RU2015129833A - Антимикробные композиции - Google Patents

Антимикробные композиции Download PDF

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Publication number
RU2015129833A
RU2015129833A RU2015129833A RU2015129833A RU2015129833A RU 2015129833 A RU2015129833 A RU 2015129833A RU 2015129833 A RU2015129833 A RU 2015129833A RU 2015129833 A RU2015129833 A RU 2015129833A RU 2015129833 A RU2015129833 A RU 2015129833A
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Russia
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composition
composition according
amino
chelating agent
bis
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RU2015129833A
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English (en)
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RU2694758C2 (ru
Inventor
Раджив Бхушан
Джерри ДЖИН
Амит Госвами
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Раджив Бхушан
Джерри ДЖИН
Амит Госвами
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    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4706—4-Aminoquinolines; 8-Aminoquinolines, e.g. chloroquine, primaquine
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Claims (49)

1. Антимикробная композиция, содержащая хелатирующий агент или его соли, усилитель транспорта и приемлемый носитель или основу для таких композиций, причем хелатирующий агент и усилитель транспорта присутствуют в композиции в количестве и соотношении, эффективном для обеспечения значительного уменьшения бактериальных и/или грибковых биопленок на обработанной указанной композицией поверхности; и содержание хелатирующего агента в композиции составляет от около 0,1% (масса/масса) до около 15% (масса/масса), содержание усилителя транспорта в композиции составляет от около 0,1% (масса/масса) до около 40% (масса/масса).
2. Композиция по п. 1, в которой усилителем транспорта является метилсульфонилметан (MSM).
3. Композиция по п. 1, в которой усилителем транспорта является диметилсульфоксид (DMSO).
4. Композиция по п. 2, в которой соотношение хелатирующего агента и метилсульфонилметана составляет от около 10:1 до около 1:20.
5. Композиция по п. 1, представленная формой, выбираемой из твердой, жидкой, вдыхаемой, разбрызгиваемой, лосьона, раствора, геля, крема, мази, жидкости для промывания при хирургической обработке или полоскания для полости рта.
6. Композиция по п. 1, в которой хелатирующий агент выбирают из этилендиаминтетрауксусной кислоты (EDTA), этиленгликольтетрауксусной кислоты (EGTA), циклогександиаминтетрауксусной кислоты (CDTA), гидроксиэтилэтилендиаминтриуксусной кислоты (HEDTA), диэтилентриаминпентауксусной кислоты (DPTA), димеркаптопропансульфоновой кислоты (DMPS), димеркаптоянтарной кислоты (DMSA), аминотриметиленфосфоновой кислоты (АТРА), лимонной кислоты, уксусной кислоты, их приемлемых солей и комбинаций.
7. Композиция по п. 6, в которой соль этилендиаминтетрауксусной кислоты выбирают из (NH4)2-EDTA, Na2-EDTA, K2-EDTA, (NH4)3-EDTA, Na3-EDTA, K3-EDTA, Na4-EDTA, K4-EDTA, CaNa2-EDTA и их комбинаций.
8. Композиция по п. 1, в которой хелатирующий агент выбирают из фосфатов, пирофосфатов, триполифосфатов и гексаметафосфатов.
9. Композиция по п. 1, в которой хелатирующий агент выбирают из хелатирующих антибиотиков, хлорохина или тетрациклина.
10. Композиция по п. 1, в которой хелатирующий агент является азотсодержащим хелатирующим агентом, содержащим два или более атомов азота, образующих координационные связи в имино-группе или в ароматическом кольце, дииминах или 2,2'-бипиридинах.
11. Композиция по п. 1, в которой хелатирующий агент является полиамином, выбранным из циклама (1,4,7,11-тетраазациклотетрадекан), N-(С1-С30)алкил-замещенных цикламов (например, гексадециклама, тетраметилгексадецилциклама), диэтилентриамина (DETA), спермина, диэтилнорспермина (DENSPM), диэтилгомоспермина (DEHOP), дефероксамина (N'-{5-[ацетил(гидрокси)амино]пентил}-N-[5-({4-[(5-аминопентил)(гидрокси)амино]-4-оксобутаноил}амино)пентил]-N-гидроксисукцинамида или N'-[5-(ацетил-гидрокси-амино)пентил]-N-[5-[3-(5-аминопентил-гидрокси-карбамоил)пропаноиламино]пентил]-К-гидрокси-бутандиамида), десферриоксамина В, десфероксамина В, DFO-B, DFOA, DFB, десферала, деферипрона, пиридоксальизоникотиноилгидразона (PIH), салицилальдегид-изоникотиноилгидразона (SIH), этан-1,2-бис(N-1-амино-3-этилбутил-3-тиола).
