Note: Descriptions are shown in the official language in which they were submitted.
`\
O ~Y~ %
BACKGROUND OF THE INVENTION
In the course of certain pre-operative and post-operative
procedures it is necessary to provide a means for the drainage of
body tissue exudates and other organic fluids. Such drainage in-
volves!the insertion of a catheter into the body cavity which drains
into a collection vessel. These collection containers are emptied
or replaced after varying periods of time of drainage collection.
The length of time during which such drainage catheters are utilized
will vary from the indeterminant period for the urinary incontinent
lo patient to the short-transition interval of the operative period
when purulent material is drained. Such drainage materials usually
comprise a high bio-organic load which is frequently contaminated
with infectious micro-organisms so that microbicidal degerming is a
necessary procedure to protect both the patient and attending hospi-
tal and nursing staff. Unfortunately, the tissue exudates with high
bio-organic load presents serious problems since germicides are in
activat~d by the organic matter, enzymes and inorganic salt content
of these drainage systems~
The catheterized urinary tract is the most common site
for infections while the patient is in a hospital, and urinary tract
infections account for approximately 30% of hospital nosocomial in-
fections. While an improvement in the diminution of catheter-asso-
ciated bacteria has been achieved by the utilization of closed,
~ ~8~)272
sterile drainage collection sy~tems, the problem remains of serious
concern to the clinician and the patient.
It has been found that a significant number of patients
with in-dwelling catheters continue to acquire urinary tract infec-
tion and the microbial contamination of the urine drainage collection
bag has been frequently observed to occur prior to the onset of a
bladder bacteremia. The use of suitable germicidal agents which are
administered prophylactically to the patient in an effort to delay
the onset of bacteria has not been successful in preventing these
lo infections because many of these systemic antimicrobial agents are
toxic and therefore may not be used for long-term routine prophylaxis.
It has been shown that bacterial contamination of the
urine drainage collection bag, which has been established to be a
common source of bacteria associated with catheterization, may be
eliminated by adding hydrogen peroxide to the collecting container.
However, hydrogen peroxide, which is a strong oxidizing agent, enters
into secondary chemical reactions with the organic matter of urine
and the container. This presents considerable limitations for the
routine germicidal use of hydrogen peroxide in such collecting systems.
Hydrogen peroxide also has a serious limitation when used as
a germicide in the presence of biologic matters containing such en-
zymes as catalase or peroxidase. These enzymes cause an inactivation
of the hydrogen peroxide by releasing gaseous, nascent oxygen into
the atmosphere, with the formation of inert water. The urine col-
lected in the course of the post-surgical and/or medical management
of genito-urinary pathology frequently cont~ins blood and pus and
microbial flora, all of which carry the peroxidase enzymes to render
peroxide germicides inert. The use of such germicides consequently
2Yi~.~
1 requires frequent multiple additions of peroxide agents which not
only increases nursing costs, but also present the patient with
the threat of microbici~al failure through enzyme inactivation of
the peroxide germicidal systems. Moreover, it has been shown that
certain microorganisms may be resistant to hydrogen peroxide germi-
cidal action which consequently provide a still further patient
threat as well as new epidemiologic problemsO
I After the surgical intervention for the treatment of gall-
bladder disease, bile drainage is a frequent necessity. In many in-
lo stance~ this drainage fluid is contaminated and presents a toxic
hazard for the patient and attending staff. The usual germicides are
not satisfactory because ~ the chemical propPrties of the bile salts
in this drainage fluid which react to degrade the germicidal syst~m.
When hydrogen peroxide is used as a germicide for a gallbladder
drainage system, the bile salts are highly chemical reactive with
peroxides to render the germicidal effect of hydrogen peroxide worth-
less.
Following certain chest procedures drainage catheters are
inserted to drain the chest cavity. These chest collection systems
involve the common hazard of microbial contamination and also because
of reflux of the exudates into the sensitive chest cavity, containing
the vital oryans, serlous patient threat results. ~he use of anti-
septics to degerm such drainage systems is severely limited because
of the inherent toxic nature of the germicide to these sensitive
oxgans, and also because of the presence of the high bio-organic load
of these exudates which serves to neutralize and destroy the conven-
tional germicides.
