Conformable structured therapeutic dressing
A conformable structured therapeutic dressing ( 120 ) has maximum available surface area ( 102 ) of a therapeutic agent ( 122 ) to stimulate therapeutic response in wounded tissue of a mammalian subject. In preferred embodiments, the therapeutic agent includes a procoagulant to quickly arrest bleeding and prevent life-threatening blood loss. The wound dressing exhibits a structured adsorbent ( 104 ) that maximizes available surface area of a functional filler ( 72 ). This is achieved with a minimal amount of binder ( 82 ) and small, porous particles of the functional filler. Minimizing the binder maximizes the amount of functional filler and reduces the chance that the binder will block access to the surface area of the functional filler. Porous particles have a large internal surface area. Structured adsorbents with higher surface areas, higher inter- and intra-fiber porosities, and low internal mass transfer resistances produce higher rates of mass transfer of an adsorbent onto the functional filler.
1. A composite nonwoven article of filled polymeric macrofibers for use as a therapeutic dressing in the treatment of a wound site of a mammalian subject, comprising:
multiple networks of microfibers, each of the multiple networks of microfibers including multiple submicron-diameter polymeric microfibers having diameters of between about 50 nm and about 500 nm and containing and binding therapeutic agent particles in a configuration that presents a large available surface area of therapeutic agent with insubstantial blockage by the microfibers, the networks of microfibers exhibiting intra-fiber porosity produced by free spaces around the therapeutic agent particles and the microfibers; and
multiple micron-diameter porous polymeric macrofibers, each of the multiple polymeric macrofibers having a diameter of greater than 10 μm and less than about 500 μm presenting a structured architecture formed of one of the multiple networks of microfibers containing and binding therapeutic agent particles, the macrofibers randomly oriented to form a composite nonwoven article exhibiting inter-fiber porosity around the macrofibers, the randomly oriented macrofibers of the composite nonwoven article exhibiting intra- and inter-fiber porosity at submicron and micron scales with appreciable free space around the therapeutic agent particles contained and bound by the network of microfibers so that blood from the wound site penetrates the composite nonwoven article of filled polymeric macrofibers to come in contact with a substantial amount of the therapeutic agent and thereby stimulate a therapeutic response in the mammalian subject.
2. The article of claim 1 , in which the therapeutic agent particles include a procoagulant and the stimulation of a therapeutic response includes promotion of blood clot formation.
3. The article of claim 1 , in which the therapeutic agent particles include a filler material that contributes to the structured architecture presented by the multiple polymeric macrofibers.
4. The article of claim 3 , in which the filler material includes silica and the therapeutic agent particles include chitosan.
5. The article of claim 4 , in which the chitosan is suffused or coated on the silica.
6. The article of claim 4 , in which the chitosan is in a condensed form on the silica.
7. The article of claim 1 , in which the therapeutic agent particles include one or both of a procoagulant that functions as an intrinsic cascade initiator and a procoagulant that contributes to coagulation at least in part by a mechanism other than intrinsic cascade initiation.
8. The article of claim 7 , in which the therapeutic agent particles are selected from the group consisting of silica, chitosan, zeolite, absorbent polymers, polysaccharides, chitin, derivatives of chitosan and chitin, starch, kaolin, celite, alum, thrombin, fibrinogen, fibrin, alginate, recombinant factor VIIa, collagen, diatomaceous earth, carbon, von Willebrand factor, fibronectin, vitronectin, thromboxane A2, thrombopoietin, intracellular adhesion molecule (ICAM)-1 and -2, vascular cell adhesion molecule (VCAM), aggretin, adenosine-di-phosphate (ADP), Ristocetin, and mixtures of them.
9. The article of claim 7 , in which the procoagulant functioning as an intrinsic cascade initiator includes silica.
10. The article of claim 7 , in which the procoagulant contributing at least in part to a mechanism other than intrinsic cascade initiation entails one or both of red blood cell agglutination and platelet stimulation.
11. The article of claim 7 , in which the procoagulant contributing at least in part to a mechanism other than intrinsic cascade initiation includes chitosan or chitosan derivative.
12. The article of claim 7 , in which the procoagulant contributing at least in part to a mechanism other than intrinsic cascade initiation is coated or suffused on the multiple polymeric macrofibers.
13. The article of claim 12 , in which the procoagulant coated or suffused on the multiple polymeric macrofibers further comprises a blood clotting adjuvant that includes alcohol, a calcium compound, or a mixture of them.
14. The article of claim 13 , in which the alcohol is selected from a group consisting of isopropyl alcohol and ethanol and the calcium compound is selected from a group consisting of calcium chloride (CaCl 2 ), calcium oxide (CaO), and calcium carbonate (CaCO 3 ).
15. The article of claim 12 , in which the procoagulant coated or suffused on the multiple polymeric macrofibers includes chitosan or chitosan derivative.
16. The article of claim 1 , in which the multiple polymeric macrofibers have a surface area exceeding a value of about 10 m 2 /g as measured by the BET nitrogen absorption technique.
17. The article of claim 1 , in which the multiple polymeric macrofibers have a moisture content of less than about 15% by weight.
18. The article of claim 1 , in which the multiple polymeric macrofibers are in segmented form of short fibers, granules, or particles and are admixed with a procoagulant or a sorbent polymer.
19. The article of claim 1 , in which the multiple polymeric macrofibers further comprise a blood clotting adjuvant that includes calcium chloride (CaCl 2 ), calcium oxide (CaO), calcium carbonate (CaCO 3 ), isopropyl alcohol, ethanol, or a mixture of them.
20. The article of claim 1 , in which the multiple polymeric macrofibers include an ultrahigh molecular weight polyolefin.
21. The article of claim 20 , in which the ultrahigh molecular weight polyolefin is ultrahigh molecular weight polyethylene.
22. The article of claim 1 , in which the therapeutic agent particles comprise no less than about 5% by weight.
23. The article of claim 1 , in which the multiple polymeric macrofibers are selected from the group consisting of polyolefins, condensation polymers, vinyl polymers, and natural polymers.
24. The article of claim 1 , in which the multiple polymeric macrofibers comprise polyolefin components that include one or more of polypropylene, polyolefin co-polymers, ethylene propylene co-polymers, metallocene polymers, and metallocene polypropylene.
25. The article of claim 1 , in which the multiple polymeric macrofibers comprise condensation polymers that include one or more of polyester, polyethylene terephthalate, polyamide, and polyimide.
26. The article of claim 1 , in which the multiple polymeric macrofibers comprise vinyl polymers that include one or more of polyvinyl chloride, polystyrene, and co-polymers of polystyrene.
27. The article of claim 1 , in which the multiple polymeric macrofibers comprise natural polymers that include one or more of polysaccharides, chitin, chitosan, and cellulosic polymers.