Note: Descriptions are shown in the official language in which they were submitted.
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Antimicrobial Materials Comprising a Silver-Containing Glass Composition
The invention relates to materials, especially self-adhesive and antimicrobial
wound
contact materials, cosmetics, especially inflammation-alleviating emulsions,
disinfectant
cleansing preparations, and antimicrobial skin contact materials, pads or
wipes.
The combination of materials, such as, for example, polyurethane as wound
contact
material, with the defined, silver-containing glasses generates a
disinfectant, skin-
calming or antimicrobial effect and at the same time ensures a high level of
product
stability and high discoloration stability of the materials in the face of
external influences.
The treatment and healing of bacterially contaminated or infected skin or
wounds poses
a great challenge to medicine and the natural sciences. Poorly healing wounds
and
chronic wounds, in particular, are often populated by a wide variety of
microorganisms,
which greatly delay or sometimes even prevent entirely the course of healing.
Even with
acute wounds, however, caused by trauma, surgical intervention, or even just a
simple
injury, the penetration of pathogenic microorganisms cannot be ruled out in
every case.
As a result of penetration by the microorganisms, the wound becomes colonized
by
them. A wound populated with more than 105 CFU/g is referred to as an infected
wound
(M.G. Robson "Clinical Research can improve the outcome of treatment of
problem
wounds: Infection as a paradigm", 8th Annual Meeting of the ETRS, Copenhagen,
DK,
August 27-30, 1998). The massive colonization of the wound environment with
microorganisms may result in a massive disruption to the course of healing,
which can
lead ultimately to mortality. Frequent causative organisms of bacterial wound
infections
belong to the genera Pseudomonas, Staphylococcus, Clostridium and, among the
yeasts
and molds, to the genera Candida and Aspergillus. Limitation to a few species
is
impossible, since many of the microorganisms may be regarded as opportunistic
pathogens.
A variety of ways have been described for removing microorganisms from the
contaminated or infected tissue of a wound and/or for killing them therein.
Apart from the
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oral administration of antibiotics, pathogenic microorganisms can be removed
from a
wound, in accordance with the prior art, by topical application of a
disinfectant or
antibiotic. Furthermore, antiseptics and antibiotics are cytotoxic, and,
moreover, many
pathogenic strains have developed resistances to antibiotics. The fact that
resistance can
even be developed to an antiseptic has been reported for triclosan-resistant
E. coli
bacteria (McMurry LM et al. (1998) FEMS Microbiol Lett 166(2): 305-9, Cookson
BD et al.
(1991) Lancet 337 (8756): 1548-9; Uhl S (1993) Lancet 342 (8865): 248). The
principal
critical factor in these cases was the widespread, prophylactic use of
triclosan (Irgasan )
in soaps, deodorants, textiles, and plastics.
A well-known use, for example, for the antimicrobial and/or preventive therapy
of
contaminated or infected wounds is that of oxidants (for example, iodine
tincture) or
antiseptics (for example, ointments containing silver sulfadiazine). In the
form, too, of
antimicrobial or antimicrobially impregnated wound contact materials and
woundcare
materials, agents of this kind are employed. Also known in this context is the
use of
silver-containing zeolites.
An overview of the prior-art antimicrobial, silver-containing woundcare
materials is
provided by DE-Al -19958458.
DE-A1-19958458 discloses wound contact materials composed of a synthetic
polymer
material that comprises zeolites containing metal ions.
Known additionally, from EP-A1-1116698 and EP-A1-1116700, are silver-
containing
glasses which exhibit antimicrobial activity. However, these are only embedded
in
thermoplastic polymers that are used in the household and sanitary sectors in
a variety of
forms, such as wallpapers, cutting boards or the like.
In addition to antimicrobial activity, the creation of a moist wound
environment, which in
contrast to the traditional dry wound treatment, such as that by means of
gauze
compresses, for example, offers physiological, and hence better, conditions
for the
natural processes of wound healing, is at the center of the development of
antimicrobial
wound healing.
EP-A1-1159972 discloses a dressing material composed of a self-adhesive
hydrocolloid
composition which permits a moist wound environment and comprises an
antimicrobial
agent containing silver, copper, and zinc.
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Available on the market under the name Contreet-He from Coloplast is an
antibacterial
hydrocolloid dressing which enables a moist wound treatment and an
antibacterial effect
through impregnation with ionic silver.
Corresponding dressings are described in WO 00/09173 and US 5,681,575 and also
in
WO 02/062403 and WO 02/078755.
WO 02/062403 describes an antimicrobial wound contact material comprising in
its
adhesive matrix a silver-containing complex comprising at least one element
from group
IV of the PTE. Preferred elements specified are titanium, hafnium or
zirconium, the
complex preferably constituting a phosphate complex.
The silver ions, in a fraction of 0.01 to 30 mg/cm2 wound contact material,
are released
only on contact with ionic solution. Suitable adhesives are only those which
do not
diminish the release of silver or its antimicrobial activity. As an example of
a matrix a
polyurethane foam is described, the foam characteristics being mandatory with
regard to
the release rate.
WO 02/078755 describes an antimicrobial wound contact material releasing
silver at 50
to 10 000 lig/cm2 wound contact material and having an absorption capacity for
wound
exudate of more than 0.09 g/cm2.
The silver compounds in this case, as in WO 02/062403, are in complex form
with
elements from group 4 of the PTE. Here as well, a zirconium phosphate complex
is
preferred.
The very broad release rate indicated in WO 02/078755 is situated within
ranges which
are likewise attained with the known, prior-art, silver-containing,
antimicrobial, wound
contact materials.
US 6,143,318 describes a method of combating wound infections, encompassing a
wound contact material comprising a water-soluble glass which is able to
release silver
and copper, magnesium or zinc.
GB 2178422 describes prosthesis material containing glass comprising CaO, ZnO,
Mg0,
P205, Na20, and K20 in a specific composition, it being possible for not more
than
5 mol /0 of the P205 to be replaced by Ag20, FeO, CuO, TiO2 or ZrO2.
DE 10213632 describes an antimicrobial, antiinflammatory, wound-healing glass
with a
specific composition, which additionally may also contain Ag, Cu and/or Zn.
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All of the above-described antimicrobial dressing materials containing silver,
known from
the prior art, however, carry at least one drawback. The silver-containing
dressing
materials after a certain time exhibit a darkening due to the formation of
elemental silver
and/or silver oxide. The darkening is accelerated in particular by heat,
moisture, light
and/or radiation effects. The unattractive dark brown or black silver oxide,
moreover, no
longer has any microbicidal effect left, so that the durability of the
activity of the known
dressing materials suffers. As a consequence, the antimicrobial activity
subsides after a
short time, or costly and inconvenient sealing and packaging steps are
necessary for
products of this kind. In particular these products do not satisfy the
esthetic demands of
consumers.
There was therefore a desire for an antimicrobial polymer material which when
employed
as dressing material, in particular as wound contact material, unites all of
the positive
qualities of the individual, known antimicrobial dressing materials and at the
same time
avoids the existing drawbacks of said materials.
The polymer material ought in particular
to be preferably self-adhesive, to obviate the need for additional fixing
materials,
to be of simple structure, so that it can be handled uncomplicatedly even by
lay
people,
- to generate, where desired, a moist wound environment,
to be antimicrobial and to do so even with a very small proportion of active
substance,
to be storable, without detractions from aforementioned qualities,
to satisfy esthetic demands on the part of consumers, and
- to be stable to external influences, such as light, moisture and/or
radiation.
In particular the antimicrobial polymer material ought to satisfy the esthetic
requirements
and ought not to discolor even after a prolonged time.
This was the nexus of problems to be solved.
The skin, particularly the epidermis, is the barrier organ of the human body
and, as such,
is subject to external exposures to a particular degree. According to current
scientific
understanding, the skin represents an immunological organ which, being an
immunocompetent peripheral compartment, plays its own part in inductive,
effective, and
regulative immune processes of the body as a whole. Effective protection,
including
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particularly that of damaged or otherwise-treated human skin, against
bacterial
penetration is therefore accorded an important role.
Substances active against bacteria have been known for a considerable time.
The term
"antibiotics", for example, which cannot be applied to all antimicrobial
substances, can be
5 dated to the year 1941, although the initial discoveries in relation to
penicillin had been
made back in 1929. Antibiotics in the present-day sense are not suitable for
all medical
applications, and certainly not all cosmetic applications, since the warm-
blooded
organism ¨ in other words, for instance, the sick patient ¨ frequently also
suffers
impairment in its metabolic functions in some way or other in the course of
application.
It is an object of the present invention to enrich the state of the art in
this direction, and
hence in particular to provide cosmetic preparations which are antimicrobial
and/or
disinfectant, without the application of the substances being associated with
an
unacceptable deterioration in the health of the individual applying them.
Disinfectant and/or antimicrobial preparations are known, for example, from
the treatment
of acne. ACNE CREME is a mildly disinfectant cream. It is suitable for those
cases of
acne which require a peeling treatment. Further known cosmetic preparations
with
disinfectant and antiinflammatory effects contain active substances, such as,
for
example, chlorhexidine, chlorhexidine gluconate, Hamamelis-zinc oxide,
panthenol,
dexpanthenol and/or pure urea.
Drawbacks of these cosmetics, however, are in some cases irritation to the
skin
(reddening, flaking) and also, in certain cases, allergic reactions.
Another object of the present invention is therefore to provide cosmetic
preparations
which combine alleviation for irritated skin conditions and/or assistance with
re-
establishment of dermal homeostasis with simultaneous care for the skin.
The cosmetic treatment of the skin and hair also includes their cleansing.
Cleansing
implies not only removing unwanted dirt and eliminating microbes of all kinds
but also
raising the level of psychological and physical wellbeing. Candidates first in
line for
cleansing purposes are surfactant preparations.
Surfactants are amphiphilic compounds with the ability to dissolve organic
apolar
substances in water. Owing to their specific molecular structure, with at
least one
hydrophilic and one hydrophobic moiety, they ensure reduction of the surface
tension of
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water, wetting of the skin, facilitation of soil removal and dissolution, easy
rinsing, and ¨
where desired ¨ foam regulation.
The hydrophilic fractions of a surfactant molecule are mostly polar functional
groups,
examples being ¨000-, -0S032-, -S03-, while the hydrophobic components are
generally
apolar hydrocarbon radicals. Surfactants are generally classified according to
the identity
and charge of the hydrophilic moiety. Four groups may be distinguished here:
= anionic surfactants,
= cationic surfactants,
= amphoteric surfactants, and
nonionic surfactants.
Antibacterial cleansing preparations, such as soaps, frequently contain
triclocarban
(TCC), triclosan (Irgasan DP 300) or chloroxylenol (PCMX). These active
substances
block a particular enzyme which needs a series of bacteria to survive. As a
result of the
widespread propagation of these active substances, however, there is
increasingly a
development-of-resistance effect on the part of the user.
It is therefore also an object of the present invention to provide a cleansing
preparation
which has an antimicrobial and/or disinfectant and also skin-calming and care
effect.
These objects are achieved by means of a material as specified in the main
claim. The
dependent claims provide advantageous developments of the material, and its
use.
It was surprising, and not to have been foreseen by the skilled worker, that a
material
suitable for placement or application to the skin, comprising antimicrobial,
silver-
containing glass of composition
P205 30-75 mol%,
Si02 5-50 mol%,
R10 20-55 mol%,
R220 0- 5 mol%,
A1203 3-
20 mol%, based on the total amount of the silver oxide-free
glass, and
0.1% to 5% by weight of Ag20, based on the total mass of the glass,
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R1 being selected from Ca, Mg, Zn and/or Cu and R2 being selected from Na, K
and/or
Li, would completely solve the nexus of problems.
The statement of the glass composition in mol% indicates the constituents
without silver
oxide. Stated additionally is the amount of silver oxide in % by weight, based
on the total
mass of the glass, which then contains silver.
Particularly a material having a glass composition
P205 40-60 mol%,
R10 35-55 mol%,
R220 0- 5 mol%,
Si02, A1203 5-20 mol%, and
Ag20 0.1%-5% by weight, and
a material having a glass composition
P205 45-55 mol%,
CaO, MgO 35-50 mol%,
Na20, K20 0- 5 mol%,
Si02 0- 5 mol%,
A1203 5-15 mol% and
Ag20 0.5%-3% by weight, and also, preferably, a material having a glass
composition
P205 50 mol%,
MgO 44 mol%,
A1203 6
mol%, based on the total amount of the silver oxide-free
glass, and
Ag20 2% by weight, based on the total mass of the glass
or having a glass composition
P205 73.35% by weight,
MgO 18.33% by weight,
A1203 6.32% by weight, and
Ag20 2.0% by weight, based on the total glass mass, has
proven
particularly application-friendly and effective.
Material of the invention comprehends all that can be placed or applied on the
human or
animal skin and is able to ensure the emission and delivery of silver to the
surrounding
area. These materials are, in particular, polymer materials, such as, for
example,
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polyurethanes, cosmetics, especially emulsion-based cosmetic preparations,
disinfectant
cleansing preparations, and antimicrobial skin contact materials, pads or
wipes.
These materials contain preferably 0.001% to 40% by weight, preferably 0.05%
to 1% by
weight, of the silver-containing glass, based on the total mass of the
material.
The antimicrobial or disinfectant silver present in these materials is
available in the form
of free silver ions and is characterized as the oxide Ag20 only in accordance
with the way
of writing the composition of the glass.
One preferred embodiment of the materials of the invention encompasses polymer
materials. The polymer material serves primarily as a dressing material for
application to
the human skin. Dressing materials are also taken to include wound contact
materials, so
that, in particular, the polymer material of the invention can be used with
advantage as
wound contact material.
The invention hence also provides a polymer material having antimicrobial
properties,
characterized in that materials which are used in wound healing, such as
synthetic
polymer materials, for example, polyurethanes, polyacrylates, SIBS compounds,
SEBS
compounds, natural rubber compounds, and chitosans, alginates, hydrogels,
hydrocolloids, but especially polyurethanes are combined with the silver-
containing
glasses, which in preferred embodiments of the invention can be incorporated
at 0.01%
to 40% by weight, with particular preference to 0.05% to 1% by weight, into
the polymer
materials. It is not necessary here for the matrix mandatorily to be foamed,
as is required
in the prior art for effective silver release.
Preference is given to selecting self-adhesive polymer materials, in order to
prevent
additional edge sticking of the wound contact material.
Deserving of particular emphasis in accordance with the invention is the use
of the silver-
containing glasses as part of a self-adhesive polyurethane matrix which can be
used as a
hydroactive wound contact material for moist wound healing.
Preference is given to employing elastic, crosslinked polyurethanes with a
mass
application weight of 50 to 2500 g/m2, as are described, for example, in
WO 97/43328 Al.
Generally speaking, polyurethanes are prepared from the known starting
compounds of
polyurethane chemistry by known processes, which are represented in patents
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DE-A 3103499, DE-A 3103500, EP 0 147 588 Al, EP 0 665 856 B1
or
DE 196 18 825 Al.
Polyurethane is used as a basis for the polymer material. The preparation of
the
polyurethane (c) is accomplished by the polymerization of an alcohol (a) with
an
isocyanate (b).
0
R¨OH + 0=C= N¨R' __________________________
(a) (b)
(c)
A decisive advantage of the polyurethane polymer matrices or gel matrices are
their self-
adhesive properties, which obviate the additional application of an adhesion
layer to the
matrix, for the purpose of fixing the polymer material in the region of the
skin. At its most
simple, the silver-containing polyurethane matrix is located between a cover
layer firmly
anchored to it, also called backing layer, and a removable release layer.
The purpose of the removable release layer is to secure the adhesive layer,
and to
improve the stability in transit and in storage, and it is removed prior to
application to the
skin.
Suitable polyurethanes as matrix are subject matter of DE 196 18 825, which
discloses
hydrophilic, self-adhesive polyurethane gels composed of
a) polyether polyols having 2 to 6 hydroxyl groups, OH numbers of 20 to
112, and an
ethylene oxide (EO) content of 10% by weight,
b) antioxidants,
c) bismuth(III) carboxylates soluble in the polyols a) and based on
carboxylic acids
having 2 to 18 carbon atoms, as catalysts, and
d) hexamethylene diisocyanate, with a product of the functionalities of the
polyurethane-forming components a) and d) of at least 5.2, the amount of
catalyst
c) being 0.005% to 0.25% by weight, based on polyol a), the amount of
antioxidants b) being in the range from 0.1% to 1.0% by weight, based on
polyol
a), and the ratio of free NCO groups of component d) to the free OH groups of
component a) (isocyanate index) being selected in the range from 0.30 to 0.70.
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It is preferred to use polyether polyols containing 3 to 4, very preferably 4-
hydroxyl
groups, with an OH number from 20 to 112, preferably 30 to 56. In the case of
the
polyether polyols used in accordance with the invention the ethylene oxide
content is
preferably 20% by weight.
