U.S. patent application number 17/566255 was filed with the patent office on 2022-05-19 for wound sealing powder.
The applicant listed for this patent is Biolife, L.L.C.. Invention is credited to Talmadge Kelly Keene, Mark Travi, Kurt Vadelund.
Application Number | 20220151930 17/566255 |
Document ID | / |
Family ID | |
Filed Date | 2022-05-19 |
United States Patent
Application |
20220151930 |
Kind Code |
A1 |
Vadelund; Kurt ; et
al. |
May 19, 2022 |
WOUND SEALING POWDER
Abstract
A wound sealing powder, method of making a wound sealing powder,
and method of using a wound sealing powder to reduce blood flow
from a wound are provided. Specifically, the wound sealing powder
utilizes a particulate powder material of an effective amount of an
insoluble cation exchange material wherein the majority of the
particles in the powder have particle sizes of less than
approximately 48 microns.
Inventors: |
Vadelund; Kurt; (Apollo
Beach, FL) ; Keene; Talmadge Kelly; (Ruskin, FL)
; Travi; Mark; (Venice, FL) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Biolife, L.L.C. |
Sarasota |
FL |
US |
|
|
Appl. No.: |
17/566255 |
Filed: |
December 30, 2021 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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16274406 |
Feb 13, 2019 |
11241386 |
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17566255 |
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International
Class: |
A61K 9/14 20060101
A61K009/14; A61P 7/04 20060101 A61P007/04; A61P 17/02 20060101
A61P017/02; A61B 17/12 20060101 A61B017/12; A61K 9/00 20060101
A61K009/00 |
Claims
1. A wound sealing composition comprising a particulate powder
consisting essentially of a mixture of a substantially anhydrous
salt ferrate compound and an effective amount of an insoluble
cation exchange material, wherein the powder contains essentially
no particles having a particle size of 158 microns or more.
2. The wound sealing composition of claim 1, wherein the powder
contains essentially no particles having a particle size of 98
microns or more.
3. The wound sealing composition of claim 1, wherein the powder
contains essentially no particles having a particle size of 77
microns or more.
4. A method of making a particulate powder for a wound sealing
composition wherein the powder consists essentially of a
substantially anhydrous salt ferrate compound combined with an
effective amount of an insoluble cation exchange material wherein
the powder contains essentially no particles having a particle size
of 158 microns or more, the method comprising steps of: a) drying
an insoluble cation exchange material to a moisture content of
approximately 3% or less; b) mixing a substantially anhydrous salt
ferrate compound having an average particle size of 2 mm or less
with the cation exchange material at a weight ratio of
approximately 1 to 2, ferrate to cation exchange material; c)
providing the dried cation exchange material at an average particle
size of less than about 70 microns; and d) blending the mixed 1:2
ferrate:cation exchange material with the dried cation exchange
material having an average particle size of less than about 70
microns to obtain an approximate 1 to 7 weight mixture of ferrate
to cation exchange material.
5. The method of claim 4 wherein the dried cation exchange material
at an average particle size of less than about 70 microns is
provided by grinding whole or reduced-size beads of the cation
exchange material.
6. The method of claim 5 where the grinding is performed utilizing
a stirred ball mill.
7. A method of arresting or reducing the blood flow from a wound on
a patient having a blood-letting wound comprising the steps of
applying a wound sealing composition comprising a particulate
powder consisting essentially of a substantially anhydrous salt
ferrate compound combined with an effective amount of an insoluble
cation exchange material wherein the majority of the particles in
the powder have particle sizes of less than approximately 48
microns and allowing a seal to form over the wound so that blood
flow from the wound is reduced.
8. A wound sealing composition comprising a particulate powder
consisting essentially of a ground insoluble cation exchange
material, wherein at least 90% of the particles in the powder have
a particle size of 77 microns or less and wherein no more than 10%,
by weight, of the particles in the particulate powder are unground
particles of the insoluble cation exchange material.
9. The wound sealing composition of claim 8 wherein no more than
5%, by weight, of the particles in the particulate powder are
unground particles of the insoluble cation exchange material.
10. A wound sealing composition comprising a particulate powder
consisting essentially of a ground insoluble cation exchange
material, wherein the majority of the particles in the powder have
particle sizes of less than approximately 48 microns and wherein no
more than a minority of the particles in the particulate powder are
unground particles of the insoluble cation exchange material.
