CA1180272A - Stabilized iodine-containing germicidal preparations for degerming body exudates - Google Patents
Stabilized iodine-containing germicidal preparations for degerming body exudatesInfo
- Publication number
- CA1180272A CA1180272A CA000415597A CA415597A CA1180272A CA 1180272 A CA1180272 A CA 1180272A CA 000415597 A CA000415597 A CA 000415597A CA 415597 A CA415597 A CA 415597A CA 1180272 A CA1180272 A CA 1180272A
- Authority
- CA
- Canada
- Prior art keywords
- iodine
- acid
- urine
- maleic acid
- iodophor
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
Landscapes
- Agricultural Chemicals And Associated Chemicals (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
STABILIZED IODINE-CONTAINING
GERMICIDAL PREPARATIONS FOR
DEGERMING BODY EXUDATES
ABSTRACT OF THE DISCLOSURE
Iodine-containing germicidal preparations are stabilized for use even in the presence of large amounts of bio-organic matter by the use of maleic acid or mixtures of maleic acid with hydro-chloric acid or phosphoric acid, the pH of the preparation being not higher than about 3. The use of the above acid in an amount such as to provide a pH of not higher than 2.95 has the effect of stabilizing aqueous solutions of iodine and or iodophors even in the presence of high organic bio-load such as occurs with the use of in-dwelling drainage catheters as in the case of urinary drainage collection bags, gallbladder drainage collection, chest cavity drain-age collection and other body exudate collection systems.
GERMICIDAL PREPARATIONS FOR
DEGERMING BODY EXUDATES
ABSTRACT OF THE DISCLOSURE
Iodine-containing germicidal preparations are stabilized for use even in the presence of large amounts of bio-organic matter by the use of maleic acid or mixtures of maleic acid with hydro-chloric acid or phosphoric acid, the pH of the preparation being not higher than about 3. The use of the above acid in an amount such as to provide a pH of not higher than 2.95 has the effect of stabilizing aqueous solutions of iodine and or iodophors even in the presence of high organic bio-load such as occurs with the use of in-dwelling drainage catheters as in the case of urinary drainage collection bags, gallbladder drainage collection, chest cavity drain-age collection and other body exudate collection systems.
Description
`\
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~
_ . . ~--~ ! ~ r O ~O .~ .~.~ ! ` .~ .~ j .~
~ ~ ~ ~ ~: ~: s~ I ~
~: ~ O o a) o o o o o a) o a) o o I o ~
O ~ ~ ~1 ~ .,1 ~) ~ 1- ,1 ~ ~1 ~ ~ ,~
~ ~ ~ -1) ~~ t~ 0 ~5 O (~1 o~' a) o ~ I o ~ ~ ~ :~ ~ ~ ~, ~1 t) ~ ~ V~ ~ U~-~ ~ ~ ~ ~1 ~ ,1 ~-~1 ~ ~ J ~~ O ~ O Q~ O 1~ O P~ O ~ O ~1 0 Q~
d O ~ ~ ~ ~ ~ ~ r-l U~ U~-~J U~ ~ ~
h U~ rl 3 t~ 3 0 t) ~) ~) O t) O
u~ I~J PJ O ~JO a) 3 a) 3 a) 3 0 3 0 3 a) 3 0 3 h O ~-,1 ~ ~h 5~ 0 4 O 1~O ~1 O ~1 O ~ O s~ o s~
::~ O ~:4 ~ ~ Q Q~Q ~ ~1 ~ ~ ~1 ~ ~1 ~ ~1 ~ ~ ~1 O ~ Q~ O O
3 ~j h h ~ ~H~ ~ a) 4~a) 4~ a) ~H a) ~11 a) ~1 o ~1 a) '~1 ~J Q Q- u~ Ou~ O ~ O ~ O~ O ~ O ~ O :>`1 O :>~ O
o~ 1l1 ~ .~
h X,C ~ a)~ a) a) a~a~ a~ a) a) a) a~ a) a) a) a) a~ a h a~ I ~ ~ a~~ a) ~ a) ~ a) ~ ~ ~ a) ~ a~ ~ ~ I ~ a O Q- ~ ~1 a) hC) h t~ h t~ h (1~ h 115 ~ ~ h ~ h I ~ h 3 h ~1h 4~ Q, 4 1 a~ ~ 4~ ~ ~ ~ 4 ~ ~1 0 O f~ ~ _ _ In D ~` CO O O ~D OC
~:~0 . . . . . . . . . .
