U.S. patent application number 13/952186 was filed with the patent office on 2013-11-21 for treatment for high pressure bleeding.
This patent application is currently assigned to Virginia Commonwealth University. The applicant listed for this patent is Virginia Commonwealth University. Invention is credited to Wayne Barbee, Gary Bowlin, Marcus E. Carr, JR., Kelman I. Cohen, Rao Ivatury, Kevin R. Ward, Gary Wnek.
Application Number | 20130310779 13/952186 |
Document ID | / |
Family ID | 30444079 |
Filed Date | 2013-11-21 |
United States Patent
Application |
20130310779 |
Kind Code |
A1 |
Wnek; Gary ; et al. |
November 21, 2013 |
TREATMENT FOR HIGH PRESSURE BLEEDING
Abstract
High-pressure bleeding wounds (and other bleeding wounds) may be
treated by applying direct pressure directly in the bleeding wound,
such as by applying a back pressure in a confined space around and
in the wound. Certain substances and articles may be inserted into
the wound, and the wound may be enclosed with that substance or
article (such as a hemostatic substance, which may be polymeric),
by swelling on contact with molecules (such as water molecules in
the blood) encountered in the wound, generates the desired pressure
to stop or at least reduce the bleeding without the detrimental
effects of a tourniquet. Clot-inducing substances may be introduced
into the wound contemporaneously with direct pressure application
directly in the wound. Compressible and non-compressible wounds are
treated. Treatment stops bleeding without producing pressure injury
or ischemic damage. Medical devices using this technology are
provided, including removable, biodegradable, medic-administrable
devices.
Inventors: |
Wnek; Gary; (Midlothian,
VA) ; Carr, JR.; Marcus E.; (Richmond, VA) ;
Bowlin; Gary; (Mechanicsville, VA) ; Cohen; Kelman
I.; (Richmond, VA) ; Ward; Kevin R.; (Glenn
Allen, VA) ; Barbee; Wayne; (Glenn Allen, VA)
; Ivatury; Rao; (Richmond, VA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Virginia Commonwealth University |
Richmond |
VA |
US |
|
|
Assignee: |
Virginia Commonwealth
University
Richmond
VA
|
Family ID: |
30444079 |
Appl. No.: |
13/952186 |
Filed: |
July 26, 2013 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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11855205 |
Sep 14, 2007 |
8497408 |
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13952186 |
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10363994 |
Aug 13, 2003 |
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PCT/US01/28295 |
Sep 12, 2001 |
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11855205 |
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60231883 |
Sep 12, 2000 |
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Current U.S.
Class: |
604/319 ;
424/445; 424/78.35; 526/307.6 |
Current CPC
Class: |
A61B 17/122 20130101;
A61L 24/106 20130101; A61B 17/0057 20130101; A61L 26/0061 20130101;
A61L 2400/04 20130101; A61L 15/22 20130101; A61F 13/0269 20130101;
A61L 24/108 20130101; A61B 17/132 20130101; A61K 9/0048 20130101;
A61B 2017/00659 20130101 |
Class at
Publication: |
604/319 ;
424/445; 424/78.35; 526/307.6 |
International
Class: |
A61L 26/00 20060101
A61L026/00 |
Claims
1-39. (canceled)
40. A medical device comprising a hemostatic substance placeable
directly in a bleeding wound, wherein the wound is a compressible
wound or a non-compressible wound.
41. The device of claim 40, wherein the wound is a battlefield
injury.
42. The device of claim 40, wherein the bleeding is high pressure
bleeding.
43. The device of claim 40, wherein the device stops bleeding at
bleeding pressures of up to about 60 to 90 mm Hg.
44. The device of claim 40, wherein the device is removable.
45. The device of claim 40, wherein the device is
biodegradable.
46. The device of claim 40, wherein the device when placed in a
bleeding wound swells at a rate of about 100 to 300%) volume
increase per minute.
47. The device of claim 40, wherein the device produces pressure of
greater than about 60 mm Hg in a confined space.
48. The device of claim 40, wherein the device is administrable by
a medic.
49. A medical device comprising a back-pressure generator placeable
directly in a bleeding wound.
50. The device of claim 49, wherein the back-pressure generator
comprises a hemostatic substance or article.
51. The device of claim 49, wherein the back-pressure generator
comprises polymer fibers of diameter about 1 micron or less.
52. The device of claim 49, wherein the back-pressure generator
swells upon contact with water molecules.
53. The device of claim 49, wherein the back-pressure generator
swells upon contact with blood.
54. The device of claim 49, wherein the back-pressure generator
comprises a lightly cross-linked material.
55. The device of claim 49, wherein the back-pressure generator
absorbs at least 10 times its weight of water.
56. The device of claim 49, including a membrane enclosing an
interior hemostatic substance or article.
57. The device of claim 56, wherein the membrane stiffens as the
interior hemostatic substance or article swells.
58. The device of claim 49, wherein the back-pressure generator
swells from an initial volume to a 10-fold volume in one minute in
a liquid.
59. The device of claim 49, including a polymeric substance.
60. The device of claim 49, including a microporous,
hydrogel-forming polymer with rapid swelling kinetics.
61. The device of claim 49, including poly(acrylamide) and/or
hydroxypropylcellulose.
62. The device of claim 49, including a flexible, highly porous
membrane.
63. The device of claim 49, including a substance that swells at a
rate of 100 to 300% volume increase per minute.
64. The device of claim 49, including a clot-inducing
substance.
65. The device of claim 49, including thrombin, batroxobin,
reptilase, or a fibrinogen activating enzyme.
66. The device of claim 49, including a substance that swells at a
rate of 100 to 300%) volume increase per minute and a clot-inducing
substance.
67. The device of claim 49, wherein the back-pressure generator
provides a pressure in the range of about 50 to 90 mm Hg.
68. The device of claim 49, including an elastic hemocompatible
shell and at least one antibiotic and/or analgesic within the
shell.
69. The device of claim 49, including a bladder within a porous
membrane.
70. The device of claim 49, including an impermeable inflatable
bladder within a porous membrane.
71-75. (canceled)
Description
BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] The invention is generally related to emergency medicine. In
particular, the invention relates to bleeding and bleeding
injuries.
[0003] 2. Background Description
[0004] The morbidity and mortality from penetrating injuries (such
as ballistic injuries in combat, knife wounds, penetrating wounds
secondary to motor vehicle accidents, etc.) has decreased over the
past fifty years. However, some undesirable results remain. Present
treatments for high pressure, i.e. arterial, bleeding can cause
ischemia that might contribute to limb loss. Tourniquet use can
contribute to the need for amputation. This is especially true if
there is a significant delay in definitive treatment.
[0005] As to military trauma, two characteristics of death due to
such trauma are seen. First, early death occurs. Soldiers who die
due to injury, die early: about 40% die immediately; 25% die within
5 minutes; 15% die within 15 minutes; i.e., a total of 80% dead in
the first 15 minutes after trauma. A second feature of military
trauma is death due to bleeding, with 2/3 of military deaths due to
trauma being due to hemorrhage.
