Doses appear in the literature attached to species and routes. Reading them outside that context is the source of most of the confusion.

A note on dosing context

The doses on this page belong to published studies, not to a recommendation. The published Tβ4 literature spans four orders of magnitude — from 0.05 µg/kg intravenously in healthy Chinese volunteers to 1,260 mg intravenously in healthy American volunteers, with rodent intraperitoneal doses clustering near 6 mg/kg. Every number here is attached to a species, a route, a model, and an outcome. None is a human recommendation, and none involves the synthetic 7-amino-acid TB-500 fragment in a controlled human trial — because no such trial exists in the published record. The subcutaneous loading protocols that circulate in research-chemical communities do not appear in any peer-reviewed paper; where those numbers came from is unclear, and they are not on this page.

What 'dosing' means in this literature

Every dose summarized below is a research-context dose attached to a species, a route, a model, and an outcome. None is a human recommendation. Most are for full-length 43-amino-acid recombinant Thymosin Beta-4, not for the synthetic 7-amino-acid TB-500 fragment. Where the two diverge, the page says so.

A second framing point: doses in the published Tβ4 literature span four orders of magnitude — from 0.05 μg/kg IV in healthy Chinese volunteers ^[12] to 1,260 mg IV in healthy American volunteers ^[11], with rodent IP doses clustering near 6 mg/kg. The 'right' dose in this body of research is the one published for the matching model, route, and endpoint, not a number transposed across species and routes.

Rodent intraperitoneal — the dominant route in CNS, peripheral, and cardiac progenitor work

Most of the rodent regenerative literature uses IP administration of recombinant full-length Tβ4.

• Rat TBI (Xiong 2011): 6 mg/kg IP at day 1, then every 3 days for 4 additional doses (5 total). Reduced CA3 neuronal loss; sustained sensorimotor and spatial-learning recovery through day 90 ^[1].
• Mouse demyelination (Zhang 2016): daily IP for 30 days (EAE) or 4 weeks (cuprizone). OPC proliferation and OL maturation ^[2].
• Mouse db/db diabetic peripheral neuropathy (Wang 2012): 6 mg/kg and 24 mg/kg IP. Restored vascular density, IENF density and myelin thickness ^[3].
• Rat compression SCI (Cheng 2014): IP at 30 min / 3 d / 5 d post-injury. +57.8% MBP; preserved oligodendrocytes; smaller lesion cavity ^[4].
• Adult mouse cardiac epicardial mobilization (Smart 2007): 150 μg IP every 3 days. Re-expression of the WT1/Tbx18 progenitor program and new coronary vessels ^[16].

The IP doses cluster around 6 mg/kg in mid-size rodents and 150 μg total in mice studied for cardiac progenitor mobilization, which is approximately 5–7 mg/kg of body weight in a 25-g animal. Dosing frequency in most CNS studies is every three days, not daily.

Intravenous — rodent, porcine, and human

Intravenous dosing of full-length Tβ4 has been studied at single-dose, multiple-dose, and large-mammal scales.

• Rat embolic stroke (Morris 2010): 3.75 mg/kg IV single dose at 24 hours post-occlusion. Durable adhesive-removal and modified Neurological Severity Score improvements days 14 through 56; no infarct-volume change ^[5].
• Mouse APP/PS1 LPS challenge (Othman 2023): 5 mg/kg IV, repeated dosing across 7 days. Prevented LPS-induced amyloid plaque accumulation ^[6].
• Pig cardiac IR (Wei 2016): 150 μg/kg IV bolus plus maintenance, before or after ischemia. NO reduction in global infarct size by TTC or MRI ^[23]. The negative result is the headline of the porcine cardiac translation literature.
• Human Phase I, US (Ruff 2010): n = 40 healthy adult volunteers, single IV doses of 42, 140, 420, and 1,260 mg, with a multiple-dose extension. No dose-limiting toxicities and no serious adverse events at doses up to 1,260 mg ^[11].
• Human Phase I, China (Wang 2021): n = 84 healthy adult Chinese volunteers, single IV doses 0.05, 0.25, 0.5, 2.0, 5.0, 12.5, and 25.0 μg/kg; multiple-dose extension 0.5–5.0 μg/kg/day x 10 days. Dose-linear PK; no SAEs; favorable immunogenicity ^[12].
• Human Phase II RGN-352 (NCT01311518): designed for ~75 post-MI patients at 450 mg or 1,200 mg IV daily x 3 then weekly x 4. Listed as Withdrawn September 2021.