5
The polyether polyols are known per se as such and prepared for example by
polymerizing epoxides, such as ethylene oxide, propylene oxide, butylene oxide
or
tetrahydrofuran, with themselves or by addition reaction of these epoxides,
preferably of
ethylene oxide and propylene oxide ¨ where appropriate as a mixture with one
another or
10 separately in succession ¨ with starter components having at least two
reactive hydrogen
atoms, such as water, ethylene glycol, propylene glycol, diethylene glycol,
dipropylene
glycol, glycerol, trimethylolpropane, pentaerythritol, sorbitol or sucrose.
Representatives
of the stated, relatively high molecular mass polyhydroxyl compounds to be
used are
listed for example in High Polymers, vol. XVI, "Polyurethanes, Chemistry and
Technology" (Saunders-Frisch, lnterscience Publishers, New York, vol. 1, 1962,
pp. 32-
42).
The isocyanate component used is monomeric or trimerized hexamethylene
diisocyanate
or hexamethylene diisocyanate modified by means of biuret, uretdione and/or
allophanate groups or by prepolymerization with polyether polyols or mixtures
of
polyether polyols based on the known starter components having 2 or > 2
reactive H
atoms and epoxides, such as ethylene oxide or propylene oxide with an OH
number of
850, preferably 100 to 600. Preference is given to using modified
hexamethylene
diisocyanate, especially hexamethylene diisocyanate modified by
prepolymerization with
polyether diols with an OH number of 200 to 600. Very particular preference is
given to
modifications of hexamethylene diisocyanate with polyether dials with an OH
number of
200-600 whose residual monomeric hexamethylene diisocyanate content is below
0.5%
by weight.
Suitable catalysts for the polyurethane gels of the invention are bismuth(III)
carboxylates
soluble in the anhydrous polyether polyols a) and based on linear, branched,
saturated or
unsaturated carboxylic acids having 2 to 18, preferably 6 to 18, C atoms.
Preference is
given to Bi(III) salts of branched saturated carboxylic acids with tertiary
carboxyl groups,
such as 2,2-dimethyloctanoic acid (for example, Versatic acids, Shell). Highly
suitable are
preparations of these Bi(III) salts in excess fractions of these carboxylic
acids. A solution
which has been found outstanding is that of 1 mol of the Bi(III) salt of
Versatic 10 acid
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(2,2-dimethyloctanoic acid) in an excess of 3 mol of this acid, with a Bi
content of
approximately 17%.
The catalysts are used preferably in amounts of 0.03% to 0.1% by weight, based
on the
polyol a).
Antioxidants suitable for the polyurethane gels of the invention include, in
particular,
sterically hindered phenolic stabilizers, such as BHT (2,6-di-tert-butyl-4-
methylphenol),
VulkanoxTM BKF (2,2 min ¨methylene-bis-(6-tert-butyl-4-methyl phenol) (Bayer
AG),
lrganoxTM 1010 (pentaerythrityl tetrakis[3-(3,5-di-tert-butyl-4-
hydroxyphenyl)propionate]),
IrganoxTm 1076 (octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate)
(Ciba-Geigy)
or tocopherol (vitamin E). Preference is given to using those of the a-
tocopherol type.
The antioxidants are used preferably in amount g of 0.15% to 0.5% by weight,
based on
polyol a).
The isocyanate index (ratio of the free NCO groups used in the reaction to the
free OH
groups) of the polyurethane gel compositions of the invention is situated,
depending on
the functionality of the isocyanate components and polyol components employed,
in the
range from 0.30 to 0.70, preferably in the range from 0.45 to 0.60. The
isocyanate index
necessary for gel formation can be estimated very easily by the following
formula:
Apoiyon 0 (45,0cyanate)-1) 0 index 2
2
index --41
Apolyone (fiLs'acYanate) ¨1)
f: functionality of the isocyanate or polyol component
Depending on the target stickiness or elasticity of the gel, the isocyanate
index for actual
use may deviate by up to 20% from the calculated figure.
The polyurethane gel compositions of the invention are prepared by customary
processes, as described for example in Becker/Braun, Kunststoff-Handbuch, vol.
7,
Polyurethane, p. 121 if, Carl-Hauser, 1983.
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With further preference polyurethane gels are employed of the kind disclosed
in
EP 0 665 856 B1.
The hydrophilic polyurethanes are obtainable, accordingly, from
1. a polyurethane gel which comprises
(A) 25-62% by weight, preferably 30-60% by weight, more preferably 40-57% by
weight, based on the total of (A) and (B), of a covalently crosslinked
polyurethane
as high molecular weight matrix and
(B) 75-38% by weight, preferably 70-40% by weight, more preferably 60-43% by
weight, based on the total of (A) and (B), of one or more polyhydroxyl
compounds
which are firmly bound in the matrix by secondary valence forces and have an
average molecular weight between 1000 and 12 000, preferably between 1500
and 8000, more preferably between 2000 and 6000, and an average OH number
between 20 and 112, preferably between 25 and 84, more preferably between 28
and 56, as liquid dispersant, the dispersant being substantially free of
hydroxyl
compounds with a molecular weight below 800, preferably below 1000, more
preferably below 1500, and also, where appropriate,
(C) 0 to 100% by weight, based on the total of (A) and (B), of fillers and/or
additives,
and which is obtainable by reacting a mixture of
a) one or more polyisocyanates,
b) one or more polyhydroxyl compounds with an average molecular weight
between 1000 and 12 000, and with an average OH number between 20 and 112,
c) where appropriate, catalysts or accelerators for the reaction between
isocyanate groups and hydroxyl groups, and, where appropriate,
d) fillers and additives known per se from polyurethane chemistry,
this mixture being substantially free of hydroxyl compounds with a molecular
weight below 800, the average functionality of the polyisocyanates (F1) being
between 2 and 4, the average functionality of the polyhydroxyl compound (Fr)
being between 3 and 6, and the isocyanate index (K) conforming to the formula
K= 300 X
+7
(F, = Fp) ¨1
in which X 120, preferably X 5_ 100, more preferably X 90, and the index K is
at values between 15 and 70, the stated average values of molecular weight and
OH number being understood as number averages,
=
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2. a water-absorbing material and/or
3. a nonaqueous foaming agent.
When preparing preferentially self-adhesive polyurethanes it is necessary to
take
account, when selecting the gel-forming components, of compliance with the
conditions
defined above, since, otherwise, tack-free elastic gels are obtained rather
than self-
adhering gels.
Preferred polyhydroxyl compounds are polyether polyols, of the kind specified
exhaustively in the laid-open specifications recited above.
Suitable polyisocyanate components include not only (cyclo)aliphatic but also
aromatic
isocyanates. Preferred (cyclo)aliphatic polyisocyanates are hexamethylene 1,6-
diisocyanate and also its biurets and trimers, and hydrogenated
diphenylmethane
diisocyanate ("MDI") products. Preferred aromatic polyisocyanates are those
obtained by
distillation, such as MDI mixtures of 4,4' and 2,4' isomers or 4,4'-MDI, and
also tolylene
diisocyanate ("TDI") products.
The diisocyanates may be selected in particular for example from the group of
the
unmodified aromatic or aliphatic diisocyanates or else from modified products
formed by
prepolymerization with amines, polyols or polyether polyols.
Advantages that may be stated of the polyurethanes of the invention in
comparison to
other polymers used for producing dressing materials include the following
points:
= Polyurethane can be provided flexibly as a self-adhesive or nonadhesive
matrix.
= As a self-adhesive system it is possible to dispense with addition of
further
adhesives, which under certain circumstances give rise to side effects such as
maceration, inflammation of the dermal areas, reduction of cutaneous
respiration, etc.
= Polyurethanes prove extremely advantageous over other adhesive materials,
such
as polyacrylates, rubber, etc., since they contain no allergenic potential.
= Polyurethane exhibits very good water vapor permeability. This ensures
that, in
the case of application for a prolonged period, there is no maceration through
the release
of water by the skin.
= The oxygen permeability of polyurethane ensures a good supply of oxygen
to the
covered skin site, thereby countering damage to the tissue.
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= Polyurethane is allergenically neutral, so that following application
there is no
likelihood of allergic reactions on the part of the body.
= In contrast to other materials such as hydrocolloids or hydrogels, for
example,
polyurethane, moreover, shows no tendency to disintegrate on prolonged contact
with
fluids such as wound exudate. Consequently, on prolonged contact with wound
fluid, a .
wound dressing produced from polyurethane does not leave residues in the wound
that
interfere with further wound healing.
= Self-adhesive polyurethane loses its adhesion on contact with liquid, so
that
sticking to newly formed tissue is prevented and, moreover, painless
detachment of the
wound cover is ensured.
= Polyurethane wound contact materials of the invention produce a moist
wound
environment, leading to more rapid wound healing.
Besides the preferred polyurethane matrices, it is also possible to use
polymer materials
having a different basis.
The silver glass which is to be incorporated, and which impairs the respective
underlying
crosslinking reaction of the polymer matrix, may be introduced into the
matrix, where
necessary, following the crosslinking reaction or the formation of the matrix,
in the form
of a solution or cosmetic emulsion.
Particularly advantageous self-adhesive matrices containing silver glass can
be produced
from the following solvent-containing or solvent-free filled or unfilled,
crosslinking or
noncrosslinking, hydrophilic or hydrophobic matrix systems:
Polyisobutylene matrices
The pressure-sensitive adhesive (PSA) matrix for controlled delivery of silver
ions from
silver glass to the skin, the PSA matrix being free from mineral oils and
tackifier resins
and being constructed from
a) synthetic scaffold polymers based on polyisobutylene, at 25% to 90% by
weight,
b) amorphous poly-a-olefin, at 5% to 30% by weight,
c) an insoluble, especially hydrophilic filler, at 0 to 60% by weight, and
d) silver glass, at 0.005% to 10% by weight.
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In one advantageous embodiment of the matrix the polyisobutylene is composed
of high
molecular weight PIB at 5% to 55% by weight and low molecular weight PIB at
20% to
60% by weight.
5 A typical PSA of the invention is therefore composed of the following
components:
high molecular weight PIB 5%-55%, preferably 25%-45% by weight
low molecular weight PIB 20%-60%, preferably 30%-50% by weight
amorphous poly-a-olefin 5%-30%, preferably 5%-10% by weight
hydrophilic filler 0-60%, preferably 0-30% by weight
10 silver glass 0.005%-10%, preferably 0.01%-5% by
weight
Optionally it is possible in addition to add up to 20% by weight of a
permeation promoter
(lipophilic solubilizer/enhancer) such as decyl oleate, isopropyl myristate,
and isopropyl
palm itate (IPM and IPP).
The stated formula constituents are defined more precisely as follows:
High molecular weight PIB denotes:
polyisobutylene having a weight-average molecular weight (M,) of 300 000 to 1
100 000,
preferably between 650 000 and 850 000. Polymers of this kind are available
commercially, for example, under the trade names OppanolTM B100 or VistanexTM
MM-
L80.
Low molecular weight PIB denotes:
polyisobutylene having a weight-average molecular weight (Mõ,,) of 40 000 to
300 000,
preferably between 60 000 and 100 000. Polymers of this kind are available
commercially, for example, under the trade names OppanolTM B15 or VistanexTM
LMMH.
Amorphous poly-a-olefin denotes:
amorphous copolymers based on ethylene and propylene, butylene or 1-hexene.
The
preferred weight-average molecular weight (M,,,) is 5000 to 100 000,
preferably between
10 000 and 30 000. Polymers of this kind are available commercially, for
example, under
the trade names Eastoflex or Vestoplastg.
In the stated polymer matrix, insoluble, hydrophilic particles based on
cellulose are
considered hydrophilic fillers. Preference is given to an average particle
size of less than
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or equal to 100 m with an extremely uniform surface. Materials of this kind
are available
commercially, for example, under the trade names AvicelTM and ElcemaTM.
The PIB matrix is preferably produced in a process in which all of the
components of the
PSA matrix are homogenized in the melt, with the addition of solvent being
omitted.
With particular preference all of the components are processed in a continuous
or batch
operation at a temperature below 100 C.
Further advantageous embodiments of the polyisobutylene matrices that may be
used
can be taken from publications DE 100 56 010 or DE 100 56 011.
Polyacrylic acid matrices
Polyacrylates are likewise advantageous in the sense of the matrices of the
invention.
Polyacrylates advantageous in accordance with the invention are acrylate-alkyl
acrylate
copolymers, particularly those selected from the group of products known as
carbomers
or Carbopols (Carbopol is a registered trade mark of the B.F. Goodrich
Company). In
particular, the acrylate-alkyl acrylate copolymer or copolymers which are
advantageous in
accordance with the invention are distinguished by the following structure:
CH3
¨C H2¨? H _______________________________ C H2-C __
C=0 C=0
OH
x - -y
In this formula R' is a long-chain alkyl radical and x and y are numbers which
symbolize
the respective stoichiometric fraction of each of the comonomers.
Particular preference in accordance with the invention is given to acrylate
copolymers
and/or acrylate-alkyl acrylate copolymers which are available from the B.F.
Goodrich
Company under the commercial designations Carbopol 1382, Carbopol 981, and
Carbopol 5984, preferably polyacrylates from the group of the Carbopols of
grades
980, 981, 1382, 2984, and 5984, and more preferably carbomer 2001.
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Further of advantage are copolymers of C10-30 alkyl acrylates and one or more
monomers
of acrylic acid, methacrylic acid or esters thereof which are cross-linked
with an allyl ether
of sucrose or with an allyl ether of pentaerythritol.
Advantageous compounds are those bearing the INCI name "Acrylates/C10-30 Alkyl
Acrylate Crosspolymer". Particularly advantageous are those obtainable under
the
commercial designations Pemulen TR1 and Pemulen TR2 from the B.F. Goodrich
Company.
Advantageous compounds include those bearing the INCI name Ammonium
acryloyldimethyltaurateNinylpyrrolidone copolymers.
Advantageously in accordance with the invention the Ammonium
acryloyldimethyltaurate/Vinylpyrrolidone copolymer or copolymers have the
empirical
formula [C71-116N2SO4]n[C6H9NO]m, corresponding to a statistical structure as
follows
-n -m
0
0" 1\1H
H30
H3C 2
I C) 0
SO3 NH4
Preferred species in the sense of the present invention are set down in
Chemical
Abstracts under the Registry numbers 58374-69-9, 13162-05-5 and 88-12-0, and
are
obtainable under the commercial designation Aristoflex AVC from the company
Clariant
GmbH.
Of advantage, furthermore, are copolymers/crosspolymers comprising
Acryloyldimethyl
Taurate, such as Simugel EG or Simugel EG from the company Seppic S.A.
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In the case of a preferred polyacrylic acid matrix of the invention containing
silver glass,
the polyacrylic acid is crosslinked with the aid of polyvinylpyrrolidone
(PVP).
Crosslinking proceeds via the formation of a quaternary ammonium salt of PVP.
This
kind of crosslinking leads to organic salts which, in contrast to the known
metal-salt
crosslinking agents, are attached via the hydroxy functions of the polyacrylic
acid
molecules. As in the case of the metal salts, the reaction is reversible and
can be
reversed by adding water or acids. The viscosity of the resultant gel can be
controlled not
only by the amount of crosslinker but also via the molecular weight of the
PVP. In this
relationship, high molecular weights lead to gels with low viscosity, and low
molecular
weights to gels with high viscosity and bond strength. The advantage of this
kind of
crosslinking is the tailored preparation, via the parameters of PVP fraction
and PVP
molecular weight, of gel matrices whose tack, cohesiveness, and viscosity can
be
adjusted individually to the particular area of application.
This effect of the influence of the molecular weight of the PVP on the
viscosity and bond
strength of the gel matrix can be attributed to the following finding: In the
case of long-
chain PVP the number of pyrrolidone subunits per macromolecule is
significantly higher
than in the case of short-chain PVP. As a result there is an increased
incidence of
reactions of the same reactants with one another, since the macromolecules are
readily
able to orient themselves to form bundles. These reactions do not lead to the
formation
of linkage points with two or more polyacrylic acid molecules. There are
therefore only a
few cross-connections made to other polyacrylic acid molecules, and hence only
a few,
large meshes are linked. This circumstance leads to a relatively loosely
linked gel of low
viscosity. In the case of short-chain PVP, in contrast, because of the greater
mobility and
lower tendency of the molecules to undergo orientation to strands, a greater
number of
links to different polyacrylic acid molecules are formed, leading to a
narrower mesh size
and to a lower flexibility and viscosity on the part of the gel.