[0006] Ballistic injury is a primary mode of trauma in combat. Such
injuries can be associated with rapid blood loss due to vascular
disruption. In the Vietnam conflict, ten percent of wounds to the
extremity were associated with major artery injury. M. E. Jabaley,
H. D. Peterson, "Early treatment of war wounds of the hand and
forearm in Vietnam," Ann Surg 1973; 177:167-73. While bleeding from
compressible vessels may respond to direct pressure, blood loss
from deep muscular branches (such as those from the profunda
femoris artery, etc., e.g., see Table 1) may be severe. S. M.
Henry, R. Tornetta III, T. M. Scalea, "Damage control for
devastating pelvic and extremity injuries," Surg Clin North Am,
77:879-95 (1997). Despite increasingly aggressive surgical
treatment, limb salvage has not improved. P. V. Sharma, S. C. Babu,
P. M. Shah, R. H. Clauss, "Changing patterns in civilian arterial
injuries," J. Caridovasc Surg (Torino), 26:7-11 (1985). Death from
hemorrhagic shock remains a problem even in very healthy
individuals. J. Valentine, S. Blocker, J. H. Chang, "Gunshot
injuries in children," J Trauma, 24:952-6 (1984). As can be
appreciated from the following Table 1, combat vascular injuries
continue to result in a 12 to 30 percent amputation rate depending
on the involved vessel.
TABLE-US-00001 TABLE 1 (Incidence of major lower extremity vascular
injuries in the three great wars) (Source: Vascular Trauma, Rich N.
M. and Spencer, F. C. (eds.), W. B. Sunders, Philadelphia, 1978).
Total Common External Common Deep Superficial War Arteries Iliac
Iliac femoral Femoral Femoral Popliteal WWI 1202 1 4 366 144 WWII
2471 13 30 106** 23 517 502 Korean 304 .sup. 95! 79# Vietnam 1000 9
17* 46*** .sup. 305@ 217# *three amputations and one death
**ligation lead to 86 amputations !12% amputation rate ***15%
amputation rate, 3 deaths @37 amputations or 12.1% #30% amputation
rate
[0007] Nor is the high incidence of deaths and amputations from
penetrating wounds only for combat injuries. Treatment of trauma
also is important in the civilian arena. At one Level I civilian
trauma center in Virginia, from 1995 to 1999, of 66 patients with
penetrating extremity vascular injuries, there were five deaths
from hemorrhagic shock. Trauma is the most frequent cause of death
in the United States in persons under the age of 34. Because trauma
occurs most in young people, trauma is the leading cause of life
years lost. Up to 80% of all early trauma deaths are from
uncontrolled hemorrhage. Each year in the United States, 1 in 100
people will visit an emergency room; 1 in 1000 people will be
admitted and transfused; 1 in 3000 will die of trauma. About 50% of
civilian deaths due to trauma are secondary to hemorrhage.
[0008] Currently available modalities for treating high pressure
bleeding include tourniquets, fibrin glue, etc. However, these
current bleeding treatments have significant disadvantages, such as
nerve damage, limb ischemia, increased risk of amputation, etc.
[0009] Tourniquets were described more than two millenia (2000
years) ago as an adjuvant to surgical amputation. L. Zimmerman, I.
Veith, Great Ideas in the History of Surgery, San Francisco,
Calif.: Norman Publishing (1993), 31. Since then, tourniquets have
become a primary a primary initial treatment for injuries
associated with high pressure bleeding. Unfortunately, tourniquet
use is associated with a variety of complications and difficulties
including nerve damage, post-tourniquet syndrome, limb ischemia
(distal ischemia), compartment syndromes, pulmonary embolus,
increased risk of amputation, and limb wastage. A. K. Palmer,
"Complications from tourniquet use," Hand Clinics, 2:301-5 (1986);
A. S. Estrera, R. P. King, M. R. Platt, "Massive pulmonary
embolism: a complication of the technique of tourniquet ischemia,"
J Trauma, 22:60-2 (1982). To decrease these risks, tourniquets must
be intermittently loosened. This typically restarts the bleeding
and is difficult for treating personnel to accomplish. Despite the
potential complications and drawbacks, recent combat (such as the
1991-92 Croatian conflict) has verified the ability of tourniquets
to delay shock in lower extremity arterial injuries. Z Lovric, V
Lehner, B Wertheimer, L Kosic-Lovric, "Tourniquet occlusion
technique for lower extremity artery reconstruction in war wound,"
J Cardiovasc Surg (Torino), 38:153-5 (1997).
[0010] While fibrin products (such as fibrin glue, fibrin sealant
and dry fibrin dressing) have been developed and shown to be
effective in stopping venous bleeding, such fibrin products do have
drawbacks. Fibrin products have had a tendency to be washed from
the wound during high pressure bleeding, relative high cost. Some
fibrin products put the patient at risk of viral exposure. Virally
inactivated fibrin sealant has been developed, and is being used as
an adjuvant to multiple types of surgery, C J Dunn, K L Goa,
"Fibrin sealant: a review of its use in surgery and endoscopy,"
Drugs, 58:863-86 (1999); M R Jackson, B M Alving, "Fibrin sealant
in preclinical and clinical studies," Curr Opin Hematol, 6:415-9
(1999). Fibrin glue has been shown to be effective in speeding
hemostasis along vascular graft suture lines. A A Milne, W G
Murphy, S J Reading, C V Ruckley, "A randomised trial of fibrin
sealant in peripheral vascular surgery," Vox Sang, 70:210-2 (1996).
Fibrin glue has been tested as an adjuvant to surgery in the
treatment of complex hepatic injury. S M Cohn, J H Cross, M E Ivy,
A J Feinstein, M A Samotowka, "Fibrin glue terminates massive
bleeding after complex hepatic injury," Trauma, 45:666-72 (1998).
Formulations of fibrinogen and thrombin containing dressings, and
dry fibrin sealant dressings have been proposed and studied in pig
models of vascular injury and grade V liver injury. M J Larson, J C
Bowersox, R C Lim, Jr., J R Hess, "Efficacy of a fibrin hemostatic
bandage in controlling hemorrhage from experimental arterial
injuries," Arch Surg, 130:420-2 (1995); J B Holcomb, A E Pusateri,
R A Harris, N C Charles, R R Gomez, J P Cole, L D Beall, V Bayer, M
MacPhee, J R Hess, "Effect of dry fibrin sealant dressings versus
gauze packing on blood loss in grade V liver injuries in
resuscitated swine," Trauma, 46:49-57 (1999); J B Holcomb, A E
Pusater, R A Harris, T Reid, L D Beall, J R Hess, M J MacPhee, "Dry
fibrin sealant dressing reduce blood loss, resuscitation volume,
and improve survival in hypothermic coagulopathic swine with grade
V liver injuries, "J Trauma, 47:233-40 (1999). Dry fibrin sealant
dressing was recently shown to be more effective than standard
gauze in decreasing bleeding and maintaining blood pressure in
ballistic injury. J Holcomb, M MacPhee, S Hetz, R Harris, A
Pusateri, "Efficacy of a dry fibrin sealant dressing for hemorrhage
control after ballistic injury," Arch Surg, 133:32-5 (1998).
