ES2554624T3 - Preparación farmacéutica - Google Patents
Preparación farmacéutica Download PDFInfo
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- ES2554624T3 ES2554624T3 ES09795982.9T ES09795982T ES2554624T3 ES 2554624 T3 ES2554624 T3 ES 2554624T3 ES 09795982 T ES09795982 T ES 09795982T ES 2554624 T3 ES2554624 T3 ES 2554624T3
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Classifications
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- General Chemical & Material Sciences (AREA)
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- Rheumatology (AREA)
- Heart & Thoracic Surgery (AREA)
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- Developmental Biology & Embryology (AREA)
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Abstract
Preparación farmacéutica para uso en el tratamiento de un estado inflamatorio interno, preferiblemente un estado interno asociado con isquemia, que comprende a) una disolución fisiológica que comprende células mononucleares de sangre periférica (PBMC) apoptóticas, o b) un sobrenadante de la disolución a), en la que la disolución a) puede obtenerse cultivando PBMC en una disolución fisiológica libre de sustancias de proliferación de PBMC y de activación de PBMC durante al menos 4 h, en la que las PBMC se someten a condiciones de inducción de estrés antes o en el transcurso del cultivo, en la que las condiciones de inducción de estrés incluyen hipoxia, ozono, calor, radiación, productos químicos, presión osmótica, cambio de pH o combinaciones de los mismos.
Description
figura 6b demuestra una fuerte inducción de la secreción de interferón-γ proinflamatorio tras la activación en comparación con PBMC no estimuladas. (Las significancias se indican tal como sigue: * p=0,05, ** p=0,001; n=8).
La figura 7a muestra resultados reunidos de análisis de citometría de flujo. Las PBMC se separaron de células T y 5 se evaluó la expresión de los marcadores de activación CD69 y CD25. (Las significancias se indican tal como sigue:
* p=0,05, ** p=0,001; n=4). La figura 7b muestra un análisis de FACS representativo de PBMC también activadas (PHA, AcM anti-CD3). La separación representa el % de células positivas.
La figura 8 muestra altas tasas de proliferación medidas mediante la incorporación de 3[H]-timidina de PBMC estimuladas cuando se comparan con PBMC viables cultivadas en RPMI sin estimulación.
La figura 9 muestra la inhibición de la respuesta de células T de secretomas de PBMC en ensayos de proliferación de células T.
15 La figura 10 (a-f) muestra los niveles en sobrenadante de interleucina-8, Gro-alfa, ENA-78, ICAM-1, VEGF e interleucina-16. Las PBMC apoptóticas muestran un patrón de secreción marcadamente diferente de estas citocinas y quimiocinas relacionadas con angiogénesis e inmunosupresión en comparación con células viables. Este efecto fue incluso más pronunciado cuando las células se incubaron a altas densidades.
La figura 11 muestra la extensión de tejido cicatricial miocárdico 6 semanas tras la ligación de LAD experimental (como % del ventrículo izquierdo). Los animales a los que se infundieron sobrenadantes de cultivo celular derivados de células apoptóticas evidencian una reducción significativa de la deposición de colágeno, menos extensión de la cicatriz y miocardio más viable.
25 La figura 12 (a-c) muestra el aspecto macroscópico de corazones de rata explantados 6 semanas tras infarto de miocardio experimental. Los animales a los que se transfundieron sobrenadantes de células apoptóticas irradiadas
(c) evidenciaron deposición de colágeno reducida y zonas infartadas mucho más pequeñas en comparación con medio (a) o sobrenadantes de células viables (b). El tejido cicatricial se tiñó de verde para una mejor visualización.
La figura 13 (a-d) muestra análisis ecocardiográficos representativos (modo M). La función cardiaca fue significativamente mejor en ratas a las que se transfundieron sobrenadantes de IA-PBMC (c) en comparación con ratas tratadas con medio (a) y células viables (b). La obtención de imágenes ecocardiográficas de una rata operada de manera simulada se representa en (d).
35 La figura 14 (a, b) muestra análisis ecocardiográficos realizados 6 semanas tras el infarto de miocardio. Las ratas sometidas a terapia con sobrenadantes de PBMC apoptóticas irradiadas evidencian una función cardiaca significativamente mejor en comparación con los animales a los que se infundió medio o sobrenadante de cultivo de células viables.
La figura 15 muestra la curva de supervivencia de Kaplan-Meier para los cuatro grupos de tratamiento. Los animales a los que se infundieron sobrenadantes de cultivo de células PBMC tanto viables como apoptóticas evidencian una mejor supervivencia en comparación con ratas inyectadas con medio. (p<0,1).
