Pharmaceutical composition for treating skin itching
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to medicine, more specifically to a composition for treating dermatologic diseases, preferentially skin itching. The composition causes antiallergic action and is used in treating allergic reactions (rash, urticaria), insect bites, ultraviolet erythema and skin burns. The pharmaceutical composition contains azelastine hydrochloride and benzocaine as active substances, and a hydrophobic ingredient, a hydrophilic ingredient, an emulsifying agent and a pH corrective agent as additive agents. As the pH corrective agent, the composition contains preferentially succinic acid. The pharmaceutical composition is presented as a soft dosage form, preferentially in the form of a cream.
EFFECT: composition according to the invention is characterised by high pharmacologic activity, good package extrusion, and storage-stability.
9 cl, 1 tbl, 14 ex
The invention relates to the field of medicine and pharmaceutics, specifically relates to compositions for external use, which can be used for the treatment of dermatological diseases, accompanied with symptoms such as itching, burning, soreness: contact dermatitis (simple and allergic), limited cutaneous itching, limited neurodermatitis (lichen Vidal), itching of the anus, perianal eczema area, dermatitis, perianal region, urticaria, insect bites, burns, including sun and burns from jellyfish.
Currently, skin diseases are very common. The vast majority of such diseases accompanied by itching sensation, but there are dermatoses, in which itching is the predominant symptom (urticaria, neurodermatitis, eczema, prurigo).
Important role in the treatment of itching plays a topical therapy. When universal itch used wiping solution antipruritic agents (2% tincture salicylic acid or carbolic acid, menthol, or Dimedrol, and divorced three times vinegar). In the treatment of localized itching apply antipruritic means in the form of powders, creams, ointments or pastes, which are applied after first thoroughly clean the affected area with disinfectant. Use diphenhydramine (1-2%), Anya is Tesin (5%) and glucocorticosteroid external means [Medical journal", No. 24/25(451-45) from 08.08.2008].
The pathogenesis of allergic reactions is determined mainly by inadequate mechanisms specific reactivity due to development of hypersensitivity delayed and immediate type. An important role is also played and nonspecific mechanisms that are manifested, in particular, increased ability of mast cells and basophils to release mediators (histamine, serotonin, prostaglandin E2), which stimulate the sensitive nerve endings, which causes skin reactions such as rash and itching [O. Zaitseva Century Allergic rhinitis: diagnosis and treatment. http://www.lvrach.ru/2010/05/13769862/].
A special group of drugs for the treatment of itching are antihistamines. The effectiveness of antihistamines is determined by the mechanism of development of itching, especially the itching of allergic nature. As you know, when exposed to an allergen on mast cells degranulation occurs, the result of which are mediators of inflammation, the most important of which is histamine. Histamine interacts with Hl-receptor and initiates the so-called allergic cascade. Antihistamines in the main block H1receptors and thereby inhibit the development of allergic inflammation [Register of medicines of Russia radar encyclopedia of Lech is STV. - 16 vol. / CH. as amended, the vishkovsky. -M.: "radar-2008", 2007. - S. 82, 1134].
The most typical representatives of antihistamine medications called antihistamines first generation (sedatives) are:
• Diphenhydramine (diphenhydramine). Applied in the form of tablets, intramuscular and intravenous solutions, in candles, in the form of eye drops. Produced in Russia.
Dimenhydrinate (dedalon). Used in tablets, produced in Hungary.
• Quirinalis (fenkarol). Used in tablets, produced in Russia.
• Promethazine (promethazine, pipolphen). Is applied in drops, tablets, intramuscular solutions. Produced in Hungary.
• Mebhydrolin (diasorin). Used in pills and pellets, produced in Russia.
• Chloropyramine (suprastin). Used in tablets, intramuscular solutions. Produced in Russia.
• Clemastin (tavegil). Used in tablets, intramuscular solutions. Produced in Hungary.
Clinical characteristics of antihistamines first generation due to basic properties: the onset of effect in 15-20 minutes after administration, the possibility of a single dose without compromising the effectiveness of the reversible binding of H1receptors, a short course of 5-7 days in the depletion of the sensitivity of Hl-cocktail recipes. is s and the disappearance of the blocking effect to a 7-10-day use. The abundance of side effects, inability to use long courses, the reception frequency several times a day dictated an urgent need for the creation of antihistamines with more positive possibilities. In the late 70-ies of XX century such drugs appeared in General medical practice. They were given the name of antihistamines second generation.
To antihistamine drugs of the second generation are:
• Loratadine (claritin), is made in USA.
• Avastin (kestin). Used in tablets, made in France.
• Astemizole. Used in tablets, made in India.
To antihistamine drugs of the second generation also includes funds used tapicerki, namely aerosols, eye drops, nasal sprays. The most famous among them:
• Sodium cromoglycate (Intal) is used in capsules, in metered aerosols. Made in France.
• Levocabastine (histime). Used as eye drops and nasal spray. Manufactured in Belgium.
• Azelastin (allergodil). Used as eye drops and nasal spray. Manufactured in Germany.
• Dimetindene. Applied in the form of drops for ingestion and gel for external use. Produced in Switzerland.
