{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T20:55:30Z","timestamp":1771534530262,"version":"3.50.1"},"reference-count":15,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T00:00:00Z","timestamp":1620172800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Cosmetic Dermatology"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Collagenase clostridium histolyticum (CCH\u2010aesthetic formulation [CCH\u2010aaes]; QWO\u2122 [Endo Aesthetics, Malvern PA, USA] is approved as a subcutaneous injection for treatment of cellulite. In the aesthetic practice, dilution of marketed products is commonly employed to tailor treatments to individual patients or off\u2010label locations. Dilution beyond the 0.23\u00a0mg\/ml achievable with the proprietary diluent supplied with the CCH\u2010aaes lyophilized powder requires diluents readily available in clinic.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To characterize the functionality and stability of CCH\u2010aaes when reconstituted and\/or diluted with alternative diluents, including normal saline, bacteriostatic saline, and\/or proprietary diluent.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients\/Methods<\/jats:title><jats:p>Each dilution was assessed for purity using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE), activity using collagenase (AUX\u2010I) and gelatinase (AUX\u2010II) assays, and aggregation using size\u2010exclusion chromatography.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>When reconstituted with either saline or proprietary diluent, and diluted with proprietary diluent or saline, purity, activity, and stability of CCH\u2010aaes is maintained for up to 24\u00a0h at 5\u00b0C or 25\u00b0C. In contrast, use of bacteriostatic saline to reconstitute and\/or dilute CCH\u2010aaes results in up to a 40% decrease in activity and aggregation of 5.3% of CCH\u2010aaes protein. Importantly, inclusion of 2% lidocaine and 1:200\u00a0000 epinephrine does not negatively impact CCH\u2010aaes purity, concentration, or activity for up to 24\u00a0h at 5\u00b0C or 25\u00b0C.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>From an efficacy and safety perspective, CCH\u2010aaes must not be\/should not be reconstituted and\/or diluted with bacteriostatic saline to avoid injection of protein aggregates. Ideally, CCH\u2010aaes should be reconstituted in proprietary diluent: further dilution with normal saline and addition of lidocaine and epinephrine is acceptable.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jocd.14078","type":"journal-article","created":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T16:00:43Z","timestamp":1616083243000},"page":"1643-1647","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Evaluation of alternative diluents for clinical use of collagenase clostridium histolyticum (CCH\u2010aaes)"],"prefix":"10.1111","volume":"20","author":[{"given":"Henry R.","family":"Wolfe","sequence":"first","affiliation":[{"name":"Endo Pharmaceuticals, Inc Horsham PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Rosenberg","sequence":"additional","affiliation":[{"name":"Endo Aesthetics LLC Malvern PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kadriye","family":"Ciftci","sequence":"additional","affiliation":[{"name":"Endo Pharmaceuticals, Inc Horsham PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jill","family":"Edgecombe","sequence":"additional","affiliation":[{"name":"Endo Aesthetics LLC Malvern PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael P.","family":"McLane","sequence":"additional","affiliation":[{"name":"Endo Pharmaceuticals, Inc Horsham PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,5,5]]},"reference":[{"key":"e_1_2_7_2_1","unstructured":"QWO [instructions for use].Malvern PA: Endo Aesthetics; Accessed December 2020."},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.5534\/wjmh.17033"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00377a004"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.2147\/CCID.S95830"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijwd.2018.09.002"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000372-200002000-00007"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/DSS.0000000000001685"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.36849\/JDD.2020.5454"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/14764170310021841"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/DSS.0000000000001803"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2013.02.022"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)83736-X"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2009.07078.x"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xphs.2015.11.002"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1208\/aapsj080359"}],"container-title":["Journal of Cosmetic Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jocd.14078","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jocd.14078","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jocd.14078","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T11:34:46Z","timestamp":1692963286000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jocd.14078"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,5]]},"references-count":15,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,6]]}},"alternative-id":["10.1111\/jocd.14078"],"URL":"https:\/\/doi.org\/10.1111\/jocd.14078","archive":["Portico"],"relation":{},"ISSN":["1473-2130","1473-2165"],"issn-type":[{"value":"1473-2130","type":"print"},{"value":"1473-2165","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,5]]},"assertion":[{"value":"2021-01-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}