{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T07:23:27Z","timestamp":1768634607584,"version":"3.49.0"},"reference-count":74,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2021,10,2]],"date-time":"2021-10-02T00:00:00Z","timestamp":1633132800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007515","name":"Universidad de Valladolid","doi-asserted-by":"publisher","award":["Post-doctoral grant S.R.R."],"award-info":[{"award-number":["Post-doctoral grant S.R.R."]}],"id":[{"id":"10.13039\/501100007515","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Union\u2019s Horizon 2020 research and innovation program","award":["IT-DED3 (H2020-MSCA-ITN-2017) grant agreement No. 765608."],"award-info":[{"award-number":["IT-DED3 (H2020-MSCA-ITN-2017) grant agreement No. 765608."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Nowadays, increasing interest in olive pomace (OP) valorization aims to improve olive\u2019s industry sustainability. Interestingly, several studies propose a high-value application for OP extracts containing its main phenolic compounds, hydroxytyrosol and oleuropein, as therapy for ocular surface diseases. In this work, the stability and accessibility of OP total phenolic and flavonoid content, main representative compounds, and antioxidant activity were assessed under different pretreatment conditions. Among them, lyophilization and supercritical CO2 extraction were found to increase significantly most responses measured in the produced extracts. Two selected extracts (CONV and OPT3) were obtained by different techniques (conventional and pressurized liquid extraction); Their aqueous solutions were characterized by HPLC-DAD-MS\/MS. Additionally, their safety and stability were evaluated according to EMA requirements towards their approval as ophthalmic products: their genotoxic effect on ocular surface cells and their 6-months storage stability at 4 different temperature\/moisture conditions (CPMP\/ICH\/2736\/99), together with pure hydroxytyrosol and oleuropein solutions. The concentration of hydroxytyrosol and oleuropein in pure or extract solutions was tracked, and possible degradation products were putatively identified by HPLC-DAD-MS\/MS. Hydroxytyrosol and oleuropein had different stability as standard or extract solutions, with oleuropein also showing different degradation profile. All compounds\/extracts were safe for ophthalmic use at the concentrations tested.<\/jats:p>","DOI":"10.3390\/molecules26196002","type":"journal-article","created":{"date-parts":[[2021,10,8]],"date-time":"2021-10-08T21:23:55Z","timestamp":1633728235000},"page":"6002","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Olive Pomace Phenolic Compounds Stability and Safety Evaluation: From Raw Material to Future Ophthalmic Applications"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7776-8948","authenticated-orcid":false,"given":"Nikolaos","family":"Katsinas","sequence":"first","affiliation":[{"name":"Research Institute on Bioeconomy (BioEcoUVa), High Pressure Processes Group, School of Engineering, University of Valladolid (UVa), Dr. Mergelina Street, 47011 Valladolid, Spain"},{"name":"Institute of Applied Ophthalmobiology (IOBA), Campus Miguel Delibes, University of Valladolid (UVa), Paseo de Bel\u00e9n 17, 47011 Valladolid, Spain"},{"name":"Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Av. Monforte de Lemos, 3\u20135, 28029 Madrid, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1274-7796","authenticated-orcid":false,"given":"Amalia","family":"Enr\u00edquez-de-Salamanca","sequence":"additional","affiliation":[{"name":"Institute of Applied Ophthalmobiology (IOBA), Campus Miguel Delibes, University of Valladolid (UVa), Paseo de Bel\u00e9n 17, 47011 Valladolid, Spain"},{"name":"Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Av. Monforte de Lemos, 3\u20135, 28029 Madrid, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3047-0586","authenticated-orcid":false,"given":"Andreia","family":"Bento da Silva","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o do Medicamento (iMed.ULisboa), Faculdade de Farm\u00e1cia, Universidade de Lisboa (FFULisboa), Av. Prof. Gama Pinto, 1649-019 Lisbon, Portugal"},{"name":"Departamento de Ci\u00eancias Farmac\u00eauticas e do Medicamento (DCFM), Faculdade de Farm\u00e1cia da Universidade de Lisboa (FFUL), Av. das For\u00e7as Armadas, 1649-003 Lisboa, Portugal"},{"name":"Faculdade de Ci\u00eancias e Tecnologia da Universidade Nova de Lisboa (FCT NOVA), Largo da Torre, 2829-516 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5016-4634","authenticated-orcid":false,"given":"Maria Ros\u00e1rio","family":"Bronze","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o do Medicamento (iMed.ULisboa), Faculdade de Farm\u00e1cia, Universidade de Lisboa (FFULisboa), Av. Prof. Gama Pinto, 1649-019 Lisbon, Portugal"},{"name":"Instituto de Biologia Experimental e Tecnol\u00f3gica (iBET), Apartado 12, 2780-901 Oeiras, Portugal"},{"name":"Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica da Universidade Nova de Lisboa (ITQB NOVA), Av. da Rep\u00fablica, 2780-157 Oeiras, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9054-1462","authenticated-orcid":false,"given":"Soraya","family":"Rodr\u00edguez-Rojo","sequence":"additional","affiliation":[{"name":"Research Institute on Bioeconomy (BioEcoUVa), High Pressure Processes Group, School of Engineering, University of Valladolid (UVa), Dr. Mergelina Street, 47011 Valladolid, Spain"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,2]]},"reference":[{"key":"ref_1","unstructured":"(2021, May 07). FAOSTAT. 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