RU2018136873A - Сложные эфиры для лечения офтальмологических воспалительных заболеваний - Google Patents
Сложные эфиры для лечения офтальмологических воспалительных заболеваний Download PDFInfo
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- RU2018136873A RU2018136873A RU2018136873A RU2018136873A RU2018136873A RU 2018136873 A RU2018136873 A RU 2018136873A RU 2018136873 A RU2018136873 A RU 2018136873A RU 2018136873 A RU2018136873 A RU 2018136873A RU 2018136873 A RU2018136873 A RU 2018136873A
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- Russia
- Prior art keywords
- acid
- resolvin
- composition
- inflammatory lipoid
- lipoid mediator
- Prior art date
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- 150000002170 ethers Chemical class 0.000 title 1
- 208000027866 inflammatory disease Diseases 0.000 title 1
- 238000000034 method Methods 0.000 claims 20
- 230000003110 anti-inflammatory effect Effects 0.000 claims 12
- 239000000203 mixture Substances 0.000 claims 12
- 239000002253 acid Substances 0.000 claims 7
- DTOSIQBPPRVQHS-PDBXOOCHSA-N alpha-linolenic acid Chemical compound CC\C=C/C\C=C/C\C=C/CCCCCCCC(O)=O DTOSIQBPPRVQHS-PDBXOOCHSA-N 0.000 claims 6
- 150000002148 esters Chemical class 0.000 claims 6
- 235000020661 alpha-linolenic acid Nutrition 0.000 claims 3
- 229960004488 linolenic acid Drugs 0.000 claims 3
- YUFFSWGQGVEMMI-JLNKQSITSA-N (7Z,10Z,13Z,16Z,19Z)-docosapentaenoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCCCCC(O)=O YUFFSWGQGVEMMI-JLNKQSITSA-N 0.000 claims 2
- GMVPRGQOIOIIMI-UHFFFAOYSA-N (8R,11R,12R,13E,15S)-11,15-Dihydroxy-9-oxo-13-prostenoic acid Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CCCCCCC(O)=O GMVPRGQOIOIIMI-UHFFFAOYSA-N 0.000 claims 2
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims 2
- 235000021294 Docosapentaenoic acid Nutrition 0.000 claims 2
- 229930184725 Lipoxin Natural products 0.000 claims 2
- 229960000711 alprostadil Drugs 0.000 claims 2
- 235000014113 dietary fatty acids Nutrition 0.000 claims 2
- 239000000194 fatty acid Substances 0.000 claims 2
- 229930195729 fatty acid Natural products 0.000 claims 2
- 150000004665 fatty acids Chemical class 0.000 claims 2
- IXAQOQZEOGMIQS-SSQFXEBMSA-M lipoxin A4(1-) Chemical compound CCCCC[C@H](O)\C=C\C=C/C=C/C=C/[C@@H](O)[C@@H](O)CCCC([O-])=O IXAQOQZEOGMIQS-SSQFXEBMSA-M 0.000 claims 2
- UXVRTOKOJOMENI-WLPVFMORSA-N lipoxin B4 Chemical compound CCCCC[C@H](O)[C@H](O)\C=C\C=C\C=C/C=C/[C@@H](O)CCCC(O)=O UXVRTOKOJOMENI-WLPVFMORSA-N 0.000 claims 2
- 150000002639 lipoxins Chemical class 0.000 claims 2
- 239000002207 metabolite Substances 0.000 claims 2
- 229920005862 polyol Polymers 0.000 claims 2
- 150000003077 polyols Chemical class 0.000 claims 2
- GMVPRGQOIOIIMI-DWKJAMRDSA-N prostaglandin E1 Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(O)=O GMVPRGQOIOIIMI-DWKJAMRDSA-N 0.000 claims 2
- XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 claims 2
- CBOMORHDRONZRN-QLOYDKTKSA-N prostaglandin E3 Chemical compound CC\C=C/C[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O CBOMORHDRONZRN-QLOYDKTKSA-N 0.000 claims 2
- 150000003180 prostaglandins Chemical class 0.000 claims 2
- CRDZYJSQHCXHEG-SFVBTVKNSA-N protectin D1 Chemical compound CC\C=C/C[C@H](O)\C=C/C=C/C=C/[C@H](O)C\C=C/C\C=C/CCC(O)=O CRDZYJSQHCXHEG-SFVBTVKNSA-N 0.000 claims 2
- OIWTWACQMDFHJG-CCFUIAGSSA-N resolvin D1 Chemical compound CC\C=C/C[C@H](O)\C=C\C=C/C=C/C=C/[C@@H](O)[C@@H](O)C\C=C/CCC(O)=O OIWTWACQMDFHJG-CCFUIAGSSA-N 0.000 claims 2
- IKFAUGXNBOBQDM-XFMPMKITSA-N resolvin D2 Chemical compound CC\C=C/C[C@H](O)[C@H](O)\C=C\C=C\C=C/C=C/[C@@H](O)C\C=C/CCC(O)=O IKFAUGXNBOBQDM-XFMPMKITSA-N 0.000 claims 2
- QBTJOLCUKWLTIC-UZAFJXHNSA-N resolvin D3 Chemical compound CC\C=C/C[C@H](O)\C=C\C=C/C[C@@H](O)\C=C\C=C\C=C/[C@@H](O)CCC(O)=O QBTJOLCUKWLTIC-UZAFJXHNSA-N 0.000 claims 2
- YKPLJNOOLKUEBS-RIYRYSNMSA-N resolvin D4 Chemical compound CC\C=C/C[C@H](O)\C=C\C=C/C\C=C/C=C/C=C/[C@@H](O)[C@@H](O)CCC(O)=O YKPLJNOOLKUEBS-RIYRYSNMSA-N 0.000 claims 2
- AOPOCGPBAIARAV-OTBJXLELSA-N resolvin E1 Chemical compound CC[C@@H](O)\C=C\C=C/C[C@@H](O)\C=C\C=C\C=C/[C@@H](O)CCCC(O)=O AOPOCGPBAIARAV-OTBJXLELSA-N 0.000 claims 2
- KPRHYAOSTOHNQA-NNQKPOSRSA-N resolvin E2 Chemical compound CC[C@@H](O)\C=C\C=C/C\C=C/C\C=C/C=C/[C@@H](O)CCCC(O)=O KPRHYAOSTOHNQA-NNQKPOSRSA-N 0.000 claims 2
- KXVFBCSUGDNXQF-DZDBOGACSA-N (2z,4z,6z,8z,10z)-tetracosa-2,4,6,8,10-pentaenoic acid Chemical compound CCCCCCCCCCCCC\C=C/C=C\C=C/C=C\C=C/C(O)=O KXVFBCSUGDNXQF-DZDBOGACSA-N 0.000 claims 1
- 102000001324 CD59 Antigens Human genes 0.000 claims 1
- 108010055167 CD59 Antigens Proteins 0.000 claims 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims 1