When the above drainage fluids comprise blood and other
~ ~8~27~,
1 tissue exudates, thc inci(lence of infection is materially increased
since such organic comp~ ition of these fluids is an excellent
medium for microbial growth.
Of the antiseptic agents utilized for environmental de-
germing, iodine is considered to be one of the best antimicrobial
agents because of its kroad spectrum rapid microbicidal action
against every species of microorganism. However, elemental iodine
is a strong, corrosive, oxidizing halogen which interacts with many
substances. Elemental iodine stains skin and natural fibers as
well as most surface materials. The tissue irritative properties of
elemental iodine presents another serious threat to its use with
patients. Because iodine has a high vapor pressure, it poses the
problem of refluxing iodine vapors from the urine collecting bag into
the genito-urinary system to cause local tissue damage.
The development of iodophor germicidal preparations elimi-
nated many of the noxious toxic chemical properties of elemental
iodine without affecting its germicidal efficacy. T~.e class of
organic iodophor compounds consists of two distinct groups; the first
is the non-detergent, iodine-containing organic germicidal prepara-
tions of which polyvinylpyrrolidone-iodine (hereinafter for convenience
referred to as "povidone-iodine"~ is the only member and the second
group consists of compounds prepared from a variety of detergent,
surface-active agents and iodine. This latter group of detergent
iodophor compounds are useful for environmental degerming such as
occurs in urine collecting bags. This group of germicidal compounds
includes such iodophor detergent-compounds as nonylphenox~poly-
(ethyleneoxy)-ethanol iodine and undecoylium chloride iodine.
l Deter~erlt-iodophor compounds may be formed by combining
iodine with a anionic, cationic or nonionic detergent compound. An
example of nonionic detergent suitable to form an iodophor compound
is the polyglycol ether-type surface activ~ compounds which are well
known in the art. (See U.S. Patents l,970,578 and 2,213,447).
Other nonionic surfactants that may be used to prepare iodophors
are disclosed in U.S. Patent 2,674,619.
Anionic detergents also form iodophor compounds, and sur-
face-active agents such as alkanoyl taurates and alkylaryl sulfonates,
as for ~xample alkyl benzene sodium sulfonate and alkyl naphthyl
sodi~m sulfonate, may be combined with iodine to ~orm such anionic
iodophors.
When a cationic detergent is desired to be used as an
iodine carrier, then the well known cationic surfactant compounds are,
for example, the quaternary ammonium salts such as are ~ormed by the
alkylation of fatty amines and straight chain fatty amine salts
having from 8 to 18 carbon atoms in chain length, as for example,
octadecyl amine; amino amides and imidazolines, may be used.
The detergent iodophor group possesses common disadvantages
for use in urine collection systems in that the surface tension re-
duction, because of the detergent content, gives rise to massive foam
formation which tend to clog catheters. While germicidal activity
is satisfactory for these surfactant iodophors, this physical proper-
ty of foam formation make these agents somewhat less than preferred.
Of the general class of iodophor germicidal preparations,
povidone-iodine is the preferred degerming compound because this
organic iodine germicide has a low systemic toxicity and it is
essentially non-ixritating to mammalian tissues while acting as a
~ ~02~l2
1 broad~spectrum ~e~nicidal agent with non-selective antimicrobial
activity. It i5 effective in dilute solutions and is established
to be active against bacteria, fungi, virus, spores, amoeba and
nematodes.
However, it is known that all iodophor preparations are not
stable in the alkaline pH range Solutions of povidone-iodine de~
scribed in compendial literature all carry the caution that the pH
of such solutions must not exceed pH 6. This inactivation of
iodophor germicidal activity in the alkaline pH range is especially
lo important to the use of these agents in urine collection systems
because the microbial action on urea liberates am~onia to result in
a strong alkaline chemical reaction.
SUMMARY OF THE INVENTION
.
It is accordingly a primary object OI the present invention
to provide for the stabilization of iodine-containing germicidal
preparations even in the presence of large amounts of bio~organic
matt~r.
It is another object of the present invention to provide
for the stabilization of iodophor compositions so that the same can
be used in connection with in-dwelling catheters, gallbladder drain-
age collection vessels and other body exudate drainage collection
systems.
