Polymeric compositions, delivery devices, and methods

Abstract

Polymeric compositions, methods, and delivery devices for inhibiting bleeding are disclosed. The method includes applying a dried material topically to a wound site, where the material may include a cross-linked biologically compatible polymer which forms a hydrogel when exposed to blood and where the material may not include an active agent such as thrombin. A spring-loaded delivery device as described herein may be used to apply the dried material.

1 . A method for inhibiting bleeding, the method comprising:
 applying a powdered or dried material topically to a wound site, the material comprising:
 a biologically compatible polymer which forms a hydrogel when exposed to blood; and 
   wherein the material does not comprise an active agent.   
     
     
         2 . The method of  claim 1 , wherein the hydrogel comprises dry, cross-linked gelatin polymer particles. 
     
     
         3 . The method of  claim 1 , wherein the biologically compatible polymer has a degradation time of at least one day. 
     
     
         4 . The method of  claim 1 , wherein the biologically compatible polymer is sized and dimensioned such that the polymer forms the hydrogel with a sub-unit size in the range from 0.01 mm to 0.5 mm. 
     
     
         5 . The method of  claim 1 , wherein the biologically compatible polymer has an equilibrium swell in the range from 30% to 1000%. 
     
     
         6 . The method of  claim 1 , wherein the biologically compatible polymer is present at from 50 percent by weight to 100 percent by weight of the material. 
     
     
         7 . The method of  claim 6 , wherein the material further comprises an additive present at from 1 percent by weight to 20 percent by weight of the material. 
     
     
         8 . The method of  claim 7 , wherein the additive is selected from the group consisting of polyvinylpyrrolidone, dextran, polyethylene glycol, sorbitol, and glycerol. 
     
     
         9 . The method of  claim 1 , wherein the biologically compatible polymer is a cross-linked protein selected from the group consisting of gelatins, collagens, albumin, hemoglobin, fibronectin, fibrinogen, fibroin, elastin, keratin, laminin, casein and fragments thereof. 
     
     
         10 . The method of  claim 1 , wherein the biologically compatible polymer is a cross-linked carbohydrate or carbohydrate derivative selected from the group consisting of glycosaminglycans, starches, celluloses, hemicelluloses, xylan, agarose, alginate, and chitosan. 
     
     
         11 . The method of  claim 1 , wherein the biologically compatible polymer is a cross-linked, non-biologic hydrogel-forming polymer or copolymer selected from the group consisting of polyacrylates, polymethacrylates, polyacrylamides, polyvinyl alcohol polymers, polylactides-glycolides, polycaprolactones, polyoxyethelenes, polyethylene glycol and copolymers thereof. 
     
     
         12 . The method of  claim 1 , wherein the material further comprises a non-cross-linked biologically compatible polymer, the polymer comprising a protein selected from the group consisting of gelatin, collagen, albumin, elastin, and keratin, preferably gelatin. 
     
     
         13 . The method of  claim 1 , wherein the material further comprises a non-cross-linked biologically compatible polymer, the polymer comprising a carbohydrate or carbohydrate derivative selected from the group consisting of glycosaminoglycans, alginate, starch, cellulose, and derivatives thereof. 
     
     
         14 . The method of  claim 1 , wherein the material is in the form of gelatin granules and swells in diameter by about 30% to about 80% upon contact with blood. 
     
     
         15 . The method of  claim 1 , wherein the active agent not present in the material is selected from the group consisting of antibiotics, anti-neoplastic agents, bacteriostatic agents, bactericidal agents, antiviral agents, anesthetics, anti-inflammatory agents, hormones, anti-angiogenic agents, antibodies, enzymes, enzyme inhibitors, and neurotransmitters. 
     
     
         16 . The method of  claim 1 , wherein the active agent is an additional hemostatic substance. 
     
     
         17 . The method of  claim 1 , wherein the active agent is a clotting factor. 
     
     
         18 . The method of  claim 1 , wherein the active agent is thrombin. 
     
     
         19 - 36 . (canceled) 
     
     
         37 . A method of enabling use of a delivery device comprising:
 enabling the coupling of a cap of a delivery device to a plunger of a syringe, including inserting a post of the cap into a proximal end of the plunger;   enabling the depressing of the cap of the delivery device, wherein, responsive to depressing the cap,
 a spring of the delivery device compresses, and 
 the plunger translates towards a distal end of the syringe; 
   enabling the releasing of the cap of the delivery device, wherein, responsive to releasing the cap,
 the spring of the delivery device expands, and 
 the plunger translates towards a proximal end of the syringe; and 
   enabling the repeating of the depressing and releasing of the cap to sequentially and intermittently expel a desired amount of a material from the distal end of the syringe with each compression stroke.   
     
     
         38 . The method of  claim 39 , wherein the material is a dry material. 
     
     
         39 . A dry powder hemostat comprising dry particles of cross-linked bovine gelatin and non-crosslinked bovine gelatin, said dry particles having a particle size of between 250 and 500 μm, with a density greater than that of other hemostatic particles, said dry powder hemostat being substantially free of added thrombin, and said dry powder hemostat, when added directly to the site of a bleeding wound absorbs blood and wound exudate fluids, remains at the bottom of the wound without floating of the particles and exhibits up to a 70% swell from a dry state, and promotes hemostasis. 
     
     
         40 . A kit comprising:
 a pre-filled syringe, including dry particles of cross-linked bovine gelatin and non-crosslinked bovine gelatin; and   a delivery device, including:
 a retainer ring, 
 a cap, and 
 a spring, disposed between the retainer ring and the cap, 
   wherein the delivery device is configured to be coupled to the pre-filled syringe, such that:
 responsive to depressing the cap,
 the spring of the delivery device compresses, 
 a plunger translates towards a distal end of the pre-filled syringe, and 
 dry particles of cross-linked bovine gelatin and non-crosslinked bovine gelatin are expelled from the distal end of the pre-filled syringe, and responsive to releasing the cap, 
 the spring of the delivery device expands, and 
 
   the plunger translates towards a proximal end of the pre-filled syringe.