The apparent advantage of antihist is mine second-generation drugs before the first-generation drugs was high selectivity of H 1receptors, the impossibility of passing through the blood-brain barrier, sustainable relationship with H1-receptors. These qualities, in turn, led to such clinical characteristics of antihistamines second generation, as the lack of sedative effect, the reception frequency 1-2 times per day, the duration of the effective rate over 10 days (up to 3 months) [Antihistamines in pediatric Allergology [http://bibicall.seo-time.ru/articles/21].
Significant breakthrough in the development of antihistamine drugs for the treatment of allergic diseases has been the emergence of new locally acting drugs in different dosage forms, which are designed to relieve local manifestations of Allergy [O. Zaitseva Century Allergic rhinitis: diagnosis and treatment. http://www.lvrach.ru/2010/05/13769862/].
Antihistamines are used to treat itching for a long time. They usually are taken into and used in parallel with traditional facilities for the treatment of itching.
In the pharmaceutical market of Russia for the treatment of itching of the skin, apply the gel, active ingredient is diphenhydramine - blocker of histamine H1-receptors, which quickly reduces the itching and has a pronounced anti-allergic effect. The preparation is indicated primarily for the treatment of itchy allergic is Matasov, and is also used for ulcers of various origins [Medical Gazette, No. 24/25(451-45) from 08.08.2008].
There is also a gel for topical application, the active substance - Gemeinden - blocker H1-histamine receptors, is a competitive antagonist of histamine released fat cells, blocks the not employed them H1-histamine receptors, and therefore most effective for preventing allergic reactions of the immediate type (or gain in connection with the release of new portions of histamine). Also blocks the effects of other mediators (serotonin, bradykinin) involved in the pathogenesis of allergic reactions. Significantly reduces the increased permeability of capillaries. Has weak anticholinergic and sedative effect.
The disadvantages of the above drugs is contraindicated, side-effects associated with the inhibition of the CNS, as well as the need to take precautionary measures in their application [Resnicow L. D. Gel with anti-inflammatory and antiallergic effect./ Schwartzman J. Y., ASNOVA O. K.// Patent RU 2 370 265 C1]. Presents gels have a unidirectional effect, and there is a need for an effective multifunctional medicines.
Azelastin - strong antiallergic drug for long periods. tositsa to pharmacological group H1-antihistamines. Selectively blocking H1-histamine receptors, reduces capillary permeability and exudation, inhibits mast cell degranulation (prevents the release of histamine and other mediators of Allergy). Dosage forms azelastina for local use (nasal spray and eye drops) are included in the standard treatment of allergic diseases (seasonal and perennial allergic rhinitis and conjunctivitis). The benefits of local treatment azelastina are fast achieving high local concentrations and lack of side effects that can occur when systemic use [Federal guidance on the use of drugs (formulary system). Issue VIII.- M: ECHO,2008.-1000]. Regardless of the method of introduction, the antagonistic action azelastina in relation to H1-receptors surpasses the similar action of antihistamines previous generations [In vivo and in vitro HI antagonist properties of azelastine./ The Pharmacologist. 1981 - Vol.23, No. 3.-p.l49]. So, according to their ability to inhibit the release of histamine from mast cells, azelastin 5000 times more effective than ketotifen, sodium cromoglycate, theophylline and astemizole [MC Tavish D, Sorkin EM.Azelastine. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential.// Drugs.-1989 - vol.38, No. 5. P. 778-800].
In the European patent E 958823 (prototype) described composition Azelastina, includes Azelastin, hydrocarbons, waxes (hydrophobic component), or higher polyhydric alcohols, water (hydrophilic component and the emulsifier and basic pH correctors or other targeted supplements, and does not contain fatty acids (prototype). In the description of the patent it is noted that to provide a satisfactory absorption Azelastina need to maintain a basic pH of the composition, i.e. more than 7, preferably of 9.5 or more, but under these conditions there is a strong irritant effect. The use of penetrants - amplifiers absorption (Japanese application JP2-124824 and JP6-40949) is not always acceptable, as penetrants may potentiate adverse irritant effect. The authors are well-known solution according to the patent EP solve the conflict with the selection of specific additional ingredients that can reduce the pH of the composition to weakly basic. Known composition has a pH of 7 or slightly above, but it is above physiological pH values, which is not always acceptable, and may increase the potential irritant effects with the introduction of other active substances, such as benzocaine.
Benzocaine is one of the very first synthetic compounds used as a local anesthetic funds. The mechanism of local anesthetic action of benzocaine due to a decrease in cell membrane permeability DL the ions Na+, the displacement of CA 2+ from receptors located on the inner surface of the membrane, the blockade of the origin and conduction of nerve impulses. Benzocaine has an active surface analgesic action, low toxicity.
Currently on the pharmaceutical market, there is no drug that would simultaneously provide antipruritic and anesthetic action. Based on the above we can conclude that the development of the new combined product containing as active ingredients azelastine and benzocaine in the form of topical cream is appropriate and relevant.
The objective of this invention is to provide pharmaceutical compositions for the treatment of dermatological diseases, in particular itching of the skin, the active ingredients which are azelastina hydrochloride (itchy skin) and benzocaine (has a local anesthetic effect).
To solve this problem is proposed pharmaceutical composition for external use in the form of soft medicinal forms, including azelastina hydrochloride and pharmaceutically acceptable excipients, which additionally contains benzocaine and pH corrector. Preferably the inventive composition includes as an auxiliary substances hydrophobic component, the Hydra is a multidisciplinary component and emulsifier. A new dosage form for the treatment of dermatological diseases is preferably in the form of cream.