It is another object of the present invention to provide
for the stabilization of iodophor compositions so that the same can
be used in connection with catheters inserted to provide a drainage
system to the chest cavity and abdominal cavity.
It is another object of the present invention to provide for
the stabilization of iodophor compositions so that the same can be
) 2f~
1 used in connection with in-dwelling catheters for body cavity wherein
the drainage fluid comprises blood, tlssue exudate and other serous
materials, to degerm the collected fluids.
It is another object of the present invention to provide
for stabilized a~ueous iodine-containing solutions which retain
germicidal iodine even in the presence o large amounts of urine,
blood, bile and other tissue exudates.
Other objects and advantages of the present invention will
be apparent from a further reading of the specification and of the
appendin!g claims.
With the above and other objects in view, the present in-
vention mainly comprises iodine-containing germicidal preparat}ons
including maleic acid or mixtures of maleic acid with hydrochloric
acid or phosphoric acid in an amount sufficient to stabiliæe the
iodine preparation in contact with large amounts of urine or the
like, the pH of the system not exceeding about 3.
While it is known that iodophor preparations are not stable
in alkaline pH range, attempts to avoid the lack of stability thereo
when used in connection with urine collecting bags by the acidifica-
tion of the bag contents for the purpose of controlling the develop-
ing alkalinity in the body exudate collecting container were not
successful in attempting to avoid the loss of iodine potency of the
iodophor solution at alkaline pH. Thus, for example, the acidi~ica-
tion of the urine with strong acids has been found to cause the
formation of precipitates when the iodophor is added thereto.
Accordinyly, this cannot be used as a menas of avoiding the loss of
iodine potency of iodophor solutions in urine collection bags and the
like systems with a high bio-organic load.
1 We have attempted to avoid the problem of loss of iodine
potency of iodo~hor solutions at alkaline pH by the addition of an
acid to the aqueous iodine solutions prior to the mixing thereof
with the drained body exudate. However, quite surprisingly it was
found that the addition of the acid to the aqueous iodine solutions
is effective only in the case of maleic acid or mixtures thereof
with hydrochloric acid, or phosphoric acid. Thus, aqueous iodine
solutions were prepared to contain about 2.0% titratable iodine and
the strong acids, as for example, acetic acid, citric acid, hydro-
lo chloric acid, lactic acid, maleic acid, phosphoric acid, suc~inic
acid and tartaric acid. Urine which is a common body drainage fluid
and typifies the high bio-organic load of such drainage fluids was
used as a r~presentative test material to demonstrate the value of
the present invention~
Exactly 40G ml. of pooled urine was then mixed with 30 ml.
of the resulting iodophor solutions, ayitated thoroughly to obtain
a homogeneous mixture and assayed for available iodine content. ~le
urine-iodophor-acid mixture was permitted to stand for at least 8
hours and reassayed for physical appearance, pH and iodine content.
The values obtained after standing were then compared with the initial
data (Table I).
All of the acids used, except hydrochloric acid, phosphoric
acid and maleic acid caused a marked drop in the initial iodine value
immediately after the addition of the iodophor compound. These acids
have a pKa value of less than 2 whereas the other strong acids have
a pKa value greater than 2. Within a matter of 5 to 10 minuteQ a
loss of approximately 50 mg. to 150 mg. of available iodine was ob-
served. The iodine levels for hydrochloric acid alone or in admixture
7 ~
1 with phosphoric acid were virtually unchanged, whereas only a small
iodine loss was observed in the maleic acid systems.
There was a strong iodine odor with the hydrochloric acid
mixture to reflect the formation of elemental iodine with high vapor
pressure which was not present in the other preparations.
The values obtained with the various acids which were
tested are set forth in Table I which follows:
1 ;
27~
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__ _ _ ~ _. _.. ,. .. ~_ ___
-- 10 --
7 Acidication with hydrochloric acid and phosphoric acid
caused a copious precipitate to develope immediately after mixing.
