Halogenated biphenols as antibacterial agents

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula (I) : or a salt thereof, wherein R1 and R5 are independently selected from H, OH and alkoxy; R2-R4 and R6-R8 are independently selected from H, OH, F, Cl, Br and I; R9 and R10 are C2-C8 alkenyl; under the condition that at least one of R1, R5 and R7 is OH or alkoxy; at least one of R2-R4, R6 and R8 is F, Cl, Br or I; and R2 and R6 are Cl. The invention also relates to an antibacterial composition and treatment methods.

EFFECT: improved properties.

18 cl, 7 ex, 10 tbl

 

COMPOUNDS AND COMPOSITIONS

The LEVEL of TECHNOLOGY

There is an urgent need for antibacterial medications and compositions containing these funds, which are effective against common oral pathogens and skin bacteria.

Summary of the INVENTION

In some embodiments embodiment the present invention provides a compound of Formula (I):

or its salt, in which R1and R5independently selected from H, OH and alkoxy; R2-R4and R6-R8independently selected from H, OH, F, Cl, Br and I; R9and R10independently selected from H, alkyl, alkenyl, alkynyl and aryl; provided that at least one of R1, R5or R7represents OH or alkoxy; and at least one of R2-R4, R6and R8represents F, Cl, Br or I; and a carrier.

In some embodiments embodiment the compound of Formula (I) has the structure of Formula (II):

Some variants of the embodiment provides a method of treating or preventing diseases or conditions of the oral cavity comprising contacting the surface of the oral cavity with any of the compositions described in this document. Other variants of the embodiment provides a method of treating or preventing the disease or condition of the skin, vkljuchajuwih� contacting the skin surface of the subject, in need, with any of the compositions described in this document.

DETAILED DESCRIPTION

As used throughout the document, ranges are used as a notation for the description of all values that are within range. Any value within the range can be selected as the boundary of the range.

All references cited in this document, therefore, incorporated by reference in their entirety.

In case of discrepancies between the definitions in this description and definitions cited in the link are using the definition given in the description.

Thus, as used herein, the term "alkyl" refers to saturated aliphatic hydrocarbon, including straight chain, branched chain and cycloalkyl group with 1-20 carbon atoms, for example propyl, isopropyl, butyl, cyclopropyl.

The term "alkenyl" refers to unsaturated hydrocarbons with an open circuit and one or more double carbon bonds, having the General formula CnH2n, such as vinyl and propenyl.

The term "alkynyl" refers to an unsaturated aliphatic hydrocarbon containing at least one carbon triple bond in the carbon chain, for example, acetylene.

The term "cycloalkyl" refers to C3-8cyclic small drop�gorodom, for example cycloalkyl or cyclopropyl.

The term "alkoxy" refers to an alkyl group with the specified number of carbon atoms, joined to the primary molecular residue through an oxygen bridge, e.g., methoxy or ethoxy.

Some variants of the embodiment provides the compound of Formula (I):

or its salt, where R1and R5independently selected from H, OH and alkoxy; R2-R4and R6-R8independently selected from H, OH, F, Cl, Br and I; R9and R10independently selected from H, alkyl, alkenyl, alkynyl and aryl; provided that at least one of R1, R5and R7represents OH or alkoxy; and at least one of R2-R4, R6and R8represents F, Cl, Br or I.

Some variants of the embodiments provide a compound in which R1and R5independently selected from OH or alkoxy; and R2and R6independently selected from H, F, Cl, Br and I. in Other variations of the embodiments provide a compound in which R1and R5represent OH. Other variations of the embodiments provide a compound in which R1and R7represent OH. Still other variations of the embodiments provide a compound in which R2and R6represent Cl.

Some variants of embodiment provide�represent the connection in which R9and R10are independently selected from C2-C8the alkyl and C2-C8alkenyl. Some variants of the embodiments provide a compound having the structure of Formula (II):

Some variants of the embodiments provide a compound having the structure of Formula (III):

Some variants of embodiment of the present invention provide a composition for treating oral or personal hygiene: a compound of Formula (I):

or its salt, in which R1and R5independently selected from H, OH and alkoxy; R2-R4and R6-R8independently selected from H, OH, F, CI, Br and I; R9and R10selected independently from H, alkyl, alkenyl, alkynyl and aryl; provided that at least one of R1, R5and R7represents OH or alkoxy; and at least one of R2-R4, R6and R8represent F, Cl, Br or I; and a carrier. In some embodiments embodiment the carrier is an orally acceptable carrier. In some embodiments embodiment the carrier is a carrier suitable for compositions for personal hygiene.

Components/ingredients suitable for the production of carrier [for funds] personal hygiene is described, for example, the publication of the patent application U.S. No. 2007/0048235. Some variants of embodiments provides a composition comprising any of the compounds described in this document.

In some embodiments, embodiments of R1and R5selected independently from OH or alkoxy; and R2and R6selected independently from H, F, Cl, Br and I. In some embodiments, embodiments of R1and R5represent OH. In other embodiments, embodiments of R1and R7represent OH. Still other variations of the embodiments provide compositions in which R2and R6represent Cl.

In other embodiments, embodiments of R9and R10selected independently from C2-C8alkyl or C2-C8alkenyl. Still other variations of the embodiments provide compositions in which the compound of Formula (I) has the structure of Formula (II):

At the same time, other options embodiments provide compositions in which the compound of Formula (I) has the structure of Formula (III):

In some embodiments embodiment the present invention provides compositions in which the compound of Formula (I) is present in a concentration of from about 0.001 to about 10 wt%. Other options embodiments provide compositions in which the compound of Formula (I) is present in a concentration of from eye�about 0.01 to about 5 wt%. Along with this, other options embodiments provide compositions in which the compound of Formula (I) is present in a concentration of from about 0.1 to about 2 wt%. Still other variations of the embodiments provide compositions in which the compound of Formula (I) is present in a concentration of about 0.5% of the mass.

In some embodiments embodiment the composition also contains one or more components selected from a fluoride ion source; means for warning the occurrence of Tartar; buffer means; abrasive and combinations of two or more of these. In some embodiments, embodiments at least one of the one or more components is a source of fluoride ions selected from tin fluoride, sodium fluoride, potassium fluoride, sodium monofluorophosphate, sodium fluorosilicate, ammonium fluorosilicate, amine fluoride, ammonium fluoride, and combinations of two or more of these.

Some variants of the embodiment provides a method of treating or preventing the disease or condition of the oral cavity comprising contacting the surface of the oral cavity with any of the compositions described in this document. In some embodiments embodiment the disease or condition of the oral cavity includes the disease or the condition of the teeth, mouth, gums or tongue. In some embodiments of the incarnation zābol�R or the condition of the oral cavity selected from caries gingivitis, periodontitis and halitosis (unpleasant breath).

