Stabilised composition for treating psoriasis

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine and describes a non-aqueous ointment containing a compound of vitamin D, corticosteroid and ester of N,N-di(C1-C8)alkylamino-substituted (C4-C18)alkyl(C2-C18)carboxylic acid in Vaseline, optionally containing mineral oil and tocopherol.

EFFECT: ointment is characterised by storage stability and high skin penetration of the corticosteroid.

23 cl, 4 dwg, 5 tbl, 3 ex

 

2420-176849RU/071

STABLE COMPOSITION FOR TREATING PSORIASIS

The technical FIELD TO WHICH the INVENTION RELATES.

The present invention relates to stable at room temperature nonaqueous compositions ointments containing vitamin D and corticosteroid used for the treatment of psoriasis.

BACKGROUND of INVENTION

Psoriasis is a non-infectious disease that affects the skin and joints. This disease is accompanied by the formation of the skin red scaly plaques, called psoriatic plaques, are areas of inflammation and excessive production of skin tissue. According to the National Institute of Health (National Institute of Health) to 7.5 million Americans are affected by psoriasis. It has been estimated that approximately 10 to 30% of people with psoriasis, there is a risk of development of diseases of the joints, known as psoriatic arthritis, which causes joint pain, stiffness and swelling.

Psoriasis is a chronic relapsing condition that can greatly vary on the severity of the symptoms. Some patients with psoriasis there are small localized areas of psoriatic plaques, while others such plaques can cover almost the entire body. This often affects the nails PA who icev hands and feet.

The cause of psoriasis is unknown, but it is believed that this disease may have a genetic component. Stress, excessive alcohol consumption and Smoking are known factors that worsen this condition. Besides the obvious physical manifestations of psoriasis may be accompanied by the affected individuals with depression and reduced self-esteem.

There are many local drug used for the treatment of psoriasis. Such tools include, for example, vitamin D-3 (calcipotriene), tar, corticosteroids (such as clobetasol, fluotsinolon and betamethasone), bark extract (such as anthralin) and retinoids (e.g., tazarotene). Were also described compositions for the treatment of psoriasis, which include compounds of vitamin D and corticosteroids (see U.S. patent No. 6753013). Combination of vitamin D and corticosteroids may be unstable, because corticosteroids favorable acidic conditions, whereas the connection of vitamin D is more stable under alkaline conditions. Local ointment TACLONEX® (TACLONEX®) is a joint product, which includes calcipotriene, and betamethasone dipropionate, stable solvent type polyoxyalkylene ether.

A BRIEF DESCRIPTION of the INVENTION

Stable PR is keeping the ointment of the present invention includes the connection of vitamin D, corticosteroid and substituted N,N-di(C1-C8)alkylamino ester (C4-C18) alkyl (C2-CI8) carboxylic acid, ester (C1-C4) alkyl (C8-C22)carboxylic acid in vaseline as a carrier and optionally contains mineral oil, tocopherol, or both. Preferably the connection of vitamin D includes calcipotriene. Corticosteroid preferably is a pharmaceutically acceptable salt clobetasol or pharmaceutically acceptable salt of betamethasone. Preferred ester N,N-di(C1-C8)alkylamino-substituted (C4-C18) alkyl (C2-CI8) carboxylic acid is a dodecyl-2-(N,N-dimethylamino)propionate (DDAIP).

The compositions of the present invention are stable during storage, comparable to commercially available ointment for local application TACLONEX®, and show unexpectedly increased penetration into the skin of calcipotriene, in comparison with a commercial product.

BRIEF DESCRIPTION of DRAWINGS

Figure 1 shows a graph showing the cumulative penetration of calcipotriene through the skin of the ear of a pig, in relation to the duration of such penetration into the skin in a standard test for penetration into the skin, conducted using com is Azizi of the present invention, containing calcipotriol, betamethasone dipropionate and a variable number of DDAIP, compared to a composition not containing DDAIP, and ointment TACLONEX®.

Figure 2 shows a graph showing the cumulative penetration of betamethasone through the skin of the ear of a pig, in relation to the duration of such penetration into the skin in a standard test for penetration into the skin, performed using the compositions of the present invention, containing calcipotriol, betamethasone dipropionate and a variable number of DDAIP, compared to a composition not containing DDAIP, and ointment TACLONEX®.

