Thrombin-carrying hemostatic sheet
Inventors
Ogino, Makoto • Yoshihara, Keiichi • Kimura, Yasuharu • Aoki, Megumi • YOSHII, Toshitaka • Egawa, Satoru
Assignees
Astellas Pharma Inc • Tokyo Medical and Dental University NUC
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Publication Number
US-12251491-B2
Publication Date
2025-03-18
Expiration Date
Abstract
Provided is a thrombin-carrying hemostatic sheet that is suitable for hemostasis during surgery, in particular, for hemostasis during spine surgery, that is convenient without preparation before use, and that is bioabsorbable and can be embedded in the body as it is. The hemostatic sheet is composed of a gelatin sponge carrying an effective amount of thrombin, wherein (A) the density is 30 to 55 mg/cm3, and (B) the shape maintaining angle in wet conditions is 55 to 120°.
Core Innovation
A hemostatic sheet is provided that comprises a gelatin sponge carrying thrombin or human recombinant thrombin. The sheet is characterized by a density of 30 to 55 mg/cm3 and a thickness in a range of 1.0 to 3.5 mm, with the thrombin loading expressed on an area basis.
The invention addresses problems associated with prior gelatin sponges coated or dipped with thrombin, including thickness, difficulty in handling in limited space, and loss of water absorption and shape when thrombin contacts the sponge in wet conditions. It also addresses problems associated with cross-linking approaches, including cracking and concerns about shape integrity and biological absorption or expansion behavior.
The hemostatic sheet is evaluated to maintain a wet-condition shape, represented by a shape maintaining angle as a spread angle between both ends of the sheet centered on a cylindrical metal rod, after physiological saline dip and stand conditions, wherein the spread angle is 55 to 120 degrees. For spine surgery use, a hemostatic sheet configuration is described that provides hemostasis and meets quantitative physical and biological performance criteria including water absorption properties and biological absorption or disappearance properties.
Claims Coverage
The document provides four independent composition/apparatus claims and one independent method claim. Across these independent claims, the inventive features emphasize specified thrombin loading on a gelatin sponge, controlled sheet density and thickness, quantitative water absorption, wet shape-maintaining behavior expressed as a spread angle, and production by thermally cross-linked sponge formation followed by thrombin infiltration, drying, and slicing to a target thickness.
Thrombin-carrying gelatin sponge sheet with controlled density and thickness plus wet shape maintenance
A hemostatic sheet comprising a gelatin sponge carrying 10 to 200 IU/cm2 of thrombin, wherein the hemostatic sheet has a density of 30 to 55 mg/cm3 and a thickness in a range of 1.0 to 3.5 mm, and wherein after a physiological saline dip and rod-based standing conditions the shape maintaining angle in a wet condition, represented by a spread angle between both ends of the sheet centered on the metal rod, is 55 to 120 degrees.
Spine-surgery hemostatic sheet with human recombinant thrombin and quantitative water absorption and wet shape maintenance
A hemostatic sheet comprising a gelatin sponge carrying 10 to 200 IU/cm2 of human recombinant thrombin, configured for hemostasis during spine surgery, wherein the hemostatic sheet has a thickness in a range of 1.0 to 3.5 mm, a density of 30 to 55 mg/cm3, water absorption properties of absorbing 0.1 mL of a phosphate buffer solution dropped on the sheet cut to have a length and a breadth of 10.0±1.0 mm within 10 seconds, and wherein after physiological saline dipping and rod-based standing conditions the shape maintaining angle in a wet condition is 55 to 120 degrees.
Human recombinant thrombin spine-surgery hemostatic sheet with specified thrombin loading range
A hemostatic sheet comprising a gelatin sponge carrying human recombinant thrombin in the claimed loading range, configured for hemostasis during spine surgery, with the same specified thickness, density, water absorption properties, and wet shape-maintaining angle.
Spine-surgery hemostatic sheet substantially free of cross-linking agent
A hemostatic sheet comprising a gelatin sponge carrying human recombinant thrombin and substantially containing no cross-linking agent, configured for hemostasis during spine surgery, with the same specified thickness, density, water absorption properties, and wet shape-maintaining angle.
Production method using thermally cross-linked gelatin sponge, thrombin infiltration, drying, and slicing to thickness
A method for producing a hemostatic sheet including a gelatin sponge carrying an effective amount of thrombin, comprising producing a thermally cross-linked gelatin sponge, infiltrating the thermally cross-linked gelatin sponge in a thrombin solution and then drying the gelatin sponge, and slicing the dried gelatin sponge or the cross-linked gelatin sponge carrying thrombin to have a thickness of 1.0 to 3.5 mm.
Across the independent claims, the coverage is anchored by a thrombin-carrying gelatin sponge hemostatic sheet with specified density and thickness, quantitative wet shape maintenance expressed as a spread angle in the range of 55 to 120 degrees, and, for spine-surgery configurations, specified water absorption behavior and the use of human recombinant thrombin. The independent method claim further defines production by thermally cross-linked gelatin sponge formation, thrombin solution infiltration, drying, and slicing to a 1.0 to 3.5 mm thickness range.
Stated Advantages
Resistance to cracking when bent in a dry state.
Low expansion.
Comparatively prompt biological absorption.
Documented Applications
Hemostasis during spine surgery, including spine hemorrhage models and spine-related eruptive hemorrhage.
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