The viscosity of the gels can be controlled, furthermore, via other factors as
well. Thus,
for example, the amount of PVP plays a co-determining part with regard to the
structure
of the gel. When a saturation point is exceeded, competing reactions of the
free PVP
molecules with those which have already crosslinked occur. These competitive
reactions
lead to crosslinking points being broken open in favor of unlinked aggregates
of
polyacrylic acid and the excess PVP molecules. The consequence of this
oversaturation
is a decrease in the total number of linkage points and hence a reduction in
the gel
viscosity. A further possibility which can be utilized for controlling the gel
viscosity is the
addition of protic solvents (e.g., water, alcohols, amines, thiols) or organic
proton donors
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(carboxylic acids, salicylic acid for example) or inorganic agents (e.g.,
Lewis acids). Here,
compounds from the classes of substance of the tertiary polyamines and of the
polyamides, especially, are appropriate. In each of these cases the addition
of the agents
contributes to diminishing the coordination sites either on the polyacrylic
acid or on the
PVP. As a result the number of potential linkage points for the formation of
gel meshes is
lowered, which has a direct influence on the viscosity of the gel.
Furthermore, the
resultant gel properties of the matrices can be influenced by way of the
molecular weight,
degree of substitution, and degree of crosslinking of the polyacrylic acid
employed.
In order to produce particular performance properties the gel matrices are
admixed with
the appropriate plasticizers, solubilizers, penetration enhancers, fillers
and/or other
known additions.
Polyacrylates advantageous as a gel basis are acrylate-alkyl acrylate
copolymers,
particularly those selected from the group of products known as carbomers or
Carbopols
(Carbopol is actually a registered trade mark of the B.F. Goodrich Company).
In
particular, the advantageous acrylate-alkyl acrylate copolymer or copolymers
are
distinguished by the following structure:
CH3
¨C H2¨CH _________________________________ CH2 C _____
1
C=0 C=0
1
OHR`
x - -y
In this formula R' is a long-chain alkyl radical and x and y are numbers which
symbolize
the respective stoichiometric fraction of each of the comonomers.
Particular preference in accordance with the invention is given to acrylate
copolymers
and/or acrylate-alkyl acrylate copolymers which are available from the B.F.
Goodrich
Company under the commercial designations Carbopol 1382, Carbopol 981, and
Carbopol 5984, preferably polyacrylates from the group of the Carbopols of
grades
980, 981, 1382, 2984, and 5984, and more preferably carbomer 2001.
Further of advantage are copolymers of C10-30 alkyl acrylates and one or more
monomers
of acrylic acid, methacrylic acid or esters thereof which are cross-linked
with an allyl ether
of sucrose or with an allyl ether of pentaerythritol.
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Polyacrylic acid and/or copolymers thereof are used preferably in an amount of
5%-55%
by weight, more preferably between 5%-30% by weight. All percentages here are
based
on weight fractions of gel matrix, unless something to the contrary is
specified.
5 The crosslinker used is polyvinylpyrrolidone (PVP) e.g., LuviskolTM from
BASF, preferably
in an amount of 0.25%-60% by weight, more preferably between 1%-30% by weight.
To
the same degree it is also possible to use PVP copolymers such as, for
example,
vinylpyrrolidone-vinyl acetate (povidone acetate; KollidonTM VA 64),
terpolymers based
on vinylpyrrolidone and acrylic acid or methacrylic acid and/or their esters
(LuviflexTM
10 VBM 35), copolymers of vinylpyrrolidone and vinylimidazolium
methochloride (LuviquatTM
products) as a so-called PVP crosslinking agent.
As further gel constituents it is possible to employ polyalcohol or
polyalcohols, e.g., 1,2-
propanediol, glycerol, and/or water, preferably in an amount of 5%-90% by
weight, more
15 preferably between 5%-45% by weight.
Further constituents of the gel matrix can be solubilizers, e.g., polyethylene
glycols
(LutrolTM E400, E600 from BASF) in an amount of 0-50% by weight, preferably 0-
30% by
weight, neutralizing agents, e.g., tromethamol, triethanolamine and/or
dexpanthenol, in
20 an amount 0-30% by weight, preferably 0-15% by weight, filler(s), e.g.,
silica, micronized
cellulose and/or gelatin, in an amount of 0-30% by weight, preferably 3%-15%
by weight,
and natural active substance(s), e.g., menthol or jojoba oil, in an amount of
0-35% by
weight, preferably 0-15% by weight.
These polyacrylic acid matrices containing silver glass are produced
solventlessly,
preferably at room temperature, in commercially customary compounders or
suitable
extruders.
Further advantageous embodiments of polyacrylic acid matrices for use as the
matrix
containing silver glass can be taken from patent application DE 101 42 918.
Silicone matrices
The moisture-absorbing, silicone-based matrix containing silver glass for
cosmetic or
pharmaceutical skin treatment, with a PSA matrix, is composed of
a) silicone
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b) gel former
c) where appropriate, a silicone resin.
In a first advantageous embodiment of the invention the matrix has the
following
composition:
a) silicone: 55% to 80%,
particularly 60% to 75% by weight
b) gel former: 20% to 40%,
particularly 25% to 40% by weight
c) silver glass: 0.01% to 10%, particularly 0.5%-5% by weight
Silicones are processed as one- or two-component systems. Crosslinking is
generally
accomplished as polycondensation, with elimination of acetic acid, or as
polyaddition,
using a platinum catalyst.
For producing the matrices described a commercially customary two-component
system
comprising polydimethylsiloxane (see figure) was used, namely 07-9600 A+B;
from
Dow Corning,
CH3 CH3
CI
H3
H3C-51-0¨Si¨O¨Si¨CH3
CH3 CH.1
- 8H3
To adjust the bond strength, optionally, a polydimethylsiloxane crosslinked
with silicone
resin (PSA MD 74602; from Dow Corning) was used.
Water absorbency on the part of the matrix was achieved by incorporating gel
former
having a high relative surface area in amounts such that the gel former can
have
intermolecular cross-connections from the surface to the interior of the
matrix. Gel
formers of this kind are, for example, polyacrylic acid, polyacrylonitrile or
microcrystalline
cellulose. Use was made primarily of polyacrylic acid products of the Carbopol
series,
Goodrich Corp.
To vary the water absorbency, additionally, strong gel formers with a low
relative surface
area were incorporated, such as, for example, sodium polyacrylate (Favorsorb;
from
Stockhausen).
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Preparation takes place at room temperature in commercially customary mixers.
First of
all, in the case of 2-component systems, the two silicone components are mixed
with one
another. Thereafter, where necessary, the silicone resin component is stirred
in, then the
gel former or formers are incorporated, and, finally, silver glass is stirred
in.
The matrix is coated onto a backing and the solvent of the silicone resin
component is
allowed to evaporate from the matrix. The duration of the crosslinking
reaction of the
silicone matrix can be controlled as a function of temperature. The adhesive
side of the
matrix is lined with a release backing.
Optionally, the silver glass that is to be incorporated can also be introduced
after the
crosslinking reaction, in the form of a solution or in a cosmetic emulsion,
via the channels
of the gel formers.
Further advantageous embodiments of silicone matrices for use as a matrix
containing
silver glass can be found in patent application DE 101 14 382.
Rubber matrices
The moisture-absorbing, rubber-based matrix containing silver glass for
cosmetic or
pharmaceutical skin treatment, having a PSA matrix, is composed of
a) rubber
b) tackifier resins
c) hydrophilic, water-absorbing, dispersed solid
d) aging inhibitor system
In one advantageous embodiment of the invention this matrix has the following
composition:
silver glass 0.1% to 10%, particularly 0.5%-5% by weight
a) rubber 20%-70%, particularly 30%-50% by weight
b) tackifier resin 10%-50%, particularly 20%-40% by weight
c) filler 10%-30%, particularly 12%-20% by weight
d) aging inhibitor system 0.5%-5%, particularly 1%-3% by weight
Rubber adhesives in the form indicated are processed in solution. The rubber
used is of
either natural or synthetic origin. The mechanical properties of the various
grades
produce, in the mix of a formula, the desired scaffold properties of a rubber
adhesive.
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The tackifier resins employed impart the necessary pressure-sensitive adhesion
or tack.
Plasticizers, such as mineral oils, serve to fine-tune the mechanical
properties of the
formula.
Water absorbency on the part of the matrix was obtained by distributing a
hydrophilic,
water-absorbing solid in fine dispersion in the formula.
As a group of substance, plant root flours and starch flours are preferably
employed; also
possible are celluloses and their derivatives and also other water-absorbing
solids. The
water absorbency can be influenced by the identity and amount of the
hydrophilic solid.
Owing to their chemistry, rubber adhesives are sensitive to oxidation. They
must
therefore be furnished with a suitable aging inhibitor system. As well as
functioning as an
antioxidant, this system must also be physiologically unobjectionable.
Production takes place at room temperature in commercially customary mixers.
The
rubber constituents are dissolved in a suitable solvent and then the remaining
components, including the active substance, are added.
The composition is coated onto a backing and the solvent is evaporated from
the
composition. The duration of the evaporation procedure can be controlled as a
function
of temperature. The adhesive side of the composition is lined with a release
backing.
SBC hotmelt matrices
In the case of the PSA matrix for controlled delivery of silver glass to the
skin, the
scaffold-forming substance of the PSA matrix is formed by styrene block
copolymers
(SBC).
In one advantageous version the latex-free PSA has the composition indicated
below:
5% to 90% by weight of block copolymers,
5% to 80% by weight of tackifiers such as oils, waxes, resins
and/or mixtures
thereof, preferably mixtures of resins and oils,
less than 60% by weight of plasticizers,
less than 15% by weight of additives,
less than 5% by weight of stabilizers,
less than 10% by weight of additions containing silver glass.
The aliphatic or aromatic oils, waxes, and resins which serve as tackifiers
are preferably
hydrocarbon-based oils, waxes and resins, the oils (such as paraffinic
hydrocarbon oils)
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or the waxes (such as paraffinic hydrocarbon waxes) having a favorable effect
on the
adhesion by virtue of their consistency. In one special form the adhesive
includes at least
one aliphatic hydrocarbon resin and at least one aromatic hydrocarbon resin.
Plasticizers
used are medium- or long-chain fatty acids and/or their esters. These
additions serve to
adjust the adhesive properties and the stability. Where appropriate, further
stabilizers
and other auxiliaries are employed.
The cohesive adhesive can be filled with mineral fillers, fibers, and hollow
or solid
microbeads.
Optionally it is also possible in addition to add up to 15% by weight of a
permeation
promoter as a lipophilic solubilizer, such as, for example, decyl oleate or
isopropyl
myristate and isopropyl palmitate (IPM and IPP).
The matrix is produced preferably by means of processes in which all
components of the
PSA matrix are homogenized in the melt, with the addition of solvents being
omitted.
With particular preference, all of the components are processed in continuous
or batch
operation at a temperature below 100 C.
Moisture-adhesive polymer film based on PVA/PAA
The moisture-activated self-adhesive polymer film for disinfectant delivery of
silver ions
from silver glass comprises a homogeneous mixture of polyvinyl alcohol having
an
average molar weight of 20 000 to 100 000 g/mol, preferably 28 000 to 40 000
g/mol, and
a degree of hydrolysis of 80% to 95%, preferably 85% to 90%, and polyacrylic
acid
having an average molar weight of 450 000 to 4 000 000, preferably 1 300 000
to
4 000 000 g/mol, the weight ratio of polyvinyl alcohol to polyacrylic acid in
the polymer
film being situated in the range 10:1 to 1:1.
In one advantageous embodiment the moisture-activated self-adhesive polymer
film
contains 0.001%-10% of silver glass.
This wound dressing of the invention constitutes a solvent-free matrix system
formed
from the synthetic polymers polyvinyl alcohol and polyacrylic acid, which
adheres only to
the moist wound region, which, after the wound has healed, detaches
automatically and
painlessly and can be produced inexpensively with simple technical means.
Furthermore,
the wound dressing is permeable to air and water vapor.
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Wound dressings which have been found particularly suitable are those for
which the
weight ratio of polyvinyl alcohol to polyacrylic acid in the film is in the
range 5:1 to 3:1.
The moisture-activated self-adhesive polymer film may additionally be equipped
with
5 other active substances for wound treatment. For improved wound healing,
therefore, the
wound dressing may be doped with active pharmaceutical and/or cosmetic
substances
for continuous release into the wound. Preferred active pharmaceutical
substances that
may be mentioned include dexpanthenol, lidocaine, and urea; preferred active
cosmetic
substances that may be mentioned include, for example, the groups of the
flavonoids
10 and sericosides. The fraction of active substances in the wound dressing is
advantageously 0.01% to 10% by weight. The active substance is introduced into
the
polymer matrix in the course of polymer formation by known processes.
In its simplest embodiment the wound dressing can be applied as a thin film
for physical
15 covering and/or for protecting against infection, application taking
place to moist
superficial wounds. Owing to the transparency of the film it is possible in
this case to
observe the course of wound healing over time, without removing the wound
cover, and
without the need for painful redetachment of the dressing and the application
of a new
wound dressing, as in the case of conventional wound dressings.
To increase the internal strength of the wound dressing it is possible for the
polymer film
to be embossed on one or two sides. Similarly, by means of an inserted mesh of
synthetic or natural fabric, the polymer film can be given a reinforced
configuration.
Examples of suitable fabrics include cotton net fabrics with a mesh size of 1
to 2 mm or a
perforated nonwoven of 67% viscose and 33% polyester.
In a further embodiment the polymer matrix is lined on one side with a backing
material
(wovens, nonwovens, foams, plastics, etc.) and applied as a composite film.
Depending
on the backing material used it is possible by this means to control the water
vapor
permeability, the strength of the wound cover, the cushioning against
pressure, and other
physical properties of the wound cover.
The co-decisive advantage of the polymer film is its property of being self-
adhesive on a
moist base, which renders additional application of an adhesion layer to the
matrix, for
the purpose of fixing the wound dressing in the region of the skin,
superfluous. One of
the consequences of this is an inexpensive and simple mode of production.
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The particular property of the moist adhesive property of the wound dressing
of the
invention is explained by the finely divided incorporation of the hydrophilic
polyacrylic acid
into an only moderately hydrophilic polyvinyl alcohol network. By virtue of
their
carboxylate function, polyacrylates of the invention have a strong charge
affinity for
water. In the case of superficial injuries of the skin, this moisture, which
is needed for the
adhesive properties, is present in the form of exudate and blood, and the
wound dressing
therefore attaches itself firmly by suction to the wound, with formation of
gel. The
substantially lower hydrophilicity of the polyvinyl alcohol ensures a uniform
distribution of
the moisture in the polymer matrix. As a result of the deficient gel formation
capacity of
the polyvinyl alcohol, however, the strength of the matrix is retained. As
soon as the
wound no longer supplies sufficient moisture, owing to advancing healing, the
polyacrylic
acid gel fraction dries out and the matrix thus loses it adhesion.
Inventively advantageous polyacrylates are acrylate-alkyl acrylate copolymers,
as
described under the heading Polyacrylic acid matrices.
The invention likewise comprises conventional wound contact materials,
equipped on the
surface with the polymer film described in accordance with the invention. The
bonding/disbonding characteristics of the wound contact materials of
commercially
customary plasters can hence be controlled. For production, a corresponding
commercially customary wound contact material is impregnated with the polymer
mixture,
which still contains water, and only then is it dried.
To produce the moisture-adhesive film, a film-forming polymer of high
cohesiveness such
as, for example, polyvinyl alcohol (MowiolTm 18/88; from Hoechst) having an
average
molar weight of 20 000 to 100 000 g/mol, preferably 28 000 to 40 000 g/mol,
and a
degree of hydrolysis of 80% to 95%, preferably 85% to 90%, is combined with a
gel-
forming polyacrylic acid polymer, such as, for example, Carbopol Tm 980 from
Goodrich,
having an average molar weight of 450 000-4 000 000 g/mol, preferably 1 300
000 to
4 000 000 g/mol, the weight ratio of polyvinyl alcohol to polyacrylic acid
being in the
range 10:1 to 1:1.
Both polymers are dissolved or swollen in water as solvent at 60 to 90 C in an
agitator
with forced mixing, such as a compounder, for example, and are homogeneously
mixed
with one another. Thereafter the viscous mass which results is coated out flat
and then
dried to form the film.
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To modify the physical properties of the film, such as the elasticity, it is
possible to
incorporate corresponding additions during the kneading operation, such as
polyethylene
glycol (LutrolTM E400; from BASF), etc.
As active pharmaceutical/cosmetic substances it is possible in addition to
incorporate
wound healing promoters, e.g., dexpanthenol, and/or other substances into the
matrix.
Thermally sensitive active substances which do not permit incorporation into
the matrix at
60 to 90 C can be incorporated by first producing the matrix without active
substance,
and drying it. These temperature-sensitive active substances, in solution in a
hydrophilic
medium, can then be drawn up by suction through the matrix. The matrix is
subsequently
dried again by evaporation of the solvent at room temperature or in a freeze-
drying unit.
To set a particularly skin-friendly pH of the moisture-adhesive polymer film,
and/or in
order to influence the gel properties of the moist polyacrylic acid, it is
likewise possible to
incorporate corresponding pH corrigents into the matrix, such as trometamol,
triethanolamine, etc.