As a local anesthetic tools included local anesthetic benzocaine. It was unexpectedly found that the introduction into the composition of benzocaine helps to enhance therapeutic activity by expanding the range of local anaesthetic activity, and simultaneously to maintain the original activity outside of the basic (alkaline) pH values of the composition without the use of penetrants, i.e. in our case, the second active ingredient is benzocaine actually acts as a penetrant Azelastina hydrochloride. Thus resolving the problem of the negative impact on the skin from basic (alkaline) pH values, which is confirmed by the results of the experiment showed the absence of the claimed composition side effects. At the same time the composition is characterized by the appearance of a new local anesthetic activity, with the declared composition characterized by stability of the dosage form during storage, including the lack of degradation of active ingredients. Thus, the proposed solution can widen the spectrum of action while maintaining a high antihistaminic activity without the use of penetrants is stable during storage, in particular there is no degradation of active ingredients.
In one embodiment of the invention in the cream can be included BHT (or Equivalent) one of the major synthetic drugs group of antioxidants, i.e. compounds which are inhibitors of free radical reactions. Used for cystitis, superficial burns, frostbite 1-2 degree long-term healing ray and trophic ulcers. Applied BHT external (5% liniment) burns, frostbite, ulcers. With massive scabs application of 5% of linemate dibunola leads to increased exclusion of Slough and necrotic tissue, which may be accompanied by phenomena of wet necrosis, intractable with the alternation of bands dibunola with wet-drying Furacilinum bandages. In the claimed compositions, he will have additional pharmacological action, i.e., to further expand the spectrum of activity.
In the most preferred embodiment of the proposed pharmaceutical composition with anti-itching action includes azelastina hydrochloride, benzocaine, BHT, a hydrophobic component, a hydrophilic component, an emulsifier, and optionally, a preservative in the following ratio of components, g/100 g composition:
Azelastina hydrochloride 0.05 to 0.15
Benzocaine 1.5 to 2.5
The hydrophobic component of 10.5-38,0
The hydrophilic component 30,01-90,08
Emulsifiers 3,00 to 12.0
As the hydrophobic phase is preferably used Dimethicone (or else silicone oil, such as cyclomethicone), and liquid paraffin, solid paraffin, vaseline, vaseline oil. The preferred ratio of hydrophobic substances phase:
Vaseline oil 4,0-20,0
As the hydrophilic phase is preferable to use polyhydric alcohols, more preferably propylene glycol and/or polyethylene oxide-400 (macrogol-400), and water. The preferred ratio of hydrophilic substances phase:
Propylene glycol 5,00-30,0
The polyethylene oxide-400 5,0-30,0
As emulsifiers use of macrogol 20 sitosterolemia ether and cetosteatil alcohol. The preferred ratio of these substances:
Of macrogol 20 sitosterolemia ether 1,5-5,0
Cetosteatil alcohol 1,5-7,0
Preferably the composition contains as proof pH organic acid, preferably succinic acid.
As preservative preferably used methyl parahydroxybenzoate and sodium propyl parahydroxybenzoate, more preferably a combination of both.
Picked up cream Foundation that provides a penetration current is of exist through the epidermis and provides them to the border of the epidermis and dermis, where are the receptors itching. It also provides sufficient duration of action of the active ingredients.
The pharmaceutical composition is a soft dosage form is preferably in the form of a cream, which is an emulsion of the first kind (oil/water). Selected qualitative and quantitative composition represented by the composition found experimentally and is the best.
The claimed composition is characterized by the stability of the dosage form during storage, achieves a creamy consistency and good extrusion of the finished dosage form of tubes.
the pH of the composition is in the range of from 5.5 to 7, which prevents the decomposition of active ingredients. To create a specified pH, if necessary, preferably succinic acid is used.
Currently, the global pharmaceutical market dosage forms azelastina for cutaneous application does not exist. Based on this specific pharmacological activity of the cream associated with such blocker H-1 histamine receptors-dimetindene maleate, which is included in the gel applied topically skin for the same reasons: if skin irritation and itching in skin allergies, hives, atopic dermatitis, measles, rubella, chickenpox, insect bites, sun ago the Ah).
On the basis of expected pharmacological orientation of the claimed composition Azelastina and Benzocaine as antihistaminic and local anesthetic means for cutaneous application of skin irritation that accompanies local manifestations of allergic reactions (rash, urticaria), insect bites, solar erythema and superficial burns, its specific pharmacological activity explored the local application of 3 series on the following parameters:
- indicators antiexudative action in acute aseptic histamine-induced inflammation of the foot rats.
- normalizing influence on pathologically elevated histamine-induced vascular tissue permeability in rats.
- indicators of local anesthetic action when thermopolium irritation tail rats (test "tail-flick").
