New peroxide derivatives, method for preparing them and using in medicine and cosmetics for treating or preventing acne

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to a compound of formula such as below , wherein Z is oxygen; Y is hydrogen or a sequence as follows: -O-C(R4)-V-(C=O)-R5; V is oxygen; R1 and R4 are identically or independently hydrogen or a C1-4 alkyl; R2 and R5 are identically or independently a C1-10 alkyl.

EFFECT: these compounds can be applicable in therapy for treating pathologies or disorders related to the presence of Propionibacterium acnes, eg acne-like skin disorders.

5 cl, 2 tbl, 2 ex

 

Acne is staggering 90% of all Teens and twenty and thirty men and women, or they can even persist throughout adulthood. The process of development of acne is described in W. J. Cunliffe in "New Approaches to Acne Treatment", published by Martin Dunitz, London, 1989.

Common acne (acne vulgaris) are a chronic disorder pilosebaceous follicles (pilosebaceous apparatus), which is characterized by black acne (blackheads), papules, pustules, cysts, nodules and often scars that appear on the most visible areas of the skin, namely on the face, chest, back and sometimes my neck and shoulders.

Philosophicaly the device is largely under the control of endogenous hormones (mainly androgens), which are present in unusually high concentrations in the blood during adolescence and puberty and cause the formation of excess sebum. This situation may deteriorate as a result of a concomitant increase in the degree of keratinization of the stratum corneum of the skin (stratum corneum). Because the cells of the stratum corneum proliferate, they can form a sealing mass or acne, which in combination with increased formation of sebum are the perfect environment for the proliferation of strains of bacteria that reside in and on the skin, such as gram-positive anaerobic bacteria�AI Propionibacterium acnes.

The affected follicles may darken due to the deposition of pigment, derived from damaged cells of the deep layer of the skin.

Acne is a condition passing several stages, and the most severe form leads to hospitalization of the patient and is very problematic from the viewpoint of long-term scars on the skin.

There is a need for improved treatment of acne, which will effectively prevent the development of the state down to its most severe form and which can be applied without causing side effects in the majority of affected patients.

Currently available in a variety of ways to treat acne, but unfortunately, each method of treatment has limitations, which are desirable to overcome.

In most cases treatment of acne includes local compositions in the form of creams, gels, emulsions or lotions containing the selected funds.

These tools include, for example, hormones or agonists and antagonists of hormones (EPA1 0563813 and US 5439923), antimicrobial agents (US 4446145, GB 2088717, GB 2090135, GB 1054124, US 5409917), salicylic acid (US 4514385, US 4355028, EPA1 0052705, FR-A 2581542 and FR-A 2607498).

The problems associated with topical treatment of acne creams, gels, emulsions or lotions include the lack of punctuality of application and the lack of accurate control of the dose in suspected places� processing. Cream, gel, emulsion or lotion includes the processing area that is significantly larger than amazed, so normal healthy skin is also exposed to zit composition. Salicylic acid, for example, irritate the normal skin in case of prolonged exposure, especially in high concentrations.

Oral administration zit remedies usually used in severe cases prevage defeat. It discusses Sykes N. I. and G. Webster In "Acne, A Review of Optimum Treatment", Drugs 48, 59-70 (1994). Many of the side effects described in the introduction zit active compounds by oral.

For example, isotretionin, which is a derivative of vitamin A, causes the risks of teratogenicity and may be dangerous for women of childbearing age.

Oral administration of antibiotics suitable for the treatment of acne, may be accompanied by side effects such as cramps in the abdomen, glasstite, cough, diarrhea, fatigue, irritation of the mouth and other undesirable symptoms.

Therefore, there is a clear medical and cosmetic needs in the treatment of disorders and related pathologies.

In this context, the present invention offers new derivatives of peroxides having improved zit efficiency, which results�atom, for example, the best bacterial activity compared with compounds known to the prior art, such as benzoyl peroxide, while controlling for potential sensitising effects, irritant effects, without adding anti-inflammatory component.

Thus, the present invention relates to compounds of the following General formula (I):

in which:

- Z is an oxygen or the following sequence:

- Y is a hydrogen or the following sequence:

- V is an oxygen or the following sequence:

-R3 and R6 are, same or independently, a hydrogen or C1-4by alkyl;

-R1 and R4 are, identically or independently, a hydrogen or C1-4by alkyl;

-R2 and R5 are, identically or independently, C1-10the alkyl or C1-10alkoxy.

In accordance with this invention, the preferred compounds corresponding to General formula (I), are compounds having the following characteristics:

- Z is an oxygen or the following sequence:

- Y is a hydrogen or the following sequence:

- V is�tsya oxygen or the following sequence:

-R3 and R6 are, same or independently, a hydrogen bromide or ethyl;

-R1 and R4 are, identically or independently, a hydrogen or bromide;

-R2 and R5 are, identically or independently, C1-4the alkyl or C1-4alkoxy.

