Anti-inflammatory and analgesic agent of 1,2-dihydro-1h-2-oxocinchoninic acid isopropylamide

FIELD: medicine.

SUBSTANCE: invention refers to an anti-inflammatory and analgesic agent of 1,2-dihydro-1H-2-oxocinchoninic acid isopropylamide of formula

EFFECT: new agent possessing effective biological properties.

1 tbl

 

Anti-inflammatory and analgesic agent-based Isopropylamine 1,2-dihydro-1H-2-oxazinone acid indicated formula

which suggests the possibility of its use in medicine as a drug for the treatment of diseases associated with the occurrence of inflammatory processes.

The closest analogue of the structure is isoamylase 1,2-dihydro-1H-2-oxazinone acid (II) [Yanborisova O. A., Konshina T. M., Employees, Y. M., Zaks, A. S., Kanapin M. E. Synthesis and antiinflammatory activity of 2-allamericanheroes acids and amides of 1,2-dihydro-2-oxazinone acid // Chem.-Pharm. Phys., - 1995. - 29. - No. 6. - P. 32-33], which is studied for the presence of anti-inflammatory activity.

In medical practice are widely used nonsteroidal anti-inflammatory drugs (NSAIDs): diclofenac sodium (ortofen) and acetylsalicylic acid (aspirin), which has been taken as standards of comparison, anti-inflammatory and Metamizole (dipyrone) - analgesic activity [M. D. Mashkovsky Medicines. Guide for doctors. 16th ed., perab. and additional M.: New wave. - 2010. 1216 S.].

The aim of the invention is found in a number of amides cinchoninic acid isoeffective domestic anti - �Uo and analgesic agents having low toxicity.

This object is achieved by carrying out biological tests Isopropylamine 1,2-dihydro-1H-2-oxazinone acid (I) [Mikhalev A. I., Kanapin M. E., M. I. Vakhrin Synthesis and transformation of amides of 2-substituted cinchoninic acids // Chemistry, heterocycl. connect. - 1997. - No. 5 - P. 697-700] on animals, and analysis of experiments.

Acute toxicity of compound I studied for Express method prozorovskiy V. B. on white mice weighing 22-24 g [Prozorovsky V. B., Prozorovsky P. M., Demchenko V. M. a rapid method of determining the average effective dose and its error // Farmakol. and toxicol. - 1978. - Vol. 41. - No. 4. Pp. 497-502] intraperitoneal route of administration. Found that LD50the inventive compounds I>1000 mg/kg, and it refers to toxic substances. It is known that LD50in the same way introducing ortofena equal - 132, aspirin - 495, and dipyrone - 2900 mg/kg [Colla V. E., syropjatov B. Y. Doses of medicines and chemicals for laboratory animals. M.: Medicine. 1998, 263 p.]. Proven connection I 7.6 times less toxic than ortofen and 2 times aspirin.

Anti-inflammatory activity (PVA) of compound I and aspirin studied on albino rats of both sexes weighing 180-220 g on carragenine models of inflammation [Gabriel R. W. Manual on experimental (preclinical) study but�'s pharmacological substances under ed. R. W. Overall Mechanism. Ed. 2nd, revised and enlarged. M.: Medicine. - 2005. - S. 695-709] created subplanetary introduction into the hind paw of rats with 0.1 ml of 1% aqueous solution carragenin. Previously measured initial volume (ml) hind legs experimental and control rats using oncometer. The results obtained were compared with the literature data on anti-inflammatory and analgesic effect of diclofenac sodium at a dose of 25 mg/kg (table) on carragenine models of inflammation [M. V. Pavlov, Mikhalev A. I., Konshin, M. E., A. S. Zaks, Vasilyuk M. V., M. I. Vakhrin Synthesis, anti-inflammatory and analgesic activity of 2-substituted amides cinchoninic acid // Chem.-Pharm. Phys., - 1999. - Vol. 33. - No. 8. - Page 18-19]. The tested compound was administered intraperitoneally at a dose of 25 mg/kg and aspirin at a dose of 50 mg/kg in 2% starch slime one hour prior to simulation of inflammation. The growth in the volume of the inflamed foot was evaluated ecometrics after 3 and 5 hours after the introduction of the phlogogenic agent, and calculated the percentage of inhibition of edema control. Conducted 5 experiments, each group contained 6 animals. The results were processed statistically using student's criterion, the results were considered significant at p<0,05 [Belenky, M. L., Elements of quantitative evaluation of the pharmacological effect, 2nd ed., Medgiz, Leningrad, 1963. Pp. 81-106].