[0011] While the development of "dry" products has increased their
potential as alternatives to tourniquets for battlefield treatment,
several potential problems remain. First, these products are
relatively expensive because they are made from human blood
(requiring a large amount of starting materials and multiple
purification processes). Second, although virally inactivated, the
fibrinogen contained in the products comes from multiple human
donors and cannot be considered totally safe in terms of viral
transmission. Third, these products must be held in place until
bleeding stops or the material may simply wash out of the wound.
The wash-out problem is especially seen when the bleeding is brisk
as with arterial involvement.
[0012] Thrombin-mediated polymerization of fibrinogen has been the
staple of hemostat technology for decades. "Hemostatic" means
anything with the ability to enhance, speed or support blood
clotting. Indeed, a recent patent dealing with hemostat systems
still focuses on this process. J J Prior, D G Wallace, D H Sierra,
F A DeLustro, "Compositions containing thrombin and microfibrillar
nanometer collagen, and methods for preparation and use thereof,"
U.S. Pat. No. 6,096,309 (2000).
[0013] Also, treatment of bleeding external wounds also has not
progressed much, with conventional treatments not offering much
beyond simply covering the wound. Most conventional dressings do
little or nothing to promote hemostatis, prevent infection or
relieve pain. Current bandages do little more than cover the wound
and absorb fluids. There are emerging products that aid in
hemostasis (fibrin glue, fibrin sealant, dry fibrin, kitosan, etc.)
but most are quite expensive and some carry a risk of viral
infection.
[0014] Another difficulty of conventional treatments for bleeding
is that the patient loses much of his or her own blood, and
transfusion is needed. Blood transfusion suffers from availability
problems, purity concerns, etc., and is expensive. Costs of
civilian blood transfusion for trauma were about $1/2 billion in
1997.
[0015] None of the current technologies adequately address the
problem of treating high pressure arterial bleeding. A tourniquet
alternative that is effective, inexpensive, lacks viral risk, and
can be easily administered (such as by an army medic) would be a
medical advance. A solution is still sought to the problem of
assuring hemostatis and homeostasis for a penetrating injury (such
as high-pressure bleeding combat wound) until the patient (such as
a soldier) can reach a hospital facility for definitive care.
Additionally, better treatment of bleeding external wounds is
timely. Overall, better treatment of hemorrhage by the first
responder would save lives, money and limbs, in military and
civilian situations.
SUMMARY OF THE INVENTION
[0016] Leakage (such as bleeding) may be stopped or reduced
relatively quickly by pressure equalization comprising enclosing a
region around the leak and applying direct-pressure in or around
the leak. Notably, bleeding (especially high-pressure bleeding from
penetrating injuries such as combat wounds) may be treated by
applying direct pressure within the wound, especially by enclosing
an area around the wound and applying direct pressure in that
enclosed area. Such direct-pressure application advantageously may
be by a simple medical device (such as a device administrable by a
medic). An inventive medical device may be placed directly in the
wound, where it stops high pressure bleeding. The acute dressing is
both removable for a definitive treatment, and biodegradable if not
removed (such as because removal is not warranted). The inventive
device is simple, easy to apply, much less expensive than other
biological products, and does not expose the patient to viral
contaminants. The invention directly addresses the problem of high
pressure by simulating the time honored treatment of direct
pressure, particularly, pressure directly within the wound.
[0017] The invention is particularly practical, in that four topics
(topics 1a, 1c, 1f, 1g) of the nine research topics proposed in the
hemorrhage control section of the Research on Combat Casualty Care
program are addressed. The inventive medical devices and methods
may be used in compressible (topic 1f) and non-compressible (topic
1a) bleeding. Medical devices and methods according to the
invention are suitable for replacing the tourniquet as the primary
field hemostat used by the medic (topic 1c). Because medical
devices and treatment methods according to the invention are
designed to avoid the ischemia associated with tourniquet use, they
have no time limit on emergent use (topic 1g). Advantageously, the
invention provides acute dressings and other medical devices that
may be removed for definitive treatment while also being
biodegradable if not removed.
[0018] Advantageously, the present invention moves away from the
conventional treatment paradigm for penetrating high-pressure
bleeding injuries of "first save the patient, then spare the limb"
to a new paradigm of "save the patient and spare the limb."
[0019] In order to accomplish these and other objects of the
invention, in a first preferred embodiment, the invention provides
a method of treating a fluid leak (such as a bleeding wound),
comprising inserting into the fluid leak a material swellable on
contact with the leaking fluid.
[0020] In a second preferred embodiment, the invention provides a
method of treating a bleeding wound, comprising applying direct
pressure directly in the bleeding wound. Particularly preferred is
to place directly in the wound a substance that swells at a rate of
100 to 300% volume increase per minute. Most preferably, direct
pressure application continues until bleeding stops.
[0021] In a third preferred embodiment, the invention provides a
medical device comprising a hemostatic substance placeable directly
in a bleeding wound, wherein the wound is a compressible wound or a
non-compressible wound. Advantageously, the invention provides
devices that may be removable and/or biodegradable; devices that
when placed in a bleeding wound swells at a rate of about 100 to
300% volume increase per minute; devices that produce pressure of
greater than about 60 mm Hg in a confined space; devices
administrable by a medic, etc.
[0022] Some aspects and features of the invention are now
mentioned, without the invention being limited thereto.
[0023] The inventive methods and devices in an especially preferred
embodiment may include applying a back pressure in a confined space
around and in the wound. In another especially preferred
embodiment, the invention may include inserting a
direct-pressure-applying substance or article into the wound and
enclosing the wound with the direct-pressure-applying substance or
article therein. In a further especially preferred embodiment, the
invention may include inserting a hemostatic substance or article
into the wound and enclosing the wound (such as by placing a
dressing over the wound) with the hemostatic substance or article
therein.
[0024] Where the invention uses a hemostatic substance or article,
in a particularly preferred embodiment, the hemostatic substance or
article includes polymer fibers of diameter about 1 micron or less.
In another particularly preferred inventive embodiment in which a
hemostatic substance or article is used, the hemostatic substance
or article swells upon contact with water molecules (such as water
molecules contained in blood leaving the wound). Where a hemostatic
substance or article is used, the hemostatic substance or article
may be lightly crosslinked. Where a hemostatic substance is used,
in a particularly preferred embodiment of the invention, the
hemostatic substance swells from an initial volume to a 10-fold
volume in one minute in a liquid; and/or the hemostatic substance
generates at least 60 mm Hg pressure within three minutes of being
placed in a bleeding wound.