In accordance with this invention C1-4alkyl means a saturated linear or branched hydrocarbon chain containing from 1 to 4 carbon atoms.

In accordance with this invention C1-10alkyl means a saturated linear or branched hydrocarbon chain containing from 1 to 10 carbon atoms.

In accordance with this invention C1-4alkoxy means an oxygen atom substituted C1-4the alkyl.

In accordance with this invention C1-10alkoxy means an oxygen atom substituted C1-10the alkyl.

Among the compounds of the General formula (I), included in the scope of this invention, it is especially necessary to note the following:

Example 1: the peroxide is bis(2-acetoxymethyl)benzoyl

Example 2: peroxide (2-acetoxyacetyl)benzoyl

Example 3: the peroxide bis(2-propionylacetate)benzoyl

Example 4: the peroxide (2-propionylacetate)benzoyl

Example 5: the peroxide bis(2-butyrylacetate)benzoyl

Example 6: peroxide (2-butyrylacetate)benzoyl

Example 7: Perek�camping bis(2-pentanedionate)benzoyl

Example 8: the peroxide (2-pentanoneoxime)benzoyl

Example 9: the peroxide bis(2-isobutyrylacetate)benzoyl

Example 10: peroxide (2-isobutyrylacetate)benzoyl

Example 11: the peroxide bis[2-(2,2-dimethylphenylacetate)]benzoyl

Example 12: peroxide [2-(2,2-dimethylphenylacetate)benzoyl]benzoyl

Example 13: the peroxide bis[2-(1-acetoacetate)]benzoyl

Example 14: peroxide [2-(1-acetoacetate)benzoyl]benzoyl

Example 15: the peroxide bis(2-ethoxycarbonylmethoxy)benzoyl

Example 16: peroxide (2-ethoxycarbonylmethoxy)benzoyl

Example 17: the peroxide bis(2-propoxycarbonyl)benzoyl

Example 18: peroxide (2-)benzoyl

Example 19: the peroxide bis(2-butoxycarbonyloxyimino)benzoyl

Example 20: peroxide (2-)benzoyl

Example 21: the peroxide bis(2-isopropoxycarbonyloxymethyl)benzoyl

Example 22: peroxide (2-)benzoyl

Example 23: the peroxide bis(2-tert-butoxycarbonyloxyimino)benzoyl

Example 24: peroxide (2-tert-)benzoyl

Example 25: the peroxide bis[2-(ethoxycarbonylmethoxy)]benzoyl

Example 26: peroxide [2-(ethoxycarbonylmethoxy)benzoyl]benzoyl

Example 27: the peroxide b�with(2-[(ethoxycarbonylmethylene)methoxy)benzoyl

Example 28: peroxide (2-[(ethoxycarbonylmethylene)methoxy]benzoyl)benzoyl

Example 29: the peroxide bis(2-[(ethoxycarbonylmethylene)methoxy)benzoyl

Example 30: peroxide (2-[(ethoxycarbonylmethylene)methoxy]benzoyl)benzoyl

Example 31: the peroxide bis(2-[(methylpropionamidine)methoxy)benzoyl

Example 32: peroxide (2-[(methylpropionamidine)methoxy]benzoyl)benzoyl

Example 33: the peroxide bis(2-[(butoxycarbonylmethylene)methoxy)benzoyl

Example 34: peroxide (2-[(butoxycarbonylmethylene)methoxy]benzoyl)benzoyl

Example 35: the peroxide bis(2-[(isopropoxycarbonyl)methoxy)benzoyl

Example 36: peroxide (2-[(isopropoxycarbonyl)methoxy]benzoyl)benzoyl

Example 37: the peroxide bis(2-[(tert-butoxycarbonylmethylene)methoxy)benzoyl

Example 38: peroxide (2-[(tert-butoxycarbonylmethylene)methoxy]benzoyl)benzoyl

Example 39: the peroxide bis[2-(1-ethoxycarbonylmethoxy)]benzoyl

Example 40: peroxide [2-(1-ethoxycarbonylmethoxy)benzoyl]benzoyl.

A General description of the methods for obtaining compounds of formula (I) are shown below. These drawings and the following description of the method, unless otherwise indicated, all substituents such as defined for compounds of formula (I).

If the group Y defined in the formula (I) is hydrogen, compounds of the General Fort�uly (I) is prepared according to reaction scheme 1 or reaction scheme 2, below.

Scheme 1

According to scheme 1, the acid chlorides of the General formula (III) is prepared from the carboxylic acid (II) by methods selected from known to those skilled in the art (EP 1219682). They include the use of thionylchloride and pyridine in a solvent such as toluene or dichloro methane, for example.

