Pain Relief Peptides

A pentadecapeptide derived from human gastric juice, studied for tissue repair and gut-protective properties.

A neuropeptide studied for its role in sleep regulation and stress modulation.

A semi-synthetic polysaccharide FDA-approved for interstitial cystitis and studied for joint health applications.

A non-erythropoietic EPO analog studied for nerve repair and neuropathic pain conditions.

Difelikefalin (Korsuva in the U.S., Kapruvia in Europe) is a synthetic tetrapeptide built entirely from D-amino acids - D-Phe-D-Phe-D-Leu-D-Lys capped with a 4-aminopiperidine-4-carboxylic acid - that acts as a selective agonist at the kappa opioid receptor. Its defining property is what it cannot do: the molecule is hydrophilic and bulky enough that it does not meaningfully cross the blood-brain barrier, so it reaches kappa receptors on peripheral sensory nerve endings, keratinocytes and immune cells while leaving the central kappa receptors that produce dysphoria and hallucinations largely untouched. It has no activity at the mu opioid receptor, so it carries neither euphoria nor respiratory depression. In the Phase 3 KALM-1 and KALM-2 trials in hemodialysis patients with moderate-to-severe chronic-kidney-disease-associated pruritus, roughly 40-51% of difelikefalin-treated patients achieved a clinically meaningful (>=3-point) reduction on the 10-point Worst Itching Intensity NRS at 12 weeks versus roughly 20-28% on placebo. The FDA approved intravenous difelikefalin in August 2021; the EU approved it as Kapruvia in April 2022.