, Valerian, glucosamine, chondroitin sulfate, chitosan, ursodeoxycholic acid,Lactobacillus acidophilus, Lactobacillus vulgaris,Bacterium Bifidum brevi, Bifidum infantis, Bifidum bacterium lactis, bacterium Bifidum longum, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacillus plantarum, Lactobacillus rhamnosus;lemon balm, cinnamon, hawthorn, passion fruit, fennel, dried garlic, onions, preparatives tea tree, sweet orange, chamomile, thyme (in the form of essential oils, uterine infusions, soaked glycerides or powders), betaine, aspartic acid, glutamine, phosphoserine, phosphatidylserine, choline, coenzyme Q10, dimethylglycine, hydroxymethylbutyrate, lactoferrin, methylsulfonylmethane, homotaurine, p-aminobenzoic acid (PABA),Monacus purpureusor mixtures thereof.

The specified at least one additional active ingredient contained in the composition according to the present invention in amounts of from 0.05% to 70%, preferably from 0.1 to 55%, relative to the weight of the entire composition.

Specified number varies depending on the characteristics of the selected additional active ingredient.

In particular, in the case when the additional active ingredient is one of the above vitamins, dose according to the present invention varies from 0.00001 to 3%, preferably from 0,00005 to 1%, relative to the weight of the entire composition.

As noted above, the introduction of the compositions of the present invention to provide improved bioavailability of the drug in comparison to those compositions which are already available on the market; and in fact the introduction of the compositions of the present invention achieves peak plasma ion SAMe plasma (maximum plasma concentration) within a lane is an ode to time 1 to 2 hours after administration of the drug, preferably within an hour and a half, while currently available on the market nabukenya resistant environment of the stomach tablets this period is 5 hours.

The specified peak plasma according to the present invention corresponds to the concentration of the SAMe ion in the plasma, which is 40-50% higher than the baseline level, preferably equivalent to a value that 48% higher than the baseline level, whereas when using currently available on the market nabukenya resistant environment of the stomach pills is the excess is only 1%.

Thus, the present invention relates also to a method for achieving peak plasma ion in the SAMe period of time from 1 to 2 hours after administration, preferably within one and a half hours after ingestion, which is a characteristic feature of the method of preparation according to the present invention.

In particular, the method according to the present invention determines the achievement of the plasma concentration of the SAMe ion, which is 40-50% higher than the baseline level, preferably higher than at the basic level of 48%.

The present invention also relates to a method of increasing the plasma concentration of the SAMe ion by introducing the compositions of the present invention.

In particular, according to the method of the present invention is a plasma con is entrale SAMe ion is increased from 30 to 40% over a period of time, component preferably from 20 to 40 minutes after injection of the indicated composition. More preferably the value of plasma concentration of the SAMe ion increases by approximately 35% after about 30 minutes after administration of the compositions of the present invention.

According to the method according to the present invention a plasma ion peak SAMe (maximum plasma concentration) is achieved within time period of 1 to 2 hours, despite the fact that its concentration increases significantly in the period from 20 to 40 minutes after taking that guarantees fast performance.

In addition, the present invention relates to soluble in the mouth and/or effervescent compositions containing at least one salt of SAMe in combination with physiologically acceptable excipients, used to treat human or animal neuropsychiatric, osteoarticular disease or liver disease and/or treatment of disorders or uncomfortable conditions arising on the basis of the above diseases, in particular diseases or disorders related to the emotional sphere (in General, depressive syndromes, anxiety) and cognitive functions (dementia), acute and chronic disorders in the liver (alcoholic steatosis acute and chronic hepatitis, alcoholic and post-viral cirrhosis of the liver, nutrition the full-time cholestasis), and degenerative musculoskeletal diseases accompanied by motor dysfunction (osteoarthritis).

The above compositions for the treatment of human or animal neuropsychiatric, osteoarticular disease or liver disease, and/or treatment of disorders or uncomfortable conditions arising on the basis of the above diseases may also contain additional active ingredients. Such additional active ingredients are preferably selected from vitamins, amino acids, glycosaminoglycans, flavolignans, hormones, natural substances of animal or vegetable origin, enzymes, polysaccharides, probiotics.

The compositions of the present invention can be manufactured by a method including the following stages:

Scheme A(soluble in the mouth and/or effervescent tablets or granules and capsules):

1) Weighing of active ingredients and excipients;

2) Mixing (rotating helical stirrer);

3) Pressing;

4) Dry granulating the obtained tablets;

5) the Final pressing or using the pellets obtained in stage 4 and immediately Packed in sachets or capsules.

Scheme:(soluble in the mouth tablets or granules and capsules):

1) the Weighting of the components except light magnesium oxide and at least od is th SAMe salt;

2) Granulating to obtain suspensions with the use of moisturizing mixture obtained from an aqueous solution spanning excipient;

3) drying in a fluidized bed to achieve a moisture level below about 1%;

4) adjustment of the granules by size using vibrating pellet mill with perforated strainer, made of stainless steel (preferably with holes with a diameter of 1.5 mm);

5) Mixing the granules + at least one SAMe salt + light magnesium oxide + flavorings;

6) the Final pressing or using the pellets obtained in stage 5 and immediately Packed in sachets or capsules.

