Note: Descriptions are shown in the official language in which they were submitted.
CA 02808263 2013-02-14
Use of a polyurethane foam
as a wound dressing in negative pressure therapy
The invention relates to a device for negative pressure wound therapy
comprising (a) a
cover material for air-tight sealing of the wound space; (b) as applicable a
means for the
connection of a negative pressure source and (c) a wound dressing comprising
an open-
cell polyurethane foam, whereby the open-cell polyurethane foam has special
characteristics, in particular a tensile strength after three days of storage
in bovine
serum, measured in accordance with DIN 53571, between 80 kPa and 300 kPa. The
invention further relates to the use of said an open-cell polyurethane foam as
a wound
dressing in negative pressure wound therapy.
A wound is defined as the separation of the coherence of tissues of the outer
body of
humans or animals. It can result in a loss of substance.
Devices for the negative pressure wound therapy are known in the prior art.
For example
WO 1993/009727 Al describes a device to promote healing of the wound by the
application of a negative pressure on the skin area which is wounded and the
area
surrounding the wound. The device according to WO 1993/009727 Al comprises a
negative pressure device to generate the negative pressure, an air-tight cover
of the
wound which has a functional connection with the negative pressure device, as
well as a
wound dressing for positioning on the wound inside the air-tight cover.
Devices for the negative pressure wound therapy are commercially available,
for example
the V.A.C. device from the company KCI. Commercially available devices often
use a
wound dressing which contains an open-cell polymer foam such as polyvinyl
alcohol
(PVA) or polyurethane (PU).
The commercially available foam dressings are compressed to a different
degree,
depending on the negative pressure applied. This can cause a constriction of
the
passages necessary for the removal of the wound exudate. Adhesion of the foam
with the
wound can also occur. Newly formed tissue can grow into the wound. This
problem is a
familiar complication in the negative pressure therapy of wounds (FDA
complaint data
base). In order to solve this problem, additional wound contact layers are
often
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CA 02808263 2013-02-14
introduced between the foam and the wound, for example a film (see, for
example,
W02001/85248). However, these additional wound contact layers can reduce the
passage of wound exudate.
When the wound dressing is to be changed, elaborate measures have to be taken
to
remove adhered foam, for example by rinsing with Ringer's solution. Tissue
which has
grown into the foam can lead to a tissue traumatization when the wound
dressing is
removed and thus delay the healing process.
When conventional wound dressings are used, particles of foam can also enter
the
wound. These can irritate the wound and delay the healing process. This
problem is
aggravated if the wound dressing is cut to the size of the wound before being
applied, as
this results, in particular, in loose foam particles at the cut edges.
It is the object of the present invention to further improve negative pressure
wound
therapy and to overcome the disadvantages of the prior art. The invention
provides
devices and methods for negative pressure wound therapy, with which a therapy
can be
carried out as effectively and gently as possible. In particular, the
invention is aimed at
preventing the build-up of foam particles in the wound.
Unexpectedly, the objects could be solved by the use of a wound dressing
comprising a
special polyurethane foam. In particular, it was found that it was possible to
simulate
the conditions prevailing in negative pressure therapy by the storage of the
polyurethane
foam in bovine serum. If the polyurethane foam is selected in such a way that
after three
days of storage in bovine serum it has an advantageous tensile strength, this
leads to a
surprisingly sharp reduction of undesired foam particles in the wound. It was
also found
that it is possible to obtain polyurethane foams which solve the
aforementioned objects
unexpectedly advantageously if certain other physical parameters are present
and the
starting materials are appropriately selected.
The object of a first aspect of the invention is, therefore, a device for
negative pressure
wound therapy comprising
(a) a cover material for air-tight sealing of the wound space;
(b) as applicable, a means for the connection of a negative pressure source;
and
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CA 02808263 2013-02-14
(c) an open-cell polyurethane foam as a wound dressing, obtainable by reaction
of a
mixture comprising the components
(i) polyisocyanate,
(ii) polyol, in particular polyester polyol,
(iii) blowing agent, and
(iv) catalyst,
whereby the open-cell foam, after three days of storage in bovine serum,
preferably has a
tensile strength, measured in accordance with DIN 53571, between 80 kPa and
300 kPa.
The object of a second aspect of the invention is, therefore, a device for
negative pressure
wound therapy comprising
(a) a cover material for air-tight sealing of the wound space;
(b) as applicable, a means for the connection of a negative pressure source;
and
(c) an open-cell polyurethane foam as a wound dressing, obtainable by reaction
of a
mixture comprising the components
(i) polyisocyanate,
(ii) polyol, in particular polyester polyol,
(iii) blowing agent, and
(iv) catalyst,
whereby the open-cell polyurethane foam preferably has an air permeability of
1,000 to
8,000 1/(m2sec), measured in accordance with DIN EN ISO 9237.
The object of a third aspect of the invention is, therefore, a device for
negative pressure
wound therapy comprising
(a) a cover material for air-tight sealing of the wound space;
(b) as applicable, a means for the connection of a negative pressure source;
and
(c) an open-cell polyurethane foam as a wound dressing, obtainable by reaction
of a
mixture comprising the components
(i) polyisocyanate, selected from MDI, PMDI, TDI and/or HDI,
(ii) polyester polyol, which is preferably obtainable by reaction of a
dicarboxylic acid with
4 to 8 carbon atoms with a µli.lcohol with 2 to A carbon .toms, and/or
preferably has a
weight average molecular weight of 500 to 4.000 g/mol,
(iii) blowing agent, and
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CA 02808263 2013-02-14
(iv) catalyst.
