U.S. patent application number 16/690784 was filed with the patent office on 2020-03-19 for wound dressing materials incorporating anthocyanins derived from fruit or vegetable sources.
The applicant listed for this patent is Allison Coomber. Invention is credited to Allison Coomber.
Application Number | 20200085991 16/690784 |
Document ID | / |
Family ID | 55748178 |
Filed Date | 2020-03-19 |
United States Patent
Application |
20200085991 |
Kind Code |
A1 |
Coomber; Allison |
March 19, 2020 |
WOUND DRESSING MATERIALS INCORPORATING ANTHOCYANINS DERIVED FROM
FRUIT OR VEGETABLE SOURCES
Abstract
A wound dressing composition, such as gauze, bandages, and
surgical tapes comprising a substrate material impregnated with a
pH sensitive dye composition comprising at least one anthocyanin
derived from fruit or vegetable sources, and methods of use
thereof.
Inventors: |
Coomber; Allison; (Auburn,
MA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Coomber; Allison |
Auburn |
MA |
US |
|
|
Family ID: |
55748178 |
Appl. No.: |
16/690784 |
Filed: |
November 21, 2019 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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15830188 |
Dec 4, 2017 |
10517981 |
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16690784 |
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14514579 |
Oct 15, 2014 |
9855364 |
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15830188 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61L 15/40 20130101;
A61L 15/56 20130101; A61L 15/44 20130101; A61K 49/006 20130101;
A61K 49/0004 20130101 |
International
Class: |
A61L 15/40 20060101
A61L015/40; A61K 49/00 20060101 A61K049/00; A61L 15/44 20060101
A61L015/44; A61L 15/56 20060101 A61L015/56 |
Claims
1.-32. (canceled)
33. A method of manufacturing a wound dressing, comprising:
providing a substrate material; and disposing pH sensitive dye
composition comprising at least one fruit or vegetable derived
anthocyanin within the substrate material.
34. The method of claim 33, wherein the at least one anthocyanin is
derived from a raspberry (Rubus sp.).
35. The method of claim 33, wherein the at least one anthocyanin is
derived from a fruit or vegetable selected from the group
consisting of a red cabbage, purple cabbage, purple carrots,
elderberry, hibiscus, purple potato, red currant, black currants,
blueberries, cherries, purple grapes, red raspberries and black
raspberries.
36. The method of claim 33, wherein the substrate material is a
woven or non-woven material.
37. The method of claim 33, wherein the substrate material
comprises a fabric, cloth or sponge material.
38. The method of claim 33, where the substrate material comprises
natural or synthetic fibers.
39. The method of claim 33, where the substrate material is an
absorbent or water-permeable material.
40. The method of claim 33, where the substrate material comprises
cotton.
41. The method of claim 33, wherein substrate material comprises
cotton gauze.
42. The method of claim 33, wherein the wound dressing is selected
from the group consisting of a pad, wrap, bandage, tape,
cotton-tipped stick and adhesive strip bandage.
43. The method of claim 33, wherein the at least one anthocyanin is
selected from the group consisting of cyaniding-3-sophoraside,
cyanide-3-glucoside or pelargonidin-3-sophoroside.
44. The method of claim 33, wherein the at least one anthocyanin is
an anthocyanadin derivative selected from the group consisting of
cyandin, delphinidin, peonidin, petunidin, pelargonidin and
malvidin anthocyanadin derivatives.
45. The method of claim 33, wherein the pH sensitive dye
composition is sensitive at least within a pH range of pH 4.0 to pH
12.0, inclusive.
46. The method of claim 33, wherein the method further comprises
disposing at least one therapeutic agent selected from the group
consisting of antimicrobial agents, antiseptic agents,
anti-inflammatory agents, pain relieving agents, wound closing
adhesive agents, and antihistamine agents on the wound
dressing.
47. The method of claim 33, wherein the pH sensitive dye
composition comprises a mordant.
48. The method of claim 47, wherein the mordant is selected from
the group consisting of aluminum potassium sulfate, copper sulfate,
iron (III) oxide, copper sulfate, citric acid, iron (III) sulfate
(Fe.sub.2(SO.sub.4).sub.3) and sodium sulfate.
49. The method of claim 47, wherein the mordant is aluminum
potassium sulfate.
Description
CLAIM OF PRIORITY
[0001] This application is a divisional application of U.S. patent
application Ser. No. 15/830,188, filed on Dec. 4, 2017, which is a
divisional application of U.S. patent application Ser. No.
14/514,579, filed on Oct. 15, 2014, now U.S. Pat. No. 9,855,364,
the entire contents of which are hereby incorporated by
reference.
TECHNICAL FIELD
[0002] The invention generally relates to wound dressings and their
methods of use. More particularly, the invention relates to wound
dressings dyed with a pH sensitive dye composition comprising at
least one anthocyanin obtained from (e.g., derived from) a fruit or
vegetable extract, and methods of using the wound dressings for
monitoring wound health.
BACKGROUND
[0003] The pH of a wound often signifies important information
about wound health. Measuring the pH of a wound can provide
information about the stage of healing and the presence of
infection. The pH of wound leakage has been shown to change as the
wound heals and if the wound becomes infected. The natural pH of
skin is slightly acidic, ranging from 4.8 to 6.0, an adaptation
which wards off bacteria on the surface, but the interstitial fluid
in the body has a pH closer to neutral (Romanelli, M, et al.,
2002). In healing wounds, pH starts slightly basic, moves to
neutral, and then approaches the pH of normal skin (Gethin, G
2007). Healthy wounds usually follow this trend, and it can be
problematic if a wound does not. If healing is not progressing, the
pH will stay basic. Wounds that remain basic usually heal more
slowly because the tissue does not have enough access to oxygen.
Small pH changes within a wound can cause large changes in oxygen
availability (Leveen, H. et al., 1973). The more oxygen available
in a wound, the faster a wound will heal. This makes pH
fluctuations critical to wound health and the healing process.
[0004] Infection inhibits wound healing by raising wound pH. Many
bacteria produce ammonia, which has a pH of 11.6 in a 1.0 M aqueous
solution. Ammonia production raises the pH of a wound and lowers
the oxygen availability. With a decreased oxygen supply, a wound
will take much longer to heal (Leveen, H. et al., 1973). The
bacteria present in an infection negatively affect the wound and
its oxygen content. Bacteria and other factors can result in long
periods of time in which the wound environment is at a basic pH.
Because this can slow healing, measures are often taken to lower
wound pH. Thus, measuring the pH of a wound can provide information
about the stage of healing and the presence of infection.
[0005] Thus, there is a need for improved bandages capable of
detecting pH to provide noninvasive, immediate information about a
wound to help individualize treatment.
SUMMARY
[0006] At least in part, the present invention relates to a wound
dressing, such as gauze, bandages, and surgical tapes, impregnated
with a pH sensitive dye composition comprising an anthocyanin
dye.
[0007] In some aspects, this disclosure provides a wound dressing.
In some embodiments, the wound dressing comprising a substrate
material and a pH sensitive dye composition disposed within the
substrate material and comprising at least one fruit or vegetable
derived anthocyanin.
[0008] As used herein, the terms "dressing" and "wound dressing"
are used interchangeably and refer to a material applied to a wound
to promote healing and/or prevent further harm.
