U.S. patent application number 10/311674 was filed with the patent office on 2003-09-25 for silver containing wound dressing.
Invention is credited to Woods, David Malcolm.
Application Number | 20030180346 10/311674 |
Document ID | / |
Family ID | 9899858 |
Filed Date | 2003-09-25 |
United States Patent
Application |
20030180346 |
Kind Code |
A1 |
Woods, David Malcolm |
September 25, 2003 |
Silver containing wound dressing
Abstract
A wound dressing having anti-microbial activity comprises a
first fibre capable of bonding with silver (1) cations. The wound
dressing comprises a blend of the first fibre to which silver (1)
cations are bonded and a second fibre which is substantially free
from silver. The wound dressing comprises from 0.01 to 5.0 percent
by weight of silver (1) cations, based on the weight of fibre.
Inventors: |
Woods, David Malcolm;
(Leicester, GB) |
Correspondence
Address: |
HOWSON AND HOWSON
ONE SPRING HOUSE CORPORATION CENTER
BOX 457
321 NORRISTOWN ROAD
SPRING HOUSE
PA
19477
US
|
Family ID: |
9899858 |
Appl. No.: |
10/311674 |
Filed: |
December 18, 2002 |
PCT Filed: |
September 21, 2001 |
PCT NO: |
PCT/GB01/04204 |
Current U.S.
Class: |
424/446 ;
442/123 |
Current CPC
Class: |
A61L 15/44 20130101;
A61L 2300/42 20130101; A61L 26/0066 20130101; A61L 15/28 20130101;
A61L 26/0052 20130101; Y10T 428/24993 20150401; A61L 2300/404
20130101; Y10T 428/24041 20150115; A61L 15/46 20130101; Y10T
442/2525 20150401; A61L 26/0023 20130101; Y10T 442/475 20150401;
A61L 15/18 20130101; Y10T 442/655 20150401; A61L 2300/104 20130101;
Y10T 442/481 20150401 |
Class at
Publication: |
424/446 ;
442/123 |
International
Class: |
A61L 015/16; B32B
027/12 |
Foreign Application Data
Date |
Code |
Application Number |
Sep 21, 2000 |
GB |
0023155.5 |
Claims
1. A wound dressing having anti-microbial activity, which wound
dressing comprises a first fibre capable of bonding with silver (1)
cations, characterised in that the wound dressing comprises a blend
of the first fibre to which silver (1) cations are bonded and a
second fibre which is substantially free from silver.
2. A wound dressing according to claim 1 characterised in that it
comprises from 0.01 to 5.0 percent by weight, of silver (1) cations
based on the weight of fibre.
3. A wound dressing according to claim 2 characterised in that it
comprises from 0.1 to 4.0 percent by weight of silver (1) cations
based on the weight of fibre.
4. A wound dressing according to claim 3 characterised in that it
comprises from 0.25 to 3.0 percent by weight of silver (1) cations
based on the weight of fibre.
5. A wound dressing according to any of claims 1 to 4 characterised
in that the first fibre is substantially insoluble in water.
6. A wound dressing according to any of claims 1 to 5 characterised
in that the first fibre comprises a carboxymethylcellulose fibre,
an alginate fibre, a chitosan or chitosan derivative fibre or an
acrylic fibre.
7. A wound dressing according to claim 6 characterised in that the
first fibre is a carboxymethyl cellulose fibre and the wound
dressing contains from 1.0 to 2.0% by weight of silver (1) cations,
based on the weight of the fibre.
8. A wound dressing according to claim 6 characterised in that the
first fibre is an alginate fibre and the wound dressing contains
from 0.25 to 0.75% by weight of silver (1) cations, based on the
weight of the fibre.
9. A wound dressing according to claim 6 or claim 7 characterised
in that the first fibre is a carboxymethylcellulose fibre which has
a degree of substitution between 0.1 and 0.4.
10. A wound dressing according to claim 6 characterised in that the
first fibre is an acrylic fibre which incorporates a comonomer to
provide dye-sites in the fibre.
