U.S. patent application number 11/542791 was filed with the patent office on 2008-04-03 for color change surgical prep solution.
Invention is credited to Nancy Barot, Yeong H. Huang.
Application Number | 20080081020 11/542791 |
Document ID | / |
Family ID | 39261403 |
Filed Date | 2008-04-03 |
United States Patent
Application |
20080081020 |
Kind Code |
A1 |
Huang; Yeong H. ; et
al. |
April 3, 2008 |
Color change surgical prep solution
Abstract
This invention discloses a surgical prep solution formulation,
either film forming or non-film forming, that changes color upon a
change in pH to indicate that the solvent has sufficiently
evaporated. The major components of this surgical prep solution
include: antimicrobial agents, solvents, pH adjusters, color
changing pH indicators, and optionally: film forming polymers, dyes
and viscosity regulators. The pH of the solution may rise or fall
depending on the pH of the original solution as compared with the
normal pH range of the acid mantle of the human skin or the normal
pH range of a sterilizing solution. As the pH changes, the pH
indicator may cause the surgical prep solution to change color.
Concurrently, as the fluids evaporate, the pH indicators interact
with atmospheric CO.sub.2, causing the solution to change color
based on the pH of the solution. The solution may also be used as
coating for medical devices.
Inventors: |
Huang; Yeong H.; (Grayslake,
IL) ; Barot; Nancy; (Mundelein, IL) |
Correspondence
Address: |
Allegiance Corporation;Attn: Kim Luna
1430 Waukegan Road
McGaw Park
IL
60085-6787
US
|
Family ID: |
39261403 |
Appl. No.: |
11/542791 |
Filed: |
October 3, 2006 |
Current U.S.
Class: |
424/9.6 ;
424/405 |
Current CPC
Class: |
A01N 31/12 20130101;
A01N 47/44 20130101; A01N 31/08 20130101; A01N 47/44 20130101; A01N
59/12 20130101; A01N 31/02 20130101; A61L 2300/606 20130101; A01N
59/12 20130101; A61L 27/54 20130101; A61P 31/12 20180101; A01N
37/36 20130101; A01N 31/02 20130101; A01N 31/08 20130101; A61L
27/34 20130101; A61L 27/50 20130101; A61P 31/10 20180101; A61L
2300/404 20130101; A01N 2300/00 20130101; A01N 37/36 20130101; A01N
31/12 20130101; A01N 31/16 20130101; A01N 31/16 20130101; A01N
59/12 20130101; A61P 31/04 20180101; A01N 2300/00 20130101; A01N
2300/00 20130101; A01N 2300/00 20130101; A01N 2300/00 20130101;
A01N 25/10 20130101; A01N 2300/00 20130101; A01N 2300/00
20130101 |
Class at
Publication: |
424/9.6 ;
424/405 |
International
Class: |
A61K 49/00 20060101
A61K049/00; A01N 25/00 20060101 A01N025/00 |
Claims
1. A composition comprising an antimicrobial agent, one or more pH
adjusters, and a color-changing pH indicator, wherein the one or
more pH adjusters is an acid, a base, a pH buffer or a combination
thereof.
2. A composition comprising an antimicrobial agent, a
topically-acceptable solvent, one or more pH adjusters, and a
color-changing pH indicator, wherein the one or more pH adjusters
is an acid, a base, a pH buffer or a combination thereof.
3. The composition according to claim 2, wherein the antimicrobial
agent is selected from the group consisting of chlorhexidine
digluconate, chlorhexidine diacetate, chlorhexidine
dihydrochloride, gluconic acid, hexachlorophene, iodophors,
povidone-iodine, iodine, para-chlorometaxylenol, triclosan, and
mixtures thereof.
4. The composition according to claim 2, wherein the
topically-acceptable solvent comprises water, ethanol, isopropanol,
acetone, or mixtures thereof.
5. The composition according to claim 2, wherein the one or more pH
adjusters are selected from the group consisting of acetic acid,
boric acid, carbonic acid, chromic acid, citric acid, lactic acid,
diluted hydrochloric acid, tartaric acid, propionic acid, malic
acid, diluted phosphoric acid, ammonium hydroxide, ammonium
carbonate, diethanolamine, ethylamine, hydrazine, methylamine,
monoethanolamine, potassium hydroxide, sodium bicarbonate, sodium
borate, sodium borate, sodium hydroxide, sodium phosphate dibasic,
trimethylamine, trolamine, pH buffer agents and mixtures
thereof.
6. The composition according to claim 2, wherein the color-changing
pH indicator is selected from the group consisting of bromophenol
blue, bromothymol blue, bromocresol green, bromocresol purple,
congo red, methyl orange, methyl red, methyl yellow, pentamethoxy,
phenophthalein, thymophthalein, p-naphtholbenzein, 4-nitrophenol,
3-nitrophenol, o-cresolphthalein, m-cresol red, thymol blue,
m-cresol purple, phenol red, and mixtures thereof.
7. The composition according to claim 2, further comprising a
film-forming polymer.