Carboxylic acids of the General formula (II) is prepared according to the methods described in scheme 7.

At the final stage of the compounds of the General formula (V) can be obtained by the combination between chloride atilov of formula (III) and peracids of formula (IV) with the use of pyridine as base in a mixture of solvents such as dichloro methane and chloroform (Evanochko, W. T.; Shevlin, P. B.; J. Org. Chem. 1979, 44(24), 4426-4430).

The superacid of the General formula (IV) is prepared according to the method described in scheme 8, from benzoyl peroxide.

Scheme 2

According to the scheme 2 peroxide of the General formula (V) is prepared by a combination of carboxylic acids of formula (II) and peracids of formula (IV), for example, using Ν,Ν'-dicyclohexylcarbodiimide as agent combinations, for example, in a mixture of solvents, such as diethyl ether and dichloro methane (Spantulescu, M. D.; Jain, R. P.; Derksen, D. J.; Vederas, J. C.; Org. Lett. 2003, 5(16), 2963-2965).

Carboxylic acids of the General formula (II) is prepared according to the methods described in scheme 7.

The superacid f�of rmula (IV) is prepared in accordance with the method, described in scheme 8, from benzoyl peroxide.

If the group Y defined in formula (I) is not hydrogen, if the group R1 as defined in formula (I), is identical to the group R4, if the group R2 defined in the formula (I), is identical to the group of R5, and if the group Z defined in formula (I) are the same group V compounds of the General formula (I) is prepared in accordance with reaction scheme 3 or reaction scheme 4 below.

Figure 3

According to scheme 3, the anhydrides of the General formula (VII) is prepared from a carboxylic acid (VI) by methods selected from known to those skilled in the art (EP 1219682). They include the use of thionylchloride and pyridine in a solvent such as toluene or dichloro methane, for example.

Carboxylic acid of the General formula (VI) is prepared according to the methods described in scheme 7.

At the final stage of the compounds of the General formula (VIII) can be obtained by a combination between the two chloride atilov of formula (VII) by methods selected from known to those skilled in the art (EP 0108821). They include the use of hydrogen peroxide and sodium bicarbonate in a solvent such as tetrahydrofuran, for example.

Scheme 4

According to the scheme 4 peroxide of the General formula (VIII) is produced by interaction between two carboxylic acids of the formula (VI) � application, for example, N,N'-dicyclohexylcarbodiimide and hydrogen peroxide in a mixture of solvents, such as diethyl ether and dichloro methane (Spantulescu, M. D.; Jain, R. P.; Derksen, D. J.; Vederas, J. C.; Org. Lett. 2003, 5(16), 2963-2965).

Carboxylic acids of the General formula (VI) is prepared in accordance with the methods described in scheme 7.

If the group Y defined in formula (I) is not hydrogen, if the group R1 as defined in formula (I), differs from group R4, if the group R2 defined in the formula (I), differs from the group of R5, and if the group Z defined in formula (I) is different from the group V, compounds of the General formula (I) is prepared in accordance with reaction scheme 5 or scheme 6, below.

Scheme 5

According to scheme 5, the anhydrides of the General formula (III) is prepared from the carboxylic acid (II) by methods selected from known to those skilled in the art (EP 1219682). They include the use of thionylchloride and pyridine in a solvent such as toluene or dichloro methane, for example.

Carboxylic acids of the General formula (II) is prepared in accordance with the methods described in scheme 7.

At the final stage of the compounds of the General formula (X) can be obtained by the combination between chloride atilov of formula (III) and peracids of formula (IX), for example, with the use of pyridine as base in a mixture of solvents, such as d�chloromethane and chloroform.

The superacid of the General formula (IX) is prepared in accordance with the method described in scheme 9, from peroxide as defined in formula (VIII).

Scheme 6

According to the scheme 6 peroxide of the General formula (X) are obtained by combination between the carboxylic acids of formula (II) and superacid of formula (IX), for example, using Ν,Ν'-dicyclohexylcarbodiimide as a combining agent in the mixture of solvents such as diethyl ether and dichloro methane.

Carboxylic acids of the General formula (II) are available commercially or can be obtained by the method described in scheme 7.

Peracids of General formula (IX) is prepared according to the method described in scheme 9, from peroxide as defined in formula (VIII).

Carboxylic acids of formula (II) can be obtained according to reaction scheme 7. Carboxylic acids of formula (VI) is prepared according to the same reaction scheme.

Scheme 7

According to scheme 7, the aldehydes of formula (XIV) is prepared from salicylic aldehyde acid (XI) by methods selected from known to those skilled in the art (Thomas, J. D.; Sloan, K. B.; Tetrahedron Lett. 2007, 48, 109-112). They include the use of a halide of formula (XII) or (XIII) and bases, such as triethylamine, pyridine, potassium carbonate, in a solvent such as acetone or dichloro methane, for example.