[0009] As used herein, the term "wound" refers to an injury to
living tissue caused by a cut, blow, laceration, surgical incision
or other impact, typically one in which the skin is cut or broken.
Types of injures include, for example, cuts, scrapes, scratches,
burns, blisters, insect bites, and surgical sites, to name a
few.
[0010] In other aspects, this disclosure provides methods for
manufacturing a wound dressing, comprising: providing a substrate
material; and disposing pH sensitive dye composition comprising at
least one fruit or vegetable derived anthocyanin within the
substrate material.
[0011] Thus, the invention provides wound dressing and methods of
use thereof, which utilize a pH sensitive dye composition
comprising at least one fruit or vegetable derived anthocyanin. For
example, a pH sensitive dye composition comprising at least one
anthocyanin is derived from a fruit or vegetable selected from the
group consisting of a red cabbage, purple cabbage, purple carrots,
elderberry, hibiscus, purple potato, red currant, black currants,
blueberries, cherries, purple grapes, red raspberries and black
raspberries. In another exemplary embodiment, wound dressing and
methods of use thereof that use a pH sensitive dye composition
utilize a pH sensitive dye composition comprising at least one
anthocyanin is derived from red cabbage. In another exemplary
embodiment, wound dressing and methods of use thereof that use a pH
sensitive dye composition utilize a pH sensitive dye composition
comprising at least one anthocyanin is derived from a raspberry
(Rubus sp.). In some embodiments, at least one anthocyanin is
selected from the group consisting of cyaniding-3-sophoraside,
cyanide-3-glucoside or pelargonidin-3-sophoroside.
[0012] Additionally, the "Anthocyanins" as used herein include
anthocyanadin derivatives selected from the group consisting of
cyandin, delphinidin, peonidin, petunidin, pelargonidin and
malvidin anthocyanadin derivatives.
[0013] In some embodiments, the pH sensitive dye composition is
sensitive at least within a pH range of pH 4.0 to pH 12.0,
inclusive.
[0014] In some embodiments, the pH sensitive dye composition
comprises a mordant, which are well known to the skilled artisan.
For example, the pH sensitive dye composition may comprise a
mordant selected from the group consisting of aluminum potassium
sulfate, copper sulfate, iron (III) oxide, copper sulfate, citric
acid, iron (III) sulfate (Fe.sub.2(SO.sub.4).sub.3) and sodium
sulfate. In an exemplary embodiment, the mordant is aluminum
potassium sulfate.
[0015] The wound dressing may be any dressing suitable for
application to the surface of a wound, including, for example an
open wound. In some embodiments, the wound dressing is selected
from the group consisting of a pad, wrap, bandage, tape,
cotton-tipped stick and adhesive strip bandage.
[0016] In some embodiments, the substrate material comprises an
absorbent or water-permeable material. The absorbent or
water-permeable material is capable of absorbing wound exudate.
Suitable absorbent materials will preferably absorb at least about
10% by weight, at least about 20% by weight, at least about 30% by
weight, at least about 50% by weight, at least about 75% by weight,
or at least about 100% by weight of fluid or exudate. The dressing
can be composed of a substrate material comprising woven materials,
non-woven materials or both. In some embodiments, the dressing
comprises a fabric, cloth or sponge material. The dressing may be
composed of natural and synthetic materials. In an exemplary
embodiment, the substrate material comprises cotton material
including, cotton fabric or cotton gauze.
[0017] In some embodiments, the wound dressing further comprises at
least one therapeutic agent selected from the group consisting of
antimicrobial agents, antiseptic agents, anti-inflammatory agents,
pain relieving agents, wound closing adhesive agents, and
antihistamine agents.
[0018] The pH sensitive dye composition provides a clear and
obvious indication of wound health. For example, the pH sensitive
dye composition can provide an indication as to whether an
antimicrobial therapy is effective for treating or preventing wound
infection.
[0019] In some aspects, this disclosure provides methods for
determining the status of a wound, the methods comprising applying
a wound dressing on a wound surface, wherein the wound dressing
comprises a substrate material, and a pH sensitive dye composition
disposed within the substrate material and comprising at least one
fruit or vegetable derived anthocyanin; and determining the status
of the wound by assessing the color change of the pH sensitive dye
composition after application of the dressing onto the wound
surface.
[0020] In some other aspects, this disclosure provides methods
treating a wound comprising: applying a wound dressing to the
surface of the wound, wherein the wound dressing comprises a
substrate material; and a pH sensitive dye composition disposed
within the substrate material and comprising at least one fruit or
vegetable derived anthocyanin; assessing the color of the wound
dressing after application of the dressing onto the wound surface;
and selecting a treatment plan based on the status of the wound
based on the color of the wound dressing application to the wound
surface.
[0021] In some embodiments, assessing the color change of the pH
sensitive dye composition comprises monitoring the color change of
the dressing over time. Assessing the color change of the pH
sensitive dye composition may comprise monitoring the color change
of the dressing for a period between 1 to 24 hours, a period of
between 2 to 16 hours, a period of between 3 to 12 hours, a period
of between 4 to 10 hours, or a period of between 6 to 8 hours after
application of the dressing onto the wound surface. Assessing the
color change of the pH sensitive dye composition may comprise
monitoring the color change of the wound dressing at predetermined
time intervals, such as, for example, one hour, two hour, four
hour, six hour, eight hour, twelve hour or twenty-four hour time
intervals following application of the dressing onto the wound
surface.
[0022] The color change of the pH sensitive dye composition may be
accomplished using the human eye or with the assistance of a
visualization aide. For instance, assessing the color change of the
pH sensitive dye composition can be performed by visual inspection
or by using a color-sensing device. In some embodiments, the
color-sensing device is selected from the group consisting of a
colorimeter and a spectrometer.
[0023] Assessing the color change of the pH sensitive dye
composition can be performed using an imaging device. In some
embodiments, the imaging device is selected from the group
consisting of a colorimeter, spectrometer, a digital camera, a
mobile phone, a smartphone, a tablet, a portable computer, a
computer, and a scanner.
[0024] In some embodiments, the methods provided herein further
comprising removing or replacing the wound dressing when the color
of the wound dressing indicates a basic pH.
[0025] In some aspects, the methods for treating a wound provided
herein comprise selecting a treatment plan based on the status of
the wound. The treatment plan can comprise removing or replacing
the wound dressing when the color or the wound dressing indicates a
basic pH. In some embodiments, the treatment plan comprises
selectively administering one or more therapeutic agents and at
least one therapeutic agent selected from the group consisting of
antimicrobial agents, antiseptic agents, anti-inflammatory agents,
pain relieving agents, wound closing adhesive agents, and
antihistamine agents to the wound.
[0026] As used herein, the term "one or more" includes at least
one, more suitably, one, two, three, four, five, ten, twenty,
fifty, one-hundred, five-hundred, etc., of the item to which "one
or more" refers. The term "at least one" as used in the present
invention stands for one, two, three, four, five, ten, twenty,
fifty, one-hundred, five-hundred, etc., or more of the item "at
least one" refers to.