O ~ ~ ~ ~ ~ ~ ~ ~ ~r ~ I Ln ~,~
h O ~~ ~ _ _ _ O ~:: ~ ~ ~ o ~ I~ o o o o o o o ~-~1 t~ a) . . . . . . . . .
h ~ ~1 ~: U) oo ~ o o o o o o o ~O rl ~ ~r LO ~
a) ~) ~ o .
N .,~ ~ H
- ~ - --Q h _ _ _., ~ ~ ~: ~ ~ ~: ~ ~: O
U~ ~ , O O O O O O O O ,~
a~ ~1 ,~ ,~ ,~ ., ~ , ~ ,~ ~1 ~
u~ . .~ a) ~ c) ~ ~ ~ ~ ~ ~ ~ I~ ~ a~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~
O O r~ ~ r1 ~ r-l r-l r-l r~ r l r-l U~ '~ O ~ O ~) O O O O O O ~ 0 a~ ~ u~- ~ u~- ~ 0 u~ ~ 0 0 u~ 3 ~: h ~ ~ ~ t:: ~ ~ ~: ~: O O
a)~ ~ ~ ~ . O au o a~ 3o 3o o o o 3 Q ~ ,~
~1 ~ aJ ~ ~ h hh h h h h h h h ~ O a) ~- h ~ ~ R ~ Q ~r4 r4 Q Q .4 Q , E~ ~ X~ ~ ~ ~ ~ X ~ X O ~ a~
a~. ~ h ~ h ~ h h ~1 h h h ~ ~ ,~
4-1 ~ 0 ~r~ d rl ~ td (~ ~ (1~ 1~ (U O 111 0 ~ E-~ . ~ 3 ~ 3 ~ h u~
,~ C,l u~ I_ o~ a~ ,~ ,~ ~ r~ co (~ ~C ~ O . . . . . . . . .
g ~:, ~ ~ ~ ~ ~ rY~ ~ ~r ~r ~'~ ~1 r~ ~
C) ~) H
a) 5 _ ~0 .
a~ ~
~1 ~3 o o o o o o o o o I o a~ ~ . . ! . . . . .
u I` ~ I` ~ ~ ~ t- ~ I O
~r ~ ~ Ln In ~ O~ l_ O rI rl ~ ~ ~ ~ t~
H
~3H
~ H H H H H H H H ¦ H ~1 ¦
.,1 ~ l l l l l l I I I O I
~, ~4 Ql P~ P~ Pl ~1 Pl~1 I P~ S-l I I
O ~> ~ ~> ~ ~> > ~>~:> I ~> IJ I I
P~ ~ P~ ~ ~ I ~ol I
aP ~tP o\ o~P ~1 ~ o~ G~P ~ o\ I o~ O
~1 ~ ~N ~ N ~`1 ~ 1 ~N 1 t~l ~5 ~`1 ~1 ~ tN N ~ ¦ N
+ + + u + + t) + o + + t) I
a~ ~~ ~ ~ o O h a~ a~ a) a) r~ a) a) a)- l a) I a) ~1 a u~ ~ ~:: ~~ 1:)~: h ~: o ~: O ~: ~ ~
a) ~.~, ,~ ~r ., ~ ,1 ~ ,~ ,~ ., ~ .~ ., ~ -,~ ,~ ~ j -,1 1 E~ X ~ h Oh a)h ~ h h h ~) h o h ~) ¦ h ~,~ ~ ~1 ~ P~~ ~~ h ~ ~~s t) ~
:~ ~ ~ ~ r~ ~ r~ ~ U ~ O I
d o'P~oo~o o~o o~o r~ r~
o r~ o ~o ~ o ~ o ~ o ~ o ~ O ~ I o o o o l o o I c~ o o c~ o o i O ~ o c) I
~ + ~r + I ~r + ~r + ~ + ~r + ~ + ~r + I ~ ~_ i ~ ~ j __ _ _ ~ _. _.. ,. .. ~_ ___ 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 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 ) 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 ~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 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