Studies have shown that the inventive compounds�tion I of the intraperitoneal route of administration at a dose of 25 mg/kg after the introduction of the phlogogenic agent inhibits the development of edema after 3 h at 68,2 and 5 h - 55.6 per cent. In General, the compound I is no less anti-inflammatory activity of diclofenac sodium in the same dose after 3 hours of observation and shows less activity after 5 hours. On the anti-inflammatory effect of compound I in a dose of 25 mg/kg is more active than aspirin at a dose of 50 mg/kg (table).

td align="center"> 65,3***
Table
Acute toxicity, anti-inflammatory and analgesic activity of compound I and drugs references.
Compound/ drug-referenceLD50mg/kg bAnti-inflammatory activity (PVA), % inhibition of edema to the control after the introduction of the phlogogenic agent throughAnalgesic activity (AA)
Dose, mg/kg b3 hours5 hDose, mg/kg b% reduction in acetic writhing"
The claimed connection I>10002568,2*55,6*25
Structural analogue Conn. II....5028,0*37,0*......
Diclofenac sodium (ortofen)1322569,4***72,2***2550,0**
Acetylsalicyl OIC acid (aspirin)4955051,2*28,7*......
Metamizole (dipyrone)2900.........5550,6*
* p<0,05; ** p<0,02; *** p<0.01 compared to control

Analgesic activity (AA) of compound I studied on the model of acetic writhing" [Gabriel R. W. Manual on experimental (preclinical) study of new pharmacological substances / under the General editorship of R. W. overall mechanism. Ed. 2nd, Rev. and d�p. M.: Medicine. - 2005. - S. 695-709] on outbred white rats-males weighing 22-24 g. the Mice were injected intraperitoneally with 0.75% aqueous acetic acid solution of 0.25 mg per 10 g of animal weight and counted the number of writhing within 10 minutes. The test substance was administered vnutribruchinno as a suspension in 2% starch mucilage in the dose of 25 mg/kg 30 min before intraperitoneal injection of acetic acid, and the reference drug analgin - at a dose of 55 mg/kg, corresponding to U50test acetic writhing" [Suraev R. F., M. D. Mashkovsky, Schwartz, G. J., V. I. Pokryshkin Comparative pharmacological activity of modern non-steroidal anti-inflammatory drugs // Chem.-Pharm. Phys. - 1986. - 20. - No. 1. - P. 33-39]. The results were assessed by the ability to inhibit the writhing number compared with control animals treated with the solvent. Each group contained 6 mice. These experiments were processed statistically with the calculation of the reliability criterion. The difference was considered significant at p<0,05 [Belenky, M. L., Elements of quantitative evaluation of the pharmacological effect, 2nd ed., Medgiz, Leningrad. - 1963, Pp. 81-106].

It is established that a proven connection I possess analgesic activity at a dose of 25 mg/kg and causes a decrease in acetic writhing on 65,35%, superior to the activity of diclofenac sodium and 50.0% in the same dose and shows a strong�e analgesic effect, than analgin - 61,0% at a dose of 55 mg/kg (table).

The positive difference between the claimed compounds (I) of the structural analogue of (II) is more pronounced anti-inflammatory and analgesic activity; from the diclofenac sodium - less toxicity, availability, receipt, the stability of the substance during storage in air; sodium metamizol (dipyrone) - higher analgesic effect.

Sources of information

1. Yanborisova O. A., Konshina T. M., Employees, Y. M., Zaks, A. S., Konshin, M. E. Synthesis and antiinflammatory activity of 2-allamericanheroes acids and amides of 1,2-dihydro-2-oxazinone acid // Chem.-Pharm. Phys. - 1995. - 29. - No. 6. - P. 32-33.

2. M. D. Mashkovsky Medicines. Guide for doctors. 16th ed., perab. and additional M.: New wave. - 2010. 1216 S.

3. Mikhalev A. I., Konshin M. E., M. I. Vakhrin, Synthesis and transformation of amides of 2-substituted cinchoninic acids // Chemistry of heterocycl. connect. - 1997. - No. 5. - S. 697-700.

4. Prozorovsky V. B., Prozorovsky P. M., Demchenko V. M. a rapid method of determining the average effective dose and its error // Farmakol. and toxicol. - 1978. - Vol. 41. - No. 4. Pp. 497-502.