In some embodiments embodiment the present invention provides a method of treating or preventing a disease or condition of the skin comprising contacting the skin surface of a subject in need, with any of the compositions described in this document. In some embodiments embodiment the disease or condition is selected from body odor, erythrasma, acne, impetigo, boils, folliculitis, cellulitis, carbuncles and toxic necrosis of the epidermis (syndrome Layla).

In some embodiments embodiment the method comprises repeatedly applying the composition to achieve the desired antibacterial effects in the subject. In some embodiments embodiment the composition is applied daily for several days, for example at least one week.

In some embodiments embodiment the compound of Formula (I) is a compound selected from

and

In some embodiments embodiment the composition also contains an active compound from an extract of Magnolia, selected from magnolol, honokiol, tetrahydroindole, tetrahydrocannabinol and combinations of two or more of them.

Suitable carrier materials include conventional and known nositelj�, used in the manufacture of toothpastes, tooth powders, prophylactic pastes, rinses for the mouth, drugs for sucking, chewing gum, granules and the like. As will be clear to experts in the art, the choice of the specific component carrier depends on the desired product form, including toothpastes, tooth powders, prophylaxis paste, mouthwash, drugs for sucking, chewing gum, gels, films, confectionery and the like.

In some embodiments, the oral composition also contains one or more components selected from cleansers, aroma tools, sweetening means, protivogaznyh funds, surfactants, modulators foaming, abrasives, tools, pH modifier, wetting agents, humectants, flavouring tools, dyes, abrasives, preservatives, fluoride ion sources, agents stimulating the production of saliva, softeners, viscosity modifiers, diluents, emulsifiers, nutrients, and combinations thereof. May include other optional additives.

Colorants, such as dyes, may represent a food coloring additives that are certified at the present time, according to the law on food, drug, and cosmetic� means, for use in food and food inside, including dyes such as FD&C Red No. 3 (sodium salt of tetraiodofluorescein), Food Red 17, disodium salt of 6-hydroxy-5-{(2-methoxy-5-methyl-4-sulfophenyl)azo}-2-naphthalenesulfonate acid, Food Yellow 13, sodium salt of mixture of mono - and disulfonic acids of chieftan or 2-(2-chinolin)indandiona, FD&C Yellow No. 5 (sodium salt of 4-p-sulfophenylazo-1-p-sulfophenyl-5-hydroxypyrazol-3-carboxylic acid), FD&C Yellow No. 6 (sodium salt of p-sulfophenylazo-B-naphthol-6-monosulfata), FD&C Green No. 3 (disodium salt of 4-{[4-(N-ethyl-p-sulfanilamide)phenyl]-(4-hydroxy-2-sulphonitric)methylene}-[1-(N-ethyl-N-p-sulfobutyl)-DELTA-3,5-cyclohexadienone], FD&C Blue No. 1 (disodium salt anhydrite trisulfonic acid), FD&C Blue No. 2 (sodium salt disulfonate acid indigotin) and their mixtures, in varying proportions. Usually the dyes, if they are present in very small quantities.

Suitable flavoring funds include, but are not limited to, natural and artificial odors. These flavorings may be chosen from synthetic fragrant oils and fragrant aromatics and/or oils, jevic and extracts derived from plants, leaves, flowers, fruits and so forth, and combinations thereof. Typical odorous oils include oil �this time curly, cinnamon oil, peppermint oil, clove oil, Bay oil, thyme oil, American juniper oil, oil of nutmeg, oil of Dalmatian sage, and oil of bitter almonds. These flavoring funds can be used individually or in mixture. Commonly used flavors include mints such as peppermint, artificial vanilla, derivatives of cinnamon, various fruit flavors, used individually or in mixture. In General, there can be used any flavouring remedies or dietary supplements, such as those described in Chemicals Used in Food Processing, publication 1274 by the National Academy of Sciences, S. 63-258. Usually flavoring means, if included, is present in a concentration of from about 0.01 to about 1 wt%. In some embodiments embodiment the flavoring agent may be present in a concentration of about 0.2% of the mass.

Sweeteners include both natural and artificial sweeteners. Suitable sweeteners include water soluble sweetening agents such as monosaccharides, disaccharides and polysaccharides such as xylose, ribose, glucose (dextrose), mannose, galactose, fructose (levulose), sucrose (sugar), maltose, water soluble artificial sweeteners such as soluble salts of saccharin, i.e., sodium or calcium salt of saccharin, podlas�a nd, based on cyclamate salts dipeptide sweeteners such as, derivatives of L-aspartic acid, such as L-aspartyl-L-phenylalanine methyl ester (aspartame). In General, an effective amount of sweetener that is used to provide the level of sweetness desired for a particular composition varies depending on your chosen sweetener. This quantity is normally from about 0.001 to about 5 wt%. In some embodiments embodiment the sweetener is a saccharinate sodium and is present in a concentration of about 0.01% wt.

Bleach, materials which are effective in achieving the effect of whitening tooth surfaces to which they are applied, such as hydrogen peroxide and urea peroxide, silicon dioxide high cleaning ability, preservatives, silicones and connection of chlorophyll can be included in compositions of the present invention. In various embodiments, the embodiment of the composition according to the invention contain peroxide whitening solution containing a peroxide compound. Peroxide is the oxidizing compound is a compound containing divalent oxygen-oxygen group. Peroxide compounds include peroxides and hydroperoxides, such as hydrogen peroxide, peroxides of alkali and alkaline earth metals, organic pyo�oxide compounds, peroxyacids, and their pharmaceutically acceptable salts and mixtures thereof. Peroxides of alkali and alkaline earth metals include lithium peroxide, potassium peroxide, sodium peroxide, peroxide of magnesium, calcium peroxide, barium peroxide, and mixtures thereof. Organic peroxide compounds include carbamide peroxide (also known as urea), glycerol, hydrogen peroxide, alkali hydrogen peroxide, dialkylamide, alkylperoxyl, complex peroxidase, diazepamonline, benzoylperoxide and monoperoxyphthalate and mixtures thereof. Peroxyacids and their salts include organic peroxyacids, such as alkylperoxyl and monoperoxyphthalate and mixtures thereof, as well as salts of inorganic peroxyketal, such as persulfate, diperchlorate, percarbonate, perphosphate, perborate and perserikatan salts of alkali and alkaline earth metals such as lithium, potassium, sodium, magnesium, calcium and barium and mixtures thereof. In various embodiments, the embodiment of the peroxide compound contains hydrogen peroxide, urea peroxide, sodium percarbonate and mixtures thereof. In some embodiments, embodiments of the peroxide compound contains a peroxide. In some embodiments, embodiments of the peroxide compound is composed mainly of hydrogen peroxide. In some embodiments, embodiments can be provided superoxide bleaching with�adsto. Whitening agents which are suitable according to this document include superoxide compounds such as chlorine dioxide, chlorites and hypochlorites. Chlorites and hypochlorites include those of alkali and alkaline earth metals such as lithium, potassium, sodium, magnesium, calcium and barium. Superoxide bleach also include colorants, such as titanium dioxide and hydroxyapatite. One or more bleaching agents in some cases are present in total amounts that are effective in whitening. In some embodiments embodiment the bleaching agent is separated from the aqueous medium. In some embodiments embodiment the bleaching agent is separated from the aqueous media encapsulation process a bleaching agent.