Scheme:(soluble in the mouth tablets or granules and capsules):

1) Weighing of all components;

2) Granulating the mixture with the use of these vegetable fats;

3) Cooling and granulating the mixture;

4) adjustment of the granules by size using vibrating pellet mill with perforated strainer, made of stainless steel (preferably with holes with a diameter of 1.5 mm);

5) the Final pressing or using the pellets obtained in stage 4 and immediately Packed in sachets or capsules.

The method according to the present invention is preferably carried out at a temperature in the range of from about 20°C to 30°C, more preferred the equipment at a temperature of about 25°C and at a relative humidity no higher than 28%.

According to the above method, the finished product has a relative humidity of preferably below 3%, more preferably below 1.5%.

In the examples below is a detailed description of the compositions of the present invention without limiting in any way its content.

EXAMPLES

Example 1

Soluble in the mouth tablet based tosilata SAMe (para-toluensulfonate)

Toilet SAMe(pair-toluensulfonate)200 mg (equivalent to 100 mg of SAMe ion) (13,33%)

Folic acid0.15 mg (0,010%)
Vitamin b120.001 mg (6,6* 10-5%)
Light magnesium oxide40 mg (2,67%)
Stearic acid90 mg (6%)
Beginat glycerin7 mg (0,47%)
Magnesium stearate10 mg (0,66%)
Mint odorantof 3.53 mg (0,24%)
The mixture of flavors (lime,
passion flower and hawthorn)
0.3 mg (0,020%)
Silica gel 4,53 mg (0,3%)
Xylitol350 mg (23,33%)
Mannitol793 mg (52,86%)
Xylitol1,45 mg (0.1%)
Neohesperidin0.16 mg (0,010%)
The TOTAL WEIGHT PILLS1500,12 mg

Preferably receive soluble in the mouth tablets with a diameter of 19 mm and weighing approximately 1.50 g,

Example 2

Soluble in the mouth tablet based tosilata SAMe (para-toluensulfonate)

Toilet SAMe (para-toluensulfonate) 233 mg (equivalent 119,76 mg SAMe ion) (10,53%)

Light magnesium oxide44 mg (2%)
Stearic acid80 mg(3,6%)
Beginat glycerin7 mg (0,3%)
Magnesium stearate10 mg (0,45%)
Mint odorantof 3.53 mg (0.16 per cent)
Essential oil of lemon balm0.1 mg (0,007%)
Anethole0,056 mg (0.005%)
Silica gel4,53 mg (0.2%)
Inositol908 mg (41,08%)
Mannitol470,21 mg (each holding 21.25%)
Xylitol450 mg (20,34%)
Sucralose1.6 mg (0.07 per cent)
Neohesperidin0.18 mg (0,008%)
The TOTAL WEIGHT PILLS2212,21 mg

Preferably receive soluble in the mouth tablets with a diameter of 22 mm and a weight of approximately 2.2,

Example 3

Soluble in the mouth tablet based tosilata SAMe (para-toluensulfonate)

Toilet SAMe (para-toluensulfonate) 420 mg (equivalent to 200 mg of SAMe ion) (17,87%)

Light magnesium oxide150 mg (6,38%)
Stearic acid160 mg (6,8%)
Beginat glycerin13 mg (0,55%)
Magnesium stearate20 mg (0,85%)
Xylitol859,57 mg (36,57%)
Mannitol700 mg (29,78%)
Sucralose4.5 mg (0,19%)
Neohesperidin0.3 mg (0,01%)
Orange perfume14,63 mg (0,62%)
Silica gel8 mg (0,34%)
The TOTAL WEIGHT PILLS2350,00 mg

Preferably receive soluble in the mouth tablets with a diameter of 22 mm and a weight of approximately 2.4,

Example 4

Effervescent soluble in the mouth tablet based tosilata SAMe (para-toluensulfonate)

Toilet SAMe(pair-toluensulfonate)233 mg (equivalent 119,762 mg SAMe ion) (10,30%)

Light magnesium oxide20,5 mg (0,9%)
L-leucine24 mg (1,06%)
Beginat glycerin4 mg (0,18%)
Magnesium stearate1 mg (0,04%)
Powder grapefruit perfumes 50 mg (2,21%)
Inositol800 mg (up RUB 35.36%)
Sucralose10 mg (0.44 per cent)
Anhydrous disodium carbonate400 mg (17,68%)
Citric acid250 mg (11,05%)
Adipic acid250 mg (11,05%)
Sodium carbonate200 mg (cent to 8.85%)
Silica gel20 mg (0,88%)
The TOTAL WEIGHT PILLS2262,50 mg

Preferably receive soluble in the mouth tablets with a diameter of 22 mm and a weight of approximately 2.2,

Example 5

Soluble in the mouth tablet based tosilata SAMe (para-toluensulfonate) (veterinary use)

Toilet SAMe(pair-toluensulfonate)233 mg (equivalent 119,762 mg SAMe ion) (9,19%)