At the final stage, the carboxylic acid of�ing formula (II) can be obtained by oxidation of the aldehydes of formula (XIV) perchlorate sodium in a mixture of solvents, such as water and tert-butanol (Marsini, M. A.; Gowin, K. M.; Pettus, T. R. R.; Org. Lett. 2006, 8 (16), 3481-3483).

Peracids of formula (IV) can be obtained according to reaction scheme 8.

Scheme 8

According to the scheme 8 superacid of formula (IV) is prepared from peroxide of Dibenzoyl (XV) by means selected from known to those skilled in the art (US 3075921). They include the use of peroxide (XV) and sodium in a mixture of solvents, such as methanol and chloroform.

Peracids of formula (IX) can be obtained according to reaction scheme 9.

Scheme 9

According to the scheme 9 peracids of formula (IX) is prepared from peroxide of the formula (VIII) by methods selected from known to those skilled in the art (US 3075921). They include the use of peroxide (VIII) and sodium in a mixture of solvents, such as methanol and chloroform.

The iodides of formula (XII) can be obtained according to reaction scheme 10, or commercially available.

Scheme 10

According to the scheme 10 chlorides of formula (XVIII) are commercially available or prepared from the chloride of formula (XVII) by means selected from known to those skilled in the art (Thomas, J. D.; Sloans, K. B.; Synthesis 2008, 2, 272-278 and Majumdar, S.; Sloan, K. B.; Bioorg. Med. Chem. 2006, 16, 3590-3594). They include the use of triazene or trioxane of formula (XVI) in a solvent such as �harmatan, for example.

On the final stage of the iodides of the formula (XII) is prepared from the chloride of formula (XVIII) by means selected from known to those skilled in the art. They include the use of chloride of formula (XVIII) and sodium iodide in a solvent such as acetone, for example.

The anhydrides of the formula (XVII) and triazine or trioxane of formula (XVI) are commercially available.

If the group Z defined in formula (I) is oxygen and if the group R2 defined in the formula (I), is C1-10alkoxy, the iodides of the formula (XII) can be obtained according to reaction scheme 11.

Scheme 11

According to the scheme 11 chlorides of formula (XVIII) is prepared from the chloride of formula (XX) by methods selected from known to those skilled in the art (Thomas, J. D.; Sloan, K. B.; Tetrahedron Lett. 2007, 48, 109-112). They include the use of alcohol of formula (XIX) and bases, such as triethylamine, pyridine, in a solvent such as dichloro methane, for example.

On the final stage of the iodides of the formula (XII) is prepared from the chloride of formula (XVIII) by means selected from known to those skilled in the art (Thomas, J. D.; Sloan, K. B.; Tetrahedron Lett. 2007, 48, 109-112). They include the use of chloride of formula (XVIII) and sodium iodide in a solvent such as acetone, for example.

Chlorides of formula (XX) and alcohols of formula (XIX) are commercially available.

The study�tion sensitivity of peroxides compared with peroxide of Dibenzoyl on Propionibacterium acnes

The principle test

The aim is to assess the antibacterial action of peroxides through the measurement of the minimum inhibitory concentration (MIC). MICK is defined as the lowest concentration of the product, is able to inhibit any visible growth.

Microbial strain and origin

The sensitivity of the products examined in two strains of Propionibacterium acnes (P. acnes) from the Pasteur Institute collection (CIP):

- P. acnes CIP53.117, equivalent ATCC6919, origin: a problem of facial acne vulgaris (1920), the source CRBIP, Pasteur Institute, Paris;

- P. acnes CIPA179, origin: sebaceous gland (1946), the source of CRBIP, Pasteur Institute, Paris.

Testing products

The products are dissolved in 1280 mg/l in a mixture of absolute ethanol/sterile Tween 80/sterile Wilkins Chalgren broth (5/10/85 about./about./vol.). Applied to the dilution adapted to the method described in CLSI for methods of cultivation in liquid medium. They include 10 concentrations from 2.5 mg/l up to 1280 mg/l at intervals of a ratio of 2.

A suspension of P. acnes get in broth Wilkins Chalgren and calibrated in optical density of about 0.4 at a wavelength of 525 nm. Then it is diluted to 1/10 in broth Wilkins Chalgren and then placed in a test Cupule with a final suspension of about 105-106CFU/ml in each test Cupule.

The solutions of the test products are placed in 96-well microplates and incubated at 36±2°C and in�aerobic atmosphere for at least 72 h. First Cupule, which is visible to the naked eye growth, believe MICK.