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~
_ . . ~--~ ! ~ r O ~O .~ .~.~ ! ` .~ .~ j .~
~ ~ ~ ~ ~: ~: s~ I ~
~: ~ O o a) o o o o o a) o a) o o I o ~
O ~ ~ ~1 ~ .,1 ~) ~ 1- ,1 ~ ~1 ~ ~ ,~
~ ~ ~ -1) ~~ t~ 0 ~5 O (~1 o~' a) o ~ I o ~ ~ ~ :~ ~ ~ ~, ~1 t) ~ ~ V~ ~ U~-~ ~ ~ ~ ~1 ~ ,1 ~-~1 ~ ~ J ~~ O ~ O Q~ O 1~ O P~ O ~ O ~1 0 Q~
d O ~ ~ ~ ~ ~ ~ r-l U~ U~-~J U~ ~ ~
h U~ rl 3 t~ 3 0 t) ~) ~) O t) O
u~ I~J PJ O ~JO a) 3 a) 3 a) 3 0 3 0 3 a) 3 0 3 h O ~-,1 ~ ~h 5~ 0 4 O 1~O ~1 O ~1 O ~ O s~ o s~
::~ O ~:4 ~ ~ Q Q~Q ~ ~1 ~ ~ ~1 ~ ~1 ~ ~1 ~ ~ ~1 O ~ Q~ O O
3 ~j h h ~ ~H~ ~ a) 4~a) 4~ a) ~H a) ~11 a) ~1 o ~1 a) '~1 ~J Q Q- u~ Ou~ O ~ O ~ O~ O ~ O ~ O :>`1 O :>~ O
o~ 1l1 ~ .~
h X,C ~ a)~ a) a) a~a~ a~ a) a) a) a~ a) a) a) a) a~ a h a~ I ~ ~ a~~ a) ~ a) ~ a) ~ ~ ~ a) ~ a~ ~ ~ I ~ a O Q- ~ ~1 a) hC) h t~ h t~ h (1~ h 115 ~ ~ h ~ h I ~ h 3 h ~1h 4~ Q, 4 1 a~ ~ 4~ ~ ~ ~ 4 ~ ~1 0 O f~ ~ _ _ In D ~` CO O O ~D OC
~:~0 . . . . . . . . . .
O ~ ~ ~ ~ ~ ~ ~ ~ ~r ~ I Ln ~,~
h O ~~ ~ _ _ _ O ~:: ~ ~ ~ o ~ I~ o o o o o o o ~-~1 t~ a) . . . . . . . . .
h ~ ~1 ~: U) oo ~ o o o o o o o ~O rl ~ ~r LO ~
a) ~) ~ o .
N .,~ ~ H
- ~ - --Q h _ _ _., ~ ~ ~: ~ ~ ~: ~ ~: O
U~ ~ , O O O O O O O O ,~
a~ ~1 ,~ ,~ ,~ ., ~ , ~ ,~ ~1 ~
u~ . .~ a) ~ c) ~ ~ ~ ~ ~ ~ ~ I~ ~ a~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~
O O r~ ~ r1 ~ r-l r-l r-l r~ r l r-l U~ '~ O ~ O ~) O O O O O O ~ 0 a~ ~ u~- ~ u~- ~ 0 u~ ~ 0 0 u~ 3 ~: h ~ ~ ~ t:: ~ ~ ~: ~: O O
a)~ ~ ~ ~ . O au o a~ 3o 3o o o o 3 Q ~ ,~
~1 ~ aJ ~ ~ h hh h h h h h h h ~ O a) ~- h ~ ~ R ~ Q ~r4 r4 Q Q .4 Q , E~ ~ X~ ~ ~ ~ ~ X ~ X O ~ a~
a~. ~ h ~ h ~ h h ~1 h h h ~ ~ ,~
4-1 ~ 0 ~r~ d rl ~ td (~ ~ (1~ 1~ (U O 111 0 ~ E-~ . ~ 3 ~ 3 ~ h u~
,~ C,l u~ I_ o~ a~ ,~ ,~ ~ r~ co (~ ~C ~ O . . . . . . . . .
g ~:, ~ ~ ~ ~ ~ rY~ ~ ~r ~r ~'~ ~1 r~ ~
C) ~) H
a) 5 _ ~0 .
a~ ~
~1 ~3 o o o o o o o o o I o a~ ~ . . ! . . . . .