The results of the study of the specific pharmacological activity suggest that developed the drug an expression inhibits the effects of histamine, giving antiexudative action at the histamine-induced edema and preventing histamine-induced disorders vascular tissue permeability. Double-exposure prophylaxis, application of the inventive composition to the skin inflamed feet have antiexudative effect observed is tsya trend towards higher activity developed cream compared to the reference drug. After 0.5 hours after the injection of histamine effect the proposed composition (example 1) was 30.8%), whereas for the reference drug, with 18.1%. To 1 hour after the induction of inflammation, the effects of the compared drugs significantly reduced, while the increase in swelling of the foot has no significant difference with that in the control group. When preventive double cutaneous application of the inventive composition has a strong antihistamine effect, preventing the development of disorders of the vascular tissue permeability. So, there is a significant significant increase latent period coloring papules to 125,0 sec (83.6% more than in the control group without drug), which is slightly more pronounced than for the comparison drug, where the latent period was 105,0 sec. Similar results were obtained for the compositions of examples 7 and 12.
The cream also has local anesthetic activity, dynamics and intensity of which corresponds to those monotherapy. According to the experiment anaesthetic effect of the inventive composition of example 1 is developing rapidly, accounting for 10 min after drug application 30.8% and gradually decreasing in the future: for 30 mines up to 20.5 per cent, to 60 min to 5.6%. On the dynamics and intensity of anaesthetic effect of the claimed composition is comparable with those for monotherapy with an equivalent amount of the of Benzocaine.
As follows from the obtained data, the expression of the suppression of histamine-induced effects cream somewhat superior to gel with dimetindene, on the basis of which conclusions can be drawn about the presence of high therapeutic activity of the claimed composition.
The resulting composition based azelastina and benzocaine meet regulatory requirements for microbiological purity.
The cream has a good sensory properties, easy to apply and spread on the skin.
A study was conducted irritant action of the drug. As a result of the research it was concluded that the composition at sub-chronic cutaneous application in experiments on rats at a dose of 0.3 g/kg for azelastina hydrochloride has no irritant effect. The drug does not cause significant changes in the content of total protein, albumin and indicator thymol turbidity test in the serum of rats compared with the original data. A study of oral toxicity, sub-chronic experiment on rats revealed no toxic effect of the drug on their General condition and behavior.
On the efficiency of the antimicrobial preservative action meets the requirements of criterion And the European Pharmacopoeia.
Thus, it is proposed pharmaceutical composition intended for coinage use as anti-allergic drugs skin irritation, accompanying local manifestations of allergic reactions (rash, urticaria), insect bites, solar erythema and superficial burns.
The composition may be obtained known from the technology of soft medicinal forms of ways, in particular according to a typical example.
A typical example.
Charged to the reactor portion of the hydrophilic component (water, propylene glycol, succinic acid), and add a hydrophobic component (vaseline, liquid paraffin, solid paraffin, Dimethicone) and emulsifier (macrogol-20 cetosteatil ether, cetosteatil alcohol). Heat the mass to 70°C and carry out the shutter speed until complete dissolution of all components. Include high-speed homogenizer and intensive mixing, are the liquid emulsion and cool it to a temperature of 60°C, add a solution azelastina hydrochloride in water and a solution of benzocaine, dibunola in macrogol (polyethyleneoxide) - 400, and optionally a preservative solution in the base of the cream and spend homogenization, if necessary, adjust pH to 5.5-7.0mm. Cool the resulting cream to room temperature with slow stirring under vacuum. Get the cream white color, which is Packed in tubes.
1. The pharmaceutical composition for external when the change in the form of soft medicinal forms, comprising as active substance azelastina hydrochloride, and as auxiliary substances hydrophobic component, a hydrophilic component and an emulsifier, characterized in that it further includes benzocaine and pH corrector.
2. The pharmaceutical composition under item 1, characterized in that it includes BHT.
3. The pharmaceutical composition under item 1 or 2, characterized in that it has a pH from 5.5 to 7.
4. The pharmaceutical composition according to p. 3, characterized in that it further includes a preservative.
5. The pharmaceutical composition according to p. 4, characterized in that the emulsifier includes a combination of macrogol 20 cetosteatil ether and cetosteatil alcohol.
6. The pharmaceutical composition according to p. 5, characterized in that as the hydrophobic component includes vaseline, solid paraffin, Dimethicone and liquid paraffin.
7. The pharmaceutical composition according to p. 6, characterized in that the hydrophilic component it contains a polyethylene oxide-400, propylene glycol and water.
8. The pharmaceutical composition according to p. 7, characterized in that it is made mainly in the form of cream.
9. The pharmaceutical composition according to p. 8, characterized in that it contains as proof pH succinic acid.
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to biotechnology. Presented are versions of an antigen-binding polypeptide specific to LIGHT polypeptide characterised by a variable domain of heavy and light chains, as well as versions of based conjugates for treating a disease or a condition. What is described is a pharmaceutical composition for inhibiting apoptosis induced by human LIGHT based on a therapeutically effective amount of the polypeptide. There are disclosed: a method of treating or a diagnosing the disease or condition on the basis of the composition. There are described versions of the recovered polynucleotide or a cell transformed by the polynucleotide for preparing the antigen-binding polypeptide, as well as a method for producing the antigen-binding polypeptide on the basis of the cell.
EFFECT: using the invention provides the antibodies, which block the human or macaque LIGHT interaction to LIGHT receptors that can find application in treating various diseases related to high T-cell activity.