The invention also includes any combinations of the cited aspects.
A further object of the invention is the use of the open-cell polyurethane
foam (c)
described above in the three aspects, e.g. the use of an open-cell
polyurethane foam
which has a tensile strength after three days of storage in bovine serum,
measured in
accordance with DIN 53571, between 80 kPa and 300 kPa, as a wound dressing for
or in
negative pressure wound therapy.
The new device in accordance with the present invention or the use of the
wound
dressing in accordance with the present invention is distinguished by several
unexpected advantages.
In particular, by selection of the characteristics of the foam it was possible
to
advantageously reduce the number of undesirable particles entering the wound.
The use of the wound dressing in accordance with the present invention also
improved
the atraumatic characteristics so that a negative pressure therapy was
possible without
additional wound contact layers.
The wound dressing in accordance with the present invention allows adequate
drainage
of wound exudates, feels relatively pleasant and thus leads to an increase in
patient
compliance (observance of the therapy instructions by the patient).
The components (a) to (c) of the device in accordance with the present
invention are
described in the following.
The device in accordance with the present invention comprises a cover material
(a) for
air-tight sealing of the wound space. The wound space is regarded as the wound
and the
area surrounding the wound. "Air-tight sealing" does not mean that there is no
exchange
of gas between the wound space and its surroundings. Rather, "air-tight
sealing" in this
context means that, taking into account the vacuum pump used, the negative
pressure
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_ CA 02808263 2013-02-14
necessary for the negative pressure wound therapy can be maintained. This
means that
cover materials can also be used which have a slight degree of gas
permeability as long
as the negative pressure necessary for the negative pressure wound therapy can
be
maintained.
In a preferred embodiment of the invention, the cover material for the air-
tight sealing of
the wound includes a water-insoluble polymer, or a metal foil. The cover
material
preferably has a thickness of 10 pm to 10,000 pm, in particular from 25 pm to
100 pm.
In a preferred embodiment of the invention, the cover material (a) is a water-
insoluble
polymer. Preferably the water-insoluble polymer has a solubility of 10 mg/1 or
less, more
preferably of 1 mg/ml or less, particularly from 0.0001 to 1 mg/ml (determined
in
accordance with the column elution method pursuant to EU Directive RL67-
548EEC,
Annex V, Chapter A6). Examples include polyurethane, polyester, polypropylene,
polyethylene, polyamide or polyvinyl chloride, polyorganosiloxane (silicone),
or a mixture
thereof. The cited polymers are preferably provided in non-cellular form.
It has been demonstrated that the objects explained at the beginning can be
solved in a
particularly advantageous manner using a cover material with a specific water
vapor
permeability. In a preferred embodiment, the cover material thus has a water
vapor
permeability of 100 to 2,500 g/m2 x 24h, more preferably from 500 to 2,000
g/m2 x 24h,
and even more preferably from 800 to 1,600 g/m2 x 24h, in particular from
1,050 to
1,450 g/m2 x 24h, determined in accordance with DIN EN 13726-2 at 23 C and
85%
relative humidity. In particular, the combination of a cover film (a) having
the
aforementioned water vapor permeability with an open-cell polyurethane foam
having
the physical properties described below is particularly advantageous.
The device in accordance with the present invention for negative pressure
wound
therapy comprises a means (b) for the connection of a negative pressure
source, i.e. a
means for the generation of a negative pressure in the wound space. In a
preferred
embodiment, this is a means (b) for the functional connection of the wound
space with a
negative pressure source outside of the cover material so that a negative
pressure can be
generated in the wound space and fluids can be sucked out of the wound space.
The expression "negative pressure in the wound space" in the context of the
invention
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describes an air pressure which is lower inside the wound dressing compared to
the
atmospheric pressure. "Within the wound dressing" refers to the cavity formed
between
the cover material and the wound.
The pressure difference between the air pressure inside the wound dressing and
the
atmospheric pressure is stated in the context of the invention in mm Hg
(millimeters of
mercury), as this is the convention in negative pressure therapy. 1 mm Hg
corresponds
to one torr or 133.322 Pa (Pascal). In the context of the invention, the
negative pressure,
i.e. the pressure difference between the pressure inside the wound dressing
and the
atmospheric pressure, is stated as a positive numerical value in mm Hg.
In one embodiment of the invention, the negative pressure is at least 25 mm Hg
up to a
maximum of 250 mm Hg, preferably at least 50 mm Hg up to a maximum of 150 mm
Hg. This negative pressure range has proved suitable for wound healing. In a
preferred
embodiment of the invention, the negative pressure is at least 80 mm Hg up to
a
maximum of 140 mm Hg, more preferably at least 120 mm Hg up to a maximum of
130
mm Hg.
The device in accordance with the present invention for negative pressure
wound
therapy preferably comprises, as set out above, a means (b) for connection of
a negative
pressure source, i.e. a means for the functional connection of the wound space
with a
negative pressure source outside of the cover material.
The functional connection can be generated, for example, by a connection line
or by a
negative pressure connector. Negative pressure connectors are known to those
skilled in
the art as "ports".
In one embodiment, the means (b) is a connection line, preferably a tube, in
particular a
silicone drainage tube. The connection line can be ducted through the cover
material.