The presence of insoluble material limits the use of hydrochloric
acid as an acidifying preservative for germicidal iodine since the
separated insoluble matter may not only clog the catheter but could
adsorb urine bio-components to interfere with laboratory diagnostic
testing. The precipitate formed with phosphoric acid dispersed and
returned to solution on standing~ There was no precipitate with
the maleic acid preservative.
lo ~fter incubation for 8 hours (at room temperature) only
the hydrochloric acid, phosphoric acid and maleic acid systems still
retained iodine in the solution. The remaining acidulated prepa-
rations were virtually colorless and without iodine content~
Uxexpectedly~ the analysis of this test data established
that strong acids with a pKa value of less than 2 stabilized the
iodophor preparation in the presence of an organic urine biologic
load; whereas those strong acids with a pKa value greater than 2
failed to maintain an effective iodine level in the presence of high
organic urine biologic load. 'rhus, only the hydrochloric acid,
phosphoric acid and maleic acid preparations are useful as stabiliz-
ing acidulants for an iodine-containing germicide in the presence of
high organic urine bio-loads, with phosphoric acid being particularly
useful for open systems
The preservative activity of strong acids was also explored
with other iodophor preparations, as for example, the detergent-
iodophor system, nonoxynol-10 iodine complex, which is known in the
trade as Biopal ~ and marketed by the GAF Corporation, New York City,
New York, and Lugol's Solution which is an aqueous solution of
--11--
I:~8~
1 elemental iodine, prepared in accord with the monograph for Strong
Iodine Solution of USP XX. Lugol's Solution, or Strong Iodine
Solution, is an aqueous solution of elemental iodine which is pre
pared by dissolving one part by weight of iodine and two parts by
weight of potassium iodide in 100 ml. of water and then adding
sufficient water to briny the volume to one liter.
When 400 ml. of urine was mixed with 11% (w/v) of Biopal,
plus 3% (w/v) of the following acids, hydrochloric acid, phosphoric
acid~ maleic acid, tartaric acid and citric acid~ a precipitate was
immediately observed to form in the preparations containing h~dro-
chloric acid, tartaric acid and citric acid~ While there was initial
transient precipitation after the addition of the phosphoric acid,
this was soon reversed and went into solution on standing. After the
8 hours of incubation, the Biopal-tartaric acid and the Biopal-citric
acid preparations had virtually no detectable iodine-content9 where-
as the iodine content for Biopal preparations acidified with hydro-
chloric acid, phosphoric acid and maleic acid ranged from low to
~oderate amounts to indicate that effective germicidal activity was
present despite the high urine bio-load (Table II).
When the Lugol's Solution (iodide-iodine aqueous solution)
was studied by adding 400 ml. of urine to a sufficient volume of
aqueous iodine-iodide solution to provide 2 2% equivalent of titra-
table iodine and 3% (w/v) of a strong acid selected from the group
of hydrochloric acid, phosphoric acid, maleic acid, tartaric acid
and citric acid, only the hydrochloric acid-I.ugol's Solution pre-
paration was found to have moderate iodine content after 8 hours of
! incubation, although it did have a formed precipitate. The remaining
other acid preparations had virtually no iodine content and no
-12-
) 2~ ~
1 precipitate material (Table II). Thus, maleic acid which is useful
to preserve organic iodophor germicides is not suitable to stabilize
elemental inorganic iodine products. This response may be due to
the iodination of the unsaturated bonds of maleic acid.
o
--13--
~8~2~
TABLE II
Effectiveness of Acidulants as Stabilizers for Two Iodophors in
the Presence of an Organic Urine Biologic Load
. . ~__
Activity as
TEST PREPARATION Measure by Physical
I2 Color* Stability
BIOPAL ~ SERIES
400 ml urine + 11% Biopal + ++ ppt
3% HC1
400 ml urine + 11% Biopal + + no ppt.
3% H3 04
400 ml urine + 11~ Biopal + + no ppt.
3% maleic acid
400 ml urine + 11% Biopal + __ ppt.
3% tartaric acid
400 ml urine + 11% Biopal + __ ppt.
citric acid
IODIDE-IODINE SERIES (Lugol's Sol )
400 ml urine + 2.2% iodine + ++ ppt.
3% HCl
400 ml urine + 2.2% iodine + __ no ppt.
3% H3PO4
400 ml urine + 2.2% iodine + -- no ppt.
3% maleic acid
400 ml urine + 2.2~ iodine -~ __ no ppt.
+ 3% tartaric acid
400 ml urine + 2.2% iodine + -- no ppt.