Optional, can be provided by means of refreshing your breath. Can be any orally acceptable means, breath freshening, including without limitation zinc salts such as zinc gluconate, zinc citrate, zinc oxide and zinc chlorite, α-ionone, and mixtures thereof. One or more means of refreshing your breath, can optionally be present in a total amount effective to freshen breath.

Optionally, the composition may include a means for controlling the formation of Tartar (anticalculus). Measures that control the formation of Tartar, among PR�fit on the document, include phosphates and polyphosphates (for example pyrophosphates), polyaminopropyl acid (AMPS), polyaluminosilicate, poliolefinas, diphosphonates such as azacycloheptane-2,2-diphosphonates (e.g., azacycloheptane-2,2-difosfonovoy acid), N-methylacetophenone-2,3-difosfonovoy acid, ethane-1-hydroxy-1,1-difosfonovoy acid (EHDP) and ethane-1-amino-1,1-diphosphonate, phosphoadenosine carboxylic acids and salts of any of these funds, for example, their alkali metal salts and ammonium salts. Suitable salts of inorganic phosphate and polyphosphate include monobasic, dibasic and tribasic sodium phosphate, sodium tripolyphosphate, metropolitical, mono-, di-, tri - and tetranitro pyrophosphates, trimetaphosphate sodium, sodium hexametaphosphate and mixtures thereof, in which sodium, optional, may be replaced by potassium or ammonium. Other suitable anti-calculus include polycarboxylate polymers and copolymers polivinilbutilovy ether/maleic anhydride (PVME/MA), such as is available from the company ISP, Wayne, N. J. under the brand name Gantrez™. In some embodiments embodiment, the phosphate is present in a concentration of from about 0.01 to about 10 wt%. In some embodiments embodiment, the phosphate is present in a concentration of from about 1% wt.

Some variants of the embodiment provides compositions that contain a buffering agent. In some�which variants of embodiment of monobasic sodium phosphate is present in a concentration of from about 0.01 to about 5 wt%. In some embodiments of the incarnation of monobasic sodium phosphate is present in a concentration of about 1 wt%. In some embodiments of the incarnation dibasic sodium phosphate is present in a concentration of from about 0.01 to about 5 wt%. In some embodiments of the incarnation dibasic sodium phosphate is present in a concentration of about 0.15% of the mass.

Other optional additives include antimicrobial (e.g., antibacterial) agent. Can be used any antimicrobial agent acceptable for oral use, including triclosan (5-chloro-2-(2,4-dichlorophenoxy)phenol); 8-hydroxyquinoline and salts thereof, sources of ions of zinc and tin, such as zinc citrate, zinc sulfate and zinc gluconate; copper compounds(II), such as copper chloride(II), fluoride, sulfate and hydroxide; phthalic acid and its salts, such as magnesium monomolecular; sanguinarine; Quaternary ammonium compounds such as the chlorides alkylpyridine (for example, cetylpyridinium chloride (CPC), combinations of CPC with zinc and/or enzymes, tetraarylporphyrin and N-tetradecyl-4-ethylpyridinium); biguanides, such as chlorhexidine digluconate, hexetidine, octenidine, alexidine; halogenated bisphenol compounds such as 2,2'-methylene-bis-(4-chloro-6-bromophenol); benzylaniline; salicylanilide, domainbased; iodine; sulfonamides; bisbiguanide; with phenolic�Ola; derivatives piperidino, such as delmopinol and Octafinal; grape seed extract; thymol; eugenol; menthol; geraniol; carvacrol; citral; eucalyptol; catechol; 4-allylation; geksilrezorzinol; salicylate. A sample list of other suitable antibacterial agents is provided in U.S. patent No. 5776435, Gaffar, et al., issued July 7, 1998 In some embodiments embodiment the antimicrobial agent is present in a concentration of from about 0.001 to about 1 wt%. In some embodiments embodiment the antimicrobial agent is a cetylpyridinium chloride. In some embodiments embodiment the cetylpyridinium chloride is present in a concentration of from about 0.001 to about 1 wt%. In other embodiments, the embodiment of the cetylpyridinium chloride is present in a concentration of about 0.05% of the mass.

Abrasives are another class of optional additives. Suitable abrasives include without limitation silica, for example in the form of silica gel, silicon hydroxide or precipitated silica, alumina, insoluble phosphates, calcium carbonate, resinous abrasives such as condensation products of urea with formaldehyde and the like. Among insoluble phosphates which are suitable as abrasives - orthophosphate, polymetaphosphate and pyrophosphates. Illustrative examples include dicalcium orthophosphate dehydrate, Pirogova� calcium β-calciparine, tricalcium phosphate, calcium polymetaphosphate and insoluble sodium polymetaphosphate.

Antioxidants are another class of optional additives. Can be any orally acceptable antioxidants, including butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), vitamin A, carotenoids, vitamin E, flavonoids, polyphenols, ascorbic acid and the antioxidant properties of medicinal herbs, chlorophyll, melatonin, and mixtures thereof.

Also it is possible to include a means of stimulating the production of saliva, for example, to irrigate the dryness of the mouth. Can be any orally acceptable means of stimulating the production of saliva, including, without limitation, food acids such as citric, lactic, malic, succinic, ascorbic, adipic, fumaric and wine-stone, and mixtures thereof. One or more agents stimulating the production of saliva, can optionally be present in quantities effective at stimulating the production of saliva.

Optional, can be enabled agent against dental plaque (e.g., destructive plaque). Can be used any orally acceptable agent against dental plaque, including, without limitation, salts of tin, copper, magnesium and strontium, copolyol dimetikona, such as copolyol of tetidination, papain, glucoamylase, glucox�Daza, urea, calcium lactate, calcium glycerophosphate, strontium polyacrylates and mixtures thereof.