Figure 3 shows a graph showing the cumulative penetration of calcipotriene through the skin of the ear of a pig, in relation to the duration of such penetration into the skin in a standard test for penetration into the skin, performed using the compositions of the present invention, containing calcipotriene, clobetasol propionate and a variable number of DDAIP, compared to a composition not containing DDAIP.

Figure 4 shows a graph showing the cumulative penetration of clobetasol through the skin of the ear of a pig, in relation to the duration of such penetration into the skin in a standard test for penetration into the skin, performed using the compositions of the present invention, containing calcipotriene, clobetasol propionate and various what's the number DDAIP, in comparison with a composition that does not contain DDAIP.

In the graphs shown in figures 1, 2, 3 and 4 columns for each time point for each group and on each of the graphs are grouped in the manner described under each graph.

DESCRIPTION of the PREFERRED embodiments of the INVENTION

The present invention relates to stable storage ointment used for psoriasis treatment. The composition according to the present invention includes the connection of vitamin D, a steroid and an ester of N,N-di(C1-C8) alkylamino-substituted (C4-C18)alkyl(C2-C18)carboxylic acid, ester (C1-C4)alkyl(C8-C22)carboxylic acid in vaseline (such as white vaseline) as a carrier and optionally contains mineral oil, tocopherol (vitamin E), or both of these components: mineral oil, and tocopherol.

Suitable connections on the basis of vitamin D, which can be used in the compositions of the present invention, include calcipotriene (also known as calcipotriol, calcitriol, tacalcitol, maximality and 1(S),3(R) - dihydroxy-20(R)-[((3(2-hydroxy-2-propyl)phenyl)methoxy)methyl]-9,10-SECO-pregna-5(Z),7(E),10(19)triene, and combinations of two or more such compounds. The preferred connection of vitamin D is calcipotriene, which depict is to place a (lR,3S)-5-[2-[(lR,3aR,7aS)-l-[(2S)-5-cyclopropyl-5-hydroxy-Penta-3-EN-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ilidene]ethylidene]-4-methylidene-cyclohexane-1,3-diol (name according to IUPAC classification) is preferably in the form of a monohydrate. The connection of vitamin D is preferably present in the composition in a concentration of from about 0.001 to about 0.01 weight percent.

Suitable corticosteroids that can be used in the compositions of the present invention, include hydrocortisone, desonide, pialat flumetazon, acetonide fluoqinolona, triamcinolone acetonide, dipropionate alklometazon, hydrocortisone valerate, prednicarbate, pialat of clocortolone, fluticasone propionate, mometasone furoate, betamethasone dipropionate betamethasone amcinonide, desoximetasone, diflorasone, fluocinonide, halcinonide, propionate halobetasol, clobetasol propionate, and combinations of two or more of these compounds. Especially preferred corticosteroids are the clobetasol propionate and betamethasone dipropionate. Preferably, the corticosteroid is present in the composition in a concentration of from about 0.01 to about 0.1 weight percent.

Tocopherol also preferably included in the compositions of the present invention, for example, in a concentration of from about 0.001 to 0.01 weight percent.

In addition, the compositions of the present invention include ester N,N-di(C1-C8) alkylamino-substituted (C4-C18)alkyl (C2-C18) carboxylic acids, for example, as a solution of the indicator, and power of penetration into the skin, preferably in a concentration of from about 0.1 to about 5 weight percent. The term "N,N-di(C1-C8)alkylamino-substituted" as applied to complex ether (C4-C18)alkyl(C2-C18)carboxylic acid indicates that either the alkyl part, or a part of the carboxylic acid on the basis of which was obtained ester contains a Deputy on the basis of the amino group NRxRywhere Rxand Ryeach independently represents (C1-C8) alkyl group. Preferably Rxand Ryboth represent a methyl group. Examples of such suitable compounds include dodecyl-2-(N,N-dimethylamino)propionate (DDAIP); dodecyl-2-(N,N-dimethylamino)acetate (DDAA) and 1-(N,N-dimethylamino)-2-propyl-dodecanoate (DAIPD), 1-(N,N-dimethylamino)-2-profilerita (DAIPM) and 1-(N,N-dimethylamino)-2-Propylaea (DAIPO). Getting DDAIP and crystalline additive salts of the acids described in U.S. patent No. 6118020 (Büyüktimkin,et. al),which is included in the present description fully by reference. Esters alkalicarbonate acid that includes a similar substitution of long-alkilani on the amino group, can be synthesized from readily available compounds as described in U.S. patent No. 4980378 (Wong,et al), which is included in the present description fully in image quality is as references in the volume which corresponds to the topic. Preferred complex ether N,N-di(C1-C8) alkylamino-substituted (C4-C18)alkyl(C2-C18)carboxylic acid is DDAIP.