La figura 16 muestra experimentos de estimulación con anticuerpo anti-CD3 y PHA realizados con PBMC.
45 La figura 17 muestra la proliferación de PBMC tras la estimulación con anticuerpo anti-CD3, PHA y linfocitos mixtos.
La figura 18 muestra el nivel de positividad para anexina V y PI del sobrenadante de células CD4+ incubadas con sobrenadantes de PBMC.
La figura 19 muestra la inhibición de la regulación por incremento de CD25 y CD69 en células CD4+ por el sobrenadante de PBMC.
La figura 20 muestra que la retirada de IL-10 y TGF-β no aumentó las tasas de proliferación de las células CD4+. 55
EJEMPLO 1:
El infarto de miocardio agudo (AMI) a menudo conduce a insuficiencia cardiaca congestiva. Pese a la revascularización farmacológica y mecánica actual, no se ha definido experimentalmente ninguna terapia eficaz para sustituir el miocardio infartado. Componentes integrales del proceso de remodelación tras AMI son la respuesta inflamatoria y el desarrollo de neoangiogénesis tras AMI. Estos procesos están mediados por citocinas y células inflamatorias en el miocardio infartado que fagocitan tejido apoptótico y necrótico e inician la migración de células 65 dendríticas intersticiales (IDC) y macrófagos. Los ensayos clínicos dirigidos a atenuar la respuesta inflamatoria inducia por AMI se abandonaron puesto que la supresión inmunitaria sistémica (esteroides) conducía a un tamaño
7
Claims (1)
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imagen1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP08450199A EP2201954A1 (en) | 2008-12-18 | 2008-12-18 | Pharmaceutical preparation |
| EP08450199 | 2008-12-18 | ||
| PCT/EP2009/067536 WO2010070105A1 (en) | 2008-12-18 | 2009-12-18 | Pharmaceutical preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2554624T3 true ES2554624T3 (es) | 2015-12-22 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES09795982.9T Active ES2554624T3 (es) | 2008-12-18 | 2009-12-18 | Preparación farmacéutica |
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| EP (2) | EP2201954A1 (es) |
| JP (1) | JP5869344B2 (es) |
| CN (1) | CN102316879B (es) |
| AU (1) | AU2009329544B2 (es) |
| BR (1) | BRPI0922173A2 (es) |
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| DK (1) | DK2379086T3 (es) |
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| RU (1) | RU2542512C2 (es) |
| WO (1) | WO2010070105A1 (es) |
| ZA (1) | ZA201104348B (es) |
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| EP2198873A1 (en) * | 2008-12-18 | 2010-06-23 | Aposcience AG | Pharmaceutical preparation comprising supernatant of blood mononuclear cell culture |
| WO2010100570A2 (en) * | 2009-03-05 | 2010-09-10 | Macrocure, Ltd. | Activated leukocyte composition |
| US10077426B2 (en) | 2012-12-06 | 2018-09-18 | Enlivex Therapeutics Ltd | Therapeutic apoptotic cell preparations, method for producing same and uses thereof |
| WO2014106666A1 (en) | 2013-01-07 | 2014-07-10 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Disease therapy using a tolerogenic pharmaceutical preparation |
| US20170166869A1 (en) * | 2014-02-04 | 2017-06-15 | Jose Javier Lopez GONZALEZ | Biologically optimized adult mesenchymal stem cells |
| US11000548B2 (en) | 2015-02-18 | 2021-05-11 | Enlivex Therapeutics Ltd | Combination immune therapy and cytokine control therapy for cancer treatment |
| CN107708811B (zh) * | 2015-04-21 | 2021-04-30 | 恩立夫克治疗有限责任公司 | 治疗性汇集的血液凋亡细胞制剂与其用途 |
| CA3014885A1 (en) | 2016-02-18 | 2017-08-24 | Enlivex Therapeutics Ltd. | Combination immune therapy and cytokine control therapy for cancer treatment |
| EP3502692A1 (en) * | 2017-12-20 | 2019-06-26 | Aposcience AG | Potency assay for secretomes |
| EP3842064A1 (en) | 2019-12-23 | 2021-06-30 | Aposcience AG | Composition for treating or preventing an allergy or allergic reaction |
| EP4074320A1 (en) | 2021-04-13 | 2022-10-19 | Aposcience AG | Treatment of skin scars |