Optional desensitizers tools include potassium citrate, potassium chloride, potassium tartrate, potassium bicarbonate, potassium oxalate, potassium nitrate, strontium salt, and mixtures thereof.

Optional additives include vitamins, herbs and proteins. Vitamins include vitamins C and D, thiamine, Riboflavin, calcium Pantothenate, Niacin, folic acid, nicotinamide, pyridoxine, cyancobalamin, pair-aminobenzoic acid, bioflavonoids, Pantothenic acid, retinyl palmitate, tocopherol acetate, and mixtures thereof. Herbs such as Chamomilla recutita, Mentha piperita, Salvia officinalis, and Commiphora myrrha can, optionally, be included. Suitable proteins include milk proteins and enzymes such as the enzymes that produce peroxide, amylase, products that destroy the plaque, such as papain, glucoamylase, glucosidase and enzymes "new generation".

S. aureus can cause a range of illnesses from minor skin infections, such as pimples, impetigo, boils, cellulites, carbuncles, toxic necrosis of the epidermis and abscesses, to diseases, life-threatening, such as pneumonia, meningitis, osteomyelitis, endocarditis, toxic shock syndrome and sepsis. S. aureus is also a frequent cause of nosocomial infections.

It is known that C. minutissimum and C. xerosis involved in the formation of �Apache body. C. minutissimum is also associated with erythrasma.

Variants of the embodiment of the present invention is further described in the following examples. The examples are merely illustrative and in no way limit the scope of the present invention, as described and claimed.

EXAMPLES

Example 1

Compounds of the present invention can be produced by chlorination diphenylene predecessor, such as magnolol or honokiol, chlorinating agent in the solvent.

For example, divinely precursor can react with chlorine in an inert solvent at a temperature of from about 0 to about 100°C, preferably from about 10 to about 80°C, and more preferably from about 10 to about 50°C. the Chlorination is achieved, if necessary, in the presence of a catalyst.

Divinely precursor can react with dichloroethane or acetic acid at room temperature for from about 2 to about 10 hours, a mixture of chlorinated diphenylene compounds. The mixture is subjected to chromatography, and each product is isolated in accordance with methods known to those skilled in the art.

Example 2

Table 1 (below) describes the antibacterial effectiveness of typical compounds of the present invention against conventional oral pathogens A. viscosus and S. mutans.

Table 1
Minimum inhibitory concentration (ppm)
The compound of Formula (II)MagnololTriclosan
The bacterium
A. viscosus0,5-1,0321-2
S. mutans0,5-1,0321-2

Example 3

The compound of Formula (II) was evaluated for its antibacterial efficacy against typical skin bacteria such as Staphylococcus aureus (S. aureus), Staphylococcus epidermidis (S. epidermidis), Corynebacterium minutissimum (C. minutissimum), Corynebacterium xerosis (C. xerosis) and Escherichia coli (E. coli). Been implemented [tests] zone of inhibition (ZOI), the minimum inhibitory concentration (MIC) test and the loss in a short period of time (long term), and the results are described in Tables 2-4 (below).

A. the Test zone of inhibition (ZOI)

The compound of Formula (II) was dissolved in polyethylene glycol (PEG 300) or in 100% ethanol at a concentration of 0.5%. 20 µl of each solution was placed on �separate filter disks and air dried for 20 minutes. After 20 minutes, drying the coated discs were placed on the bacterial lawn and the plates were incubated at 37°C for 18 hours, after which the ZOI was measured. The results are presented in Table 2 (below).

Table 2
Zone of inhibition (mm)
Active ingredient
S. aureusS. epiderm.C. minutissimumC. xerosis
0.5% of the compound of Formula (II) + PEG 30015162115
0.5% of the compound of Formula (II) + EtOH13151714
PEG 3000000
EtOH0 00

The data described in Table 2, demonstrate the antibacterial efficacy of a compound of formula (II) against four normal skin bacteria S. aureus and S. epidermidis (skin infections and soft tissue) and C. minutissimum and G. xerosis (bacteria that cause the smell).

B. Minimum inhibitory concentration (MIC)

MIC for four normal skin pathogens were evaluated for compounds of Formula (II) by applying the following method: preparing a two-fold dilution of a compound of Formula (II) in a 96-well plate and an equal number of bacteria was added to each well. After 18-24 hours of incubation, bacterial growth was measured using a spectrophotometric reader of microplates and determined MIC. The results are presented in Table 3 (below).

Table 3
Minimum inhibitory concentration (ppm)
Active ingredient
S. aureusS. epiderm.C. minutissimum C. xerosis
The compound of Formula (II) + PEG 30019,5399,7778
The compound of Formula (II) + EtOH393939156
PEG 300156156156625
EtOH3126256251250
Triclosan<2,44<2,44of 4.889,76

The results described in Table 3 (above) further demonstrate the antibacterial efficacy of a compound of Formula (II) against normal skin pathogens.

C. Test loss over short periods (long term)

Long term determines the effect the death of [act] test means for a pre-set exposure time. This test determines the effect of death from a tested means for a pre-set exposure time. Briefly, 1.2 ml of compound f�of rmula (II) + PEG 300 was transferred into a sterile test tube, which was added 0.2 ml of freshly prepared bacterial suspension (OD set at 0.1 at 620 nm) and gently stirred. The reaction was neutralized by 1 minutes or 5 minutes by adding a neutralizing environment. The reaction mixture was then diluted with latinoam broth 10 times and put on tablets (MCA agar for counting of microorganisms) for counting viable bacteria. The results are presented in Table 4 (below).

Table 4
Active ingredientTime
1 minute5 minutes
0.5% of the compound of formula (II) + PEG 30065,1887,37
0.5% of TCC56,5474,11

The data described in Table 4 (above), are further evidence of the antibacterial effectiveness of the compound of Formula (II).

Example 4

Antibacterial efficacy of a compound of Formula (II) measured in comparison with triclosan, using various tests. The results are presented below in Tables 5 and 6.

Table 5
Active ingredientZone of inhibition (mm)
S. aureusC. minutissimumE. coli
0.5% of the compound of Formula (II)20220
0.15% of triclosan502140

Table 6
Active ingredientMinimum inhibitory concentration (ppm)
S. aureusC. minutissimumE. coli
0.5% of the compound of Formula (II)2,449,71250
0.15% of triclosan<2,44of 4.88<2,44

Example 5

A quick investigation on the agar cups (RAP)

The compound of formula (II) is mixed with the main piece of solid soap and tested for any residual antibacterial activity against S. aureus and E. coli by a rapid research on the agar cups (RAPA). Briefly, the method involves washing of cups TSA samples of soap for 10 seconds, the content in the foam for another 40 seconds and finally, rinsing for 10 seconds. After drying in air for 30 minutes, 100 µl of freshly prepared bacterial suspension (density was set to 0.1 OD at 620 nm) was coated on the treated cups and then the cups were incubated at 37°C for 18 hours. Cups TSA, washed with ordinary tap water was used as negative control. The next day, bacterial colonies were counted and took the decimal logarithm (log10) [this number] and calculated the reduction. as a result of washing the samples. The results are summarized in Table 7 (below).