23 cl, 11 dwg, 8 tbl, 3 ex
SUBSTANCE: invention represents methods for treatment of an autoimmune disease, including introduction of a pharmaceutical composition to a subject, containing a pharmaceutically acceptable carrier and a humanised anti-CD4-antibody, capable of activating regulatory T-cells CD4+CD25+, where the specified antibody contains a V-domain of an H-chain, containing sequences DCRMY, VISVKSENYGANYAESVRG and SYYRYDVGAWFAY, and a V-domain of an L-chain, containing sequences RASKSVSTSGYSYIY, LASILES and QHSRELPWT. The specified composition is introduced to a subject with frequency from daily intake to introduction every 31st day and with a dose of a humanised anti-CD4-antibody from 20 to 200 mg, or from 8 to 60 mg/m2 of the subject body surface area, or from 0.2 to 2 mg/kg. This invention also discloses a set for treatment of an autoimmune disease, which contains multiple doses of the above pharmaceutical composition.
EFFECT: invention makes it possible to introduce a pharmaceutical composition containing a humanised anti-CD4-antibody, with more lengthy intervals of dosing and in higher doses, not losing the therapeutical effect and not causing side effects.
59 cl, 41 dwg, 27 tbl, 9 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to biotechnology and represents methods of treating an autoimmune disease involving administering into an individual a pharmaceutical composition containing a pharmaceutically acceptable carrier and a humanised anti-CD4-antibody, able to activate the regulatory C-cells CD4+CD25+, wherein the above antibody contains V-domain of H-chain containing the sequences DCRMY, VISVKSENYGANYAESVRG and SYYRYDVGAWFAY, and V-domain of L-chain containing the sequences RASKSVSTSGYSYIY, LASILES and QHSRELPWT; the above composition is administered subcutaneously into the individual in a dose of the humanized anti-CD4-antibody 20 to 200 mg or 8 to 60 mg/m2 of the individual's body surface, or 0.2 to 2 mg/kg. The present invention also discloses the pharmaceutical compositions applicable in the above methods of treating the autoimmune disease.
EFFECT: invention enables administering the pharmaceutical composition containing the humanised anti-CD4-antibody in higher doses losing no therapeutic effect and causing no intensification of any side effects.
46 cl, 20 dwg, 21 tbl, 8 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to field of biochemistry, in particular to single variable domain, aimed against IL-6R, to polypeptide and construction, directed against IL-6R, containing said single variable domain, as well as to methods of obtaining them. Disclosed are nucleic acids, coding said single variable domain, polypeptide and construction, as well as genetic constructions, containing said nucleic acids. Described are host cells and host organisms, containing said nucleic acids. Invention also deals with composition for blocking interaction of IL-6/IL-6R, containing effective quantity of described single variable domain, polypeptide, construction, nucleic acid or genetic construction. Also disclosed is method of prevention and/or treatment of at least one of diseases or disorders, associated with IL-6, IL-6R, complex IL-6/IL-6R and/or signal pathways, in which IL-6, IL-6R or complex IL-6/IL-6R is involved and/or biological functions and reactions, win which IL-6, IL-6R or complex IL-6/IL-6R takes part with application of described single variable domain, polypeptide, construction or composition.
EFFECT: invention makes it possible to block interaction of IL-6/IL-6R effectively with increased affinity and biological activity.
25 cl, 70 dwg, 56 tbl, 61 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: group of inventions refers to organic chemistry, namely to a compound of formula I and to their pharmaceutically acceptable salt or their ester, wherein W means C(H)2, C(H)2-C(H)2 or C(H)(CH3); X is specified in a group consisting of: (1) O, (2) N(H), (4) S, (5) S(O) and (6) S(O)2; Y means carbon or nitrogen; R1 is specified in a group consisting of: (1) hydrogen, (2) halogen, (3) methyl optionally substituted by fluorine, (4) C1-7alkoxygroup optionally substituted by fluorine, (5) cyano group and (6) C1-7alkylsulphonyl; R2 means hydrogen, fluorine, chlorine or C1-7alkoxygroup; R3 means hydrogen, fluorine, chlorine, bromine or methyl; R4 is specified in a group consisting of: (1) hydrogen, (2) halogen, (3) C1-7alkyl optionally substituted by fluorine, (4) C3-7cycloalkyl, and (5) ethenyl; R5 and R6 are independently from each other specified in a group consisting of: (1) hydrogen, (2) halogen, (3) C1-7alkyl, (4) cyanogroup and (5) C3-7cycloalkyl; R7 means cyano group or S(O)2-R8, wherein R8 is specified in a group consisting of: (1) C1-7alkyl, (2) C3-7cycloalkyl, (4) C1-7alkylamino group, (5) C1-7dialkylamino group, (6) lower heterocycloalkyl optionally substituted by halogen, C1-7alkyl, or C1-7alkoxycarbonyl and (7) 2-oxa-6-azaspiro[3.3]hept-6-yl, wherein lower heterocycloalkyl means a saturated or partially unsaturated non-aromatic ring fragment containing 3 to 7 atoms bound together to form a ring structure, wherein one, two or three ring atoms are heteroatoms, whereas the rest ring atoms are carbon atoms; and pharmaceutically acceptable esters represent methyl and ethyl acid esters of formula I acceptable as prodrugs. The invention also refers to a pharmaceutical composition based on the compound of formula .
EFFECT: prepared are new compounds possessing the CRTH2 receptor antagonist or partial agonist activity.