Alternatively, the at least one connection line can be led under the edge of
the cover
material. In both cases the penetration point must be sealed air-tight so that
the desired
negative pressure can be maintained in the dressing.
In a further preferred embodiment, the means (b) is a negative pressure
connector (port)
which can be fastened to one of the inner or outer sides of the cover
material, whereby
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the cover material has the corresponding openings. In this embodiment it is
also
important to ensure air-tight sealing either of the penetration opening
(inside port) or
the surface of the dressing (outside port). Sealing can be achieved, for
example, with an
adhesive foil, an adhesive paste or an adhesive strip.
Alongside the components (a) and, optionally, (b) described above, the device
in
accordance with the present invention also has a component (c). The wound
dressing (c)
used in the device in accordance with the present invention is described in
more detail
in the following. All of the explanations on the wound dressing (c) refer not
only to the
device in accordance with the present invention, but also to the method in
accordance
with the present invention for the manufacture of the wound dressing and the
use in
accordance with the present invention of the wound dressing in negative
pressure
wound therapy.
The wound dressing (c) comprises of an open-cell polyurethane foam (PUR foam).
Foams
are usually materials with cells (open, closed, or both) distributed over
their whole mass.
Such materials thus usually have a raw density (in accordance with DIN EN ISO
845),
which is lower than the density of the basic substance.
A cell is an individual cavity formed in the manufacture of the foam which is
partially or
fully enclosed by the cell walls and/or cell struts.
A closed cell is usually a cell which is completely enclosed by its walls and
has no
connection via the gas phase with the other cells. An open cell is usually a
cell which is
connected with other cells via the gas phase. In the context of this
application, the term
open-cell means that in the polyurethane foam there is at least 60% open
cells,
preferably at least 90% open cells, even more preferably 98% open cells, in
particular
essentially 100% open cells relative to the total number of cells. The open
cell content of
the polyurethane foam is usually determined in accordance with ASTM D 2856-87,
procedure B.
The cell wall is usually taken to mean the wall enclosing the cell. The cell
wall can also
be referred to as the cell membrane. The cell strut is usually taken to mean
the area of
the cell wall which separates more than two cells. Cell struts are preferably
at least 1.5
times the thickness, even more preferably at least twice the thickness of the
rest of the
cell wall.
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CA 02808263 2013-02-14
The open-cell polyurethane foam can be a reticulated foam or a non-reticulated
foam. A
reticulated foam is taken to mean a foam which consists largely of cell
struts. In a
reticulated foam, therefore, the cell walls are largely absent. The
reticulation is usually
carried out in a pressure chamber, e.g. a steel chamber. When the foam is
introduced to
the steel chamber, the air is sucked out (preferably from 50 to 100 weight per
cent, more
preferably from 70 to 99 weight per cent) and replaced by a combustion gas
mixture,
preferably by a mixture containing hydrogen and oxygen, in particular in a
molar ratio of
2:1. When the gas mixture is ignited, the cell skins are torn by the resulting
heat and
the pressure wave. There may also be at least a partial melting of the cell
struts so that
these are reinforced.
The foam (c 1) usually has a cell number (= number of pores along a straight
line per cm)
of 3 to 40 cm-1, preferably 5 to 25 cm-1, more preferably 7 to 18 cm-1, even
more
preferably from 8 to 15 cm-1. The cell number is preferably determined by
microscope.
In principle, the open-cell polyurethane should fulfill certain physical
requirements. It
has been demonstrated that the objects set out above can be solved
unexpectedly
advantageously if the polyurethane foam has a specific tensile strength, a
specific
ductile yield and/or a specific hardness.
In accordance with the present invention, the polyurethane foam usually has a
tensile
strength after three days of storage in bovine serum between 80 kPa and 300
kPa,
preferably between 110 kPa and 250 kPa, more preferably between 120 kPa and
230
kPa, even more preferably from 130 to 220 kPa, especially preferably from 140
to 200
kPa, very especially preferably from 155 to 190 kPa and in particular from 160
to 185
kPa.
Bovine serum is known in the prior art. This is a serum gained from bovine
blood.
Preference is given to the use of the "Standard Fetal Bovine Serum" sold under
the trade
name of HyClone by the company Thermo Scientific. In a preferred embodiment,
the
bovine serum used essentially has the following composition and properties:
Prm-pin r.nnterit anti nthpr
Albumin 1.9 gm/di
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Alkaline phosphatase 213 mU/m1
Blood urea nitrogen 12 mg/di
Creatinine 2.77 mg/d1
Gamma globulin 1.7 tp
Blood sugar (glucose) 107 mg/di
Glutamic oxaloacetic transaminase (SGOT) 152 mU/m1
Glutamic pyruvic transaminase (SGPT) 37 mU/m1
IgG - nephelometer 0.14 mg/ml
Lactate dehydrogenase 2,479 mU/m1
Osmolality 312 mOsm/kg
pH 7.18
Total bilirubin 0.4 mg/di
Total protein 3.7 gm/d1
Content of trace elements and iron
Calcium 13.1 mg/di
Chloride 99 mEq/1
Inorganic phosphorus 9.6 mg/di
Iron 160 g/d1
Saturation concentration (iron) 79
Potassium > 10.0 mEq/1
Sodium 133 mEq/1
Total iron-binding capacity (TIBC) 201 pg/d1
The specimen to be measured is placed in bovine serum and immersed for 3 days
at
23 C. Then the tensile strength is determined in accordance with DIN 53571.
In the
context of this application, the expression in accordance with DIN 53571"
means that
the tensile strength is determined in accordance with this standard in
principle,
whereby, in deviation from the standard, the specimen immersed for three days
in
bovine serum is not completely dried out. Instead, the specimen is taken from
the bovine
serum and immersed in 1 liter of water to be rinsed. Then the test body is
squeezed out
with cellulose paper. Also, in deviation from the standard, a rectangular test
body is
used with the dimensions 10 x 12.5 x 75.