StrainExample # 1Example # 2
CIP53.117320160
CIPA17932080

Example 1: the peroxide is bis(2-acetoxymethyl)benzoyl

1-1: 2-acetoxyisobutyryl

20 g (185 mmol) of acetate chlormethyl dissolved in acetone, there was added 35 g (230 mmol) of sodium iodide. After stirring for 24 hours of 14.8 g (138 mmol) of salicylic aldehyde and 38,20 g (276 mmol) of potassium carbonate dissolved in 100 ml of acetone. The mixture was stirred at room temperature and add a freshly prepared suspension of acetate itmetal. After stirring for 24 hours at 50°C, water is added and the mixture was extracted with ethyl acetate. The organic phase is dried over magnesium sulfate, filtered and then concentrated. The residue is purified by chromatography on silica gel and eluted with a mixture of heptane/ethyl acetate, 7/3. 21,79 g of 2-atsetoksibetulinola was obtained as a yellow oil with a yield of 98%.

1-2: 2-acetoxybenzoic acid

21,79 g (112,2 mmol) 2-acetoxy�of oxybenzaldehyde and 100 ml (900 mmol) of 2-methyl-2-butene was diluted in 400 ml of tert-butanol. A solution containing 41 g (337 mmol) of sodium hydrophosphate and 35 g (393 mmol) of sodium chlorite in 100 ml of water was added dropwise to the reaction mixture, which was stirred for 2 hours at room temperature. The mixture was evaporated under reduced pressure, and the residue dissolved in dichloromethane. The organic phase was washed with water, dried over magnesium sulfate, filtered and concentrated. The obtained white solid substance precipitated in heptane at 0°C. the Precipitate was filtered, then washed with heptane and dried. To 14.8 g of 2-acetoxybenzoic acid was obtained as a white powder with a yield of 63%.

1-3: the peroxide bis(2-acetoxymethyl)benzoyl

To 4.9 g (24 mmol) of N,N'-dicyclohexylcarbodiimide dissolved in 50 ml of diethyl ether at -18°C. Add of 3.37 ml (60 mmol) of an aqueous hydrogen peroxide solution with 5 g (24 mmol) of 2-acetoxybenzoic acid dissolved in 50 ml of dichloromethane. After stirring for 1 hour at -18°C add 50 ml of diethyl ether, and the reaction mixture was filtered and then concentrated. The obtained solid substance precipitated in diethyl ether, and the filtrate concentrated under reduced pressure. 3 g of the peroxide bis(2-acetoxymethyl)benzoyl obtained as a white solid with a yield of 60%.

1H-NMR/CDCl3: δ=2,31 (s, 6H), 5,94 (s, 4H), 7,20 (m, 4H), 7,60 (t, J=7,6 Hz, 2H), 7,92 (d, 7.5 Hz, 2H).

Example 2: peroxide (acetoxyacetyl)benzoyl

2-1: Parmentola acid

19 g (78 mmol) of peroxide of dibenzyl dissolved in 125 ml of chloroform at -5°C. 2.2 g (94 mmol) of sodium dissolved in 50 ml of methanol in a stream of nitrogen, was added dropwise. After stirring for 30 minutes at -5°C is added ice water, and the environment of the aqueous solution was acidified with 2 n sulfuric acid. The mixture was extracted with dichloromethane, then the organic phase is dried over magnesium sulfate, filtered and concentrated. 9 g of perbenzoic acid was obtained as a white solid with a yield of 83%.

2-2: peroxide (2-acetoxyacetyl)benzoyl

5 g (24 mmol) of 2-acetoxybenzoic acid (obtained according to the method of example 1-2) and 3.3 g (24 mmol) benzonorbornadiene dissolved in 150 ml of mixture of diethyl ether/dichloromethane, 6/4. The solution was cooled to 0°C, then added dropwise to 4.9 g (24 mmol) of N,N'-dicyclohexylcarbodiimide dissolved in 85 ml of diethyl ether. After stirring for 3 hours at 0°C the reaction mixture was filtered and then concentrated. The residue was precipitated in diethyl ether, and the filtrate concentrated under reduced pressure. 5 g of peroxide (2-acetoxyacetyl)benzoyl obtained as a white solid with a yield of 63%.

1H-NMR/CDCl3: δ=2,06 (s, 3H), 5.78% was established (s, 2H), 7,11 (m, 2H), 7,44 (t, J=7,8 Hz, 2H), 7,52 (t, J=7.5 Hz, 1H), members, 7.59 (t, J=7,8 Hz, 1H), a 7.85 (DD, J=1,72 Hz, J=7,7 Hz, 1H), 8,00 (DD, J=8,5 Hz, J=1.4 Hz, 2H).

Evaluation of anti-inflammatory action of peroxides after a single local injection caused on TPA ear edema

Principle of the test:the aim is to evaluate anti-inflammatory action of peroxides through the measurement of the thickness of the mouse ear after topical application of TPA. Anti-inflammatory effect is defined as the percentage of inhibition caused by TAP edema of the ear.