Optionally to the production in a compounder, the polymer film can also be
produced
continuously in an extruder.
Hydrocolloids
The group of the cosmetically and pharmaceutically relevant hydrocolloids can
be divided
as follows into:
= organic, natural compounds, such as, for example, agar agar, carrageen,
tragacanth,
gum arabic, alginates, pectins, polyoses, guar flour, carob bean flour,
starch, dextrins,
gelatins, casein,
= organic, modified natural substances, such as, for example,
carboxymethylcellulose
and other cellulose ethers, hydroxyethylcellulose and hydroxypropylcellulose,
and
microcrystalline cellulose,
= organic, fully synthetic compounds, such as, for example, polyacrylic and
polymethacrylic compounds, vinyl polymers, polycarboxylic acids, polyethers,
polyimines, polyamides, polyurethanes
= inorganic compounds, such as, for example, polysilicic acids, clay
minerals such as
montmorillonites, zeolites, silicas.
Microcrystalline cellulose is an advantageous hydrocolloid for the matrices of
the
invention. It is obtainable, for example, from the "FMC Corporation Food and
Pharma-
ceutical Products" under the trade name Avicel . A particularly advantageous
product for
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28
the purposes of the present invention is the Avicel grade RC-591, which is
modified
microcrystalline cellulose which is composed of 89% of microcrystalline
cellulose and
11% of sodium carboxymethylcellulose. Further commercial products of this
class of raw
material are Avicel RC/ CL, Avicel CE-15, and Avicel 500.
Further hydrocolloids which are advantageous are, for example,
methylcelluloses, which
is the term used for the methyl ethers of cellulose. They are characterized by
the
following structural formula
ROCH2 OR
RO 0"-'-
R0 0
0
OR ROCH2
-n
in which R may be a hydrogen or a methyl group.
Particularly advantageous for the purposes of the matrices of the invention
are the
cellulose mixed ethers, generally likewise referred to as methylcelluloses,
which contain,
in addition to a predominance of methyl groups, additionally 2-hydroxyethyl
groups, 2-
hydroxypropyl groups or 2-hydroxybutyl groups. Particular preference is given
to
(hydroxpropyl)methylcelluloses: for example, those available under the trade
name
Methocel E4M from Dow Chemical Comp.
Also advantageous according to the invention is sodium carboxymethylcellulose,
the
sodium salt of the glycolic acid ether of cellulose, for which R in the
structural formula
may be a hydrogen and/or CH2¨COONa. Particular preference is given to the
sodium
carboxymethylcellulose available under the trade name Natrosol Plus TM 330 CS
from
Aqualon and also referred to as cellulose gum.
Further preferred for the purposes of the matrices of the invention is xanthan
(CAS No.
11138-66-2), also called xanthan gum, which is an anionic heteropolysaccharide
which is
usually formed by fermentation from corn sugar and is isolated as the
potassium salt. It is
produced by Xanthomonas campestris and some other species under aerobic
conditions
and has a molecular weight of from 2x106 to 24x106. Xanthan is formed from a
chain
comprising I3-1,4-bonded glucose (cellulose) with side chains. The structure
of the
subgroups consists of glucose, mannose, glucuronic acid, acetate, and
pyruvate.
Xanthan is the name given to the first microbial anionic heteropolysaccharide.
It is
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produced by Xanthomonas campestris and some other species under aerobic
conditions
and has a molecular weight of 2-15 106. Xanthan is formed from a chain
comprising
13-1,4-bonded glucose (cellulose) with side chains. The structure of the
subgroups
consists of glucose, mannose, glucuronic acid, acetate, and pyruvate. The
number of
pyruvate units determines the viscosity of the xanthan. Xanthan is produced in
two-day
batch cultures with a yield of 70-90%, based on carbohydrate used. In this
process,
yields of 25-30 g/I are achieved. After the culture has been killed off, work-
up takes place
by precipitation with, for example, 2-propanol. Xanthan is then dried and
ground.
An advantageous gel former for the purposes of the matrices of the invention
is also
carrageen, a gel-forming extract with a similar structure to agar, from North
Atlantic red
algae which belong to the Florideae (Chondrus crispus and Gigartina stellata).
The term carrageen is frequently used for the dried algal product and
carrageenan for
the extract thereof. The carrageen precipitated from the hot-water extract of
the algae is
a colorless to sand-colored powder with a molecular weight range of 100 000-
800 000
and a sulfate content of about 25%. Carrageen, which is very readily soluble
in warm
water, forms a thixotropic gel upon cooling, even if the water content is 95-
98%. The
rigidity of the gel is effected by the double helix structure of carrageen. In
the case of
carrageenan, three main constituents are differentiated: the gel-forming K
fraction
consists of D-galactose 4-sulfate and 3,6-anhydro-a-D-galactose, which have
alternate
glycoside bonds in the 1,3- and 1,4-position (by contrast, agar contains 3,6-
anhydro-a-L-
galactose). The nongelling Xr fraction is composed of 1,3-glycosidically
linked D-galactose
2-sulfate and 1,4-bonded D-galactose 2,6-disulfate radicals, and is readily
soluble in cold
water. t-Carrageenan, composed of D-galactose 4-sulfate in 1,3 bond and 3,6-
anhydro-
a-D-galactose 2-sulfate in 1,4 bond, is both water-soluble and gel-forming.
Further
carrageen grades are likewise referred to using Greek letters: a, 13, 7, v,
it, to, x. The
type of cations present (Kt, NH4, Nat, Mg2+, Ca2+) also influences the
solubility of the
carrageens.
The use of chitosan in cosmetic preparations is known per se. Chitosan
represents a
partially deacylated chitin. This biopolymer has, inter alia, film-forming
properties and is
characterized by a silky feel on the skin. A disadvantage, however, is its
severe
stickiness on the skin, which occurs in particular ¨ temporarily ¨ during
application. In
individual cases, corresponding preparations may not then be marketable since
they are
unacceptable to and/or viewed negatively by the consumer. As is known,
chitosan is
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used, for example, in haircare. It is suitable, to a better degree than the
chitin on which it
is based, as a thickener or stabilizer and improves the adhesion and water
resistance of
polymeric films. A representative of a large number of literature references
for the prior
art is: H.P. Fiedler, "Lexikon der Hilfsstoffe fur Pharmazie, Kosmetik und
angrenzende
5 Gebiete" [Lexicon of Auxiliaries for Pharmacy, Cosmetics and Related
Fields], third
edition 1989, Editio Cantor, Aulendorf, p. 293, keyword "Chitosan".
Chitosan is characterized by the following structural formula:
CH2OH CH2OH CH2OH
OH
OH 0 OH o OH
HI
NH¨X NH¨X NH¨X
where n assumes values of up to about 10 000, and X is either the acetyl
radical or
hydrogen. Chitosan forms by deacetylation and partial depolymerization
(hydrolysis) of
chitin, which is characterized by the structural formula
CH2OH CH2OH CH2OH
OH
OH o OH o OH
HI
NH¨CO NH¨CO NH¨CO
CH3 CH3 CH3
Chitin is an essential constituent of the ectoskeleton xvuov = Greek:
integument] of
arthropods (e.g., insects, crabs, spiders) and is also found in supporting
tissues of other
organisms (e.g., mollusks, algae, fungi).
In the region of about pH <6, chitosan is positively charged and in that range
is also
soluble in aqueous systems. It is incompatible with anionic raw materials. For
this reason,
to prepare chitosan-containing oil-in-water emulsions, the use of nonionic
emulsifiers is
appropriate. These are known per se, from EP 0 776 657 Al for example.
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Preference is given according to the invention to chitosans with a degree of
deacetylation
of > 25%, in particular > 55 to 99% [determined by means of 1H-NMR]).
It is advantageous to choose chitosans with molecular weights between 10 000
and
1 000 000, in particular those with molecular weights between 100 000 and 1
000 000
[determined by means of gel permeation chromatography].
Gel matrix based on agar agar/PAA
The self-adhesive polymer matrix comprising a polymer which is gel-forming in
water
preferably comprises at least one polyacrylic acid polymer, water, seaweed
extract, and
alcohol, and also silver glass for disinfectant delivery of silver ions to the
skin or wound.
The matrix is composed of a polymer which is gel-forming in water, preferably
polyacrylic
acid gel, as a bond strength-determining component. The seaweed extract used
is
preferably agar agar. The alcohol used comprises, in particular, monohydric or
polyhydric
alcohols, preferably glycerol, which act as consistency factors.
A seaweed extract preferred for use besides agar agar is carrageenan.
Carrageenan is a
hydrophilic polysaccharide of high molecular weight, which is obtained from
various red
algae, principally Chondrus crispus, by hot-water extraction, followed by
freezing-out and
subsequent purification. The structure of carrageenan is composed primarily of
repeating
galactose and 3,6 anhydrogalactose units, both in both sulfated and unsulfated
form. The
most important difference between kappa, iota, and lambda carrageenan is the
number
and position of the ester sulfate groups on the repeating galactose units.
Carrageenan can form gel only in the presence of cations. Inventively
preferred are
kappa and iota carrageenan, which form gels in the presence of calcium ions
(kappa and
iota) and potassium and ammonium ions (kappa only). Particularly advantageous
is the
use of corresponding cation hydroxides, since the polyacrylic acid that is
likewise used to
produce gel matrix systems of the invention requires neutralization for the
formation of
stable gels.
Carrageenan is available industrially, for example, from Lehmann 8, Voss & Co.
under
the names GelcarinTM, ViscarinTM, and SeaspenTM.
Seaweed extract, such as agar agar with particular preference in accordance
with the
invention, is a hydrophilic colloid of polysaccharide structure, composed of
the gelling
agarose and the nongelling agaropectin, which is obtained from a variety of
seaweeds of
the Rhodophyceae class by means of hot-water extraction, followed by freezing-
out and
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subsequent purification. Agar agar is available industrially, for example,
from Riedel de
Haen AG.
The extract, especially agar agar or carrageenan, is used preferably in an
amount of
0.1%-15% by weight, more preferably between 0.5%-5% by weight. All percentages
here
are based on weight fractions of the polymer matrix, in the absence of any
indication to
the contrary.
Mono- or polyhydric alcohols such as glycerol (1,2,3-propanetriol), for
example, are
pharmaceutical industry auxiliaries which enjoy widespread use, among other
things, as
solubilizers or humectants.
Mono- or polyhydric alcohols such as glycerol are inventively used preferably
in an
amount of 1%-85% by weight, more preferably between 5%-45% by weight.
The fraction of polymer which is gel-forming in water, such as polyacrylic
acid gel, in the
matrix governs the adhesion. In contrast to agar agar, however, polyacrylic
acid forms
gels both with water and with alcohols, so that the adhesion formulated
through the
polyacrylic acid fraction remains constant independently of the respective
alcohol
fraction.
The fraction of silver glass in the matrix is preferably 0.001%-10% by weight.
Inventively advantageous polyacrylates are acrylate-alkyl acrylate copolymers,
as
described under the heading Polyacrylic acid matrices.
Further of advantage are copolymers of C10_30 alkyl acrylates and one or more
monomers
of acrylic acid, of methacrylic acid or esters thereof, which are cross-linked
with an allyl
ether of sucrose or with an allyl ether of pentaerythritol.
The polymer which is gel-forming in water, especially polyacrylic acid and/or
copolymers
thereof, is used preferably in an amount of 2%-55% by weight, more preferably
between
5%-30% by weight.
The polymer matrices are produced without the use of organic solvents,
preferably at 40-
95 C, in commercially customary mixers/compounders or continuously in suitable
extruders.
Other polymers which form gel in water include baobab flour.
In this way it is possible, using only water, polymer which forms gel in
water, seaweed
extract, and monohydric or polyhydric alcohol as starting materials, to
produce, in a
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33
targeted fashion, soft, smooth, self-adhesive hydrogel matrices as a basis for
production
and use as silver glass-containing patches, TTS, cataplasms or pads.
In order to produce particular performance properties it is possible for the
polymer
matrices to be admixed with appropriate plasticizers, solubilizers,
penetration enhancers,
neutralizing agents such as tromethamol (2-amino-2-(hydroxymethyl)-1,3-
propanediol),
triethanolamine (2,2',2"-nitrilotriethanol) or NaOH, for example, fillers
and/or other known
additives, although it is not mandatory to add them.
The gel matrix can thus be doped with hydrophilic active substances, or else,
given an
appropriate solubilizer, with hydrophobic active substances, for wound healing
or
skincare. In the case of incorporation of hydrophobic active substances it may
be of
benefit to use cyclodextrins for encapsulation.
Cyclodextrins (cycloamyloses, cycloglucans) are known per se in cosmetic and
pharmaceutical preparations.
Improving the solubility of substances of sparing solubility, in the presence
of
cyclodextrins in an aqueous medium, has been described for individual
substances.
Advantage may be possessed both by the inclusion compounds ,of a substance,
also
called the guest, with a cyclodextrin species - in this context both 1:1 or
1:2 complexes
and complexes with other molar ratios (guest : cyclodextrin) are possible -
and by the
physical mixture thereof.
The cyclodextrins are cyclic oligosaccharides composed of a-1,4-linked glucose
units. In
general, six to eight glucose units (a-, r3-, or y-cyclodextrin) are joined to
one another.
Cyclodextrins are obtained when starch is acted on by Bacillus macerans. They
possess
a hydrophobic interior and a hydrophilic exterior. By virtue of their
structure, cyclodextrins
and their derivatives are able to form inclusion complexes. They are suitable
for the
"molecular encapsulation" of active substances (e.g., as a protective envelope
around
sensitive molecules in cosmetic and pharmaceutical formulations).
These applications are also described in a series of patents (e.g., WO
98/55148,
EP 0 579 435, EP 0 392 608). In these publications, however, usually only one
active
substance is complexed by the cyclodextrin (derivative). Multi-component
inclusion
complexes are, it is true, described in EP 0756 493, but when looked at more
closely the
latter relates to a salt and not to a two-component mixture of acid and base.
The phrase "cyclodextrin and/or a derivative thereof" refers below both to
cyclodextrins
having different numbers of glucose units in the ring molecule, and to
derivatives of these
compounds.
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34
HocH2
HocH.2
OH HO 0
HO HO CH2OH
0
0 OH H 0O
0
HOCH2 OH OH
0 OH HO
CH2OH
0
0
0
CH2OH
a-Cyclodextrin
HOCH
0
HOCHi7N _______________________________
2 '7H0
OH HO 0
I HO
--0 HO CH2OH
0 0
\yH HO
HOCH2
0
OH
OH
0
OH CH2OH
HO
0 OH
HO OH 0 0
HOC H2 0
0H20H
0
13-Cyclodextrin
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0 HOCH2
HOCH2 0 HO \
OH HO 0
HO
0 CH2OH
0 0
OH
HO )
HOC H2
OH 0
0
CH2OH
HO
0
0
0-7
HO CH2 OH
0 OH HO
0 CH2OH
0
CH2OH 0
y-Cyclodextrin
In accordance with the invention the cyclodextrin or cyclodextrins is or are
used
preferably in cosmetic or dermatological compositions in a concentration of
0.0005% to
5 20.0% by weight, in particular 0.01% to 10% by weight, and more
preferably in a
concentration of 0.1% to 5.0% by weight.
It is advantageous in accordance with the invention to use native
cyclodextrins or
cyclodextrins with polar and/or apolar substitution. These include preferably,
but not
10 exclusively, methyl-, especially random-methyl-p-cyclodextrin, ethyl- and
also
hydroxypropyl-cyclodextrins, such as HP-p-cyclodextrin or HP-y-cyclodextrin,
for
example.
The cyclodextrin species that are particularly preferred in accordance with
the invention
are y-cyclodextrin and also hydroxypropyl-p-cyclodextrin.
Further prior art is contained in the following publications:
K. Uekama et al., Chemical Reviews, 1998, 98, 2045-2076, "Cyclodextrin drug
carrier
systems"
T. Loftsson, Int. J. Dermatology, 1998, 37, 241-246, "Cyclodextrins: new drug
delivery
systems in dermatology".
J. Zatz et al. Cosmetics & Toiletries, 1997, 112, July, p. 39 ff,
"Applications of
cyclodextrins in skin products".
U. Citernesi, Cosmetics & Toiletries, 1995, 110, March, p. 53 ff,
Cyclodextrins in
functional dermocosmetics.
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The inventively used cyclodextrins and/or cyclodextrin-guest inclusion
complexes and/or
the cyclodextrin substance mixtures can be incorporated without difficulties
into the
polymer matrix.
In one inventively particularly preferred embodiment the polymer matrix or gel
matrix
contains the active pharmaceutical substances, for controlled local or
systemic delivery
(in) to the skin, in amounts of 0-35% by weight, preferably 0-15% by weight.
