RU2363473C1 - Way of antiphlogistic activation in experiment - Google Patents
Way of antiphlogistic activation in experiment Download PDFInfo
- Publication number
- RU2363473C1 RU2363473C1 RU2008106364/14A RU2008106364A RU2363473C1 RU 2363473 C1 RU2363473 C1 RU 2363473C1 RU 2008106364/14 A RU2008106364/14 A RU 2008106364/14A RU 2008106364 A RU2008106364 A RU 2008106364A RU 2363473 C1 RU2363473 C1 RU 2363473C1
- Authority
- RU
- Russia
- Prior art keywords
- acetylsalicylic acid
- experiment
- agent
- antiphlogistic
- medicine
- Prior art date
Links
- 239000002260 anti-inflammatory agent Substances 0.000 title claims abstract 3
- 230000001741 anti-phlogistic effect Effects 0.000 title abstract 2
- 230000004913 activation Effects 0.000 title 1
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 8
- 206010061218 Inflammation Diseases 0.000 claims abstract description 6
- 230000004054 inflammatory process Effects 0.000 claims abstract description 6
- 238000010171 animal model Methods 0.000 claims abstract description 5
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical class OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 claims abstract description 5
- 241001465754 Metazoa Species 0.000 claims abstract description 4
- 125000005273 2-acetoxybenzoic acid group Chemical group 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 claims description 2
- 238000006467 substitution reaction Methods 0.000 claims description 2
- 239000008186 active pharmaceutical agent Substances 0.000 claims 1
- 229940121363 anti-inflammatory agent Drugs 0.000 claims 1
- 229940088679 drug related substance Drugs 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 abstract description 9
- 229960001138 acetylsalicylic acid Drugs 0.000 abstract description 9
- 206010030113 Oedema Diseases 0.000 abstract description 6
- 230000003110 anti-inflammatory effect Effects 0.000 abstract description 6
- 239000003814 drug Substances 0.000 abstract description 6
- 229920000858 Cyclodextrin Polymers 0.000 abstract description 4
- 230000001154 acute effect Effects 0.000 abstract description 4
- 230000000694 effects Effects 0.000 abstract description 4
- 235000011175 beta-cyclodextrine Nutrition 0.000 abstract description 3
- 230000002757 inflammatory effect Effects 0.000 abstract description 3
- 239000000126 substance Substances 0.000 abstract description 3
- 239000012907 medicinal substance Substances 0.000 abstract 1
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- 230000000793 phophlogistic effect Effects 0.000 description 4
- 229940079593 drug Drugs 0.000 description 3
- 239000001116 FEMA 4028 Substances 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 229960004853 betadex Drugs 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000011287 therapeutic dose Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- BSYNRYMUTXBXSQ-FOQJRBATSA-N 59096-14-9 Chemical compound CC(=O)OC1=CC=CC=C1[14C](O)=O BSYNRYMUTXBXSQ-FOQJRBATSA-N 0.000 description 1
- 102100031786 Adiponectin Human genes 0.000 description 1
- 101000775469 Homo sapiens Adiponectin Proteins 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 229940097362 cyclodextrins Drugs 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 210000000548 hind-foot Anatomy 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 238000009958 sewing Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Изобретение относится медицине, а именно к экспериментальной фармакологии.The invention relates to medicine, namely to experimental pharmacology.
Известно применение в эксперименте и медицинской практике ацетилсалициловой кислоты, обладающей противовоспалительным действием [1]. На сегодняшний день этот фармакологический препарат является устаревшим [3].Known use in experiment and medical practice of acetylsalicylic acid, which has anti-inflammatory effect [1]. To date, this pharmacological drug is obsolete [3].
Цель изобретения - расширение арсенала средств для снижения острой воспалительной реакции у лабораторных животных в эксперименте.The purpose of the invention is the expansion of the arsenal of tools to reduce the acute inflammatory reaction in laboratory animals in the experiment.
Поставленная цель достигается применением синтезированного химического соединения АКЦД, состоящего из β-циклодекстрина и ацетилсалициловой кислоты (АКЦД) в качестве средства, обладающего противовоспалительным свойством.This goal is achieved by using the synthesized chemical compound AKDC, consisting of β-cyclodextrin and acetylsalicylic acid (AKDC) as an agent with anti-inflammatory properties.