12. Композиция по п. 1, в которой хелатирующий агент является конъюгатом EDTA-4-аминохинолин, выбираемым из ([2-(бис-этоксикарбонилметил-амино)-этил]-{[2-(7-хлорхинолин-4-иламино)-этилкарбамоил]-метил}-амино)-уксусной кислоты этилового эфира, ([2-(бис-этоксикарбонилметил-амино)-пропил]-{[2-(7-хлорхинолин-4-иламино)-этилкарбамоил]-метил}-амино)-уксусной кислоты этилового эфира, ([3-(бис-этоксикарбонилметил-амино)-пропил]-{[2-(7-хлорхинолин-4-иламино)-этилкарбамоил]-метил}-амино)-уксусной кислоты этилового эфира, ([4-(бис-этоксикарбонилметил-амино)-бутил]-{[2-(7-хлорхинолин-4-иламино)-этилкарбамоил]-метил}-амино)-уксусной кислоты этилового эфира, ([2-(бис-этоксиметил-амино)-этил]-{[2-(7-хлорхинолин-4-иламино)-этилкарбамоил]-метил}-амино)-уксусной кислоты этилового эфира, ([2-(бис-этоксиметил-амино)-пропил]-{[2-(7-хлорхинолин-4-иламино)-этилкарбамоил]-метил}-амино)-уксусной кислоты этилового эфира, ([3-(бис-этоксиметил-амино)-пропил]-{[2-(7-хлорхинолин-4-иламино)-этилкарбамоил]-метил}-амино)-уксусной кислоты этилового эфира, ([4-(бис-этоксиметил-амино)-бутил]-{[2-(7-хлорхинолин-4-иламино)-этилкарбамоил]-метил}-амино)-уксусной кислоты этилового эфира.
13. Композиция по п. 1, в которой хелатирующий агент является четырехзамещенной натриевой солью иминодиянтарной кислоты.
14. Композиция по п. 1, в которой хелатирующий агент является полиаспарагиновой кислотой или ее солью.
15. Композиция по п. 1, в которой хелатирующий агент является четырехзамещенной натриевой солью L-глутаминовой-N,N-диуксусной кислоты.
16. Композиция по п. 1, в которой хелатирующий агент является природным хелатирующим агентом, выбираемым из лимонной кислоты фитиновой кислоты, молочной кислоты, уксусной кислоты, их солей и куркумина.
17. Композиция по п. 1, дополнительно содержащая антибиотик.
18. Композиция по п. 17, в которой антибиотик является антибактериальным или фунгицидным агентом.
19. Композиция по п. 1, предназначенная для перорального введения.
20. Композиция по п. 19, представляющая собой пастилку/таблетку для рассасывания или полоскание для полости рта.
21. Композиция по п. 1, предназначенная для парентерального введения.
22. Композиция по п. 1, предназначенная для местного введения.
23. Композиция по п. 1, представляющая собой мазь, крем или лосьон.
24. Композиция по п. 1, предназначенная для интраназального введения.
25. Композиция по п. 1, являющаяся препаратом с замедленным высвобождением.
26. Способ подавления бактериальных инфекций, связанных с биопленками, включающий введение субъекту композиции по п. 1 в сочетании с антибиотиком или перед введением антибиотика.
27. Медицинское устройство, покрытое композицией по п. 1.
28. Медицинское устройство по п. 27, являющееся имплантируемым устройством.
29. Медицинское устройство по п. 28, выбираемое из группы, состоящей из катетеров для центральных вен, внутрисосудистых катетеров, мочевых катетеров, катетеров Хикмана, катетеров для перитонеального диализа, эндотрахеальных катетеров, искусственных клапанов сердца, водителей ритма сердца, артериовенозных шунтов, склеральных пломб, протезов суставов, трубок для тимпаностомии и трахеостомии, голосовых протезов, протезов полового члена, искусственных сфинктеров мочевого пузыря, синтетических лоскутов для лобково-влагалищных операций с подвешиванием, хирургического шовного материала, костных фиксаторов, костных винтов, внутриглазных линз, контактных линз, внутриматочных спиралей, аорто-феморальных протезов и сосудистых протезов.
30. Медицинское устройство по п. 27, являющееся хирургическим инструментом.
31. Медицинское устройство по п. 30, в котором хирургический инструмент является зажимом, пинцетом/щипцами, ножницами, кожным крючком, трубкой, иглой, ретрактором, скалером, сверлом, долотом, распатором или пилой.
32. Перевязочный материал, пропитанный композицией по п. 1.
33. Перевязочный материал по п. 32, представляющий собой губку, марлю/бинт или повязку для защиты раны входного отверстия катетера.
34. Трансдермальный пластырь, обеспечивающий чрескожное введение препарата, содержащий композицию по п. 1.
35. Способ для облегчения отделения бактериальных или грибковых клеток от биопленки, включающий контактирование указанных клеток с композицией по п. 1.