Examples of active substances which can be used include essential oils. By
essential oils
are meant plant-derived concentrates which as natural raw materials are used
primarily in
the fragrance and foodstuffs industries and are composed more or less of
volatile
compounds. Examples that may be mentioned of these compounds include 1,8-
cineol,
limonene, menthol, borneol and camphor. The term "essential oils" is often
used for the
volatile constituents still present in the plants. In their true sense,
however, essential oils
are understood to be mixtures of volatile compounds prepared by steam
distillation from
plant raw materials.
Essential oils are composed exclusively of volatile components, whose boiling
points are
in general between 150 and 300 C. They include predominantly hydrocarbons or
monofunctional compounds such as aldehydes, alcohols, esters, ethers and
ketones.
Parent compounds are mono- and sesquiterpenes, phenylpropane derivatives and
longer-chain aliphatic compounds.
In some essential oils, one constituent is dominant (for example, eugenol in
clove oil, at
more than 85%), while other essential oils constitute complex mixtures of the
individual
constituents. Often the organoleptic properties are determined not by the main
components but by subsidiary or trace constituents, such as, for example, by
the
1,3,5-undecatrienes and pyrazines in galbanum oil. The number of identified
components
in many of the commercially significant essential oils is up into the
hundreds. Very many
constituents are chiral, with very often one enantiomer being predominant or
being
present exclusively, such as (-)-menthol in peppermint oil or (-)-linaly1
acetate in lavender
oil, for example.
Preferred essential oils that may be mentioned include oleum eucalypti, oleum
menthae
piperitae, oleum camphoratum, oleum rosmarini, oleum thymi, oleum pini
sibricum and
oleum pini silvestris, and the terpenes 1,8-cineol and levomethanol.
Further essential oils that may be mentioned include oleum abietis albae,
oleum anisi,
oleum aurantii floris, oleum bargarmottae, oleum calendulae infusum, oleum
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camphoratum, oleum caryophylli, oleum chamomillae, oleum cinnamomi ceylanici,
oleum
citri, oleum citronellae, oleum cupressi, oleum cymbopogonis, oleum jecoris,
oleum
lavendulae, oleum macidis, oleum majoranae, oleum melaleucae viridiflorae,
oleum
melissae, oleum menthae arvensis, oleum menthae piperatae, oleum millefolium,
oleum
myrrhae, oleum myrte, oleum oregani, oleum pini sibricum, oleum
pinisilvestris, oleum
salviae, oleum santali, oleum terebinthinae rectificat., oleum thymi, oleum
valerianae,
oleum zingiberis and/or tea tree oil.
Peppermint oils are essential oils obtained by steam distillation from leaves
and
blossoms of various varieties of peppermint, and occasionally also those from
Mentha
arvensis.
Citrus oils are essential oils obtained from the peel of citrus fruits
(bergamot, grapefruit,
lime, mandarin, orange, lemon), often also called agrumen oils.
Citrus oils are composed largely of monoterpene hydrocarbons, principally
limonene
(exception: bergamot oil, which contains only about 40%).
Menthol can be used for example for surface anesthesia in cases of skin
irritation as a
result of light burns. The products produced in this way generate a pleasant
feeling of
cold and can be used for cooling minor burns that do not require specialist
medical
treatment.
Menthol has three asymmetric C atoms and accordingly exists in four
diastereomeric
pairs of enantiomers (cf. the formulae; the other four enantiomers are the
corresponding
mirror images).
CH3 CH3 CH3 CH3
(R)
(S)
(s , (S) (R)
OH
OH
(IR) 'OH OH
) ; (S)
(R)
H3C> (.4_1 r,
H3C CH3 H3C CH3
(-)-Menthol (+)-Neomenthol (+)-isomenthol (4)-Neoisomenthol
(1) (2) (3) (4)
The diastereomers, which can be separated by distillation, are referred to as
neoisomenthol, isomenthol, neomenthol [(+) form: a constituent of Japanese
peppermint
oil], and menthol. The most important isomer is (-)-menthol (levomenthol),
shiny prisms
with a strong peppermintlike odor.
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As further active substances it is possible to add camphor, for example, to
the matrix in
order to treat rheumatic pain, neuralgias and inflammation. By camphor is
meant 2-
bornanone, 1,7,7-trimethylbicyclo[2.2.1]heptan-2-one; see diagram below.
9 CH3
H3C
0
4
6 3
H3C
5 10 0
(+)-Camphor
In combination also with care substances such as jojoba oil or aloe vera,
though, the
polymer matrix of the invention can be used. Depending on the definition of
application,
such combinations may turn a drug into a cosmetic and hence drastically reduce
the time
to market, owing to the reduction in approval times.
For advantageous embodiments of hydrogels/cataplasms of the invention it is
also
possible, additionally, to mention active hyperemic substances such as natural
active
substances of cayenne pepper or synthetic active substances such as
nonivamide,
nicotinic acid derivatives, preferably benzyl nicotinate or propyl nicotinate,
and
antiinflammatories and/or analgesics.
By way of example mention may be made of:
Capsaicin
0
H3C0 CH3
CH3
HO
[8-Methyl-trans-6-nonenoic acid (4-hydroxy-3-methoxybenzyl amide)]
Nonivamide
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39
0
I I
H3C¨(CH2)7¨C¨NH¨CH2
OCH3
OH
Nicotinic acid benzyl ester
1.1
0
0
Benzyl nicotinate.
Flavone and its derivatives, often also collectively called "flavones", are
also
advantageous additives in the sense of the present invention. They are
characterized by
the following basic structure (substitution positions indicated):
7 0 4.
0
7 5
0
3
5
0
Some of the more important flavones, which can also be used with preference in
preparations of the invention, are listed in the table below:
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OH substitution positions
3 5 7 8 2' 3' 4' 5'
-
Flavone - - - - - - -
Flavonol + - - - - - - -
,
Chrysin - + + - - - - -
Galangin + + + - - - - -
Apigenin - + + - - - + -
Fisetin + - + .. .. + + _
,
Luteolin - + + - - + + -
Kampferol + + + - - - + -
I _________________________________________________________________________
,
Quercetin + + _ + - + + ..
-
. ,
Morin + + + - + - + -
,
Robinetin + - + - - + + +
,
. .
Gossypetin + + + + - + + -
'+
. .
Myricetin + + + - - + +
-
5 In nature, flavones occur ordinarily in glycosylated form.
In accordance with the invention the flavonoids are preferably chosen from the
group of
substances of the generic structural formula
Z2
z1 4
4 0 0
Z4
0 I 4
0
I
1
Z6 0
where Z1 to Z7 are chosen independently of one another from the group
consisting of H,
OH, alkoxy- and also hydroxyalkoxy-, where the alkoxy and hydroxyalkoxy groups
respectively may be branched and unbranched and may have 1 to 18 C atoms, and
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41
where Gly is chosen from the group of the mono- and oligoglycoside residues.
In accordance with the invention the flavonoids can, however, also be chosen
advantageously from the group of substances of the generic structural formula
Z2
zi Z3
Gly -0 0
0 Z Z4
5
where Z1 to Z6 are chosen independently of one another from the group
consisting of H,
OH, alkoxy- and also hydroxyalkoxy-, where the alkoxy and hydroxyalkoxy groups
respectively may be branched and unbranched and may have 1 to 18 C atoms, and
where Gly is chosen from the group of the mono- and oligoglycoside residues.
Such structures can be chosen with preference from the group of substances of
the
generic structural formula
Z2
zi Z3
G1y2¨G1y1 -0 0
0Z4
Gly3
15 where Glyi, G1y2, and G1y3 independently of one another represent
monoglycoside
residues or G1y2 and/or Gly3 may also, individually or together, represent
saturations by
hydrogen atoms.
Preferably Glyi, G1y2, and G1y3 are chosen independently of one another from
the group
20 of the hexosyl radicals, particularly of the rhamnosyl radicals and
glucosyl radicals. Other
hexosyl radicals as well, however, examples being allosyl, altrosyl,
galactosyl, gulosyl,
idosyl, mannosyl and talosyl, can be used with advantage where appropriate. It
may also
be of advantage in accordance with the invention to use pentosyl radicals.
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Z1 to Z5 advantageously are chosen independently of one another from the group
consisting of H, OH, methoxy-, ethoxy- and also 2-hydroxyethoxy-, and the
flavone
glycosides have the structure:
Z2
Z1 Z3
Z7 0 0
0
Z4
0
4 0
GI ly1¨Gly2
Gly3
The flavone glycosides of the invention which become of particular advantage
are those
from the group represented by the following structure:
Z2
Z3
HO 0
0
OH 0
Glyi¨Gly2
Gly3
where Glyi, G1y2, and G1y3 independently of one another represent
monoglycoside
residues or oligoglycoside residues. G1y2 and/or G1y3 may also, individually
or together,
represent saturations by hydrogen atoms.
Preferably Glyi, G1y2, and G1y3 independently of one another are chosen from
the group
of the hexosyl radicals, in particular the rhamnosyl radicals and glucosyl
radicals. Other
hexosyl radicals as well, however, examples being allosyl, altrosyl,
galactosyl, gulosyl,
idosyl, mannosyl, and tallosyl, can also be used with advantage where
appropriate. It
may also be an advantage in accordance with the invention to use pentosyl
radicals.
In the sense of the present invention it is particularly advantageous to
choose the flavone
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glycoside or glycosides from the group consisting of a-glucosylrutin, a-
glucosylmyricetin,
a-glucosylisoquercitrin, a-glucosylisoquercetin and a-glucosylquercitrin.
Of particular preference in accordance with the invention is a-glucosylrutin.
Also advantageous in accordance with the invention are naringin (aurantiin,
naringenin
7-rhamnoglucoside), hesperidin (3',5,7-trihydroxy-4'-methoxyflavanone 7-
rutinoside,
hesperidoside, hesperetin 7-0-rutinoside), rutin (3,3',4',5,7-
pentahydroxyflavone
3-rutinoside, quercetin 3-rutinoside, sophorin, birutan, rutabion, taurutin,
phytomelin,
melin), troxerutin (3,5-dihydroxy-3',4',7-tris(2-hydroxyethoxy)flavone 3-(6-(0-
(6-deoxy-
a-L-mannopyranosy1)-8-D-glucopyranoside)), monoxerutin
(3,3',4',5-tetrahydroxy-
7-(2-hydroxyethoxy)flavone
3-(6-(0-(6-deoxy-a-L-man nopyranosyl)-13-D-g lucopyrano-
side)), dihydrorobinetin (3,3',4',5',7-pentahydroxyflavonone), taxifolin
(3,3',4',5,7-penta-
hydroxyflavanone), eriodictyol-7-glucoside (3',4',5,7-tetrahydroxyflavanone 7-
glucoside),
flavanomarein (3',4',7,8-tetrahydroxyflavanone 7-glucoside) and isoquercetin
(3,3%4%5,7-
pentahyd roxyflavanone-3-(13-D-glucopyranoside)).
Further preferred classes of active pharmaceutical substance for a gel matrix
of the
invention include the following - without making any claim to completeness in
the context
of the present invention:
antimycotics, such as nafitine, amorrolfine, tolnaftate, ciclopirox
nonsteroidal antiinflammatories, such as glycol salicylate, flufenamic acid,
ibuprofen,
etofenamate, ketoprofen, piroxicam, indomethacin
antipruritics, such as polidocanol, isoprenaline, crotamiton
local anesthetics, such as lidocaine, benzocaine
antipsoriatics, such as ammonium bitumasulfonate
keratolytics, such as urea
In a further embodiment the polymer matrix, which if appropriate comprises not
only
silver but also active substance, may be located between a cover layer which
is firmly
anchored to it and is also called backing layer, and a removable release
layer. The
purpose of the removable release layer is to secure the adhesive layer and to
improve
the transport stability and storage stability, and it is removed prior to
application to the
skin.
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The polymer matrix may have been applied to a backing layer or backing sheet
such as
is known from the prior art. The backing sheet is composed of an air- and
water vapor-
permeable but water-impervious polymer layer having a thickness of
approximately 10 to
100 p.m. The possibly flexible backing sheet is composed preferably of
polymers of
polyurethane, PE, PP, polyamide, polyester or polyether-ester.
The wound dressing of the invention, generally in the form of a plaster,
comprises an
active substance polymer matrix of the invention, which is self-adhesive in
the presence
of moisture; a back layer, which where appropriate is impermeable to active
substance;
and a detachable protective layer, which is removed prior to application to
the skin.
Further ingredients, such as fillers, stabilizers, enhancers and/or cosmetic
adjuvants,
may be incorporated in the matrix in order to adapt the dressing to the
different fields of
use and in order to provide a dressing which is application-friendly.
Finally, the matrix may be lined with an adhesive-repellent backing material,
such as
siliconized paper, or may be provided with a wound contact material or
cushioning. On its
moisture-self-adhesive side which later faces the skin, the dressing of the
invention is
normally lined over its whole width, up until the time of use, with an
adhesive-repellent
backing material. This material protects the self-adhesive layer, which
comprises the
highly skin-compatible adhesive of the matrix and has been applied preferably
by the
transfer method, and, additionally, stabilizes the entire product. The lining
may be
designed in a known way as a single piece or, preferably, in two parts.
For application as plasters, the gel matrices of the invention are applied as
a layer to a
release medium made of paper, or the like, this application taking place by
compression,
rolling or the like, and on the reverse are laminated with any desired backing
material
such as, for example, a polymer sheet, textiles or the like. With particular
preference in
accordance with the invention the gel matrices are applied in the hot state to
a backing
material by means of a metering pump, and with very particular preference are
implemented by corresponding cavities in the presses or roller mechanisms, in
a three-
dimensional form. The form of the plasters produced is determined by the form
of the
cavities and is not subject to any restriction; it may, for example, be
ellipsoidal with edges
which run out flat, or, for example, may be of angular implementation.
In summary it can be stated that suitable backing materials include all rigid
and elastic
sheetlike structures of synthetic and natural raw materials. Preference is
given to backing
materials which can be employed in such a way that they fulfill properties of
a functional
dressing. Recited by way of example are textiles such as wovens, knits, lays,
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nonwovens, laminates, nets, films, foams, and papers. Furthermore, these
materials may
be pretreated and/or aftertreated. Common pretreatments are corona and
hydrophobicizing; customary aftertreatments are calendering, thermal
conditioning,
laminating, diecutting, and enveloping.
5 It is particularly advantageous if the backing material is sterilizable,
preferably y-
(gamma) sterilizable.
Very particular preference in accordance with the invention is given to
backing materials
having good oxygen, air, and water vapor permeability which have been provided
10 pointwise by screen printing or analogous methods with the adhesive
polymer matrix and
which outwardly overlap the applied gel matrix at the side edges. Matrices of
the
invention manufactured in this form can be attached self-adhesively to parts
of the body
which are subject to severe mechanical stress, such as elbows or knee joints,
where the
inherent adhesion of the hydrogels/cataplasms is no longer sufficient for long-
term
15 application.
The stated properties of the adhesive matrix suggest in particular its utility
for medical
products, especially plasters and patches, medical fastenings, wound covers,
orthopedic
or phlebological bandages, and dressings.
In particular the use of the self-adhesive polymer matrix, composed of a
polyacrylic acid
polymer, agar agar, glycerol, and water, in plasters, strips, wound covers
and/or
bandages is an extremely simple, skin-compatible possibility for woundcare
and/or
skincare with disinfectant silver ions from silver glass. The plasters, wound
covers or
bandages thus equipped have an individually adjustable consistency and bond
strength
and are extremely inexpensive as compared with known medical materials. The
polymer
matrix can be employed alone or in combination with suitable, coated backing
materials.
It is therefore possible to produce products which can be employed even on
moving body
parts, such as fingers or elbows, for example.
Also particularly suitable is the use of the polymer matrices with water-
soluble or
hydrophobic actives incorporated therein as active substance patch systems or
TTS for
the controlled delivery of active substance to the skin.
The use of the self-adhesive polymer matrix is to be regarded advantageously
in
particular as an active substance administration form for topical or buccal
application or
as a component of a TTS, especially of a monolithic TTS.
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By way of example, through the use of menthol on a fleece material coated by
screen
printing it is possible to produce a plaster comprising the polymer matrix,
which by virtue
of the evaporation, the delivery of menthol and/or water, leads to a cooling
effect in the
case of minor burns and at the same time, by virtue of the silver ions given
off, disinfects
the damaged tissue. The use of the self-adhesive polymer matrix comprising
silver glass
and menthol as active substance for application in the case of skin burns is
therefore
preferred.
Similarly, the use of essential oils as active substances allows the polymer
matrix to be
employed in the case of colds and also for aromatherapy.
Finally the gel matrix comprising silver glass can be lined with an adhesive-
repellent
backing material, such as siliconized paper, or provided with a wound contact
material or
a cushion. On its self-adhesive side which later faces the skin, the plaster
of the invention
is lined over its whole width, until used, usually with an adhesive-repellent
backing
material. This protects the self-adhesive layer comprising the highly skin-
compatible
adhesive of the gel matrix, which has preferably been applied by a transfer
method, and
additionally stabilizes the product as a whole. The lining can be designed, in
a known
way, in one piece or, preferably, in two parts.