[0027] Unless otherwise defined, all technical and scientific terms
used herein have the same meaning as commonly understood by one of
ordinary skill in the art to which this invention belongs. Methods
and materials are described herein for use in the present
invention; other, suitable methods and materials known in the art
can also be used. The materials, methods, and examples are
illustrative only and not intended to be limiting. All
publications, patent applications, patents, sequences, database
entries, and other references mentioned herein are incorporated by
reference in their entirety. In case of conflict, the present
specification, including definitions, will control.
[0028] Other features and advantages of the invention will be
apparent from the following detailed description and figures, and
from the claims.
DESCRIPTION OF DRAWINGS
[0029] The patent or application file contains at least one drawing
executed in color. Copies of this patent or patent application
publication with color drawing(s) will be provided by the Office
upon request and payment of the necessary fee.
[0030] FIG. 1 is a photograph demonstrating the gradient of colors
for raspberry puree at pH 4.0, pH 5.0, pH 6.0, pH 7.0, pH 8.0, and
pH 9.0 (top row, left to right: pH 4.0, pH 5.0, pH 6.0; bottom row,
left to right: pH 7.0, pH 8.0, pH 9.0).
[0031] FIG. 2 is a photograph showing the bright red color of
sample gauze and other medical bandages dyed with raspberry juice
in an aluminum potassium sulfate solution without magnesium.
[0032] FIG. 3 are photographs demonstrating the color of dyed
fabric before (left hand images) and after (right hand images) pH
exposure (pH 5.0 (top row), pH 6.0 (middle row) and pH 7.0 (bottom
row)).
[0033] FIG. 4 is a graph demonstrating blue RGB values plotted
against red RGB values before and after soaking. Each line
represents a pH, connecting the initial Red-Blue point, noted in
black, to the final Red-Blue point.
[0034] FIG. 5 is a graph demonstrating blue RGB values plotted
against red RGB values before and after pH soaking. Each line
represents a pH, connecting the initial Red-Blue point, noted in
black, to the final Red-Blue point.
[0035] FIG. 6 is a graph demonstrating blue RGB values plotted
against red RGB values before and after bacterial exposure. Each
line represents a pH, connecting the initial Red-Blue point to the
final Red-Blue point, noted in black.
DETAILED DESCRIPTION
[0036] The present invention is based, in part, on the discovery
that wound dressing materials impregnated with a pH-sensitive dye
composition comprising at least one anthocyanin derived from a
fruit or vegetable source, including for example an anthocyanin
derived from raspberries (Rubus sp.), can be used on patients with
long-term or chronic wounds to detect wound health and infection.
Thus, in one aspect, the disclosure provides wound dressings
designed for application to a wound, the wound dressing comprising
a substrate material, and a pH sensitive dye composition disposed
within the substrate material and comprising at least one
anthocyanin dye derived from a fruit or vegetable. Advantageously,
the wound dressings described herein absorb wound exudate and
provide an indication of wound pH, and thus indication of wound
health. The dressings provided herein provide noninvasive,
immediate information about a wound to help individualize
treatment.
[0037] In one aspect, the disclosure further provides methods for
determining the pH of a wound, comprising contacting the wound with
a dressing containing at least one anthocyanin dye derived from a
fruit or vegetable; and monitoring the color change of the dressing
material to determine the pH of the wound.
[0038] Wound dressings are often integral to wound healing. Wound
dressings are prepared in many forms and for many different uses.
Generally, a dressing is designed to be in direct contact with the
wound and may be used in the form of a wrap or bandage. Aside from
the major function of reducing the risk of infection, wound
dressings are also important for providing a protective barrier
from outside sources of irritation and provide mechanical support
to the fragile wound surface. Wound dressings also function to
absorb wound byproducts (e.g. excess blood, plasma, or other
fluids) that tend to accumulate and complicate healing. Would
dressings serve to form an occlusive barrier to provide an optimal
environment for certain wound types, and act as an agent for wound
debridement, which acts to clean and prepare a wound bed for
healing.
[0039] The pH of a wound may be assessed using a wound dressing as
disclosed herein, which changes color in dependence upon pH. Such
wound pH information may be used to facilitate selection of the
appropriate treatment to which the wound should be subjected. The
wound dressing can be sterilized in an autoclave and loaded with
antibacterial/antiseptic agents to provide a wound dressing which
will indicate the pH of wound exudates in a non-invasive and simple
manner.
[0040] In practice, a wound dressing as disclosed herein would be
applied to a wound site of a subject with a surface of the wound
dressing in contact with a surface of the wound. The wound dressing
then would be monitored over a predetermined time period to assess
the extent of the exudate present in the dressing.
Anthocyanins
[0041] In chemistry, chromism is a process that induces a
reversible change in the colors of compounds. In most cases,
chromism is based on a change in the electron states of molecules,
so this phenomenon is induced by various external stimuli which can
alter the electron density of substances. It is known that there
are many natural compounds that have chromism, and many artificial
compounds with specific chromism have been synthesized to date.
Chromism is classified by what kinds of stimuli are used.
[0042] Color change can occur by changes in electromagnetic
radiation, reflection, absorption or scattering. Thus, for example,
photochromism signifies color change triggered by electromagnetic
radiation; thermochromism signifies color change triggered by
changes in temperature; electrochromism signifies changes in color
occurring due to gain or loss of electrons; solvatochromism
signifies color change resulting from changes in solvent polarity;
ionochromism signifies color change caused by ions; tribochromism
caused by changes in mechanical friction; piezochromism signifies
changes caused by mechanical pressure; and halochromism signifies
color change caused by a change in pH. Although fundamentally the
halochromism is pH-dependent, the temperature-dependence of the
acid-base equilibrium means that pH sensitivity can result in
thermochromic behavior.
[0043] Anthocyanins are a class of halochromatic substances which
respond to the level of acidity in an environment with a color
change (Van der Schueren, L. & De Clerck, K., 2012).
Anthocyanins pigments are responsible for the red, purple, and blue
colors of many fruits and vegetables, including red and purple
cabbage, beets, purple carrots, elderberry, hibiscus, purple
potato, red and black currants, blueberries, cherries, purple
grapes, and red and black raspberries. Within the plant they serve
as key antioxidants and pigments contributing to the coloration of
flowers. Anthocyanin pigment has a color gradient from orange to
blue in the visible light spectrum, following the range of possible
pH values. In the ultraviolet spectrum, the colors range from
browns and yellows to purples and blues.
[0044] The color the anthocyanin molecule displays can change in
relation to its environment; it is behind the color transition of
green to red leaves from summer to autumn. These pigments are
formed inside the plant through a metabolic pathway utilizing
phenylalanine. Inside a plant cell, anthocyanins are dissolved in
the water of the central vacuole where they can reflect outside
light and give the plant cell its color. Bright pigments such as
anthocyanins are evolutionarily beneficial to plants because they
attract potential pollinators and may play a role in protecting
photosynthetic pigments from light induced stress (Glover &
Martin, 2012).
[0045] The color an anthocyanin molecule reflects is dependent on
hydroxylation of two carbon rings in its molecular structure. For
this reason, the pigment changes color in relation to the pH of its
environment. When dissolved in an acidic solution containing a
lower concentration of hydroxide ions, the pigments display colors
ranging from orange to red. These colors are present in nature in a
variety of plants, including raspberries and most other red fruits
and vegetables. At a neutral pH, anthocyanins can appear violet or
colorless, but as the pH increases, the color transitions to blue.