The compositions of the present invention may include up to about 10 weight percent (e.g. 1-10%) of mineral oil. Preferably the composition includes from about 1 to about 5 weight percent of mineral oil

In a preferred embodiment, the composition according to the present invention includes from about 0.001 to about 0.01 weight percent of compounds of vitamin D; from about 0.01 to about 0.1 weight percent of corticosteroid; from about 0.001 to about 0.01 percent by weight of tocopherol; from about 0.1 to about 5 weight percent of ester N,N-di(C1-C8)alkylamino-substituted (C4-C18)alkyl (C2-C18)carboxylic acid, ester (C1-C4)alkyl(C8-C22)carboxylic acid in vaseline as a carrier and optionally contains mineral oil.

In especially preferred embodiments of implementing the present invention, the connection of vitamin D includes calcipotriene, corticosteroid selected from the group consisting of clobetasol propionate and diplopia is and betamethasone and an ester of N,N-di(C1-C8)alkylamino-substituted (C4-C18)alkyl(C2-C18)carboxylic acid is a DDAIP, registration number CAS No. 224297-43-2. One such preferred embodiment of the invention relates to a composition that includes from about 0.001 to about 0.01 weight percent of calcipotriene; from about 0.01 to about 0.1 weight percent of a corticosteroid selected from propionate clobetasol and betamethasone dipropionate; from about 0.001 to about 0.01 percent by weight of tocopherol; about 10 weight percent of mineral oil and from about 0.1 to about 5 weight percent of ester N,N-di(C1-C8) alkylamino-substituted (C4-C18)alkyl(C2-C18)carboxylic acid, ester (C1-C4)alkyl(C8-C22)carboxylic acid in vaseline as a carrier.

Following non-limiting examples are given to illustrate certain aspects and features of the present invention.

EXAMPLE 1

Get two compositions according to the present invention. The compositions described in tables 1 and 2. In table 1 and table 2, as well as in subsequent tables, the abbreviation "CAL" refers to calcipotriene; abbreviated designation is their "BET-D" refers to dipropionate betamethasone and the abbreviation "CLO-P" refers to clobetasol propionate.

Table 1
Connection 1CALBET-DDDAIPVitamin EMineral oilWhite petrolatum
0,005%0,064%1%0,002%3%q.s.100

Table 2
Connection 2CALCLO-PDDAIPVitamin EMineral oilWhite petrolatum
0,005%0,05%1%0,002%3%q.s.100

EXAMPLE 2

The stability data of the combined compositions, describe the data in example 1, shown in table 3. As reference drug was taken ointment TACLONEX® (TACLONEX®) (commercial product containing calcipotriol and dipropionate betamethasone stable complex with ether, poly(accelerated) as a solvent)in respect of which it is known that it is a stable product. The composition of example 1 and ointment TACLONEX® kept at the specified temperature conditions, as described in table 3, and further analyzed by the method of high performance liquid chromatography for detection of active pharmaceutical ingredient (API). In table 3 the numbers indicate the percent of the target of the active ingredient relative to known drugs compositions obtained by analyzing samples taken at appropriate time points during storage at specified temperatures.

Table 3
25°C40°C
CompositionAPI
(active pharmaceutical ingredient)
Original value4 weeksthe similar value 1 week2 weeks4 weeks
TACLONEX®CAL89,9296,94100,2398,78
BET-D104,33104,66104,63105,57
Composition 1CAL103,72105,32103,72104,79to 100.4106,61
BET-D99,5099,8499,5098,6894,77of 99.75
Composition 2CAL99,5799,5899,57101,44106,08 106,23
CLO-Pefficiency of 99.7898,64efficiency of 99.78100,8695,92102,21

In table 3 the data clearly show that the compositions of the present invention have a storage stability which is comparable with that of the reference commercial product.