| EP4197547A1 (en) | 2021-12-20 | 2023-06-21 | Aposcience AG | Composition for treating or preventing vasculitis and diseases associated with vasculitis |
| WO2024105193A1 (en) * | 2022-11-17 | 2024-05-23 | Koptyug Andrey V | Novel compounds and methods |
Family Cites Families (10)
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| EP0080600B1 (fr) * | 1981-11-27 | 1985-06-19 | Firmenich Sa | Utilisation de 2-hydroxy-3,4,4-triméthyl-cyclopent-2-ène-1-one à titre d'ingrédient odoriférant |
| BR0309890A (pt) * | 2002-05-09 | 2005-05-10 | Medigenes | Composição farmacêutica contendo plasma sanguìneo, ou soro sanguìneo utilizada no tratamento de lesões, bem como seu método e processo de aplicação |
| US20070110737A1 (en) * | 2003-12-29 | 2007-05-17 | Allan Mishra | Compositions and method for decreasing the appearance of skin wrinkles |
| RU2262941C2 (ru) * | 2004-01-05 | 2005-10-27 | Государственное учреждение Научно-исследовательский институт клинической иммунологии СО РАМН | Способ иммунотерапии злокачественных опухолей головного мозга |
| JP2007528222A (ja) * | 2004-03-09 | 2007-10-11 | アブソルバー， アーベー | 内皮前駆細胞およびその使用方法 |
| WO2005123107A2 (en) * | 2004-06-09 | 2005-12-29 | Research Development Foundation | Immune response suppressor and treatment of multiple sclerosis |
| US20060004189A1 (en) * | 2004-07-02 | 2006-01-05 | James Gandy | Compositions for treating wounds and processes for their preparation |
| CN100552022C (zh) * | 2004-09-20 | 2009-10-21 | 上海市第一人民医院 | 一种诱导分化人外周血单个核细胞的方法 |
| CN101267829A (zh) * | 2005-06-24 | 2008-09-17 | 卡迪拉保健公司 | 血小板反应蛋白-1的衍生肽以及治疗方法 |
| EP2019590A4 (en) * | 2006-05-03 | 2011-08-03 | Therakos Inc | METHODS FOR TREATING DISEASES INVOLVING STRESS-RELATED CONDITIONS AND CONDITIONS |
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2008
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- 2009-12-18 WO PCT/EP2009/067536 patent/WO2010070105A1/en active Application Filing
- 2009-12-18 US US13/140,120 patent/US10478456B2/en active Active
- 2009-12-18 NZ NZ593365A patent/NZ593365A/xx unknown
- 2009-12-18 ES ES09795982.9T patent/ES2554624T3/es active Active
- 2009-12-18 RU RU2011129672/15A patent/RU2542512C2/ru active
- 2009-12-18 DK DK09795982.9T patent/DK2379086T3/en active
- 2009-12-18 JP JP2011541478A patent/JP5869344B2/ja active Active
- 2009-12-18 BR BRPI0922173A patent/BRPI0922173A2/pt not_active Application Discontinuation
- 2009-12-18 AU AU2009329544A patent/AU2009329544B2/en active Active
- 2009-12-18 PL PL09795982T patent/PL2379086T3/pl unknown
- 2009-12-18 EP EP09795982.9A patent/EP2379086B1/en active Active
- 2009-12-18 HU HUE09795982A patent/HUE028152T2/en unknown
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2011
- 2011-06-10 ZA ZA2011/04348A patent/ZA201104348B/en unknown
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2019
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Also Published As
| Publication number | Publication date |
|---|---|
| EP2201954A1 (en) | 2010-06-30 |
| US10478456B2 (en) | 2019-11-19 |
| WO2010070105A1 (en) | 2010-06-24 |
| ZA201104348B (en) | 2012-02-29 |
| HUE028152T2 (en) | 2016-11-28 |
| BRPI0922173A2 (pt) | 2015-12-29 |
| RU2011129672A (ru) | 2013-01-27 |
| CA2747207A1 (en) | 2010-06-24 |
| PL2379086T3 (pl) | 2016-01-29 |
| EP2379086A1 (en) | 2011-10-26 |
| CN102316879B (zh) | 2014-01-22 |
| AU2009329544B2 (en) | 2015-01-22 |
| JP5869344B2 (ja) | 2016-02-24 |
| AU2009329544A1 (en) | 2011-07-07 |
| US20200254019A1 (en) | 2020-08-13 |
| JP2012512843A (ja) | 2012-06-07 |
| EP2379086B1 (en) | 2015-09-02 |
| RU2542512C2 (ru) | 2015-02-20 |
| DK2379086T3 (en) | 2015-10-05 |
| NZ593365A (en) | 2012-11-30 |
| CA2747207C (en) | 2017-11-21 |
| CN102316879A (zh) | 2012-01-11 |
| US20110250190A1 (en) | 2011-10-13 |
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