8. The composition according to claim 7, wherein the film-forming
polymer is selected from the group consisting of polyvinyl acetate,
polyvinyl alcohol, methacrylic acid-ethyl acrylate copolymer,
vinylpyrrolidone-vinyl acetate copolymer, polyvinyl
alcohol-polyethylene glycol graft copolymer, ethyl acrylate-methyl
methacrylate copolymer, acrylic polymer, polyacrylate copolymer,
and mixtures thereof.
9. The composition according to claim 2, further comprising a
dye.
10. The composition according to claim 9, wherein the dye is
selected from the group consisting of Green #5, Green #8, Orange
#4, Red #4, Red #17, Red #22, Red #28, Red #33, Violet #2, Yellow
#8, Yellow #10, Yellow #11, Blue #1, Blue #2, Carmine, Emerald
Green, Green #3, Red #3, Red #40, Yellow #5, Yellow #6, and
mixtures thereof.
11. The composition according to claim 2, further comprising a
viscosity regulator.
12. The composition accordingly to claim 11, wherein the viscosity
regulator is selected from the group consisting of polyethylene
glycol, polyethylene glycol derivatives, ethyl cellulose,
methoxycellulose, hydroxyethylcellulose, polyvinylpyrrolidone/vinyl
acetate copolymer, crosslinked pyrrolidone and mixtures
thereof.
13. The composition according to claim 2, wherein the composition
undergoes a visible color change upon a change in pH.
14. The composition according to claim 13, wherein the composition
reversibly undergoes a visible color change upon change in pH.
15. The composition according to claim 13, wherein the rate of
color change is controlled by the combination of pH adjusters.
16. The composition according to claim 13, wherein the composition
undergoes a visible color change upon a change in pH from greater
than about 6.5 to between about 4.5 to about 5.5.
17. The composition according to claim 13, wherein the composition
undergoes a visible color change upon a change in pH from less than
about 3.0 to between about 4.0 to about 5.5.
18. The composition according to claim 13, wherein the composition
undergoes a visible color change upon a change in pH from less than
about 4.5 to between about 4.5 to about 5.5.
19. A method of preparing a surgical prep solution used to
disinfect a pre-operative surgical site comprising combining an
antimicrobial agent, one or more pH adjusters, and a color changing
pH indicator to form a solution, wherein the one or more pH
adjusters is an acid, a base, a pH buffer or a combination
thereof.
20. A method of preparing a surgical prep solution used to
disinfect a pre-operative surgical site comprising combining an
antimicrobial agent, a topically-acceptable solvent, one or more pH
adjusters, and a color-changing pH indicator to form a solution,
wherein the one or more pH adjusters is an acid, a base, a pH
buffer or a combination thereof.
21. A method of disinfecting comprising: applying a composition to
a selected surface, evaporating the composition, and visually
inspecting the residue of the composition on the selected surface
for a change in color, wherein the composition comprises an
antimicrobial agent, one or more pH adjusters, and a color-changing
pH indicator, and wherein the one or more pH adjusters is an acid,
a base, a pH buffer or a combination thereof.
22. A method of disinfecting comprising: applying a composition to
a selected surface, evaporating the composition, and visually
inspecting the residue of the composition on the selected surface
for a change in color, wherein the composition comprises an
antimicrobial agent, a topically-acceptable solvent, one or more pH
adjusters, and a color-changing pH indicator, and wherein the one
or more pH adjusters is an acid, a base, a pH buffer or a
combination thereof.
23. The method according to claim 22, wherein the selected surface
is skin.
24. The method according to claim 22, wherein the selected surface
is a medical device.
25. The method according to claim 24, wherein the medical device is
a needleless injection connector.
26. The method according to claim 22, wherein the antimicrobial
agent is an antimicrobial agent sensitive to the environmental
pH.
27. The method according to claim 26, wherein the antimicrobial
agent sensitive to the environmental pH is selected from the group
consisting of iodine, idophor, chlorhexidine and chlorhexidine
gluconate.
28. The method according to claim 22, further comprising preparing
the composition of the applying step.
29. The method according to claim 28, wherein the preparing step
includes adding the one or more pH adjusters to the composition in
situ prior to application of the composition to the skin.
30. The method according to claim 28, wherein the preparing step
includes adding the pH indicator to the composition in situ prior
to application of the composition to the skin.
31. A medical device comprising: a coating comprising one or more
pH adjusters, and a color-changing pH indicator, wherein the one or
more pH adjusters is an acid, a base, a pH buffer or a combination
thereof.
32. The medical device according to claim 31, wherein the coating
reversibly undergoes a visible color change upon change in pH.
33. The medical device according to claim 31, wherein the coating
further comprises an antimicrobial agent.
34. The medical device according to claim 31, wherein the medical
device is one of a needle-free connector or a needle-free
valve.
35. A method of disinfecting comprising: coating a composition of a
first color to a selected surface, the coating comprising one or
more pH adjusters and a color-changing pH indicator, applying a
disinfecting solution to the selected surface, visually inspecting
the coating for a change in color to a second color, evaporating
the disinfecting solution, and visually inspecting the coating for
a change in color to the first color, wherein the one or more pH
adjusters is an acid, a base, a pH buffer or a combination thereof.
