Hemostatic microspheres

{
  "publication_number": "US11246938B2",
  "country": "US",
  "kind": "B2",
  "title": "Hemostatic microspheres",
  "abstract": "Provided herein are hemostatic compositions. In one embodiment, the hemostatic composition includes cross-linked polymer microspheres, such as cross-linked gelatin microspheres with pores. In another embodiment, the hemostatic composition comprises an additive such as a wetting agent, a suspending agent, or both. The hemostatic compositions may also include a hemostatic agent such as thrombin, and may include a high concentration of thrombin. The hemostatic compositions may also include plasma. Also provided herein are devices for dispersing said hemostatic compositions in a diluent, and delivering said dispersed hemostatic composition. The hemostatic compositions may also fabricated with a selected geometry as administration suggests.",
  "claims": [
    "1. A dry powder hemostatic composition comprising: a plurality of porous cross-linked gelatin microspheres; a wetting agent; and a suspending agent; wherein the porous cross-linked gelatin microspheres have a diameter from about 50 μm to about 500 μm, inclusive, when fully hydrated, and wherein the porous cross-linked gelatin microspheres contain pores having a pore diameter from about 15 μm to about 25 μm, inclusive, wherein the wetting agent is either poloxamer 188 or polysorbate 80, and wherein the suspending agent is carboxymethylcellulose.",
    "2. The hemostatic composition of claim 1, wherein the porous gelatin microspheres have a diameter from about 110 μm to about 400 μm, inclusive, when fully hydrated.",
    "3. The hemostatic composition of claim 1, further comprising thrombin.",
    "4. The hemostatic composition of claim 3, wherein the thrombin concentration is in a range of about 1,000 IU to about 2,000 IU per ml of rehydrated microsphere gel, inclusive.",
    "5. The hemostatic composition of claim 3, wherein the thrombin concentration is in a range of about 1,000 IU to about 5,000 IU per ml of rehydrated microsphere gel, inclusive.",
    "6. The hemostatic composition of claim 3, wherein the thrombin concentration is in a range of about 5,000 IU to about 50,000 IU per ml of rehydrated microsphere gel, inclusive.",
    "7. The hemostatic composition of claim 1, wherein the hemostatic composition, when fully hydrated, remains flowable for at least 90 minutes.",
    "8. A hemostatic composition delivery device comprising a syringe, wherein the syringe contains the hemostatic composition of claim 1.",
    "9. The hemostatic composition delivery device of claim 8, further comprising a second syringe and a diluent.",
    "10. The hemostatic composition delivery device of claim 9, wherein thrombin is present in the diluent.",
    "11. The hemostatic composition delivery device of claim 9, wherein the diluent is or contains plasma.",
    "12. The hemostatic composition delivery device of claim 9, wherein the second syringe and the syringe containing the hemostatic composition are interconnected.",
    "13. The hemostatic composition delivery device of claim 12, wherein the syringes are interconnected by a male/female luer lock system.",
    "14. The hemostatic composition of claim 1, wherein the wetting agent and the suspending agent are present in a ratio of microspheres:the wetting agent and suspending agent of 3:1 to 60:1 (w/w)."
  ],
  "description_excerpt": "This invention relates to hemostatic compositions, such as cross-linked polymers including porous cross-linked gelatin microspheres, that may include hemostatic agents such as thrombin and/or plasma. In certain embodiments, the hemostatic compositions may include doses of thrombin that encompass a range of thrombin concentrations in order to provide for rapid and reliable onset of hemostasis. In particular embodiments, the hemostatic compositions may comprise high doses of thrombin, e.g., 1000 IU/ml or higher, to provide for rapid and reliable onset of hemostasis.\n\nBleeding as a result of surgery or injury may be controlled by passive hemostats and/or hemostatic agents. Passive hemostats control bleeding mechanically, through pressure and absorption, and may be fragmented or otherwise mechanically disrupted powders, gauze, or sponges made from oxidized regenerated cellulose, or cross-linked gelatin. Often, a passive hemostat is combined with an active hemostat, such as thrombin. There remains a need, however, for improved hemostatic compositions, particularly those that render superior clot formation.\n\nFIGS. 1A and 1B demonstrate that a formulation comprising thrombin and polymer microspheres rehydrated into a gel improves clot strength and shortens clotting reaction time. FIG. 1A is a plot of clot strength with increasing concentrations of microsphere gel. FIG. 1B is a plot of clot time (minutes reaction time) with increasing concentrations of microsphere gel. ♦ IU thrombin/mg dry microspheres; ▪ microspheres only; error±1 IU/mL Thrombin.",
  "cpc": [
    "A61K 47/42",
    "A61K 38/4833",
    "A61K 47/10",
    "A61K 47/26",
    "A61K 47/32",
    "A61K 47/38",
    "A61K 9/0024",
    "A61K 9/06",
    "A61P 7/00",
    "A61P 7/04",
    "C12Y 304/21005",
    "Y10T 428/2982"
  ],
  "ipc": [
    "A61K 38/48",
    "A61K 47/10",
    "A61K 47/26",
    "A61K 47/32",
    "A61K 47/38",
    "A61K 47/42",
    "A61K 9/00",
    "A61K 9/06"
  ],
  "assignees": [
    "Baxter International Inc"
  ],
  "inventors": [
    "Richard I. Senderoff",
    "Jeffrey D. Meyer",
    "Emily N. Rollins",
    "Steven D. Hughes",
    "Richard M. Garcia",
    "Paul D. Bishop",
    "Gerald W. Lasser"
  ],
  "filing_date": "2019-03-04",
  "publication_date": "2022-02-15",
  "grant_date": "2022-02-15",
  "priority_date": "2008-04-03",
  "application_number": "US-201916291854-A",
  "family_id": "41135906",
  "cited_by_count": 9,
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}