# US 2013/0157339 A1 · Stabilized protease composition > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2013/0157339 A1 - Document ID: US20130157339A1 - Status: Published application - Kind: A1 - Application number: 13/760,148 - Filed: 2013-02-06 - Published: 2013-06-20 - Earliest claimed: 2008-03-14 - Assignees: Trobio AB - Inventors: Lars-Olov ANDERSSON; Hans AGELAND - Web page: https://patentgrep.com/patent/US20130157339A1 ## CPC - C12N 9/96: Stabilising an enzyme by forming an adduct or a composition; Forming enzyme conjugates - A61K 31/13: Amines {(A61K31/04 takes precedence)} - A61K 31/5377: not condensed and containing further heterocyclic rings, e.g. timolol - A61K 38/4833: {Thrombin (3.4.21.5)} - A61K 38/484: {Plasmin (3.4.21.7)} - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61K 47/18: Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids - A61K 47/22: Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones - A61L 15/32: Proteins, polypeptides; Degradation products or derivatives thereof, e.g. albumin, collagen, fibrin, gelatin {(A61L15/225 takes precedence)} - A61L 31/047: {Other specific proteins or polypeptides not covered by A61L31/044 - A61L31/046} - A61P 7/00: Drugs for disorders of the blood or the extracellular fluid - C07D 295/088: to an acyclic saturated chain - C07D 295/13: to an acyclic saturated chain - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - 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) - A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) ## Abstract A composition is provided, which comprises a serine protease; a reversible inhibitor of said serine protease; and a stabilizing agent M having the formula I: Also provided are uses of the composition as a medicament, and other uses and methods employing its various properties. ## Claims ### Claim 1 A stabilized serine protease composition comprising an aqueous solution of a) thrombin; b) a reversible inhibitor of thrombin which exhibits a Ki value of between 0.01 and 2 mM; and c) a stabilizing agent M, wherein M is 3-(N-morpholino)propane sulfonic acid and M is present in a concentration in the range of 0.1-0.3M. ### Claim 2 (depends on 1) The composition according to claim 1, in which said thrombin is human thrombin. ### Claim 3 (depends on 1) The composition according to claim 1, which further comprises a viscous and adhesive polysaccharide. ### Claim 4 (depends on 3) The composition according to claim 3, in which the polysaccharide is selected from starch, its derivatives, cellulose, its derivatives, and mixtures thereof. ### Claim 5 (depends on 4) The composition according to claim 4, in which the polysaccharide is selected from carboxymethyl cellulose, ethyl hydroxyethyl cellulose and mixtures thereof. ### Claim 6 (depends on 3) The composition according to claim 3, in which the polysaccharide is carboxymethyl chitosan. ### Claim 7 (depends on 3) The composition according to claim 3, in which said polysaccharide is present in a concentration of 0.1-5%. ### Claim 8 (depends on 1) The composition according to claim 1, in which thrombin is present in a concentration of 0.001-2 mg/ml. ### Claim 9 (depends on 1) The composition according to claim 1, in which the concentration of thrombin is 5-3500 activity units/ml. ### Claim 10 (depends on 9) The composition according to claim 9, in which the concentration of thrombin is 200-1000 activity units/ml. ### Claim 11 (depends on 9) The composition according to claim 9, in which the concentration of thrombin is 5-20 activity units/ml. ### Claim 12 (depends on 1) The composition according to claim 1, in which said reversible inhibitor of thrombin is present in a concentration of 0.1-10 mM. ### Claim 13 (depends on 1) The composition according to claim 1, in which the reversible inhibitor exhibits a K value between 0.04 mM and 0.5 mM. ### Claim 14 (depends on 1) The composition according to claim 1, in which the reversible inhibitor is selected from benzamidine, N,N-diethylethylenediamine, aminobenzamidine, amidinopyridin, tert-butylamidin, and a compound having the formula IV: wherein R1 is selected from H, C3-C7-cyclo alkyl, phenyl, benzyl acetyl and benzoyl; X is selected from oxygen, nitrogen and sulfur; R2 and R3 is each individually selected from H, halogen, hydroxyl, C1-C6-alkyl, C3-C7-cyclo alkyl, C1-C6-alkyloxy; and R4 is selected from H, arylalkyl and acyl. ### Claim 15 (depends on 14) The composition according to claim 14, in which the reversible inhibitor is selected from N,N-diethylethylenediamine, amidinopyridin, tert-butylamidin, and a compound having the formula IV: wherein R1 is selected from H, C1-C6-alkyl, C3-C7-cyclo alkyl, phenyl, benzyl acetyl and benzoyl; X is selected from oxygen, nitrogen and sulfur; R2 and R3 is each individually selected from H, halogen, hydroxyl, C1-C6-alkyl, C3-C7-cyclo alkyl, C1-C6-alkyloxy; and R4 is selected from H, C1-C6-alkyl, arylalkyl and acyl. ### Claim 16 (depends on 14) The composition according to claim 14, in which the reversible inhibitor is a compound having the formula IV: wherein R1 is selected from H, C1-C6-alkyl, C3-C7-cyclo alkyl, phenyl, benzyl acetyl and benzoyl; X is selected from oxygen, nitrogen and sulfur; R2 and R3 is each individually selected from H, halogen, hydroxyl, C1-C6-alkyl, C3-C7-cyclo alkyl, C1-C6-alkyloxy; and R4 is selected from H, C1-C6-alkyl, arylalkyl and acyl. ### Claim 17 (depends on 7) A composition according to claim 7, in which said polysaccharide is present in a concentration of 1.0-2.0%. ### Claim 18 A stabilized serine protease composition comprising an aqueous solution of a) thrombin, wherein said thrombin is present in a concentration of 0.001-2 mg/ml; b) a reversible inhibitor of thrombin, wherein said reversible inhibitor of thrombin is present in a concentration of 0.1-10 mM; and c) a stabilizing agent M, wherein M is 3-(N-morpholino)propanesulfonic acid and M is present in a concentration in the range of 0.1-0.3M.