Description
FIELD OF THE INVENTION
[0001] The invention relates to disinfectants for use in medical
procedures that breach the skin, such as surgery, surgical
procedures and intravenous injections. In particular, the invention
pertains to surgical prep solutions used to disinfect a selected
surface, for example, pre-operative surgical sites and medical
devices.
BACKGROUND OF THE INVENTION
[0002] Pre-operative preparation of the skin with a topical
antimicrobial agent is necessary to reduce the likelihood that the
patient will contract a hospital-acquired infection during a
surgery or surgical procedure. Typically, the healthcare
practitioners, for example, prep nurses, apply a topical
antimicrobial agent to a surgical or needle entry site before the
procedure. Similarly, it is essential that medical devices that
breach the skin be disinfected prior to penetrating the skin at an
entry site or accessing an intravenous system. Healthcare
practitioners typically disinfect these medical devices by applying
an antimicrobial solution, e.g., alcohol, prior to use. Such
treatment reduces the infection rate at the site or within the
blood stream by hindering the growth of microorganisms or
disinfecting a wound, surgical incision, or needle puncture
site.
[0003] The human skin is normally covered with microorganisms such
as bacteria, fungi, and viruses. The microorganisms are either
transient, found on the skin's surface or are resident in deeper
areas of the skin, such as the hair follicles.
[0004] The microorganisms are prevented from entering the body by
the physical barrier of skin and the acid mantle, a protective
layer formed by the mixture of sweat and sebum. The acid mantle
maintains a moderately acidic covering for the normal human skin.
The pH means and ranges for the normal skin of both adults and
neonates are 5.7.+-.0.16 (range: 4.5-6.7) and 7.08.+-.0.17 (range:
6.6-7.5), respectively.
[0005] The function of the acid mantle is not completely understood
even though the acidic environment of the skin's surface has been
recognized for a century. However, the acid mantle is believed to
assist the body in processing the lipids required for the skin to
function as a barrier. Acidic environments also generally hinder
bacterial growth, and hence, help resist bacterial infection.
[0006] Potential pathogens usually cannot enter the body if the
skin and acid mantle remain intact. However, the integrity of the
skin barrier is breached during surgical procedures, potentially
exposing the surgical site or wound to microorganisms, increasing a
patient's risk of infection. Thus, standard surgical procedures
require that the skin at the surgical site be disinfected prior to
surgery to reduce the patient's risk of infection. Therefore, there
is a need in the art for a topical agent that will both kill the
transient and resident microorganisms quickly and provide sustained
antimicrobial activity throughout the entire surgery or surgical
procedure.
[0007] Healthcare practitioners have long used ethanol or
isopropanol, either alone or as a solvent along with other
antimicrobial agents, to disinfect the skin at the surgical
incision or needle puncture site and medical devices that penetrate
the skin since these alcohols quickly reduce the population of
bacteria, fungi, and some viruses at the site. Alcohol also
provides rapid and sustained antimicrobial activity when it is
combined with antimicrobial agents. However, alcohol based surgical
prep solutions are flammable and certain surgical procedures cannot
begin until the alcohol is completely evaporated. Hospital fires
have been caused by unevaporated flammable solvents within surgical
prep solutions. For the patient's safety, it is critical that
healthcare practitioners be able to determine whether the flammable
solvents within surgical prep solutions are completely evaporated
prior to initiating energized surgical procedures, for example,
electrocautery.
[0008] Solvent evaporation in particular presents a major challenge
for healthcare practitioners for several reasons. First, it is
difficult to visually determine when a colorless solvent (e.g.,
alcohol) has sufficiently evaporated to begin surgery or the
surgical procedure. Second, the healthcare practitioners will often
physically touch the skin surface or the medical device with a
glove to determine the level of dryness. However, if the skin or
medical device is not dry when touched, such a touch may breach the
applied prep solution and provide a pathway for microorganisms to
enter the body through the skin or via the medical device. Thus, it
is necessary and desirable for the healthcare practitioners to have
an easy way to determine if a solvent within a surgical prep
solution has completely evaporated from the surgical site or the
medical device without touching the skin, the medical device, or
the applied surgical prep solution.
[0009] An effective film forming polymer may also be added to the
surgical prep solution to provide better adherence of the solution
to the skin or the medical device. Film forming polymers are either
water soluble or insoluble and most of the water insoluble films
adhere poorly to the skin. Poor adherence is especially problematic
in orthopedic surgery or surgical procedures in which patients are
draped after the surgical prep solution has dried. If the surgical
prep solution adheres poorly to the skin or is water soluble, the
drape will typically fall off during the procedure, contaminating
the sterile surgical environment and increasing the chance of a
hospital-acquired infection.
[0010] U.S. Pat. No. 5,763,412 teaches a film-forming composition
containing chlorhexidine gluconate. U.S. Pat. No. 5,547,662
(hereinafter "the '662 patent") is directed to a film-forming
composition for preparation of a skin surface as a surgical site
containing an antimicrobial agent and Dowicide A and D&C Red
17, which changes color from purple (wet) to red (dry), but does
not teach color changes triggered by pH indicators. The
disadvantages of the '662 patent include inter alia the particular
combination is not applicable to antimicrobial with inherent color,
such as iodine or iodophors and the color change is not reversible.
