JP2021532182A - Ready-to-use, finally sterile packaging and usage for surgical disinfectants - Google Patents

Abstract

Sufficient to provide an initial non-toxic concentration of povidone iodine above the minimum effective concentration of available iodine and to provide donor iodine after gamma irradiation to stabilize povidone iodine and maintain the minimum effective concentration of available iodine. A ready-to-use gamma-sterile surgical disinfectant composition comprising an amount of iodine and buffered saline.

Description

(Refer to related applications)
This application is based on US Provisional Application No. 62 / 702,863 filed July 24, 2018 and US Provisional Application No. 62 / 703,830 filed July 26, 2018. Both full texts are incorporated herein by reference.

The invention generally relates to ready-to-use sterilized surgical antiseptic and packaging for it, more specifically in the operating room. Non-toxic concentrations of iodine in terminally sterilized or sterilable packages to facilitate its use in sterile fields that do not require dilution as well as in surgical procedures that do not require initial preparation. With respect to a sterilized povidone-iodine solution.

Povidone iodine is a chemical complex of povidone, hydrogen iodide, and elemental iodine. It is a disinfectant that acts by releasing iodine, which results in the killing of a range of microorganisms. Povidone iodine is available without a doctor's prescription at an available iodine concentration of 9% to 12%.

Povidone iodine has traditionally been used for skin disinfection before and after surgery. It may be used for both disinfecting the patient's skin and disinfecting the hands of health care providers. It may be used "as is" without a physician's prescription for locally or mild wounds, but for larger wounds, surgical applications and generally to mammalian tissues, the concentration without a physician's prescription is high. Too much. In fact, povidone iodine can be toxic at concentrations greater than 3% if applied directly to mammalian tissue. Therefore, the surgeon typically reduces the concentration of povidone iodine below 3% in the operating room. This dilution requires opening the povidone iodine package in the operating room and mixing it with saline at the time of use. This is typically done outside the sterile field. This is because conventional packaging maintains the integrity of the povidone iodine solution, but is ultimately not sterile or sterile. Therefore, the povidone iodine solution is typically prepared by opening the non-sterile packaging just outside the sterile field and then passing the sterile solution through the sterile field.

This technique is effective in disinfecting the incision and reducing the likelihood of infection, but the task of mixing povidone iodine in the operating room to reduce the concentration of povidone iodine is a feeling of intraoperative illness. It tends to be scattered and a waste of precious time. What is needed is a ready-to-use solution of povidone iodine with non-toxic concentrations of povidone iodine. In addition, what is needed is to maintain the integrity of the povidone iodine solution so that the packaging can be opened and used in the sterile field without opening and / or mixing the solution outside the sterile field. However, it is a ready-to-use package that is finally sterilized (or sterilizable).

Providing low concentrations of povidone iodine solution for surgical applications is complicated by the need to use sterile solutions only. Sterile povidone iodine is required because non-sterile forms of povidone iodine are susceptible to endogenous contamination with Burkholderia cepacia and other opportunistic pathogens. However, sterilizing povidone iodine, especially with gamma rays, tends to degrade povidone iodine and generally reduces available iodine. This reduction in available iodine is acceptable for relatively high concentrations of povidone iodine found in doctor-free products, but if the concentration is reduced to less than 3%, as used in surgical applications. Or if it is reduced to less than 1%, the deterioration of povidone iodine is unacceptable. This is because it results in available iodine that drops below the minimum effective concentration.

Therefore, what is needed is a ready-to-use gamma-sterilized package containing a gamma-sterilized povidone iodine solution with an available iodine concentration above the minimum effective concentration. The present invention, among other things, meets this need.

In the following, a schematic summary of the invention is presented to provide a basic understanding of some aspects of the invention. This summary is not an extensive overview of the invention. It is not intended to identify key / important elements of the invention or to demarcate the scope of the invention. Its sole purpose is to present some of the concepts of the invention in a simplified form as a preface to a more detailed description to be presented later.

