# TB-500 and Thymosin Beta-4 dosage research context > Research-context dosing summary for Thymosin Beta-4 and the synthetic TB-500 7-AA fragment: rodent topical and intraperitoneal doses, human Phase I intravenous dose escalation, half-life data, and notes on the absence of fragment-specific pharmacokinetic literature. What the rodent studies actually used, what the Phase I trials actually tested, and why the 'two milligrams per week' schedule circulating online has no peer-reviewed basis for the fragment. ## What the studies actually dosed Every dose figure on this page comes from a published study, and nearly all of them are doses of full-length Thymosin Beta-4 — not of the TB-500 fragment. The rodent studies used topical microgram quantities for wound healing and milligram-per-kilogram intraperitoneal doses for cardiac and neurological models. The human Phase I trials tested intravenous full-length Tβ4 at doses ranging from 42 mg to 1,260 mg single dose, with a clean safety record. The 'two to three milligrams per week subcutaneous' schedules that circulate in research-use communities have no peer-reviewed basis for the fragment; this page lays out exactly what the published record does and does not support. The framing throughout is research context only — these numbers describe what investigators administered under research protocols, not human therapeutic recommendations. ## Doses reported in animal studies The published Tβ4 animal literature reports a narrow set of dose schedules. The four most-cited are: - **Topical, 5 micrograms per wound, twice daily.** The dermal punch-wound studies in rats (Malinda 1999) [3] and the corneal alkali-burn studies in mice (Sosne 2002) [4] both used 5 micrograms of Tβ4 in a small PBS volume (50 µL dermal, 5 µL ocular). The corneal study dosed twice daily; the dermal study compared single-dose topical and intraperitoneal administration. These two studies are the foundation of essentially every later wound-healing experiment in the Tβ4 record. - **Intraperitoneal, 150 micrograms every three days.** This is the regimen Smart and colleagues used for adult-mouse epicardial progenitor cell mobilization and coronary neovascularization in the heart [7]. Scaled by body weight in mice, this corresponds to roughly 6 mg per kilogram per dose. - **Intravenous, 3.75 mg per kilogram, single dose.** This is the dose Morris and colleagues used in rats 24 hours after embolic middle cerebral artery occlusion, with improved neurological function from day 14 through day 56 [12]. - **Intracoronary retroperfusion (porcine).** Hinkel and colleagues administered Tβ4 by retroperfusion to the site of injury in pigs at the end of ischemia, with improved subendocardial segment shortening 24 hours after reperfusion [8]. The competing porcine study used 150 micrograms per kilogram IV bolus plus maintenance and did not reduce infarct size [21]. Every dose above is the dose of full-length 43-AA Thymosin Beta-4, not the 7-AA TB-500 fragment. ## Doses tested in human Phase I trials Two human Phase I dose-escalation trials of intravenous recombinant Tβ4 have been published. Ruff and colleagues (2010) tested single IV doses of 42, 140, 420, and 1,260 mg in 40 healthy adult volunteers, followed by a multiple-dose extension. The trial reported no dose-limiting toxicities and no serious adverse events across the full dose range. The 1,260 mg single dose is roughly four orders of magnitude above the per-kilogram range typically reported in rodent studies [13]. Wang and colleagues (2021) tested single IV doses of recombinant Tβ4 (NL005) at 0.05, 0.25, 0.5, 2.0, 5.0, 12.5, and 25.0 micrograms per kilogram in 84 healthy Chinese adults, with a multiple-dose arm at 0.5 to 5.0 micrograms per kilogram per day for 10 days. The trial reported dose-proportional Cmax and AUC, no SAEs, no dose-limiting toxicities, and a favorable immunogenicity profile [14]. The two Phase I trials use different units (Ruff fixed-mg, Wang per-kg) and span roughly three orders of magnitude in dose, so direct comparison is awkward — but together they constitute the only peer-reviewed human safety dataset for any Tβ4 molecule. Both used full-length Tβ4, not the TB-500 fragment. ## Half-life and pharmacokinetics Published pharmacokinetic data exist only for full-length recombinant Tβ4. In the human IV PK reported by Ruff and colleagues, and confirmed by Wang and colleagues, Tβ4 plasma concentrations declined biphasically with rapid distribution and terminal exposure measured over hours, without dose-dependent accumulation across the tested range [13][14]. No peer-reviewed pharmacokinetic study of the synthetic 7-AA TB-500 heptapeptide exists in humans. Rodent estimates of a 1.5- to 3-hour plasma half-life for the heptapeptide after subcutaneous or intramuscular injection circulate widely online but trace back to vendor and aggregator pages rather than primary literature [22]. These estimates should be treated as low-confidence. The N-terminal acetylation that defines TB-500 does block aminopeptidase cleavage in vitro and improves solution stability versus the unmodified LKKTETQ heptapeptide, which is the main pharmacokinetic claim that has some structural basis [22]. Both molecules are inactivated by gastric proteases, so oral administration is not pharmacologically meaningful and every published preclinical and clinical study has used parenteral or topical routes. ## Routes that have been studied Published Tβ4 research has used six administration routes: - **Topical** — dermal wound and corneal-surface studies [3][4] - **Intraperitoneal** — rodent systemic dosing [3][6][7] - **Intravenous** — rodent, porcine, and human Phase I trials [12][13][14][21] - **Subcutaneous** — rodent and equine doping-control PK [20] - **Intracoronary retroperfusion** — porcine ischemia-reperfusion models [8] - **AAV-delivered overexpression** — mouse cardiac fibrosis models [17] Oral and inhaled routes do not appear in the published research record for either Tβ4 or the TB-500 fragment. ## What vendor literature claims versus what the literature shows Vendor pages for TB-500 typically promote subcutaneous schedules in the range of 2 to 10 milligrams per week, sometimes structured as a loading phase followed by a maintenance phase. These schedules have no peer-reviewed clinical basis for the 7-AA fragment. The doses are not derived from any published human pharmacokinetic study of the fragment, not derived from any registered clinical trial of the fragment, and not derived from any rodent dose-finding study of the fragment [22]. What the published literature does show is: 1. Topical microgram-range doses of the parent Tβ4 accelerate wound and corneal healing in rodents [3][4]. 2. Milligram-range IV doses of the parent Tβ4 are safe in humans across two Phase I trials [13][14]. 3. The fragment retains in vitro actin binding (the LKKTET core) and at least some wound-healing activity in mice when synthetic peptides containing the actin-binding domain are tested [5]. 4. No fragment-specific human PK, efficacy, or safety dataset exists [22]. The gap between (1)–(3) and the multi-milligram-per-week subcutaneous schedules circulating in non-clinical use is large. This site does not provide a recommended schedule for human use; the framing is research-context only. --- An editorial record of the peer-reviewed Thymosin Beta-4 literature — not a clinic, not a vendor, not medical guidance.