5. Call V. E., syropjatov B. Y. Doses of medicines and chemicals for laboratory animals. M.: Medicine. - 1983, 263 p.

6. Gabriel R. W. Manual on experimental (preclinical) study of new pharmacological� substances under ed. R. W. Overall Mechanism. Ed. 2nd, revised and enlarged. M.: Medicine. - 2005. - S. 695-709.

7. Belenky, M. L., Elements of quantitative evaluation of the pharmacological effect, 2nd ed., Medgiz, Leningrad. - 1963. Pp. 81-106.

8. Pavlov, M. V., Mikhalev A. I., Konshin, M. E., A. S. Zaks, Vasilyuk M. V., M. I. Vakhrin Synthesis, anti-inflammatory and analgesic activity of 2-substituted amides cinchoninic acid // Chem.-Pharm. Phys., - 1999, - Vol. 33, No. 8 Pp. 33-39.

9. Subev R. F., M. D. Mashkovsky, Schwartz, G. J., V. I. Pokryshkin Comparative pharmacological activity of modern non-steroidal anti-inflammatory drugs // Chem.-Pharm. Phys. - 1986. - 20. - No. 1. - P. 33-39.

Anti-inflammatory and analgesic agent-based Isopropylamine 1,2-dihydro-1H-2-oxazinone acid indicated formula



 

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FIELD: chemistry.

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13 cl, 10 tbl, 6 dwg

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7 cl, 1 tbl, 102 ex

FIELD: medicine, pharmaceutics.

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15 cl, 6 tbl, 32 ex

FIELD: medicine, pharmaceutics.

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22 cl, 32 ex

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15 cl, 4 tbl, 3 ex

FIELD: chemistry.

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11 cl, 83 tbl, 71 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel quinoline derivatives of general formula

,

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7 cl, 26 tbl, 41 ex

FIELD: medicine, pharmaceutics.

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EFFECT: preparation of the new biologically active compounds used for treatment of disease caused by autoimmune or pathological inflammation.

39 cl, 17 ex, 5 tbl, 3 dwg

Fingolimod salts // 2543621

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new 2-amino-2-[2-(4-C2-20alkylphenyl)ethyl]propan-1,3-diol salts specified in tartrate, lactate benzoate, succinate, malonate, acetate and propionate in the crystalline form. Each of the above salts is characterised by powder X-ray pattern data. Compounds in the therapeutically effective amount can be used in treating autoimmune diseases.

EFFECT: crystalline salts of the present invention possess higher stability, better solubility, more convenient to store and handle.

11 cl, 7 dwg, 1 tbl, 10 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a novel complex of 5-hydroxy-6-methyluracil with 5-aminosalicylic acid of formula . The compound has anti-inflammatory activity and can be used as a basic active substance when producing novel medicinal preparations having anti-inflammatory action. The invention also relates to a method of obtaining said complex. The method includes reacting 5-hydroxy-6-methyluracil with 5-aminosalicylic acid in equimolar amounts in an aqueous medium at room temperature for 24 hours, followed by removal of water from the reaction mixture and obtaining the product.

EFFECT: wider range of pharmacological preparations with low toxicity, having higher anti-inflammatory activity.

2 cl, 1 tbl, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to the pharmaceutical industry, particularly to a preparation possessing anti-inflammatory, analgesic and wound-healing action. The preparation possessing the anti-inflammatory, analgesic and wound-healing action represents a mixture of an alcoholate of lilac blossom and plantain leaves with honey and extracted juice of unpeeled pomegranate.

EFFECT: preparation possesses the pronounced anti-inflammatory, analgesic and wound-healing action.

6 ex

FIELD: medicine.

SUBSTANCE: present invention refers to compounds having formula III such as below, wherein: Q represents C(Y3) or N; R represents H, -R1, -R1-R2-R3, -R1-R3 or -R2-R3; R1 represents heteroaryl or heterocyclyl each of which is optionally substituted by one or more C1-6alkyls, hydroxyC1-6alkyls, oxogroups or halogenC1-6alkyls; R2 represents -C(=O), -O, -C(R2')2, -C(R2')2C(=O), -C(R2')2C(=O)NR2', C(R2')2 N(R2')C(=O), -C(=NH), -C(R2')2NR2' or -S(=O)2; each R2' independently represents H or C1-6alkyl; R3 represents H or R4; R4 represents C1-6alkyl, C1-6alkoxygroup, aminogroup, C1-6alkylaminogroup, di(C1-6alkyl)aminogroup, heterocyclyl, C1-10alkylheterocycloalkyl, heterocycloalkylC1-10alkyl each of which is optionally substituted by one or more C1-6alkyls, C1-6alkylaminogroups, di(C1-6alkyl)aminogroups, hydroxygroups, hydroxyC1-6alkyls, C1-6alkoxygroups, oxogroups or halogenC1-6alkyls; X represents CH; X' represents CH; and the rest symbols have values as specified in the patent claim. The compounds of formula III inhibit Bruton's tyrosine kinase (Btk). There are also described compositions containing the compounds of formula III, and at least one carrier, thinner or excipient, and a method for producing the compound of formula X in accordance with the following procedure.