The object of this study is to demonstrate anti-inflammatory effects of a new peroxide compared to BPO (benzoyl peroxide).

Testing products

Swelling cause a single local application of 20 µl of TPA dissolved in acetone at 0.01 percent.

Then spend a single local application of the test compounds, dissolved in a solution of TPA.

Method of evaluation

The ear thickness was measured at T6h.

The results are expressed in percentage on the basis of inhibition of edema induced by application of TPA.

Benzoyl peroxide (BPO) test 2 times as a reference peroxide.

Swelling of the earInhibition
AverageWITHto TPA (%)
TPA 0,01% Of 28.801,67N/A
TPA 0,01%+BPO 5%17,604,45A 21.4
TPA 0,01%+BPO 5%20,802,5927,8
TPA 0,01%+example 2 a 1%20,40To 2.7419,7
TPA 0,01%+example 2 2,5%14,602,7342,5
TPA 0,01%+example 2 5%7,201,8571,7
TPA 0,01%+example 1 1%13,803,5345,7
TPA 0,01%+example 1 2,5%6,401,3874,8
TPA 0,01%+example 1 5%4,600,5881,9

Conclusion

The aim of this study is to demonstrate the anti-inflammatory action of new peroxides after a single local Nan�t in the model caused by TPA ear edema mouse.

Sample No. 2 showed moderate anti-inflammatory effect.

Example No. 1 showed a strong, dose-dependent anti-inflammatory effect.

Compared to BPO at 5% it is possible to rank the tested compounds are as follows.

Example No. 1 at 5% shows a slightly better result, compared with example No. 2, and both are superior BPO 5%.

1. The following compounds of the General formula (I):

in which:
- Z is oxygen;
- Y is a hydrogen or the following sequence:

- V is oxygen;
- R1 and R4 are, identically or independently, a hydrogen or C1-4by alkyl;
- R2 and R5 are, identically or independently, C1-10the alkyl.

2. Compounds according to claim 1, characterized in that:
a. Z is oxygen;
b. Y is a hydrogen or the following sequence:

c. V is oxygen;
d. Rl and R4 are, identically or independently, a hydrogen or bromide;
e. R2 and R5 are, identically or independently, C1-4the alkyl.

3. Connection according to one of claims.1 or 2 selected from the group comprising the following compounds:
example 1: the peroxide is bis(2-acetoxymethyl)benzoyl;
example 2: peroxide (2-acetoxyacetyl)benzoyl.

4. The compound according to claim 1 for the treatment of pathologies or disorders, SV�connected with the presence of Propionibacterium acnes.

5. The compound according to claim 1 for insertion into a cosmetic composition, characterized in that it inhibits the proliferation of pathogens involved in the development of skin disorders prevage type, namely P. acnes.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: present invention relates to hardeners for unsaturated polyester resins, as well as some other compounds containing double bonds. The hardener is a composition which contains 100 pts. wt benzoyl peroxide, 40-177 pts. wt phthalic ester, 0.6-1.3 pts. wt polyoxyalkylated alkylphenols, 13-97 pts. wt polyoxyalkylated di- or triatomic alcohols with average molecular weight 1000-6000, 1.6-6.0 pts. wt mixture of sodium salts of alkylarylsulphonic acid and 33-43 pts. wt water.

EFFECT: obtaining stable, non-flaking paste with wide range of benzoyl peroxide content.

5 cl, 7 ex, 1 tbl

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to methods for polymerization of ethylene-unsaturated monomers in the presence of free radical initiating agents. Method involves the following steps: peroxidation step wherein an aqueous mixture is prepared and this mixture contains diacylperoxide of the formula (I): by interaction of one or some acid halogen anhydrides of the formula (II): with (i) MOOH/M2O2 wherein M represents any metal or ammonium-containing group that interacts with H2O2 to form MOOH/M2O2 without decomposition of one or some peroxides taking part in the process; M is chosen from group consisting of ammonium, sodium, potassium, magnesium, calcium and lithium, and/or (ii) one or some peracids of the formula (III): , or with their M salts in aqueous phase. Acid halogen anhydride or mixture of acid halogen anhydrides contact with water only containing MOOH/M2O2 and/or one or some peracids or peracid salts, preferably M2O2 or peracid salt M. Values of radicals in formulae (I), (II) and (III) are given in the invention description. One or some solvents for acid halogen anhydride, one or some salts, one or some colloidal and/or surface-active substances can be added before, in process or after the peroxidation step. Also, the process can comprise one or some steps for purification of an aqueous mixture, one or some steps of homogenization of an aqueous mixture. Then the process involves a step for transfer of product from precede steps that comprises diacylperoxide of the formula (I) into polymerization reactor, and thermal decomposition of this diacylperoxide to form organic free radicals in the presence of one or some ethylene-unsaturated monomers with polymerization of indicated monomers in indicated polymerization reactor. Invention provides synthesis and using peroxides in process for short time period that solved problems associated with peroxides.

