What doses the studies used — and why none of them is a prescribing protocol

What the studies administered

This page lists the doses, routes and species from published research — not a prescribing protocol. No clinical protocol exists for the TB-500 fragment because the fragment has never been in a registered human trial. The numbers here come from animal studies (rats, mice, pigs, horses) and from the two published Phase I trials of full-length intravenous Tβ4 in healthy volunteers. Vendor-circulated figures — '2 to 10 mg per week subcutaneous' — appear nowhere in peer-reviewed literature and are noted as market-origin claims. The study doses are listed so readers can place those vendor numbers against the actual published record.

A note on what this page is

This page summarizes the doses and routes used in published animal and human studies of Thymosin Beta-4 and the synthetic TB-500 fragment. It is research-context only.

It is not a dosing protocol. It is not a prescribing schedule. No clinical dosing protocol exists for the synthetic seven-residue TB-500 fragment, because the fragment has never been the subject of a registered human trial and is not a prescribable substance under United States regulation ^[22][26]. The numbers below describe what was administered in published experiments, in the units the experiments used, with the routes the experiments used. They are presented so that readers can place vendor marketing claims and underground-use anecdotes against the actual published record.

Routes used in the published work

Published studies of Tβ4 and TB-500 have used six routes of administration:

• Topical, for dermal wound healing in rats and mice and for corneal surface application in mice ^[3][4][5].
• Intraperitoneal, for systemic rodent dosing in cardiac and epicardial models ^[6][7].
• Intravenous, for rodent cardiac and stroke models, for the porcine ischemia-reperfusion work, and for every published human Phase I trial of recombinant Tβ4 ^{[6][12][13][14][17][23]}.
• Subcutaneous, in rodent and equine doping-control studies ^[22].
• Intracoronary retroperfusion, in the 2008 porcine LAD-occlusion model that combined Tβ4 with embryonic endothelial progenitor cells ^[8].
• Intramyocardial AAV-delivered overexpression, in mouse fibrosis models — a delivery system that is not the peptide itself but a viral vector encoding it ^[18].

Oral administration has not been studied in any peer-reviewed efficacy trial because both the parent peptide and the fragment are inactivated by gastric proteases ^[22]. All published preclinical and clinical work has used parenteral or topical routes.

Doses used in the animal research

In the dermal-wound work that founded the field, Malinda and colleagues used 5 μg of Tβ4 in 50 μL of PBS per wound, applied topically or by intraperitoneal injection, in Sprague-Dawley rats ^[3]. The 2003 Philp paper used 0.1 to 5 μg per wound topically in db/db diabetic and aged mice ^[5].

In the corneal work, Sosne and colleagues used 5 μg in 5 μL PBS topically twice daily in 129 Sv mice after alkali burn ^[4].

In the cardiac mouse work, the original Bock-Marquette paper used a single intraperitoneal bolus plus continued dosing over four weeks after coronary artery ligation ^[6]. Smart and colleagues used 150 μg intraperitoneally every three days to mobilize adult epicardial progenitor cells ^[7]. In the AAV-delivered mouse cardiac fibrosis work, a single 10^12 vg dose of AAV9-Tβ4 was administered intramyocardially or intravenously ^[18].

In the porcine cardiac work, the 2008 Hinkel paper used Tβ4 retroperfused to the site of injury during reperfusion ^[8]. The 2016 Wei paper used 150 μg/kg IV bolus plus maintenance dosing, given either before or after ischemia, and found no reduction in global infarct size at 24 hours ^[23].

In the stroke work, Morris and colleagues used a single 3.75 mg/kg IV dose administered 24 hours after embolic middle-cerebral-artery occlusion in rats ^[12].

Doses used in the human trials

The Ruff 2010 Phase I study escalated single IV doses of recombinant Tβ4 from 42 mg through 140 mg and 420 mg to 1,260 mg in 40 healthy adult volunteers, with a multiple-dose extension ^[13]. No dose-limiting toxicities and no serious adverse events were observed.

The Wang 2021 Chinese Phase I study escalated single IV doses from 0.05 to 0.25 to 0.5 to 2.0 to 5.0 to 12.5 to 25.0 μg/kg in 84 healthy Chinese adults, with a multiple-dose extension of 0.5 to 5.0 μg/kg per day intravenously for ten days ^[14]. PK was dose-proportional and no SAEs were reported.

The planned RGN-352 Phase II cardiac regimen was 450 mg or 1,200 mg IV daily for three days followed by weekly for four weeks in approximately 75 post-AMI patients ^[17]. The trial did not complete enrollment and did not report efficacy.

The RGN-259 ophthalmic clinical program used a 0.1% Tβ4 ophthalmic solution administered topically twice daily in Phase II/III dry-eye work and six times daily for 28 days in the Phase III neurotrophic-keratopathy trial ^[15][16].

These are the doses on the human record. Every one of them was administered with full-length recombinant Tβ4. None of them was administered with the synthetic seven-residue TB-500 fragment.

Pharmacokinetics, such as they are

Published PK data for full-length recombinant Tβ4 in humans (Ruff 2010 IV; Wang 2021 IV) show biphasic plasma concentration-time curves with rapid distribution and terminal exposure measured over hours, with no dose-dependent accumulation across the studied range ^[13][14].

No peer-reviewed pharmacokinetic study of the synthetic seven-residue TB-500 heptapeptide exists in humans. The closest published fragment-specific PK is the Esposito 2012 equine doping-control work, which validated an LC-MS detection method for TB-500 in horse plasma and urine after intravenous administration ^[22]. Rodent estimates for the heptapeptide — typically quoted as a 1.5- to 3-hour plasma half-life after SC or IM injection — come from vendor and aggregated commercial sources rather than primary literature and should be read as low-confidence ^[22].

The N-terminal acetylation of TB-500 blocks aminopeptidase cleavage and improves solution stability versus the unmodified LKKTETQ sequence ^[22]. This is a chemistry observation, not a clinical PK measurement.

What vendor literature reports — and why it isn't here

Vendor pages and underground-use writing routinely quote TB-500 dosing as 2 to 10 mg per week subcutaneously, sometimes as a loading-and-maintenance schedule ^[22]. These figures are not derived from any published clinical trial. They have no peer-reviewed safety basis. They cannot be a prescribing protocol because the substance cannot be prescribed in the United States ^[26].

This page documents their existence as a feature of the marketplace and declines to reproduce them as if they were research-grounded. The published research used the doses listed above, in the species listed above, with the routes listed above. That is the record.