{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T05:42:27Z","timestamp":1783575747796,"version":"3.55.0"},"reference-count":43,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,4,9]],"date-time":"2024-04-09T00:00:00Z","timestamp":1712620800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministerio de Ciencia, Tecnolog\u00eda e Innovaci\u00f3n","award":["589-2018\/CIQF-289"],"award-info":[{"award-number":["589-2018\/CIQF-289"]}]},{"name":"Ministerio de Ciencia, Tecnolog\u00eda e Innovaci\u00f3n","award":["202000010059"],"award-info":[{"award-number":["202000010059"]}]},{"name":"Sistema General de Regalias","award":["589-2018\/CIQF-289"],"award-info":[{"award-number":["589-2018\/CIQF-289"]}]},{"name":"Sistema General de Regalias","award":["202000010059"],"award-info":[{"award-number":["202000010059"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>In Colombia, Micrurus snakebites are classified as severe according to the national clinical care guidelines and must be treated with specific antivenoms. Unfortunately, these types of antivenoms are scarce in certain areas of the country and are currently reported as an unavailable vital medicine. To address this issue, La Universidad de Antioquia, through its spin-off Tech Life Saving, is leading a project to develop third-generation polyvalent freeze-dried antivenom. The goal is to ensure access to this therapy, especially in rural and dispersed areas. This project aims to evaluate the physicochemical and preclinical parameters (standard quality characteristics) of a lab-scale anti-elapid antivenom batch. The antivenom is challenged against the venoms of several Micrurus species, including M. mipartitus, M. dumerilii, M. ancoralis, M. dissoleucus, M. lemniscatus, M. medemi, M. spixii, M. surinamensis, and M. isozonus, following the standard quality characteristics set by the World Health Organization (WHO). The antivenom demonstrates an appearance consistent with standards, 100% solubility within 4 min and 25 s, an extractable volume of 10.39 mL, a pH of 6.04, an albumin concentration of 0.377 mg\/mL (equivalent to 1.22% of total protein), and a protein concentration of 30.97 mg\/mL. Importantly, it maintains full integrity of its F(ab\u2032)2 fragments and exhibits purity over 98.5%. Furthermore, in mice toxicity evaluations, doses up to 15 mg\/mouse show no toxic effects. The antivenom also demonstrates a significant recognition pattern against Micrurus venoms rich in phospholipase A2 (PLA2) content, as observed in M. dumerilii, M. dissoleucus, and M. isozonus. The effective dose 50 (ED50) indicates that a single vial (10 mL) can neutralize 2.33 mg of M. mipartitus venom and 3.99 mg of M. dumerilii venom. This new anti-elapid third-generation polyvalent and freeze-dried antivenom meets the physicochemical parameters set by the WHO and the regulators in Colombia. It demonstrates significant efficacy in neutralizing the venom of the most epidemiologically important Micrurus species in Colombia. Additionally, it recognizes seven other species of Micrurus venom with a higher affinity for venoms exhibiting PLA2 toxins. Fulfilling these parameters represents the first step toward proposing a new pharmacological alternative for treating snakebites in Colombia, particularly in dispersed rural areas, given that this antivenom is formulated as a freeze-dried product.<\/jats:p>","DOI":"10.3390\/toxins16040183","type":"journal-article","created":{"date-parts":[[2024,4,9]],"date-time":"2024-04-09T04:37:27Z","timestamp":1712637447000},"page":"183","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Standard Quality Characteristics and Efficacy of a New Third-Generation Antivenom Developed in Colombia Covering Micrurus spp. Venoms"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7260-1194","authenticated-orcid":false,"given":"Santiago","family":"Tabares V\u00e9lez","sequence":"first","affiliation":[{"name":"Grupo de Toxinolog\u00eda y Alternativas Terap\u00e9uticas\u2014Serpentario, Facultad de Ciencias Farmac\u00e9uticas y Alimentarias, Universidad de Antioquia (UdeA), Medellin 050010, Colombia"},{"name":"Tech Life Saving (TLS), Tech Innovation Group Company, Medellin 050022, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3096-2134","authenticated-orcid":false,"given":"Lina Mar\u00eda","family":"Preciado","sequence":"additional","affiliation":[{"name":"Grupo de Toxinolog\u00eda y Alternativas