In addition, U.S. Pat. No. 4,584,192 teaches chlorhexidine or its
derivative, but does not disclose which chlorhexidine compound is
suitable and has no visualization feature.
SUMMARY OF THE INVENTION
[0011] This invention discloses a surgical prep solution
formulation, either film forming or non-film forming, that changes
color upon drying to indicate when the surgical prep solution has
completely dried. Advantageously, the surgeon can determine that a
selected surface, such as a surgical site or a medical device, is
dry and the solvent has evaporated by visual determination.
DETAILED DESCRIPTION OF THE INVENTION
[0012] The present description emphasizes certain embodiments of
the invention, but is not meant to be comprehensive of the entire
scope of the invention. The full scope of the invention is measured
by the appended claims.
[0013] The surgical prep solution comprises: topically-acceptable
solvent(s), pH adjuster(s), color changing pH indicator(s) and
optionally: antimicrobial agent(s), film forming polymer(s), dye(s)
and viscosity regulator(s). After the solution is applied on the
skin, the fluid components evaporate and the color changing pH
indicator(s) interact with the human skin. The pH of the residue of
the solution may rise or fall if the pH of the original solution is
different from the normal pH range of the acid mantle of the human
skin. As the pH of the residual solution changes, the pH indicator
in the surgical prep solution may cause the residue to change
color. Similarly and concurrently, as the fluid evaporates, the
color changing pH indicator(s) may interact with atmospheric
CO.sub.2, changing the pH of the solution because CO.sub.2 is
mildly acidic. As such, the color changes according to the color
properties of the pH indicator as the solution becomes less basic
or more acidic. The rate of color change may be synchronized with
the rate of fluid evaporation through the selection of pH
indicators and pH adjusters so that the color change is complete
when the fluid is sufficiently evaporated. Additionally, different
color dyes and pH indicators may be utilized, to provide for a
particular desired color.
[0014] The term "topically-acceptable solvent" as used here is a
fluid that is compatible with the other ingredients of the
composition and is non-toxic when applied to human skin. Suitable
solvents include, but are not limited to, water, alcohols, acetone,
esters, chlorinated hydrocarbons and chlorofluorohydrocarbons.
Preferred solvents include, but are not limited to, water, and/or
isopropanol, ethanol and other alcohols.
[0015] The term "antimicrobial agent" as used here is a chemical,
such as a compound or salt that destroys or inhibits the growth of
microorganisms. The term "microorganisms" as used here includes,
but is not limited to, bacteria, fungi, and viruses. The
antimicrobial agent may be, but is not limited to, alcohols (e.g.,
ethanol, isopropanol), chlorhexidine (e.g., chlorhexidine
digluconate (CHG), chlorhexidine diacetate, chlorhexidine
dihydrochloride, gluconic acid), hexachlorophene, iodophors,
povidone-iodine, iodine, para-chlorometaxylenol (PCMX), and
triclosan. Desirably, the antimicrobial agent is present in a
quantity sufficient to inhibit microbial growth on the surface of
the skin.
[0016] The term "antimicrobial agent sensitive to the environmental
pH" as used here is an antimicrobial agent whose stability is
influenced by the ambient pH. The antimicrobial agent sensitive to
the environmental pH is a subset of the antimicrobial agents
described above and may include, but is not limited to, iodine,
iodophor, chlorhexidine and its derivatives, such as chlorhexidine
gluconate. For instance, iodine and iodophor are naturally acidic
and may gradually lose their antimicrobial activity if the
environmental pH is basic. If the selected pH indicator changes
color in the higher pH range (e.g., bromocresol purple which is
yellow at pH below 5.2 and violet above 6.8), the antimicrobial
activity of the iodophor solution may last up to several hours once
a pH adjuster is added and the environmental pH turns basic. In a
preferred embodiment where a pH adjuster is used where the
environmental pH is not stable for antimicrobial agents, the
solution should be applied immediately after the pH adjuster is
added. In a more preferred embodiment, the two different pH
components: (a) pH adjuster and/or pH indicator and (b)
antimicrobial agents may be separately contained and mixed in situ
through devices such as a dual channel syringe.
[0017] The term "film forming polymer" as used here is a polymer
that forms a film that coats a surface (e.g., the skin) upon drying
of the solution. The film is intact, resists both blood and saline,
and contains the antimicrobial agent. Such polymer may include, but
is not limited to, polyvinyl acetate, polyvinyl alcohol,
methacrylic acid-ethyl acrylate copolymer, vinylpyrrolidone-vinyl
acetate copolymer, polyvinyl alcohol-polyethylene glycol graft
copolymer, ethyl acrylate-methyl methacrylate copolymer, acrylic
polymers such as Eudragit.RTM., and polyacrylate copolymer.