11. The wound sealing composition of claim 10 wherein no more than
5%, by weight, of the particles in the particulate powder are
unground particles of the insoluble cation exchange material.
12. The wound sealing composition of claim 1, 8, or 10 further
comprising a pigment.
13. The wound sealing composition of claim 1, 8, or 10 further
comprising an antimicrobial.
14. The wound sealing composition of claim 1, 8, or 10 further
comprising a multivalent hemostatic salt.
15. A wound sealing composition comprising a particulate powder
consisting essentially of an insoluble cation exchange material,
wherein at least 90%, by weight, of the particles in the powder
have a particle size of 77.4 microns or less and the moisture
content of the powder is 20% or less.
16. The wound sealing composition of claim 15 wherein the moisture
content of the powder is 3% or less.
17. The wound sealing composition of claim 15 wherein the moisture
content of the powder is approximately 1%.
18. A wound sealing composition comprising a particulate powder
consisting essentially of a ground insoluble cation exchange
material wherein the majority of the particles in the powder have
particle sizes of less than approximately 48 microns and the
moisture content of the powder is 20% or less.
19. The wound sealing composition of claim 18 wherein the moisture
content of the powder is 3% or less.
20. The wound sealing composition of claim 18 wherein the moisture
content of the powder is approximately 1%.
21. A compressed tablet comprising the wound sealing composition of
claim 1, 8, 9, 10, 11, 15, 18, or 19.
Description
RELATED APPLICATIONS
[0001] The present application is a division of U.S. patent
application Ser. No. 16/274,406, filed on Feb. 13, 2019, the entire
disclosure of which is incorporated by reference as if set forth
verbatim herein.
FIELD OF THE INVENTION
[0002] The present invention relates generally to hemostatic wound
sealing topically-applied powders that arrest bleeding, and methods
of preparing and using such wound sealing powders.
BACKGROUND OF THE INVENTION
[0003] Hemostatic agents are well known in the prior art. For
example, Patterson et al., U.S. Pat. No. 6,187,347, which is
incorporated herein in its entirety by reference thereto, discloses
a free flowing powder to arrest bleeding from a wound by (1)
providing a substantially anhydrous compound of a salt ferrate
which will hydrate in the presence of blood to produce Fe+++ to
clot blood and produce oxygen; and (2) applying this compound to
the wound for a time sufficient for arresting blood flow, reducing
the microbial population, and forming a protective coating over the
wound. In one embodiment, a cation exchange material is mixed with
the salt ferrate to provide a protective coating over the wound for
protection. The salt ferrate provides the oxygen to substantially
reduce the level of bacteria, virus and fungus at the wound site.
The combination of salt ferrate and an acid cation exchange resin
produces Fe+++ in a form that allows the iron cation to covalently
interact with blood to effect coagulation and create a protective
scab over the wound with antimicrobial properties.
[0004] Hemostatic agents other than powders are also known in the
prior art. For example, U.S. Pat. No. 8,961,479, Hen, et al., which
is incorporated herein in its entirety by reference thereto,
discloses a tablet form made from a hemostatic powder that may
include potassium ferrate and a cation ion exchange resin
(sometimes referred to as a hydrogen resin). The powder is pressure
formed into a tablet for delivery to a bleeding wound. The tablet
improves the rate of adhesion to a bleeding wound surface, and
allows a significantly greater and more uniform pressure to be
exerted by manual compression of the tablet on the wound site, as
compared to that of a thin layer of scattered hemostatic powder.
After the seal is formed from the interaction of blood or exudates
with the immediate contacting surface of the tablet, the bulk of
the unused tablet easily delaminates from the seal making clean-up
easier. If the unused portion of the tablet is not removed from the
wound site, a reservoir of hemostatic dressing stops further
bleeding. The tablet may be applied to any surface orientation and
take any shape and thickness possible. Unlike known hemostatic
powders, a tablet may be applied to a vertical surface.
[0005] In making the wound sealing powder disclosed by Patterson,
the cation exchange resin is prepared in the washed hydrogen form,
dried at approximately 110.degree. C. for 24 hours and then
powdered in a grinder to about 100 mesh size. A 100 mesh powder
particle is 149 microns (or 0.149 mm) in diameter.