0,09
Table 7
Active ingredientThe logarithm of the reduction in the number of bacterial colonies
E. coliS. aureus
0.5% of the compound of Formula (II) in the soap0,506
A piece of soap0,004of 0.021
0,25% triclosan soap2,3872,409
0.4% of TCC soap0,1672,409

The data described in Table 7 (above), demonstrate that a piece of solid soap containing 0.5% of a compound of Formula (II) inhibits the growth of S. aureus 0.5 log that is >50% reduction in growth of this specific body.

Example 6

Table 8 (below) provides a typical form of a composition for caring for the oral cavity according to the present invention.

Table 8
Ingredient% wt./masses.
Water30
Sorbitol30
Glycerin15
Zeodent 11411
Zeodent l0510
Carboxymethylcellulose sodium 1,1
Flavoring1
Titanium dioxide0,5
The compound of Formula (II)0,5
Carrageenan0,4
Saccharinate sodium0,3
Sodium fluoride0,24

The form described in Table 8 (above), may be manufactured by methods known in the art. A typical method is shown below.

Can be made two premix. The sodium saccharinate, sodium sulfate and fluoride was dissolved in water to obtain a 1 premix. The compound of Formula (II) was added to a flavoring component and mixed until dissolution or dispersion, to obtain a premix 2. Resins (carboxymethylcellulose and carrageenan) and titanium dioxide were dispersible in glycerol and mixed for 5 minutes. Added sorbitol and the combination was mixed for another 5 minutes. The resulting mixture contains gel phase. Premix 1 was then added to the gel phase and mixed for about 5 minutes. Gel phase was transferred to a Ross mixer, to which was added silica and mixed for about 20 minutes at high imminent�STI under vacuum. Was then added to Premix 2 and sodium lauryl sulfate in a Ross mixer, in which the combination was mixed in a liquid state for about 10 minutes at low speed under vacuum.

Example 7

The compositions described in Tables 9 and 10 (below), can be manufactured according to known methods of manufacturing compositions for personal hygiene, for example, described in published patent application U.S. No. 2007/0048235. Table 9 provides the forms of standard liquid soap compositions of the present invention.

Table 9
Ingredient% wt./masses.
Water68,3
α-olefin sulfonate sodium22,3
Lauramide DEA3,1
Cocoamidopropyl betaine3,1
Sodium chloride0,6
Polyquaternium-71
DMDM Hydatoin0,4
Flavoring0,3
Lemon �iSlate 0,3
The compound of the Formula II0,5
The tetrasodium EDTA0,1
Gel Aloe vera0,01
Glycerin0,01

Table 10 (below) describes the shape of a typical composition of solid soap of the present invention.

Table 10
Ingredient% wt./masses.
Tall fat/bars of soap with laurinova acid96,7
Flavoring1,25
Diethylenetriaminepentaacetic acid, intenationa Sol0,025
Heteronomy acid0,017
Citric acid0,5
The compound of the Formula II0,5
Extrapone seaweed0,05
Tinopal CBS-X 0,005
Titanium dioxide0,8
Softben-10 Green ASF 140,2

As is clear to experts in the art, numerous changes and modifications may be made in the variants of implementation, described herein without going beyond the scope of this invention. Have in mind that all such variations fall within the scope of the attached claims.

1. The compound of Formula (I):

or its salt, in which
R1and R5independently selected from H, OH and alkoxy;
R2-R4and R6-R8independently selected from H, OH, F, Cl, Br and I;
R9and R10are C2-C8the alkenyl;
provided that
at least one of R1, R5and R7is a HE or alkoxy;
at least one of R2-R4, R6and R8represents F, Cl and br, or I; and
R2and R6represent Cl.

2. The compound according to claim 1, in which
R1and R5independently selected from OH or alkoxy; and R2and R6represent Cl.

3. The compound according to claim 1, wherein R1and R5represent OH.

4. The compound according to claim 1, wherein R1and R7represent Soboh� IT.

5. The compound according to claim 1, wherein the compound of Formula (I) has the structure of Formula (II):

6. The compound according to claim 1, wherein the compound of Formula (I) has the structure of Formula (III):

7. Antibacterial composition comprising the compound according to any one of claims. 1-6, and the media.

8. A composition according to claim 7, in which the carrier is an orally acceptable carrier.

9. A composition according to claim 7 in which the compound of Formula (I) is present in a concentration of from about 0.01 to about 1 wt.%.

10. A composition according to claim 7 in which the compound of Formula (I) is present in a concentration of from about 0.1 to about 0.75 wt.%.

11. A composition according to claim 7 in which the compound of Formula (I) is present in a concentration of about 0.5 wt.%.

12. A composition according to claim 7, further comprising one or more components selected from a fluoride ion source; means for controlling the formation of Tartar; buffer means; abrasive and a combination of two or more of them.

13. A composition according to claim 12, in which at least one of the one or more components is a source of fluoride ions selected from tin fluoride, sodium fluoride, potassium fluoride, sodium monofluorophosphate, fertilitate sodium, fertilitate ammonium, amine fluoride, ammonium fluoride, and combinations of two or more of them.

14. With�personages of treating or preventing a disease or condition of the oral cavity, comprising contacting the surface of the oral cavity of a subject in need, with a composition according to any one of claims. 7-13.

15. A method according to claim 14, wherein the disease or condition of the oral cavity selected from gingivitis, periodontitis and bad breath.

16. A composition according to claim 7, in which the carrier is a carrier for personal care products.

17. A method of treating or preventing the disease or condition of the skin comprising contacting the skin surface of the needy in this subject a composition according to claim 16.

18. A method according to claim 17, wherein the disease or condition is selected from body odor, erythrasma, acne, impetigo, boils, folliculitis, cellulitis, carbuncles and toxic necrosis of the epidermis.



 

Same patents:

FIELD: medicine.