11. A wound dressing according to claim 10 characterised in that
the comonomer isitaconic acid or 2-acrylomido methyl propane
sulphonic acid.
12. A wound dressing according to any of claims 1 to 11
characterised in that the first fibre and the second fibre are
similar.
13. A wound dressing according to any of claims 1 to 12
characterised in that the ratio of the first fibre to the second
fibre is in the range of from 0.5 to 25% by weight of the total
weight of the fibre.
14. A wound dressing according to claim 13 characterised in that
the ratio of the first fibre to the second fibre is in the range of
from 5 to 20% by weight of the total weight of the fibre.
15. A wound dressing according to any of claims 1 to 10
characterised in that the first fibre includes about 10% by weight,
based on the weight of fibre, of silver (1) cations.
16. A wound dressing according to any of claims 1 to 12
characterised in that the silver ions are preferably chemically
bonded to the first fibre.
17. A wound dressing according to any of claims 9 to 14
characterised in that the first fibre is a carboxymethylcellulose
fibre and the degree of substitution is in the range from 0.20 to
0.35.
18. A wound dressing according to claim 14 characterised in that
the degree of substitution is about 0.3.
19. A wound dressing according to any of claims 1 to 15
characterised in that the silver ions are introduced into the first
fibre by ion-exchange.
20. A wound dressing according to any of claims 1 to 16
characterised in that the first fibre is a carboxymethylcellulose
fibre and the carboxymethylcellulose is derived from lyocell.
21. A wound dressing according to any of claims 1 to 17
characterised in that the fibrous carboxymethylcellulose is in the
form of a staple fibre or continuous filament yarn.
22. A wound dressing according to any one of the preceding claims
characterised in that the carboxymethylcellulose is present in a
needlepunched nonwoven textile.
23. A wound dressing substantially as herein described and with
reference to the Example 5.
Description
[0001] This invention relates to a wound dressing, in particular to
a wound dressing having antimicrobial activity.
[0002] International Patent Applications WO 93/12275, WO 94/16746
and PCT/GB99/02093 disclose the carboxymethylation of lyocell fibre
and the use of such carboxymethylated fibre in wound dressings.
[0003] European Patent Application No. 707,793 discloses a
silver-containing antimicrobial agent which comprises
carboxymethylcellulose containing silver in an amount of 0.02 to 1
percent by weight and having a degree of substitution of at least
0.4.
[0004] Japanese Published Unexamnined Patent Application 11-001,895
discloses a hygienic product such as a disposable diaper, sanitary
napkin or incontinence pad which comprises water-insoluble
carboxymethylcellulose (derived from woodpulp) containing 0.32% by
weight silver ions.
[0005] The silver-containing fibre used in the prior art dressings
discolour (turn dark brown or black) on exposure to light. In
consequence, such dressings may exhibit an unsightly appearance.
Attempts have been made to overcome this problem and are described
for example in International Patent Application WO 00/90173.
[0006] It is an object of the present invention to provide a wound
dressing in which the above disadvantages are reduced or
substantially obviated.
[0007] The present invention provides a wound dressing having
anti-microbial activity, which comprises a first fibre capable of
bonding with silver (1) cations, characterised in that the wound
dressing comprises a blend of the first fibre to which silver (1)
cations are bonded and a second fibre which is substantially free
from silver.
[0008] The wound dressing according to the invention preferably
comprises from 0.01 to 5%, more preferably from 0.1 to 4%, even
more preferably from 0.25 to 3% by weight of silver (1) cations,
based on the weight of fibre. Most preferably, the wound dressing
contains 1 to 2% by weight based on fibre, of silver (1) cations,
where the fibre is carboxymethyl cellulose fibre and 0.25% to 0.75%
silver (1) cations, where the fibre is an alginate fibre by weight
based on the weight of fibre, of silver (1) cations.