[0006] WoundSeal.RTM. topical powder is a commercially available
(in 2018) wound sealing product for arresting bleeding from a
wound. The current WoundSeal.RTM. topical powder consists of a
hydrophilic polymer (such as the hydrogen resin referred to above)
and potassium ferrate. To use WoundSeal.RTM. topical powder, the
wound is first cleaned and the powder is poured onto the wound
after bleeding resumes because blood must be present for the powder
to work.
[0007] A flow chart representing the steps in making the 2018
Version of WoundSeal.RTM. topical powder is set forth in FIG. 4 and
is described as follows. The hydrogen resin may be the hydrogen
form of 2% crosslinked, sulfonated polystyrene resin. The hydrogen
resin may be available in whole insoluble, generally round, beads
having an average particle size of approximately 500 microns in
diameter (for purposes of this specification, "diameter" and
"particle size", with respect to a particle or particles, are
synonymous), or alternatively, the resin may be available in, or
ground into, much finer fragments averaging in size from 80 microns
to 200 microns in diameter.
[0008] The hydrogen resin (with Purolite CT122 available from
Purolite Corporation of Bala Cynwyd, Pa. being a suitable such
resin) is initially dried, for example, in an oven at a temperature
of approximately 100.degree. C. to 110.degree. C. for an average of
121/2 days, depending on the ambient moisture. The goal of drying
the resin is to achieve a moisture content of 3% or less, and
typically a moisture content of approximately 1%. During the drying
process, the particle size of the resin is typically reduced due to
the dehydration of the water molecules from the resin. Drying the
resin reduces the ability for the resin to transport or exchange
protons, and, therefore, a dry resin is rendered generally inert.
It is necessary to dry the resin to a certain degree if the resin
is to be mixed with another dry proton acceptor.
[0009] The ferrate may be purchased or may be produced by mixing
iron oxide with an oxidizing agent and then heating, until ferrate
cakes are produced. When ferrate cakes are used, the cake is broken
into smaller pieces, typically manually or with known machinery,
and then a knife grinder, or other known suitable device, is used
to break up the cake. In a typical instance, a knife grinder with a
2 mm screen may be used. This breaking process results in the
ferrate having a particle size of 2 mm or less in diameter.
[0010] WoundSeal.RTM. topical powder is typically made from an
approximately 1:7 weight mixture of potassium ferrate:hydrogen
resin, although weight mixtures ranging from 1:3 to 1:12 will
adequately arrest bleeding, depending on the particular
application. In one embodiment, the ferrate (after breaking) and
the resin (after drying) are mixed and then ground in a Turbo Mill,
which is a rotor mill style grinder that utilizes a high speed
rotor contained in a grinding chamber with a screen that reduces
the particle size through impact with the rotor and screen. The
particle size is controlled via rotor speed and screen opening
size. Based on the size of the unground beads and the size of the
openings in the grinding screen, a fraction of the unground (whole)
bead will pass through the grinding process and there is typically
no post-grind screening process.
[0011] The Turbo Mill has a continuous feed into the mill, and a
continuous flow of particles out of the mill of particles that have
passed through the control screen. The screen used in this
embodiment is a 1 mm screen and the mill is run at a production
speed of 20 kg/hr to 25 kg/hr to obtain the WoundSeal.RTM. topical
powder. After production, the powder is stored in closed
containers, such as plastic tubs, in order to deter re-hydration
until the powder can be packaged in consumer-ready packaging for
sale.
[0012] Although WoundSeal.RTM. topical powder is a reliable,
hemostatic product, users have indicated a need for certain
improvements to the product. First, users have noted that the color
of the product is less than desirable, often described as appearing
"dirty" or having the color of dirt. This color contrasts greatly
with certain skin coloration and is noticeable when in use. Second,
users have noted that achieving adherence to an angled or near
vertical skin surface is difficult. The powder is readily applied
to horizontal surfaces, such as when the patient's wound is in a
near horizontal position. The unground portion of resin (the
remaining generally round beads) causes the powder to spread out
relatively evenly on a completely horizontal surface. However, when
the powder is applied to a more vertical surface, such as the
patient's face or neck area, or a curved or irregular surface, such
as the patient's arm, the powder 2018 version of WoundSeal.RTM.
topical powder tends to roll off. Some of the powder is wasted as
it falls off and fails to achieve cohesion to other particles or
adhesion with the more vertical or rounded skin surface.
[0013] Thus, there is a need to have an effective wound-sealing
powder that exhibits more acceptable color to consumers and that
allows for less waste, more adhesion of the powder onto more
vertical surfaces of the body, and greater cohesiveness of the
powder. The present invention attempts to fulfill those long-felt
needs.
