Methods of treating burns with i.v. cP12 in a window from 2 to 6 hours after injury
Inventors
Clark, Richard August • Lin, Fubao
Assignees
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Publication Number
US-10729741-B2
Publication Date
2020-08-04
Expiration Date
Abstract
A treatment window for the intravenous treatment of wounds, including thermal and chemical burns, with cP12 is presented. In particular, Applicants have unexpectedly found that delaying intravenous treatment with fibronectin-derived peptides, such as cP12, from 2 to 6 hours, particularly about 4 hours, after wounding, provides superior wound-closing results than treatment at 1 hour or after 8 or more hours.
Core Innovation
The invention relates to a method of treating a patient having a wound selected from surgical incision or extirpation, traumatic injury, thermal burn, chemical burn, lesion or ulceration of skin, mucosa, connective tissue, fascia, ligament, tendon, cartilage, nerve, or muscle, and a wound to bone. The method comprises intravenously administering a therapeutically effective amount of a cyclized form of a polypeptide consisting of amino acids PSHISKYILRWRPK (SEQ ID NO:2), also identified as cyclized fibronectin-derived peptide cP12.
The dosage is from 0.003 to 0.1 mg/kg, and the intravenous administration occurs from about 2 hours to about 6 hours after formation of the wound. In disclosed embodiments, the infusion is described as an intravenous infusion with timing within the stated 2–6 hour window and a duration of about 30 minutes.
The delayed intravenous treatment is reported to provide an unexpectedly improved wound-healing/closure outcome, including re-epithelialization described in a porcine vertical injury progression burn model.
Claims Coverage
The disclosed independent claim defines a method for treating a patient with specified wound types by intravenously administering a cyclized polypeptide (cP12; PSHISKYILRWRPK; SEQ ID NO:2) with dosage and delayed post-injury initiation constraints. Dependent claims further refine the wound subset and narrow initiation timing and infusion characteristics, and add cyclization mechanism options.
Delayed intravenous administration of cyclized PSHISKYILRWRPK polypeptide
A method in which a cyclized form of a polypeptide consisting of amino acids PSHISKYILRWRPK (SEQ ID NO:2) is intravenously administered to the patient, wherein the intravenous administration occurs from about 2 hours to about 6 hours after formation of the wound.
Dosage range for intravenous therapy
The cyclized PSHISKYILRWRPK polypeptide is administered at a therapeutically effective amount with a dosage from 0.003 to 0.1 mg/kg.
Wound type selection for treatment
The method applies to wounds selected from a group consisting of a surgical incision or extirpation, a traumatic injury, a thermal burn, a chemical burn, a lesion or ulceration of skin, mucosa, connective tissue, fascia, ligament, tendon, cartilage, nerve, or muscle, and a wound to bone.
Thermal or chemical burn subset
The method further restricts the wound to either a thermal burn or a chemical burn.
Initiation about 4 hours after wound formation and about half-hour infusion duration
The intravenous administration is initiated about 4 hours after formation of the wound and is administered over about a half-hour period.
Narrowed dosage range for burns
The method uses a dosage ranging from 0.03 to 0.1 mg/kg.
Cyclization of the PSHISKYILRWRPK polypeptide by crosslinking or ligation
The cyclized polypeptide is cyclized by chemical crosslinking or by intramolecular ligation, wherein the intramolecular ligation is chemical or enzymatic.
Overall, the claim coverage centers on intravenously administering a cyclized form of the PSHISKYILRWRPK polypeptide (SEQ ID NO:2) at a specified dosage and within a delayed 2–6 hour post-wound window, with dependent claims narrowing to thermal/chemical burns, further specifying initiation about 4 hours after wound formation and an about half-hour administration period, narrowing the dosage range to 0.03–0.1 mg/kg, and specifying cyclization by chemical crosslinking or intramolecular ligation (chemical or enzymatic).
Stated Advantages
Unexpectedly improved wound-healing/closure outcome when intravenous treatment is delayed within the 2–6 hour window after injury.
Re-epithelialization is reported as 100% at the 14-day assessment in the cited porcine vertical progression burn model embodiments.
Infusion-rate relevance is noted to help avoid an anaphylactoid response.
Documented Applications
Treating wounds including thermal burn and chemical burn using delayed intravenous administration of cyclized fibronectin-derived peptide cP12 (SEQ ID NO:2).
Using a porcine vertical injury progression burn model to evaluate re-epithelialization and wound closure outcomes following intravenous infusion initiated at multiple post-burn times and assessed at 14 days.
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