u I` ~ I` ~ ~ ~ t- ~ I O
~r ~ ~ Ln In ~ O~ l_ O rI rl ~ ~ ~ ~ t~
H
~3H
~ H H H H H H H H ¦ H ~1 ¦
.,1 ~ l l l l l l I I I O I
~, ~4 Ql P~ P~ Pl ~1 Pl~1 I P~ S-l I I
O ~> ~ ~> ~ ~> > ~>~:> I ~> IJ I I
P~ ~ P~ ~ ~ I ~ol I
aP ~tP o\ o~P ~1 ~ o~ G~P ~ o\ I o~ O
~1 ~ ~N ~ N ~`1 ~ 1 ~N 1 t~l ~5 ~`1 ~1 ~ tN N ~ ¦ N
+ + + u + + t) + o + + t) I
a~ ~~ ~ ~ o O h a~ a~ a) a) r~ a) a) a)- l a) I a) ~1 a u~ ~ ~:: ~~ 1:)~: h ~: o ~: O ~: ~ ~
a) ~.~, ,~ ~r ., ~ ,1 ~ ,~ ,~ ., ~ .~ ., ~ -,~ ,~ ~ j -,1 1 E~ X ~ h Oh a)h ~ h h h ~) h o h ~) ¦ h ~,~ ~ ~1 ~ P~~ ~~ h ~ ~~s t) ~
:~ ~ ~ ~ r~ ~ r~ ~ U ~ O I
d o'P~oo~o o~o o~o r~ r~
o r~ o ~o ~ o ~ o ~ o ~ o ~ O ~ I o o o o l o o I c~ o o c~ o o i O ~ o c) I
~ + ~r + I ~r + ~r + ~ + ~r + ~ + ~r + I ~ ~_ i ~ ~ j __ _ _ ~ _. _.. ,. .. ~_ ___ 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 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 ) 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 ~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 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.
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.
~ ~ 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 0 2~ ~
1 urine samples because of an upper urinary tract infection both these organisms were destroyed in the treated urine bag collecting system.
1 ~8~
f~
,1 ~ fd fd u~ (n -~1 o ~: ,~ ~:
O rl rl fV f ~ ~: ,q ~) s~ ~ ~d ,1,~ ,~
E~ ,~ o o fl) \ O ~ L' U~ fl) fV flJ~_) fD fV fV fl) O fl) fV fl~ f~ fV fl~ fV fl) fl) O
l ~ I r1 r-l r l r-l ~I r I r-l r-l r-l rl r~ r-l f~ rl fVr-l .rl rl rl rl rl rl ~ rl rl r~ rl rl \ rl r-l ~ rl~rl ~ ~ rl ~ ~) V h ~ h ~ h f~l h 4 s~ f~ f~
~ ~ ~ fV fv fVf~ fV f~ fl)fY- a) a) f~ fV a) ~ fVf~ fV ~Ln Ln v N
fV fd ~ .~ ~ o ~ ~ ~ o~ ~ .~ ~ ~ ~ ~ o ~ ~ o o ~ ,1 m O ~n ~n ~n ,~ tn ~n tn rl ~n ~n ~n u~ ~n ~n ~n ,~ ~n ~n ,~ n h O Z ~::
~1 ~rl ~ f~
~ ~C ~) f~ fd v ~ .
~ r~l fV u) O ,~
E~
~n ~::
fd 3 ~ ~ fd fv ~d ,~ ~ O O E3 ~ ~ f~d f~ .~ .~r-l ~ ~; f:l .~ ~) fa O H m ~ h ~ h fd 4~ . ~ E~ ~ O fV O fl) ~ fv ~ ~ u~ s~
~1~--I 1:l fV fD fV fV fV fV fV fV fl1 fV fV fV fl) W fd a) fV ~ fV
fd ~rl F O r-l --1 ~1 ~ ~1 ~ ~1 ~ ~1 ~I r-l r-l ~1 f~ f,~ fV ~ H . . . ~1 r~;
:~ fd S~ ~ ~ .,~ .,~ rl .~ .~ .,~ rl rl ,1 ~1 ,1 rl rl ~ ~ ~ rJ W -1 ~ ~ P~ 'I f~o ~
m~ ~a h h h S~ h s~ h h h ~ h h h \ ~ h h h \ fd ~1 H fV fl) fV fV fV fV fV fV fV fD fV fV a) O ~r fD fr) fV f` Lr~ fX~ fV 11~ r-l ~> rl ~ .~ I IJ ~ ~ ~ ~ ) ~ ~ Z O ~J O -1-) 0 0 0 IJ Q
H ~rd fV ~ u~ n ~n u~ ~n u~ O ~ cn ~ u~ n ~ m c~
f O ~ . ~ E~ ., o n fd ~ i Z I ~i O E~
E-~ r-l ~i ~;i U~ \
O O . H U~
~n f~ X ~ H ,-1 fD ~ f H > ,-1 h . E~ f~ f~
H V !~! . O ~-1 fV ~ fd o rd Ni f~ m ~ f~ f~O f~ ,~ f~ f~ f~ f Ln fY, f.~ er I f~i ~ f~ f~ ,1 o f~l f.~ o ~
,~ .,,.,, i . . . . . . . . . . . . . o . . . . . . . . .