[0014] The foregoing examples of the related art and limitations
related thereto are intended to be illustrative and not exclusive.
Other limitations of the related art will become apparent to those
skilled in the art upon a reading of the specification and a study
of the drawings.
SUMMARY OF THE INVENTION
[0015] Briefly, the present invention is directed, in an
embodiment, to a composition useful as a wound sealing powder that
comprises a particulate powder consisting essentially of a
substantially anhydrous salt ferrate compound combined with an
effective amount of an insoluble cation exchange material wherein
the particle size distribution range of the particles in the powder
is 160 microns or less.
[0016] In another embodiment, the invention is directed to a wound
sealing composition comprising a particulate powder consisting
essentially of a substantially anhydrous salt ferrate compound
combined with an effective amount of an insoluble cation exchange
material wherein the majority of the particles in the powder have
particle sizes of less than approximately 48 microns.
[0017] In another embodiment, the invention is directed to a wound
sealing composition comprising a particulate powder consisting
essentially of a substantially anhydrous salt ferrate compound
combined with an effective amount of an insoluble cation exchange
material wherein the powder contains essentially no particles
having a particle size of 158 microns or more.
[0018] In other embodiment, the invention is directed to a method
of making a particulate powder for a wound sealing composition
wherein the powder consists essentially of a substantially
anhydrous salt ferrate compound combined with an effective amount
of an insoluble cation exchange material wherein the powder
contains essentially no particles having a particle size of 158
microns or more, the method comprising steps of drying an insoluble
cation exchange material to a moisture content of approximately 3%
or less; mixing a substantially anhydrous salt ferrate compound
having an average particle size of 2 mm or less with the cation
exchange material at a weight ratio of approximately 1 to 2,
ferrate to cation exchange material; providing the dried cation
exchange material at an average particle size of less than about
70; blending the mixed 1:2 ferrate:cation exchange material with
the dried cation exchange material having an average particle size
of less than about 70 microns to obtain an approximate 1 to 7
weight mixture of ferrate to cation exchange material.
[0019] In yet another embodiment, the invention is directed to a
method of arresting or reducing the blood flow from a wound on a
patient having a blood-letting wound comprising the steps of
applying a wound sealing composition comprising a particulate
powder consisting essentially of a substantially anhydrous salt
ferrate compound combined with an effective amount of an insoluble
cation exchange material wherein the majority of the particles in
the powder have particle sizes of less than approximately 48
microns and allowing a seal to form over the wound so that blood
flow from the wound is reduced.
[0020] In another embodiment, the invention is directed to a wound
sealing composition comprising a particulate powder consisting
essentially of a ground insoluble cation exchange material wherein
the particle size distribution range of the particles in the powder
is 160 microns or less. And, in another embodiment, the invention
is directed to a wound sealing composition comprising a particulate
powder consisting essentially of a ground insoluble cation exchange
material wherein the majority of the particles in the powder have
particle sizes of less than approximately 48 microns.
[0021] In yet another embodiment, the invention is directed to a
wound sealing composition comprising a particulate powder
consisting essentially of an insoluble cation exchange material
wherein the particle size distribution range of the particles in
the powder is 160 microns or less and the moisture content of the
powder is 20% or less. And, in yet another embodiment, the
invention is directed to a particulate powder consisting
essentially of a ground insoluble cation exchange material wherein
the majority of the particles in the powder have particle sizes of
less than approximately 48 microns and the moisture content of the
powder is 20% or less.
BRIEF DESCRIPTION OF THE DRAWINGS
[0022] FIG. 1A illustrates the angle of repose for the powder
particles of the present invention.
[0023] FIG. 1B illustrates a magnified portion showing the powder
particles of FIG. 1A.
[0024] FIG. 2 illustrates the particle size distribution of the
inventive wound sealing powder ("Inv. Process") versus the particle
size distribution of the 2018 Version of WoundSeal.RTM. ("WS")
topical powder and two test powders (Test #1, Test #2) in table
form.
[0025] FIG. 3 illustrates the same particle size distribution of
FIG. 2 in the alternate graph form ("BP03 1.0 mm" is the 2018
Version of WoundSeal.RTM. topical powder; "BP03 0.35 mm" and "BP03
0.25 mm" are Test #1 and Test #2), and "BP08 Process" is the
topical powder of the present invention).