SUBSTANCE: method involves: a) preparing a polymer matrix film containing a water-soluble polymer and a hydrophobic/lipophilic additive and being substantially free from a poorly-soluble flavour; b) preparing a dental care base containing the poorly-soluble flavour; c) combining the polymer matrix film with the prepared base; and d) keeping the combined polymer matrix film and base for the period of time adequate to transfer an effective amount of the above flavour from the base of the dental care agent into the above polymer matrix film. That involves using the flavour specified in a certain list of poorly-soluble flavours (menthol, thyme oil, etc.), and one or more hydrophobic/lipophilic additives specified in a group of specific additives (Vaseline, silicone oil, etc.). The agent prepared by the above method has the same characteristics as the agents prepared by a common method, when the prepared films containing the flavour are added to the base of the dental care agent.

EFFECT: method provides such advantages as compared to the common method for preparing these agent, as a possibility to avoid using ethanol in preparing the film, otherwise required to solve the flavours if following the common method for preparing the film, as well as eliminating the flavour loss in heating during the film drying.

14 cl, 9 tbl, 2 ex

FIELD: cosmetology.

SUBSTANCE: invention is a natural cosmetic oil for face and body skin care, based on olive plant oil, sterilized under conditions of water bath, where the olive plant oil is used as highly purified first cold pressed olive oil, sterilized under conditions of water bath, with the temperature made up to 100°C, for 5-7 hours and treated for 30-40 min using the device with ultra-small electricity values ranging from 100 to 500 nA to the pH 5.1-5.5 of the final product.

EFFECT: expanding the arsenal of means for face and body skin care.

2 ex

FIELD: medicine.

SUBSTANCE: method for producing an oral care composition involves preparing a mixture of dental powder and biologically active ingredients, wherein the biologically active ingredients are pale Indian plantain fresh leaves tincture in 60% ethanol; the prepared infusion 50 g is mixed with dental powder 75 g, cooled at temperature from 18°C to 25°C, mixed until the moisture evaporates, and the mixture is ground in a mill. The pale Indian plantain tincture is either filtered, or contains ground leaves.

EFFECT: antibacterial and wound healing action on the oral cavity, applicable for daily use; the qualitative and quantitative formulation of the composition is balanced so that the dental powder has preventive and health-improving action.

3 cl

Elastase inhibitor // 2548794

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical and cosmetic industries, namely to an elastase inhibitor. The elastase inhibitor containing active ingredients presented by raspberry (Rubus idaeus L.) extract and hydroxyproline in the dry state in a certain amount, wherein the raspberry extract is prepared by using an extraction solvent specified in a group consisting as follows: water, methanol, ethanol, hydroethanol, 1,3-butylene glycol, acetone and/or ethyl acetate. The composition for external skin application containing the elastase inhibitor.

EFFECT: agent is the effective elastase inhibitor.

6 cl, 2 dwg, 6 ex

FIELD: cosmetology.

SUBSTANCE: invention is a perfumery-cosmetic product for care of normal and dry skin, containing the active ingredient and thermal and/or mineral water. As the active ingredient the product comprises a thick licorice extract, and water is used as water from the well SUV-1, in which silver sulphate and essential oils of peppermint or lavender are preliminary dissolved. The components in the product are in a certain ratio, and the product is obtained by gradual and successive adding and mixing the components at room temperature.

EFFECT: more efficient and beneficial effect with the highest tonic effect.

5 tbl

FIELD: chemistry.

SUBSTANCE: invention represents a cosmetic preparation for skin in the form of a "water-in-oil" type emulsion, which contains water, ethanol, volatile oily component, carboxydecyltrisiloxane of formula (1): 0.1-5 wt % and one, two or more components, selected from the group, consisting of hydrophibised titanium dioxide, hydrophibised zinc dioxide and hydrophibised iron dioxide.

EFFECT: removal of powder squeakiness on the skin in the course of time after application and simultaneous improvement of absorption into the skin during application and absence of stickiness after application on the skin.

3 cl, 2 tbl, 8 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to oral hygiene preparations. An oral care composition contains a) an aqueous phase; b) stannous tin ions dissolved in the aqueous phase; c) nitrates in the aqueous phase; wherein total nitrates is that a molar amount of nitrogen measured as a nitrate in the aqueous phase makes 1.8-0.1 of the molar amount of stannous tin ions; and d) a flavouring agent. What is also presented is a method for storage and a storage container for this composition; using nitrate for stabilising oxidised stannous tin ions dissolved in the aqueous phase. What is also presented is also a version of the composition, wherein the composition is aqueous.

EFFECT: using the group of inventions stabilises oxidised stannous tin ions dissolved in the aqueous phase by the above molar ratio of nitrate and stannous tin ions.

17 cl, 2 tbl, 15 ex

FIELD: chemistry.

SUBSTANCE: invention relates to versions of cationic polyelectrolytic composition for application in personal care products and household chemicals and method of its obtaining. Composition includes: 1) cationic synthetic water-soluble polyelectrolyte, which contains (meth)acrylamide polymer and one or several of the following substances: I) cationic (meth)acrylamide monomer, and II) cationic monomer of (meth)acrylic acid, and III) hydrolysis-resistant cationic monomers, where polyelectrolyte has weight average molecular weight from approximately 10000 to approximately 2000000, charge density from, 0.001 to 2.5 meq./g, and level of acrylamide monomer that did not react constitutes less than 50 ppm, 2) surface-active substance and 3) solvent.

EFFECT: preparations, obtained on the base of composition, possess higher transparency.

17 cl, 3 dwg, 12 tbl, 106 ex

FIELD: personal use articles.

SUBSTANCE: group of invention relates to oral care means suitable for application with oral care appliances and their use methods. The oral care comprises the following components: 5 - 45 wt % of antibacterial agent selected from among copper (II) compounds, zinc ions sources, phthalic acid and salts thereof, hexetidine, octenidine, sanguinarine, benzalkonium chloride, domiphen bromide, alkylpyridine chlorides, iodine, sulphanilamides, bis-biguanides, magnolia extract, grapeseed extract, Augmentin, amoxicillin, tetracycline, doxycycline, minocycline, metronidazole, neomycin, kanamycin and clindamycin; 5 - 70 wt % of a flavouring agent and an orally acceptable liquid carrier The composition has certain viscosity parameters. Additionally proposed are a method for introduction of the antibacterial agent into a mammal's oral cavity using such composition; an oral care device including an oral care appliance including a vessel, positioned inside it and accommodating the said composition, as well as an applicator element and a transfer mechanism for the composition transfer from the vessel to the applicator element surface; as well as application of the said composition for introduction of the antibacterial composition into the oral cavity with the help of the above device.

EFFECT: usage of the group of inventions ensures the possibility of efficient antibacterial effect, reduction of the quantity of volatile sulphur compounds and, optionally, a cooling sensation in the oral cavity in case of usage of such insignificant quantity of the composition as 50 ml.