Light magnesium oxideof 38.5 mg (1,52%)
Beginat glycerin7 mg (0,27%)
Stearic acid80 mg (3,15%)
Additive tastefully liver2 mg (0,08%)
Yeast additive1 mg (0,04%)
Silica gel20 mg (0,79%)
Dry liver500 mg (of 19.72%)
Dry yeast1200 mg (47,32%)
Glucosamin sulfate250 mg (9,87%)
Gluconate monolatry50 mg (1,97%)
Sodium chloride20 mg (0,79%)
Xylitol134 mg (5,28%)
Neohesperidin0.2 mg (0,01%)
The TOTAL WEIGHT PILLS2535,70 mg

Preferably receive soluble in the mouth tablets with a diameter of 22 mm and a weight of about 2.5,

Example 6

Soluble in the mouth tablet-based butanedisulfonate SAMe (veterinary use)

BcandisplaySAMe 233 mg (equivalent 119,762 mg SAMe ion) (10,19%)

Easy OK the ID of magnesium of 38.5 mg (1,68%)
Beginat glycerin7 mg (0,31%)
Stearic acid80 mg (3.5 per cent)
Additive tastefully liver2 mg (0,09%)
Yeast additive1 mg (0,04%)
Silica gel20 mg (0,87%)
Dry liver500 mg (21,88%)
Dry yeast1200 mg (52.5 per cent)
MSG monolatry50 mg (2,19%)
Sodium chloride20 mg (0,88%)
Xylitol134 mg (5,86%)
Neohesperidin0.2 mg (0,01%)
The TOTAL WEIGHT PILLS2285,70 mg

Preferably receive soluble in the mouth tablets with a diameter of 22 mm and a weight of approximately 2,25,

Example 7

Soluble in the mouth tablet on the basis of phytate SAMe

Phytate SAMe 215 mg (equivalent 113,10 mg SAMe ion)

(14,41%)

Silymarin100 mg (6,7%)
Restored glutathione25 mg (1,68%)
Ursodeoxycholic acid150 mg (of 10.05%)
Light magnesium oxide42 mg (2,82%)
Palm oil25 mg (1,68%)
Maltodextrin200 mg (13,52%)
Lures700 mg (46,94%)
Magnesium stearate15 mg (1%)
Dextrose5 mg (0,33%)
Dried by spray drying malt2.5 mg (0,17%)
The mixture of flavors (thyme, mint, spearmint, vanilla)6 mg (0.4%)
Silica gel4 mg (0,20%)
Sucralose2 mg (0.10%)
The TOTAL WEIGHT PILLS1491,50 mg

Preferably receive instant the mouth tablets with a diameter of 19 mm and a weight of about 1.5 g

Example 8

Soluble in the mouth tablet based tosilata SAMe (para-toluensulfonate)

Toilet SAMe (para-toluensulfonate) 243 mg (equivalent to 121.5 mg SAMe ion) (11.61 percent)

Valerian150 mg (7,17%)
St. John's wort7 mg (0,33%)
Tryptophan100 mg (4,78%)
Light magnesium oxide33 mg (1.58 per cent)
Beginat glycerin85 mg (4,06%)
Magnesium stearate11 mg (0,52%)
Xylitol500 mg (23,90%)
Mannitol950 mg (45,40%)
Silica gel3.7 mg (0,18%)
Acesulfame K1.2 mg (0,05%)
Cyclamate0.9 mg (0,04%)
A mixture of flavourings (peppermint, fennel and cinnamon)4.5 mg (0,21%)
Silica gelthe 3.5 is g (0,17%)
The TOTAL WEIGHT PILLS2092,80 mg

Preferably receive soluble in the mouth tablets with a diameter of 22 mm and a weight of about 2 g

Example 9

Effervescent soluble in the mouth tablet based tosilata SAMe (para-toluensulfonate) and butanedisulfonate SAMe

Toilet SAMe (para-toluensulfonate) 90 mg (equivalent to 45 mg of SAMe ion) (7,37%)

ButanedisulfonateSAMe90 mg (equivalent to 45 mg of SAMe ion) (7,37%)
N-acetylcysteine50 mg (4.09 to%)
Vitamin C60 mg (4,91%)
Bioflavonoids150 mg (12,29%)
Light magnesium oxide29 mg (2,37%)
The potassium bicarbonate400 mg (32,77%)
Tartaric acid230 mg (18,85%)
Citric acid50 mg (4,1%)
Leucine40 mg (3,28%)
Beginat glycerin6 is g (0,49%)
Magnesium stearate7 mg (0,57%)
Aspartate sodium3.5 mg (0.28 per cent)
▫ Maltitol5 mg (0,42%)
A mixture of flavourings (fragrant mint, sage)5 mg (0,42%)
Silica gel5 mg(0,42%)
The TOTAL WEIGHT PILLS1220,50 mg

Preferably receive soluble in the mouth tablets with a diameter of 19 mm and a weight of about 1.2 g

Example 10

Soluble in the mouth tablet-based butanedisulfonate SAMe

Butanedisulfonate SAMe 243 mg (equivalent 127,8 mg SAMe ion) (14,38%)