[0009] The first fibre is preferably substantially insoluble in
water and preferably comprises a sodium carboxyinethylcellulose
fibre, an alginate fibre, a chitosan or chitosan derivative fibre
or an acrylic fibre. Where the fibre is a carboxymethylcellulose
fibre, it preferably has a degree of substitution between 0.1 and
0.4. Where the fibre is an acrylic fibre, it is preferably an
acrylic fibre which incorporates a comonomer such as itaconic acid
or 2-acrylamido methyl propane sulphonic acid to provide dye-sites
in the fibre.
[0010] Where the fibre is an alginate fibre, it may be a calcium
alginate fibre or a mixed metal alginate fibre such as a
calcium/sodium alginate fibre. The alginate polyemr amy be one with
a high mannuoronate or a high guluronate.
[0011] Wound dressings in which the first fibre is a
carboxymethylcellulose fibre are particularly preferred. The second
fibre may be similar or different to the first fibre. Similar
fibres are preferably used. The second fibre should be such as not
to discolour to an objectionable degree in light, and as such
should, for example, contain no silver or such low levels of silver
that it does not discolour at all or discolours only to an degree
which is not objectionable aesthetically.
[0012] The ratio of the first silver-containing fibre to the second
fibre is preferably in the range from 0.5 to 25% by weight, more
preferably 5 to 20% by weight, of the total weight of the fibre
[0013] In order to achieve the desired overall concentration of
silver ions, the first fibre preferably includes about 10% by
weight, based on the weight of fibre, of silver (1) cations and is
blended with a large proportion of unsilvered fibre so as to give a
blended product containing the desired weight of silver. The silver
ions are preferably chemically bonded to the first fibre.
[0014] As specified above, the degree of substitution (D.S.) of the
sodium carboxymethylcellulose (CMC) is preferably at least 0.1, and
is preferably less than 0.4. Such CMC is inherently insoluble in
water and also in saline solution. A higher D.S. gives at least
partial solubility in water, which is undesirable in the field to
which the invention relates. The D.S. is more preferably in the
range from 0.20 to 0.35, for example about 0.3.
[0015] The silver ions are preferably introduced into the first CMC
fibre by ion-exchange, for example by contacting CMC with an
aqueous solution of a salt such as, silver(I) nitrate. As CMC often
contains sodium chloride as a by product of the reaction between
cellulose and chloroacetic acid and as silver chloride is highly
insoluble. It maybe preferred to perform the ion-exchange reaction
on a salt free grade of CMC. It is preferred that the balance of
the carboxyl groups in the CMC be neutralised with sodium ions.
[0016] The CMC is preferably derived from lyocell, as disclosed for
example in WO 93/12275, WO 94/16746 and PCT/GB99/02093.
[0017] The fibrous CMC is preferably in the form of staple fibre or
continuous filament yarn. It is preferably contained within a
textile article such as a woven, knitted or most preferably a
nonwoven fabric, such as a needlepunched nonwoven fabric.
[0018] The dressings of the invention are preferably gel-forming,
which makes them advantageously low-adherent to wounds and
consequently easy to remove. They are soft, conformable and
absorbent. Silver metal ions are released slowly over an extended
period of time from a wetted dressing of the invention.
[0019] The second fibre which does not contain silver is preferably
also CMC, but other kinds of gel-forming fibre or of textile fibre
may also be utilised. If the dressings are blended from unexposed
fibre, on exposure to light, such dressings develop either a
speckled appearance or a light brown or light grey colour which is
not unsightly. However, it is preferred to pre-expose the
silver-containing fibre to light before blending, so that after
blending the dressing is light stable and the uniformity of
blending can be checked visually.
[0020] The wound dressings of the invention may contain other
medicaments if desired.
[0021] The wound dressings of the invention are useful in the
treatment of infected wounds, and as a prophylactic measure against
infection of uninfected wounds, also for the reduction or
elimination of unpleasant odours produced by wounds.
[0022] The invention is illustrated by the following Examples, in
which parts and proportions are by weight unless otherwise
specified.