EFFECT: compositions are effective for modulating Btk activity and treating diseases related to Btk hyperactivity, and can be used for treating inflammatory and autoimmune diseases related to disturbed B-cell proliferation, such as rheumatoid arthritis.

22 cl, 2 tbl, 260 ex

FIELD: medicine.

SUBSTANCE: method for preparing an agent possessing anti-inflammatory, diuretic and antioxidant activity, involving milling Spiraea salicifolia shoots representing a mixture of leaves, blossom and shoots, extracting them three times by gradual maceration, mixing in infusing, filtering, condensing, separating, drying in the certain environment.

EFFECT: agent shoes the pronounced anti-inflammatory, diuretic and antioxidant activity.

2 dwg, 12 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine and represents a controlled-release preparative form of diacerein administered once a day for treating or autoimmune diseases or their complications. The preparative form contains a core, an active layer, a sustained-release film layer and a delayed-release film layer, wherein the active layer is followed by the sustained-release film, and the delayed-release film layer thereafter. The sustained-release film layer contains ethyl cellulose polymer, povidone, triethylacetate and talc; the delayed-release film layer contains Eudragit polymer, triethylacetate and talc.

EFFECT: reducing the negative side action of diacerein.

18 cl, 23 ex, 33 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to microbiology, namely to using bacteria, and describes a composition containing microorganisms, a method for preparing probiotics with the anti-inflammatory action and a method for preparing an anti-inflammatory composition containing the probiotics. The composition according to the invention is characterised by the microorganism count subject to the short-time high-temperature processing at 120-140°C for 5-15 seconds.

EFFECT: invention can be used for preparing the compositions for treating or preventing the inflammatory disorders for the probiotics for dairy products.

10 cl, 7 dwg

Antiviral compounds // 2541571

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of formula I, such as below, or its pharmaceutically acceptable salts. What is described is a method for preparing them.

,

wherein: A independently from B means phenyl,

, or ,

and B independently from A means phenyl,

, or ,

and the values Z, Y, D, L1, L2, L3, Z1, Z2 are presented in the patent claim.

EFFECT: compounds are effective for hepatitis C virus (HCV) replication inhibition.

17 cl, 3 tbl, 8 dwg, 177 ex

FIELD: medicine.

SUBSTANCE: group concerns using undecapeptide - H-Tyr-Pro-D-Arg-D-Arg-D-Arg-D-Arg-D-Arg-D-Arg-D-Arg-D-Arg-Gly-OH·9HCl as an analgesic agent. The group of inventions also concerns a dosage form containing the above peptide as an active substance for treating acute and chronic pain syndromes.

EFFECT: stable and prolonged analgesic effect both in the enteral, and oral route of administration.

3 cl, 2 ex, 2 dwg, 5 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention can be used in chemical-pharmaceutical industry for preparing effective tranquilising salamide preparations and analgesics. What is presented is using salicyloyl morpholine sodium salt of formula (I) as a tranquilising, nootropic and analgesic agent possessing low gastric toxicity.

EFFECT: implementing the declared application with the therapeutic index of salicyloyl morpholine of formula (I) is 3 times higher than that of mexidole, and 9,5 times higher than that of aspirin.

5 tbl

FIELD: chemistry.

SUBSTANCE: invention discloses a method of preventing agglomeration of particles of an aripiprazole or 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butox]-1H-quinolin-2-one active ingredient in a suspension containing silicone oil and/or a silicone oil derivative in a dispersion medium, wherein the particle size of the active ingredient is 0.1-200 mcm. The method comprises mixing an active ingredient with silicone oil and/or silicone oil derivative in a dispersion medium such that the silicone oil and/or silicone oil derivative is contained in an amount of 0.001-0.2 pts.wt per 100 pts.wt of the active ingredient contained in the suspension. The invention also relates to a hardened composition for preparing a suspension administered by injection or orally.

EFFECT: preventing agglomeration of active ingredients in a suspension without special treatment.

9 cl, 4 tbl, 9 ex

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