EFFECT: improved method of polymerization.

13 cl, 3 ex

The invention relates to organic chemistry, namely the synthesis of the perforated deciphered specifically PERFLUORO-2-methyl-3-oxohexanoate used as an initiator radical copolymerization of fluorinated olefins

The invention relates to a technology for benzoyl peroxide interaction of benzoyl chloride with hydrogen peroxide in aqueous-alkaline medium under stirring and cooling

The invention relates to the field of chemical industry, particularly to the industrial production of benzoyl peroxide

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed is emulsified composition for improvement of skin condition, which contains (A) 0.001-10 wt % of organic compound, which has two or more hydroxyl groups, inorganic value 220-450 and organic value 300-1000; (B) 0.001-10 wt % of organic compound, which has one hydroxyl group, inorganic value 100-200 and organic value 280-700; (C) 0.001-10 wt % of organic substance, represented by formula (2), in which R1 is C4-C30 hydrocarbon group; Z is methylene group, methane group or oxygen atom; X1, X2, X3 are hydrogen atom, hydroxyl group or acetoxy group; X4 is hydrogen atom, acetyl group or glyceryl group; each of R2 and R3 is hydrogen atom, hydroxyl group, hydroxymethyl group or acetoxymethyl group; R4 is C5-C60 hydrocarbon group; and R5 is hydrogen atom or hydrocarbon group, containing in total 1-30 carbon atoms; (D) (D) 0.00012-10 wt % of at least one compound, selected from group, consisting of non-ionic surface-active substance, which has polyoxyethylene group and HLB 10 or higher, ionic surface-active substance and sphingosine salt; (E) 0.003-15 wt % of at least one compound, selected from group, consisting of sugar alcohol, selected from group, consisting of erythritol, threitol, xylitol and mannitol, disaccharide and trisaccaride, and (F) water.

EFFECT: emulsion composition preserves water in skin for long time.

13 cl, 1 dwg, 18 tbl, 64 ex

FIELD: chemistry.

SUBSTANCE: present invention refers to developing brewing products. According to the invention, a method for preparing an extract of polyphenols as a result of brewage involves the stages: contacting partially purified beer with resin, which adsorbs polyphenols; desorbing polyphenols adsorbed on the resin contacting with partially purified beer; adsorbing polyphenols on the second resin different from the first one; the above second resin is hydrophobic and non-ionic; and desorbing polyphenols adsorbed on the second resin with using an organic solvent; implementing the method is ethylacetate-free. The invention also refers to the method for preparing the extract of polyphenols as a result of brewage that involves the following stages: contacting partially purified beer with hydrophobic and non-ionic resin, which adsorbs polyphenols; and desorbing polyphenols adsorbed on the resin used at the previous stage of contacting with using the organic solvent; a desorption product contains at least 0.85 g of polyphenols per one gram of a dry matter. The invention also refers to the extract of polyphenols prepared by the above method and containing catechin, epicatechin, thyrozol and ferulic acid. The invention also refers to a cosmetic product, a functional food product, a food additive, which contain the above extract of polyphenols in an effective amount. Also the invention provides using the above cosmetic product for skin moistening and/or ageing prevention or delay, using the extract of polyphenols for producing an antioxidant composition.

EFFECT: invention provides preparing the extract of ethylacetate-free and high-purity polyphenols.

19 cl, 23 dwg, 22 tbl, 6 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to an oral care composition, methods for preparing and using it. The presented composition containing a pre-mix containing arginine in the free form or in the form of a salt, a soluble carbonate salt and arginine bicarbonate formed in situ when mixing arginine in the free form or in the form of a salt with the soluble carbonate salt. The method for preparing the composition involves preparing the pre-mix by mixing arginine in the free form or in the form of the salt and soluble carbonate salt. What is also presented is an oral care procedure involving coating the patient's oral cavity with an effective amount of the above composition.

EFFECT: using the group of inventions provides positive effects achieved by using the oral care composition containing arginine bicarbonate in a combination with a simplified process of preparation of this composition.

15 cl, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to the field of pharmaceutics and represents a composition for oral cavity care in the form of dental varnish, containing bioactive glass and fluoride, where the said fluoride is present in the composition in an amount of up to 5% by weight. An increased ionic release is observed for the dental varnish containing bioactive glass and fluoride.

EFFECT: invention provides the creation of compositions, containing bioactive glass, for which in case of applying fluoride in lower concentrations (lower than 900 mln-1) its efficiency is the same as for higher concentrations (900 - 1450 mln-1).

3 cl, 2 ex, 6 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to a compound with a woody note having structural formula I. In formula , the ring with 6 carbon atoms is saturated or has a double bond between carbon atoms C1 and C2 or between carbon atoms C1 and C6, R is selected from a C2-C5 alkyl or C2-C5 alkenyl group.