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The tensile strength is measured by using a tensile strength testing device in
accordance
with EN ISO 527-1 [April 1996] by the company Zwick (Ulm). The following test
parameters apply:
Test speed = 500 mm/min
Clamping length: 50 mm
Initial load: 0.1 N
Specimen width b0: 12.5 mm.
Furthermore, the polyurethane foam (c) preferably has a ductile yield of 150%
to 700%,
more preferably from 200% to 650%, even more preferably from 240% to 340%,
particularly 260% to 320%, measured in accordance with DIN 53571 (Procedure 1,
body
A). In addition to this, the polyurethane foam preferably has a hardness of 20
to 70
Shore A, more preferably from 30 to 60 Shore A, even more preferably from 40
to 50
Shore A, measured in accordance with DIN 53505, whereby the measurement was
taken
at 23 C on a slab-like, flat and smooth test body with a thickness of 6 mm.
It has also been demonstrated that the objects set out above can be solved
unexpectedly
advantageously if the polyurethane foam has a specific air permeability. In a
preferred
embodiment the polyurethane foam has an air permeability of 1,000 to 8,000
1/(m2sec),
more preferably from 1,500 to 6,000 1/(m2sec), even more preferably from 2,000
to 5,000
1/ (m2sec), especially preferably from 2,300 to 4,000 1/(m2sec), and in
particular from
2,400 to 3,300 1/(m2sec) measured in accordance with DIN EN ISO 9237 (20 mm
test
thickness, 20 cm2test area, 200 Pa differential pressure).
It has also been demonstrated that the objects set out above can be solved
unexpectedly
advantageously if the polyurethane foam displays visco-elastic behavior. This
means
that the behavior of the polyurethane foam under strain looks like a
combination of an
elastic solid and a viscous fluid. The visco-elastic behavior can be
characterized by a
torsional vibration test in accordance with DIN 53445, Procedure A. It is
preferred that
the foam, when determined in accordance with DIN 53445, Procedure A at 23 C,
has a
mechanical loss factor of 0.1 to 1.0, more preferably from 0.15 to 0.8, even
more
preferably from 0.2 to 0.6.
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It has also been demonstrated that the objects set out above can be solved
unexpectedly
advantageously if the foam (c) has a raw density between 15 and 55 kg/m3, more
preferably between 20 and 35 kg/m3, even more preferably between 22 and 30
kg/m3, in
particular between 24 and 28 kg/m3, measured in accordance with DIN EN ISO 845
(test body with dimensions 100 mm x 100 mm x 50 mm, conditioning for 24 h in a
standard climate (23 C, 50% relative humidity, 1013 mbar)).
Insofar as the relevant standards do not state otherwise, the tests are
generally carried
out at 23 C and 50% relative humidity and at a pressure of 1013 mbar.
Preferred embodiments of the usable polyurethane foams (c-PUR) are explained
below.
The polyurethane foam is usually obtained by reaction of a curable mixture
comprising
the components
(i-PUR) polyisocyanate,
(ii-PUR) compounds reactive to isocyanate, in particular polyol,
(iii-PUR) catalyst,
(iv-PUR) blowing agent, and
(v-PUR) additives, as applicable.
Generally known aliphatic, cycloaliphatic and/or, in particular, aromatic
polyisocyanates can be used as isocyanates (i-PUR). For example,
diphenylmethane
diisocyanate (MDI), in particular, 4,4'-diphenylmethane diisocyanate (4,4'-
MDI),
mixtures of monomeric diphenylmethane diisocyanates and higher-nucleus
homologues
of diphenylmethane diisocyanate (polymeric MDI), tetramethylene diisocyanate
(TMDI),
hexamethylene diisocyanate (HDI), toluylene diisocyanate (TDI) or mixtures
thereof can
be used to produce the polyurethanes.
Preference is given to MDI, in particular 4,4'-MDI and/or HDI. The preferably
used 4,4'-
MDI can contain small quantities, up to around 10 weight per cent, of
allophanate or
uretonimine-modified polyisocyanates. Small quantities of polyphenylene
polymethylene
polyisocyanate (PMDI) can also be used. The total quantity of these PMDI
should not
exceed 5 weight per cent of the isocyanate used.
The polyisocyanate component (i-PUR) is preferably used in the form of
polyisocyanate
prepolymers. These polyisocyanate prepolymers are obtainable by reaction of
the
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CA 02808263 2013-02-14
polyisocyanates described above (i-PUR), for example at temperatures of 30 to
100 C,
preferably at around 80 C, with a substoichiometric amount of the polyols (ii-
PUR)
described below to form a prepolymer. The polyol-polyisocyanate ratio is
selected in such
a way that the NCO content of the prepolymer is 8 to 28 weight per cent,
preferably 14
to 26 weight per cent, particularly preferably 17 to 23 weight per cent.