EXAMPLE 3

The compositions of the present invention were also evaluated with respect to their ability to penetrate the skin of the ear of a pig. Leather ear pig is traditionally used to assess the penetration of local products due to the fact that the result of this assessment, penetration is close to the corresponding characteristic for the skin in humans. Investigated the composition of the present invention, which consisted of 0.005 wt.% calcipotriene, 0.002 wt.% tocopherol, 3 wt.% mineral oil, or 0.05 wt.% propionate clobetasol or 0,064 wt.% dipropionate betamethasone in white vaseline as a carrier, and which also contained varying concentrations of DDAIP (1, 1,5, 2 and 2,5 wt.%) together with a control composition that does not contain DDAIP, as well as ointment TACLONEX® (TACLONEX®). Estimated penetration of calcipotriene, clobetasol and betamethasone. The results is provided in tables 4 and 5, as well as in figures 1, 2, 3 and 4. The numerical values shown in tables 4 and 5, as well as on the relevant drawings, given in units of nanograms of dissolved matter per square centimeter of skin (ng/cm2). Figure 1 shows a graph showing the cumulative penetration of calcipotriene through the skin of the ear of a pig, with respect to the number of songs that were on the skin at a certain time, in a comparative perspective for the specified compositions containing calcipotriene/betamethasone and ointments TACLONEX® (TACLONEX®). Figure 2 shows a graph showing the cumulative penetration of betamethasone through the skin of the ear of a pig, with respect to the number of songs that were on the skin at a certain time, in a comparative perspective for the specified compositions containing calcipotriene/betamethasone and ointments TACLONEX® (TACLONEX®). Figure 3 shows a graph showing the cumulative penetration of calcipotriene through the skin of the ear of a pig, with respect to the number of songs that were on the skin at a certain point in time, to compositions containing calcipotriene/clobetasol. Figure 4 shows a graph showing the cumulative penetration of clobetasol through the skin of the ear of a pig, with respect to the number of songs that were on the skin at a certain point in time, for composers is s, containing calcipotriene/clobetasol.

Table 4
API
(active pharmacy-static ingredient)
Period of timeTACLONEX®Without
DDAIP
1% DDAIP1,5% DDAIP2% DDAIP2,5% DDAIP
CAL-P24 hours23,956,8215,9447,0142,8735,49
48 h47,4318,6669,5597,2592,4080,11
96 h101,6229,13134,29168,62191,46172,08
120 h121,8533,40 the concentration is207,99236,98207,97
BET-D24 hours1170,26886,74825,64710,73961,47732,73
48 h2305,961911,062199,421547,331857,531672,54
96 h4769,363675,044678,473141,543493,813613,49
120 h6016,934608,58the concentration is3856,934540,464569,25

The data shown in table 4 and figures 1 and 2 clearly demonstrate that DDAIP in the concentration range of 1.5-2.5 % provide unexpectedly increased effect from the point of view of the penetration of calcipotriene all measured time points in comparison with the composition, not steriade is DDAIP, as compared to ointment TACLONEX® (TACLONEX®), which contains as a solvent, an ester of poly(alkalophiles). Similarly, a composition containing 1% DDAIP, also showed an unexpected increase penetration of calcipotriene when estimating the period of time from 24 to 96 hours, compared to a composition not containing DDAIP and ointment TACLONEX® (TACLONEX®). Composition containing 2% DDAIP, was characterized by approximately 7.1 times higher penetrating power of calcipotriene in comparison with a composition that did not contain DDAIP, and was characterized by penetration, which is 1.9 times higher than the figure for ointments TACLONEX®.

Table 5
API
(active pharmacy-static ingredient)
Period of timeWithout
DDAIP
1% DDAIP1,5% DDAIP2% DDAIP2,5% DDAIP
Calcipotriene24 hours4,7022,0226,7224,8524,63
48 hof 12.7364,7086,3771,0777,02
96 h20,61126,10160,21129,09142,59
120 h27,82177,36215,60180,32189,47
Propionate clobetasol24 hours216,65308,81333,98594,61563,00
48 h479,48740,02917,701361,731319,23
96 h823,641312,231650,362389,202321,16
120 h1180,691799,703323,453151,98

The data shown in table 5 and on drawings 3 and 4 clearly demonstrate that DDAIP in the concentration range of 1-2 .5% provide unexpected increased effect from the point of view of the penetration of calcipotriene all measured time points compared to a composition not containing DDAIP, similarly to this effect to the increase that was observed for compositions containing betamethasone. The penetration of clobetasol also significantly increased in the presence of DDAIP. The presence of DDAIP at a concentration of 2% provided the penetration clobetasone after 120 hours, which is approximately 2.8 times higher than the corresponding level of penetration for clobetasol in compositions that do not contain DDAIP. The presence of 1.5% DDAIP has provided such a level of penetration of calcipotriene after 120 hours, which is approximately 7.7 times higher than the corresponding figure for calcipotriene in the case of compositions not containing DDAIP.