[0026] FIG. 4 illustrates the process of making the 2018 Version of
WoundSeal.RTM. topical powder in flow chart form.
[0027] FIG. 5 illustrates the process of making the inventive wound
sealing powder in flow chart form.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
[0028] Reference now will be made in detail to the embodiments of
the invention, one or more examples of which are set forth below.
Each example is provided by way of explanation of the invention,
not a limitation of the invention. In fact, it will be apparent to
those skilled in the art that various modifications and variations
can be made in the present invention without departing from the
scope or spirit of the invention. For instance, features
illustrated or described as part of one embodiment, can be used on
another embodiment to yield a still further embodiment. The
following embodiments and aspects thereof are described and
illustrated in conjunction with systems, tools and methods which
are meant to be exemplary and illustrative and not limiting in
scope. In various embodiments one or more of the above-described
problems have been reduced or eliminated while other embodiments
are directed to other improvements.
[0029] Thus, it is intended that the present invention covers such
modifications and variations as come within the scope of the
appended claims and their equivalents. Other objects, features and
aspects of the present invention are disclosed in or are obvious
from the following detailed description. It is to be understood by
one of ordinary skill in the art that the present discussion is a
description of exemplary embodiments only, and is not intended as
limiting the broader aspects of the present invention.
[0030] It should be understood that the examples and embodiments
described herein are for illustrative purposes only and that
various modifications or changes in light thereof will be suggested
to persons skilled in the art and are to be included within the
spirit and purview of this application and the scope of the
appended claims. In addition, any elements or limitations of any
invention or embodiment thereof disclosed herein can be combined
with any and/or all other elements or limitations (individually or
in any combination) or any other invention or embodiment thereof
disclosed herein, and all such combinations are contemplated with
the scope of the invention without limitation thereto.
[0031] Ion exchange resins are typically prepared as spheres with a
particle size that typically range from less than 10 microns for
high pressure liquid chromatography, from 40 microns to 250 microns
for ingestible drug delivery resins, and from 300 microns to 1200
microns for some industrial applications. These sizes are fully
hydrated sizes, because the vast majority of all resin is used in
the fully hydrated state. Resin, as manufactured, has an average
size (diameter) with a Gaussian distribution, and the variation of
bead size is based on the manufacturing process. The resin can then
be further sized by grinding and/or fractional screening to acquire
the proper size to suit an application. For drug delivery systems,
similar sizes with a narrow Gaussian distribution are needed to
ensure consistent delivery. For industrial liquid processing
applications using an ion exchange resin bed, if the size
distribution is too broad, the bead stacking will be affected and
flow characteristics through the bed will be impeded, resulting in
high pressure drops across the column of the ion exchange resin.
The pressure drop increase occurs because the smaller particles can
fit into the spaces between the larger particles, thus impeding
liquid flow.
[0032] When a dry strong acid cation resin in hydrogen form
(hereinafter SACR-H) is applied to blood, the SACR-H floats on the
blood surface, rapidly absorbing liquid from the blood. The pores
of the resin are too small to absorb blood solids or large
proteins. This rapid absorption of the liquid, while excluding the
blood solids, causes the solids to stack up beneath the SACR-H.
These solids continue to stack until the liquid can no longer be
transferred through the barrier of blood cells that have been
formed. If this barrier is pushed into contact with a surface it
will adhere to the surface, due to the natural glue-like nature of
dried blood. If this surface is a bleeding wound, then the barrier
will adhere to the wound site and stop further bleeding.
[0033] If dry, essentially round, SACR-H beads are poured onto a
bleeding site, the beads that contact the blood will adhere to the
blood, but additional beads will simply roll off the wound site,
particularly if the wound site is not positioned horizontally, but
is instead more vertical such as the neck, chest, or head region of
a standing patient. This is also observed where the wound site is
on a curved portion of the body, such as an arm, finger, or toe. A
monolayer of beads that may adhere to such rounded or more
vertically-positioned skin surfaces will provide less adequate
absorption capacity and a reduced ability to stop a bleeding wound
without multiple applications. Several layers may be needed to
absorb sufficient liquid from the blood to create a barrier of
sufficient strength to stop bleeding from a wound.
[0034] The inventors have found that, in order to solve this need
to adhere more of the powder at the wound site, the resin may be
ground to smaller particles so that the angle of repose when the
powder is applied is increased because the frictional contact area
from particle to particle (i.e., cohesion between particles) is
increased. Typically, the amount of unground, relatively round
beads remaining in the inventive powder will be 5% or less in the
final powder. These effects are shown in FIG. 1A and, in magnified
form, 1B.