[0025] In a particularly preferred embodiment of the invention, a
membrane or shell encloses the swellable material, hemostatic
substance or article, or the like. Most preferably, the membrane or
shell stiffens as the interior hemostatic substance or article or
swellable material swells.
[0026] The invention in a particularly preferred embodiment
provides for using (such as placing in a wound or disposing in a
device) a polymeric substance, such as a polymeric substance that
is a microporous, hydrogel-forming polymer with rapid swelling
kinetics. Preferably, the polymeric substance may be
poly(acrylamide), hydroxypropyl cellulose, or a hydrophilic
material.
[0027] The invention in a particularly preferred embodiment
provides for placing a clot-inducing substance (such as thrombin,
batroxobin, reptilase, a fibrinogen activating enzyme, etc.) in a
wound to be treated.
DETAILED DESCRIPTION OF THE DRAWINGS
[0028] FIG. 1A is a schematic of an apparatus for electrospraying
or electrospinning production. FIG. 1B shows the apparatus of FIG.
1A in the process of electrospinning production.
[0029] FIGS. 2A-2B are microphotographs showing PEVA deposited from
a solution in chloroform that is 9 wt % solution in chloroform
(FIG. 2A) and 15 wt % solution in chloroform (FIG. 2B).
[0030] FIG. 3 is a screening apparatus for substances for pressure
development during swelling in a confined space.
[0031] FIGS. 4A-4B are perspective views of a medical device
according to the invention, with FIG. 4A showing a wound treatment
device before use and FIG. 4B showing a wound treatment device
expanded after exposure to blood, water or another liquid.
[0032] FIGS. 5A-5B are representational views of a molecular scale
depiction of behavior of a device according to the invention.
[0033] FIGS. 6A-C are representational drawings of the invention at
a molecular-level, in use treating a bleeding wound, including FIG.
6A where a fresh inventive device has been placed at a wound to be
treated;
[0034] FIG. 6B where the device has been in contact with the
bleeding wound for a time; and FIG. 6C where the device has been in
contact with the bleeding wound for a sufficient time to equalize
pressure.
[0035] FIG. 7A is a scanning electron microphotograph of an
ethylene vinyl acetate (EVA) electrospun mat; FIG. 7B is a scanning
electron microphotograph of EVA
[0036] FIGS. 8A-8B are a graph of swelling properties of swellable
materials according to the invention electrospun ethylene-vinyl
acetate (EVA) copolymer bags, with time (minutes) plotted against
grams water/grams polymer, for poly(acrylamide)co-acrylic acid
copolymer (FIG. 8A) and poly(acrylamide)co-acrylic acid copolymer
potassium salt (FIG. 8B), respectively.
[0037] FIGS. 9A-9F are representational cross-sections of an
initially healthy blood vessel (FIG. 9A) that is disrupted (FIG.
9B), with the invention used in treating the disrupted blood vessel
(FIGS. 9C-9D).
[0038] FIGS. 10A-10B diagram filling according to the
invention.
[0039] FIG. 11 is a representative view of an exemplary
layered-system device according to the invention.
[0040] FIG. 12 is an exemplary system according to the invention
for use with external hemorrhage.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS OF THE INVENTION
[0041] With the invention, a liquid leak (such as a bleeding wound,
etc.) may be stopped or at least reduced by applying direct
pressure inside the leak. The direct pressure to be applied may be
generated by a swellable material, by pneumatic filling of a
bladder, singly or in combinations thereof, etc.
[0042] Where a swellable material is used, the swellable material
is selected based on the leaking liquid to which it will be
exposed, such as blood in a patient, water in a plumbing system,
etc. Most preferably, the swellable material absorbs at least 10
times its weight of the leaking liquid, such as, in the case of
bleeding, about 10 times its weight of water.
[0043] In a particularly preferred embodiment, the invention
provides an exemplary method of treating a bleeding wound,
comprising applying direct pressure directly in the bleeding wound,
most preferably applying direct pressure in the range of about 50
to 90 mm Hg directly in a high-pressure bleeding wound (such as a
wound bleeding at about 60 to 90 mm Hg pressure). The wounds
treatable by the invention include high-pressure bleeding wounds,
compressible wounds, non-compressible wounds, external wounds, etc.
The invention advantageously may be used for treating wounds
bleeding in a range of about 60 to 140 mm Hg, or higher, and also
may be applied for treating low-pressure bleeding.
[0044] In the case of high-pressure bleeding wounds, a preferred
example of applying direct pressure directly in the bleeding wound
is to insert a hemostatic (i.e., hemocompatible
direct-pressure-producing) substance or article into the wound and
to enclose the wound with the hemostatic substance or article
therein. By establishing around the wound a confined space, such as
the wound covered with an elastic dressing, swelling of a swellable
material enclosed therein may be used to produce a back pressure
that advantageously stops or at least slows bleeding. By provision
of such a back pressure within the wound, clot formation may be
supported and enhanced, and high pressure (arterial) bleeding may
be stopped or at least slowed, advantageously without compromising
collateral blood flow (as occurs with a constrictive treatment such
as a tourniquet).
[0045] The application of direct pressure preferably is pressure
generated by swelling of at least one swellable material. The
amount of pressure applied is in an amount for stopping or at least
minimizing bleeding from the wound, preferably such as about 50 to
90 mm Hg pressure (most preferably, about 80 mm Hg pressure)
generated from a swelling substance or article in four minutes or
less (most preferably about three minutes or less).
[0046] As preferred examples of swellable materials for use in the
invention may be mentioned polymers, such as polymers that are
hydrogel-forming, micro-fibrous and/or water-absorbing,
poly(acrylic acid), poly(ethylene oxide), poly(acrylamide),
hydroxypropyl cellulose, other polymers or substances used in
diapers and/or incontinence pads, etc., and their salts (such as
ammonium, sodium, etc.) and derivatives thereof. Most preferred
examples of swellable materials are swellable hemostatic substances
including the following: poly(acrylic acid); polyacrylamide
polyacrylamide (crosslinked); poly(acrylic-co-acrylamide)
crosslinked (such as N,N-methylene bis-acrylamide crosslinked);
crosslinked and modified polyacrylamide; polyhydroxyethyl
methacrylate) PHEMA; hydrogels based on poly(vinyl alcohol) (PVA);
alginate based hydrogels; HEM-co-acrylic acid-co-sodium acylate
copolymeric hydrogels; isopropylacrylamide-co-acrylic
acid-co-sodium acrylate hydrogels; and gelatin gels. Some polymer
structures are shown in Table 2, below.