The above examples are given merely to illustrate the preferred embodiments of the present invention, and should not be interpreted in terms of any limitation of the scope of the present invention.

1. Nonaqueous stable during storage ointment suitable for the treatment of psoriasis, comprising:
soedineniya D;
corticosteroid and
ester N,N-di(C1-C8)alkylamino-substituted (C4-C18)alkyl(C2-C18)carboxylic acid;
in vaseline as a carrier, optionally containing mineral oil, tocopherol, or a combination of mineral oil and tocopherol.

2. Stable when stored ointment according to claim 1, characterized in that the connection of vitamin D includes calcipotriene.

3. Stable when stored ointment according to claim 1, characterized in that the corticosteroid selected from the group consisting of pharmaceutically acceptable salts clobetasol and pharmaceutically acceptable salts of betamethasone.

4. Stable when stored ointment according to claim 1, characterized in that an ester of N,N-di(C1-C8)alkylamino-substituted (C4-C18)alkyl(C2-C18)carboxylic acids include dodecyl-2-(N,N-dimethylamino)propionate (DDAIP).

5. Stable when stored ointment according to claim 1, wherein the liquid carrier comprises white petrolatum.

6. Stable when stored ointment according to claim 1, characterized in that the connection of vitamin D is present in the concentration range from 0.001 to 0.01 weight percent.

7. Stable when stored ointment according to claim 1, characterized in that the corticosteroid is present in a concentration range from 0.01 to 0.1 weight percent.

8. Stable when stored MAZ who according to claim 1, characterized in that it comprises tocopherol in a concentration range from 0.001 to 0.01 weight percent.

9. Stable when stored ointment according to claim 1, characterized in that an ester of N,N-di(C1-C8)alkylamino-substituted (C4-C18)alkyl(C2-C18)carboxylic acid is present in the concentration range from 0.1 to 5 weight percent.

10. Stable when stored ointment according to claim 1, characterized in that it comprises from 1 to 10 weight percent of mineral oil.

11. Nonaqueous stable during storage ointment suitable for the treatment of psoriasis, including:
(a) from 0.001 to 0.01 weight percent of compounds of vitamin D;
(b) from 0.01 to 0.1 weight percent of corticosteroid;
(c) from 0.001 to 0.01 percent by weight of tocopherol and
(d) from 0.1 to 5 weight percent of ester N,N-di(C1-C8)alkylamino-substituted (C4-C18)alkyl(C2-C18)carboxylic acid, ester (C1-C8)alkyl(C8-C22)carboxylic acid in a liquid medium and optionally containing mineral oil.

12. Stable when stored ointment according to claim 11, characterized in that a derivative of vitamin D includes calcipotriene.

13. Stable when stored ointment according to claim 11, characterized in that the corticosteroid selected from the group consisting of clobetasol propionate and dipropionate betametha is on.

14. Stable when stored ointment according to claim 11, characterized in that an ester of N,N-di(C1-C8)alkylamino-substituted (C4-C18)alkyl(C2-C18)carboxylic acids include dodecyl-2-(N,N-dimethylamino)propionate (DDAIP).

15. Stable when stored ointment according to claim 11, characterized in that the liquid medium comprises white petrolatum.

16. Nonaqueous stable during storage ointment suitable for the treatment of psoriasis, including:
(a) from 0.001 to 0.01 weight percent of calcipotriene;
(b) from 0.01 to 0.1 weight percent of a corticosteroid selected from the group consisting of clobetasol propionate and betamethasone dipropionate;
(c) from 0.001 to 0.01 percent by weight of tocopherol; and
(d) from 0.1 to 5 weight percent dodecyl-2-(N,N-dimethylamino)propionate (DDAIP);
in liquid media containing up to 10 weight percent of mineral oil.

17. Stable when stored ointment on item 16, characterized in that it contains from 0.005 weight percent of calcipotriene.

18. Stable when stored ointment on item 16, characterized in that it contains 0.05% by weight of clobetasol propionate.

19. Stable when stored ointment on item 16, characterized in that it contains 0,064 weight percent of betamethasone dipropionate.