АКЦД синтезировано на кафедре органической химии Московского государственного педагогического института путем ковалентного пришивания остатков ацетилсалициловой кислоты к остову β-циклодекстрина. Соединение имеет среднюю степень замещения 3, 5, представляет собой желтоватый порошок с ограниченной растворимостью в воде [2]. В настоящее время активно исследуются биологические свойства циклодекстринов [4, 5].ACDC is synthesized at the Department of Organic Chemistry of the Moscow State Pedagogical Institute by covalently sewing on acetylsalicylic acid residues to a β-cyclodextrin backbone. The compound has an average degree of substitution of 3, 5, is a yellowish powder with limited solubility in water [2]. Currently, the biological properties of cyclodextrins are being actively studied [4, 5].
В опытах на белых неинбредных крысах-самцах массой 180-200 г изучалось действие АКЦД по снижению реакции воспаления после создания модели острого воспалительного отека, вызванного субплантарным введением в заднюю лапу 0,1 мл 2% водного раствора формалина.In experiments on white non-inbred male rats weighing 180-200 g, the effect of AKDC to reduce the reaction of inflammation after creating a model of acute inflammatory edema caused by subplant implantation of 0.1 ml of 2% aqueous formalin into the hind paw was studied.
АКЦД вводили внутрибрюшинно в дозе 50 мг/кг за 1 час до введения флогогенного агента. Измерения объема лапок проводили с помощью водяного плетизмометра до инъекции растворов флогогенного агента и затем через 1, 2, 4 и 24 ч после его введения. Для сравнения были взяты ацетилсалициловая кислота (28 мг/кг). Доза АКЦД была эквивалентна Ѕ терапевтической дозе ацетилсалициловой кислоты [3].AKDC was administered intraperitoneally at a dose of 50 mg / kg 1 hour before the administration of the phlogogenic agent. Measurement of the volume of the legs was carried out using a water plethysmometer prior to the injection of solutions of the phlogogenic agent and then 1, 2, 4, and 24 hours after its administration. Acetylsalicylic acid (28 mg / kg) was taken for comparison. The dose of AKCD was equivalent to Ѕ the therapeutic dose of acetylsalicylic acid [3].
Через 4 ч с момента начала флогогенного воздействия у группы лабораторных животных, получавших АКЦД, отмечалась достоверно значимая разность с контролем, составившая 25,99%. К 24 ч интенсивность отека снизилась у всех исследуемых групп. Тем не менее, между значениями выборки с АКЦЦ и контролем имелась достоверно значимая разность (18,05%, p<0,05). У групп с препаратом сравнения данные значения распределились следующим образом: ацетилсалициловая кислота - 9,3% при p>0,05.4 hours after the start of phlogogenic exposure, a group of laboratory animals treated with AKDC showed a significantly significant difference with the control, which amounted to 25.99%. By 24 hours, the intensity of edema decreased in all studied groups. However, there was a significantly significant difference (18.05%, p <0.05) between the values of the sample with ACCC and control. In the groups with the comparison drug, these values were distributed as follows: acetylsalicylic acid - 9.3% at p> 0.05.
Пример 1Example 1
С помощью 2%-го раствора формалина формировался острый воспалительный отек у крыс, которым за 1 час до введения флогогенного агента вводилось внутрибрюшинно вещество АКЦД (состоящее из β-циклодекстрина и ацетилсалициловой кислоты). Через 4 часа от формирования отека выявлена достоверно значимая разница (p<0,05) прироста объема между АКЦД (50 мг/кг) и контрольной группой (таблица). Также выявлена достоверно значимая разница (p<0,05) между группой экспериментальных животных, получавших ацетилсалициловую кислоту (28 мг/кг) и контрольной выборкой, но при этом терапевтическая доза ацетилсалициловой кислоты была в 2 раза выше, чем используемая в эксперименте доза АКЦД. Следовательно, синтезированное вещество АКЦД обладает высокой противовоспалительной активностью.Using a 2% formalin solution, acute inflammatory edema was formed in rats, which, 1 hour before the introduction of the phlogogenic agent, were administered intraperitoneally with the substance AKCD (consisting of β-cyclodextrin and acetylsalicylic acid). After 4 hours from the formation of edema, a significantly significant difference (p <0.05) of the volume increase between AKDC (50 mg / kg) and the control group (table) was revealed. A significantly significant difference (p <0.05) was also found between the group of experimental animals treated with acetylsalicylic acid (28 mg / kg) and the control sample, but the therapeutic dose of acetylsalicylic acid was 2 times higher than the dose of AKDC used in the experiment. Therefore, the synthesized substance of AKDC has a high anti-inflammatory activity.
