Hemostatic compositions

Patent metadata

Field	Value
Publication number	US-2016271228-A1
Application number	US-201615080026-A
Country	US
Kind code	A1
Filing date	Mar 24, 2016
Priority date	Oct 11, 2011
Publication date	Sep 22, 2016
Grant date	—

Abstract

The invention discloses a hemostatic composition comprising:
a) a biocompatible polymer in particulate form suitable for use in hemostasis, and b) one hydrophilic polymeric component comprising reactive groups.

First claim

1 . A hemostatic composition for treating a patient, the composition comprising:
a hemostatic biocompatible polymer in particulate form selected from the group consisting of a protein, a polysaccharide, a biologic polymer, a non-biologic polymer, and derivatives and combinations thereof, wherein the hemostatic biocompatible polymer in particulate form is present as granular particles having a median particle size range of 50 μm to 700 μm, and an equilibrium swell within a range from 400% to 1300%; one hydrophilic crosslinker comprising electrophilic reactive groups, wherein the electrophilic reactive groups retain their reactivity until the composition is exposed to blood of the patient, wherein the electrophilic reactive groups are configured to cross-link with blood proteins of the patient to form a gel with sealing and hemostatic properties; and a binder that does not react with the electrophilic reactive groups of the one hydrophilic crosslinker; wherein the hemostatic composition is free from a second or further hydrophilic crosslinkers comprising electrophilic reactive groups; and wherein the hemostatic composition is in paste form.

2 . The hemostatic composition according to claim 1 , wherein the one hydrophilic crosslinker is a polyalkylene oxide polymer.

3 . The hemostatic composition according to claim 1 , wherein the one hydrophilic crosslinker with electrophilic reactive groups is a polyethylene glycol (PEG).

4 . The hemostatic composition according to claim 1 , wherein the binder contains or is a substance selected from the group consisting of glycerol, a derivative of glycerol, DMSO, ethanol, a polyethyleneglycol, a Poloxamer, and combinations thereof.

5 . The hemostatic composition according to claim 1 , wherein the binder has a water content (% v/v) below 5%.

6 . A method of treating a patient with a hemostatic composition in paste form, the composition comprising a hemostatic biocompatible polymer in particulate form selected from the group consisting of a protein, a polysaccharide, a biologic polymer, a non-biologic polymer, and derivatives and combinations thereof, wherein the hemostatic biocompatible polymer in particulate form is present as granular particles having a median particle size range of 50 μm to 700 μm and an equilibrium swell within a range from 400% to 1300%; one hydrophilic crosslinker comprising electrophilic reactive groups, wherein the electrophilic reactive groups retain their reactivity until the composition is exposed to blood of the patient; and a binder that does not react with the electrophilic reactive groups of the one hydrophilic crosslinker, wherein the hemostatic composition is free from a second or further hydrophilic crosslinkers comprising electrophilic reactive groups, the method comprising:
administering to the patient the hemostatic composition for treatment of an injury selected from the group consisting of a wound, a hemorrhage, a damaged tissue, a bleeding tissue, and a bone defect, wherein the electrophilic reactive groups of the hydrophilic crosslinker cross-link with blood proteins of the patient to form a gel with sealing and hemostatic properties.

7 . A kit for treatment of an injury of a patient selected from the group consisting of a wound, a hemorrhage, a damaged tissue, and a bleeding tissue, comprising:
a hemostatic composition in paste form comprising: a hemostatic biocompatible polymer in particulate form selected from the group consisting of a protein, a polysaccharide, a biologic polymer, a non-biologic polymer, and derivatives and combinations thereof, wherein the hemostatic biocompatible polymer in particulate form is present as granular particles having a median particle size range of 50 μm to 700 μm and an equilibrium swell within a range from 400% to 1300%; one hydrophilic crosslinker comprising electrophilic reactive groups, wherein the electrophilic reactive groups retain their reactivity until the composition is exposed to blood of the patient, wherein the electrophilic reactive groups are configured to cross-link with blood proteins of the patient to form a gel with sealing and hemostatic properties; and a binder that does not react with the electrophilic reactive groups of the one hydrophilic crosslinker; wherein the hemostatic composition is free from a second or further hydrophilic crosslinkers comprising electrophilic reactive groups; and instructions for use.

8 . A method for producing a hemostatic composition in paste form for treating a patient, the composition comprising a hemostatic biocompatible polymer in particulate form selected from the group consisting of a protein, a polysaccharide, a biologic polymer, a non-biologic polymer, and derivatives and combinations thereof, wherein the hemostatic biocompatible polymer in particulate form is present as granular particles having a median particle size range of 50 μm to 700 μand an equilibrium swell within a range from 400% to 1300%; one hydrophilic crosslinker comprising electrophilic reactive groups; and a binder that does not react with the electrophilic reactive groups of the one hydrophilic crosslinker; wherein the hemostatic composition is free from a second or further hydrophilic crosslinkers comprising electrophilic reactive groups, the method comprising:
mixing the hemostatic biocompatible polymer and the one hydrophilic crosslinker comprising electrophilic reactive groups with the binder, wherein the electrophilic reactive groups of the one hydrophilic crosslinker retain their reactivity until the composition is exposed to blood of the patient, wherein the electrophilic reactive groups are configured to cross-link with blood proteins of the patient to form a gel with sealing and hemostatic properties.

9 . The hemostatic composition according to claim 2 , wherein the polyalkylene oxide polymer is pentaerythritolpoly(ethyleneglycol)ether tetrasuccinimidyl glutarate.

10 . The hemostatic composition according to claim 3 , wherein the polyethylene glycol (PEG) comprises two or more electrophilic reactive groups selected from succinimidylesters (—CON(COCH 2 ) 2 ), aldehydes (—CHO) and isocyanates (—N═C═O).

11 . The hemostatic composition according to claim 5 , wherein the water content (% v/v) is below 2%.

12 . The hemostatic composition according to claim 5 , wherein the water content (% v/v) is below 1%.

13 . The hemostatic composition according to claim 1 , wherein the hemostatic biocompatible polymer in particulate form comprises the protein.

14 . The hemostatic composition according to claim 13 , wherein the protein comprises a member selected from the group consisting of chitosan, gelatin, collagen, albumin, hemoglobin, fibrinogen, fibrin, casein, fibronectin, elastin, keratin, and laminin, and derivatives and combinations thereof.

15 . The hemostatic composition according to claim 13 , wherein the protein comprises gelatin.

16 . The hemostatic composition according to claim 13 , wherein the protein comprises non-fibrillar collagen.

17 . The hemostatic composition according to claim 1 , wherein the binder comprises a Poloxamer.

18 . The hemostatic composition according to claim 17 , wherein the Poloxamer is ethylene oxide(2)/propylene oxide(32)/ethylene oxide(2).

19 . The method according to claim 6 , wherein the binder comprises a Poloxamer.

20 . The method according to claim 19 , wherein the Poloxamer is ethylene oxide(2)/propylene oxide(32)/ethylene oxide(2).

21 . The kit according to claim 7 , wherein the binder comprises

Assignees

• Baxter Int
• Baxter Healthcare Sa

Inventors

• Gulle Heinz
• Hoefinghoff Joris
• Goessl Andreas
• Gorna Katarzyna

Classifications

• A61K38/39 Primary

  Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG] · CPC title

• A61L26/0052

  Mixtures of macromolecular compounds · CPC title

• A61L2400/04

  Materials for stopping bleeding · CPC title

• A61K31/77

  of oxiranes · CPC title

• A61L24/0031

  Hydrogels or hydrocolloids · CPC title