36. Способ подавления заражения медицинского устройства или хирургического инструмента бактериями или грибками, включающий контактирование медицинского устройства или хирургического инструмента с композицией по п. 1.
37. Способ подавления заражения медицинского устройства или хирургического инструмента бактериями или грибками, включающий покрывание медицинского устройства или хирургического инструмента композицией по п. 1.
38. Способ подавления заражения медицинского устройства или хирургического инструмента бактериями или грибками, включающий погружение медицинского устройства или хирургического инструмента в раствор, содержащий композицию по п. 1.
39. Способ подавления или лечения бактериальных или грибковых инфекций, включающий введение субъекту фармацевтически приемлемой композиции, содержащей композицию по п. 1.
40. Способ по п. 39, в котором бактерии выбирают из группы, состоящей из Acidothermus cellulyticus, Actinomyces odontolyticus, Alkaliphilus metalliredigens, Alkaliphilus oremlandii, Arthrobacter aurescens, Bacillus amyloliquefaciens, Bacillus clausii, Bacillus halodurans, Bacillus licheniformis, Bacillus pumilus, Bacillus subtilis, Bifidobacterium adolescentis, Bifidobacterium longum, Caldicellulosiruptor saccharolyticus, Carboxydothermus hydrogenoformans, Clostridium acetobutylicum, Clostridium beijerinckii, Clostridium botulinum, Clostridium cellulolyticum, Clostridium difficile, Clostridium kluyveri, Clostridium leptum, Clostridium novyi, Clostridium perfringens, Clostridium tetani, Clostridium thermocellum, Corynebacterium diphtheriae, Corynebacterium efficiens, Corynebacterium glutamicum, Corynebacterium jeikeium, Corynebacterium urealyticum, Desulfitobacterium hafniense, Desulfotomaculum reducens, Eubacterium ventriosum, Exiguobacterium sibiricum, Fingoldia magna, Geobacillus kaustophilus, Geobacillus thermodenitrificans, виды рода Janibacter, Kineococcus radiotolerans, Lactobacillus fermentum, Listeria monocytogenes, Listeria innocua, Listeria welshimeri, Moorella thermoacetica, Mycobacterium avium, Mycobacterium bovis, Mycobacterium gilvum, Mycobacterium leprae, Mycobacterium paratuberculosis, Mycobacterium smegmatis, Mycobacterium tuberculosis, Mycobacterium ulcerans, Mycobacterium vanbaalenii, виды рода Nocardioides, Nocardia farcinica, Oceanobacillus iheyensis, Pelotomaculum thermopropionicum, виды рода Rhodococcus, Saccharopolyspora erythraea, коагулазо-отрицательные виды рода Staphylococcus, Staphylococcus aureus, Staphylococcus aureus, устойчивые к метициллину (MRSA), Staphylococcus epidermidis, Staphylococcus epidermidis, устойчивые к метициллину (MRSE), Streptococcus agalactiae, Streptococcus gordonii, Streptococcus mitis, Streptococcus oralis, Streptococcus pneumoniae, Streptococcus sanguinis, Streptococcus suis, Streptomyces avermitilis, Streptomyces coelicolor, Thermoanaerobacter ethanolicus, Thermoanaerobacter tengcongensis и их комбинаций.
41. Способ по п. 39, в котором бактерии являются грамположительными.
42. Перевязочный материал, пропитанный безопасным и эффективным количеством композиции по п. 1, который подавляет образование биопленок на коже.
43. Очищающая композиция индивидуального пользования для личной гигиены, содержащая эффективное количество композиции по п. 1, которая подавляет образование биопленок на коже.
44. Очищающая композиция индивидуального пользования для личной гигиены по п. 43, представляющая собой средство для обработки рук перед хирургическими процедурами, гель для душа, жидкое или твердое мыло.
45. Очищающая композиция для твердых поверхностей, содержащая эффективное количество композиции по п. 1, которая подавляет образование биопленок на твердой поверхности.
46. Полоскание для полости рта для подавления образования биопленок, содержащее эффективное количество композиции по п. 1.
47. Композиция по п. 1, пригодная для применения на поверхностях и содержащая около 0,4-15% хелатирующего агента, около 0,5-30% метилсульфонилметана; один или более загущающих или желирующих агентов; 10-99% воды и при необходимости поверхностно-активные вещества, детергенты и/или омыляющие агенты.
48. Композиции по п. 47, содержащая около 1-5% хелатирующего агента, около 1-10% метилсульфонилметана; 0,1-6% одного или более загущающих агентов и 80-97% воды.
49. Композиция по п. 1, пригодная для применения в полости рта и содержащая около 0,4-8% хелатирующего агента и около 0,5-16% метилсульфонилметана.
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