[0018] The term "pH indicator" as used here is a compound that is
added in trace amounts to the surgical prep solution to determine
its pH by visual observation. The pH indicator changes color based
on the pH of the surgical prep solution. Such pH indicators
include, but are not limited to, bromophenol blue, bromothymol
blue, bromocresol green, bromocresol purple, congo red, methyl
orange, methyl red, methyl yellow, pentamethoxy, phenolphthalein,
thymophthalein, p-naphtholbenzein, 4-nitrophenol, 3-nitrophenol,
o-cresolphthalein, m-cresol red, thymol blue, m-cresol purple,
phenol red, and mixtures thereof. The pH indicator may be
separately contained and added in situ prior to application to the
skin at the surgical site. In a preferred embodiment, the
composition undergoes a visible color change upon a change in pH
from greater than about 6.5 to between about 4.0 to about 5.5.
Alternatively, in another preferred embodiment, the composition
undergoes a visible color change upon a change in pH from less than
about 3.0 to between about 4.0 to about 5.5. More preferably, the
composition undergoes a visible color change upon a change in pH
from less than about 4.5 to between about 4.5 to 5.5.
[0019] The term "color dye" as used here are commonly used dyes or
pigments. Such color dyes include, but are not limited to, D&C
dyes (Green #5, Green #8, Orange #4, Red #4, Red #17, Red #22, Red
#28, Red #33, Violet #2, Yellow #8, Yellow #10, Yellow #11),
FD&C dyes (Blue#1, Blue#2, Carmine, Emerald Green, Green #3,
Red #3, Red #40, Yellow #5, Yellow #6) and mixtures thereof.
[0020] The term "pH adjuster" as used here is an acid, a base or a
pH buffer. The pH adjuster is used to adjust the solution pH so
that the solution pH falls within one extreme of the color spectrum
of the selected pH indicator. The rate of color change is
controlled by the pH adjuster (i.e., acid, base or pH buffer). For
instance, if one selects bromothymol blue as the pH indicator which
is yellow when pH is below 6 and blue when pH is above 7.6, a pH
adjuster is needed to change the solution pH to either below 6 or
above 7.6. Such acids include, but are not limited to, acetic acid,
boric acid, carbonic acid, chromic acid, citric acid, lactic acid,
diluted hydrochloric acid, tartaric acid, propionic acid, malic
acid, diluted phosphoric acid and mixtures thereof. Such bases
include, but are not limited to, ammonium hydroxide, ammonium
carbonate, ethylamine, dimethylamine, glycine, methylamine,
trimethylamine, diethanolamine, sodium bicarbonate, sodium borate,
sodium hydroxide, hydrazine, monoethanolamine, potassium hydroxide,
sodium phosphate dibasic, trolamine and mixtures thereof. The pH
adjuster may also include pH buffer agents such as the Hydrion.TM.
buffer mixture produced by Micro Essential Laboratory, Inc.
(Brooklyn, N.Y.) which contains a powdery mixture of potassium
phosphate monobasic and sodium phosphate dibasic. The pH adjuster
may be separately contained and added in situ prior to application
because some antimicrobial agents have a shorter shelf life
depending on the pH of their environment.
[0021] In a preferred embodiment, the composition according to the
present invention is a liquid solution with a viscosity similar to
water and/or ethanol. Alternatively, the composition may take
various physical forms such as creams, gels, lotions, emulsions,
foams, and the like. Viscosity regulators may be used to control
the viscosity and rheological properties of the composition
according to the invention. Suitable viscosity regulators include,
but are not limited to, polyethylene glycol, polyethylene glycol
derivatives, ethyl cellulose, methoxycellulose,
hydroxyethylcellulose, polyvinylpyrrolidone/vinyl acetate
copolymer, and crosslinked pyrrolidone.
[0022] A preferred embodiment of the surgical prep solution
includes compounds that provide a first color which visually
indicates the skin area covered by the composition and a second
color which gives a visual indication that the solvent has been
substantially eliminated by evaporation. These compounds usually
refer to pH indicators, but it may also be other colored
ingredients in the formulation, such as an antimicrobial agent or
film forming polymers, as they alter the overall color.
[0023] In an alternative embodiment, the color change surgical prep
solution is applied to medical devices, for example, needle-free
connectors and valves. Generally, devices used for needle-free
intravenous administration include one or more needle-free
connectors. Preferably, the needle-free connectors include central
venous catheters capable of accessing a patient's bloodstream. The
needle-free connectors may function as access ports to the
patient's bloodstream and may be used for injecting medication or
drawing blood samples. The needle-free devices are designed to
reduce accidental needle punctures and exposure to potentially
infectious blood samples by substituting needles with needle-less
devices for intravenous administration. The needle-free valve opens
and fluid may flow therethrough when a fitting, preferrably a male
luer fitting, is inserted into the valve through a valve port. The
valve seals when the fitting is removed and prevents fluid flow
through the valve thereafter. The valve may, for example, be
activated by a luer lock syringe, a secondary intravenous
administration device or other intravenous products. In general,
healthcare practitioners disinfect the needle-free connectors and
valves with alcohol prep pads immediately prior to use.
[0024] It is essential that these medical devices are thoroughly
disinfected in order to reduce a patient's risk of infection.