TABLE-US-00002 TABLE 2 Examples of absorbent polymers Polymer
Structure Poly (acrylic acid) (linear) ##STR00001## Polyacrylamide
Polyacrylamide (Crosslinked) (linear) ##STR00002## Poly(acrylic-co-
acrylamide) crosslinked (N,N-methylene bis- acrylamide crosslinked)
(linear copolymer structure) ##STR00003## Crosslinked and modified
Polyacrylamide ##STR00004## X = various groups Poly(Hydroxyethyl
methacrylate) PHEMA (linear) ##STR00005## Hydrogels based on
Poly(vinyl alcohol) PVA (linear) ##STR00006## "n" = an integer "m"
= an integer which may be the same or different from "n"
[0047] As to the polymer size, preferable to use are polymer fibers
of diameter about 10 microns or less, most preferably 1 micron or
less. That small-diameter polymer fibers are particularly preferred
may be seen by considering that, for a gel fiber, the contraction
rate t is equal to a contraction rate constant c times the square
of the diameter; this relationship may be used to evaluate
particular polymer fibers (such as fibers of particular diameters)
for whether they have rapid swelling kinetics. For example, for
polyacrylamide, c is approximately 2.times.10.sup.9 s/m.sup.2 and
therefore polyacrylamide gels with a diameter of 1 cm take about
2.5 days to swell, while micron diameter polyacrylamide fibers take
milliseconds, See E S Matsuo, T Tanka, "Kinetics of discontinuous
volume-phase transition of gels," J Chem Phys, 89:1988 (1988).
[0048] For formulating polymers useable in the invention,
preferably electric field-mediated polymer processing is used, most
preferably with electrospraying and/or electrospinning. J Stetzel,
G L Bowfin, K Mansfield, G E Wnek, D G Simpson, "Electrospraying
and electrospinning of polymers for biomedical appliations,
poly(lactaic-co-glycolic acid) and poly(ethylene-co-vinylacetate),
Proc. SAMPE Conf., Boston, November 2000; D H keneker, I Chun,
"Nanometer diameter fibers of polymer produced by electrospinning,"
Nanotechnology, 7:216-223 (1996). Electrospinning may be used to
afford small diameter (i.e., 10 microns or less) hydrogel-forming
polymer fibers having rapid swelling kinetics.
[0049] Starting materials suitable for electrospinning or
electrospraying include elastomeric materials such as thermoplastic
elastomers, such as segmented polyurethanes, ethylene-vinylene
acetate (EVA) copolymer, etc. Biocompatible starting materials
(such as EVA copolymer) are particularly preferred, and
biocompatible starting materials that serve as a host for the
delivery of a wide variety of small and large therapeutic molecules
(such as EVA copolymer) are most preferred. J Folkman, R Langer,
"Polymers for the Sustained Release of Proteins and Other
Macromolecules," Nature, 263:797 (1976). Although theoretically
non-biocompatible materials could be used if enclosed in an
expandable impermeable membrane (such as a syringe port), such a
course is not preferred and to be avoided when the starting
materials are to be used to formulate a system for wound treatment
or other use on or in a patient.
[0050] As shown in FIG. 1A, an apparatus for an electrospraying or
electrospinning system comprises a syringe pump 100 for pumping a
starting material solution or melt 100A to be sprayed or spun, a
high voltage system 99 (such as a 15 kV system), a collector
(ground) electrode 98, and a source electrode 97. The starting
material solution or melt 100A is preferably confined in any
material formed into a nozzle with various tip bore diameters (such
as a disposable pipette tip), with a very thin source electrode 97
immersed in it. The collector 98 can be a flat plate, wire mesh,
rotating metal drum or plate on which the polymer is wound, etc.
The solution 100A to be spun or sprayed can be doped with various
substances, such as, in the case of electrospun fibers, doping with
various substances that can be released from the electrospun
fibers. The electrospinning process preferably is continued until a
mat accumulates (such as an EVA mat) of approximate dimensions as
desired, such as on the order of nun by mm, or cm by cm by length
and width, and micrometers to millimeters for thickness.
[0051] Additionally, swellable materials may be obtained
commercially, such as alginate based hydrogels; HEMA-co-Acylic
acid-co-Sodium acylate copolymeric hydrogels; poly(vinyl
alcohol)/poly(acylic acid) hydrogels;
isopropyylacrylamide-co-acrylic acid-co-sodium acrylate hydrogels;
gelatin gels; etc.
[0052] When a polymer is used as the swellable material, the
polymer may be uncrosslinked or crosslinked, preferably
crosslinked. Crosslinking can be accomplished during polymerization
with the use of polyfunctional monomers such as bisacrylamide, or
by treatment of the polymer with ionizing radiation (e.g.,
.quadrature.-radiation). Where electrospinning is carried out from
solution or the melt using un-crosslinked polymers, preferably the
polymer is treated with ionizing radiation.
[0053] The swellable material may be provided for use with a
leaking material in a variety of forms, such as a mat of a swelling
material, a swelling material contained within a shell or membrane,
a swelling material dispensed from a tube or aerosol, etc. The form
used may be selected based on the characteristics of the leak to be
treated, the likely treatment setting, etc.
[0054] In the case of wound treatment, especially high-pressure
wound treatment, the swellable material preferably is contained
within a biocompatible, hemocompatible shell or membrane that
permits the leaking liquid to pass through the shell or membrane to
reach the swellable material. The shell or membrane is selected
with regard to the leaking material (such as blood), the swellable
material, and any other treating material (such as clotting
promoters, antibiotics, analgesics, etc.) disposed within the shell
or membrane. For selecting a shell or membrane, preferably, the
shell or membrane is porous, elastic, provides stiffness as the
hydrogel inside swells, and/or allows easy ingress of the
particular leaking material (such as blood), and most preferably
meets all of these characteristics. Elastomeric polymers and
hydrophilic, expansile polymers are particularly preferred as
shells or membranes as they typically increase in stiffness when
stretched due to chain orientation. Such stiffening of the shell
upon swelling of the interior hemostatic substance or article is
desirable for generating back pressure. Preferably the to-be-used
membrane is formed as a relatively flat bag, with relatively little
unoccupied space around the swellable material. Loose-fitting
placement of the swellable material within the membrane is
preferred, corresponding to the expansion geometry. Namely, as the
membrane limits the material expansion, a too-tight between the
swellable material and the membrane is not desired because
expansion of the membrane would be impeded. Namely, if membrane
expansion is limited, correspondingly the amount of pressure that
the membrane is able to put on its surroundings (such as a bleeding
wound) is limited. The membrane preferably is non-leaking with
regard to the swellable material, and, where a polymer is used as
the swellable material, polymer leakage may be minimized by
crosslinking the outermost portions of the polymer matrix to the
membrane.
[0055] When a membrane is used for enclosing the swellable
material, preferably the membrane is perforated. Pore sizes are
such as to limit the leakage of polymer; the pores can increase
with swelling because the size of the polymer inside increases as
it binds the water, permitting more blood/water to enter and
bringing about equilibrium. The membrane is not required to be
completely uniform in its characteristics, and may be customized.