Thus, the color or anthocyanin pigments has a direct relationship
with the environment and follows a scale transitioning from red to
blue as pH increases.
[0046] Anthocyanidins are the basic structures of anthocyanins,
with formula (I) where R.sub.1 to R.sub.7 are, independently, H, OH
or OMe.
##STR00001##
[0047] When anthocyanidins are found in their glycoside form
(bonded to a sugar moiety) they are known as anthocyanins. There
are reports of more than 500 different anthocyanins in nature. The
main differences between them are the number of hydroxylated or
methoxylated groups, the nature and number of sugars bonded to
their structure, the aliphatic or aromatic carboxylates bonded to
the sugar in the molecule and the position of these bonds. The
substitution pattern of the six most common anthocyanidins and
their abbreviations are shown in Table 1. The numbering of the
substituents R.sub.n is as drawn in the formula (I) above.
TABLE-US-00001 TABLE 1 Common anthocyanidins Name (Abbreviation)
R.sub.1 R.sub.2 R.sub.3 R.sub.4 R.sub.5 R6 R.sub.7 Cyanidin (CN) OH
OH H OH OH OH H Delphinidin (Pp) OH OH H OH OH OH OH Pelagonidin
(Pg) OH OH H OH H OH H Peonidin (Pn) OH OH H OH OMe OH H Petunidin
(Pt) OH OH H OH OMe OH OH Malvidin (Mv) OH OH H OH OmE OH OME
[0048] In order of relative abundance, the sugars found bound to
anthocyanidins to form anthocyanins are glucose, rhamnose,
galactose, xylose, arabinose and glucuronic acid. The term
"anthocyanin" as used herein is intended to include both
glycosylated anthocyanins and acylated anthocyanins. The main
glycoside derivatives in nature are 3-monosides, 3-biosides,
3,5-diglucosides and 3,7-diglucosides. Acylated anthocyanins
derivatives include one or more molecules of the acyl acids;
p-coumaric, ferulic and caffeic; or the aliphatic acids; malonic
and acetic; and may be esterified to the sugar molecule. Overall,
the most widespread anthocyanin is cyanidin-3-O-glucoside. The
anthocyanins of the present invention may have the formula (I)
wherein R.sub.1, R.sub.2 and R.sub.4 are each independently H, OH,
OMe, a sugar residue, or an acylated sugar residue; and R.sub.3,
R.sub.5, R.sub.6 and R.sub.7 are each independently H, OH or OMe.
The anthocyanins may be synthetic and/or natural anthocyanins.
[0049] In some embodiments, the at least one type of fruit or
vegetable derived anthocyanin is obtained from a fruit or vegetable
extract. By "obtained" or "obtaining" is meant purifying,
extracting, synthesizing, purchasing, or otherwise acquiring an
anthocyanin dye composition naturally found in raspberries.
[0050] An "extract" as used herein is a preparation made from any
part or parts of a fruit or vegetable that comprises, generally in
concentrated form, one or more anthocyanin compounds. The term
"extract" is intended to include anthocyanin materials obtained
from plant sources, such as leaves, roots, seeds, flowers, berries,
fruit, for example, by routine isolation methods suitable from
suitable plant sources. There are various methods for the
extraction of anthocyanins known to those of skill in the art. The
extract may be obtained from a fruit or vegetable selected from the
group consisting of a red and purple cabbage, purple carrots,
elderberry, hibiscus, purple potato, red and black currants,
blueberries, cherries, purple grapes, and red and black
raspberries.
[0051] The extract is typically concentrated by various methods to
provide a solution enriched in anthocyanins. For example,
ultrafiltration can be used to remove unwanted components by
molecular weight cut offs. The retentate from the filtration can be
stored as a liquid or, for example, can then be further
concentrated into a powder by spray drying, freeze drying, flash
drying, fluidized bed drying, ring drying, tray drying, vacuum
drying, radio frequency drying or microwave drying. Ultimately, the
extract should contain at least 10% by weight anthocyanin content.
The extracts, therefore, contain anthocyanin(s) and may also
contain other plant materials such as other flavinoids, sugars,
etc.
[0052] In one embodiment, the disclosure provides a pH sensitive
dye comprising at least one type of raspberry (Rupus sp.)
anthocyanin (e.g., an anthocyanin extracted from a raspberry (Rupus
sp.)). Raspberries belong to the genus Rubus. Cultivated
raspberries have been derived mainly from two species, the wild red
raspberry (Rubus ideaus) and black raspberry (Rubus occidentalis).
Purple type is a cross between the black and red raspberry, and
yellow type is a mutant red raspberry. There are over 200 species
of raspberries. Raspberries can be grown from the Arctic to the
equator. Anthocyanins obtained from raspberries (Rubus sp.)
include, for example, an anthocyanin selected from the group
consisting of cyanidin-3-sophoraside, cyanide-3-glucoside or
pelargonidin-3-sophoroside.
[0053] In some embodiments, the anthocyanin is sensitive at least
within a pH range of pH 6.0 to pH 8.0, a pH range of pH 5.0 to pH
9.0, a pH range of pH 4.0 to pH 10.0, a pH range of pH 2.0 to pH
13.0, or a pH range of pH 1.0 to pH 14.0. In one embodiment, the pH
sensitive dye composition is sensitive at least within a pH range
of pH 5.0 to pH 10.0.
[0054] In some aspects, the disclosure provides a pH sensitive dye
composition comprising at least one type of anthocyanin derived
from a fruit or vegetable. For example, the anthocyanin can be
derived from red and purple cabbage, purple carrots, red and black
currants, blackberries, blueberries, cherries, purple grapes, or
red and black raspberries. In some embodiments, at least one type
of anthocyanin is an anthocyanadin derivative selected from the
group consisting of cyandin, delphinidin, peonidin, petunidin,
pelargonidin and malvidin anthocyanadin derivatives. In some
embodiments, the at least one type of anthocyanin is obtained from
a raspberry (Rubus sp.) extract. In yet another embodiment, the at
least one type of anthocyanin is obtained from a red cabbage
extract.
[0055] The color change anthocyanin undergoes is not permanent, but
will continue to respond to different stimuli as the environment
changes. Thus, anthocyanins have reversible properties that make
them reusable. This property makes anthocyanin useful as a pH
indicator of solutions and substances, including washable and
reusable dressings.
[0056] The pH sensitive dye composition changes color in response
to changes in pH and provides an indicator of wound health. In some
embodiments the pH sensitive dye composition is sensitive at least
within a pH range of pH 6.0 to pH 8.0, a pH range of pH 5.0 to pH
9.0, a pH range of pH 4.0 to pH 10.0, a pH range of pH 4.0 to pH
12.0, a pH range of pH 2.0 to pH 13.0, or a pH range of pH 1.0 to
pH 14.0. In one embodiment, the pH sensitive dye composition is
sensitive at least within a pH range of pH 5.0 to pH 10.0.