20. Stable when stored ointment on item 16, characterized in that it comprises 1 weight percent DDAIP.

22. Stable when stored ointment on item 16, characterized in that it contains 3 weight percent mineral oil.

23. Stable when stored ointment on clause 16, wherein the liquid carrier comprises white petrolatum.



 

Same patents:

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In the above formula, R1 represents S-Alk-R, wherein Alk represents methylene, C2-C6 polymethylene bond or C3-C6 alkenylene bond, R represents -N=C(NR3R4)(NR5R6) or -NR7[(NR3R4)C=NR5], or -N=C(R8)(NR9R10), wherein R3-R10 represents H, Alk, Ar or (CH2)nAr, wherein Ar represents an aryl group, and n represents an integer from 1 to 13, or R3 and R4, or R4 and R5, or R5 and R7, or R3 and R7, or R9 and R10, or R8 and R9 together can represent -(CH2)x-, wherein x represents an integer from 2 to 5, and R2 is specified in a group consisting of hydroxyl, alkyl having from 1 to 7 carbon atoms, and substituted by alkyl hydroxyl having from 1 to 7 carbon atoms.

EFFECT: preparing new cyclosporine derivatives.

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22 cl, 1 tbl

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15 cl, 1 tbl, 3 ex

FIELD: biotechnologies.

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

,

where R1 represents NR7C(O)R8 or NR9R10; R2 represents hydrogen; R3 represents halogen; R4 represents hydrogen, halogen, cyano, hydroxy, C1-4alkyl, C1-4alkoxy, CF3, OCF3, C1-4alkylthio, S(O)(C1-4alkyl), S(O)2(C1-4alkyl), CO2H or CO2(C1-4alkyl); R5 represents C1-6alkyl (replaced with NR11R12 or heterocyclyl that represents nonaromatic 5-7-membered ring containing 1 or 2 heteroatoms independently chosen from a group containing nitrogen, oxygen or sulphur); R6 represents hydrogen, halogen, hydroxy, C1-4alkoxy, CO2H or C1-6alkyl (possibly replaced with NR15R16 group, morpholinyl or thiomorpholinyl); R7 represents hydrogen; R8 represents C3-6cycloalkyl (possibly replaced with NR24R25 group), phenyl or heteroaryl, which represents aromatic 5- or 6-membered ring containing 1 to 3 heteroatoms independently chosen from the group containing nitrogen, oxygen and sulphur, and which is probably condensed with one 6-membered aromatic or nonaromatic carbocyclic ring or with one 6-membered aromatic heterocyclic ring, where the above 6-membered aromatic heterocyclic ring includes 1 to 3 heteroatoms independently chosen from a group containing nitrogen, oxygen and sulphur; R9 represents hydrogen or C1-6alkyl (possibly replaced with pyrazolyl); R10 represents C1-6alkyl (possibly replaced with phenyl or heteroaryl group, which represents aromatic 5- or 6-membered ring containing 1 or 2 heteroatoms independently chosen from the group containing nitrogen, oxygen or sulphur, and which is possibly condensed with one 6-membered heterocyclic ring, where the above 6-membered aromatic heterocyclic ring contains 1 or 2 heteroatoms independently chosen from the group containing nitrogen, oxygen or sulphur; where the above phenyl and heteroaryl groups in R8, R9 and R10 are possibly independently replaced with the following group: halogen, hydroxy, C(O)R42, C1-6alkyl, C1-6hydroxyalkyl, C1-6halogenoalkyl, C1-6alkoxy(C1-6)alkyl or C3-10cycloalkyl; unless otherwise stated, heterocyclyl is possibly replaced with group of C1-6alkyl, (C1-6alkyl)OH, (C1-6alkyl)C(O)NR51R52 or pyrrolidinyl; R42 represents C1-6alkyl; R12, R15 and R25 independently represent C1-6alkyl (possibly replaced with hydroxy or NR55R56 group); R11, R16, R24, R51, R52, R55 and R56 independently represent hydrogen or C1-6alkyl; or to its pharmaceutically acceptable salts.

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18 cl, 6 dwg, 6 ex

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2 ex, 1 tbl

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1 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: invention refers to a method of treating psoriasis by introducing an antibody or an antigen-binding determinant thereof able to bind to the IL-12 and/or IL-23 subunit p40 in a dose of approximately 0.1 5.0 mg/kg under therapeutic regimen into an individual. The antibody or antigen-binding determinant thereof can be introduced once every two weeks, once a week or once in various doses depending on the patient's state. The method is applicable for treating chronic psoriasis. The therapeutic course is cyclic; each cycle makes at least 12 weeks, i.e. the first long-term cycle which involves introducing the antibody; then the introduction of the antibody or determinant thereof is terminated for at least 12 weeks that is followed by another long-term cycle of at least 12 weeks that involves introducing the antibody or fragment thereof. A dose of the antibody or determinant thereof to be introduced makes approximately 100 mg to 200 mg. The treatment is controlled by a psoriasis area and severity index (PASI).