[0035] This increase in angle of repose allows for multiple layers
of powder to remain over a bleeding wound while reducing the amount
of material that readily falls off the wound site during
application. In addition to an increase in angle of repose, the
increased angularity also allows the product to adhere better to a
more inclined or curved wound surfaces. The angle of repose
obtained with the present inventive wound sealing powder is
typically in the range of 40.degree. to 50.degree. as compared to
the angle of repose typically found with the currently available
WoundSeal.RTM. topical powder which ranges from 25.degree. to
30.degree.. The newly invented powder has both better cohesion
between particles and better adhesion to the patient or wound
site.
[0036] SACR-H has a negative pKa (indicative of a strong acid),
similar to that of hydrochloric acid. When applied to blood, a
portion of the hydrogen atoms attached to the resin backbone are
neutralized, but the remaining hydrogen atoms on the resin backbone
have anti-bacterial properties. Due to stacking properties, if
whole beads are applied and adhered to a blood barrier above a
wound, there will be spaces between the beads large enough for
bacterial intrusion versus the tightly-spaced packing created by a
more finely ground SACR-H product.
[0037] However, a powder that is ground too finely could create a
small dust cloud when applied. In addition, if the particles are
too small, they may also create lung inhalation issues. To overcome
some of these traits, in certain embodiments, additional
coagulating agents or wound healing agents may be combined with the
SACR-H.
[0038] To fulfill the long-felt need of increasing the adhesion of
the powder to all skin surfaces by increasing the cohesion amongst
the particles, appropriate starting materials with the appropriate
grinding and screening methodologies are employed. Screening out
the "too low" and "too high" fractions or particle sizes results in
a narrower and lower range of particle size distribution allowed by
the present invention in order to provide the required adhesiveness
to the wound.
[0039] In the present invention, SACR-H used in the hemostatic
powder is purchased from a supplier as spherical beads ranging in
size from 150 microns to 1000 microns after drying to a moisture
content of less than about 3% (although, typical drying results in
a moisture content of approximately 1% or less). The dried SACR-H
resin beads are then ground to a suitable particle size
distribution to disperse onto a wound to result in a good adhesion
to reduce the amount of powder that fails to adhere to the wound
and simply falls off the skin surface during application.
[0040] Another benefit of the use of a SACR-H with a smaller
particle size distribution that meets another of the long-felt
needs is that the resulting powder becomes lighter in color. Unlike
the 2018 version of WoundSeal.RTM. topical powder, which is
typically a dark amber brown color, the present inventive wound
sealing powder exhibits a color that more buff tan and which more
closely matches a Caucasian skin color. This more favorable color
has major marketing implications as an acceptable product in that
the more uniform buff tan color is more consistent and is not
perceived as being a "dirty brown" powder. The more finely ground
powder has a color and texture more similar to that of a cosmetic
material.
EXAMPLE 1
[0041] In this example, a wound sealing powder that exhibits better
adhesion and cohesion properties and a more acceptable uniform
color than the 2018 version of WoundSeal.RTM. topical powder is
made as shown in the flow chart set forth in FIG. 5 and as
described below.
[0042] One hydrogen resin that may be employed is Purolite CT122
available from Purolite Corporation of Bala Cynwyd, Pa. However, it
will be understood by one of ordinary skill in the art that other
hydrophilic cationic resins in hydrogen form may be used. The
particular resin employed in one embodiment has a particle size
distribution of: 1) up to 10% of greater than 1400 microns; 2) up
to 5% of less than 850 microns; and 3) up to 2% of less than 425
microns, with the primary particle size range being from 850
microns to 1400 microns.
[0043] Initially, the resin is dried, for example, in a static
dryer such as an oven at a temperature of approximately 100.degree.
C. to 110.degree. C. for an average of 121/2 days. The variation of
drying time may be depending on the drying conditions, including
but not limited to ambient moisture. The goal of drying the resin
is to achieve a moisture content of 3% or less, and typically a
moisture content of approximately 1%, this drying process converts
the resin from an active proton exchange state to a relatively
inactive proton exchange state until rehydrated. During the drying
process, the particle size of the resin is typically reduced due to
the dehydration of the water molecules from the resin.