Dressing/Substrate Materials
[0057] The pH sensitive dye composition of the present invention
may be used to color a variety of substrate materials. According to
an aspect of the present invention, the pH sensitive dye
composition is disposed within the substrate material of a wound
dressing. More particularly, the pH sensitive dye composition is
disposed within (e.g., impregnated within) said substrate material
and trapped with the matrix of the substrate material. In some
embodiments, the pH sensitive dye is dispersed homogenously (i.e.,
uniformly dispersed) throughout the dressing.
[0058] Conventional dressings include, for example, absorbent pads,
absorbent cotton, gauze (e.g., gauze bandages and/or gauze pads),
wrap (e.g., elastic wraps and/or gauze wraps), dermal patches,
surgical drapes, bandage, tapes, cotton-tipped stick, adhesive
bandages, or other support wrap or medical bandage or wound cover.
The term "dressing" as used herein is also intended to cover casts
(e.g., orthopedic cast, body cast, plaster cast, or surgical cast),
frequently made from plaster, encasing a limb (or, in some cases,
large portions of the body) to stabilize and hold anatomical
structures, most often a broken bone (or bones), in place until
healing is confirmed. In some embodiments, the dressing is a
sterile dressing. The dressing may be disposable, washable and/or
reusable.
[0059] In some embodiments, the dressing is an adhesive bandage. An
adhesive bandage is usually covered by a woven fabric, plastic, or
latex strip which has an adhesive. Adhesive bandages usually have
an absorbent pad, which is sometimes medicated with an antiseptic
solution. Some bandages have a thin, porous-polymer coating over
the pad to keep it from sticking to the wound. The bandage is
applied such that the pad covers the wound, and the fabric or
plastic sticks to the surrounding skin to hold the dressing in
place and prevent dirt from entering the wound. Adhesive bandages
may include, but are not limited to, strip bandages, winged
bandages, fingertip bandages, butterfly bandages, knuckle bandages,
triangular bandages, tube bandages, compression bandages, elastic
bandages, gauze bandages, donut bandages, pressure bandages,
sterile-strips, eye bandages, sterile burn sheets, and adhesive
tape.
[0060] In some embodiments, the substrate material comprises an
absorbent or water-permeable material. The absorbent or
water-permeable material is capable of absorbing wound exudate. The
dressing can be composed of a substrate material comprising woven
materials, non-woven materials or both. In some embodiments, the
dressing comprises a fabric, cloth or sponge material. The dressing
may be composed of natural and synthetic materials (e.g., natural
or synthetic fibers). For example, the substrate material may be
composed of natural or synthetic fibers selected from the group
consisting of rayon, polyester, polyurethane, polyolefin,
cellulose, cellulose derivatives, cotton, orlon, nylon, hydrogel
polymeric material, and combinations thereof.
[0061] In use, the substrate material can be an elastic substrate.
Materials suitable for use as an elastic substrate in the present
invention include materials which are elastic, conformable, porous,
provide adequate compression and which are self-adhering. In
general, the material is sufficiently porous if the material allows
for the transmission of air and moisture vapor through the
material.
Mordants
[0062] In some aspects, the pH sensitive dye compositions disclosed
herein further comprise a "mordant" or "mordanting agent." As used
herein, the term "mordant" and "mordanting agent" are used
interchangeably and refer to a substance capable of fixing and/or
setting dyes on fabrics or tissue sections by forming a
coordination complex with the dye, which then attaches to the
fabric or tissue. A mordant may comprise metallic cations such as
Al.sup.3+ or Fe.sup.3+ ions. In some embodiments, the mordant
includes tannic acid, alum, chrome alum, sodium chloride, and
certain salts of aluminum, chromium, copper, iron, iodine,
potassium, sodium, and tin. Exemplary mordants for use in the dye
compositions disclosed herein include, for example aluminum
potassium sulfate, copper sulfate, iron (III) oxide, copper
sulfate, citric acid, iron (III) sulfate (Fe.sub.2(SO.sub.4).sub.3)
and sodium sulfate.
Therapeutic Agents
[0063] In some aspects, the wound dressings disclosed herein
further comprise at least one therapeutic agent. For example, in
addition to the pH sensitive dye compositions, the wound dressings
of the present invention may further comprise at least one
therapeutic agent disposed within the substrate material. Examples
of therapeutic agents include, but are not limited to, antibiotic
agents (e.g., antimicrobial agents and/or antiseptic agents),
anti-inflammatory agents, pain-relieving agents, wound closing
adhesive agents, or antihistamine agents.
[0064] In one embodiment, the wound dressings of the present
invention advantageously comprise at least one antibiotic agent.
For example, the wound dressings of the present invention may
further comprise at least one antibiotic agent disposed within the
substrate material. The antibiotic agent can be composed of any
antibacterial compound that effectively prevents the growth of
bacteria (e.g., bacteriostatic) or yeast (e.g. anti-yeast) and/or
kills bacteria (e.g., bactericidal) or yeast once they are formed.
The antimicrobial or antiseptic agents should preferably be safe,
non-irritating, and hypoallergenic such that it does not cause any
adverse reactions to the skin of the patient. Antibiotic agents
that are suitable for use in the wound dressings include, for
example, amikacin, amikacin sulfate, bacitracin, bacitracin zinc,
chlortetracycline hydrochloride, dihydrostreptomycin sulfate,
crystalline dihydrostreptomycin sulfate, dihydrostreptomycin
hydrochloride, gentamicin sulfate, sterile gentamicin sulfate,
kanamycin sulfate, sterile kanamycin sulfate, neomycin sulfate,
sterile neomycin sulfate, netilmicin sulfate, oxytetracycline,
paromomycin sulfate, polymyxin B, polymyxin B sulfate, sisomicin
sulfate, sterile streptomycin sulfate, tetracycline hydrochloride,
tobramycin and sterile tobramycin sulfate.
[0065] Methods for Assessing Wound Health
[0066] The treatment of body tissues, for example wounds to human
or animal bodies can be problematic due to difficulties in
assessing characteristics of the wound, for example the pH of
exudates. To facilitate detailed assessment of a wound, correct
diagnosis and hence selection of an appropriate treatment is
needed.
[0067] In some aspects, the disclosure provides methods for
determining the status of a wound by assessing the pH of a wound
and/or wound exudate. Such wound pH information may be used to
facilitate selection of the appropriate treatment to which the
wound should be subjected.
[0068] In some embodiments, the methods for determining the status
of a wound disclosed herein comprise applying a dressing on a wound
surface, wherein the dressing comprises a substrate material, and a
pH sensitive dye composition disposed within the substrate material
comprising at least one type of fruit or vegetable derived
anthocyanin; and determining the status of the wound by assessing
the color change of the pH sensitive dye after application of the
dressing onto the wound surface. The color change of the pH
sensitive dye provides information about the pH of the wound, and
thus provides information as to the status (e.g., health) of the
wound.
[0069] In one embodiment, the pH of the wound is assessed on the
basis of a change in the visual appearance of said substrate
material. More specifically, the pH of the wound is assessed on the
basis of the color of said substrate material. Assessing the color
change of the pH sensitive dye composition comprises monitoring the
color change of the dressing over time. Appropriate timing for
monitoring the color change of the wound dressing may be determined
by a healthcare professional or caregiver attending to the subject.
