# US 8,771,684 B2 · Method of using salmon thrombin to alleviate pain > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 8,771,684 B2 - Document ID: US8771684B2 - Status: Granted - Kind: B2 - Application number: 13/208,479 - Filed: 2011-08-12 - Published: 2012-01-12 - Granted: 2014-07-08 - Earliest claimed: 2009-10-20 - Assignees: Sea Run Holdings, Inc. - Applicants: Evelyn S. Sawyer; Paul A. Janmey; Beth A. Winkelstein - Inventors: Evelyn S. Sawyer; Paul A. Janmey; Beth A. Winkelstein - Web page: https://patentgrep.com/patent/US8771684B2 ## CPC - A61K 38/4833: {Thrombin (3.4.21.5)} - A61P 25/02: for peripheral neuropathies - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract A method of alleviating pain associated with tissue damage includes applying salmon thrombin at a tissue damage site, as a single substance in liquid form, or as a powder, a foam, and/or a gel that includes salmon thrombin. A pain relief substance includes a salmon thrombin preparation. ## Claims ### Claim 1 A method of alleviating nociceptive pain associated with tissue damage, consisting essentially of administering salmon thrombin at a tissue damage site to slow the rate of protease activated receptor 1 (PAR1) activation at the tissue damage site, as demonstrated by the relative rate at which salmon and human thrombin cleave tetrapeptides based on the activation sites of PAR1, thereby diminishing a degree of pain experienced at the site. ### Claim 2 (depends on 1) The method of claim 1, wherein administering salmon thrombin includes administering the salmon thrombin substantially alone in liquid form. ### Claim 3 (depends on 1) The method of claim 1, wherein administering salmon thrombin includes administering at least one of a powder, a foam, and a gel substantially composed of the salmon thrombin. ### Claim 4 (depends on 1) The method of claim 1, wherein administering salmon thrombin includes administering at least one of gauze, foam, and platelet-rich plasma combined with the salmon thrombin. ### Claim 5 (depends on 1) The method of claim 1, wherein administering salmon thrombin includes administering a substance that includes salmon thrombin, wherein the substance also includes fibrinogen. ### Claim 6 (depends on 5) The method of claim 5, wherein the fibrinogen is salmon fibrinogen. ### Claim 7 (depends on 5) The method of claim 5, wherein the substance also includes any one or more of polyethylene glycol, a synthetic molecule preparation, collagen, and alginates. ### Claim 8 (depends on 5) The method of claim 5, wherein administering the substance includes spraying the substance. ### Claim 9 (depends on 1) The method of claim 1, further comprising: obtaining a salmonid that is a progeny of domesticated broodstock that are reared under consistent and reproducible conditions; obtaining blood from the salmonid; separating plasma from the blood; and extracting the salmon thrombin from the plasma. ### Claim 10 (depends on 9) The method of claim 9, wherein the salmonid from which the blood is obtained is at least one of sexually immature, in the log-phase of growth, larger than two kilograms, and reared by standard husbandry methods. ### Claim 11 (depends on 9) The method of claim 9, wherein obtaining blood from the salmonid includes: rendering the salmonid to a level of loss of reflex activity; and drawing blood from a caudal blood vessel. ### Claim 12 (depends on 11) The method of claim 11, wherein obtaining blood from the salmonid includes, prior to rendering the salmonid to a level of loss of reflex activity, reducing the levels of proteolytic enzymes and non-protein nitrogen present in the blood of the salmonid. ### Claim 13 (depends on 9) The method of claim 9, wherein separating plasma from the blood includes centrifuging the blood. ### Claim 14 (depends on 9) The method of claim 9, wherein extracting the salmon thrombin from the plasma includes performing an extraction process on the plasma such that: all process temperatures are no greater than 6° C.; no cytotoxic chemical residues remain in the one or more plasma components; and no oxidation of plasma lipids occurs. ### Claim 15 (depends on 9) The method of claim 9, further comprising adding at least one of an antioxidant and a protease inhibitor to the plasma prior to extracting the salmon thrombin. ### Claim 16 (depends on 9) The method of claim 9, wherein the salmonid is an Atlantic salmon. ### Claim 17 (depends on 1) The method of claim 1, further comprising obtaining the salmon thrombin using recombinant technology. ### Claim 18 (depends on 1) The method of claim 1, further comprising obtaining the salmon thrombin by fractionation. ### Claim 19 (depends on 1) The method of claim 1, further