23 cl, 90 ex
SUBSTANCE: invention refers to molecular biotechnology and medicine. There are described methods of treating an autoimmune disease. The methods provide administering a pharmaceutical composition containing CD4 humanised antibody. The antibody is able to activate CD4+ CB25+ regulatory T-cells.
EFFECT: presented group of inventions can be used in medicine.
33 cl, 41 dwg, 20 tbl, 5 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: present invention refers to immunology. There are presented: an antibody binding to interleukin-17 (IL-17) characterised by 6 CDR of a light and heavy chain, as well as a coding nucleic acid and a vector for expression of the above antibody. What is described is a pharmaceutical composition for treating a patient with multiple sclerosis, rheumatoid arthritis, psoriasis, Crohn's disease, chronic obstructive pulmonary disease, asthma, graft rejection on the basis of the above antibody. What is disclosed is a method for preparing the antibody by means of expressing the respective nucleic acid and recovering the antibody from a cell culture or a cell culture supernatant.
EFFECT: using this invention provides the antibody with IC50 twice as much as shown by in vitro IL-6 and IL-8 neutralisation as compared to the known NVP-AIN-497 antibody, which binds human IL-17A and IL-17F that can find application in medicine in therapy of various inflammatory diseases.
9 cl, 6 tbl, 11 ex
SUBSTANCE: composition contains tacrolimus as an active substance in a therapeutically effective amount, a hydrophobic ingredient, a hydrophilic ingredient, an emulsifier and a stabiliser - disodium edentate and phenoxyethanol. As tacrolimus, the composition contains tacrolimus monohydrate. The composition contains phenoxyethanol in a combination with ethylhexyl glycerol in a ratio of 9:1. The composition is presented in the form of a semi-solid dosage form.
EFFECT: formulation is characterised by stability, uniform distribution of the active substance, usability and good pack extrusion.
6 cl, 2 tbl
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to substituted isoquinolines and isoquinolinones of formula (I) and to their stereoisomer and/or tautomer forms and/or pharmaceutically acceptable salts, wherein R1 is H, OH or NH2; R3 is H; R4 is H, halogen or (C1-C6)alkylene-R'; R5 is H, halogen, (C1-C6)alkyl; R7 is H, halogen, (C1-C6)alkyl, O-(C1-C6)alkyl; R8 is H; R6 is absent; or is one of (C1-C4)alkylene related to a cycloalkyl ring related to a cycloalkyl ring, wherein (C1-C4)alkylene forms a second bond to another carbon atom of the cycloalkyl ring to form a bicyclic ring system, R10 is H, phenyl, or pyridine, wherein phenyl is unsubstituted or substituted; R11 is H, (C1-C6)alkyl; or R11 and R12 together with the carbon atom to which they are attached form (C3)cycloalkyl; R12 is (C1-C6)alkyl, (C3-C8)cycloalkyl or phenyl; or R12 is H, provided r=2 and another R12 is other than H; or R11 and R12 together with the carbon atom to which they are attached form (C3)cycloalkyl; R13 and R14 are independently H, (C1-C6)alkyl, (C1-C6)alkylene-R', C(O)O-(C1-C6)alkyl, n is equal to 0; m is equal to 1 or 2; s is equal to 1 or 2; r is equal to 1 or 2; L is O, NH; R' is (C3-C8)cycloalkyl, (C6-C10)aryl; wherein in R11 and R12 residues, alkyl is unsubstituted or optionally substituted by one OCH3; wherein in R11 and R12 residues, alkyl is unsubstituted or optionally substituted by one or more halogens; wherein in R10 and R12 residues, (C6-C10)aryl is unsubstituted or optionally substituted by one or two groups optionally specified in halogen, CN, (C1-C6)alkyl, O-(C1-C6)alkyl, SO2-(C1-C6)alkyl, CF3 and OCF3. Also, the invention refers to using a compound of formula (I).
EFFECT: there are prepared new isoquinoline and isoquinolinone derivatives effective in treating and preventing the diseases related to Rho-kinase inhibition.
38 cl, 132 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to compounds of formula I wherein R means C1-6alkyl, C1-6halogenalkyl, hydroxy-C1-6alkyl, hydroxygroup or halogen; m, n is equal to 0 or 1; Z1 means CH or NH; Z2 means CH or N; Z3 means CR1, N or NR2; R1 means H, C1-6alkyl, C3-7cycloalkyl, cyanogroup, cyano-C1-6alkyl or halogen; R2 means H or C1-6alkyl; X means CH, CR' or N; X' means CH, CR' or N; r is equal to 1; Y means CH or CR'; R' means R'a or R'b; R'a means a halogen or cyanogroup; R'b means C1-6alkyl, heterocycloalkyl specified in piperazinyl, morpholinyl, piperidinyl, thiomorpholinyl, azetidinyl, pyrrolidinyl, OR", SR", S(=O)2R" or NR"R", optionally substituted by one or more R'c; R'c means a hydroxygroup, oxogroup, cyanogroup, C1-6alkyl, pyridinyl, carboxy-C1-6alkyl, aminocarbonyl-C1-6alkylaminogroup, C1-6alkylaminogroup, C1-6dialkylaminogroup or C1-6alkoxygroup; R" means H, C1-6alkyl, hydroxy-C1-6alkyl, piperidinyl, C3-7cycloalkyl or pyridinyl; Q means S(=O)2Q1, C(=O)Q2, C(=O)OQ3 or Q4; Q1 means C1-6alkyl, C3-7cycloalkyl-C1-6alkyl, C1-6alkylaminogroup or C1-6dialkylaminogroup optionally substituted by one or more Q1'; each Q1' independently means C1-6alkyl or cyanogroup; Q2 means C1-6alkyl optionally substituted by one or more Q2'; each Q2' independently means a cyanogroup; Q3 means C1-6alkyl; Q4 means C1-6alkyl, oxetanyl optionally substituted by one or more Q4'; each Q4' independently means a halogen, cyanogroup, cyano-C1-6alkyl; p is equal to 0, 1 or 2; q is equal to 1 or 2; each means a single bond or a double bond; provided one of Z1 and Z2, and Z3 and Z3 bonds are double and single.