Further embodiments may be such that between the reverse of the matrix and the
lining
backing there is a second matrix possessing higher active-substance
solubility, as a
reservoir. Instead of a second matrix and backing, this might also be a
thermoformed film
with pure active substance.
Located on part (e.g., at the edge) of the adhesive side of the matrix is a
second matrix
possessing higher bond strength for the purpose of additional fixing, but
possessing
insufficient active-substance solubility.
The active substance-free matrix is located between two nonanchoring films and
is
utilized for fastening. The active substance-free matrix comprising silver
glass could also
serve (with or without wound contact material) as adhesive layer for a simple
wound
plaster/sticking plaster.
The use of the polymer matrix comprising silver glass as a medical plaster
system, as a
patch, pad, wound contact material or bandage, is suitable particularly in two-
dimensional
embodiment with a total surface area of 0.2 to 1000 cm2. As a result, for
example, small
(0.2-2 cm2) regions of the skin are covered, or extensive regions (up to 1000
cm2), for the
purpose, for example, of cooling.
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Preference is also given in this context to the use of the self-adhesive
polymer matrix
comprising silver glass, in two- or three-dimensional embodiments, with a
polymer matrix
weight fraction of 0.1 to 1000 g, in particular of 500 g. The shape may in
this case be
circular, oval or angular or may be adapted to the sections of the skin.
The polymer matrix, in particular a polyurethane matrix, may be used with no
foaming
and/or with partial or full-area foaming, with no filling or with additional
fillers, such as, for
example, superabsorbents, titanium dioxide, zinc oxide, plasticizers, dyes,
etc.
Via the formation of foam it is possible to produce a relatively soft matrix
system, which
has a positive tactile sensation for the user and which allows a dressing to
be produced
which is more conforming. Moreover, foamed wound contact materials afford a
cushioning effect, which in the case of pressure-sensitive application such as
with burn
injuries, for example, may be of advantage.
Also advantageous, however, is the fact that the entire polymer material is
unfoamed and
yet has outstanding application properties, since in accordance with the
invention the
foaming characteristics have no effect on the release of silver.
The polymer matrix may where appropriate comprise additives known per se from
the
prior art, such as, for example, fillers and short, organic- or inorganic-
based fibers, metal
pigments, surface-active substances or liquid extenders such as substances
having a
boiling point of above 150 C. As inorganic fillers mention may be made by way
of
example of heavy spar, chalk, gypsum, kieserite, sodium carbonate, titanium
dioxide,
cerium oxide, quartz sand, kaolin, carbon black, and hollow microbeads.
The addition, in particular, of titanium dioxide with a fraction of 0.01% to
2% by weight,
based on the preferred polyurethane matrix, enhances the esthetic aspect of
the silver-
containing dressing material in the sense that the user, for example, is
unable to see any
unesthetic blood through the dressing.
As organic fillers it is possible for example to employ powders based on
polystyrene,
polyvinyl chloride, urea-formaldehyde, and polyhydrazodicarbonamide. Suitable
short
fibers include, for example, glass fibers 0.1-1 mm in length or fibers of
organic origin,
such as polyester fibers or polyamide fibers, for example. Metal powders, such
as iron,
aluminum or copper powder, for example, may likewise be used with regard to
gel-
forming. In order to endow the matrix with the desired coloration it is
possible to use the
organic- or inorganic-based color pigments or dyes which are known per se in
connection
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with the coloring of, say, polyurethanes, such as, for example, iron oxide
pigments or
chromium oxide pigments, phthalocyanine- or monoazo-based pigments. Examples
of
surface-active substances that may be mentioned include cellulose powders,
activated
carbon, and silica products.
The addition of these colorants is not mandatory in accordance with the
invention, since
discoloration of the matrices comprising the silver-containing glasses is not
observed.
Coloring with additional substances serves for individual design of the
finished polymer
material in order to make it attractive to children, for example, and also for
adaptation to
the parameters of the surroundings, such as the skin color, for example.
To modify the adhesive properties of the polymer matrix it is possible where
appropriate
to make additions of polymeric vinyl compounds, polyacrylates, and other
copolymers
customary in adhesive technology, and/or adhesives based on natural
substances, in an
amount of up to 10% by weight, based on the weight of the polymer composition,
without
watering down the advantageous properties of the polymer matrix, particularly
the
polyurethanes.
In accordance with the invention a silver-containing glass of the composition
claimed is
inserted into the polymer matrix, which advantageously is composed of
polyurethane and
is self-adhesive.
Customary glass additions, such as other metal oxides, which where appropriate
alter the
color, or soda and potash, in order to lower the melting point, for example,
may
additionally be present where appropriate.
The glass to be used is advantageously colorless.
Silver glasses of the composition indicated above which have been found
particularly
advantageous are those having a volume-based particle size of between 0.1 pm
and
10 pm and a residual moisture content below 5%.
The specially manufactured antimicrobial glasses are available, for example,
from
Ishizuka Glass Co. Ltd., Japan.
Surprisingly it has been found that the silver-containing glasses of the
invention can be
incorporated into the polymer matrix and in particular into a polyurethane
matrix by
admixing the glasses to the polymer base materials, without disrupting the
reaction, and
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despite full incorporation into the polymer are able to develop their
antimicrobial or
disinfectant action. Also surprising, and unforeseeable, is the fact that the
glasses do not
contribute to any deterioration in the properties of the polymer matrix.
Likewise extremely surprising is the fact that even an amount of just 0.005%-
1% by
weight of the silver glass into the material of the invention, preferably into
the polymer
matrix, exhibits an antimicrobial activity. Furthermore, the activity is at a
constant high
level over a relatively long period of time, so that the material, in the form
for example of
a wound contact material, can be worn on the skin for a prolonged period
without
detractions in terms of activity. In this context, in particular, the skin-
friendly polyurethane
matrix has a synergistic action, so that the polymer matrix as well does not
lead to any
observations of disadvantages from a long period of wear.
The most prominent, unforeseeable advantage, however, is that the inventive
combination of a polymer material suitable as wound contact material with the
antimicrobial glass results in a durable stability of the wound contact
material with respect
to discoloration.
The polymer material of the invention at the same time exhibits discoloration
stability with
respect to radiation, heat or other effects.
Depending on the amount of silver glass, the silver-containing polymer
material of the
invention exhibits silver release at up to 50 mg Ag/kg polymer. A preferred
silver ion
release rate is from 5 to 30 mg/kg; the rate of release can be controlled via
the amount of
silver glass or alternatively by further suitable additions to the polymer
matrix. The
antimicrobial activity of the wound contact material of the invention has also
been
demonstrated with relatively low release rates in accordance with JIS
(Japanese
Industrial Standard) 2801:2000 on
= Escherichia coli IFO 3972
= Staphylococcus aureus IFO 12732.
The release of antimicrobial silver ions from the polymer materials of the
invention is
observed over a period of 2 to 240 h, in particular of 10 to 96 h, thereby
ensuring long-
term treatment of the wound with a wound contact material. This advantage
avoids the
need otherwise frequently to change the wound contact material.
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The polymer matrix can advantageously be made transparent. As transparent,
water
vapor-permeable, and adhesive, a polyurethane matrix thus fulfills, in
particular, aspects
of esthetics and application-friendliness. This constitutes a significant
advantageous
difference from the polyacrylate- and silicone gel-based plaster systems.
Moreover the
5 transparency increases user acceptance, since the plaster can usually be
worn on the
skin for a relatively long time.
To store fluid it is possible with preference to incorporate a superabsorbent
polymer in
the form of a powder into the polymer matrix. This ensures that fluid released
in the
10 region of the skin is bound, thereby countering maceration and the
premature
detachment of the dressing. In addition, as a result of the increased
absorption of wound
secretion and the associated increased absorption of pathogenic microbes, a
considerable product advantage is provided in the case of open wounds.
15 Preferred water-absorbing materials are water-absorbing salts of
polyacrylates and their
copolymers that are known as superabsorbents, particularly the sodium or
potassium
salts. They may be noncrosslinked or crosslinked and are also available as
commercial
products. Suitability is possessed in particular by products of the kind
disclosed in
DE 37 13 601 Al and also by new-generation superabsorbents with only small
fractions
20 of water which can be extracted by drying, and with a high swelling
capacity under
pressure.
Preferred products are acrylic acid/sodium acrylate-based polymers with low
degrees of
crosslinking. Sodium polyacrylates of this kind are available as FavorTM 22-SK
(Stockhausen & Co. KG., Germany). Further absorbers, carboxymethylcellulose
and
25 karaya for example, are likewise suitable.
It is therefore of advantage to incorporate superabsorbents or superabsorbent
polymer
into the polymer in an amount of 0.01% to 40% by weight, in particular from
0.5% to 30%
by weight, especially 20% by weight, based on the total mass of the polymer
matrix.
A further preferred embodiment envisages further admixing elemental aluminum,
zinc
and/or magnesium and/or their basic compounds, such as zinc hydroxide or
magnesium
chloride, in water-free form during the production of the polymer matrix and
incorporation
of the silver glass.
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This enables, on the one hand, high amounts of added silver glass, or the
additional
adding of antimicrobial silver compounds, such as silver zeolites, for
example, as is
known from the prior art. The addition of aluminum, zinc or magnesium and/or
their basic
compounds additionally avoids the blackening of the customary silver
compounds, which
is to be avoided.
As a result of the ingress of moisture via the wound or the surroundings, the
silver
undergoes conversion to silver chloride or silver oxide, which, as mentioned,
can lead to
unattractive appearance and loss of activity of known silver-containing
dressings. The
addition of aluminum, zinc or magnesium makes it possible, in accordance with
the
electrochemical potentials of the reaction systems
2 AgCI + Zn, 2/3 Al, Mg ¨> 2 Ag + ZnCl2, Mg C12, 2/3 AICI3,
for the antimicrobial silver to be re-formed.
In accordance with the invention the substances Al, Zn, Mg and/or their basic
compounds
can be used in an amount of 0.01% to 5% by weight, based on the total mass of
the
material.
It has been found that, therefore, in addition to the discoloration-stable
silver glasses, it is
also possible to incorporate discoloration-unstable silver compounds into the
polymer
material without accepting detractions from the desired activity and, in
particular,
esthetics.
The thickness of the wound contact material may be between about 100 to 2000
m,
preferably 400 to 1500 m, in particular between 600 to 1200 m.
If the wound contact material of the invention is self-adhesive then there is
no need for
additional means of fixing. The wound contact material is placed directly as
dressing
material on the wound to be covered, and attaches by virtue of its self-
adhesive
properties to the skin surrounding the wound.
In the case of very large wounds, when additional adhesive bonding is desired
or when
the polymer matrix is not self-adhesive, the wound contact material can be
adhered to
the skin by the addition of an edge layer bonding system.
In that case the dressing material of the invention is constructed in
accordance with
known wound dressings. They are composed, generally speaking, of a backing
material
provided on one side with a self-adhesive layer. The wound contact material of
the
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invention is then applied atop this self-adhesive coating. In order to ensure
ease of
handling, the self-adhesive coating is additionally lined with a protective
layer ¨ a sealing
paper, for example.
A suitable adhesive for the edge layer bonding system over the additional
backing
material is set out in the text DE 27 43 979 C3; in addition, the acrylate-
based or rubber-
based pressure-sensitive adhesives that are commercially customary can be used
with
preference for the adhesive coating.
Particular preference is given to thermoplastic hotmelt adhesives based on
natural and
synthetic rubbers and on other synthetic polymers such as acrylates,
methacrylates,
polyurethanes, polyolefins, polyvinyl derivatives, polyesters or silicones
with appropriate
adjuvants such as tackifier resins, plasticizers, stabilizers, and other
auxiliaries where
necessary. If desired, aftercrosslinking by UV or electron beam irradiation
may be
appropriate.
Incorporation of the silver glass
The silver glass can be distributed homogeneously throughout the polymer
matrix. This is
achieved by dispersing it homogeneously either in one of the starting
components of the
polymerization, or in the finished polymer mixture.
This can be done either in solution or else ¨ owing to the good heat stability
of the silver
glass ¨ in the melt (extruder).
The silver glass can also be distributed with local limitation in the matrix,
on the surface
for example, by means of layer construction.
For this purpose it is possible, for example, to apply a polymer solution
containing the
silver glass to the surface of the polymer matrix, by spraying, extrusion or
casting, for
example.
The polymer with silver glass added can be coated out with uniform flatness.
The
resulting coat can be diecut to a wound contact material of any desired shape.
The polymer coated out with uniform flatness can also be modified in form by
varying the
thickness as desired. For example, the middle of the wound contact material
can be left
in the original coated-out thickness, while the edges are flattened off.
The polymer can also be coated out not flat from the outset, but instead can
be cast in
any desired shapes.
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The dimensions are governed by the intended field of use (relatively small
injuries, on the
finger, for example; larger injuries ¨ e.g., grazes) and are freely
selectable.
An inventively furnished dressing material, with or without additional edge
bonding
system, is placed on the wound in customary fashion.
The wound contact material comes into contact with the wound exudate and
absorbs
said exudate, as a result of which the polymer matrix is observed to swell.
Particularly
when using polyurethane matrices, especially with superabsorbent materials
added,
advantageous absorption of the wound exudate in the polymer matrix is
observed. It is
possible subsequently to identify two steps which are essential for wound
healing. On the
one hand, silver ions are then released from the finely divided glass in
contact with the
exudate, and, on the other hand, microbes from the wound can be taken up into
the
polymer matrix. A dressing of the invention containing silver glass, following
application
to an exuding wound, by virtue of the contact of fluid with the silver
particles, will kill the
microbes that are located in the wound fluid, and/or prevent colonization, and
possibly
infection, of the wound with microorganisms. Both steps, alone or
synergistically in
unison, lead to a reduction in microbe growth and/or to the dying-off of the
microbes. The
antimicrobial wound contact material of the invention therefore has both
bacteriostatic
and bactericidal properties, which allows purposive application of
antimicrobial dressing
materials.
When the silver-containing dressing is removed, the antibacterial action is
stopped.
Subsequent washing of the wound to remove antibiotics and antiseptics applied
temporarily beforehand is unnecessary.
The described invention is based, therefore, on the described antimicrobial
action of
silver-containing particles in combination with a highly absorbent wound
contact material,
which together achieve a synergetic effect. Furthermore, a wound contact
material, such
as the polyurethane wound contact material of the invention, for instance, may
possess
self-adhesive properties which allow it to be fixed to the intact skin with
the edge of the
patient's wound. It relates to an innovative wound contact material which can
be used to
treat infected wounds or for preventive protection against wound infections.
In this
context, the dressing forms a barrier for microorganisms, preventing
penetration from
outside, by killing the microorganisms on contact with the antimicrobial wound
contact
material.
The unique combination of the hydroactive polyurethane polymer material with a
silver-
containing glass compound permits an advantageous acceptance of the product by
the
consumer, and a high level of product stability. In particular, the dark
coloration which is
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unattractive, is not accepted by the end user, and is initiated as a result in
particular of
moisture, light or 7 rays, such as exhibited by known, silver-containing
materials, is
significantly improved or even avoided completely.
A factor essential to the invention is that the antimicrobial silver glass is
readily
incorporable into the polyurethane matrix and so in fact makes it possible to
provide an
antimicrobial wound contact material. Surprisingly, not only the silver glass
fractions in
the polymer but also their distribution in the polymer and the fractions of
further additions
can be selected within wide ranges without exhibiting detractions in terms of
the
advantages depicted.
Furthermore, active skincare or wound-healing substances can additionally be
incorporated into the polymer matrix, these substances, when applied to the
skin,
supporting skin regeneration. Active substances which can be added include
vitamins,
such as vitamin E or vitamin C, essential oils, flavone and its derivatives,
or
antiinflammatories and/or analgesics.
The silver-containing polymer material of the invention can therefore be used
in wound
treatment as a self-adhesive wound contact material or a wound contact
material with an
additional edge bonding system. Moreover, in addition to use in wound healing,
provision
is made for use in skincare, application as skin protection, and use as a
preventative
against skin damage.
Inventive polymer materials and wound dressings are described below in
preferred
configuration with reference to a number of examples, without wishing thereby
to restrict
the invention in any way whatsoever. The fractional data relate to the total
mass of
polymer material, unless otherwise indicated.
Cosmetics
The present invention also relates to cosmetics comprising silver glass,
especially
emulsion-based cosmetic, pharmaceutical or dermatological preparations. By
virtue of
the antimicrobial and/or disinfectant action of the silver glass, the
preparations serve,
inter alia, for the prophylaxis and treatment of inflammatory skin conditions
and/or for
skin protection.
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The preparations comprising silver glass are generally emulsions or aqueous
hydrogels
which in addition to customary moisturizing substances may also include
specific active
substances, such as, for example,
= inflammation-alleviating and cooling substances,
5 = local anesthetics and/or
= other active cosmetic, pharmaceutical and/or dermatological substances
for
topical application.