EFFECT: using the method enables higher clinical effectiveness in chronic psoriasis.

40 cl, 35 dwg, 12 tbl, 8 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, specifically dermatology, and may be used for treating the patients with psoriatic erythroderma. For this purpose, detoxification hormone therapy combined with external ointment therapy is preceded by prescribing Galavit in a therapeutic dose of 100 mg intramuscularly every day within the course of 10 procedures.

EFFECT: method provides higher clinical effectiveness ensured by a shorter length of therapy, no side effects and prolonged remission.

2 ex, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to cosmetic industry and represents dermatological composition, which as active ingredient contains combination of glycerol, vaseline and vaseline oil in form of emulsion of oil-in-water or water-in-oil type, where vaseline has temperature of dropping from 51°C to 57°C, consistence from 175 1/10 mm to 195 1/10 mm (conic penetration at 25°C) and viscosity from 4 cSt to 5 cSt at 100°C.

EFFECT: invention ensures improvement of stability in storage and treatment of small superficial burns and exacerbation of eczematous process.

23 cl, 3 ex, 1 tbl, 1 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to the pharmaceutical industry, namely to an ointment for burns, folliculitis, furunculosis, vasculitis treatment and wound healing. The ointment for burns, folliculitis, furunculosis, vasculitis treatment and wound healing containing: bees wax, line seed oil, kerosene and visceral fat of pig taken in certain proportions.

EFFECT: ointment possesses a biostimulating effect, reduces the wound healing time with no post-therapeutic cicatrisation with good fixation, uniform distribution on the skin surface and ease of use.

9 dwg, 9 ex

FIELD: medicine.

SUBSTANCE: invention relates to the application of a solid medicinal product, which is heated under the impact of an alternating magnetic field, for further therapeutic treatment after surgical ablation of tumours and cancerous ulcers. The medicinal product represents a surgical implant, presented in the form of a physiologically acceptable fabric, sponge or film. The medicinal product contains magnetic particles, which generate heat when excited by an impact of the alternating magnetic field, and in this way, heat the medicinal product.

EFFECT: invention ensures considerable improvement of further treatment after operation on cancerous tumour in comparison with chemotherapy.

21 cl, 14 ex

FIELD: veterinary medicine.

SUBSTANCE: method of preparing the anti-inflammatory veterinary ointment for outward application consists in mixing while heating to the temperature of 40-50°C in the reactor of molten petrolatum, pine oleoresin, chlorophyll-carotene paste until homogenous consistency, then glycerine and olive oil is fed portionwise with continuous stirring, after which again mixing of the components is carried out for 10-30 minutes until the homogeneous mass, the resulting ointment is cooled and packaged, at that the components of the mixture are taken in the following ratio, wt %: pine oleoresin 3.0; chlorophyll-carotene paste 3.0; petrolatum 69.0; glycerine 5.0; olive oil 20.0.

EFFECT: improved efficacy of treatment.

2 ex

FIELD: medicine.

SUBSTANCE: drug preparation for treating tuberculosis contains an active substance isoniaside, and a pharmaceutical carrier tiozol gel with the isoniaside concentration of 5.7-54.5 wt % and the tiozol gel concentration of 45.5-94.3 wt %.

EFFECT: higher clinical effectiveness in tuberculosis and lower toxicity.

2 cl, 2 tbl

Burn ointment // 2523551

FIELD: medicine.

SUBSTANCE: ointment contains biologically active substances which are Apis mellifera in an amount of 21-23 wt %, St. John's wort oil in an amount of 12-14 wt %, propolis in an amount of 10-12 wt % and wax in an amount of 7-9 wt %, as well as Vaselin and lanolin as the ointment base.

EFFECT: invention accelerates cell regeneration processes considerably due to a synergetic action of the ingredients.

7 ex

FIELD: medicine.

SUBSTANCE: pharmaceutical composition can additionally contain ethylenediaminotetraacetic acid, polyvinyl pyrrolidone, polyvinyl alcohol, a preserving agent specified in a group: Nipagin, Nipasol, benzoic acid, sodium benzoate, sorbic acid, benzalkonium chloride. As a body-forming base, the composition can contain distilled water, polyethylene oxide 400, polyethylene oxide 4000, polyethylene glycol, propylene glycol, a phosphate buffer, a borate buffer, an acetate-borate buffer depending on a dosage form.