The two Phase I cohorts span a 25,000-fold range in tested dose. Both came out clean on the endpoints they measured.

Topical ocular and aerosol — the routes with human Phase III data

Topical ocular Tβ4 has produced the most clinically advanced human data in the program.

• Mouse alkali corneal burn (Sosne 2002): 5 μg in 5 μL PBS, BID topical. Accelerated re-epithelialization; reduced corneal IL-1β, KC, MIP-2 mRNA ^[14].
• Human Phase III neurotrophic keratopathy (NCT02600429): 0.1% RGN-259 ophthalmic solution, 6 times per day for 28 days. 60% vs 12.5% complete healing at day 29 (p = 0.066); statistically significant healing at day 43 (p = 0.036); durable benefit two weeks after washout ^[13].
• Human Phase III ARISE-3 dry-eye disease: same 0.1% formulation. Missed prespecified co-primary endpoints with positive secondary signals.

Nebulized aerosol Tβ4 is the newer route, studied in pulmonary fibrosis.

• Mouse bleomycin pulmonary fibrosis (Yu 2024): rhTβ4 nebulized at 20, 100, or 500 μg per dose across days 0–6 / 7–13 / 14–20. 100 μg optimal. Reduced hydroxyproline content and Ashcroft score; suppressed lung-fibroblast activation ^[9].

Topical dermal and transdermal microneedle delivery have produced the 2024–2025 frontier work, with Tβ4 delivered via dissolvable microneedles at 248 μg per patch in mice ^[18] and via stem-cell-exosome-loaded HAMA/PLMA hydrogels in diabetic mouse wounds ^[19].

Pharmacokinetics and stability — what is and is not known

Published peer-reviewed pharmacokinetic data exist only for full-length recombinant Tβ4. The Ruff 2010 and Wang 2021 Phase I cohorts both reported biphasic IV plasma decline with rapid distribution and terminal exposure over hours, with dose-proportional AUC and Cmax and no accumulation across the multiple-dose extensions ^[11][12].

For the synthetic 7-amino-acid TB-500 fragment, no peer-reviewed human pharmacokinetic study has been published. The widely cited '2–3 hour half-life' for TB-500 traces to vendor materials and should be treated as low-confidence. The only peer-reviewed in-vivo PK-adjacent data on the synthetic fragment are the equine LC-MS doping-control work by Esposito and colleagues, which validated detection of intact TB-500 and several of its metabolites in horse plasma and urine after single IV dosing but did not generate a formal multi-compartmental PK profile ^[22].

Stability is somewhat better characterized. Both native Tβ4 and the synthetic TB-500 heptapeptide are inactivated by gastric proteases — oral administration is not pharmacologically meaningful, and every published preclinical or clinical study uses parenteral or topical routes. The N-terminal acetyl cap on TB-500 blocks aminopeptidase cleavage and improves solution stability versus the bare LKKTETQ sequence. Full-length Tβ4 is highly water-soluble and stable in plasma due to its largely unstructured, hydrophilic sequence. In septic-shock patients, endogenous plasma Tβ4 is consumed to undetectable levels — an in-vivo clearance signal that may eventually anchor a clinical trial of exogenous supplementation ^[10].

What the research dosing does not say

The published dosing record is silent on several things that research-chemical literature routinely fills in.

First, no peer-reviewed study supports the 2–10 mg/week subcutaneous 'loading' protocols circulated in vendor materials. Those numbers do not appear in any published preclinical or clinical paper. Where they came from is unclear. They are not in this record.

Second, no published study converts a rodent IP dose into a human equivalent dose for the synthetic 7-AA TB-500 fragment. The two species differ in metabolic rate, route, distribution volume, and (critically) in whether the synthetic fragment is even cleaved into AcSDKP — which carries a meaningful portion of the antifibrotic activity attributed to full-length Tβ4 ^[20]. Any number obtained by allometric scaling from a rodent IP dose is an extrapolation, not data.

Third, the synthetic 7-AA fragment has never been administered to a human in a registered clinical trial. The entire human exposure record published in peer-reviewed literature is for the 43-AA recombinant parent. Whether the safety envelope of the parent translates to the fragment is, like several other Tβ4-to-TB-500 questions, mechanistically plausible and empirically open.

Doses cited above are tied to specific published animal models, large-mammal models, or human trials, and do not constitute a recommendation for any human use.