- 239000004386 Erythritol Substances 0.000 claims 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 claims 1
- OPGOLNDOMSBSCW-CLNHMMGSSA-N Fursultiamine hydrochloride Chemical compound Cl.C1CCOC1CSSC(\CCO)=C(/C)N(C=O)CC1=CN=C(C)N=C1N OPGOLNDOMSBSCW-CLNHMMGSSA-N 0.000 claims 1
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 claims 1
- SHGAZHPCJJPHSC-NUEINMDLSA-N Isotretinoin Chemical compound OC(=O)C=C(C)/C=C/C=C(C)C=CC1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-NUEINMDLSA-N 0.000 claims 1
- QPCDCPDFJACHGM-UHFFFAOYSA-N N,N-bis{2-[bis(carboxymethyl)amino]ethyl}glycine Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(=O)O)CCN(CC(O)=O)CC(O)=O QPCDCPDFJACHGM-UHFFFAOYSA-N 0.000 claims 1
- 150000001200 N-acyl ethanolamides Chemical class 0.000 claims 1
- 239000002202 Polyethylene glycol Substances 0.000 claims 1
- 239000004372 Polyvinyl alcohol Substances 0.000 claims 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims 1
- 229930003427 Vitamin E Natural products 0.000 claims 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims 1
- JAZBEHYOTPTENJ-JLNKQSITSA-N all-cis-5,8,11,14,17-icosapentaenoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O JAZBEHYOTPTENJ-JLNKQSITSA-N 0.000 claims 1
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 claims 1
- LGEQQWMQCRIYKG-DOFZRALJSA-N anandamide Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(=O)NCCO LGEQQWMQCRIYKG-DOFZRALJSA-N 0.000 claims 1
- 239000003963 antioxidant agent Substances 0.000 claims 1
- 230000003078 antioxidant effect Effects 0.000 claims 1
- 235000006708 antioxidants Nutrition 0.000 claims 1
- LGEQQWMQCRIYKG-UHFFFAOYSA-N arachidonic acid ethanolamide Natural products CCCCCC=CCC=CCC=CCC=CCCCC(=O)NCCO LGEQQWMQCRIYKG-UHFFFAOYSA-N 0.000 claims 1
- 229910021538 borax Inorganic materials 0.000 claims 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims 1
- 239000004327 boric acid Substances 0.000 claims 1
- 229960002645 boric acid Drugs 0.000 claims 1
- 125000004432 carbon atom Chemical group C* 0.000 claims 1
- 239000013522 chelant Substances 0.000 claims 1
- 239000007795 chemical reaction product Substances 0.000 claims 1
- CYQFCXCEBYINGO-IAGOWNOFSA-N delta1-THC Chemical compound C1=C(C)CC[C@H]2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3[C@@H]21 CYQFCXCEBYINGO-IAGOWNOFSA-N 0.000 claims 1
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- 239000002621 endocannabinoid Substances 0.000 claims 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 claims 1
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- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims 1
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- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 claims 1
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- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 235000020660 omega-3 fatty acid Nutrition 0.000 claims 1
- 229940012843 omega-3 fatty acid Drugs 0.000 claims 1
- 229960003330 pentetic acid Drugs 0.000 claims 1
- 150000003904 phospholipids Chemical class 0.000 claims 1
- 229920001223 polyethylene glycol Polymers 0.000 claims 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims 1
- 229920000053 polysorbate 80 Polymers 0.000 claims 1
- 229940068968 polysorbate 80 Drugs 0.000 claims 1
- 229920002451 polyvinyl alcohol Polymers 0.000 claims 1
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- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 claims 1
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- BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 0.000 claims 1
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Classifications
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Claims (25)
1. Способ обеспечения осмопротекции, включающий применение офтальмологической композиции для обеспечения осмопротекции поверхности глаза пациента,
где композиция содержит:
сложный эфир противовоспалительного липоидного медиатора, который представляет собой продукт реакции противовоспалительного липоидного медиатора и полиола, имеющего длину цепи от 4 до 10 атомов углерода,
где сложный эфир выбирают из группы, состоящей из этерифицированного ресольвина или его метаболически стабильного аналога, этерифицированного протектина или его метаболически стабильного аналога, этерифицированного липоксина или его метаболически стабильного аналога, этерифицированного простагландина или его метаболически стабильного аналога, этерифицированной ретиноевой кислоты, их метаболитов, эндоканнабиноида, фосфолипида, который содержит остаток по меньшей мере одной жирной кислоты Омега-3, и их смеси; и
водную систему доставки;
при этом состав практически не содержит кислоты.