EXAMPLE 1
[0023] Manufacture of Master Batch Material
[0024] The optimum conditions for manufacture of a master batch
material were determined as follows:
[0025] Sodium carboxy methyl cellulose fibre (CMC), Hydrocel.RTM.,
available from Acordis Speciality Fibres Limited of Coventry
England, was soaked in silver nitrate (AgNO.sub.3) solution in 50
volume % industrial methylated spirit/50 volume % water and the
following table shows the percentage silver take-up after soakin,
as measured by x-ray fluorescence.
1 % AgNO.sub.3 Conditions 4% AgNO.sub.3 8% AgNO.sub.3 15 minutes @
65.degree. C. 8.1 6.1 15 minutes @ ambient 12.6 11.2 4 hours @
ambient 8.0 9.0
[0026] From the above results, it was determined that higher
concentrations of silver nitrate did not appear to be beneficial
and that the use of a solution having a concentration of
approximately 4% silver nitrate to produce a fibre having a silver
content of 8% would give the optimum results. It was therefore
decided to produce the master batch material using such a
solution.
[0027] CMC tow or staple (50 g) was added to a solution of 4%
silver nitrate (300 g) in industrial methylated spirit/water 50/50
at ambient temperature. The solution was held for convenience in a
round screw top bottle so that it could be rolled on a laboratory
bottle roller. The bottle was rolled for 15 minutes whereupon an
ion exchange mechanism took place which produced silver containing
CMC--referred to herein as silver CMC (8%w/w, Ag).
[0028] The spent silver nitrate solution was discarded and replaced
with 50/50 industrial methylated spirit/water wash liquor (300 g)
followed by shaking for five minutes. This washing process was
repeated and finally a soft finish was used. This consisted of 0.5%
polysorbate 20 (Tween) 20 in 90:10 industrial methylated
spirit/water (i.e. 1.5 g in 300 g).
[0029] Excess liquor was squeezed out of the fibre, which was then
allowed to dry at ambient temperature. The silver CMC tow was then
opened out and spread onto an open bench to allow maximum access to
light. The discolouring tow was handled periodically to expose new
surfaces to the light. This was continued until the majority of the
tow assumed a chocolate brown coloration (about two weeks).
[0030] The predominantly brown silver CMC tow produced was blended
with untreated carboxymethyl cellulose (CMC) fibre at the ratios
shown as follows to produce blends having 0.5%, 1.0% and 2.0%
silver:
6.25% silver CMC +93.75% CMC fibre=0.5% Ag
12.5% silver CMC +87.50% CMC fibre=1.0% Ag
25.0% silver CMC +75.00% CMC fibre=2.0% Ag
[0031] Blending was accomplished by carrying out a carding
operation twice to achieve a uniform blend, on hand pre-mixed
fibre. The carded web was then cross-folded to give the desired
basis weight. The web was then bonded on a needle loom to give a
coherent web from which individual dressings were cut. In addition,
a conventional carboxymethyl cellulose fibre control sample was
manufactured by the same method.
[0032] Absorbency Results
[0033] The master batch material was produced by the soaking of CMC
fibre tow in silver nitrate and the absorbency tests were first of
all carried out on tow using a free swell test. It was found that
the CMC fibre control had an absorbency of 28 g/g and the silver
CMC had an absorbency of 30 g/g. These differences were not
considered to be significant.
[0034] Absorbency tests were then carried out on fabric produced by
needle felting from fibres as above.
[0035] Fabric absorbencies as measured by the test identified in
the British Pharmacopoeia 1993 Addendum 1995 page 1706, Alginate
Dressing Absorbency were found to be as shown in the following
table, in which gsm=grams per square metre and is a measure of the
amount of fabric produced.