Lactobacillus acidophilus(150 mld)10 mg (0,59%)
Bacterium Bifidum longum(100 mld)20 mg (1,18%)
Sodium citrate100 mg (5,91%)
Stearic acid85 mg (5,22%)
Corn starch50 mg (2,95%)
Stearamide 14 mg (0,93%)
Silica gelthe 4.3 mg (0.25%)
Inulin400 mg (23,65%)
Mannitol300 mg (17,74%)
Sucrose300 mg (17,74%)
Glycine151 mg (8,99%)
A mixture of flavourings (lemon balm, passion flower and hawthorn)3 mg (0,18%)
Silica gel4 mg (0,23%)
Acesulfame K1 mg (0.06%)
The TOTAL WEIGHT PILLS1691,30 mg

Preferably receive soluble in the mouth tablets with a diameter of 19 mm and a weight of about 1.6,

Example 11

Soluble in the mouth tablet based tosilata SAMe (para-toluensulfonate) (sublingual)

Toilet SAMe (para-toluensulfonate) mg (equivalent 30,84 mg SAMe ion) (24,83%)

tr>
Melatonin1 mg (0,42%)
Light magnesium oxide4,8 mg (1,99%)
Beginat glycerin19 mg (7,86%)
Magnesium stearate2.5 mg (1,03%)
Xylitol95 mg (39,32%)
Hydroxypropylcellulose55 mg (22,77%)
Sucralose0.5 mg (0,21%)
A mixture of flavourings (oil of sweet orange and cinnamon)1.8 mg (0,74%)
Silica gel2 mg (0,83%)
The TOTAL WEIGHT PILLS241,60 mg

Preferably receive sublingual tablets with a weight of 0.24,

Example 12

Effervescent granules based tosilata SAMe (para-toluensulfonate)

Toilet SAMe(pair-toluensulfonate)mg (equivalent to 80 mg of SAMe ion) (13,20%)

Glucosamine100 mg (8,25%)
Chondroitin sulfate100 mg (8,25%)
Hyaluronic acid5 mg (0,41%)
Light magnesium oxide 29 mg (2,2%)
The potassium bicarbonate400 mg (33,00%)
Tartaric acid230 mg (18,98%)
Citric acid150 mg (12,37%)
Magnesium stearate4 mg (0,33%)
Aspartame4 mg (0,33%)
Xylitol20 mg (1,76%)
The mixture of flavors: passion fruit, hawthorn and chamomile)5 mg (0,41%)
Silica gel5 mg (0,41%)
TOTAL WEIGHT1212,00 mg

Preferably get Sasha with a weight of about 1.2 g

Example 13

Slightly soluble effervescent in the mouth tablet based tosilata SAMe (para-toluensulfonate)

Toilet SAMe (para-toluensulfonate) 400 mg (equivalent to 200 mg of SAMe ion) (32,24%)

N-acetylcysteine50 mg (4,03%)
Vitamin C60 mg (a 4.83%)
Bioflavonoids 150 mg (12,09%)
Light magnesium oxide29 mg (2,34%)
The potassium bicarbonate200 mg (16,12%)
Tartaric acid230 mg (18,54%)
Citric acid50 mg (4,0,3%)
Leucine40 mg (3,22%)
Beginat glycerin6 mg (0.48 per cent)
Magnesium stearate7 mg (0,56%)
Aspartate sodium3.5 mg (0.28 per cent)
Citrus extract5 mg (0.4%)
A mixture of flavourings (bitter orange)5 mg (0.4%)
Silica gel5 mg (0.4%)
The TOTAL WEIGHT PILLS1240,50 mg

Preferably receive soluble in the mouth tablets with a diameter of 19 mm and a weight of about 1.2 g

EXPERIMENTAL PART

Using the composition soluble in the mouth tablets tosylate SAMe (para-toluensulfonate) according to the about example 2 (Quietosan ♦) conducted a comparative test to assess bioavailability of specified composition compared to the composition, made in the form nabukenya resistant environment of the stomach tablets currently available on the market (Samir® ■).

For this purpose, six subjects of both sexes among healthy volunteers took on an empty stomach in the mode of a randomized cross-over study (i.e. in a mode in which all patients received both treatments each other) 119,76 mg SAMe ion, manufactured according to the present invention (composition of example 2), and 200 mg of SAMe ion in the form Nabakevi resistant environment of the stomach pills currently available on the market (Samir®).

The results were normalized to account for the difference in concentration between two pharmaceutical forms.

Bioavailability in plasma, expressed as AUC, composition soluble in the mouth the tablets containing toilet SAMe, according to the present invention was significantly higher, on average, higher by about 150% to about 200%, relative to Nabakevi resistant environment of the stomach of the composition.

The time to reach peak concentration was approximately one hour, an hour and a half (plasma bioavailability started to grow immediately after admission) for soluble mouth tablets of the present invention and about 5 hours for Nabakevi resistant environment of the stomach tablets (Fig. 1).

In addition, as shown in Fig. 1, the plasma concentration is Oia after 1 hour - a half hour after taking soluble in the mouth tablets of the present invention was 48% higher than the baseline level, whereas plasma bioavailability after 1 hour - an hour and a half after taking Nabakevi resistant environment of the stomach tablets was approximately 1% higher than baseline values.