2. Способ по п.1, в которой сложный эфир присутствует в терапевтически эффективном количестве.
3. Способ по п.1, где композиция практически не содержит жирных кислот.
4. Способ по п.1, где композиция содержит 10% по весу или менее кислотной формы противовоспалительного липоидного медиатора.
5. Способ по п.4, где композиция содержит 5% по весу или менее кислотной формы противовоспалительного липоидного медиатора.
6. Способ по п.5, где композиция содержит 1% по весу или менее кислотной формы противовоспалительного липоидного медиатора.
7. Способ по п.1, в которой сложный эфир присутствует в количестве от приблизительно 0,01% до 5,0% по весу в расчете на общую массу композиции.
8. Способ по п.7, в которой сложный эфир присутствует в количестве от приблизительно 0,025% до 0,5% по весу в расчете на общую массу композиции.
9. Способ по п.1, в которой противовоспалительный липоидный медиатор является простагландином, выбранным из группы, состоящей из простагландина E1 (PGE1), простагландина Е3 (PGE3) или метаболически стабильного аналога и их комбинации.
10. Способ по п.1, в которой противовоспалительный липоидный медиатор является ресольвином, выбранным из группы, состоящей из ресольвина E1 (RvE1), ресольвина E2 (RvE2), ресольвина D1 (RvD1), ресольвина D2 (RvD2), ресольвина D3 (RvD3), ресольвина D4 (RvD4) или метаболически стабильного аналога и их комбинации.
11. Способ по п.1, в которой противовоспалительный липоидный медиатор является липоксином, выбранным из группы, состоящей из липоксина A4 (LXA), липоксина B4 (LXB4) или метаболически стабильного аналога и их комбинации.
12. Способ по п.1, в которой противовоспалительный липоидный медиатор содержит протектин D1 (PD1) или метаболически стабильных аналог.
13. Способ по п.1, в которой противовоспалительный липоидный медиатор содержит 13-цис-ретиноевую кислоту.
14. Способ по п.5, в которой противовоспалительный липоидный медиатор содержит анандамид.
15. Способ по п.1, в которой противовоспалительный липоидный медиатор содержит по меньшей мере одну жирную кислоту, выбранную из группы, состоящей из: альфа-линоленовой кислоты, стеаридоновой кислоты, эйкозатетраеновой кислоты, эйкозапентаеновой кислоты, докогексаеновой кислоты (DHA), докозапентаеновой кислоты (DPA), тетракозапентаеновой кислоты и тетракозагексаеновой кислоты (низиновая кислота), производных, метаболитов и их смесей.
16. Способ по п.1, в которой сложный эфир содержит этерифицированную альфа-линоленовую кислоту.
17. Способ по п.16, в которой этерифицированная альфа-линоленовая кислота присутствует в количестве от приблизительно 0,01% до 5,0% по весу в расчете на общую массу композиции.
18. Способ по п.1, в которой водная система доставки содержит одно или несколько веществ, выбранных из: поверхностно-активного вещества, эмульгатора, смачивающего агента, хеланта и антиоксиданта.
19. Способ по п.1, в которой водная система доставки содержит один или более ингредиентов, выбранных из группы, состоящей из полисорбата 80™, Тилоксапола™, метил глюцета-20, витамина Е, диэтилентриаминпентауксусной кислоты, борной кислоты, бората натрия и хлорида натрия.
20. Способ по п.1, в которой полиол выбран из группы, состоящей из полиэтиленгликоля, поливинилового спирта, инозитола, сорбитола, ксилитола, эритритола, а также их комбинации.
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