For example, where the membrane is perforated, most preferably the
perforations are relatively large and numerous on the part of the
membrane that is to contact the bleeding (or other leaking
material), so that exiting blood and other liquid may enter the
membrane and activate the swellable material so that the swellable
material swells and exerts a backpressure. It will be appreciated
that if the membrane where it contacts the wound is resistant to
the exiting blood and liquid and does not permit their entry, they
will find an alternate path, i.e., traveling around the resistant
membrane and exiting the wound; thus, a too-resistant membrane on
the wound side is to be avoided as the swellable material would not
be swelled.
[0056] Customizing the membrane on the non-wound side (i.e., the
dressing side or medic side) may include features to retain the
swelled material, blood, liquid, etc., such as non-perforation,
reinforcement of the membrane, coating, etc. It will be appreciated
that on the non-wound side, it is not desired that blood, body
fluids, or other materials escape. Where a customized membrane with
a wound-side and non-wound differential is used, the person to be
applying the membrane-enclosed swellable material will require
training and/or specific markings on the membrane are included. In
determining whether to customize a membrane or to provide a unitary
membrane, there may be considered the training of the person who
will administer the membrane-enclosed swellable material, whether
the membrane can be marked to direct the person administering the
swellable material which side to place into the wound, etc.
[0057] To the hemostatic substance or article and/or to the shell,
there may be added further substances, such as a clot-promoting
substance (such as thrombin, preferably lyophilized thrombin).
Including a clot-promoting substance in the shell advantageously
promotes blood clotting around the periphery of the shell,
Preferably, a concentration of the clot-promoting substance is one
that speeds clotting without clogging the swellable material with
clot.
[0058] It will be appreciated that, until ready for use, the
swellable material must be kept away from materials which may cause
it to swell. For example, in the case of a swellable material
intended for use with blood and aqueous materials, the swellable
material must be kept dry.
[0059] The invention also provides certain devices (such as medical
devices), especially those comprising a swellable material (as
mentioned above) within a shell (as mentioned above). Most
preferable devices are those such as that of FIGS. 4A-4B, FIGS.
5A-5B and FIGS. 6A-6C. As shown in FIG. 4A, before exposure, a
device 1 of which the exterior is a membrane 2 is relatively small
in size. FIGS. 5A and 6A are respective molecular-scale versions
corresponding to FIG. 4A, with some molecules 3 constituting the
swellable material shown. (Only a few swellable material molecules
3 are shown for simplicity; it will be appreciated that generally a
device comprises a large population of molecules 3). Before the
device has been exposed to a liquid, the membrane 2 is loose and
there is a void 4 inside the membrane 2 (FIG. 5A).
[0060] As shown in FIGS. 6A-6C, a device comprising a swellable
material 3 within a membrane 2 is contacted with a leaking material
5 (such as blood) and the leak (such as a wound) is enclosed with
an enclosure material 6 (such as a dressing).
[0061] Membrane 2 on the wound side 2Y permits leaking molecules
(such as blood molecules, water, etc.) 5 to pass into the interior
of the device, and that as such blood molecules, water and other
leaking molecules 5 come in contact with swellable material
molecules 3, the blood and other water-containing molecules 5 bond
to the molecules 3 and remain inside the membrane, causing the
membrane to expand. At a certain point expanded membrane 2A has
reached its maximum expansion for the pressure being applied by the
leaking molecules 5. Leaking molecules 5 inside the membrane 2A
cannot readily exit the membrane 2A on the wound side 2Y because
more leaking molecules 5 are entering at the wound side 2Y of the
membrane 2A. While some leaking molecules 5 may escape through
expanded membrane 2A at the dressing side 2Z of the membrane 2A,
the relatively greater number of leaking molecules 5 that have been
retained within in the device and within the wound should be
appreciated. Additionally, the membrane 2 on the dressing side 2Z
during production may have been reinforced or treated to be
relatively less porous or less perforated than on the wound side
2Y.
[0062] As the device is used in a bleeding wound, the swellable
material 3, the leaking molecules 5 contained within the membrane
2A, the membrane 2A (including the membrane 2A on the wound side 2Y
and on the dressing side 2Z) together and respectively act as a
barrier to leaking molecules 5 that are newly approaching the
membrane 2A on the wound side 2Y, so that where leaking molecules 5
earlier had encountered no or little force blocking their exit,
they encounter some back-pressure (FIG. 613) as the device operates
and then as the device is maximally activated, they encounter
pressure equalization (FIG. 6C).
[0063] During exposure to a liquid, device 1 accepts additional
molecules and membrane 2 expands, forming expanded device 1A (see
FIG. 4B) of which the exterior is expanded membrane 2. Such
expansion is possible because a swellable material within the
device controllably swells when exposed to aqueous solutions (such
as found in a bleeding wound), with the desired result of the
expansion being to generate a back pressure. When a medical device
containing a swellable material is introduced into a bleeding
wound, and the wound and device enclosed together, bleeding can be
stopped or at least reduced by the back pressure generated by the
device.
[0064] An exemplary device 1 according to the inventive is a
clotting-promoter containing device, such as a thrombin-containing
device. An example of using a clotting-promoter containing device
may be appreciated with regard to FIGS. 9A-9E. In FIG. 9A is shown
a healthy blood vessel 7 (such as a vessel having a typical
pressure of T=90 mmHg). The healthy blood vessel 7 suffers injury
and becomes disrupted blood vessel 7A (FIG. 9B) having a wound 8.
In FIG. 9C is shown moving a clotting-promoter containing device 9
(such as a thrombin-containing device) towards the bleeding wound
8. In FIGS. 9A, 9B and 9C, arrows show the direction in which blood
travels. As shown in FIG. 9D, the device 9 is inserted directly
into the bleeding wound 8, and covered with a dressing 6. Once the
device 9 is provided into the bleeding wound 8, blood begins to
enter the device 9 and to contact the dressing 6.
[0065] After the device 9 has been in the wound 8 held by the
dressing 6 for a time (such as about three minutes), the device
will have expanded and will have released clotting-promoters, with
the wound 8A containing clotting promoters, as shown in FIG. 9E.
Expanded device 9A as a result of its expansion exerts pressure on
its environment, namely on the patient's blood. In addition to the
pressure exertion effects provided by expanded device 9A, the
bleeding wound 8A also experiences clotting promotion from the
clotting promoters released from the device 9, 9A.
[0066] As the expanded device 9A continues to expand (see FIG. 9F),
such as at about four minutes after device insertion, the
more-expanded device 9B will take up more space in the wound. As
time progresses (see FIG. 9F), such as about four minutes pass
since insertion of the device 9 into the bleeding wound,
further-expanded device 913 exerts an equalized pressure on its
surroundings in the wound 8A, and a pressure equilibrium is
reached. As the clotting promoters take further effect, clotted
regions 10 are formed. The equilibrium situation of FIG. 9F is
maintained. Advantageously, the expanding device 9, 9A, 9B reduces
and stops blood loss. In this particularly preferred inventive
embodiment shown in FIGS. 9C-9F, direct pressure application inside
the wound is combined with clotting promotion to stop blood loss
from a penetrating wound in as little as 3 or 4 minutes, or even
less.