comprising purifying the salmon thrombin from at least one of fresh salmon blood plasma and frozen salmon blood plasma by at least one of prothrombin precipitations and chromatographic techniques. ### Claim 20 (depends on 1) The method of claim 1, wherein the tissue damage site includes damaged soft tissue. ### Claim 21 (depends on 1) The method of claim 1, wherein administering salmon thrombin includes administering the salmon thrombin on a substrate that is not fibrinogen-based. ### Claim 22 (depends on 1) The method of claim 1, further comprising monitoring the degree of pain experienced at the site using a well-accepted and validated test for pain, after administering the salmon thrombin. ### Claim 23 (depends on 22) The method of claim 22, further comparing the degree of pain experienced at the site after administering the salmon thrombin to the degree of pain experienced at the site before administering the salmon thrombin. ### Claim 24 (depends on 22) The method of claim 22, further comprising administering salmon thrombin at the tissue damage site again if it is determined that the degree of pain experienced at the site exceeds a predetermined level as measured by a well-accepted and validated test for pain. ### Claim 25 (depends on 1) The method of claim 1, further comprising using the salmon thrombin to provide a biochemical reduction of pain experienced at the site. ### Claim 26 (depends on 1) The method of claim 1, wherein administering the salmon thrombin includes spraying the salmon thrombin. ### Claim 27 A method of alleviating nociceptive pain associated with tissue damage, consisting of administering salmon thrombin at a tissue damage site, thereby diminishing a degree of pain experienced at the site, wherein diminishing a degree of pain experienced at the site includes providing analgesic relief unrelated to wound healing. ### Claim 28 (depends on 27) The method of claim 27, further comprising obtaining the salmon thrombin by one of: obtaining a salmonid that is a progeny of domesticated broodstock that are reared under consistent and reproducible conditions, obtaining blood from the salmonid, separating plasma from the blood, and extracting the salmon thrombin from the plasma; recombinant technology; and fractionation. ### Claim 29 A method of alleviating nociceptive pain associated with tissue damage, consisting of administering salmon thrombin at a tissue damage site, thereby diminishing a degree of pain experienced at the site, wherein diminishing a degree of pain experienced at the site includes providing analgesic relief unrelated to structural repair at the tissue damage site. ### Claim 30 (depends on 29) The method of claim 29, further comprising obtaining the salmon thrombin by one of: obtaining a salmonid that is a progeny of domesticated broodstock that are reared under consistent and reproducible conditions, obtaining blood from the salmonid, separating plasma from the blood, and extracting the salmon thrombin from the plasma; recombinant technology; and fractionation. ### Claim 31 A method of alleviating nociceptive pain associated with tissue damage, comprising: blotting the tissue damage site, and administering salmon thrombin directly to the tissue damage site to slow the rate of protease activated receptor 1 (PAR1) activation at the tissue damage site, as demonstrated by the relative rate at which salmon and human thrombin cleave tetrapeptides based on the activation sites of PAR1. ### Claim 32 (depends on 31) The method of claim 31, wherein blotting the tissue damage site includes blotting with a gauze pad. ### Claim 33 (depends on 31) The method of claim 31, wherein administering salmon thrombin includes administering more than 10 Units/ml salmon thrombin. ### Claim 34 (depends on 31) The method of claim 31, further comprising closing the tissue damage site. ### Claim 35 (depends on 34) The method of claim 34, wherein closing the tissue damage site includes suturing the site. ### Claim 36 (depends on 31) The method of claim 31, further comprising monitoring the degree of pain experienced at the site using a well-accepted and validated test for pain, after administering the salmon thrombin. ### Claim 37 (depends on 36) The method of claim 36, further comparing the degree of pain experienced at the site after administering the salmon thrombin to the degree of pain experienced at the site before administering the salmon thrombin. ### Claim 38 (depends on 36) The method of claim 36, further comprising administering salmon thrombin at the tissue damage site again if it is determined that the degree of pain experienced at the site exceeds a predetermined level as measured by a well-accepted and validated test for pain.