Further, given that the plasma concentration of tosylate SAMe 12 hours after taking the tablet of the present invention, as shown in Fig. 2, was approximately 30% above baseline values of plasma concentration tosilata SAMe 12 hours after taking Nabakevi resistant environment of the stomach tablets was approximately 11% higher than the baseline values.

A similar test was performed on two healthy volunteers using soluble in the mouth effervescent compositions of example 2 of the present invention, which demonstrated the pharmacokinetics, the nature of which was an intermediate relatively soluble in the mouth tablet form of the present invention and Nabakevi resistant environment of the stomach pills currently available on the market.

Soluble in the mouth effervescent composition was characterized by this AUC value that is about 30-40% higher than the corresponding figure for Nabakevi resistant environment of the stomach pills and the time was about 1-2 hours.

So about the time, from the above data show the benefits of the compositions of the present invention on the basis of at least one salt of SAMe in a form soluble in the mouth and/or sparkling form with her characteristic good taste.

1. Pharmaceutical, dietary or nutritional composition comprising at least one salt of S-adenosylmethionine in combination with physiologically acceptable excipients, characterized in that the composition has a form soluble in the mouth tablets and these physiologically acceptable excipients include light magnesium oxide.

2. The composition according to claim 1, where the specified at least one salt of S-adenosylmethionine selected from tosilata (para-toluensulfonate), butanedisulfonate, phytate, or a mixture thereof.

3. Composition according to any one of the preceding paragraphs, where the specified at least one salt of S-adenosylmethionine is contained in an amount of 5 to 70 wt.% relative to the weight of the entire composition.

4. The composition according to claim 3 where the specified at least one salt of S-adenosylmethionine is contained in an amount of from 7 to 50 wt.% relative to the weight of the entire composition.

5. The composition according to claim 1, comprising at least one other active ingredient.

6. The composition according to claim 5, where the specified at least one other active ingredient selected from vitamins, amino acids, glycosaminoglycans, LAF is ulignano, hormones, natural substances of animal or vegetable origin, enzymes, polysaccharides, copolymers or mixtures thereof.

7. The composition according to claim 5, where the specified at least one other active ingredient selected from the B group vitamins, methylfolate, vitamin C, magnesium salts, taurine, tryptophan, restored glutathione, n-acetylcysteine, tyrosine, hyaluronic acid, silymarin, silybin, melatonin, L-theanine, bromeline, St. John's wort, lipoic acid, Liapunov, bioflavonoids, rutin, Valerian, glucosamine, chondroitin sulfate, chitosan, ursodeoxycholic acid; Lactobacillus acidophilus, Lactobacillus vulgaris, bacterium Bifidum brevi, Bifidum infantis, Bifidum bacterium lactis, bacterium Bifidum longum, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacillus plantarum, Lactobacillus rhamnosus, lemon balm, cinnamon, hawthorn, passion fruit, fennel, dried garlic, onions, tea tree, sweet orange, chamomile, thyme, betaine, phosphoserine, phosphatidylserine, asparagine, glutamine, choline, coenzyme Q10, dimethylglycine, hydroxymethylbutyrate, lactoferrin, methylsulfonylmethane, homotaurine, p-aminobenzoic acid (RAV), Monacus purpureus or mixtures thereof.

8. The composition according to claim 1, characterized in that the composition has good taste.

9. The composition according to claim 1 for use in the treatment of neuropsychiatric, bone and joint diseases or diseases of the liver.

10. The composition according to P9 for use in the treatment of depressive syndromes anxiety, dementia, alcoholic steatosis, acute hepatitis, chronic hepatitis, alcoholic cirrhosis, post-viral cirrhosis of the liver, intrahepatic cholestasis and degenerative musculoskeletal diseases and musculoskeletal dysfunctions.

11. The composition according to claim 9 or 10 for use in the treatment of a human or animal.

12. The way to achieve peak plasma ion in the SAMe period of time from 1 to 2 hours, including the introduction of a composition according to any one of claims 1 to 8.

13. The method according to item 12 achieve peak plasma ion in the SAMe period of time about one and a half hours after administration of the composition.

14. The way to obtain a plasma concentration of the SAMe ion in excess of 40-50% of the appropriate base level, during the period of time from 1 to 2 hours, including the introduction of a composition according to any one of claims 1 to 8.

15. The method according to 14 obtain a plasma concentration of the SAMe ion in excess of 48% of the appropriate base level, after about a half hour after taking.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmacy and medicine. What is presented is using a therapeutic agent containing a compound of the general formula

in a combination with at least one more therapeutic agent specified in biguanide and an α-glucosidase inhibitor for treating type 2 diabetes mellitus, diabetes complications, impaired glucose tolerance, insulin resistance or obesity, as well as the therapeutic agent based on the above combination for the same application.

EFFECT: technical effect consists in the synergetic action on an increase of the GLP-1 administration following administration of saccharose, a combination SK-0403 (a compound described by the general formula (I)) with Miglitol or metformin.