~1~I: h L~ O ~O ~ Lt~ ~O ~D ~O
r~4 ,4~) O C~ V
~n f~; f~ fd f~ fl~
rd ~v E~ *
o m ~ E~ f~ f~ ~r f~ fO ~ f~ O f~f~l O f~l ~D z f;O f~ fX) O O fY. f~ ,~ O
rl U~ ~ ~ o ..... ,, ... , fd :~ ~ ~ f~l fr) f~ fr) fr) fr) ~r fr) fr) fY) f~ ~r fr~ fr~ ~ ~ o u~ D i) t) ~ f~
rl h 4~ . rd ,-i ~ h fl Ed ~ S~ ft~ . fV
fd o o o o o o f~ o f~ ~ o o o o o o o fV f O ~ O U~ O ~ O O O O O f~l ~ f~ O O f~ O f ~r o o ~r f~ rf ~ d' f~ In o o o o u~ ~ o o ~ o ~ f~ f ~r 1` f~l r~ ,C rd ~ ~I f ,~ ~> fN ,~ f~ ,~ ~-1 fN f~ fN fN ,~
h U h F
W ~- I I 1 1 1 1 1 1 1 1 1 1 1 ~-- I I I I I I I l l ~ ~ ooo ooooo ooo oo oooooooo o fd ~ fd o ~ o o o ~ o ~o u~ fr) ~r o ~r f~ o u~ f~ fJ~
m ~ m fr, ,, fY, ,, ~ f.~l U. f.~l ~r f.
, ,~ ,~
~ fV~ ..
O f. t) h fV
V
~ tJ~-r~ R fd fd ~ ,~ f~J f`~) ~D r o ,-i f."l q~f~ ~ f fS~ f~ ~D f o s~
~ r-l r-i r-l r-l r-l r~r-l f~l r-1 r~ r-l fN fD
~ U~ Z
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 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.
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.
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 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.
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.
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.
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 ~ ~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.
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.
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.
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.
~ ~ 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 0 2~ ~
1 urine samples because of an upper urinary tract infection both these organisms were destroyed in the treated urine bag collecting system.
1 ~8~
f~
,1 ~ fd fd u~ (n -~1 o ~: ,~ ~:
O rl rl fV f ~ ~: ,q ~) s~ ~ ~d ,1,~ ,~
E~ ,~ o o fl) \ O ~ L' U~ fl) fV flJ~_) fD fV fV fl) O fl) fV fl~ f~ fV fl~ fV fl) fl) O
l ~ I r1 r-l r l r-l ~I r I r-l r-l r-l rl r~ r-l f~ rl fVr-l .rl rl rl rl rl rl ~ rl rl r~ rl rl \ rl r-l ~ rl~rl ~ ~ rl ~ ~) V h ~ h ~ h f~l h 4 s~ f~ f~
~ ~ ~ fV fv fVf~ fV f~ fl)fY- a) a) f~ fV a) ~ fVf~ fV ~Ln Ln v N
fV fd ~ .~ ~ o ~ ~ ~ o~ ~ .~ ~ ~ ~ ~ o ~ ~ o o ~ ,1 m O ~n ~n ~n ,~ tn ~n tn rl ~n ~n ~n u~ ~n ~n ~n ,~ ~n ~n ,~ n h O Z ~::
~1 ~rl ~ f~
~ ~C ~) f~ fd v ~ .