Terap\u00e9uticas\u2014Serpentario, Facultad de Ciencias Farmac\u00e9uticas y Alimentarias, Universidad de Antioquia (UdeA), Medellin 050010, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1332-5106","authenticated-orcid":false,"given":"Leidy Johana","family":"Vargas Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Tech Life Saving (TLS), Tech Innovation Group Company, Medellin 050022, Colombia"},{"name":"Facultad de Medicina, Universidad Cooperativa de Colombia, Medellin 050012, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Alberto","family":"Madrid Bracamonte","sequence":"additional","affiliation":[{"name":"Tech Life Saving (TLS), Tech Innovation Group Company, Medellin 050022, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelica","family":"Zuluaga","sequence":"additional","affiliation":[{"name":"Tech Life Saving (TLS), Tech Innovation Group Company, Medellin 050022, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeisson","family":"G\u00f3mez Robles","sequence":"additional","affiliation":[{"name":"Grupo de Toxinolog\u00eda y Alternativas Terap\u00e9uticas\u2014Serpentario, Facultad de Ciencias Farmac\u00e9uticas y Alimentarias, Universidad de Antioquia (UdeA), Medellin 050010, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila","family":"Renjifo-Iba\u00f1ez","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Tibaitat\u00e1, Corporaci\u00f3n Colombiana de Investigaci\u00f3n Agropecuaria\u2014AGROSAVIA, Bogota 250047, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7326-5873","authenticated-orcid":false,"given":"Sebasti\u00e1n","family":"Estrada-G\u00f3mez","sequence":"additional","affiliation":[{"name":"Grupo de Toxinolog\u00eda y Alternativas Terap\u00e9uticas\u2014Serpentario, Facultad de Ciencias Farmac\u00e9uticas y Alimentarias, Universidad de Antioquia (UdeA), Medellin 050010, Colombia"},{"name":"Tech Life Saving (TLS), Tech Innovation Group Company, Medellin 050022, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,9]]},"reference":[{"key":"ref_1","unstructured":"Lynch, J., Angarita, T., and Ruiz, F. (2014). Programa Nacional Para La Conservaci\u00f3n De Las Serpientes Presentes En Colombia."},{"key":"ref_2","first-page":"49","article-title":"The Reptile Database","volume":"49","author":"Uetz","year":"2012","journal-title":"Choice Rev. Online"},{"key":"ref_3","unstructured":"Instituto Nacional de Salud (2023, April 18). Accidente Of\u00eddico Periodo Epidemiol\u00f3gico 2022, Available online: https:\/\/www.ins.gov.co\/buscador-eventos\/Informesdeevento\/ACCIDENTEOFIDICOPEXIII2022.pdf."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.toxicon.2016.09.008","article-title":"Venoms of Micrurus Coral Snakes: Evolutionary Trends in Compositional Patterns Emerging from Proteomic Analyses","volume":"122","author":"Lomonte","year":"2016","journal-title":"Toxicon"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/j.jprot.2011.09.003","article-title":"Proteomic and Biological Characterization of the Venom of the Redtail Coral Snake, Micrurus Mipartitus (Elapidae), from Colombia and Costa Rica","volume":"75","author":"Lomonte","year":"2011","journal-title":"J. Proteom."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.jprot.2016.02.006","article-title":"Integrative Characterization of the Venom of the Coral Snake Micrurus Dumerilii (Elapidae) from Colombia: Proteome, Toxicity, and Cross-Neutralization by Antivenom","volume":"136","author":"Lomonte","year":"2016","journal-title":"J. Proteom."},{"key":"ref_7","unstructured":"(2023, May 07). Naturalista Comisi\u00f3n Nacional Para El Conocimiento y Uso de La Biodiversidad. Available online: https:\/\/colombia.inaturalist.org\/."},{"key":"ref_8","unstructured":"Campbell, J., Lamar, W., and Brodie, E. (2004). The Venomous Reptiles of the Western Hemisphere, Comstock, Cornell University Press."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1590\/S0036-46652010000600009","article-title":"Envenenamento Por Coral Do G\u00eanero Micrurus Na Amaz\u00f4nia Brasileira: Relato de Dois Casos","volume":"52","author":"Pardal","year":"2010","journal-title":"Rev. Inst. Med. Trop. Sao Paulo"},{"key":"ref_10","first-page":"1","article-title":"Envenomation by the Red-Tailed Coral Snake (Micrurus mipartitus) in Colombia","volume":"23","year":"2017","journal-title":"J. Venom. Anim. Toxins Incl. Trop. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1055\/s-2004-830904","article-title":"Snake Venoms and the Neuromuscular Junction","volume":"24","author":"Lewis","year":"2004","journal-title":"Semin Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"171","DOI":"10.2147\/DHPS.S367757","article-title":"Epidemiology of Snake Bites Linked with the Antivenoms Production in Colombia 2008\u20132020: Produced Vials Do Not Meet the Needs","volume":"14","year":"2022","journal-title":"Drug Healthc. Patient. Saf."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.26633\/RPSP.2017.109","article-title":"La Producci\u00f3n P\u00fablica de Antivenenos En La Regi\u00f3n de Las Am\u00e9ricas Como Factor Clave En Su Accesibilidad","volume":"41","author":"Temprano","year":"2017","journal-title":"Rev. Panam. De Salud P\u00fablica"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1093\/jas\/sky467","article-title":"Factors That Can Influence the Survival Rates of Coral Snakes (Micrurus coralnus) for Antivenom Production","volume":"97","author":"Mendes","year":"2019","journal-title":"J. Anim. Sci."},{"key":"ref_15","unstructured":"(2021, November 13). INVIMA Medicamentos Vitales No Disponibles, Available online: https:\/\/www.invima.gov.co\/medicamentos-vitales-no-disponibles."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1016\/S0041-0101(97)00160-8","article-title":"Venoms, Antivenoms and Immunotherapy","volume":"36","author":"Chippaux","year":"1998","journal-title":"Toxicon"},{"key":"ref_17","first-page":"30","article-title":"Comparaci\u00f3n de La Eficacia, La Seguridad y La Farmacocin\u00e9tica de Los Antivenenos Antiof\u00eddicos: Revisi\u00f3n de Literatura","volume":"61","author":"Sarmiento","year":"2019","journal-title":"Univ. M\u00e9dica"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.toxicon.2013.09.004","article-title":"Production of Anti-Horse Antibodies Induced by IgG, F(Ab\u2019)2 and Fab Applied Repeatedly to Rabbits. Effect on Antivenom Pharmacokinetics","volume":"76","author":"Olvera","year":"2013","journal-title":"Toxicon"},{"key":"ref_19","unstructured":"World Health Organization (2017). WHO Expert Committee on Biological Standardization, World Health Organization. Available online: http:\/\/www.jstor.org\/stable\/resrep44225.16."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.toxicon.2019.05.001","article-title":"Comparative Venomics of Brazilian Coral Snakes: Micrurus Frontalis, Micrurus Spixii Spixii, and Micrurus Surinamensis","volume":"166","author":"Sanz","year":"2019","journal-title":"Toxicon"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.jprot.2019.03.014","article-title":"New Insights into the Phylogeographic Distribution of the 3FTx\/PLA 2 Venom Dichotomy across Genus Micrurus in South America","volume":"200","author":"Sanz","year":"2019","journal-title":"J. Proteom."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/0041-0101(92)90855-Y","article-title":"Efectos Farmacologicos y Enzimaticos de Los Venenos de Serpientes de Antioquia y Choco (Colombia)","volume":"30","author":"Otero","year":"1992","journal-title":"Toxicon"},{"key":"ref_23","unstructured":"(2023, May 01). Istvan Lazar GelAnalyzer. Available online: http:\/\/www.gelanalyzer.com\/index.html."},{"key":"ref_24","unstructured":"Diehl, L., and Morse, M. (2015). A Comparison of Selected Organ Weights and Clinical Pathology Parameters in Male and Female CD-1 and CByB6F1 Hybrid Mice 12\u201314 Weeks in Age, Charles River."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/j.toxicon.2012.05.023","article-title":"Mipartoxin-I, a Novel Three-Finger Toxin, Is the Major Neurotoxic Component in the Venom of the Redtail Coral Snake Micrurus Mipartitus (Elapidae)","volume":"60","author":"Floriano","year":"2012","journal-title":"Toxicon"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-Vargas, A., Franco-V\u00e1squez, A.M., Bol\u00edvar-Barbosa, J.A., Vega, N., Reyes-Monta\u00f1o, E., Arregu\u00edn-Espinosa, R., Carbajal-Saucedo, A., Angarita-Sierra, T., and Ruiz-G\u00f3mez, F. (2023). Unveiling the Venom Composition of the Colombian Coral Snakes Micrurus Helleri, M. Medemi, and M. Sangilensis. Toxins, 15.","DOI":"10.3390\/toxins15110622"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"369","DOI":"10.2174\/187152811797200669","article-title":"Antivenoms for Snakebite Envenomings","volume":"10","author":"Lomonte","year":"2011","journal-title":"Inflamm. Allergy Drug