Hemostatic compositions

{
  "publication_number": "US9833541B2",
  "country": "US",
  "kind": "B2",
  "title": "Hemostatic compositions",
  "abstract": "The invention discloses a hemostatic composition comprising crosslinked gelatin in particulate form suitable for use in hemostasis, wherein the composition is present in paste form containing 15.0 to 19.5% (w/w), preferably 16.0 to 19.5% (w/w), 16.5 to 19.5% (w/w), 17.0 to 18.5% (w/w) or 17.5 to 18.5% (w/w), more preferred 16.5 to 19.0% (w/w) or 16.8 to 17.8% (w/w), especially preferred 16.5 to 17.5% (w/w), and wherein the composition comprises an extrusion enhancer.",
  "claims": [
    "1. A hemostatic composition comprising crosslinked gelatin in particulate form suitable for use in hemostasis and albumin as an extrusion enhancer, wherein the composition is present in paste form containing 15.0 to 19.5% (w/w) crosslinked gelatin and 0.5 to 5.0% (w/w) extrusion enhancer, wherein the composition is present in a syringe, wherein the hemostatic composition has a mean extrusion force of 40 N or lower, wherein the hemostatic composition is free of polyethylene glycol, sorbitol, and glycerol, wherein (w/w) crosslinked gelatin is defined as the weight of dry crosslinked gelatin per weight of the hemostatic composition, and wherein (w/w) extrusion enhancer is defined as the weight of extrusion enhancer per weight of the hemostatic composition.",
    "2. The hemostatic composition according to claim 1, wherein the crosslinked gelatin is glutaraldehyde-crosslinked gelatin or genipin-crosslinked gelatin.",
    "3. The hemostatic composition according to claim 1, wherein the crosslinked gelatin is type B gelatin.",
    "4. The hemostatic composition according to claim 1, wherein the crosslinked gelatin is present as granular material.",
    "5. The hemostatic composition according to claim 1, wherein the crosslinked gelatin has a mean particle size of 100 to 1000 μm.",
    "6. The hemostatic composition according to claim 1, wherein the composition contains thrombin.",
    "7. The hemostatic composition to claim 1 for use in the treatment of an injury selected from the group consisting of a wound, a hemorrhage, a damaged tissue, a bleeding tissue, and a bone defect.",
    "8. The hemostatic composition according to claim 1, wherein the composition contains 16.0 to 19.5% (w/w) crosslinked gelatin.",
    "9. The hemostatic composition according to claim 1, wherein the composition contains 16.5 to 19.5% (w/w) crosslinked gelatin.",
    "10. The hemostatic composition according to claim 1, wherein the composition contains 16.5 to 19.0% (w/w) crosslinked gelatin.",
    "11. The hemostatic composition according to claim 1, wherein the composition contains 17.0 to 18.5% (w/w) crosslinked gelatin.",
    "12. The hemostatic composition according to claim 1, wherein the composition contains 16.5 to 17.5% (w/w) crosslinked gelatin.",
    "13. The hemostatic composition according to claim 1, wherein the composition has a mean extrusion force of 35 N or lower.",
    "14. The hemostatic composition according to claim 1, wherein the composition has a mean extrusion force of 20 N or lower.",
    "15. The hemostatic composition according to claim 1, wherein the composition is characterized by a mean extrusion force of 40 N or lower, wherein mean extrusion force corresponds to a force required to extrude the hemostatic composition from a 5 ml standard syringe having a cylindrical body with an inner diameter of 12.2 mm coupled with a luer having an inner nozzle lumen diameter of 2.54 mm, using a 100 N load cell operating at a cross-beam speed of 250 mm/min with a cross-beam displacement of 34 mm.",
    "16. The hemostatic composition according to claim 1, wherein the albumin extrusion enhancer is included in the paste at a concentration of between 1% and 5% (w/w).",
    "17. The hemostatic composition according to claim 1, wherein the albumin extrusion enhancer is included in the paste at a concentration of between 2% and 4.5% (w/w).",
    "18. The hemostatic composition according to claim 1, wherein the albumin extrusion enhancer is included in the paste at a concentration of between 1.5% and 5% (w/w).",
    "19. The hemostatic composition according to claim 1, wherein the albumin extrusion enhancer is included in the paste at a concentration of about 1.5% (w/w).",
    "20. The hemostatic composition according to claim 1, wherein the albumin extrusion enhancer is included in the paste at a concentration of between 0.8% and 3.3% (w/w).",
    "21. The hemostatic composition according to claim 1, wherein the composition has a mean extrusion force in the range of 15 to 30 N.",