For example, assessing the color change of the color of the pH
sensitive dye composition may be performed by monitoring the color
change of the dressing for a period between 1 to 24 hours, a period
of between 2 to 16 hours, a period of between 3 to 12 hours, a
period of between 4 to 10 hours, or a period of between 6 to 8
hours after application of the dressing onto the wound surface. In
some embodiments, assessing the color change of the pH sensitive
dye composition comprises monitoring the color change of the
dressing at predetermined time intervals after application of the
dressing onto the wound surface, i.e., at fifteen minute, thirty
minute, one hour, two hour, four hour, six hour, eight hour, twelve
hour or twenty hour time intervals after application of the
dressing onto the wound surface.
[0070] The color change of the pH sensitive dye can be monitored by
visual inspection (e.g., visual inspection by the human eye) or
with the aid of a color-sensing device. Color sensing devices
include, for example, a colorimeter or spectrophotometer.
Colorimeters and spectrophotometers are well-known in the art and
are used to measure certain optical properties of various
materials. In addition to colorimeters and spectrometers, the color
change of the pH sensitive dye can be monitored using an imaging
device, such a digital camera, a mobile phone, a smartphone, a
tablet, a portable computer, a computer, and a scanner.
[0071] Information on wound health aids healthcare professionals
(e.g., a physician, physician assistant, pharmacist, nurse
practitioner, nurse or case manager) and caregivers in determining
the best treatment plan for a subject. In some embodiments, the
method comprises assessing the color change of the pH sensitive dye
after application of the dressing onto the wound surface; and,
subsequently, carrying out another step in dependence upon the pH
assessed. For example, the additional step can be advising a
healthcare professional or caregiver to provide or select a
treatment regimen for said wound, or advising a caregiver to
remove/change/replace the wound dressing from the wound surface
when the color of the wound dressing indicates a basic pH.
[0072] The pH sensitive composition may serve as an indicator of
bacterial growth in the wound through the change in color thereof
(the pH will stay basic). Following evidence of bacterial growth in
the wound, the wound can be cleaned, disinfected, and dressed with
a sterile dressing immediately after a wearer is aware of it.
[0073] The method may involve comparing the visual appearance, for
example color, of the dressing with a reference means, for example
a color reference means such as a color chart (or the like) to
assess the pH of the dressing or environment.
[0074] The dressing material may be arranged to enable pH
information to be obtained directly from it without recourse to any
external reference means. For example, said test material may
incorporate a said reference means suitably arranged to enable pH
information to be obtained directly from the test material.
[0075] In some embodiments, the methods disclosed herein can
include the step of recording information relating to the visual
appearance (e.g., the color) of the substrate material. The color
of the dressing may be recorded and/or the pH may be recorded. In
yet another embodiment, the methods further comprise modifying the
subject's clinical record to include information relating to the
visual appearance (e.g., the color) of the wound dressing and the
status of the wound. The clinical record may be stored in any
suitable data storage medium (e.g., a computer readable
medium).
EXAMPLES
[0076] The invention is further described in the following
examples, which do not limit the scope of the invention described
in the claims.
[0077] Experiments were conducted to evaluate the potential of
anthocyanin in raspberries as a pH-sensitive dye. Raspberry juice
(Rubus sp.) was mixed with an aluminum potassium sulfate mordant
and processed, resulting in a dye that can be used to color cotton
textiles. Cotton gauze bandages were dyed with this solution and
wrapped around decomposing chicken, which had been treated with a
range of pH values to simulate wound conditions. Changes in gauze
color were observed by comparing RGB values before and after the
bandages were exposed to the chicken. All bandages were sterilized
in either an ethylene oxide machine or an autoclave before
experimentation. The fabric was also detected Staphylococcus aureus
in culture and could respond to pH changes more than once. The dye
indicated pH and could safely be used on patients with long-term or
chronic wounds to detect infection.
Description of Methods and Procedures:
[0078] A dye was made from raspberry juice and aluminum potassium
sulfate. Cotton bandages were dyed and exposed to different pH
levels as well as bacterial growth. Photographs were taken before
and after the bandages were placed in different environments. The
environments tested were pH values 5-9. Also, one group was exposed
to bacterial growth on decomposing chicken. Red, green and blue
values were extracted from the images using Adobe Photoshop
Elements 11, and averaged to find before and after colors of each
piece of cotton. The resulting color values were used to analyze
the changes in color between each pH.
Testing for Halochromic Properties:
[0079] As an initial experiment, the inventor sought to test the
halochromic properties of raspberry juice. Organic raspberries were
pureed in a food processor until a thick, smooth mixture resulted.
Petri dishes were prepared containing solutions varying in pH from
3 to 11 using baking soda, acetic acid (5% aqueous solution), and
water. Each solution also contained a magnesium source which
influenced pH; milk of magnesia (Mg(OH).sub.2) (CVS Brand,
unflavored) was used in the basic solutions and magnesium citrate
(MgO.sub.7C.sub.6H.sub.6) (CVS Brand, lemon flavored) was used in
the acidic petri dishes. When 6.0 grams of raspberry juice were
added to the solutions they displayed a gradient of colors, shown
in FIG. 1. Acidic pH solutions turned the raspberry puree redder,
and a neutral environment changes the puree to a purplish color.
Basic environments resulted in a drastic transformation to a
blue-green color. The apparent color changes provided evidence that
the main pigment (anthocyanin) is halochromic, which enabled the
next test to be conducted.
Making a Raspberry Dye Preparation:
[0080] Raspberry juice does not fix naturally into cotton textiles,
so two mordants were tested for their usefulness in attaching the
juice to the fabric. Iron (III) oxide and aluminum potassium
sulfate were selected as mordants. Each mordant was added to a
solution consisting of equal parts water and raspberry puree and to
a solution containing raspberry puree, water, and magnesium
hydroxide (CVS Brand unflavored Milk of Magnesia).
Dyeing Fabric:
[0081] Pieces of fabric were placed in each of the four prepared
solutions, and the solutions were heated to 65.degree. C. The
aluminum mordant without the added magnesium worked best, producing
a bright red color like that of raspberry fruit. (FIG. 2) The iron
mordant without aluminum produced a duller, lighter red. Both
pieces of fabric that were exposed to magnesium in solution did not
dye evenly and resulted in spotted, uneven coloring. When exposed
to different pH values, only the fabric dyed in an aluminum
potassium sulfate solution without magnesium was capable of color
change. This dye was selected as the optimum for dyeing fabric in
future experiments.
Extracting Pigment:
[0082] In addition to dyeing fabric, attempts were made to extract
a pigment from the dye for use in printing. The dye was
concentrated by evaporating water and tested by writing with a
quill. The aluminum potassium sulfate solution was tested with
magnesium and without magnesium. The iron (III) oxide dye was not
used in this testing due to the previous success of the aluminum
potassium sulfate dye. The dyes were heated in test tubes in a
beaker of water on a hot plate, and allowed to settle afterward.
The solutions separated into different strata, but no solid pigment
was available for extraction.
[0083] Both solutions were then used as pen ink. The magnesium
containing solution did not adhere to paper and resulted in a light
lavender, barely visible stain. The dark red solution without
magnesium stained the paper where applied and turned a dark purple
upon contact with the paper. It is presumed that this was due to
the high pH of paper. The solutions were then tested against
commercial calligraphy ink by exposing them to water and observing
any running or fading. The calligraphy ink showed no change and the
produced dye showed minimal fading. A solid pigment could not be
extracted easily, and the dye was not concentrated enough to be
used as professional ink, so dyeing fabric was pursued further. In
addition, there are more potential uses for halochromic fabric than
halochromic ink.