8 cl, 8 dwg, 4 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutically acceptable (R)-7-[3-amino-4-(2,4,5-trifluorophenyl)-butanoyl]-3-trifluoromethyl-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine-1-carboxylic acid salts, wherein an acid addition salt is specified in a group consisting of phosphate, malate and tartrate; a base addition salt is specified in a group consisting of sodium salt, lithium salt, potassium salt, calcium salt, magnesium salt, tetramethylammonium salt, tetraethylammonium salt, ethanolamine salt, choline salt and arginine salt. The invention also refers to methods for preparing the above salts, to a therapeutic agent as a dipeptidyl peptidase (DPP-IV) inhibitor based thereon.

EFFECT: there are prepared new (R)-7-[3-amino-4-(2,4,5-trifluorophenyl)-butanoyl]-3-trifluoromethyl-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine-1-carboxylic acid salts which can find application in medicine as the therapeutic agent for treating type 2 diabetes, hyperglycemia, obesity or insulin resistance.

16 cl, 4 tbl, 13 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to the chemical-pharmaceutical industry, and represents using a biologically active agent for preparing a drug for metabolic disorders specified in a group consisting of insulin resistance syndrome and diabetes mellitus, including type I diabetes mellitus and type II diabetes mellitus, and obesity, wherein the agent represents a compound of formula

,

wherein n=1 or 2; m=0, 1, 2, 4 or 5; q=0; t=0 or 1; R3 represents hydrogen; A is phenyl, unsubstituted or substituted by 1 or 2 alkyls having 1 or 2 carbon atoms; and R1 is hydrogen or alkyl having 1 or 2 carbon atoms; or when R1 represents hydrogen - a pharmaceutically acceptable salt of the compound.

EFFECT: preparing the drug for metabolic disorders.

18 cl, 6 ex, 22 tbl

FIELD: food industry.

SUBSTANCE: inventions group relates to the animal feeding filed, in particular, to a fodder product and to a method for treatment of disorders and diseases associated with overweight. The fodder product contains: 30 wt % - 37 wt % of crude protein (in terms of dry weight); 7.5 wt % - 9 wt % of crude fat (in terms of dry weight); 30 wt. % - 35 wt % of total food fibres (in terms of dry weight); 20 wt % - 25 wt % of crude fibres (in terms of dry weight); 0.1 wt % - 6 wt % of omega-3 polyunsaturated fatty acids (in terms of dry weight).

EFFECT: fodder product usage in the method for treatment of disorders and diseases associated with overweight positively affects weight loss as well as allows to preserve lean muscle mass and mineral substances in bones.

7 cl, 2 dwg, 6 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: invention relates to granules as a laxative, containing particles of magnesium oxide of formula Mg2+1-xZn2+x)O (1) with the average diameter of secondary particles 0.1-25 mcm and apparent specific volume 3-20 ml/g. In formula (1) X represents number from 0 to 0.02, content of magnesium oxide particles constitutes from 80 to 95 wt %. Granules also include mannitol and carmellose and have the average particle diameter 0.2-0.4 mm and bulk density 0.4-0.7 g/ml. Content of particles in granules, which have particle diameter from less than 500 mcm to not less than 355 mcm, constitutes from 30 to 45 wt %, content of particles, which have particle diameter from less than 355 mcm to not less than 180 mcm constitutes from 40 to 50 wt %, content of particles, which have particle diameter from less than 180 mcm to not less than 150 mcm, constitutes from 10 to 28 wt %.

EFFECT: granules of magnesium oxide possess good solubility, attractive taste and outlook and do not leave sense of roughness in the oral cavity.

4 cl, 7 tbl, 2 dwg, 7 ex

FIELD: medicine.

SUBSTANCE: group of inventions refers to medicine and concerns methods of treating growth hormone or insulin-like growth factor 1 deficiency in a patient involving administering an immunogenic amount of a vaccine containing a chimeric somatostatin-14 based polypeptide bound to inactivated chloramphenicol acetyltransferase (CAT), and an adjuvant; the vaccine for treating the patient having growth hormone or insulin-like growth factor 1 deficiency; a method of treating obesity in the patient involving administering the immunogenic amount of the vaccine.

EFFECT: group of inventions provide the immunogenicity for somatostatin and higher release of endogenously produced growth hormone and/or insulin-like growth factor 1.

22 cl, 8 ex, 6 dwg, 2 tbl

FIELD: chemistry.

SUBSTANCE: group of inventions relates to field of biotechnology. Strain Bifidobacterium breve MCC 1274 FERM BP-11175 demonstrates low coefficient of conversion of linoleic acid into conjugated linoleic acid. Strain demonstrates coefficient of conversion of linoleic acid into conjugated linoleic acid not higher than 10%. To reduce or prevent obesity or to improve tolerance to glucose said strain is introduced in efficient quantity to subject requiring it. Also claimed are food product and drink, which contain preparation based on said strain.