Polyols such as polyetherols and/or polyesterols are usually used as compounds
reactive to isocyanates (ii-PUR).
It is also possible to use polyether polyalcohols (referred to in this
application as
"polyether polyols") with an OH functionality of 1.9 to 8.0, a hydroxyl number
of 50 to
1,000 mg KOH/g and, as applicable, 10 to 100% primary hydroxyl groups. These
types
of polyether polyols are known, commercially available and based, for example,
on
starter compounds which can be reacted with alkylene oxides, for example
propylene
oxide and/or ethylene oxide, under generally known conditions. The content of
primary
hydroxyl groups can be achieved by eventually reacting the polyols with
ethylene oxide.
To produce the open-cell foam (c) it is preferable not to use polyether
polyols.
Preference is given to the use of polyester polyols in the component (ii-PUR).
The
polyesterols (ii-PUR) are generally produced by condensation of
multifunctional alcohols,
preferably diols, with 2 to 12 carbon atoms, preferably 2 to 6 carbon atoms,
with
multifunctional carboxylic acids with 2 to 12 carbon atoms, preferably 4 to 8
carbon
atoms. Examples of suitable acids include succinic acid, glutaric acid, adipic
acid,
phthalic acid, isophthalic acid and/or terephthalic acid and mixtures thereof.
Adipic
acid is especially preferred. Examples of suitable di- and multi-valent
alcohols include
ethanediol, diethylene glycol, 1,4-butanediol, 1,5-pentanediol, and/or 1,6-
hexanediol
and mixtures thereof. 1,4-butanediol is especially preferred.
The reaction conditions of carboxylic acid and alcohol are usually selected in
such a way
that the resulting polyesterols do not have any free acid groups. The
resulting
polyesterols also generally have a weight average molecular weight (determined
using gel
permeation chromatography) of 500 to 3,500 g/mol, preferably of more than
1,000
g/mol to 3,000 g/mol, in particular from 1,500 to 2,500 g/mol. In general, the
polyesterols used have an average theoretical functionality of 2.0 to 4,
preferably of more
than 2 to less than 3. The polyesterols used also generally have an average OH
number
of 20 to 150, preferably from 30 to 80.
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In a preferred embodiment, the polyesterols used have a viscosity of 150 mPa=s
to 600
mPa=s, preferably from 200 mPa=s to 550 mPa=s, more preferably from 220 mPa=s
to
500 mPa=s, especially preferably from 250 mPa=s to 450 mPa=s and in particular
from
270 mPa=s to 350 mPa=s, measured in accordance with DIN 53 015 at 75 C.
The compounds (ii-PUR) can be mixed with chain extenders and/or cross-linking
agents.
The chain extenders are mainly 2-functional alcohols with molecular weights
from 60 to
499, for example ethylene glycol, propylene glycol, butanedio1-1,4,
pentanedio1-1,5,
dipropylene glycol and/or tripropylene glycol. The cross-linking agents are
compounds
with molecular weights from 60 to 499 and 3 or more active H atoms, preferably
amines,
and especially preferably alcohols, for example glycerin, trimethylol propane
and/or
pentaerythrite.
In a preferred embodiment the component (ii-PUR) preferably contains (or
consists of) 0
to 25 weight per cent, preferably 1 to 20 weight per cent, chain extenders
and/or cross-
linking agents and 75 to 100 weight per cent, preferably 80 to 99 weight per
cent
polyol(s), in particular polyester polyol(s), relative to the total weight of
the component
(ii-PUR).
Compounds which accelerate the reaction of the component (i-PUR) with the
component
(ii-PUR) can be used as catalysts (iii-PUR). These could include, for example,
tertiary
amines and/or organo-metallic compounds, in particular tin compounds. The
following
compounds can be used, for example, as catalysts: triethylene diamine,
aminoalkyl
and/or aminophenyl imidazoles and/or tin (II) salts of organic carboxylic
acids.
Catalysts are generally used in a quantity of 0.1 to 5 weight per cent
relative to the
weight of the component (u-FUR).
Generally known chemically or physically active compounds can be used as
blowing
agents (iv-PUR). Water can be used preferably as a physically active blowing
agent,
which, when reacted with the isocyanate groups, forms carbon dioxide. Examples
of
physical blowing agents include (cyclo)aliphatic hydrocarbons, preferably
those with 4 to
8, especially preferably 4 to 6, and in particular 5 carbon atoms, partially
halogenated
hydrocarbons or ethers, ketones or acetates. The amount of blowing agents used
depends on the desired density of the foams: The different blowing agents can
be used
individually or in any mixture with each other. Special preference is given to
the use of
only water as a blowing agent, generally in a quantity of 0.1 to 5 weight per
cent, in
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particular from 2.5 to 4 weight per cent relative to the weight of the
component (ii-PUR).
Physical blowing agents are preferably used in a quantity of < 0.5 weight per
cent
relative to the weight of the component (ii-PUR).
The reaction takes place as applicable in the presence of (v-PUR) auxiliaries
and/or
additives, for example fillers, cell regulators, cell openers, surfactants,
and/or stabilizers
against oxidative, thermal or microbial decomposition or ageing.