~ 3~ citric acid
* ++-moderate, + low, - nil (pale yellow)
(a) nonoxynol-10 iodophor series
,,
o ~
Thus, it was unexpectedly found that preferred useful
stabilizers ~or iodine containing germicides in the presence of
high urine bio~loads are maleic acid, hydrochloric acid, phosphoric
acid and mixtures of these. ~Iydrochloric acid was unexpectedly
found to be an excellent stabilizer of germicidal iodine activity
in the presence of a high urine bio-burden but the presence of a
precipitate limited its use to those systems used for urine drainage
collection wherein such ~ormed precipitated matter does not inter-
fere with the catheter urine drainage.
lo Further examination of the gener~l utility of strong acids
as stabilizing agents for iodine-containing germicides in the pres-
ence of a urine load indicated that while other inorganic acids such
as nitric acid and sulfuric acid may possess a stabilizing role to
the available iodine content, these inorganic acids present other
limitations which so seriously interfere-with their use in urine-
collection systems as to render these aci.ds useless. Thus, for
example, there is a strong vapor of elemental iodine present when
nitric and sulfuric acids are used. The .iodine vapors are apparent
and iodine may reflux into the kidney from the urine collection
system to be a potential source of injury as well as to injure the
surrounding surfaces. When hydrochloric acid was used the known
volatility of hydrochloric acid presented a problem of its own
volatilization to render such use a problem in the closed system
while preserving the iodine content. However, hydrochloric acid is
of value in the open collection system wherein refluxing of halogen
vapors does not occur and ~e strong acid properties of hydrochloric
acid is not an environmental problem.
Y We have further found that maleic acid and phosphoric acid
-15-
7 ~
1 have preferred properties and can be used to stabilize the germi-
cidal iodine content in the presence of a high urine biologic load
even over periods as long as 8 hours, which is the maximum period
before changing the urine collection bag when an in-dwelling
catheter is used. Furthermore, we have found that hydrochloric acid
is useful for certain systems as well as for the inorganic iodine
germicide. Other organic acids such as acetic acid, citric acid,
lactic acid, succinic acid and tartaric acid failed to stabilize
the iodine content of the different iodine-containing germicides and
therefore although closely related in chemical structure and chemical
~roperties to maleic acid, these are essentially of no value.
In order to demonstrate the scope of utility for maleic
acid as a s-tabilizing preservative for iodophor preparations used in
degerming body exudate urine drainage collection bags, a series of
solutions of maleic acid were prepared and mixed with 400 ml. of
urine and a sufficient amount of povidone-iodine solution to provide
2% available iodine, the range in the amount of maleic acid used was
from 2% to 6% (w/v). The pH of these preparations was measured and
the observations were made of the length of time wherein the iodine
content was found to be present. The results of this study are
reported in Table III.
The results of this test confirm that the addition of at
least 2% maleic acid to an iodophor preparation is sufficiently
capable of preserving iodine germicidal activity even when large
amounts of urine are present to maintain an essentially germ-free
sanitized urine pool. A concentration of 3% maleic acid is pr~ferred
and the use of additional amounts of maleic acid above 3% (w/v) does
not improve the effective degerming properties of the product.
- -16-
2 7 ,~
1 However, lar~er amo~nts of maleic acid may be found useful for
special use conditions as for example when genito-urinary infection
is present or significant bleeding occurs.
,,
1 1 8~72
Table III
The Range of Efficacy of Maleic Acid in Preserving Iodophor Potency
in the Presence of High Urine Bio-Load
Initial Residual
'lolume Amount Amount Available Available lodine
Human Iodine Maleic Acid Iodine Content After 24
Urine + Solution Added % (w/v) Observation Content Hr. Study Period
400 ml + 60 ml none No iodine color 1.3 mg/ml Nil
(control) after 24 hrs.
400 ml ~ 45 ml none No iodine color 1.35 mg/ml Nil
(control) after 12 hrs.
(pH 3.55)
400 ml + 30 ml none No iodine color 1.40 ml/ml Nil
(control) after 8 hrs.
400 ml + 30 ml 2% Slight iodine 1.40 mg/ml < 0.1 mg/ml
color after
24 hrs.
(pH 2.95)
400 ml + 30 ml 3% Good iodine 1.40 mg/ml 0.5 mg/ml
color after
24 hrs.