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22 cl, 4 dwg, 2 tbl, 7 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to medication for treatment or prevention of disease, which developed on the basis of structural and/or functional, and/or compositional changes of lipids in cell membranes, selected from cancer, vascular diseases, inflammatory diseases, metabolic diseases, obesity and excessive body weight, neurological or neurodegenerative disorders, which represents compound of formula COOR1-CHR2-(CH2)a-(CH=CH-CH2)b-(CH2)c-CH3 (I) or its pharmaceutically acceptable salts and derivatives, selected from esters, ethers, alkyl, acyl, phosphate, sulfate, ethyl, methyl or propyl; in which a and c can have independent values from 0 to 7; b can have independent values from 2 to 7, where R1 is selected from the following radicals: H, Na, K, CH3O, CH3-CH2O and OPO(O-CH2-CH3)2, and R2 is selected from the following radicals: OH, OCH3, O-CH3COOH, CH3, Cl, CH2OH, OPO(O-CH2-CH3)2, NOH, F, HCOO and N(OCH2CH3)2.Invention also relates to application of formula (I) compound and pharmaceutical composition, which contains it.

EFFECT: medications, based on claimed compound, are more efficient than medications of preceding level of technology.

22 cl, 7 dwg, 16 tbl, 10 ex

FIELD: chemistry.

SUBSTANCE: compound has formula I: |Chemical formula 1| where A is O, NR, S, S(=O), S(=O)2 or Sc; B is hydrogen or ; R1 is hydrogen, C1-C8 alkyl or halogen; R2 is hydrogen, C1-C8 alkyl, or ; Xa and Xb is independently CR or N; R is hydrogen or C1-C8 alkyl; R3 is hydrogen, C1-C8 alkyl; R4 and R5 are independently hydrogen, halogen or C1-C8 alkyl; R6, is hydrogen. C1-C8 alkyl, or a pharmaceutically acceptable organic salt; R21, R22 and R23 are independently hydrogen, halogen, NO2, C1-C7 alkyl, unsubstituted or substituted with halogen, C3-C12 heteroaryl, containing one or more heteroatoms selected from N, O and S; m equals an integer from 1 to 4; p equals an integer from 1 to 5; s equals an integer from 1 to 5; u equals an integer from 1 to 3; w equals an integer from 1 to 4; and alkyl in R1, R3, R4, R5 and R6 can further be substituted with one or more halogens, C3-C7 cycloalkyl or C1-C5 alkylamine. Also disclosed are methods of producing selenazole derivatives, a pharmaceutical composition, a functional feed additive composition, a functional beverage, a food additive, animal feed, a functional cosmetic composition, a peroxisome proliferator-activated receptor (PPAR) activator composition.

EFFECT: invention enables to obtain a selenazole derivative which activates a peroxisome proliferator-activated receptor.

15 cl, 1 dwg, 6 tbl, 298 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel omega-3 lipid compounds of general formula (I) or to their pharmaceutically acceptable salt, where in formula (I): R1 and R2 are similar or different and can be selected from group of substitutes, consisting of hydrogen atom, hydroxy group, C1-C7alkyl group, halogen atom, C1-C7alkoxy group, C1-C7alkylthio group, C1-C7alkoxycarbonyl group, carboxy group, aminogroup and C1-C7alkylamino group; X represents carboxylic acid or its carbonate, selected from ethylcarboxylate, methylcarboxylate, n-propylcarboxylate, isopropylcarboxylate, n-butylcarboxylate, sec-butylcarboxylate or n-hexylcarboxylate, carboxylic acid in form of triglyceride, diglyceride, 1-monoglyceride or 2-monoglyceride, or carboxamide, selected from primary carboxamide, N-methylcarboxamide, N,N-dimethylcarboxamide, N-ethylcarboxamide or N,N-diethylcarboxamide; and Y stands for C16-C22 alkene with two or more double bonds, which have E- and/or Z-configuration.

EFFECT: described are pharmaceutical and lipid compositions, which contain said compounds, for application as medications, in particular, for treatment and/or prevention of peripheral insulin resistance and/or condition of diabetes, for instance, type 2 diabetes, increased levels of triglycerides and/or levels of non-HDL cholesterol, LDL cholesterol and VLDL cholesterol, hyperlipidemic condition, for instance, hypertriglyceridemia (HTG), obesity or condition of excessive body weight, fatty liver disease, for instance, non-alcoholic fatty liver disease (NAFLD) or inflammatory disease or condition.

60 cl, 3 tbl, 65 ex

FIELD: medicine.

SUBSTANCE: invention concerns an antidepressant drug representing the amino acid glycine immobilised on the detonation-synthesised nanodiamond particles of 2-10 nm in size, and a method for preparing it.

EFFECT: antidepressant drug possesses higher efficacy.

4 cl, 7 dwg, 7 tbl, 2 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of enhancing cognitive function in an animal or human being. Said method includes administering a compound which is selected from a group consisting of: steviol, isosteviol, and a mixture of steviol and isosteviol in a cognitive function enhancing amount. The invention also relates to a composition and nutraceutic agent containing one of said compounds or a mixture thereof.

EFFECT: invention improves learning capacity, intelligence and memory.

8 cl, 10 dwg, 6 tbl, 14 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds possessing a high effectiveness in modulation of NMDA receptor activity.

EFFECT: compounds are applicable in treating the diseases and disorders, such as disturbed learning, cognitive activities, as well as for relieving and/or reducing neuropathic pain.