Preferrably, the color change surgical prep solution has a pH
different from that of medical devices (e.g., needle-free
connectors). The color change surgical prep solution may be swabbed
onto a medical device. The solution may interact with surfaces of
the medical device along with atmospheric CO.sub.2, resulting in a
pH change. As such, the color may change according to the color
properties of the pH indicator as the solution becomes less basic
or more acidic. A healthcare practitioner may visually inspect the
color of the medical device to determine whether the medical device
has been thoroughly disinfected. The use of the color change
surgical prep solution may allow healthcare practitioners to
visually identify the disinfected area based on the color
change.
[0025] In another alternative embodiment, the color change surgical
prep solution may be applied as a coating onto medical devices. The
coating may contain a pH buffer having a pH different from that of
disinfecting solutions (e.g., alcohol) typically used in hospitals.
As soon as the sterilizing solutions (e.g., alcohol) are applied to
the coated medical devices, the solution (e.g., alcohol) may
interact with the coating and cause a change in pH. Accordingly,
the color may change based on the color properties of the pH
indicator as the solution becomes less basic or more acidic. A
healthcare practitioner may visually inspect the color of the
medical devices to determine whether the medical device has been
thoroughly disinfected.
[0026] Preferably, the interaction between and the coating and the
disinfecting solution is reversible and that the coating returns to
its original color once the disinfecting solution fully evaporates.
The reversible color change may be utilized repeatedly. For
example, a medical device, such as a needle-free connector, needs
to be disinfected every time the device is used. During the period
of use, a healthcare practitioner may access the same needle-free
connector to inject medicaments or draw blood samples. The
connector may be disinfected by a disinfecting solution and change
color. Once the disinfecting solution has fully evaporated, the
connector may return to its original color. The connector may be
repeatedly disinfected by the disinfecting solution. A color change
may occur every time the disinfecting solution is applied to the
connector and the connector may return to its original color every
time the disinfecting solution becomes fully evaporated.
[0027] The invention offers several advantages over the prior art.
First, the invention applies to both film forming and non-film
forming prep solutions whereas the prior art is directed to
film-forming color change surgical prep solutions.
[0028] Second, the prior art excludes antimicrobial agents with
inherent color. For instance, the inclusion of iodine would render
ineffective the color change abilities of the surgical prep
solutions of the prior art. The invention overcomes such a
limitation, allowing flexibility in choice of antimicrobial
agents.
[0029] Third, the invention allows flexibility in the potential
skin hues of patients. No two skin hues are the same and patients
themselves might have variations of skin tone or even a colored
tattoo. Thus, color flexibility in the surgical prep solution is
imperative. In the invention, the color possibilities are more
flexible than the prior art allows and hence, the surgical prep
solution's color may be tailored to the needs of both patient and
surgeon.
[0030] Fourth, for embodiments of the invention that include a
film-forming polymer, the tinted color is embedded within the film
and cannot easily be washed off because the film strongly adheres
to the skin. This feature is especially important for orthopedic
surgeons employing drapes on the patient.
[0031] Fifth, the invention reduces the risk of flammability.
Surgeons regularly use electrocautery to burn or destroy tissue and
hence, must be absolutely sure no flammable gases or liquids are
present. Isopropanol is widely used as an antimicrobial agent, but
it's flammability presents a problem to surgeons. The invention
allows a surgeon to know when the isopropanol has been eliminated,
thus reducing the risk of fire.
[0032] The invention also differs from the prior art in that pH
indicators are used to change the color of the surgical prep
solution. Known surgical prep solutions use chemicals such as
Dowicide A and D&C Red 17 to change the color of the solution.
Contrary to the present invention, the solvated Dowicide A and the
dye form a complex and as the solvent evaporates, the complex
shifts the wavelength of the light absorbed, thus changing the
color of the complex. The mechanism is different from a
pH-indicated color change.
[0033] The invention also differs from prior art in that the color
change of the prep solution is reversible, if the environment pH
change occurs during the procedure.
[0034] Finally, the invention facilitates the stability of
antimicrobial agents that are unstable in certain pH ranges. The pH
indicator and/or pH adjuster may be separately contained and added
in situ prior to application to maintain the integrity of the
antimicrobial agents and increase their effectiveness.
EXAMPLES
[0035] The following non-limiting examples illustrate particular
embodiments of the invention. The examples are not meant to be
comprehensive of the entire scope of the invention.
[0036] The following table lists both the composition of the one
step surgical prep solution composition and a preferred
embodiment.
TABLE-US-00001 Amount, preferred embodiment Ingredient Amount
(wt./wt. %) (wt./wt. %) Solvent about 10 about 90 about 60 about 80
Antimicrobial agent about 0 about 5 about 1.5 about 2.5 (e.g.
iodine or CHG, excluding alcohols) Water about 3 about 35 about 15
about 25 Color Dye (optional) about 0 about 0.1 about 0.005 about
0.05 Film forming polymer about 0 about 20 about 0 about 10
(optional) pH indicator Trace Trace pH adjuster Trace Trace
Viscosity regulator about 0 about 5 about 0 about 5
[0037] In preparing the solutions, solid ingredients, such as
polymers (including viscosity regulator), solvents, and color dye
were first mixed to allow the slower-dissolving ingredients (i.e.,
film forming polymers, if used) time to dissolve in the solvent
system. Afterwards, the antimicrobial agents were mixed in,
followed by the pH indicator and pH adjuster. Each solution was
mixed at room temperature using a magnetic stirring bar. These
conditions apply to all the following examples.