    "22. A kit for making a flowable paste of crosslinked gelatin for the treatment of an injury selected from the group consisting of a wound, a hemorrhage, a damaged tissue, and a bleeding tissue, comprising: a) a dry hemostatic composition comprising crosslinked gelatin in particulate form to be reconstituted to a flowable paste containing 15.0 to 19.5% (w/w) crosslinked gelatin, wherein (w/w) crosslinked gelatin is defined as the weight of dry crosslinked gelatin per weight of the flowable paste; and b) a pharmaceutically acceptable diluent for reconstitution of the hemostatic composition, wherein either the composition or the diluent comprises albumin in an amount which leads to an albumin concentration in the reconstituted paste of between 0.5 to 5.0% (w/w), wherein (w/w) albumin is defined as the weight of albumin per weight of the hemostatic composition, wherein the reconstituted paste has a mean extrusion force of 40 N or lower, and wherein the reconstituted paste is free of polyethylene glycol, sorbitol, and glycerol.",
    "23. The kit according to claim 22, wherein the pharmaceutically acceptable diluent comprises a buffer or buffer system.",
    "24. The kit according to claim 22, wherein the pharmaceutically acceptable diluent comprises thrombin.",
    "25. The kit according to claim 22, wherein the pharmaceutically acceptable diluent contains a substance selected from the group consisting of NaCl, CaCl 2, and sodium acetate.",
    "26. A method of treating an injury selected from the group consisting of a wound, a hemorrhage, a damaged tissue, and a bleeding tissue, comprising administering a hemostatic composition according to claim 1 to the injury.",
    "27. A method for providing a ready to use form of a hemostatic composition according to claim 1, wherein the hemostatic composition is provided in a first syringe and a diluent for reconstitution is provided in a second syringe, the first and the second syringe are connected to each other, and the fluid is brought into the first syringe to produce a flowable form of the hemostatic composition.",
    "28. The method according to claim 27, wherein the flowable form of the hemostatic composition contains particles, where more than 50% (w/w) of the particles have a size of 100 to 1000 μm."
  ],
  "description_excerpt": "The present invention relates to hemostatic compositions and processes for making such compositions.\n\nHemostatic compositions in dry storage-stable form that comprise biocompatible, biodegradable, dry stable granular material are known e.g. from WO98/008550A or WO2003/007845A. These products have been successfully applied on the art for hemostasis. Floseal® is an example for a highly effective haemostatic agent consisting of a granular gelatin matrix swollen in a thrombin-containing solution to form a flowable paste.\n\nSince such products have to be applied to humans, it is necessary to provide highest safety standards for quality, storage-stability and sterility of the final products and the components thereof. In addition, manufacturing and handling should be made as convenient and efficient as possible.\n\nA successful product in this field (the Floseal® product mentioned above) utilizes a gelatin matrix used in conjugation with a reconstituted lyophilized thrombin solution. The gelatin matrix is applied as a flowable granular form of gelatin and thrombin with a gelatin content of about 11 to 14.5%. Lower gelatin content results in a runny product with diminished performance due to difficulties in having the product remain at the treatment site, especially under conditions of high blood flow. Higher gelatin particle concentration leads to a product that is difficult to deliver by usual means of administration, such as syringes or catheters, due to higher resistance to flow.",
  "cpc": [
    "A61L 26/0052",
    "A61K 38/17",
    "A61K 38/38",
    "A61K 38/4833",
    "A61K 9/06",
    "A61L 24/104",
    "A61L 24/108",
    "A61L 2400/04",
    "A61L 2400/06",
    "A61M 5/19",
    "A61P 17/02",
    "A61P 41/00",
    "A61P 7/04",
    "A61P 9/14"
  ],
  "ipc": [
    "A61L 26/00",
    "A61M 5/19",
    "A61K 38/17",
    "A61K 38/38",
    "A61K 38/48",
    "A61K 9/06",
    "A61L 24/10"
  ],
  "assignees": [
    "Baxter Healthcare SA",
    "Baxter International Inc"
  ],
  "inventors": [
    "Jill McCoy",
    "Joseph F. Dwyer",
    "Ziping Yang"
  ],
  "filing_date": "2016-06-01",
  "publication_date": "2017-12-05",
  "grant_date": "2017-12-05",
  "priority_date": "2011-10-27",
  "application_number": "US-201615169872-A",
  "family_id": "47080512",
  "cited_by_count": 16,
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