[0067] FIGS. 9C-9F show a device 9, 9A, 9B being used to treat a
bleeding wound, with the fresh device 9 slightly smaller than the
wound 8 into which it is being placed. When selecting a device size
for inserting into a bleeding wound, it is desired that the
expanded device 913 be of a volume at least equal, preferably
greater, than the wound. Thus, when confronted with a wound S for
treatment, it is desirable to use a device 9 that will expand into
an expanded device 9B of greater volume than the wound to be
treated. Devices 9 of different starting size may be provided.
Also, depending on the swellable material used, expanded devices 9B
of different volumes may be provided.
[0068] Further, combinations of two or more devices (such as device
9) may be used for treating a bleeding wound, such as treating a
relatively large penetrating wound with two or more devices (which
may be the same or different). In determining how many devices 9 to
use, or what expanded device 9B may be desirable for a particular
bleeding wound to be treated, it is preferred to insert into the
wound a higher direct-pressure application capability than may be
needed (such as to use more devices 9 or a device 9 having the
potential of a larger-volume expanded device 9B than may be needed
to stop bleeding), than to insert into the wound insufficient
direct-pressure application capability to stop the bleeding.
[0069] In the case where an initial application of direct pressure
in the wound (such as insertion into the wound of a first device 9
that expands into expanded device 9B) only reduces bleeding but is
insufficient to stop bleeding, further direct pressure in the wound
(such as insertion into the wound of a follow-up device) may be
applied.
[0070] When bleeding stops after insertion of a device 9 into a
bleeding wound, expanded device 913 may be permitted to remain in
the wound or may be removed. Whether to remove the expanded device
913 or not may be based on factors such as need for access to an
internal area for surgery, etc. Preferably the device 9B is left in
the patient unless a reason appears for removing the device 9B.
[0071] In using the invention, formulations are desired that
promote clotting at a rate of preferably about less than one
minute, with relatively faster clotting being preferred. Clotting
is desired to proceed apace with the swelling, with clotting to be
complete as expansion is complete. Promoting more rapid clotting
raises the possible complication of clotting before the device
swells sufficiently to develop adequate back pressure. For a device
comprising a membrane-encased swellable material, approximate
clotting rate can be provided by the amount of hemostatic agent
and/or amount of clotting promoter used, and/or by the size and
amount of pores in the membrane.
[0072] For the direct pressure useable in the invention, another
technique for generating direct pressure comprises filling (such as
pneumatic filling, etc.) of a bladder, most preferably, a bladder
comprising a membrane enclosing a swellable material wherein the
swellable material swells on contact with the leaking material
(such as blood in a bleeding wound). An exemplary filling process
according to the invention is shown in FIGS. 10A-10B, As shown in
FIG. 10A, a device 14 (which may be device 9) is provided with a
syringe port 13 for receiving a syringe 11 (such as a syringe
containing a volume of clotting promoter (such as thrombin) or
other biocompatible material; a syringe containing air; a syringe
containing water or another liquid, etc.). An initial-setting
pressure monitor 12 is provided. Upon depressing the syringe
plunger 11Z, the contents of the syringe 11 are transferred through
the syringe port 13 and the device 13 is inflated. As shown in FIG.
10B, depressed syringe plunger 11Y corresponds to activated
pressure monitor 12A. The inflated device 14A by virtue of its
greater volume provides direct pressure on its surroundings (shown
by arrows). The device 14A may be inflated entirely due to
pneumatic filling, or may be inflated by pneumatic filling combined
with one or more other inflating methods (such as swelling of a
swellable material).
[0073] A filler according to the invention may be separable from,
or attached to, the device into which it is inserted. The device
into which the filler is inserted may be a bladder with or without
a swellable material contained therein, such as a bladder
comprising a membrane as mentioned herein. As preferred examples of
a bladder may be mentioned an elastic non-permeable bladder, an
impermeable bladder, a permeable membrane, singly or in
combinations thereof, etc.
[0074] A device according to the invention optionally may comprise
a layered system, such as a layered system of membrane(s) (such as
a permeable membrane), bladder(s) (such as an impermeable bladder),
membrane contents, and/or bladder contents. An exemplary layered
system 15 is shown in FIG. 11, comprising an impermeable expandable
bladder 16 inside a permeable membrane 17. The expandable bladder
16 may be expanded by adding water, air, etc., such as addition
through syringe port 13 using syringe 11. Between the membrane 17
and the bladder 16 no contents are required but most preferably are
included contents 18 comprising one or more of a swellable material
(such as an absorbent polymer), a clotting promoter (such as
thrombin), antibiotics, analgesics, anesthetics, singly or in
combination, etc. As contents 18, a swelling material preferably
included, most preferably a swelling material including an
absorbent polymer.
[0075] A layered system 15 preferably may be used by, once the
layered system 15 is placed in a bleeding wound, inflating or
expanding bladder 16. The expansion of bladder 16 applies force to
the contents 18 in the direction of moving the contents 18 towards
the membrane 17. Where a swellable material is included in contents
18, the swellable material preferably is treated (such as by
crosslinking) to minimize passage of the swellable material out of
the membrane 18. Where a clotting promoter (such as thrombin),
antibiotics, analgesics, and/or anesthetics are included in
contents 18, such materials are provided in a form to maximize
their passage through the membrane 18 and to the exterior of the
system 15, and their expulsion from the system 15 is aided by the
expansion of the bladder 16 and/or swelling of any swellable
material in contents 18.
[0076] The inventive methods and devices are particularly usable by
a combat medic in treating bleeding wounds such as combat wounds.
As to early treatment of combat wounds, it will be appreciated that
the combat medic is a skilled individual, and may readily use the
invention. Inventive methods and devices also may be used by less
skilled or relatively unskilled individuals in treating bleeding
wounds.
[0077] Advantageously, the invention provides the treatment
paradigm of saving the patient without compromising limb salvage.
An acute treatment is provided for both civilian and military
medical treatment of penetrating wounds, in human and veterinary
medicine. The wounds that may be treated include wounds suffered by
human patients and by animals; battlefield injuries and civilian
injuries; etc. The invention advantageously stops bleeding without
producing pressure injury or ischemic damage. By retaining the
patient's blood, the amount of transfused blood is reduced, and the
risks associated with transfusion are correspondingly reduced.