To produce polyurethane foams, the components (i-PUR) and (ii-PUR) are
generally made
to react with each other in such quantities that the equivalence ratio of NCO
groups to
the sum of the reactive hydrogen atoms (in particular to the sum of the OH
groups) is
1:0.8 to 1:1.25, preferably 1:0.9 to 1:1.15. A ratio of 1:1 corresponds here
to an NCO
index of 100. The desired open cell content of the polyurethane foam is
generally
achieved by a suitable selection as recognized by those skilled in the art of
the
components (i-PUR) to (v-PUR). As applicable, after setting the resulting PUR
foam is
reticulated. For more information on this, reference is made to the
explanations given
above.
It has also been demonstrated that the objects set out above can be solved
unexpectedly
advantageously if the polyurethane foam (c) contains silver in the form of
silver ions or
in the form of atomic silver. Preferably, a silver coating is applied after
production of the
polyurethane foam. Alternatively the silver can be added to the curable
composition.
Preferably, the polyurethane foam contains 0.000001 to 0.1 weight per cent,
more
preferably 0.0001 to 0.01 weight per cent silver relative to the total weight
of the
polyurethane foam.
It has also been shown that the objects described at the beginning could not
always be
solved satisfactorily with polyurethanes solely on the basis of aliphatic
starting
materials. Rather, the use of aromatic structural components (i-PUR and/or ii-
PUR)
proves advantageous. In a preferred embodiment the polyurethane foam (c) thus
has a
proportion of aromatic compounds of 5 to 50%, more preferably from 10 to 45%,
in
particular from 15 to 40%. The proportion of aromatic compounds is determined
by the
ratio of the weight of aromatic rings to the total weight of the foam.
In a preferred embodiment of the invention, the open-cell polyurethane foam
has a
thickness of 1 to 50 mm, in particular from 15 to 35 mm.
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The open-cell polyurethane foam can also be used in a dry condition soaked
with an
ointment base, in particular a triglyceride ointment base. An especially
preferred
ointment base contains:
20 to 90 weight per cent, preferably 55 to 80 weight per cent triglycerides,
in particular
containing fatty acid residues selected from caprylic acid, capric acid,
lauric acid and/or
stearic acid;
5 to 75 weight per cent, preferably 15 to 45 weight per cent triglycerides, in
particular
containing fatty acid residues selected from isostearic acid, stearic acid, 12-
hydroxy-
stearic acid and/or adipic acid; and
0 to 30 weight per cent, preferably 5 to 20 weight per cent polyethylene
glycol with a
weight average molecular weight of 500 to 3,000 g/mol. In a preferred
embodiment the
proportion of ointment base is 10 to 95 weight per cent, more preferably 30 to
92 weight
per cent, even more preferably 45 to 90 weight per cent, especially preferably
55 to 88
weight per cent, in particular 65 to 85 weight per cent relative to the total
weight of the
foam and the ointment base.
The foam is preferably not soaked, for example, with an activation solution
(e.g. Ringer's
solution). It is also preferred that the open-cell polyurethane foam is not
coated or
impregnated with a silicone gel, e.g. a hydrophobic silicone gel.
The polyurethane foam can also contain substances with antimicrobial action.
Substances with antimicrobial action can include for example, substances with
amino or
imino groups. Substances with antimicrobial action can also be antimicrobially
active
metal cations, in particular silver cations, for example a complex of 1-viny1-
2-
pyrrolidones with silver cations. Other especially suitable substances with
antimicrobial
action further include biguanide derivatives such as chlorhexidine or
polybiguanides
such as polyethylene biguanide (PEB), polytetramethylene biguanide (PTMB) or
polyethylene hexamethylene biguanide (PEHMB). An especially preferred
polybiguanide
is polyhexamethylene biguanide (PHMB or polyhexanide). Other suitable
substances
with antimicrobial action are polyguanidines such as polyhexamethylene
guanidine
(PHMG), N-octy1-1-[10-(4-octyliminopyridine-1-yl)decyl]pyridine-4-imine
(octenidine),
quaternary ammonium compounds such as benzalkonium chloride or cetylpyridinium
chloride, triazines such as 1-(3-chloroally1)-3,5,7-triaza- I -azonia-
adamantan-chloride or
the ammonium compound taurolidine.
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Preferably the open-cell polyurethane foam is impregnated or coated with the
aforementioned substances with antimicrobial action.
Substances with antimicrobial action are usually contained in the polyurethane
foam in
a quantity of 0 to 30 weight per cent, preferably from 0.1 to 15 weight per
cent relative
to the total weight of the polyurethane foam.