20 cl, 4 tbl, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to cosmetic industry, and represents a cosmetic skin care composition of oil-in-water emulsion containing (a) paraffin wax and/or polyethylene wax, (b) microcrystalline wax and (c) animal/vegetable wax, which as a basic ingredient contains ester of higher fatty acid containing 20 to 32 carbon atom, and alcohol containing 28 to 34 carbon atoms, and has a melting point falling within the range of 75 to 100°C, wherein the ratio of the ingredient (a) and the ingredient (b) falls within the range of 70/30 to 95/5 wt., a total amount of the ingredient (a) and the ingredient (b) falls within the range of 0.01 to 2 wt % and an amount of the ingredient (c) falls within the range of 0.005 to 2 wt %.

EFFECT: invention provides the excellent sensation of skin plasticity and elasticity with no stickiness and stability.

2 cl, 2 tbl, 8 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical industry, and represents a pharmaceutical composition in the form of gel, which contains clindamycin phosphate, a combination of gel-forming polymer and hydrophilic dispersion phase, pH control agent, allantoin and lauryliminodipropionate sodium tocopheryl phosphate; the ingredients of the composition are taken in certain ratio, in g per 100 g.

EFFECT: invention provides the high level of antibacterial activity and stability.

5 cl, 1 tbl

FIELD: medicine.

SUBSTANCE: present group of inventions refers to medicine, namely to dermatology, and concerns treating telangiectasia or related symptoms. To this effect, an involved skin area is coated with a composition containing from approximately 0.4 wt % to approximately 0.6 wt % brimonidine providing its blood serum or plasma concentration, Cmax of approximately 54±28 pg/ml or less and AUC0-24h of approximately 568±277 pg·h/ml or less.

EFFECT: method provides the effective treatment of telangiectasia or related symptoms with no side local and systemic effects.

20 cl, 6 dwg, 6 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to the pharmaceutical industry and represents a composition for treating acne, rosacea and hyperpigmentation, in the form of a gel which contains anchoic acid, a hydrophobic ingredient, a non-aqueous solvent, an emulsifying agent, a gel-forming polymer, a preserving agent, a pH control agent and additionally methylpyrrolidone with anchoic acid having a particle size of less than 100 mcm, while anchoic acid is related to methylpyrrolidone as 1:0.025 to 1:4.

EFFECT: invention provides easy penetration of anchoic acid through a horny layer and its resolution into the oil grand ducts and between skin cells, providing high concentration of anchoic acid that promotes better antibacterial, keratolytic and de-pigmentation effects.

5 cl, 2 tbl, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to a compound of Formula

,

where Y represents a group of formula -(CR9R10)-; X is selected from the group, consisting of -C(=O)-, -OC(=O)-, -NHC(=O)-, -(CR11R12)- and -S(-O)2-; Z represents a group of formula -(CR13R14)q-; R1 is selected from the group, consisting of C1-C12alkyl, optionally substituted with one substituent, selected from naphthyl, indole and biphenyl; C2-C12alkenyl, substituted with a substituent, selected from thienyl, naphthyl and phenyl, with the said phenyl being optionally substituted with 1-2 substituents; selected from halogen, trifluoroalkyl, C1-C6alkyl, methoxy and hydroxy; C3-C6cycloalkyl; C6-C10aryl, optionally substituted with 1-2 substituents, selected from halogen, phenyl, amino, phenoxy, C1-C6alkyl, methoxy, hydroxyl and carboxy; and C4-C9heteroaryl, selected from indole, quinoline, quinoxaline, benzofuranyl, benzothiophene, benzimidazole, benzotriazole, benzodioxin, benzothiasole, pyrazole, furyl and isoxazole, optionally substituted with a substituent, selected from C1-C6alkyl and phenyl; R2 and R3 each is independently selected from the group, consisting of H and C1-C12alkyl; R4a is selected from the group, consisting of H, C1-C12alkyl, optionally substituted with phenyl; C2-C12alkenyl, C3-C6cycloalkyl, C6aryl, C(=O)R15, C(=O)NR15R16, C(=O)OR15, SO2R15 and -C(=NR15)-NR16R17; R4d represents hydrogen or R4a and R4b, taken together with a nitrogen atom, which they are bound to, form an optionally substituted heterocyclic fragment, selected from piperidine, morpholine, pyrrolidine and azetidine, where the substituent is selected from C1-C12alkyl, hydroxy, halogen, carboxy and oxo; each R5a and R5b represents H, or R6, R7 and R8 each is independently selected from the group, consisting of H, C1-C12alkyl, C3-C6cycloalkyl, C6-C10aryl, optionally substituted with halogen, or taken together with a carbon atom, which they are bound to, two or more of R6, R7 and R8 form a fragment, selected from the group, consisting of C2-C12alkenyl; C3-C6cycloalkyl, optionally substituted with C1-C6alkyl; C6aryl, optionally substituted with 2 substituents, selected from halogen; each R9 and R10 represents H or C1-C12alkyl, substituted with naphthyl; each R11 and R12 represents H; R13 and R14 represent H, or each R15, R16 and R17 is independently selected from the group, consisting of H, C1-C12alkyl, C3-C6cycloalkyl, C6aryl, substituted with one substituent, selected from C1-C6alkyl; and C5-heteroaryl, additionally containing one nitrogen atom, with the said heteroaryl representing pyridyl; q represents an integer number, selected from the group, consisting of 2, 3 and 4; r represents 1; or its pharmaceutically acceptable salt. The invention also relates to particular compounds of 1,4-diazepan-2-one derivatives.

EFFECT: obtaining 3-aminoalkyl-1,4-diazepan-2-one melanocortin-5 receptor antagonists.