Targets"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Castillo-Beltr\u00e1n, M.C., Hurtado-G\u00f3mez, J.P., Corredor-Espinel, V., and Ruiz-G\u00f3mez, F.J. (2018). A Polyvalent Coral Snake Antivenom with Broad Neutralization Capacity. PLoS Negl. Trop Dis., 13.","DOI":"10.1371\/journal.pntd.0007250"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/0041-0101(94)90107-4","article-title":"A New Antivenom to Treat Eastern Coral Snake (Micrurus Fulvius Fulvius) Envenoming","volume":"32","author":"Rawat","year":"1994","journal-title":"Toxicon"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.biologicals.2011.11.006","article-title":"Low PH Formulation of Whole IgG Antivenom: Impact on Quality, Safety, Neutralizing Potency and Viral Inactivation","volume":"40","author":"Solano","year":"2012","journal-title":"Biologicals"},{"key":"ref_31","first-page":"21","article-title":"Influencia Del PH Sobre La Estabilidad de Preparados de Inmunoglobulinas Intravenosas Para Uso Humano Durante El Almacenamiento","volume":"9","author":"Castillo","year":"2000","journal-title":"Vaccimonitor"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.biologicals.2020.08.005","article-title":"Critical Aspects on Traditional Antivenom Production Processes and Their Optimization by Factorial Analysis","volume":"68","author":"Zurbano","year":"2020","journal-title":"Biologicals"},{"key":"ref_33","first-page":"1","article-title":"Envenenamientos Por Mordeduras de Serpientes En Am\u00e9rica Latina y El Caribe: Una Visi\u00f3n Integral de Car\u00e1cter Regional","volume":"51","year":"2011","journal-title":"Bol. Malariol. Salud Ambient."},{"key":"ref_34","first-page":"124","article-title":"Escenario Epidemiol\u00f3gico Del Accidente Of\u00eddico En Colombia, 2023","volume":"9","year":"2023","journal-title":"Rev. Exp. En Med. Del Hosp. Reg. Lambayeque"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1258\/la.2012.150312","article-title":"Guide for the Care and Use of Laboratory Animals (8th Edn)","volume":"46","author":"Albus","year":"2012","journal-title":"Lab. Anim."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"He, F. (2011). Laemmli-SDS-PAGE. Bio. Protoc., 1.","DOI":"10.21769\/BioProtoc.80"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.measurement.2017.08.013","article-title":"Measurement of the Total Protein in Serum by Biuret Method with Uncertainty Evaluation","volume":"112","author":"Zheng","year":"2017","journal-title":"Measurement"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1093\/clinchem\/27.10.1642","article-title":"A Candidate Reference Method for Determination of Total Protein in Serum. I. Development and Validation","volume":"27","author":"Doumas","year":"1981","journal-title":"Clin. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/0009-8981(71)90365-2","article-title":"Albumin Standards and the Measurement of Serum Albumin with Bromcresol Green","volume":"31","author":"Doumas","year":"1971","journal-title":"Clin. Chim. Acta"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1111\/j.1699-0463.1949.tb00751.x","article-title":"Antigen-Antibody Reactions in Gels","volume":"26","author":"Ouchterlony","year":"1949","journal-title":"Acta Pathol. Microbiol. Scand."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1038\/227680a0","article-title":"Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4","volume":"227","author":"Laemmli","year":"1970","journal-title":"Nature"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.toxicon.2011.11.017","article-title":"Comparative Study of the Efficacy and Safety of Two Polyvalent, Caprylic Acid Fractionated [IgG and F(Ab\u2019)2] Antivenoms, in Bothrops Asper Bites InColombia","volume":"59","author":"Segura","year":"2012","journal-title":"Toxicon"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Weil, C.S. (1952). Tables for Convenient Calculation of Median-Effective Dose (LD 50 or ED 50 ) and Instructions in Their Use. Biometrics, 8.","DOI":"10.2307\/3001557"}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/16\/4\/183\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:25:17Z","timestamp":1760106317000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/16\/4\/183"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,9]]},"references-count":43,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["toxins16040183"],"URL":"https:\/\/doi.org\/10.3390\/toxins16040183","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,9]]}}}