In principle, the explanations of preferred embodiments of individual
parameters of the
polyurethane foam (c) must not be seen in isolation, but in combination with
the
explanations of preferred embodiments of other parameters or in combination
with the
explanations of the substance compositions. Accordingly, the device in
accordance with
the present invention and its use in accordance with the present invention can
be an
open-cell foam (c) which,
after three days of storage in bovine serum, has a tensile strength of 80 kPa
to 300 kPa,
preferably from 110 kPa to 250 kPa, more preferably from 120 kPa to 230 kPa,
even
more preferably from 130 kPa to 220 kPa, especially preferably from 140 kPa to
200
kPa, most especially preferably from 155 kPa to 190 kPa and in particular from
160 kPa
to 185 kPa;
a ductile yield of 150% to 500%, more preferably from 200% to 380%, even more
preferably from 240% to 340%, in particular 260% to 320%;
a mechanical loss factor of 0.1 to 1.0, more preferably from 0.15 to 0.8, even
more
preferably from 0.2 to 0.6;
a hardness of 20 to 70 Shore A, more preferably from 30 to 60 Shore A, even
more
preferably from 40 to SO Shore A;
a cell number (= number of pores along a straight line per cm) from 3 to 40 cm-
1,
preferably from 5 to 25 cm-1, more preferably from 7 to 18 cm-,, even more
preferably
from 8 to 15 cm-l;
a raw density between 15 and 55 kg/m3, more preferably between 20 and 35
kg/m3,
even more preferably between 22 and 30 kg/m3, in particular between 24 and 28
kg/m3;
and/or
an air permeability of 1,000 to 8,000 1/(m2sec), more preferably from 1,500 to
6,000
1/(m2qec), even more preferably from 2,000 to 5,000 1/(m2sec), especially
preferably from
2,300 to 4,000 1/(m2sec) and in particular from 2,400 to 3,300 1/(m2sec);
and is preferably obtainable by reaction of a polyisocyanate (i), selected
from MDI, PMDI
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and/or TDI, with a (ii) polyester polyol, which is preferably obtainable by
reaction of a
dicarboxylic acid with 4 to 8 carbon atoms with a dialcohol with 2 to 6 carbon
atoms,
whereby the (ii) polyester polyol preferably has a weight average molecular
weight of 500
to 4,000 g/mol; and/or
the open-cell polyurethane foam has a proportion of aromatic compounds of 5 to
50%,
more preferably from 10 to 45%, in particular from 15 to 40%.
The present invention also comprises any combinations of the cited aspects.
Accordingly, an especially preferred foam, for example after three-day storage
in bovine
serum, has a tensile strength between 155 kPa and 190 kPa; a ductile yield of
260% to
320%; a cell number of 8 to 15 crn-1; a raw density between 24 and 28 kg/m3;
and/or an
air permeability of 2,400 to 3,3001/(m2sec).
This foam is preferably obtainable by reaction of a polyisocyanate (i),
selected from MDI,
PMDI and/or TDI, with a (ii) polyester polyol, which is preferably obtainable
by reaction
of a dicarboxylic acid with 4 to 8 carbon atoms with a dialcohol with 2 to 6
carbon
atoms, whereby the (ii) polyester polyol preferably has a weight average
molecular weight
of 500 to 4,000 g/mol.
Furthermore, the invention provides a ready-to-use set for negative pressure
wound
therapy, including the device in accordance with the present invention,
whereby the
polyurethane foam is suitable as a wound dressing and is provided in a ready-
to-use
pack.
The object of the invention is thus a ready-to-use set for negative pressure
wound
therapy comprising
(a) a cover material for air-tight sealing of the wound space, i.e. the wound
and the area
surrounding the wound,
(b) as applicable, a means suitable for the connection of a negative pressure
source,
preferably a means for the functional connection of the wound space with a
negative
pressure source outside of the cover material in such a way that a negative
pressure can
be generated in the wound space and fluids can be drawn out of the wound space
by
suction,
and
(c) a wound dressing in a ready-to-use pack, comprising an open-cell
polyurethane foam
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which has the properties described above, e.g. a tensile strength after three-
day storage
in bovine serum, measured in accordance with DIN 53571, between 80 kPa and
300 kPa.
The wound dressing (c) included in the set as a ready-to-use pack should
preferably be
provided in a damp-proof pack. Preferably the ready-to-use wound dressing is
provided
in sterile form, whereby especially radiation and/or ethylene oxide can be
used for
sterilization. The set can contain further optional elements such as adhesive
means to
fix the dressing, sealing means to generate an air-tight seal of the dressing,
pressure
sensors, connection elements for pressure sensors, additional tubes,
connectors for
tubes, disinfectants, skin care products, pharmaceutical preparations or
instructions for
use. The set in accordance with the present invention preferably also contains
scissors,
pads and/or pincers, in particular in sterile form. Preferably the set also
contains a
ready-to-use negative pressure unit.
A further object of the invention is the use of the wound dressing (c)
explained above for
or in the negative pressure wound therapy. An object of the invention is thus
also the
use of the special open-cell polyurethane foam described above for the
negative pressure
therapy of wounds, in particular as a wound dressing. In particular, the
object of the
invention is the use of an open-cell polyurethane foam which has a tensile
strength after
three days of storage in bovine serum, measured in accordance with DIN 53571,
between 80 kPa and 300 kPa for the negative pressure therapy of wounds, in
particular
as a wound dressing (c). All of the above explanations of preferred
embodiments
regarding the component (c), i.e. the open-cell polyurethane foam, apply not
only to the
device in accordance with the present invention, but also to the use of the
device in
accordance with the present invention.
Special advantages of the device in accordance with the present invention, the
set in
accordance with the present invention or the use or application in accordance
with the
present invention, arise when the wounds are burn wounds, wounds caused by
mechanical trauma, wounds caused by exposure to chemicals, wounds caused by a
metabolic disorder, wounds caused by a circulatory disorder or wounds caused
by
pressure ulcers, particularly when these wounds are chronic wounds.
Furthermore,
wounds caused by diabetic foot ulcer can be treated particularly
advantageously. In
addition, wounds caused by radiation induced ulcer can be treated
advantageously with
the means of the present invention.