EFFECT: compounds of formula I as JAK inhibitors.
23 cl, 2 tbl, 121 ex
SUBSTANCE: therapeutic agent contains carboxymethyl cellulose sodium salt as a base and a combination of antiseptic, 0.01% Myramistinum and metronidazole as therapeutic ingredients. The invention provides preparing the therapeutic agent possessing the antiseptic, wound-healing and sorption action on local pyoinflammatory processes in soft tissues and mucous membranes, used in surgery, dermatology, obstetrics and gynaecology, otorhinolaryngology.
EFFECT: agent possesses the higher efficacy.
2 tbl, 2 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to immunology. What is presented is a prophylactic or therapeutic agent for IL-31 related itching, containing an effective amount of anti-NR10 antibody, possessing NR10-neutralising (alternative name IL-31RA) activity as an active ingredient, and pharmaceutically acceptable additives, wherein the anti-NR10 antibody represents an antibody, which contains the heavy-chain amino acid sequence SEQ ID NO: 17 and the light-chain amino acid sequence SEQ ID NO: 18, or its humanised antibody. What is presented is using the anti-NR10 antibody containing the heavy- and light-chain amino acid sequences SEQ ID NO: 17 and SEQ ID NO: 18 respectively, or its humanised antibodies for preparing the prophylactic or therapeutic agent for IL-31 related itching. What is described is a method for preventing or treating IL-31 related itching, which involves the stage of administering the anti-NR10 antibody containing the heavy-chain amino acid sequence SEQ ID NO: 17 and the light-chain amino acid sequence SEQ ID NO: 18, or its humanised antibodies.
EFFECT: invention enables suppressing IL-31 overexpression itching.
3 cl, 5 dwg, 2 ex
SUBSTANCE: course of the complex exposure of audio-, video- and reflex therapy with an unconscious suggestion is carried out. That is preceded by administering epitalamine 10 mg dissolved in a physiological solution 5 ml by electrophoresis. Administration is binasal from a positive pole into a patient's nasal passages in a number of 10-15 procedures. The second electrode is placed on the occipital lobe or the cervicothoracic spine. The complex exposure involves watching video information, listening to audio musical information with an introduced suggestive relaxing fable repeated every 1 minute, and exposing through electrodes provided on the skin projections in biologically active points within the lesions to electrical current a spectral structure of which is formed by the same musical signal by an electric musical massager. That is combined with the electric stimulation of the reflex areas arranged in the lesions if feeling itching therein. The exposure length is 45-60 minutes, domiciliary in any time of the day, daily for 3-4 weeks.
EFFECT: effective exposure on the mechanisms eliminating or relieving the itching intensity by preparing the neuroregularoty structures of the patient's central nervous system by the following therapeutic stage of the two-staged integrated exposure according to the presented regimen.
SUBSTANCE: invention refers to ligands in the form of synthetic peptide amides of a kappa-opiate receptor, and namely to agonists of the kappa-opiate receptor, which show a low inhibition degree of P450 CYP and a low degree of penetration into brain. According to the invention, synthetic peptide amide is described by the following formula:
EFFECT: pharmaceutical compositions containing the above compounds are suitable for prophylaxis and curing of pain and inflammation, which are related to different diseases and states.
19 cl, 11 dwg, 53 ex
SUBSTANCE: invention relates to novel omega-3 lipid compounds of general formula (I) or to their pharmaceutically acceptable salt, where in formula (I): R1 and R2 are similar or different and can be selected from group of substitutes, consisting of hydrogen atom, hydroxy group, C1-C7alkyl group, halogen atom, C1-C7alkoxy group, C1-C7alkylthio group, C1-C7alkoxycarbonyl group, carboxy group, aminogroup and C1-C7alkylamino group; X represents carboxylic acid or its carbonate, selected from ethylcarboxylate, methylcarboxylate, n-propylcarboxylate, isopropylcarboxylate, n-butylcarboxylate, sec-butylcarboxylate or n-hexylcarboxylate, carboxylic acid in form of triglyceride, diglyceride, 1-monoglyceride or 2-monoglyceride, or carboxamide, selected from primary carboxamide, N-methylcarboxamide, N,N-dimethylcarboxamide, N-ethylcarboxamide or N,N-diethylcarboxamide; and Y stands for C16-C22 alkene with two or more double bonds, which have E- and/or Z-configuration.
