{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:22:00Z","timestamp":1760235720234,"version":"build-2065373602"},"reference-count":27,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T00:00:00Z","timestamp":1632182400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shedir Pharma S.r.l","award":["Shedir Pharma srl"],"award-info":[{"award-number":["Shedir Pharma srl"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Epistaxis is one of the most frequent hemorrhages resulting from local or systemic factors. Its management without hospitalization has prompted an interest in locally applied hemostatic agents. Generally, the therapy approaches involve sprays or creams acting as a physical barrier, even used as tampons or gauze. In this study, we have investigated the activity of Emoxilane\u00ae, a combination of sodium hyaluronate, silver salt, \u03b1-tocopherol acetate and D-panthenol, which is known to be able to separately act in a different biological manner. Our in vitro results, obtained on endothelial and nasal epithelial cells, have shown that the association of these molecules presented a notable antioxidant activity mainly due to the \u03b1-tocopherol and D-panthenol and a significant antimicrobial role thanks to the silver compound. Moreover, remarkable hemostatic activity was found by evaluating plasmin inhibition attributable to the sodium hyaluronate. Interestingly, on human plasma, we have confirmed that Emoxilane\u00ae strongly induced the increase of thrombin levels. These data suggest that the use of this association could represent an appealing pharmacological approach to actively induce hemostasis during epistaxis. Our future perspective will aim to the creation of a formulation for an easy topical application in the nose which is able to contrast the bleeding.<\/jats:p>","DOI":"10.3390\/life11090992","type":"journal-article","created":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T08:04:23Z","timestamp":1632211463000},"page":"992","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The Procoagulant Activity of Emoxilane\u00ae: A New Appealing Therapeutic Use in Epistaxis of the Combination of Sodium Hyaluronate, Silver Salt, \u03b1-tocopherol and D-panthenol"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5036-7869","authenticated-orcid":false,"given":"Raffaella","family":"Belvedere","sequence":"first","affiliation":[{"name":"Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nunzia","family":"Novizio","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6967-1812","authenticated-orcid":false,"given":"Daniela","family":"Eletto","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5947-9472","authenticated-orcid":false,"given":"Amalia","family":"Porta","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonino","family":"Bagnulo","sequence":"additional","affiliation":[{"name":"Neilos Srl, Via Bagnulo 95, 80063 Piano di Sorrento, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Cerciello","sequence":"additional","affiliation":[{"name":"Neilos Srl, Via Bagnulo 95, 80063 Piano di Sorrento, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Umberto","family":"Di Maio","sequence":"additional","affiliation":[{"name":"Shedir Pharma Group Spa, Via Bagnulo 95, 80063 Piano di Sorrento, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6945-5295","authenticated-orcid":false,"given":"Antonello","family":"Petrella","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kullar, P., Weerakkody, R., Cathcart, R., and Yates, P. (2017). Locally applied haemostatic agents in the management of acute epistaxis (nosebleeds). Cochrane Database Syst. Rev., 2017.","DOI":"10.1002\/14651858.CD009373.pub2"},{"key":"ref_2","first-page":"12","article-title":"Current Approaches to Epistaxis Treatment in Primary and Secondary Care","volume":"115","author":"Beck","year":"2018","journal-title":"Dtsch. Aerzteblatt Online"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.pop.2013.10.007","article-title":"Epistaxis","volume":"41","author":"Morgan","year":"2014","journal-title":"Prim. Care: Clin. Off. Pr."},{"key":"ref_4","first-page":"5832","article-title":"A new double-lumen hemostatic device for treatment of intractable traumatic epistaxis induced by craniofacial basicranial fractures","volume":"10","author":"Shao","year":"2017","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_5","first-page":"305","article-title":"Management of epistaxis","volume":"71","author":"Kucik","year":"2005","journal-title":"Am. Fam. Physician"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"64","DOI":"10.3389\/fcvm.2017.00064","article-title":"Role of Dietary Antioxidants in the Preservation of Vascular Function and the Modulation of Health and Disease","volume":"4","author":"Varadharaj","year":"2017","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1002\/mnfr.200900399","article-title":"In vitro antioxidant activity of tocopherols and tocotrienols and comparison of vitamin E concentration and lipophilic antioxidant capacity in human plasma","volume":"54","author":"Theile","year":"2010","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_8","first-page":"361","article-title":"Skin moisturizing effects of panthenol-based formulations","volume":"62","author":"Camargo","year":"2011","journal-title":"J. Cosmet. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2014\/635490","article-title":"Clinical Efficacy of a Spray Containing Hyaluronic Acid and Dexpanthenol after Surgery in the Nasal Cavity (Septoplasty, Simple Ethmoid Sinus Surgery, and Turbinate Surgery)","volume":"2014","author":"Gouteva","year":"2014","journal-title":"J. Allergy"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Xue, J., Chen, J., Shen, Q., Chan, D., Li, J., Tanguay, A.P., Schmidt, T.A., Niazi, F., and Plaas, A. (2020). Addition of High Molecular Weight Hyaluronic Acid to Fibroblast-Like Stromal Cells Modulates Endogenous Hyaluronic Acid Metabolism and Enhances Proteolytic Processing and Secretion of Versican. Cells, 9.","DOI":"10.3390\/cells9071681"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Choi, E., Kang, Y.-G., Hwang, S.-H., Kim, J.K., Hong, Y.D., Park, W.-S., Kim, D., Kim, E., and Cho, J.Y. (2019). In Vitro Effects of Dehydrotrametenolic Acid on Skin Barrier Function. Molecules, 24.","DOI":"10.3390\/molecules24244583"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Belvedere, R., Bizzarro, V., Parente, L., Petrella, F., and Petrella, A. (2017). The Pharmaceutical Device Prisma\u00ae Skin Promotes in Vitro Angiogenesis through Endothelial to Mesenchymal Transition during Skin Wound Healing. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18081614"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/19336918.2017.1340137","article-title":"Effects of Prisma\u00ae Skin dermal regeneration device containing glycosaminoglycans on human keratinocytes and fibroblasts","volume":"12","author":"Belvedere","year":"2017","journal-title":"Cell Adhes. Migr."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"De Torre, M.P., Cavero, R.Y., Calvo, M.I., and Vizmanos, J.L. (2019). A Simple and a Reliable Method to Quantify Antioxidant Activity In Vivo. Antioxidants, 8.","DOI":"10.3390\/antiox8050142"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Bizzarro, V., Fontanella, B., Carrat\u00f9, A., Belvedere, R., Marfella, R., Parente, L., and Petrella, A. (2012). Annexin A1 N-Terminal Derived Peptide Ac2-26 Stimulates Fibroblast Migration in High Glucose Conditions. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0045639"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4926","DOI":"10.1002\/jcp.30207","article-title":"Mesoglycan exerts its fibrinolytic effect through the activation of annexin A2","volume":"236","author":"Belvedere","year":"2021","journal-title":"J. Cell. Physiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.transci.2007.12.005","article-title":"Thrombin generation, fibrin clot formation and hemostasis","volume":"38","author":"Wolberg","year":"2008","journal-title":"Transfus. Apher. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1177\/0194599816667295","article-title":"Demographic, Seasonal, and Geographic Differences in Emergency Department Visits for Epistaxis","volume":"156","author":"Chaaban","year":"2016","journal-title":"Otolaryngol. Neck Surg."},{"key":"ref_19","first-page":"S1","article-title":"Clinical Practice Guideline: Nosebleed (Epistaxis)","volume":"162","author":"Tunkel","year":"2020","journal-title":"Otolaryngol. Neck Surg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3219","DOI":"10.1007\/s00018-014-1598-z","article-title":"Redox regulation of endothelial cell fate","volume":"71","author":"Song","year":"2014","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1111\/j.0105-1873.2003.00184.x","article-title":"Efficacy of dexpanthenol in skin protection against irritation: A double-blind, placebo-controlled study","volume":"49","author":"Biro","year":"2003","journal-title":"Contact Dermat."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"427","DOI":"10.2165\/00128071-200203060-00005","article-title":"Topical Use of Dexpanthenol in Skin Disorders","volume":"3","author":"Ebner","year":"2002","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"R268","DOI":"10.1186\/ar1487","article-title":"Inhibition of antithrombin by hyaluronic acid may be involved in the pathogenesis of rheumatoid arthritis","volume":"7","author":"Chang","year":"2005","journal-title":"Arthritis Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1039\/C9MH00157C","article-title":"A serotonin-modified hyaluronic acid hydrogel for multifunctional hemostatic ad-hesives inspired by a platelet coagulation mediator","volume":"6","author":"An","year":"2019","journal-title":"Mater. Horiz."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/S0022-5193(86)80076-5","article-title":"A model for the role of hyaluronic acid and fibrin in the early events during the inflammatory response and wound healing","volume":"119","author":"Weigel","year":"1986","journal-title":"J. Theor. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2010\/807935","article-title":"Hyaluronan Immobilized Polyurethane as a Blood Contacting Material","volume":"2010","author":"Gong","year":"2010","journal-title":"Int. J. Polym. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1017\/S0022215108003460","article-title":"Nasal bacterial carriage in adult epistaxis: Is neomycin the answer?","volume":"123","author":"Walker","year":"2008","journal-title":"J. Laryngol. 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