Источники информацииInformation sources
1. Азнабаев М.Т., Имаева А.Р., Башкатов С.А., Габдрахманова А.Ф. Противовоспалительная активность гиалуроновой кислоты // Журн. эксперим. и клин. фармакологии, 2003. Том 66. №5. С.28-29.1. Aznabaev M.T., Imaeva A.R., Bashkatov S.A., Gabdrakhmanova A.F. Anti-inflammatory activity of hyaluronic acid // Journal. an experiment. and wedge. Pharmacology, 2003. Volume 66. No. 5. S.28-29.
2. Кудрявцева Н.А. Особенности фосфорилирования и ацилирования β-циклодекстрина и его производных. Автор. канд. дисс., Москва. 2006.2. Kudryavtseva N.A. Features of phosphorylation and acylation of β-cyclodextrin and its derivatives. Author. Cand. Diss., Moscow. 2006.
3. Машковский М.Д. Лекарственные средства. Москва. Изд. «Новая волна» 2005 г. 1206 с.3. Mashkovsky M.D. Medicines Moscow. Ed. “New Wave” 2005, 1206 p.
4. Uekama К., Hirayama F., Irie Т. // Chem. Rev. 1998. V.98, №5. P.2045-2076.4. Uekama K., Hirayama F., Irie T. // Chem. Rev. 1998. V. 98, No. 5. P.2045-2076.
5. Davis M.E., Brewster M.E. // Nature Rev. Drug Discovery. 2004. V.3. P.1023-1035.5. Davis M.E., Brewster M.E. // Nature Rev. Drug Discovery. 2004. V.3. P.1023-1035.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| RU2008106364/14A RU2363473C1 (en) | 2008-02-18 | 2008-02-18 | Way of antiphlogistic activation in experiment |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| RU2008106364/14A RU2363473C1 (en) | 2008-02-18 | 2008-02-18 | Way of antiphlogistic activation in experiment |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| RU2363473C1 true RU2363473C1 (en) | 2009-08-10 |
Family
ID=41049470
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2008106364/14A RU2363473C1 (en) | 2008-02-18 | 2008-02-18 | Way of antiphlogistic activation in experiment |
Country Status (1)
| Country | Link |
|---|---|
| RU (1) | RU2363473C1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2440370C2 (en) * | 2010-04-05 | 2012-01-20 | Государственное Образовательное Учреждение Высшего Профессионального Образования Амурская Государственная Медицинская Академия Росздрава | Method of intensifying antiaggregant activity |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2129564C1 (en) * | 1993-05-24 | 1999-04-27 | Юэрофармасетикалс С.А. | Nimezulide salt-cyclodextrin inclusion complexes, method of preparing thereof and pharmaceutical agent having antiinflammatory and analgesic activities |
| FR2845917A1 (en) * | 2002-10-21 | 2004-04-23 | Negma Gild | PHARMACEUTICAL COMPOSITION COMBINING TENATOPRAZOLE AND AN ANTI-INFLAMMATORY |
| RU2006127443A (en) * | 2003-12-31 | 2008-02-10 | Сайдекс, Инк. (Us) | INHALATION COMPOSITION CONTAINING SULFALKYL ETHER CYCLODEXTRIN AND CORTICOSTEROID |
-
2008
- 2008-02-18 RU RU2008106364/14A patent/RU2363473C1/en not_active IP Right Cessation
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2129564C1 (en) * | 1993-05-24 | 1999-04-27 | Юэрофармасетикалс С.А. | Nimezulide salt-cyclodextrin inclusion complexes, method of preparing thereof and pharmaceutical agent having antiinflammatory and analgesic activities |
| FR2845917A1 (en) * | 2002-10-21 | 2004-04-23 | Negma Gild | PHARMACEUTICAL COMPOSITION COMBINING TENATOPRAZOLE AND AN ANTI-INFLAMMATORY |
| RU2006127443A (en) * | 2003-12-31 | 2008-02-10 | Сайдекс, Инк. (Us) | INHALATION COMPOSITION CONTAINING SULFALKYL ETHER CYCLODEXTRIN AND CORTICOSTEROID |
Non-Patent Citations (2)
| Title |
|---|
| КУРОЧКИНА Г.И. и др. Исследование ацилирования бета-циклодекстрина и его сильного производного хлорангидридами бензойной и ацетилсалициловой кислот. Журнал общей химии, 2007, т.77, №3, с.485-493. ARIMA H. Enhancement of the antiinflammatory effect of ethyl 4-biphenylyl acetate in ointment by beta-cyclodextrin derivatives: increased absorption and localized activation of the prodrug in rats. Pharm Res. 1990 Nov; 7(11):1152-6 (abstr). * |