EFFECT: invention also relates to a fragrant composition containing said compound.

13 cl, 16 ex

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

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: medicine, pharmaceutics.

SUBSTANCE: claimed is emulsified composition for improvement of skin condition, which contains (A) 0.001-10 wt % of organic compound, which has two or more hydroxyl groups, inorganic value 220-450 and organic value 300-1000; (B) 0.001-10 wt % of organic compound, which has one hydroxyl group, inorganic value 100-200 and organic value 280-700; (C) 0.001-10 wt % of organic substance, represented by formula (2), in which R1 is C4-C30 hydrocarbon group; Z is methylene group, methane group or oxygen atom; X1, X2, X3 are hydrogen atom, hydroxyl group or acetoxy group; X4 is hydrogen atom, acetyl group or glyceryl group; each of R2 and R3 is hydrogen atom, hydroxyl group, hydroxymethyl group or acetoxymethyl group; R4 is C5-C60 hydrocarbon group; and R5 is hydrogen atom or hydrocarbon group, containing in total 1-30 carbon atoms; (D) (D) 0.00012-10 wt % of at least one compound, selected from group, consisting of non-ionic surface-active substance, which has polyoxyethylene group and HLB 10 or higher, ionic surface-active substance and sphingosine salt; (E) 0.003-15 wt % of at least one compound, selected from group, consisting of sugar alcohol, selected from group, consisting of erythritol, threitol, xylitol and mannitol, disaccharide and trisaccaride, and (F) water.

EFFECT: emulsion composition preserves water in skin for long time.

13 cl, 1 dwg, 18 tbl, 64 ex

FIELD: chemistry.

SUBSTANCE: present invention refers to developing brewing products. According to the invention, a method for preparing an extract of polyphenols as a result of brewage involves the stages: contacting partially purified beer with resin, which adsorbs polyphenols; desorbing polyphenols adsorbed on the resin contacting with partially purified beer; adsorbing polyphenols on the second resin different from the first one; the above second resin is hydrophobic and non-ionic; and desorbing polyphenols adsorbed on the second resin with using an organic solvent; implementing the method is ethylacetate-free. The invention also refers to the method for preparing the extract of polyphenols as a result of brewage that involves the following stages: contacting partially purified beer with hydrophobic and non-ionic resin, which adsorbs polyphenols; and desorbing polyphenols adsorbed on the resin used at the previous stage of contacting with using the organic solvent; a desorption product contains at least 0.85 g of polyphenols per one gram of a dry matter. The invention also refers to the extract of polyphenols prepared by the above method and containing catechin, epicatechin, thyrozol and ferulic acid. The invention also refers to a cosmetic product, a functional food product, a food additive, which contain the above extract of polyphenols in an effective amount. Also the invention provides using the above cosmetic product for skin moistening and/or ageing prevention or delay, using the extract of polyphenols for producing an antioxidant composition.

EFFECT: invention provides preparing the extract of ethylacetate-free and high-purity polyphenols.

19 cl, 23 dwg, 22 tbl, 6 ex

FIELD: medicine.

SUBSTANCE: invention refers to dentistry and concerns treating chronic generalised periodontitis. Implementing the above method is ensured by a complex preparation in the form of an ointment of the following composition: Vaselin - lanolin base (1:1) - 88.5 g, 70% ipecac infusion - 5.0 g, 70% scholar tree - 5.0 g, Ecdysterone - 0.02 g; eucalyptus oil - 1.0 g. The oil is applied as a therapeutic periodontal applicate on a gingival surface following application anaesthesia with 10% lidocaine, chairside oral hygiene, drug-induced treatment of the gingival margin with 1% Iodinolum and separation of salivary glands in the oral cavity, once a day for 2 hours for 4 weeks; the patients are recommended not to eat or drink for two hours. The preparation composition particularly provides capillary-reinforcing, anti-inflammatory, reparative and anaesthetic action.

EFFECT: method of treating is easy to use, physiologically-friendly, and provides the complete recovery.

2 ex

FIELD: medicine.

SUBSTANCE: method of treating chronic generalised periodontitis includes the influence on an affected area by the therapeutic diode laser "HELBO" 2075 F/Theralite" with photosensitase "HELBO Blue Photosensitizer", with the application after the laser influence on the periodontium affected area of an adhesive gingival bandage, to prepare which the antioxidant "Melaxen", kalanchoe sap, glycosamine hydrochloride, dimethylsulphoxide, water dentine and solcoseryl dental adhesive paste are applied in specified quantities.

EFFECT: achievement of an anti-inflammatory, antiseptic and reparative effect, which makes it possible to stop inflammation in the tissues of periodontium and obtain stable long-lasting remission.

1 tbl, 2 ex

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