26 cl, 21 dwg, 2 tbl, 9 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (1), having affinity to the µ-opioid receptor and the to the ORL1 receptor, a medicinal agent containing said compounds and use thereof to obtain a medicinal agent for treating pain and other diseases. In general formula (1), Y1, Y1', Y2, Y2', Y3, Y3', Y4 and Y4' denote -H; R1 and R2 independently denote -CH3; R3 denotes R0, where R0 denotes C1-8-alkyl; aryl, selected from phenyl which is unsubstituted or mono-substituted with -F, -Cl, -Br, -I, -CN or -OR0, where R0 denotes -C1-3-alkyl; unsubstituted heteroaryl, selected from a 5-member heteroaryl with one S atom as a heteroatom; R4 denotes R0, where R0 denotes aryl, selected from phenyl which is unsubstituted or mono-substituted with -F, -Cl, -Br, -I, -CN or -OR0, where R0 denotes -C1-3-alkyl; 2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indolyl, mono-substituted with -S(O)2-phenyl; unsubstituted -dihydroisoindolyl or unsubstituted -indolyl; or R4 denotes -OR0 or -SR0, where R0 denotes a cycloaliphatic group selected from -C5-6-cycloalkyl; aryl, selected from unsubstituted phenyl; C1-2-alkylaryl, where aryl denotes phenyl, which is unsubstituted or mono-substituted with -OR0, where R0 denotes -C1-3-alkyl; and R5 denotes -H or -CH3.

EFFECT: obtaining a medicinal agent for treating pain and other diseases.

7 cl, 3 tbl, 22 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel medication possessing antidepressant, anxiolytic and nootropic activity, which represents compound of general formula where: X is NH or 1,4-piperasino; R1=H or CH3; R2=H, OCH3 or N(CH3)2.

EFFECT: on experimental models in vivo compounds, possessing original spectrum of psychotropic action, exceed medications of different pharmacological groups - aphobazolum, melipramin, phenotropil, diazepam in complex of useful qualities, and can be applied in treatment of patients with anxiety and depressive disorders.

4 tbl, 8 ex

FIELD: chemistry.

SUBSTANCE: invention relates to tranquilising compounds, contributing to reduction of anxiety, increase of cognitive and motor activity, namely to 4-(1-hydroxy-1-methyl-2-morpholinoethyl)benzoic acid (1) and 4-(1-hydroxy-2-morpholinocyclohexyl)benzoic acid (2), their pharmaceutically acceptable salts and esters. In addition, object of invention is also presented by method of obtaining and compounds.

EFFECT: compounds, possessing anxiolytic activity, which do not manifest considerable sedative action, hypotension and excitatory action on central nervous system.

2 cl, 3 tbl

FIELD: chemistry.

SUBSTANCE: described are racemic- or enantiomer-rich 3-substituted piperidine compounds of formula (I) or pharmaceutically acceptable salts thereof, where A denotes phenyl, naphthyl, optionally substituted, or benzothiophenyl; B denotes an azole selected from a group consisting of triazole, benzotriazole, 5-methyl- or 5-phenyltetrazole; Y-CH2 and X- N-R, where R denotes hydrogen or C1-4alkyl, pharmaceutical compositions containing said compounds, and methods of treating depression, anxiety or pain disorder in mammals.

EFFECT: high efficiency of using compounds.

11 cl, 4 tbl, 126 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are presented a method for preventing, suppressing or treating a depressive disorder associated with multiple sclerosis, involving administering a therapeutically effective amount of a S1P receptor modulator specified in 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol in the free form or in the form of a pharmaceutically acceptable salt, and FTY720-phosphate and using the above compounds for preparing a drug preparation for the same application.

EFFECT: patient's health improvement in recurrent multiple sclerosis, either relapsing-remitting, or secondary-progressive has been shown.

5 cl, 6 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical industry, namely preparing an agent of hindu lotus seed extract (Nelumbo nucifera) possessing anxiolytic and antidepressive action. The agent possessing anxiolytic and antidepressive action prepared by extraction of hindu lotus seed extract (Nelumbo nucifera) in 50% ethanol in a Soxhlet extraction apparatus in the specific proportions.

EFFECT: agent possess the effective anxiolytic and antidepressive action.

3 tbl, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical industry and represents the use of a compound which exhibits inhibitory activity on arginase as a therapeutically active agent for treating and/or preventing depression and/or depression-associated conditions.

EFFECT: invention provides extending the range of products for treating and/or preventing depression and/or depression-associated conditions.

9 cl, 3 ex, 2 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to the field of pharmaceutics. An extract of Fraxinus excelsior seeds, capable of activating PPAR-alpha, which contains nuzhenide GI3, oleoside methyl ester, excelside B, GI5, salidroside, in effective quantities. An application of the extract of Fraxinus excelsior seeds to obtain a medication for treating a state, in which the PPAR-alpha activation is useful, is described. Also described is a method of treating a subject with the state, in which the PPAR-alpha activation is useful. A method of obtaining the extract of Fraxinus excelsior seeds is disclosed.

EFFECT: application of the claimed extract makes it possible to treat states, in which the PPAR-alpha activation is useful in an efficient way.

14 cl, 11 dwg, 2 tbl, 13 ex

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