[0044] The ferrate may be purchased or may be produced by cooking
iron oxide with an oxidizing agent and then heating, until ferrate
"cakes are produced. When ferrate cakes are used, the cake is
broken into smaller pieces, typically manually or with known
machinery, and then a knife grinder, or other known suitable
device, is used to break up the cake. In a typical instance, a
knife grinder with a 2 mm screen may be used. This breaking process
results in the ferrate having a particle size of 2 mm or less in
diameter.
[0045] The first step in the powder mixing process is to mix the
screened ferrate (2 mm screen) with dried resin at a ratio of 1:2
ferrate:hydrogen resin. This mixture may then be subjected to
grinding in a Turbo Mill (described above) using a 0.25 mm screen
at a production rate, for example, of 20 to 25 kg/hr to obtain an
intermediary product.
[0046] The next step is to grind dried hydrogen resin alone in an
Attritor Mill at a production rate, for example, of 20 kg/hr to 25
kg/hr. Unlike the Turbo Mill, an Attritor Mill is a stirred ball
mill that uses larger hard stainless steel spheres (for example, 9
mm-10 mm in diameter) agitated by rotating agitator arms to crush
smaller and softer material. The grinding action is caused by the
impact of the stainless steel spheres, agitator arms, and sides of
the grinding tank. Particle size is controlled via agitator arm
speed, size of grinding media, and grinding time. In one particular
embodiment, the Attritor Mill is used to grind the dried hydrogen
resin to an average particle size of approximately 40 microns (but
one of ordinary skill in the art will appreciate that average
particle sizes of up to 70 microns would be suitable for the
present invention).
[0047] This 40 micron-sized dried resin is then blended with the
1:2 ferrate:hydrogen resin mixture to obtain an approximately 1:7
weight mixture of ferrate:hydrogen resin, although weight mixtures
ranging from 1:3 to 1:12 will adequately arrest bleeding, depending
on the particular application. After blending, the powder is stored
in closed containers, such as plastic tubs, in order to deter
re-hydration until the powder can be packaged in consumer-ready
packaging for sale.
[0048] FIG. 2 (table form) illustrates the particle size
distributions of the inventive wound sealing powder ("Inv.
Process") versus the particle size distribution of the 2018 Version
of WoundSeal.RTM. ("WS") topical powder and two test powders (Test
#1, Test #2). Likewise, FIG. 3 (graph form) illustrates the same
particle size distribution of FIG. 2 ("BP03 1.0 mm" is the 2018
Version of WoundSeal.RTM. topical powder; "BP03 0.35 mm" and "BP03
0.25 mm" are Test #1 and Test #2), and "BP08 Process" is the
inventive wound sealing powder).
[0049] As shown in FIG. 2, wound sealing powders consisting of the
ferrate and resin mixture, including WoundSeal.RTM. topical powder
as it existed in 2018 and before and two test wound sealing powders
that are not commercially available and that heretofore have not
been disclosed, demonstrated a particle size distribution ranging
from approximately 100 microns to approximately 700 microns when
employing a 1.0 mm screen (WoundSeal.RTM. topical powder 2018
Version); from approximately 60 microns to approximately 700
microns when employing a 0.35 mm screen (Test #1); and from
approximately 60 microns to approximately 200-300 microns when
employing a 0.25 mm screen (Test #2). In contrast, the present
inventive powder and process results in a particle size
distribution ranging from approximately 2 microns to 158
microns.
[0050] In the wound sealing powders screened with a 1.0 mm screen
(WoundSeal.RTM. topical powder 2018 Version) or 0.35 screen (Test
#1), the majority of particles (approximately 65%) had a particle
size of more than approximately 158 microns; and screened with a
0.25 mm screen (Test #2), the majority of particles (approximately
80%) had a particle size of more than approximately 98 microns. In
contrast, the inventive wound sealing powder had essentially no
particle sizes (0.3%) of more than approximately 158 microns and
only a small minority (3.9%) of particles more than approximately
98 microns. For purposes of this specification "essentially no
particles sizes" means 10% or less of the particles have the stated
diameter.
[0051] In further comparison, none of the wound sealing powders
analyzed had particle sizes less than about 48 microns but the
inventive wound sealing powder had an overwhelming majority of
particles sized (83.3%) less than 48 microns.