Example 1
Skin Simulation Experiment
[0084] Varying pH was shown to affect the dye, so an experiment was
designed to test the color changes of the fabric in conditions
mimicking the environment produced by a skin wound. Unflavored
gelatin (Knox Brand) was set in petri dishes to replicate the
surface of human skin, and holes were poked into the gelatin with a
sewing needle to imitate pores that would leak bodily fluid. Each
sample was then brushed with a solution of a different pH, varying
from 5 to 9. The mixtures were allowed to briefly soak into each of
the artificial pores, but some solution still remained on the
surface of the gelatin. The pH solutions were produced with
household items: lemon and lime juice were used to acidify pH
values, water was used to neutralize pH values, and baking soda was
used to alkalize pH values. A piece of sterilized gauze (CVS Brand)
was then laid on the top of the gelatin in each petri dish. Four
gauze samples were tested in each pH: two samples that had been
previously soaked in acetic acid and two samples that had been
previously rinsed in water. Before the samples were tested, they
were sterilized in an ethylene oxide machine. The newly sterilized
bandage squares were left on petri dishes of varying pH values for
approximately 15 minutes to fully absorb the solution. After the
allotted time, each piece was placed onto a white sheet of paper
and photographed with a camera (Nikon D3100).
[0085] Color changes were observed and photographed, and numerical
color values were extracted using Adobe Photoshop Elements 11. Each
image was uploaded into the program and the brightness levels in
the image were regulated. The color of the white paper surrounding
the bandage in the photograph was set to be equal to absolute white
in the image. This leveling process adjusted all of the colors
accordingly, providing consistency between the colors in the images
when they were all edited in this way. Next, each bandage was
divided into squares and the Red-Green-Blue ("RGB") value of all of
the pixels in each square was averaged. The RGB values of these
squares were used for statistical testing.
Microbial Infection Simulation Experiment
[0086] Bacterial growth conditions were tested to determine if the
dyed fabric could be used to signal bacterial infection by changing
color when in contact with infected areas. First, 4 pieces of raw
chicken (Purdue chicken breasts) were basted with solutions with pH
5 through pH 9. Then, strips of medical gauze dyed with the
aluminum potassium sulfate dye were placed on pieces of chicken.
The samples were each sealed in individual bags (Ziploc sandwich
bags) and left in a residential garage for three days. The chicken
was purposefully left to decompose to see what color changes the
gauze would undergo in the presence of bacterial growth.
[0087] All 4 samples changed from their original color to the same
shade of light blue when they were exposed to the microbial
colonies. This color change began to occur during day 1 and day 2
of exposure to the chicken, as the bacteria began to grow. On the
morning of the 3rd day, each gauze sample was photographed. The
photographs were then uploaded to Adobe Photoshop Elements 11,
where the RGB values of each pixel of the fabric were averaged and
recorded. The resulting numbers were used in data analysis.
Staphylococcus Aureus Infection Simulation
[0088] The dyed fabric was exposed to S. aureus in petri dishes.
The cultures were obtained from a laboratory at Becker College and
remained in the laboratory and sealed for the duration of the
observation. Before exposure to the bacteria, the bandages were
dyed and rinsed in water to remove excess dye, resulting in a
purple color. They were also autoclaved to before being exposed to
the cultures to prevent outside contamination. The purple bandages
were laid on top of S. aureus in petri dishes and observed after a
two-day growth period. Photographs of the bandages were taken at
this time to access color change. The bacterial colonies were
autoclaved and discarded by a professional biohazard disposal
company.
Results
[0089] The data shows a clear relationship between pH and color. In
the first test, the dyed fabric was rinsed with water to remove all
extra dye. Specifically, two pieces of dyed, sterilized cotton
bandage were washed in water and soaked in each pH 5 to 9 on top of
gelatin to simulate skin conditions. Photos were taken before the
pH was changed and afterward, and RGB values were obtained from
these images and are recorded above. The photographs taken of the
fabric after this process all show similar RGB values, shown by the
low standard deviations (STDEV R=3.66, G=0.79, B=3.72) of each
color value. When each square of fabric was exposed to the neutral
pH of water, pH 7, the sections of bandage all displayed a similar
color, which was violet. This color can be observed in FIG. 3, and
in the RGB values in Table 1. FIG. 4 shows the blue RGB values
obtained were plotted against the red RGB values before and after
pH soaking. Each line represents a pH, connecting the initial
Red-Blue point, noted in black, to the final Red-Blue point. In
each fabric square, green is the lowest value and is not
predominantly seen in the images. The blue value is the highest,
followed by red, which combine to make the bluish purple seen in
the fabric.
TABLE-US-00002 TABLE 1 Before Before Before After After After pH R
G B R G B 5.0 167.0 151.5 197.5 186.0 136.5 172.0 6.0 173.0 152.0
200.5 179.0 147.0 214.5 7.0 172.0 152.5 200.0 160.0 165.5 210.0 8.0
167.5 151.0 194.0 125.5 127.0 150.5 9.0 175.5 153.0 204.0 138.5
138.5 156.0 STDEV 3.7 0.8 3.7 25.8 14.5 30.0
[0090] After this information was obtained, two bandage pieces were
exposed to each of the pH values ranging from 5-9, inclusive. The
photographs taken after this exposure show a much larger variance
in color. Each RGB value was correlated to the pH, and there were
large differences among them (STDEV R=25.81, G=14.50, B=29.99).
Although each piece of fabric began at relatively the same color,
different pH levels in each environment lead to varying colors. The
color the fabric produced at each pH was also consistent. As seen
by the similarities in the two sample groups (Appendix A), each pH
caused a reliable color change. Exposing different cotton bandages
dyed with the same dye to the same pH values used in this
experiment would result in very similar RGB values. To ensure the
results of this experiment were not by chance, an ANOVA test was
run on the percent differences of both the red and blue values. An
ANOVA was run on these values because they show that the Red-Blue
color change, in comparison with the original values, was different
in each environment. The test shows that this result is extremely
unlikely to be achieved by random chance and that the data was
statistically significant (p=8.45*10.sup.-27).
[0091] In the second experiment, the dyed fabric was rinsed with
acetic acid before being exposed to varying pH values.
Specifically, two pieces of dyed, sterilized cotton bandage were
rinsed in acetic acid and then soaked in each pH 5 to 9 on top of
gelatin to simulate skin conditions. Photos were taken before the
pH was changed and afterward, and RGB values were obtained from
these images and are recorded in the chart above. The acetic acid
rinse was done to simulate the application of acetic acid to a
wound, which is done to lower pH and promote healing. The starting
RGB values for each separate bandage square obtained from images
taken after the acetic acid rinse were very similar (STDEV R=3.65,
G=1.85, B=2.56), showing that each bandage began at approximately
the same color (Table 2, FIG. 5). This color was light pink, seen
in the overall high RGB values that add brightness and the
elevation of the Red value above the other two.