EFFECT: high therapeutic effectiveness, prolonged corneal contact of the preparation which reduces the number of instillations, avoids a risk of side effects and provides good tolerance.

5 cl, 5 ex

FIELD: medicine.

SUBSTANCE: invention refers to the veterinary science and is applicable for treating bovine digital dermatitis. A method involves applying a preparation in the form of an ointment of the following formulation, wt %: veterinary copper sulphate 35-45, zinc oxide 9-11, an ointment base - the rest. The preparation is made by mixing the ingredients until smooth. The preparation is applied on the involved regions 1-2 times with or without a protective dressing.

EFFECT: method is effective in treating bovine digital dermatitis.

1 tbl, 1 ex

FIELD: medicine.

SUBSTANCE: topical gel composition for treating erythema or a related symptom contains brimonidine 0.4 wt % to 0.6 wt %, preferentially in the form of brimonidine tartrate, a gelatinising agent, and at least one polyol. The topical application of the gel composition on the skin involved in erythema or having a manifestation of the related symptom has an effect on a serum or plasma profile of brimonidine with an average Cmax approximately 54±28 pcg/ml or less and an average AUC0-24h approximately 568±277 pcg·h/ml or less.

EFFECT: safe and effective treatment of erythema causing no inadequate drug-related side effects.

19 cl, 3 dwg, 5 tbl, 3 ex

FIELD: medicine.

SUBSTANCE: invention refers to a composition containing encapsulated triterpenic acid: betulinic acid, ursolic acid or derivatives thereof in the form of salts and esters, or triterpene alcohol - betulin, which may be used in medicine for treating and preventing viral infections caused by DNA and RNA-containing viruses, such as influenza viruses, oncogenic viruses, herpes virus, herpes zoster virus, as well as infections caused by gram-positive and gram-negative bacteria: Staphylococcus spp., Streptococcus spp., Enterococcus spp., Shigella spp., Escherichia spp., Salmonella spp., Proteus spp., Acinetobacter spp., Citrobacter spp., Pseudomonas spp., Serratia spp., Klebsiella spp., Antracoides spp., Cryptococcus spp., pathogenic fungi of the genus Microsporum, Trichophyton, Nocardia, Aspergillus, yeast-like fungi of the genus Candida, including multiresistant strains, as well as Actinomycetes and some pathogenic protozoa: Entamoeba histolytica, Trichomonas vaginalis. The invention presents the composition containing an active ingredient presented by 0.5 wt % of betulin or 0.5 wt % of encapsulated triterpenic acid: betulinic acid, ursolic acid or derivatives thereof in the form of salts and esters and others, and carriers presented by: β-cyclodextrins, fullerene, lecithins and polymers binding to the ingredients to form ingredient-carrier complexes, and excipients.

EFFECT: higher efficacy of using the composition.

3 cl

Wound-healing drug // 2517065

FIELD: chemistry.

SUBSTANCE: invention relates to a wound-healing drug which consists of stearic acid; castor oil; zinc stearate; 70% alcohol extract of a plant collection including oak tree bark, marigold flowers, wild chamomile flowers, nettle leaves, taken in ratio of 1:3:2:1, respectively; Na salts of fatty acids of wool fat; boric acid; vaseline; glycerine; triethanolamine; treated water; vegetable oil; Tipton weed extract; wild rose oil or sea buckthorn oil; 10% propolis oily solution; natural L-amino acid-peptide biocomplex obtained by extracting native paunch manure of ruminants with 2.0-3.0% NaCl solution; purified lanolin and derivatives thereof.

EFFECT: improved bactericidal, anti-inflammatory, regenerating, antioxidant and antimicrobial properties, drug does not have allergic action.

4 ex

FIELD: food industry.

SUBSTANCE: invention relates to functional food products and represents a method for production of a non-aqueous health-improving product that is administrated in the form of drops and contains strain of lactic bacteria suspended in vegetable food oil; vegetable food oil is mixed with vitamin D; Lactobacillus rhamnosus GG lactic bacteria are suspended in the produced oil mixture.

EFFECT: invention ensures combination of beneficial effects of the proposed composition ingredients and easiness of the latter dosing during intake.

11 cl, 1 dwg, 1 ex

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