(pH 2.85)
400 ml ~ 30 ml 4% Good iodine 1.40 mg/ml 0.5 mg/ml
color after
24 hrs.
(pH 2.65)
400 ml + 30 ml 6% Good iodine 1040 mg/ml 0.5 mg/ml
color after
24 hrs.
(pH 2045)
_ _ _ _
q7 2
1 The impact of precipitate formation was explored and it
was found that when phosphoric acid and/or hydrochloric acid is
combined with the maleic acid, so that an effective concentration
of these acids is equivalent to at least 2% by weight/volume of
the combined acids, then immediate precipitation was avoided and
effective iodine stabilization occurred.
When it is desired to stabilize an iodine-containing
germicide solution in the presence of a high urine bio-load in
order to sanitize the urine collected in the catheter drainage
collection ba~, then a germicidal solution is prepared by dissolving
30 gm. of povidone-iodine USP in 80 gm. of purified water and 3 gm.
of maleic acid is added and the volume brought to 100 ml. Approxi-
mately 30 ml. of this solution is added to the empty urine drainage
collection bag and connected into the system. When urine samples
are removed to determine the presence of microorganisrns to demon-
strate the efficacy of the system, even prior to emptying the bag
after 8 hours of drainage, the urine will be found to be essentially
sterile.
Over the usual 8 hour period that urine drains into the
collection bag, the volume of fluid increases so that the stabilized
iodophor germicide solution, as described herein, is at full iodine
strength at the time the drainage period starts, but may be diluted
to 4% of the original strength after 8 hours since the mean urine
volume in the collection system after 8 hours is approximately 840
ml. (average). The mean and standard deviation of urine volumes
determined for 253 urine collection bags was 840 ml. + 450 ml. with
an average iodophor iodiné germicide concentration after 8 hours of
30 x 100 or 4% or original strength.
840
--19--
~ ~ 8 ~
1 ~le results of a controlled study of the microbicidal
efficacy of an iodophor-maleic acid preserved collection system in
21 patients is reported in Table IV. The average volume of urine
collected from the patients was 840 ml. with a range of from 100 ml.
to 3430 ml. The microbial and pH testing of the collected urine
was conducted in the usual manner and demonstrated the acid pH
present throughout and that the available iodine content was pre-
served and was sufficient to maintain a virtually sterile urine
collection environment during the entire catheterization and urine
lo drainage period.
The pH of the urine in the collection bag averaged pH 3.6
with a range of from pH 2.2 to pH 4.3 over the entire study period,
while the pH of the bladder urine was found to average pH 6.2 with
a range of from pH 5.8 to pH 7.1 for the same period. Thus the
maintenance of the acid pH reflects the excellent stabilizing
properties of the new preparations. Results are reported in Table
IV .
The microbiological testing conducted in accord with the
methods known in the art, established that the urine samples taken
from the urine collecting bags treated with the new preparations
during 8 hours of urine drainage were essentially sterile in contrast
to the presence of microorganisms such as yeast cells, E~ coli and
Pseudomonas aeruginosa present in the control group where no
stabilized iodine germicidal solution was added to the collection
bag.
When a sample of bladder urine was obtained and micro-
biologically studied, two of the subjects Nos. 6 and 12, were found
to have E. coli present and Pseudomonas mirabilis in the bladder
-20-
0 2~ ~
1 urine samples because of an upper urinary tract infection both these
organisms were destroyed in the treated urine bag collecting system.
-21-
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-- 22 --
2~
1 For the control group, E. coli and Pseudomonas aeruginosa
were found in bladder urine but no yeast cells; all of these were
found in the urine collecting bag. Thi~ study cl~arly demonstrates
that an iodine germicidal preparation stabilized with maleic acid
is capable of rendering the urine in the catheter drainage collec-
tion bag germ-free thereby reducing -the chance for inf~ction during
and after in-dwelling catheterization.
In a similar manner, the degerming of the fluia exudate
drained post-operatively after surgical intervention in gallbladder
lo disease is accomplished by adding to the container vessel a volume
of from 10 ml. to 40 ml. of a stock iodophor germicidal solution
prepared by dissolving 30 gm. of povidone-iodine USP in 80 gm. of
purified water and adding thereto from 1 gm. to 4 gms. of maleic
acid and the volume brought to 100 ml.