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In a further preferred embodiment, the wound dressing (c) is provided for use
in negative
pressure therapy in the treatment of a wound caused by a skin graft. The
application
includes the treatment of wounds caused by split-skin and full-skin
transplants using
negative pressure therapy. Advantageous effects arise due to the structure of
the special
open-cell polyurethane foam, which preferably has a tensile strength after
three days of
storage in bovine serum, measured in accordance with DIN 53571, between 80 kPa
and
300 kPa, and due to the uniform distribution of pressure. When the wound
dressing (c)
is used in the treatment of a wound caused by a skin graft, the skin graft can
be
adequately fixed while avoiding undesired shear forces.
The wound dressing (c) described above can be used advantageously as a wound
dressing in the negative pressure therapy of pressure wounds in patients with
a body-
mass index (BMI = body weight over height squared) of less than 18.0, in
particular with
a body mass index of 14 to 17.5. This applies in particular to patients aged
over 60. The
advantageous effect of the device in accordance with the present invention or
the set in
accordance with the present invention is manifested in particular in such
patients.
Another object of the invention is a method for negative pressure wound
therapy,
comprising the steps of
a) providing a device according to one of the claims 1 to 13;
b) applying the negative pressure dressing to the wound;
c) generating a negative pressure of 25 mm Hg to 250 mm Hg, preferably 50 mm
Hg to
150 mm Hg in the wound space for at least 30 minutes and up to a maximum of 7
days,
preferably for at least 1 day and up to a maximum of 6 days.
FIGURES
Figure 1: Schematic view of the device in accordance with the present
invention
(side view)
1 Wound surroundings (i.e. generally undamaged skin)
2 Air-tight cover material (a)
3 Wound dressing (c) = open-cell polyurethane foam
4 Negative pressure connector (port)
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Negative pressure connection line
6 Collector
7 Negative pressure unit
8 Wound
5 The device in accordance with the present invention for negative pressure
wound
therapy is explained in more detail in Figure 1. Fig. 1 shows a schematic view
(side
view) of the device in accordance with the present invention. The device
comprises an
air-tight cover material (2), a means (4-5) for the functional connection of
the wound
space with a negative pressure source (7) outside of the cover material, and
the open-cell
foam (3). The cover material (2) is fastened in the area of the wound
surroundings (1),
usually consisting of undamaged skin. The size of the cover material must be
such that
the cover material can be fastened outside of the wound space in the area of
the wound
surroundings (1). The cover material (2) can have different dimensions and
shapes, for
example circular, oval or rectangular. It can also have an irregular shape
matched to the
individual wound. The cover material (2) is usually fastened in the area of
the wound
surroundings (1) and sealed air-tight. This can be achieved, for example, by
providing an
adhesive edge on the cover material (2). Alternatively, an adhesive substance
can be
applied either to the edge of the cover material (2) and/or the intact skin
around the
wound. This has the advantage that it is easier to match the cover material to
the shape
and size of the wound. In the preferred embodiment shown here, the negative
pressure
connector (4) is attached to the outside of the air-tight cover material (2)
facing away
from the wound. In order to functionally connect the wound space with a
negative
pressure unit (7) outside of the cover material in this arrangement, there
must be one or
more openings passing through the cover material (2) in the proximity of the
negative
pressure connector (4).
In a preferred embodiment of the invention the device for the negative
pressure wound
therapy includes no wound contact layer between the wound dressing (3) and the
wound
surface (8).
Figure 2 illustrates the determination of undesired foreign particles in
wounds in
accordance with Example 2.
The invention is illustrated by the following examples.
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Example 1: Determination of the tensile strength
A foam in accordance with the present invention was produced and a foam
commercially
available for negative pressure therapy was used as a comparison:
Foam A (in accordance with the present invention), obtainable by reaction of
polyester
polyol and isocyanate, tensile strength after dry storage in a standard
climate 160 kPa,
tensile strength after three days of storage in bovine serum: 170 kPa.
Foam B (comparison), obtainable by reaction of polyether polyol and
isocyanate, tensile
strength after dry storage in a standard climate 115 kPa, tensile strength
after three
days of storage in bovine serum: 72 kPa.
Example 2: Determination of undesired foreign particles in wounds
6 pigs were treated on 8 wounds each with a device for negative pressure wound
therapy
comprising either the foam A in accordance with the present invention from
example 1
or the comparison foam B for 7 days. A systematic diagram of the test set-up
is shown
in Figure 2. Figure 2 shows a pig's back from above. Si to S8 are the wounds
covered
with foam, 1 and 2 represent a wound dressing of the foams A or B, each
covering four
wounds. 3 and 4 are openings for connection with the negative pressure system.
5 is the
head of the pig, 6 the tail.
When the treatment period ended, the wounds were examined for undesired foam
particles. The result was as follows:
Foam in accordance with the present invention A: 0% of the wounds contained
foam
particles.
Comparison foam B: 25% of the wounds contained foam particles.
Example 3: Histological examination of inflammatory activity in wounds
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As described in Example 2, a foam A according to the present invention and a
comparative foam B were used as wound dressings.
Granulation tissues were examined histologically.
The histological examination of a wound treated with the inventive foam A
shows only
little inflammatory foci (IF), as illustrated in Figure 3. The inflammatory
foci show only
minimal neutrophil infiltration, see Figure 4.
Contrary, there are more areas with inflammatory activity in the granulation
tissue of a
wound treated with the comparative foam B, as illustrated in Figure 5. The
inflammatory
foci (IF) consist of foreign body giant cells, neutrophil granulocytes and
lymphocytic cells,
as illustrated in Figure 6.
Consequently, using a foam according to the present invention is associated
with less
inflammatory activity.
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