~ r~l fV u) O ,~
E~
~n ~::
fd 3 ~ ~ fd fv ~d ,~ ~ O O E3 ~ ~ f~d f~ .~ .~r-l ~ ~; f:l .~ ~) fa O H m ~ h ~ h fd 4~ . ~ E~ ~ O fV O fl) ~ fv ~ ~ u~ s~
~1~--I 1:l fV fD fV fV fV fV fV fV fl1 fV fV fV fl) W fd a) fV ~ fV
fd ~rl F O r-l --1 ~1 ~ ~1 ~ ~1 ~ ~1 ~I r-l r-l ~1 f~ f,~ fV ~ H . . . ~1 r~;
:~ fd S~ ~ ~ .,~ .,~ rl .~ .~ .,~ rl rl ,1 ~1 ,1 rl rl ~ ~ ~ rJ W -1 ~ ~ P~ 'I f~o ~
m~ ~a h h h S~ h s~ h h h ~ h h h \ ~ h h h \ fd ~1 H fV fl) fV fV fV fV fV fV fV fD fV fV a) O ~r fD fr) fV f` Lr~ fX~ fV 11~ r-l ~> rl ~ .~ I IJ ~ ~ ~ ~ ) ~ ~ Z O ~J O -1-) 0 0 0 IJ Q
H ~rd fV ~ u~ n ~n u~ ~n u~ O ~ cn ~ u~ n ~ m c~
f O ~ . ~ E~ ., o n fd ~ i Z I ~i O E~
E-~ r-l ~i ~;i U~ \
O O . H U~
~n f~ X ~ H ,-1 fD ~ f H > ,-1 h . E~ f~ f~
H V !~! . O ~-1 fV ~ fd o rd Ni f~ m ~ f~ f~O f~ ,~ f~ f~ f~ f Ln fY, f.~ er I f~i ~ f~ f~ ,1 o f~l f.~ o ~
,~ .,,.,, i . . . . . . . . . . . . . o . . . . . . . . .
~1~I: h L~ O ~O ~ Lt~ ~O ~D ~O
r~4 ,4~) O C~ V
~n f~; f~ fd f~ fl~
rd ~v E~ *
o m ~ E~ f~ f~ ~r f~ fO ~ f~ O f~f~l O f~l ~D z f;O f~ fX) O O fY. f~ ,~ O
rl U~ ~ ~ o ..... ,, ... , fd :~ ~ ~ f~l fr) f~ fr) fr) fr) ~r fr) fr) fY) f~ ~r fr~ fr~ ~ ~ o u~ D i) t) ~ f~
rl h 4~ . rd ,-i ~ h fl Ed ~ S~ ft~ . fV
fd o o o o o o f~ o f~ ~ o o o o o o o fV f O ~ O U~ O ~ O O O O O f~l ~ f~ O O f~ O f ~r o o ~r f~ rf ~ d' f~ In o o o o u~ ~ o o ~ o ~ f~ f ~r 1` f~l r~ ,C rd ~ ~I f ,~ ~> fN ,~ f~ ,~ ~-1 fN f~ fN fN ,~
h U h F
W ~- I I 1 1 1 1 1 1 1 1 1 1 1 ~-- I I I I I I I l l ~ ~ ooo ooooo ooo oo oooooooo o fd ~ fd o ~ o o o ~ o ~o u~ fr) ~r o ~r f~ o u~ f~ fJ~
m ~ m fr, ,, fY, ,, ~ f.~l U. f.~l ~r f.
, ,~ ,~
~ fV~ ..
O f. t) h fV
V
~ tJ~-r~ R fd fd ~ ,~ f~J f`~) ~D r o ,-i f."l q~f~ ~ f fS~ f~ ~D f o s~
~ r-l r-i r-l r-l r-l r~r-l f~l r-1 r~ r-l fN fD
~ U~ Z
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 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.
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.
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 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.
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.
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.
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 ~ ~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.
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.
Claims (17)
THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE PROPERTY OR PRIVILEGE
IS CLAIMED ARE DEFINED AS FOLLOWS:
1. Germicidal preparation for use in the presence of bio-organic matter, said preparation comprising as an iodine-contain-ing germicide polyvinylpyrrolidone-iodine or an iodophor formed by combining iodine with a detergent compounds and a stabilizing effective amount of maleic acid or a mixture of maleic acid with hydrochloric acid or phosphoric acid, the pH of the preparation being not higher than about 3Ø
2. Composition according to claim 1 wherein the acid is present in an amount of at least about 2% weight to volume.
3. Composition according to claim 1 wherein the acid is present in an amount of about 2 - 6% weight to volume.
4. Composition according to claim 1 wherein the acid is present in an amount of about 3% weight to volume.
5. Composition according to claim 1 wherein the germicide is polyvinylpyrrolidone-iodine.
6. Composition according to claim 1 wherein the germicide is an iodophore formed by combining iodine with a detergent compound.