TABLE-US-00003 TABLE 2 Before Before Before After After After pH R
G B R G B 5.0 242.0 189.0 203.5 218.5 161.0 166.0 6.0 250.0 191.0
204.0 212.5 151.5 151.0 7.0 246.0 194.0 204.0 222.5 200.0 195.0 8.0
251.0 191.5 208.5 127.5 125.5 118.5 9.0 249.0 192.5 201.5 151.5
147.5 142.5 STDEV 3.7 1.9 2.6 43.9 27.3 28.4
[0092] Despite starting at a very low pH (2 to 3), the fabric
responded to environmental changes in pH and retained its
halochromic properties. Two separate fabric sections were exposed
to pH values 5 through 9 as in the previous test. The two samples
in each environment were similar colors after testing (data not
shown), showing the consistency of the color change. The colors
resulting from the environments were very different (STDEV R=43.88,
G=27.28, B=28.39)(Table 2). This shows that color changed
drastically in the presence of unique pH values. To test if this
result could be obtained by chance, an ANOVA was run on the
distance between the percent differences of each color, as was done
in the previous experiment. These numbers were chosen for the ANOVA
because they represent the total Red-Blue color change for each pH
compared with the original color. It can be said with confidence
that the results show a color change that could not be achieved
randomly and was statistically significant (p=4.62*10.sup.-44). The
bandages continued to respond to environmental pH changes even
after they had been rinsed in acetic acid.
[0093] The color change after the acetic acid rinse followed the
same gradient as the color change after the water rinse in the
first experiment. Bandages in basic environments of pH 8-9 had
lower RGB values overall resulting in a darker color and similar
red and blue values, which give a blue-purple shade. Cotton pieces
in neutral pH 7 had generally high RGB values, making them a
lighter purple than the bandages in basic environments. The gauze
in acidic environments of pH 5-6 displayed higher Red values
compared to almost all of the other trials, giving them a more
reddish hue than any of the other samples.
[0094] The dyed gauze also showed a response to pH changes due to
bacterial contamination. Cotton pieces were presoaked in each pH
ranging from 5 to 9 and exposed to decomposing chicken. Before
exposure to microbial populations, each square of fabric varied in
RGB value (STDEV R=44.22, G=17.88, B=15.73), because each was a
different color. After exposure to bacteria, the RGB values were
much more similar between initial pH groups (STDEV R=13.20,
G=10.49, B=11.28) (Table 3, FIG. 6). All of the Red, Green, and
Blue values of the five samples increased, showing a consistently
lighter color in the fabric when bacteria were present. Microbial
contamination usually causes wound pH to become more basic, and the
data collected also show this trend. The fabric squares in the
previous experiment that were exposed to basic pH values exhibited
a blue color, and the fabric in this experiment did the same. The
Blue values are consistently higher than the Red values, showing
that the basic environment produced by bacteria again resulted in a
blue hue.
TABLE-US-00004 TABLE 3 Before Before Before After After After pH R
G B R G B 5 188 141 155 216 241 238 6 192 158 169 209 220 225 7 111
122 156 233 243 249 8 108 116 130 198 247 253 9 109 119 137 222 239
248 STDEV 44.2 17.9 15.7 13.2 10.5 11.3
[0095] The fabric was also exposed to a specific type of bacteria,
Staphylococcus Aureus. The fabric was sterilized in an autoclave
before exposure to the bacteria to ensure no outside contamination
would occur. The fabric began at a purple color after being rinsed
in water, shown in Table 4.
TABLE-US-00005 TABLE 4 Before Colors After Color R G B R G B 196
175 221 172.33 183.67 189.67 197 194 219
Two shades of purple, which had high red and blue values, were used
as starting colors: one from light rinsing in water with some
excess dye still remaining and the other from a complete water
rinse removing all unfixed dye. Both beginning colors turned into
the same final color after the fabric was exposed to S. aureus.
Three bandage samples were exposed to different S. aureus colonies
in different petri dishes and the average RGB values were obtained
from photographs of each sample. These values are in Table 4. This
color change is significant because it shows that the fabric will
indicate the presence of S. aureus with a color change to a bluish
grey. The color change in the presence of this type of bacteria is
consistent regardless of starting color, as shown by the starting
color variations leading to the same final color. The fabric
responded as was predicted because bacteria often create high pH
environments, which would result in a bluish grey color similar to
the final color of previous experiments. The dyed cotton gauze
responded to changes in environmental pH in each test
performed.
[0096] The data gathered in this experiment supported the
hypothesis; the pH of an environment has an effect on the color of
gauze dyed with a solution derived from raspberry juice. The color
change follows a red to purple to blue gradient in accordance with
pH as it changes from acidic to neutral to basic. The results of
this project show that the raspberry dye made is halochromic and
reusable, meaning it can react to changing pH more than once. Also,
the dyed fabric can be easily sterilized using preexisting
machinery, and it is still responsive to pH changes afterward. This
includes environmental pH changes caused by bacteria, such as S.
aureus, and other sources.
[0097] The experiments completed in this study provide strong
evidence for the potential of halochromic gauze for use in the
medical industry. Patients with long-term wounds such as lower
extremity ulcers caused by diabetes could monitor their wounds at
home with more certainty if they knew the pH of their wounds and
the possible causes of pH changes. Color change was shown to be
easily detectable in the fabric, and a layperson could observe the
variations in color without outside assistance. This would provide
more information about the health, stage of healing, and presence
of infection in a wound to both the patient and the caretaker. The
dyed gauze could also be used for patients who are advised to keep
their bandages on for extended periods of time, such as a person
wearing an Unna's boot. The fabric could also be used on patients
with burns in order to learn more about the health of their wounds
without removing the bandage, which is often a very painful
process. In addition, the dyed gauze was sterilized successfully in
both an autoclave and an ethylene oxide machine, showing it could
be sterilized with existing equipment.
[0098] To be helpful to hospital patients with closely monitored
wounds or people who are monitoring long-term wounds without
professional assistance, the dyed cotton fabric used in this
experiment could be made into smaller products for home use. This
could help the layperson identify infection in small wounds and
cuts. Overall, the cotton bandages in this experiment would be
helpful in monitoring the state of any injury leaking bodily
fluid.
LIST OF REFERENCES CITED
[0099] Gethin, G. (2007). The significance of surface pH in chronic
wounds. Wounds uK, 3(3), 52. [0100] Leveen H, et al., (1973)
Chemical acidification of wounds. An adjuvant to healing and the
unfavourable action of alkalinity and ammonia. Ann Surgery 178(6):
745-50. [0101] Van der Schueren, L., & De Clerck, K. (2012).
Coloration and application of ph-sensitive dyes on textile
materials. Coloration Technology, 128, 82-90. [0102] Glover, B. J.,
& Martin, C. (2012). Anthocyanins. Current Biology, 22(5),
R147-R150. [0103] Romanelli, M, et al., (2002) Technological
Advances in Wound Bed Measurements, Wounds. 14(2).
Other Embodiments
[0104] It is to be understood that while the invention has been
described in conjunction with the detailed description thereof, the
foregoing description is intended to illustrate and not limit the
scope of the invention, which is defined by the scope of the
appended claims. Other aspects, advantages, and modifications are
within the scope of the following claims.
* * * * *