21 cl, 7 tbl, 110 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to dermatology, and can be used for selecting a therapeutic approach to acne in females by examining biological fluids and prescribing preparations depending on the clinical findings. The biological fluids are blood and urine; blood serum hormones and steroid urine profile are tested, and the derived values are compared to the standard norms specific for the absence of acne, while the preparations are prescribed according to the comparison results. Specifically, if observing an increase of blood luteinising hormone up to 16 mIU/ml, testosterone up to 4 ng/ml, an increase of urine androsterone up to 20 mcmole/24 hours, etiocholanolone up to 11 mcmole/24 hours, total 17-ketosteroids up to 35 mcmole/24 hours, van de Calseyde's discriminant up to 3, the combined oral contraceptive Jess with the anti-androgenic effect. If also observing an increase of immunoreactive protein up to 12.90 mcUnit/ml and insulin-line growth factor 1 up to 361.04 ng/ml, the combined oral contraceptive Jess and Metformine or Metformine are prescribed. If observing a decrease of blood oestradiol up to 140 pmole/l or an increase of the concentration of luteinising hormone up to 7 mIU/ml, dihydroepiandrosterone sulphate up to 4 mmole/l, 17 - hydroxyprogesterone up to 4 nmole/l and testosterone up to 4 nmole/l in blood and an increase of urine androsterone up to 17 mcmole/24 hours, etiocholanolone up to 17 mcmole/24 hours, 11 - ketoandrosterone up to 2.5 mcmole/24 hours, 11 - ketoetiocholanolone up to 2.5 mcmole/24 hours, 17 - ketosteroids up to 50 mcmole/24 hours and van de Calseyde's discriminant up to 3, the glucocorticoid Metypred is prescribed. The high blood concentration of luteinising hormone up to 15 mIU/ml, dihydroepiandrosterone sulphate up to 6.82 mcmole/l, 17 - hydroxyprogesterone up to 4 nmole/l and an increase of urine androsterone up to 19.5 mcmole/24 hours, etiocholanolone up to 16 mcmole/24 hours, dihydroepiandrosterone up to 7 mcmole/24 hours, 17 - ketosteroids up to 45 mcmole/24 hours and van de Calseyde's discriminant up to 3.5 enables using the combined oral contraceptive Jess and the glucocorticoid Metypred. And the preparation Dostinex is prescribed in observing the above values in a combination with an increase of blood prolactin up to 750 IU/ml and a decrease of blood oestradiol up to 95.48 pcg/ml.

EFFECT: method enables providing higher therapeutic selectivity and clinical effectiveness in acne without the need of thorough examination to be conducted.

4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to field of pharmaceutics, in particular represents composition for topic application, which includes, into physiologically acceptable medium at least one derivative of naphthoic acid, benzoylperoxide and at least one film-forming component.

EFFECT: invention is characterised by the fact that said compound of naphthoic acid and benzoylperoxide are in dispersed in said composition form.

23 cl, 14 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to an herbal formulation of topical nanoemulsion for treating acne-related skin disorders. The above formulation contains an aqueous phase comprising a therapeutic agent, rose water and/or lemon juice, and an oil phase containing an essential oil, a non-ionic surfactant and an accessory surfactant. The aqueous and oil phases are related within the range of 1:1 to 1:2, while a particle size of the herbal formulation is less than 5 nm. The essential oil is presented by tea tree oil, basil oil, rosemary oil, lavender oil, jojoba oil, bergamot oil, clove oil and peppermint oil. The invention also refers to a method for preparing the herbal formulation which involves providing the aqueous and oil phases, mixing the above phases to produce a mixture to be emulsified with the non-ionic surfactant to prepare a macroemulsion. The prepared macroemulsion is mixed with ethanol to produce a nanoemulsion with a particle size less than 5 nm.

EFFECT: invention provides the herbal formulation with good penetration, prolonged effect causing no irritation.

8 cl, 4 dwg, 7 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to compounds of the following formula , in which n equals integer number from 1 to 15, m equals 0, 1, 2 or 3, and R represents hydrocarbon chain of polyunsaturated fatty acid, selected from omega-3 and omega-6 polyunsaturated fatty acids, and to method of obtaining them.

EFFECT: development of pharmaceutical or cosmetic composition based on said compounds and to method of acne or seborrheic dermatitis treatment for cosmetic purposes.

16 cl, 4 dwg, 2 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to a compound of formula (I)

where Y represents a group of formula -(CR9R10)n-; X represents -C(=O)-; Z represents a group of formula -(CR13R14)q-; R1 is selected from a group, consisting of (a) C2-C12alkenyl, substituted with 4-chlorophenyl; or (b) C6-C10aryl, optionally substituted with one or two halogen atoms; R2 and R3 represent H; R4 is selected from a group, consisting of H, C1-C12alkyl, optionally substituted with hydroxyl, methoxy or benzyloxy, C3-C12cycloalkyl, C6aryl, optionally substituted with an amino group or pyperidine, C-bound C1-C18heteroaryl, selected from pyridine and imidazole, C(=O)R15, C(=O)NR16R17 and ONR16C(=NR17)NR18R19; each R5a and R5b represents H, each R6, R7 and R8 is independently selected from a group, consisting of H, C1-C12alkyl and C6-C18aryl, each R9 and R10 represents H; each R13 and R14 represents H; R15 represents H, each R16, R17, R18, R19 and R20 is independently selected from a group, consisting of H, C1-C12alkyl, C3-C12cycloalkyl, C6aryl and pyridyl, or any two of R16, R17, taken together with atoms, to which they are bound, form a cyclic group, containing 5 carbon atoms, or n equals to 1; q represents an integer number, selected from a group, consisting of 1, 2, 3, 4 and 5; r equals to 1; or its pharmaceutically acceptable salt.

EFFECT: invention relates to a pharmaceutical composition for treatment of MC5R-associated conditions, which contains a formula (I) compound and a pharmaceutically acceptable carrier, a diluent or a filling agent.

23 cl, 6 tbl, 53 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to pharmaceutical industry, in particular to a composition, possessing immunomodulating and anti-inflammatory properties. The dermatological composition, possessing immunomodulating and anti-inflammatory properties, as an active ingredient, contains an extract of the aboveground part/parts of oat, collected before ear formation. The cosmetic composition, possessing immunomodulating and anti-inflammatory properties. Application of the extract of the aboveground part/parts of oat, collected before ear formation, possessing immunomodulating and anti-inflammatory properties, as a medication.

EFFECT: composition and extract possess expressed immunomodulating and anti-inflammatory properties.

15 cl, 1 tbl, 3 ex

FIELD: medicine.

SUBSTANCE: agent for treating inflammatory periodontal and oral mucosal diseases associated with Helicobacter infection contains silicone glycerohydrogel of Si(C3H7O3)4·6C3H8O3·24H2O and bismuthate tripotassium dicitrate of formula [HOC(CH2COO)2COO]2K3Bi in the following proportions, wt %: bismuthate tripotassium dicitrate 1.0-2.5; silicone glycerohydrogel - the rest up to 100. The method of treating inflammatory periodontal and oral mucosal diseases consists in a combination of systemic standard anti-Helicobacter therapy and a local effect of the above agent on the involved region. Particularly, treating periodontitis is ensured by applying the agent on the gingival surface and introducing it into the gingival pockets once a day for 10 min; the therapeutic course makes 5-6 days. The oral mucosal diseases are treated by applying the agent 0.1 mm thick with a glass spatula on the involved oral mucosa 2 times a day; the therapeutic course is 12 days.

EFFECT: formulation of the agent provides achieving the high therapeutic effect; the dosage form is easy to be applied locally.

4 cl, 2 dwg, 1 tbl, 2 ex

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