Use is made, for example, of plant-derived, inflammation-alleviating or
¨inhibiting active
10 substances such as azulene and bisabolol (camomile), glycyrrhizin
(licorice root),
hamamelin (witch hazel) or total extracts, from aloe vera or camomile for
example. These
exhibit good success in the case of milder forms and locally limited erythema
reactions.
The same is true of creams containing a high level of essential oils or
panthenol.
15 Aftersun products are intended, for example, to cool the skin after
sunbathing and to
enhance its moisturization, the imparting of the cooling effect playing a
central part. This
cooling effect is achieved, for example, by means of large amounts of ethanol,
which
evaporates spontaneously when the formulation is spread over the skin.
Hydrogels, 0/W
emulsions (lotions) or aqueous suspensions also have a pronounced cooling
effect by
20 virtue of the cold due to evaporation of the aqueous phase. For the
prophylaxis of
inflammatory processes, preparations of this kind can be admixed with silver
glass for the
disinfection of the damaged tissue.
The formulations of the invention are products which are entirely satisfactory
in every
25 respect and are distinguished by an outstanding action. When the cosmetic,
dermatological or pharmaceutical preparations, containing an effective amount
of silver
glass, used in accordance with the invention, are applied, effective treatment
and also
prophylaxis of inflammatory skin conditions ¨ including atopic eczema ¨ and/or
for skin
protection in the case of dry skin which has been determined as being
sensitive, is
30 possible.
The invention, it will be appreciated, is not restricted to topical
application forms which
are applied after sunbathing, but instead, of course, embraces all cosmetic,
pharmaceutical, and dermatological applications in which an inflammation-
alleviating
35 effect could be desirable or advantageous.
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It is advantageous in accordance with the invention if the cosmetic,
pharmaceutical or
dermatological preparations contain 0.001% to 10% by weight, in particular
0.05% to 5%
by weight, very particularly 0.1% to 2% by weight of silver glass, based in
each case on
the total weight of the preparation.
It is preferred in the context of the present invention if the cosmetic or
dermatological
preparations of the invention comprise one or more alcohols, particularly if
the
formulations are present in the form of an aftersun product and are intended
to be
distinguished by a particular cooling effect.
It is further preferred in the context of the present invention if the
cosmetic,
pharmaceutical, and dermatological preparations of the invention contain
glycerol in an
amount of 0.1%-30% by weight, more preferably of 2%-10% by weight, in order to
ensure
effective moisturization of the skin.
In addition to one or more oil phases, the cosmetic, pharmaceutical or
dermatological
formulations for the purposes of the present invention may additionally
comprise one or
more water phases and may be in the form, for example, of W/0, 01W, W/O/W or
0/VV/0 emulsions. Emulsions of this kind may with preference also be a
microemulsion,
a Pickering emulsion or a sprayable emulsion. In this case, plasterlike
application forms
could be impregnated with these emulsions. Emulsions of this kind are
described in more
detail in patent application DE 101 21 092.
The formulations or application forms of the invention preferably further
comprise
additional antiinflammatory substances, such as allantoin, a-bisabolol,
panthotenic acid,
panthenol, royal jelly, chamomile extracts, azulene or aloe vera extract, and
also
unsaponifiable fractions of avocado oil or soybean oil, and other substances
which calm
the irritated skin. Further advantageous active substances are tannins, which
have an
astringent, antiinflammatory and/or secretion-inhibiting effect.
In one preferred embodiment of the formulations of the invention containing
silver glass,
they find use in particular as aftersun skincare products.
One particularly preferred field of application of the preparations of the
invention is
situated within care and decorative cosmetology. That is, it is possible also
to provide
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solid, semisolid or stick-form cosmetic preparations for decorative purposes,
viz makeup
formulations, or care preparations, such as lipcare sticks, for example, which
likewise
exhibit outstanding dispersibility and, furthermore, have an antimicrobial
and/or
disinfectant and care effect.
In the case of the decorative preparations in stick form a distinction is made
between
primarily two kinds of formulation. Sticks contain principally an oil
substance or more
recent formulations are anhydrous and for that purpose require particular
thickener
systems, based for example on mixtures of stearyl alcohol and hydrogenated
castor oil,
and based on natural or synthetic waxes.
Anhydrous solid or semisolid formulations are characterized in that one or
more solid,
particulate agents are in suspension in a vehicle. The vehicle is composed at
least of one
or more highly volatile oils, one or more nonvolatile emollients, and one or
more
thickeners.
In particular, however, the properties of the preparations containing silver
glass expound
a use in cosmetic, pharmaceutical, and dermatological products which combine
alleviation in the case of irritated skin conditions and/or supporting of the
re-
establishment of dermal homeostasis with a simultaneous skincare function.
In particular it is advantageous for makeup products, for the purposes of the
present
invention, to incorporate dyes and/or color pigments, additionally, into the
preparations
according to the invention.
In the case of application forms according to the invention which comprise
silver glass,
cosmetic or pharmaceutical auxiliaries may be present, such as are commonly
used in
preparations of this kind, examples being preservatives, dyes, pigments which
have a
coloring action, solubilizers, penetration enhancers, hydrophilic fillers,
thickeners, resins,
moistening and/or moisturizing substances, fats, oils, waxes or other
customary
constituents of a cosmetic or pharmaceutical formulation, such as alcohols,
polyols,
polymers, foam stabilizers, electrolytes, organic solvents and/or silicone
derivatives, and
also moisturizers.
As thickeners it is possible with advantage, for example, to select inorganic
gel formers
from the group of the modified or unmodified, naturally occurring or synthetic
phyllosilicates.
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Although it is entirely favorable to use single components, it is also
possible, in
advantageous fashion, to incorporate mixtures of different modified and/or
unmodified
phyllosilicates into the silver glass preparations of the invention.
For application, the cosmetic and dermatological formulations of the invention
are applied
to the skin and/or hair in a sufficient amount in a customary fashion, i.e.,
for example,
directly ¨ following removal from a bottle, tube, pot or any other container ¨
or using an
(impregnated) wipe.
A particular advantage of the preparations of the invention is that the silver
glasses, by
virtue not least of their advantageous fine division, do not lead to any
detractions
whatsoever in application, in comparison to customary cosmetics. The advantage
according to the invention lies in the storage stability and hence activity
over a relatively
long period of time, and, in particular, in the stability toward discoloration
by external
influences such as heat or sunlight. In relation to other silver-containing
cosmetics,
therefore, the preparations of the invention do not exhibit any blackening or
darkening.
Wipes, pads, skin contact material
Impregnated wipes find broad use, as articles of everyday utility, in a wide
variety of
segments. Among other things, they permit efficient skin-friendly cleaning and
care, not
least in the absence of (running) water.
The actual article of use is composed of two components:
a) a dry cloth constructed from materials such as paper and/or any of a
very wide
variety of mixtures of natural or synthetic fibers, and
b) a low-viscosity impregnating solution.
The present invention accordingly further provides cosmetic, pharmaceutical,
and
dermatological wipes moistened with cosmetic, pharmaceutical or dermatological
impregnating solutions and comprising silver glass.
"Dry" cloths preferred in accordance with the invention are composed of
nonwoven,
especially water-jet-consolidated and/or water-jet-embossed nonwoven.
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Nonwovens of this kind may have macroimpressions in any desired pattern. The
selection to be made is governed firstly by the impregnation to be applied and
secondly
by the field of use in which the subsequent wipe is to be used.
It has been found advantageous for the cloth to have a weight of 35 to 120
g/m2,
preferably from 40 to 60 g/m2 (measured at 20 C 2 C and at an atmospheric
humidity
of 65% 5% for 24 hours).
The thickness of the nonwoven is preferably 0.4 mm to 2 mm, especially 0.6 mm
to
0.9 mm.
Starting materials which can be used for the nonwoven of the cloth may,
generally, be
any organic and inorganic, natural and synthetic fiber materials. By way of
example
mention may be made of viscose, cotton, cellulose, jute, hemp, sisal, silk,
wool,
polypropylene, polyester, polyethylene terephthalate (PET), aramid, nylon,
polyvinyl
derivatives, polyurethanes, polylactide, polyhydroxyalkanoate, cellulose
esters and/or
polyethylene, and also mineral fibers such as glass fibers or carbon fibers.
The present
invention, though, is not restricted to the materials stated; rather, it is
possible to employ
a multiplicity of further fibers to form the nonwoven. It is particularly
advantageous for the
purposes of the present invention if the fibers employed are not water-
soluble.
In one particularly advantageous embodiment of the nonwoven the fibers are
composed
of a blend of 70% viscose and 30% PET.
Also of particular advantage are fibers made of high-strength polymers such as
polyamide, polyester and/or highly drawn polyethylene.
Furthermore, the fibers may also be colored, in order to allow the visual
attractiveness of
the nonwoven to be emphasized and/or increased. The fibers may further
comprise UV
stabilizers and/or preservatives.
The fibers used to form the cloth preferably have a water absorption rate of
more than
60 mm/[10 min] (measured with the EDANA test 10.1-72), in particular more than
80 mm/[10 min].
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The fibers used to form the cloth further have, preferably, a water absorbency
of more
than 5 g/g (measured by the EDANA test 10.1-72), in particular more than 8
g/g.
It is advantageous for the purposes of the present invention if the weight
ratio of the
5 unimpregnated cloth to the impregnating solution is selected from the
range from 2:1 to
1:6.
The inventive cosmetic, pharmaceutical and dermatological formulations and
preparations referred to in the course of the description of the present
invention
10 constitute advantageous impregnating solutions for cosmetic and
dermatological wipes in
the sense of the present invention.
It is advantageous if the impregnating solutions of the invention are of low
viscosity,
being, in particular, sprayable, and having, for example, a viscosity of less
than
15 2000 mPa.s, in particular less than 1500 mPa-s (measuring instrument:
Haake
Viskotester VT-02 at 25 C). The impregnating solutions may also correspond to
the
cosmetic preparations of the invention which comprise the silver glass.
Cleansing preparations
20 Examples of cleansing preparations of the invention are bath foams and
shower
products, solid and liquid soaps or what are called "syndets" (synthetic
detergents),
shampoos, handwash pastes, intimate washes, special cleansing products for
infants,
shower gels, cleansers, makeup removers or shaving products. The preparations
may be
solid (soaps), of low viscosity or gellike, may foam slightly or strongly,
and/or may be
25 used as antibacterial rinse-off formulations. The cleansing products are
very mild to the
skin and are advantageously of esthetic transparency. As microemulsions they
can also
be used as an impregnating medium for cloths, fabrics, which are employed wet
or dry by
the user, as described above.
30 Cosmetic or dermatological preparations and cleansing products are
frequently in the
form of finely disperse multiphase systems in which one or more fatty or oily
phases are
present in addition to one or more water phases. Of these systems, in turn,
the actual
emulsions are the most widespread.
35 In simple emulsions, finely disperse droplets of one phase (water
droplets in W/O
emulsions or lipid vesicles in 0/W emulsions), surrounded by a shell of
emulsifier, are
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present in a second phase. The droplet diameters of the usual emulsions are
situated in
the range from about 1 pm to about 50 pm. Such "macroemulsions", absent
further
coloring additions, are milky white in color and opaque. Finer
"macroemulsions", whose
droplet diameters are situated in the range from about 10-1 pm to about 1 pm,
again
absent coloring additions, are bluish white in color and nontransparent.
Only micellar and molecular solutions with particle diameters smaller than
about 102 pm
appear clear and transparent.
The droplet diameter of transparent or translucent microemulsions, in
contrast, is situated
in the range from about 10-2 pm to about 10-1 pm. Microemulsions of this kind
are
generally of low viscosity. The viscosity of many microemulsions of the 0/W
type is
comparable with that of water.
An advantage of microemulsions is that active substances can be present in a
more
finely disperse form in the disperse phase than in the disperse phase of
"macroemulsions". A further advantage is that they are sprayable, as a result
of their low
viscosity.
The cosmetic and dermatological preparations of the invention, and especially
cleansing
preparations, may comprise cosmetic auxiliaries such as are commonly used in
such
preparations, examples being preservatives, bactericides, perfumes, dyes,
pigments
having a coloring action, thickeners, moistening and/or moisturizing
substances, fats,
oils, waxes or other customary constituents of a cosmetic or dermatological
formulation,
such as alcohols, polyols, polymers, foam stabilizers, electrolytes, organic
solvents or
silicone derivatives.
The cosmetic and/or dermatological cleansing preparations of the invention are
produced
in a customary manner which is known to the skilled worker, generally such
that the
substances used in accordance with the invention, or a preliminary solution of
these
substances, is or are dissolved and/or dispersed, accompanied by uniform
stirring and,
where appropriate, by heating. The silver glass of the invention can be simply
added,
advantageously in amounts of 0.005% to 10% by weight, based on the total mass
of the
preparation.
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Subsequent contact with water releases the silver ions, which develop their
disinfectant
and/or antimicrobial effect.
The examples which follow elucidate the materials of the invention.
All amounts, fractions, and percentages, unless otherwise indicated, are based
on the
weight and the total amount, or on the total weight, of the preparations
comprising silver
glass.
Example 1
A polymer material comprising silver glass was produced, having the following
composition:
Polyether polyol (Levagel) = 16.50 g
Crosslinker (Desmodur) = 1.70 g
Vitamin E = 0.10 g
Favor T (superabsorbent) = 2.05 g
lonpure = 0.10 g
Coscat catalyst = 0.04 g
20.50 g,
the silver-containing glass lonopure from lshizuka exhibiting the following
composition,
based on the total mass of glass:
`)/0 by weight
P205 73.35
MgO 18.33
A1203 6.32
Ag20 2.00
Example 2
The polymer material produced in Example 1 was used to investigate the release
of Ag+
ions into 0.9% strength NaCI solution.
A flatly coated specimen A (1 g of sample per 100 ml of 0.9% strength NaCI
solution) of =
the above composition, with a weight per unit area of approximately 800 g/m2,
released
silver ions in the following amounts, shown in Table 1.
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Comparable specimens from the prior art with silver zeolites (B) or silver
zirconium
phosphates (C), for which antimicrobial activity was detected in
investigations, also from
the prior art, released the following amounts of silver ions:
Table 1
Release of silver from polymer material of Example 1 (A) in comparison to
standard
dressing materials (B, C)
Time (h) / silver release (mg/kg) Dressing material
A
24 23.8 14.4 28.5
72 25.4 25.0 23.4
168 28.3 26.5 29.6
The example shows that release of silver ions from the polymer material of the
invention
is observed in the same order of magnitude as from antimicrobial dressing
materials
known from the prior art, with silver zeolites (B) or silver zirconium
phosphates (C),
respectively.
Example 3
Production of wound contact materials of the invention, containing different
levels of
silver glass.
Specimen D:
A wound contact material was produced with the following composition (0.01% by
weight
silver glass):
Polyether polyol (Levagel) = 14.505 g
Crosslinker (Desmodur) = 1.391 g
Vitamin E = 0.057 g
Favor T (superabsorbent) = 4.524 g
lonpure = 0.002g
Coscat = 0.041 g
20.520 g
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Specimen E
A wound contact material was produced with the following composition (0.05% by
weight
silver glass):
Polyether polyol (Levagel) : 14.41 g
Crosslinker (Desmodur) 1.38 g
Vitamin E = 0.06 g
Favor T (superabsorbent) = 4.50 g
lonpure = 0.01 g
Coscat = 0.04g
20.39 g
Specimen F
A wound contact material was produced with the following composition (0.075%
by
weight silver glass):
Polyether polyol (Levagel) : 14.41 g
Crosslinker (Desmodur) 1.38 g
Vitamin E = 0.06 g
Favor T (superabsorbent) = 4.51 g
lonpure = 0.016 g
Coscat = 0.04g
20.41 g
Specimen G
A wound contact material was produced with the following composition (0.1% by
weight
silver glass):
=
Polyether polyol (Levagel) : 79.03 g
Crosslinker (Desmodur) 7.65 g
Vitamin E = 0.30 g
= Favor T (superabsorbent) : 22.76 g
lonpure 0.11 g
Coscat = 0.36 g
110.22g
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Specimen H
A wound contact material was produced with the following composition (0.25% by
weight
silver glass):
5
Polyether polyol (Levagel) : 78.68 g
Crosslinker (Desmodur) 7.57 g
Vitamin E = 0.30 g
Favor T (superabsorbent) : 22.66 g
lonpure 0.28 g
Coscat 0.36g
109.86 g
Specimen I
A wound contact material was produced with the following composition (0.52% by
weight
silver glass):
Polyether polyol (Levagel) : 78.95 g
Crosslinker (Desmodur) 7.58 g
Vitamin E = 0.31 g
Favor T (superabsorbent) : 22.74 g
lonpure 0.57 g
Coscat = 0.36 g
110.51 g
Specimen J
A wound contact material was produced with the following composition (1.02% by
weight
silver glass):
Polyether polyol (Levagel) : 79.16 g
Crosslinker (Desmodur) 7.55 g
Vitamin E = 0.30 g
Favor T (superabsorbent) : 22.91 g
lonpure 1.14g
Coscat = 0.36 g
111.42 g
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Example 4
The specimens D-J (about 800 g/m2) of Example 3 produced were investigated for
their
release of silver ions after 24 h in accordance with the following specified
procedure.