[0038] If the antimicrobial agents are sensitive to pH, the pH
adjuster and pH indicator may be initially separated and
incorporated through devices such as a two-cylinder syringe with a
static mixer or any other mixing mechanism and mixed with other
components in situ prior to application.
Example A
Non-Film Forming
TABLE-US-00002 [0039] Ingredient Amount (wt./wt. %) Isopropanol
77.5 Water 20.5 0.1% Bromothymol blue in IPA 1 1% Ammonium
hydroxide 1
[0040] In preparing the solution in Example A, isopropanol and
water were mixed first. Subsequently, bromothymol blue was added
and the solution pH was adjusted to between 8 to 10 using ammonium
hydroxide. When applied to the skin, Example A changed from blue to
light yellow/colorless after the solvent evaporated.
Example B
Non-Film Forming
TABLE-US-00003 [0041] Ingredient Amount (wt./wt. %) Isopropanol
64.2 20% CHG aqueous solution 11.7 Water 22.05 FD&C Red 40 .05
0.1% Bromothymol blue in IPA 1 1% Ammonium hydroxide 1
[0042] In preparing the solution in Example B, Red 40, isopropanol,
20% CHG aqueous solution, and water were mixed first. Subsequently,
bromothymol blue was added and the solution pH was adjusted to
between 8 to 10 using ammonium hydroxide. When applied to the skin,
Example B changed from purple to red after the solvent
evaporated.
Example C
Non Film Forming
TABLE-US-00004 [0043] Ingredient Amount (wt./wt. %) Isopropanol
68.2 20% CHG aqueous solution 8.5 Water 21.3 0.1% Bromothymol blue
in IPA 1.1 1% Ammonium hydroxide 0.9
[0044] In preparing the solution in Example C, isopropanol, 20% CHG
aqueous solution, and water were mixed first. Subsequently,
bromothymol blue was added and the solution pH was adjusted to
between 8 to 10 using ammonium hydroxide. When applied to the skin,
Example C changed from blue to colorless after the solvent
evaporated.
Example D
Film Forming
TABLE-US-00005 [0045] Ingredient Amount (wt./wt. %) Polyacrylate
copolymer 7.4 Isopropanol 74.8 Iodine 0.68 Sodium iodide 0.62 Water
16.5 Bromophenol blue trace Propionic acid trace
[0046] The components in Example D were combined to form a
solution. Specifically, the polyacrylate was first dissolved in
isopropanol and water, and then iodine, sodium iodide, and
bromophenol blue were added. Propionic acid was used to adjust the
solution pH to between 3.5 and 4. When applied on skin, the color
changed from iodine gold color to green after the solvent
evaporated. For this example, the integrity of the film was
maintained for several hours and confirmed by visual
observation.
Example E
Film Forming
TABLE-US-00006 [0047] Ingredient Amount (wt./wt. %) Polyacrylate
copolymer 7.5 Isopropanol 74.9 Water 15.6 CHG 2.0 FD&C Red 40
0.022 Bromothymol blue trace Methylamine trace
[0048] In Example E, the polyacrylate copolymer and FD&C Red 40
were first dissolved in isopropanol and water. Subsequently, CHG
and bromothymol blue were added and the solution pH was adjusted to
between 8.5 and 9 using methylamine. When applied on skin, the
color changed from purple to pink/red after the solvent evaporated.
For this example, the integrity of the film was maintained for
several hours and confirmed by visual observation.
Comparative Time-Kill Study (Examples F-I)
[0049] The following Examples F-I were made to assess the
formulation's antimicrobial effectiveness when dry.
[0050] Bacterial suspensions of Escherichia coli ATCC # 11229 and
Staphylococcus aureus, ATCC # 6538 were made in sterile saline to
final inoculum level of 1.5.times.10.sup.8 CFU/ml. Thirty (30)
microliters of the testing antimicrobial solution were aseptically
spread on a sterile microslide covering a surface of 25.times.25
sq. mm and dried for ten (10) minutes. One (1) microliter of the
microbial suspensions was applied on a sterile cover slip. The
antimicrobial films were applied to these microbial suspensions for
exposure times of 1, 5, or 10 minutes. After the exposure time had
elapsed, both the cover slip and the micro slide were dropped into
a test tube containing 10 ml sterile neutralizing solution. The
Standard Plate Count Method was used for enumeration of the
survival cells (CFU/ml). The log reduction in bacterial count was
calculated from the log of the inoculum titers, which were
enumerated by following the same procedure except without the
presence of antimicrobial films.
[0051] Examples F-I present the results of the Time-Kill Study with
the respective film solution.