In place of the povidone-iodine USP there may be substi-
tuted a sufficient quantity of the surfactant iodophor preparation
nonoxynol iodine complex, which is known in the art as Biopal and
which is available as an article of co~nerce from the GAF Corporation,
New York, U.S.A., in an amount sufficient to provide 2% (w/vl of
titratable iodine or povidone-iodine aqueous solution to provide 2%
titratable iodine (w/v). For the preparation of all of these stock
solutions, the concentration of maleic acid used will range from 1%
to 4% (w/v) depending on the anticipated volume and bio-organic load
of the particular exudate drainage fluid being collected.
The exact volume of the iodophor germicidal stock solution
to be added to the fluid drainage vessel will depend on the bio-
organic load and the volume of fluid to be degermed. If the volume
is small and the organic load light, then a volume of about 10 ml.
b ~8~'7~
1 of the selected stock solution is used, but when the drainage volume
is large and the organic load hiyh, then 40 ml. of the stock solution
is used to achieve degerming over an 8 hour period. The fluid volume
of the drainage solution, as well as the degree of bio-organic load
present is readily discernible to one trained in the art upon in-
spection of the vessel contents and detection of odor.
When the contents of the chest cavity drainage collection
vessel is intended to be degermed, then a volume of between 20 ml.
and 40 ml. of the iodophor germicidal stock solution prepared, as
descFibed above, is used. The presence of blood serous exudate and
microbial contaminents will direct that the higher volume of 40 ml.
of the germicidal stock solution to be added to the container while
lesser degrees of organic material evident in the drainage fluid
will require the smaller amounts of stock solution.
While-generally-the same amounts of th-e iodophor maleic
acid containing stock solution are used, as described above for
urine bag degerming to degerm the contents of the vessel receiving
the exudate from the gallbladder drainage systems and chest cavity
drainage systems, it will be found that smaller amounts of the
20 detergent iodophor active substance will be required. However, a
preferred stock solution is one that is prepared to provide 2% (w/v)
titratablè iodine and to contain 3% of maleic acid (w/v) with a
preferred volume of the stock solution to be added will be 30 cc.
added directly to the drainage fluid container to achieve an 8 hour
effective degerming.
DESCRIPTION OF PREFERRED EMBODIMENTS
The following examples are given to further illustrate
the invention. The scope of the invention is not, however, meant to
-24-
t7 2
1 be limited to the specific details of the examples.
XAMPLE I
In a suitable glass container is placed 80 gms. of purified
water and 20 gms. of povidone-iodine USP. The mixture is stirred
until a solution is achieved and 3 gms. of maleic acid are added.
When the maleic acid has dissolved, sufficient water is added to
bring the volume to 100 ml. thus forming a 20% solution of the
iodophor germicide, povidone-iodine (w/v) and maleic acid 3% (w/v~.
Thirty (30) cc. of this solution is then added to the body exudate
lo drainage collection container in order to render the colhection
vessel contents virtually sterile over the common collection period
of about 8 hours.
EXAMPLE 2
In place of the povidone-iodine used in Example 1, there
is added a sufficient quantity of a povidone-iodine aqueous solution
to provide the equivalent amount of titratable iodine to the drainage `
collection vessel and 2% (w/v) of maleic acid are added to the
povidone-iodine solution. The samples of the drainage contents
obtained after 8 hours of drainage are virtually sterile.
EXAMPLE 3
In place o~ the iodophor germicide used in Examples 1 and
2 above, there is substituted a sufficient quantity of the aqueous
iodine solution described in the U.S. Pharmacopeia (20th Ed., pO 406),
and which is known as Iodine Topical Solution or 5trong Iodine
Solution, to provide an equivalent iodine content to that obtained
from the iodophor used in Examples 1 and 2 above. A volume of the
iodine solution, sufficient to provide at least 2% (w/v) of available
or titratable iodine and from 2% to 3% (w/v) of maleic acid is then
-25-
7 2
1 added to the urine collection bag. Samples of the drainage fluids
taken over appropriate periods will be found to be virtually free
of microorganisms.