7. Composition according to claim 1 wherein the acid is maleic acid alone.
8. Composition according to claim 1 wherein the acid is maleic acid mixed with hydrochloric acid or phosphoric acid.
9. Method for the stale collection of a body exudate in a drainage collection container, which comprises introducing into said container an aqueous solution of an iodine-containing germicide which is polyvinylpyrrolidone-iodine or an iodophor formed by combining iodine with a detergent compound and a stabilizing effective amount of maleic acid or a mixture of maleic acid with hydrochloric acid or phosphoric acid, the pH of the aqueous solution being not higher than about 3Ø
10. Method according to claim 9 wherein the body exudate drainage collection container is a urine drainage collection con-tainer.
11. Method according to claim 9 wherein the body exudate drainage collection container is a gallbladder drainage collection container.
12. Method according to claim 9 wherein said body exudate drainage collection container is a chest cavity drainage collection container.
13. Method according to claim 9 wherein the amount of aqueous solution introduced into the body exudate drainage collection container is at least about 10 ml.
14. Method according to claim 9 wherein the acid is present in the solution in amount of at least about 2% weight to volume.
15. Method according to claim 9 wherein the amount of acid is about 2 - 6% weight to volume.
16. Method according to claim 9 wherein said iodine-containing germicide is polyvinylpyrrolidone-iodine.
17. Method according to claim g wherein said iodine-containing germicide is an iodophor formed by combining iodine with a detergent compound.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US32173881A | 1981-11-16 | 1981-11-16 | |
| US321,738 | 1981-11-16 | ||
| US440,408 | 1982-11-09 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1180272A true CA1180272A (en) | 1985-01-02 |
Family
ID=23251813
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000415597A Expired CA1180272A (en) | 1981-11-16 | 1982-11-15 | Stabilized iodine-containing germicidal preparations for degerming body exudates |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA1180272A (en) |
-
1982
- 1982-11-15 CA CA000415597A patent/CA1180272A/en not_active Expired
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Fleischer et al. | Povidone-iodine in antisepsis–state of the art | |
| US5071648A (en) | Polymeric broad-spectrum antimicrobial materials | |
| CN1816330B (en) | Antiseptic compositions, methods and systems | |
| EP0662783B1 (en) | Antimicrobial composition and method of preparation | |
| US20120189493A1 (en) | Anti-microbial systems and methods | |
| EP0391741B1 (en) | Polymeric broad-spectrum antimicrobial materials | |
| Lawrence | The use of iodine as an antiseptic agent | |
| Burlibasa et al. | Halogen compounds-theoretical, physiological and practical aspects regarding the decontamination, disinfection and sterilisation of instruments and biomaterials in dental medicine practice | |
| US5962029A (en) | Iodine germicides that continuously generate free molecular iodine | |
| CN102614113A (en) | Compound washing-free disinfection gel | |
| Rani et al. | Irrigation with N, N-dichloro-2, 2-dimethyltaurine (NVC-422) in a citrate buffer maintains urinary catheter patency in vitro and prevents encrustation by Proteus mirabilis | |
| CA1180272A (en) | Stabilized iodine-containing germicidal preparations for degerming body exudates | |
| EP0079782B1 (en) | Stabilized iodine-containing germicidal preparation | |
| CA1039183A (en) | Oxydiacetaldehyde compositions and processes | |
| US4867897A (en) | Germicidal iodophor composition | |
| CN1889829B (en) | Antimicrobial compositions comprising polymeric stabilizers | |
| JPH0635390B2 (en) | Medicinal iodine carrier fungicide and method for producing the same | |
| RU2337715C1 (en) | Disinfectant "sonata-dez" | |
| JP4228175B2 (en) | Disinfectant composition liquid and disinfecting method | |
| US11554137B2 (en) | Composition and method for arresting blood flow and for forming a persistent microbial barrier | |
| EP0799570A1 (en) | Preparation and uses of microbicidal formulations | |
| EP0095377B1 (en) | Improvements in or relating to iodophors | |
| US6592768B1 (en) | Compositions for disinfecting wastes | |
| WO2013085502A1 (en) | Composition and method for arresting blood flow and for forming a persistent antimicrobial barrier | |
| WO2022208365A1 (en) | Cleaning and disinfecting compositions with wound-healing properties |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEC | Expiry (correction) | ||
| MKEX | Expiry |