| МАШКОВСКИЙ М.Д. Лекарственные средства. - М.: Новая волна, 2001, т.1, с.164. * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2440370C2 (en) * | 2010-04-05 | 2012-01-20 | Государственное Образовательное Учреждение Высшего Профессионального Образования Амурская Государственная Медицинская Академия Росздрава | Method of intensifying antiaggregant activity |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Xu et al. | Hyaluronic acid thiol modified injectable hydrogel: Synthesis, characterization, drug release, cellular drug uptake and anticancer activity | |
| Abeyrathna et al. | Nonmetallic carbon monoxide releasing molecules (CORMs) | |
| Liu et al. | Chitosan derivatives co-delivering nitric oxide and methicillin for the effective therapy to the methicillin-resistant S. aureus infection | |
| Truong et al. | Self‐assembled gels for biomedical applications | |
| Naseroleslami et al. | Simvastatin-loaded nano-niosomes confer cardioprotection against myocardial ischemia/reperfusion injury | |
| Qian et al. | Therapeutic delivery of nitric oxide utilizing saccharide-based materials | |
| RU2005135433A (en) | SUCTION AMPLIFIERS, SUCH AS VNT, VNA OR PROPYLGALLATE | |
| CN102370638B (en) | Application of 3,3'-diindolylmethane and 3,3'-diindolylmethane derivatives in preparation of drugs for treating liver diseases | |
| Wang et al. | Clickable, acid labile immunosuppressive prodrugs for in vivo targeting | |
| EA020784B1 (en) | COMPLEX INCLUSION OF PINOCEMBRIN WITH CYCLODEXTRIN, METHOD FOR ITS PREPARATION AND APPLICATION | |
| Bai et al. | Nanoparticles that target the mitochondria of tumor cells to restore oxygen supply for photodynamic therapy: design and preclinical validation against breast cancer | |
| RU2363473C1 (en) | Way of antiphlogistic activation in experiment | |
| WO2009144578A2 (en) | Synergistic osteogenic compound | |
| Shah et al. | Synthesis of S-nitrosoglutathione-alginate for prolonged delivery of nitric oxide in intestines | |
| Liu et al. | Co-delivery of indomethacin and uricase as a new strategy for inflammatory diseases associated with high uric acid | |
| Parida et al. | Spatiotemporal biointeraction and morphodynamics of a gastro-retentive Saccharopolyspora-derived macrolide system in the vertebrate gut: A study on absorptive microecology and transit kinetics | |
| US20100021398A1 (en) | Compositions and methods for lightening skin and protecting skin from ultraviolet radiation with glutathione | |
| Galenko-Yaroshevsky et al. | Study of the anti-inflammatory, analgesic, ulcerogenic and anti-ulcerogenic activity of Nisopropenylimidazole zinc complex derivative | |
| Gao et al. | NIR/pH-responsive arginine-ε-polylysine/black phosphorus nanocomposites for synergistic therapy of bacterial infections | |
| JP6362005B2 (en) | Silk fibroin aqueous solution and method for producing the same | |
| CN100460413C (en) | Compound synthesized from carboxylic acid non-steroidal anti-inflammatory drug and glucosamine or its salt, its synthesis method and application | |
| CA3000409C (en) | Formulation of hypericin for photodynamic therapy | |
| RU2283848C1 (en) | Method for production of alginic acid conjugates | |
| EP4330264A1 (en) | Hydroxybisphosphonic derivatives of meloxicam for the treatment of inflammatory joint diseases | |
| CN102429901B (en) | Application of indole-3-carbinol, diindolylmethane and derivatives thereof in preparation of medicaments for preventing and treating renal fibrosis |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | The patent is invalid due to non-payment of fees |
Effective date: 20100219 |