[0078] While particular mention has been made herein of the
invention's applicability for treating penetrating injuries,
external wounds are treatable using the present invention, such as
by applying (e.g., self-applying, medic-applying, etc.) a wound
care dressing comprising a swellable material to the external
wound. Where an external wound cannot receive immediate definitive
treatment, application of a wound care dressing according to the
invention provides a preferred holding treatment. A wound dressing
according to the invention promotes hemostasis, prevents infection,
and/or relieves pain, delivering one or more features in a
relatively quick time frame. The external wound dressings may be
self-administrable. A exemplary system according to the invention
for treating an external wound is shown in FIG. 12, with the system
comprising a swellable material 19 (such as an absorbent polymer)
disposed behind a porous membrane 20 (such as a telfa pad) to be
placed in contact with the to-be-treated external wound. To the
swellable material 19 optionally may be added one or more of a
clotting promoter (such as thrombin), an antibiotic, an analgesic,
an anesthetic, etc. An impermeable material 21 (such as an
impermeable plastic) is provided for avoiding contact of the
swellable material 19 and/or the membrane 20 with the air, etc. A
fastener system is provided attached to the impermeable material
21, with a fastener system comprising an elastic fastener 22 and a
Velcro material 23 being preferred. A fastener system (such as a
Velcro-free adhesive fastener system, etc.) may be provided
depending on the size and/or location of the wound-to-be
treated.
[0079] While much discussion has been provided of the invention's
use in connection with wounds, especially penetrating wounds, and
limbs, the invention may be extended to other forms of bleeding
(such as intra-abdominal and intra-pleural), including bleeding
that otherwise would be difficult to treat (especially in the acute
setting). The device is placed in the wound, expanded, and held in
place (at least initially) by mechanical pressure.
[0080] The invention further provides a drug delivery system (such
as a time released drug delivery system), usable in the presence of
a wound (such as by insertion into the wound) or absence of a wound
(such as by ingestion, surgical implantation, etc.). Such a drug
delivery system comprises a swelling material and at least one drug
(such as a hemostatic agent, antibiotic, analgesic, etc.). A
swellable material (such as a polymer system) may be used as a drug
delivery system, such as to simultaneously enhance hemostasis,
prevent infection and/or provide pain relief to acute
non-penetrating injuries. E.g., such a drug delivery may be
provided as a self-administered dressing (such as an acute
dressing). Advantageously, such a self-administered dressing may
prolong the "golden period" between injury and treatment.
[0081] While much has been said above about bleeding and medical
applications of the invention, it will be appreciated that the
invention provides leakage control systems extending beyond the
medical and bleeding areas, such as to pressure equalization
techniques for a quick temporary plug for any type of liquid high
pressure leak (such as a plumbing leak, a boating leak, a container
or tanker leak, etc.). Any system where even temporary drops in
pressure due to leakage is a significant problem may benefit from
the inventive pressure equalization methods. Leaks may be treated
by inserting a swellable material into the leak, preferably while
maintaining the swellable material in the leak. Where the leak does
not involve treating a patient, less biocompatibility may be
acceptable than for treatment of wounds, wound dressings, etc. The
swellable material is selected based on the leaking liquid to which
the swellable material will be exposed. Where the leaking liquid is
water or water-based, the water absorbent swellable materials
mentioned above for wound treatment may be used.
[0082] The invention also provides a screening apparatus for
evaluating the efficacy of a particularly formulation of a
swellable material (such as a polymer) when in contact with a
particular leaking material (such as a watery liquid), with an
exemplary screening apparatus that may be used to screen substances
for pressure development during swelling in a confined space shown
in FIG. 3. Substances (such as polymers of varying diameters) may
be tested for compaction, flexibility and ability to rapidly swell
in the presence of liquid. The ability of a substance to produce
pressure in a confined space may be evaluated using a screening
apparatus, such as the exemplary apparatus shown in FIG. 3. With
reference to FIG. 3, a receptable 200 (such as a petri dish) is
provided for receiving a to-be-tested substance 202, such as a
to-be-tested substance is contained in a highly perforated flexible
membrane 201 (such as thin latex). The to-be-tested substance is
placed in the receptable 200 and secured there by a wrap 203 (such
as by a cling gauze wrap), optionally including other materials
such as a gauze pad 205. Liquid to be poured onto the upper surface
of the to-be-tested substance is disposed in a bathing solution
container 204. A pressure probe 206 is placed between the membrane
201 and the wall of the receptable 200. As liquid is poured on the
upper surface of the to-be-tested substance, the pressure within
the confined space 207 is monitored by the pressure probe 206
hooked to pressure monitor 208. A baseline criterion of a certain
amount of generated pressure (preferably, 80 mm Hg) in a certain
time frame (preferably, within 3 minutes or sooner) may be
established.
Example 1A
[0083] In an example of production by electrostatic spraying (or,
more simply, electrospraying), charged droplets are generated at
the tip of a metal needle (or pipette with a wire immersed in the
liquid) with a several kV dc field, and are subsequently delivered
to a grounded target. The droplets are derived by charging a liquid
typically to 5-20 kV, which leads to charge injection into the
liquid from the electrode. The sign of the injected charge depends
upon the polarity of the electrode; a negative electrode produces a
negatively charged liquid. The charged liquid is attracted to an
electrode of opposite polarity some distance away, forming a
so-called Taylor cone at the needle tip, Droplets are formed when
electrostatic repulsions within the liquid exceed its surface
tension. If the liquid is relatively volatile, evaporation leads to
shrinkage of the droplets and an increase in excess charge density,
leading to break-up into smaller droplets. This can happen many
times prior to reaching the target, thereby affording very small
droplets. Relatively dilute polymer solutions deposit as nodules as
the result of electrospraying.
Example 1B
[0084] In an example of production by electrospinning, referring to
FIGS. 1A-1B, polymer solutions or melts 100A are deposited as
fibrous mats 100B (rather than droplets as in electrospraying),
with the advantage taken of chain entanglements in melts or at
sufficiently high polymer concentrations in solution to produce
continuous fibers, such as a PEVA deposited from 15 wt % solution
in chloroform (see FIG. 2B which is a microphotograph of such a
fiber). See Stetzel et al, supra. Electrospinning is believed to be
mechanistically similar to electrospraying, with differences being
that chain entanglements yield a fiber from the Taylor cone.
Moreover, rather than break-up into small droplets, entanglements
lead to splaying of fibers into thinner ones, which is a
particularly attractive aspect of electro spinning.
Example 2A
[0085] Poly(acrylamide-co-acrylic acid copolymer was disposed in
electrospun ethylene-vinyl-acetate (EVA) copolymer bags of
dimensions about 6 cm by 6 cm by about 5 mm thick. The bags were
exposed to water, and the bags were weighed as time progressed,
with the results shown in FIG. 8A where g water/g polymer is
plotted against time (minutes).
Example 2B
[0086] A sample was prepared and tested as in Example 2A, except
that instead of using poly(acrylamide-co-acrylic acid copolymer,
there was used poly(acrylamide-co-acrylic acid copolymer potassium
salt). The results are shown in FIG. 8B.
[0087] While the invention has been described in terms of its
preferred embodiments, those skilled in the art will recognize that
the invention can be practiced with modification within the spirit
and scope of the appended claims.
* * * * *