[0052] As shown in FIG. 3, the median particle size for the tested
wound sealing powders screened with 1.0 mm (WoundSeal.RTM. topical
powder 2018 Version) and 0.35 mm (Test #1) screens was
approximately 190 microns and for those screened with 0.25 mm (Test
#2) screens was approximately 110 microns. In contrast, the median
particle size for the inventive wound sealing powder is
approximately 55 microns.
[0053] The comparative bulk densities of the products are
approximately 0.75 g/cc for the 2018 Version of WoundSeal.RTM.
topical powder and approximately 0.60 g/cc for the inventive wound
sealing composition.
[0054] Unexpected Results
[0055] The inventive wound sealing powder was found to exhibit
several unexpected results when applied to a wound in the same
manner as the 2018 Version of the WoundSeal.RTM. topical
powder.
[0056] First, one of ordinary skill in the art would expect a finer
ground power due to the migration activity of smaller particles.
However, during end-user testing in a hospital setting, the
finer-ground inventive powder was found to be less messy than the
2018 version of WoundSeal.RTM. topical powder.
[0057] Second, the color of the powder was lighter and more
appealing to the hospital staff. The new inventive powder looks
more like makeup, than dirt.
[0058] It was also unexpectedly found that the inventive more
uniform and more finely ground powder, when compressed into a
tablet, exhibits a reduction in deterioration rate caused by
atmospherically-absorbed moisture. A tablet made with from the
powder used to make the 2018 version of WoundSeal.RTM. topical
powder deteriorates to the point that it cannot be properly handled
and packaged if exposed to typical atmospheric conditions.
[0059] Third, the more uniformly ground particles of the present
invention expand at a more similar rate, thus unexpectedly keeping
the powder in better and longer position on a vascular catheter
site as compared to the larger powder particles of the 2018 version
of WoundSeal.RTM. topical powder.
[0060] Another unexpected result of the newly invented powder is
that when the powder is compressed into a tablet the reduction in
overall bulk expansion of the mass of particle create a table with
more structural integrity as it absorbs moisture from the
surrounding air. The dried material will uptake water from the
surrounding air and expand. Tablets created with the finer powder,
nearly void of spherical particles, are more uniform in appearance,
and the resulting tablets are harder than tablets created with the
2018 powder under the same compression force.
[0061] In addition to the tablets being harder and stronger, the
tablets can be manufactured thinner. This reduction in heights will
reduce the likelihood for a compressed tablet to create a pressure
ulcer in a patient. The minimum height limit for the 2018 powder is
thicker than the newly invented powder due to the number of round
particles that will not tightly interlock. Even with the tightly
interlocking of the newly invented powder tablets, and lack of
expansion in air, the tablets will still delaminate upon
application to a bodily liquid. The difference in expansion
characteristics in air and upon application to a bodily liquid is
the due to the difference in relative expansion within the
tablet.
[0062] In addition, the dried blood barrier that is created between
the powder and the wound also lessens interaction between the wound
and any pigments that are added to affect the final color of the
product, including entrapment as the wound heals. These and other
unexpected results demonstrate the patentability of the presently
claimed wound sealing powder.
[0063] Finally, it is to be understood that the described grinding
and formation processes above could be utilized to form a wound
sealing powder consisting of only the hydrogen resin (without the
ferrate or pigment), and without the 3% moistures level constraint,
as described in U.S. patent application Ser. No. 14/147,143, which
is incorporated by reference herein in its entirety.
[0064] All references cited in this specification, including
without limitation, all papers, publications, patents, patent
applications, provisional patent applications, presentations,
texts, reports, manuscripts, brochures, books, internet postings,
journal articles, and/or periodicals are hereby incorporated by
reference into this specification in their entireties, including
all figures and tables, to the extent they are not inconsistent
with the explicit teachings of this specification. The discussion
of the references herein is intended merely to summarize the
assertions made by their authors and no admission is made that any
reference constitutes prior art. Applicants reserve the right to
challenge the accuracy and pertinence of the cited references.
[0065] These and other modifications and variations to the present
invention may be practiced by those of ordinary skill in the art,
without departing from the spirit and scope of the present
invention, which is more particularly set forth in the appended
claims. In addition, it should be understood that aspects of the
various embodiments may be interchanged in whole or in part.
Furthermore, those of ordinary skill in the art will appreciate
that the foregoing description is by way of example only, and is
not intended to limit the invention so further described in such
appended claims. Therefore, the spirit and scope of the appended
claims should not be limited to the description of the versions
contained therein.
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