Sample designation % by weight silver glass Concentration of Ag
[mg Ag/kg polymer material]
0.01 1.5
0.05 5.2
0.075 9.4
0.1 13.0
0.25 20.0
0.52 22.0
1.02 20.0
Example 5
Samples D to J produced were investigated for their antimicrobial activity in
accordance
with JIS 2801:2000 on
= Escherichia coli IFO 3972
= Staphylococcus aureus IFO 12732.
The activity of the samples is calculated in accordance with the following
equation (1):
Number of living bacteria at beginning (1)
Intimicrobial activity = log10 Number of living bacteria after 24 h
Antimicrobial activity can be assumed, accordingly, when the activity is >2,
i.e., the
number of bacteria investigated is reduced by a factor of 100.
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Table 2: Antimicrobial activity
Specimen Agrelease after 24 h Antimicrobial activity as per
(1)
[mg/mg] Escherichia coli Staphylococcus aureus
13 >3.6 >3.3
22 >3.6 >3.3
I sterile 20 >3.6 >3.3
Example 6
To compare the discoloration stability of the wound contact materials of the
invention,
specimens D to J were investigated for their change in color by addition of
the silver
glass. No change is apparent from the undoped reference up to specimen H. Only
at a
concentration above 0.25% by weight silver glass (specimen H) is it possible
to
determine a slight color change, which is difficult to discern with the naked
eye.
Example 7
In order to test the stability of the silver glass on sterilization, specimen
J was 7-sterilized
with 26 kGy. No color change was caused by the 7-sterilization. 7-
Sterilization of the
ready-produced plaster did not result in any detractions whatsoever in terms
of
antimicrobial activity in accordance with JIS Z 2801:2000 and,
extraordinarily, did not
lead to any discoloration of the dressing material.
Example 8
In order to test the aging stability of the wound dressings of the invention,
specimens G
were subjected to accelerated aging at 50 C for six months and inspected for
color
stability. In this case too, no color changes whatsoever were found.
Example 9
Details of the polymer matrix
I propose the following properties (in addition to the thickness) for
characterization:
Fluid absorption: 0.5-10 g/g
preferably 1.0-6 g/g
more preferably 1.5-3.5 g/g
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Method:
A circular sample with a diameter of 22 mm is punched out and conditioned for
one hour
at 23 2 C and 50 5% rh. The samples are weighed and immersed for 3 hours
completely in physiological saline solution at 23 0.5 C. The samples are
weighed again
and the fluid absorption is calculated from the weighed difference.
Water vapor permeability: 100-5000 g/(m2*24h)
preferably 250-2500 g/(m2*24h)
more preferably 300-1500 g/(m2*24h)
Method:
Testing takes place in accordance with ASTM E 96 (water method), with the
following
differences:
The aperture of the test vessel is 804 mm2
The material is conditioned for 24 hours at 23 2 C and 50 5% rh
The distance between the level of water in the test vessel and the sample is
35 5 mm
The reweighing of the test vessels equipped with samples is made after 24 h,
during
which time the test vessels are stored in a conditioning cabinet at 37 1.5 C
and
30 3% rh.
Example 10 ¨ Polvisobutylene matrices
VistanexTM LM MH: 48.33% by weight
VistanexTM MM L80: 28.00% by weight
Eastoflex TM PLS E1003D 10.00% by weight
Cetiol TM V 13.17% by weight
Silver glass 0.50% by weight
Example 11 ¨ Polvacrylic acid matrices
Polyacrylic acid 22.5% by weight
Polyvinylpyrrolidone, PVP 25 3.5% by weight
Propanediol 37.49% by weight
Polyethylene glycol 20.0% by weight
Silica 11.5% by weight
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Dexpanthenol 5.0% by weight
Silver glass 0.01% by weight
Example 12 ¨ Silicone matrices
Carbopol TM 32.0% by weight
Q7-9600A 23.4% by weight
Q7-9600B 13.9% by weight
Silicone-PSA 29.7% by weight
Silver glass 1.0% by weight
Example 13¨ Rubber matrices
Silver glass 1.000%
Golan TM 46 2.099%
KerometTM MD 100 0.262%
Filler IR 13.120%
Crepe 11.546%
AmeripolTM 1011 21.591%
Natsyn TM 2200 8.397%
Resin 115 11.021%
Resin 95 9.971%
Resin SE 10 8.922%
Yellow oil 7.347%
Lanolin DAB* 4.724%
* German Pharmacopeia
Example 14 ¨ SBC hotmelt matrices
Kraton TM D-1113, Kraton: 43.87% by weight
EscorezTM 5380, Exxon: 24.54% by weight
Sylvares TM TR 7115, Arizona 21.90% by weight
WhitemorTM WOM 14, Castrol 3.84% by weight
CetiolTM V, Henkel 4.35% by weight
I rganox TM 1010, Ciba-Geigy 0.78% by weight
Silver glass 0.72% by weight
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Example 15 - PVA/PAA-based polymer film
MowiolTM 18/88 73.40% by weight
Carbopol TM 980 16.00% by weight
Dexpanthenol 5.00% by weight
Lutrolrm E 400 5.00% by weight
Q 10 0.50% by weight
Silver glass 0.10% by weight
5 Example 16-20: PIT sprays
16 17 18 19 20
Glyceryl monostearate SE 0.50 3.00 2.00 4.00
Ceteareth-12 5.00 1.00 1.50
Ceteareth-20 2.00
Ceteareth-30 5.00 1.00
Stearyl Alcohol 3.00 0.50
Cetyl Alcohol 2.50 1.00 1.50
Ethylhexyl Methoxycinnamate 5.00 8.00
Aniso Triazine 1.50 2.00 2.50
Butyl Methoxydibenzoylmethane 2.00
Dioctyl Butamidotriazone 1.00 2.00 2.00
Ethylhexyl Triazone 4.00 3.00 4.00
4-Methylbenzylidene Camphor 4.00 2.00
Octocrylene 4.00 2.50
Bisimidazylate 0.50 1.50
Phenylbenzimidazole Sulfonic Acid 0.50 3.00
C12_15 Alkyl Benzoate 2.50 _ 5.00
Titanium dioxide 0.50 1.00 3.00 2.00
Zinc oxide 2.00 3.00 0.50 1.00
Dicaprylyl Ether 3.50
Butylene Glycol Dicaprylate/Dicaprate 5.00 6.00
Dicaprylyl Carbonate 6.00 2.00
Dimethicone 0.50 1.00
Phenyltrimethicone 2.00 0.50 0.50
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Shea Butter 2.00 0.50
PVP Hexadecene Copolymer 0.50 0.50 1.00
Glycerol 3.00 7.50 5.00 7.50 2.50
Vitamin E Acetate 0.50 0.25 1.00
Silver glass 0.30 0.10 0.60 0.20 0.30
Alpha Glucosylrutin 0.10 0.20
DMDM Hydantoin 0.60 0.40 0.20
Koncyl-L 0.20 0.15
Methylparaben 0.50 0.25 0.15
Phenoxyethanol 0.50 0.40 1.00 0.60
Ethanol 3.00 2.00 1.50 1.00
Perfume q.s. q.s. q.s. q.s. q.s.
Water ad 100 ad 100 ad 100 ad 100 ad 100
Example 21-25: 0/W creams
21 22 23 24 25
Glyceryl Stearate Citrate 2.00 2.00
Glyceryl Stearate SE 3.00
Cetearyl Alcohol + PEG-40 Castor Oil 3.00
+ Sodium Cetearyl Sulfate
Polyglycery1-3-Methylglucose 3.00
Distearate
Sorbitan Stearate 2.00
Stearic add 1.00
Stearyl Alcohol 5.00
Cetyl Alcohol 2.00 3.00
Cetylstearyl alcohol 2.00
Caprylic/Capric Triglyceride 5.00 3.00 4.00 3.00 3.00
Octyldodecanol 2.00 2.00
Dicaprylyl ether 4.00 2.00 1.00
Mineral oil 2.00 3.00
Cyclomethicone 3.00
TiO2 1.00
4-Methylbenzylidene Camphor 1.00
Butyl Methoxydibenzoylmethane 0.50
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Silver glass 0.30 0.30 0.50 0.10 1.00
Tocopherol 0.20 0.20
Hydroxypropyl Methylcellulose 0.30
Trisodium EDTA 0.10 0.1
Preservative q.s. q.s. q.s. q.s.
Xanthan Gum
Carbomer 0.30 0.1 0.1 0.1
Sodium hydroxide solution 45% q.s. q.s. q.s. q.s. q.s.
Glycerol 6.00 3.00 4.00 3.00 3.00
Ethylhexylglycerol 0.25
Butylene Glycol 3.00
Alcohol Denat. 7.0
Perfume q.s. q.s. q.s. q.s. q.s.
Aqua ad 100 ad 100 ad 100 ad 100 ad 100
Example 26-30; 0/W creams
26 27 _ 28 29 30
Glyceryl Stearate Citrate 2.00 2.00
Glyceryl Stearate SE 5.00
Stearic acid 2.50 3.50
Stearyl Alcohol 2.00
Cetyl Alcohol 3.00 4.50
Cetylstearyl alcohol 3.00 1.00 0.50
C12_15 Alkyl Benzoate 2.00 3.00
Caprylic/Capric Triglyceride 2.00
Octyldodecanol 2.00 2.00 4.00 6.00
Dicaprylyl ether
Mineral oil 4.00 2.00
Cyclomethicone 0.50 2.00
Dimethicone 2.00
TiO2 2.00
4-Methylbenzylidene Camphor 1.00 1.00
Butyl Methoxydibenzoylmethane 0.50 0.50
Silver glass 0.10 0.30 0.20 0.10 0.20
Tocopherol 0.05
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Trisodium EDTA 0.20 0.20
Preservative q.s. q.s. q.s. q.s. q.s. _
Xanthan Gum 0.20
Carbomer 0.15 0.1 0.05 0.05
Sodium hydroxide solution 45% q.s. q.s. q.s. q.s. q.s.
Glycerol 3.00 3.00 5.00 3.00
Butylene Glycol 3.00
Alcohol Denat. 3.00 3.00
Perfume q.s. q.s. q.s. q.s. q.s.
Aqua ad 100 ad 100 ad 100 ad 100 ad 100
Examele 31-37. W/O emulsions
31 32 33 34 35 36 37
Cetyldimethicone 2.50 4.00
Copolyol
Polyglycery1-2-dipoly- 5.00 4.50 4.00 5.00
hydroxystearate
PEG-30-dipolyhydroxy- 5.00
stearate
Lanolin Alcohol 0.50 1.50
lsohexadecane 1.00 2.00
Myristyl Myristate 0.50 1.50
Cera Microcristallina + 1.00 2.00
Paraffinum Liquidum
Ethylhexyl Methoxy- 8.00 5.00 4.00
cinnamate
Aniso Triazine 2.00 2.50 2.00 2.50
Butyl Methoxydibenzoyl- 2.00 1.00 0.50 1.50
methane
Dioctyl Butamidotriazone 3.00 1.00 3.00
Ethylhexyl Triazone 3.00 4.00
4-Methylbenzylidene 2.00 4.00 2.00 1.00 3.00
Camphor
Octocrylene 7.00 2.50 4.00 2.50
Dioctylbutamidotriazone 1.00 2.00
Bisimidazylate 1.00 2.00 0.50
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Phenylbenzimidazole 0.50 3.00 2.00
Sulfonic Acid
Titanium dioxide 2.00 1.50 3.00
Zinc oxide 3.00 1.00 2.00 0.50
Mineral oil 10.0 8.00
C12-15 Alkyl Benzoate 9.00
Dicaprylyl Ether 10.00 7.00
Butylene Glycol 2.00 8.00 4.00 4.00 5.00
Dicaprylate/Dicaprate
Dicaprylyl Carbonate 5.00 6.00
Dimethicone 4.00 1.00 5.00
Cyclomethicone 2.00 25.00 2.00
Shea Butter 3.00 0.50
PVP Hexadecene 0.50 0.50 1.00
Copolymer
Butylene Glycol 6.00
Octoxyglycerol 0.30 1.00 0.50 3.00
Glycerol 3.00 7.50 7.50 2.50 5.00
Glycine Soya 1.00 1.50
MgSO4 1.00 0.50 0.50
MgC12 1.00 0.70
Vitamin E Acetate 0.50 0.25 1.00 0.50 1.00
Silver glass 0.10 0.30 0.20 0.40 0.30 1.00 0.60
Trisodium EDTA 0.20 0.20
DMDM Hydantoin 0.60 0.40 0.20
Methylparaben q.s. q.s. q.s. q.s. q.s. q.s. q.s.
Phenoxyethanol q.s. q.s. q.s. q.s. q.s. q.s. q.s.
Ethanol 3.00 1.50 1.00 3.00
Perfume q.s. q.s. q.s. q.s. q.s. q.s. q.s.
Water ad ad ad ad ad ad ad
100 100 100 100 100 100 100
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Example 38-42: Hydrodispersions
38 39 40 41 42
Ceteareth-20 1.00 0.5
Cetyl Alcohol 1.00
Sodium Carbomer 0.20 0.30
Acrylates/C10-30 Alkyl Acrylate 0.50 0.40 0.10 0.10
Crosspolymer
Xanthan Gum 0.30 0.15 0.50
Ethylhexyl Methoxycinnamate 5.00 8.00
Aniso Triazine 1.50 2.00 2.50
Butyl Methoxydibenzoylmethane 1.00 2.00
Dioctyl Butamidotriazone 2.00 2.00 1.00
Ethylhexyl Triazone 4.00 3.00 4.00
-
4-Methylbenzylidene Camphor 4.00 4.00 2.00
Octocrylene 4.00 4.00 2.50
Dioctylbutamidotriazone 1.00 2.00
Bisimidazylate 1.00 0.50 2.00
Phenylbenzimidazole Sulfonic acid 0.50 3.00
Titanium dioxide 0.50 2.00 3.00 1.00
Zinc oxide 0.50 1.00 3.00 2.00
C12-15 Alkyl Benzoate 2.00 2.50
Dicaprylyl Ether 4.00
Butylene Glycol Dicaprylate/Dicaprate 4.00 2.00 6.00
-
Dicaprylyl Carbonate 2.00 6.00
Dimethicone 0.50 1.00 _
Phenyltrimethicone 2.00 0.50 2.00
_
Shea Butter 2.00
PVP Hexadecene Copolymer 0.50 0.50 1.00
Octoxyglycerol 1.00 0.50
Glycerol 3.00 7.50 7.50 2.50
Glycine soya 1.50
Vitamin E Acetate 0.50 0.25 1.00
Silver glass 0.30 0.10 0.50 0.30 0.20
DMDM Hydantoin 0.60 0.40 0.20
Koncyl-L q.s. q.s. q.s. q.s. q.s.
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Methylparaben q.s. q.s. q.s. q.s. q.s.
Phenoxyethanol q.s. q.s. q.s. q.s. q.s.
Ethanol 3.00 2.00 1.50 1.00
Perfume q.s. q.s. q.s. q.s. q.s.
Water ad 100 ad 100 ad 100 ad 100 ad 100
Example 43 Gel cream
Mass content (%)
Acrylate/C10-30 Alkyl Acrylate Crosspolymer 0.40
Carbomer 0.20
Xanthan Gum 0.10
Cetearyl Alcohol 3.00
C12-15 Alkyl Benzoate 4.00
Caprylic/Capric Triglyceride 3.00
Cyclomethicone 5.00
Dimethicone 1.00
Silver glass 0.30
Glycerol 3.00
Sodium hydroxide q.s.
Preservative q.s.
Perfume q.s.
Water, demineralized ad 100.0
pH adjusted to 6.0
Example 44 W/O cream
Lameform TGI 3.50
Glycerol 3.00
Dehymuls PGPH 3.50
Silver glass 0.10
Preservative q.s.
Perfume q.s.
Water, demin. ad 100.0
Magnesium sulfate 0.6
Isopropyl Stearate 2.0
Caprylyl Ether 8.0
Cetearyl Isononanoate 6.0
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Example 45 W/O/W cream
Mass content (%)
Glyceryl Stearate 3.00
PEG-100 Stearate 0.75
Behenyl alcohol 2.00
Caprylic/Capric Triglyceride 8.00
Octyldodecanol 5.00
C12-15 Alkyl Benzoate 3.00
Silver glass 1.00
Magnesium Sulfate (MgSO4) 0.80
EDTA 0.10
Preservative q.s.
Perfume q.s.
Water, demineralized ad 100.0
pH adjusted to 6.0
=