2 gsm Absorbency g/g Absorbency g/piece CMC control 111 16.0 18.0
0.5% silver CMC 99 20.0 19.5 1.0% silver CMC 91 20.5 18.7 2.0%
silver CMC 65 22.3 14.5
[0036] As can be seen from the above table, the addition of silver
was found to have very little effect on the absorbency, if anything
increasing the absorbency on a gram per gram basis, though having
less effect on absorbency on a gram per piece basis.
[0037] After wetting for 30 minutes in saline, the fabrics which
were initially a fairly dark fawn, changed colour and became
lighter and more translucent as time passed.
[0038] It appeared that there was no difference in the gelling
properties between the CMC and the silver CMC, which is an
important observation in that the silver addition does not destroy
the valuable gelling properties.
[0039] Microbial Activity
[0040] To measure the efficiency of the silver containing material
in reducing microbial activity, 250 g of milk was mixed with 0.2 g
of fibre. The results were as follows:
3 Control (milk alone) Malodour in 2 days Control (CMC in milk)
Malodour in 2 days 0.5% Silver (web) Malodour in 2 weeks 8.0%
Silver (tow) No Malodour in 3 weeks
[0041] These tests were repeated with 0.9 wt/. sodium chloride
additions (chosen to be equivalent to the salt level in body
fluids) to the milk, and the same results were obtained. This shows
that the chloride ions in the salt were not detrimental to the
antimicrobial properties of the silver in the silver CMC.
[0042] As can be seen from the above results, milk alone and milk
containing CMC fibre alone went off in two days, as could be easily
determined by the smell. By comparison, where the web contained
0.5% silver, there was a two week period before the milk went off
and could be smelt. With unblended tow containing 8% silver, no
smell could be detected after a three week period when the test was
stopped.
[0043] In practice, the wound treatment products utilising the
invention are unlikely to be left on a wound for more than a few
days, and certainly no more than a week, so that it an be seen that
a blend containing 0.5% silver retains its efficiency in terms of
antimicrobial effect for at least twice the period that would be
required in practice.
EXAMPLE 2
[0044] A solution of water (33.1 g) and industrial methylated
spirit (IMS) (36.0 g) was made up in a black glass bottle suitable
for rolling on a bottle roller. To it was added silver nitrate
(30.0 g) and the latter was stirred until it dissolved. No heat was
required. To this solution was added 12g of high manuronic calcium
alginate tow and the whole was rolled on a bottle roller for four
hours. After this period of time the tow was removed and washed in
a solution (70 g) containing IMS and water as a 50/50 mixture. Soft
finish in the form of polysorbate 20 (0.7 g) was dissolved in (70
g) solution of IMS/water as a 95/5 mixture and the tow was soaked
in this medium for approximately 50 minutes. The silver alginate
master batch was then dried in a fume cupboard to give a product
having 13.7% of silver overall on the fibre.
[0045] 5 g of the above silver alginate master batch was weighed
and cut into staple and opened by hand. 95 g of standard high
manuronic calcium alginate fibre was also cut into staple and
opened. The two were blended on the in-put feed belt of a
laboratory carding machine.
[0046] The diluted silver alginate fibre was then carded,
cross-folded and needled into a non-woven web. By calculation the
final product would contain silver at an average level of 0.6%. It
had a light grey-brown flecked mottled appearance.
[0047] In a comparative example, the same level (0.68%) of silver
was applied uniformly to a batch of the same calcium alginate
fibre, and it was then carded, cross-folded, and needled to form a
nonwoven web. The web was exposed to light and developed a uniform
darkish brown colour, appearing much darker than the mottled
appearance of the blended web having the same average amount of
silver present.
[0048] The invention also contemplates multiple layer dressings
some or all of which layers may comprise blended product
incorporated silver additions. For example, a silver containing
blended layer of a non-gel forming fibre, such as a silver
containing acrylic fibre blended with pure acrylic fibre could be
faced with a wound contact layer of a gel forming fibre. An example
of the contact layer could be an alginate fibre and the alginate
layer could be blended with a silver added fibre or may have no
silver at all, being a simple gel forming alginate fibre.
* * * * *