EXAMPLE 4
When a surfactant iodophor preparation is desired to be
used to render germ-free the contents of the urine co]lection bag
then the detergent iodophor, nonoxynol-iodine comples, which is
known in the art as Biopal and marketed by the GAF Corporation, New
York, New York, may be mixed with a sufficient amount of maleic acid
lo to prpvide at least 2% (w/v) and the whole is dissolved in sufficient
distilled water to provide 2% (wjv) titratable iodine. Ahout 30 ml
of this solution will be found sufficient to degerm the urine
collected in the catheter drainage bags.
EXAMPLE 5
When an iodophor germicidal preparation is desired to be
used to degerm the contents of a urine collection bag, then 20 gm.
of povidone-iodine USP are dissolved in about 90 ~m. of purified
water and 3 gm. of maleic acid added to this solution. Sufficient
water is then added to bring the volume to 100 ml. thus forming a
20% solution of the non-surfactant iodophor germicide povidone~iodine
(w/v) and maleic acid 3% (w/v).
In place of the povidone-iodine ~SP~described above there
may be added a sufficient quantity of povidone-iodine aqueous solution
to provide an equivalent amount of titratable iodine (2% w/v) to the
urine drainage collection bag and 2% (w/v) of maleic acid is added to
the povidone-iodine solution before adding to the urine drainage
collection bag.
The urine samples obtained after 8 hours of urine drainage
are virtually sterile when either povidone-iodine USP and maleic acid
1 stock solution or povidone-iodine aqueous solution and maleic acid
are used.
In place of the iodophor germicide povidon~-iodine used
to prepare the stock solution as described above, there is substi
tuted a sufficient quantity of a~ueous iodine solution which is
descri~ed in the U.S. Pharmacopeia as Iodine Topical Solution or
Strong Iodine Solution, to provide an equivalent iodine content to
that obtained from the iodophor compound. An equi~alent volume of
the iodine stock solution to provide at least 2% titratable iodine
lo and containing from 2% to 3% of maleic acid i5 added to the urine
collection bag.
When 30 cc. of this stock solution is added to the urine
drainage collection bagl the contents of the collection bag remain
virtually sterile over a common continuous collection period of about
8 hours.
EXAMPLE 6
When it is desired to degerm the contents of a gallbladder
drainage collection vessel, then between 10 cc. and 4~ cc. of an
iodine containing germicidal stock solution is prepared to contain
20 20% (w/v) of povidone-iodine USP or nonoxynol-iodine comples, which
is`known in the art as Biopal, to provide at least 2% (w/v) of
titratable iodine and from 1% to 4% of maleic acid (w/v).
I~e aqueous solution described in the U.S. Pharmacopeia
as Iodine Topical Solution may be used in place of the iodophor to
prepare the stock solution and is used in an amount to provide at
least 2% (w/v) o~ titratable iodine and to contain from 2% to 4~/0 of
maleic acid is prepared.
An amount of from 10 ml. to 30 ml, of this tock solution
will be found to be sufficient to degerm the gallbladder exudate
-27-
~ ~v~
1 collectiorl vessel over a period of from 6 to 12 hours.
FXAMP~E 7
When it is desired to degerm the contents of the chest
cavity drainage collection vessel then any of the germicidal stock
solutions prepared as described in Examples 1 through 5 above con-
taining either a non-suxfactant or a surfactant or an aqueous
iodine solution and maleic acid may be used. When the drainage
exudate fluid contains a large proportion of blood then approxi-
mately 30 ml. to 40 ml. of the stock solution is used to degerm
lo the dr,ainage collection vessel conte~ts but in the absence of a
large amount of serous and bio-organic exudate, smaller amounts
such as 20 ml. of the iodine containing germicide stock solution
will provide adequate degerming of the contents of the chest cavity
drainage collection vessel.
EXAMPLE 8
In place of the maleic acid used in Examples 1 through 7
above, there may be substituted, in part, hydrochloric acid and/or
phosphoric acid in sufficient amounts such that the total amount of
combined acids which is present in the iodophor solution, is not
less that at least 2% (w/v).
In all of the preparations described above, the pH of the
initially used solution does not exceed about 3Ø
While the invention has been described in particular with
respect to specific compositions and specific collection systems, it
is apparent that variations and modifications of the invention can be
made without departing from the spirit and scope of the invention.
-28-