EFFECT: described are pharmaceutical and lipid compositions, which contain said compounds, for application as medications, in particular, for treatment and/or prevention of peripheral insulin resistance and/or condition of diabetes, for instance, type 2 diabetes, increased levels of triglycerides and/or levels of non-HDL cholesterol, LDL cholesterol and VLDL cholesterol, hyperlipidemic condition, for instance, hypertriglyceridemia (HTG), obesity or condition of excessive body weight, fatty liver disease, for instance, non-alcoholic fatty liver disease (NAFLD) or inflammatory disease or condition.
60 cl, 3 tbl, 65 ex
SUBSTANCE: invention refers to synthetic peptide amides of formula I
, which are agonists of a kappa-opiate receptor and show a low inhibition degree P450 CYP and lower brain penetration degree. Besides, the invention refers to pharmaceutical compositions containing the above compounds.
EFFECT: possibility of using compounds for prophylaxis and curing of pain and inflammation, which are related to different diseases and states.
17 cl, 9 tbl, 8 dwg, 39 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to veterinary, namely to veterinary mycology, bacteriology and parasitology. Complex medication for treating dogs and cats with cutaneous mycoses, bacterioses and acaroses includes as active and auxiliary components (wt %): chlorhexidine digluconate - 0.05-0.075; cypermethrin - 10.0-15.0; tetramethrin - 1.5-2.25; pyperonyl butoxide - 10.0-15.0; dimethyl sulfoxide - 15.0-22.5; polyethylene glycol M-200 or M 400 - 10.0-15.0; glycerol - 10.0-15.0, 1,2-propylene glycol - the remaining part.
EFFECT: medication has complex effect, without staining skin and its derivatives, is easily washed away with water, is efficient at temperature from minus 30 to plus 30°C and higher, has 2-year long storage term.
FIELD: medicine, pharmaceutics.
SUBSTANCE: present invention refers to crystalline modifications: 1 (polymorphous form F), 2 (polymorphous form I) and 3 (polymorphous form X) of monosodium salt of D-isoglytamyl-D-tryptophan (1:1) characterised by powder X-ray pattern peaks presented in the application materials, as well as to pharmaceutical compositions containing them. The invention describes their use for treating various diseases and body conditions of at least one autoimmune diseases specified in a group consisting of psoriasis, atopic dermatitis and rheumatoid arthritis.
EFFECT: present invention describes the methods for producing the declared crystalline modifications of monosodium salt of D-isoglytamyl-D-tryptophan (1:1).
42 cl, 4 ex, 9 dwg
SUBSTANCE: invention relates to a quinazoline derivative of general formula , or a pharmaceutically acceptable salt thereof , where R1-R6 assume values given claim 1, except compounds in which R5 is hydrogen and R6 is -NH2. The invention also relates to a pharmaceutical composition having the activity of an antipruritic agent, containing as an active ingredient said quinazoline derivative or pharmaceutically acceptable salt thereof.
EFFECT: obtaining a novel quinazoline derivative with low irritant action on skin and excellent action of significant suppression of scratching behaviour, as well as an antipruritic agent containing such a quinazoline derivative as an active ingredient.
9 cl, 250 ex, 7 tbl
FIELD: medicine, pharmaceutics.
SUBSTANCE: present invention refers to new benzimidazole derivatives of general formula (I) or to its pharmacologically acceptable salts wherein R1 represents a C6-aryl group which can be substituted by 1-3 groups optionally specified in a group of substitutes (a), or a heterocyclic group which represents pyridyl, dihydrobenzofuranyl, 1,3-benzodioxolyl, tetrahydropyranyl, tetrahydrofuranyl which can be substituted by 1-3 groups optionally specified in a group of substitutes (a), R2 represents a C1-C6 alkyl group, R3 represents a C6-aryl group which can be substituted by 1-2 groups optionally specified in a group of substitutes (a), Q represents a group represented by formula =CH-, or a nitrogen atom and a group of substitutes (a) represents a group consisting of a halogen atom, a C1-C6 alkyl group, a C1-C6 halogenated alkyl group, a carboxyl group, a C2-C7 alkylcarbonyl group, a C2-C7 alkoxycarbonyl group, a C1-C6 alkoxy group, a C1-C6 halogenated alkoxy group, an amino group, a 4-morpholinyl group and a di-C1-C6 alkyl)amino group. Also, the invention refers to a pharmaceutical composition based on a compound of formula (I), to a PPARγ activator/modulator based on the compound of formula (I), to using the compound of formula (I), to a method of reducing blood glucose, to a method of activating PPARγ, a method of treating and/or preventing said pathological conditions.
EFFECT: there are produced new benzimidazole derivatives showing PPARγ modulatory activity.
41 cl, 2 dwg, 6 tbl, 76 ex
SUBSTANCE: composition contains dexpanthenol, 20% chlorhexidine bigluconate, propylene glycol, a mixture of dimethicone, isopropyl myristate and Vaselin oil, a mixture of macrogol 20 cetostearyl ester and cetostearyl alcohol, glycoceramides, DL-pantolactone, a propellant and a solvent.
EFFECT: composition is safe and effective; it complies with the requirements of current officinal requirements for pharmaceutical foams, regulatory requirements for microbiological purity and has a 2-year shelf life.
5 cl, 4 ex, 1 tbl