Example F
Antimicrobial Efficacy
TABLE-US-00007 [0052] Ingredient Amount (wt./wt. %) Film forming
polymer 7.37 Iodine 0.67 Sodium iodide 0.71 Isopropanol 73.69 Water
16.38 Formic acid 1.16 Bromophenol blue 0.02
[0053] In preparing the solution in Example F, the film forming
polymer was first dissolved in isopropanol and water. Afterwards,
iodine, sodium iodide and bromophenol blue were added. The final pH
was then adjusted to between 3.5 to 4 using formic acid.
TABLE-US-00008 Log reduction/ml at time Storage time at intervals
Microorganism tested ambient conditions 1 min. 5 min. 10 min. E.
coli, gram negative 0 time >4.98 >4.98 N/A bacterium 2 week
>5.04 >5.04 N/A 1 month >4.86 >4.86 >4.86 2 months
>5.05 >5.05 >5.05 S. aureus, gram 0 time 1.25 4.56 N/A
positive bacterium 2 week 1.21 3.92 N/A 1 month 2.21 >4.62
>4.62 2 months 4.29 >5.49 >5.49
Example G
Antimicrobial Efficacy
TABLE-US-00009 [0054] Ingredient Amount (wt./wt. %) Film forming
polymer 7.42 Iodine 0.68 Sodium iodide 0.72 Isopropanol 74.17 Water
16.49 Formic acid 0.5 Bromophenol blue 0.02
[0055] In preparing the solution in Example G, the film forming
polymer was first dissolved in isopropanol and water. Afterwards,
iodine, sodium iodide, and bromophenol blue were added. The final
pH was then adjusted to between 3.5 to 4 using formic acid.
TABLE-US-00010 Storage time Log reduction/ml at time at ambient
intervals Microorganism tested conditions 1 min. 5 min. 10 min. E.
coli, gram negative 0 time >5 >5 N/A bacterium 2 week 3.72
>5.04 N/A 1 month 4.01 >4.86 >4.86 2 months >5.05
>5.05 >5.05 S. aureus, gram positive 0 time >4.75 >4.75
N/A bacterium 2 week 1.45 >5.07 N/A 1 month 2.09 >4.62
>4.62 2 months 5.01 >5.49 >5.49
Example H
Antimicrobial Efficacy
TABLE-US-00011 [0056] Ingredient Amount (wt./wt.) Film forming
polymer 7.40 Iodine 0.68 Sodium iodide 0.70 Isopropanol 74.64 Water
16.45 Formic acid 0.03 Citric acid, anhydrous 0.08 Bromophenol blue
0.02
[0057] In preparing the solution in Example H, the film forming
polymer was first dissolved in isopropanol and water. Afterwards,
iodine, sodium iodide and bromophenol blue were added. The final pH
was then adjusted to between 3.5 to 4 using both citric acid and
formic acid.
TABLE-US-00012 Storage time Log reduction/ml at time at ambient
intervals Microorganism tested conditions 1 min. 5 min. 10 min. E.
coli, gram negative 1 month >5.05 >5.05 >5.05 bacterium S.
aureus, gram positive 1 month 4.13 >5.49 >5.49 bacterium
Example I
Antimicrobial Efficacy
TABLE-US-00013 [0058] Ingredient Amount (wt./wt.) Film forming
polymer 7.29 Iodine 0.67 Sodium iodide 0.62 Isopropanol 74.79 Water
16.20 Propionic acid, 99.5% 0.31 Citric acid, anhydrous 0.10
Bromophenol blue 0.02
[0059] In preparing the solution in Example I, the film forming
polymer was first dissolved in isopropanol and water. Afterwards,
iodine, sodium iodide and bromophenol blue were added. The final pH
was then adjusted to between 3.5 to 4 using both citric acid and
propionic acid.
TABLE-US-00014 Storage time Log reduction/ml at time at ambient
intervals Microorganism tested conditions 1 min. 5 min. 10 min. E.
coli, gram negative 10 days >5.05 >5.05 >5.05 bacterium S.
aureus, Gram 10 days 4.38 >5.49 >5.49 positive bacterium
Examples J-M (Rate of Color Change)
[0060] Examples J-M illustrate the rate of color change controlled
through different acid combinations. Specifically, the higher
proportion of acid, the slower the color change when applied on
skin.
TABLE-US-00015 Ingredient (wt/wt %) Example J Example K Film
forming polymer 8.967 8.950 Iodine 0.727 0.726 Sodium iodide 0.777
0.776 Isopropanol 72.350 72.293 Water 16.937 16.907 Citric acid
0.157 0.263 Formic acid 0.060 0.060 Bromophenol blue 0.025
0.025
[0061] After being applied on skin, Example J changes color within
1 minute while Example K changes color within 2 to 3 minutes.
TABLE-US-00016 Ingredient (wt/wt %) Example L Example M Film
forming polymer 7.43 7.43 CHG 2.00 2 Isopropanol 74.81 74.81 Water
15.63 15.63 Bromothymol blue 0.07 0.07 Ammonium hydroxide 0.06 --
Dimethylamine -- 0.06
[0062] After being applied on skin, Example L color changes from
blue to colorless within 1 minute while it takes Example M more
than 2 minutes to change color.
* * * * *