Diluted non-toxic concentrations of povidone iodine in buffered physiological saline are pharmaceutically stable by the inclusion of certain excipients, even after being sterilized by gamma irradiation as an antibacterial cleaning solution. It was unexpectedly discovered that its efficacy could be maintained. Applicants, without being bound by any particular theory or in any way, this unexpected result provides donor iodide during gamma irradiation to stabilize povidone iodine. I presume that it may be the result of iodide. More specifically, the povidone-iodine complex is initially _{formed by the reaction of elemental iodine (I 2} ) with polyvinylpyrrolidone (also known as povidone or simply PVP), as follows:

この反応は、以下の平衡定数式によって支配される。

ここで、括弧内の量は、平衡条件下の種の濃度を反映する。Ｋ_ｅｑの値は大きくなく、ポビドンヨードの水溶液は、溶液中のポビドンヨードの濃度が低下するにつれて、より多くの解離（すなわち、遊離ポビドン及び遊離ヨウ化物へのポビドンヨードの変換）を進行的に受けることが文献において知られている。このため、過去には、ポビドンヨードの適度に安定した溶液は、高濃度の溶解した錯体の使用を通じて達成されてきた。 When in the solid state, the povidone iodine complex is very stable. However, when the povidone-iodine complex dissolves in water, an equilibrium reaction occurs that causes some dissociation of the complex, producing iodide ions (I￣) as an effective degradation product. In simplified terms, the equilibrium between the povidone-iodine complex and the iodide ion can be described as follows.

This reaction is governed by the following equilibrium constant equation.

Here, the amount in parentheses reflects the concentration of the seed under equilibrium conditions. The value of K _eq is not high and the aqueous solution of povidone iodine may undergo more dissociation (ie, conversion of povidone iodine to free povidone and free iodide) as the concentration of povidone iodine in the solution decreases. Known in the literature. For this reason, in the past, moderately stable solutions of povidone iodine have been achieved through the use of high concentrations of dissolved complexes.

However, in the study of the chemical equilibrium of formula (2), the addition of extra iodide ions (in the form of potassium iodide, sodium iodide, ammonium iodide) to the aqueous solution containing the povidone iodo complex made the copper of the povidone iodine complex. By maintaining better, it is revealed that the dissociation reaction is suppressed and the solution is stabilized. In other words, the addition of additional product to the solution favors the presence of the complex. This principle is achieved in our formulation, in which we find that the aqueous solution of the povidone iodine complex is acceptable and stable, even at one-tenth the concentration present in conventional formulations. Found to maintain sex,

Furthermore, we find that the equilibrium position of formula (2) favors the additional level of the povidone-iodine complex with respect to the starting amount when the dilute formulation of our invention is sterilized by gamma ray radiation. , Shown to be further shifted. This observation can only be explained by an increase in _{the equilibrium constant value (Keq} ) for reaction (2) during the irradiation process. We used the correct ratio of povidone iodine to iodide ion in our first prepared formulation, and subsequently by sterilizing these solutions with gamma radiation, about 10 minutes compared to conventional formulations. It was found that a povidone iodine solution was obtained that was stable and effective even at a complex concentration value of magnitude 1.

Thus, in one embodiment, the invention is a ready-to-use gamma-sterile surgical disinfectant composition in which (a) an initially non-toxic concentration of povidone iodine that exceeds the minimum effective concentration of available iodine. And (b) an amount of iodide sufficient to provide donor iodine after gamma irradiation to stabilize povidone iodine and maintain the minimum effective concentration of available iodine, and (c) buffered saline. , Concerning the composition.

In another embodiment, the invention relates to a method of using the composition described above, comprising applying the composition non-locally to mammalian tissue without diluting the composition.

In yet another embodiment, the present invention is the method of preparing the composition according to claim 1, wherein (a) the composition is placed in a package and (b) a package containing the composition. Including sterilizing the package and composition by exposing the package and composition to gamma radiation, (c) while being irradiated, the iodide donates iodine to stabilize povidone iodine and the least effective iodine available. Concerning how to maintain the concentration.

In yet another embodiment, the invention relates to a package containing the above composition. In a specific embodiment, the package is a polypropylene injection bottle.

In yet another embodiment, the invention relates to a package containing a surgical disinfectant composition. In a specific embodiment, the package stabilizes povidone iodine by providing (a) an initially nontoxic concentration of povidone iodine above the minimum effective concentration of available iodine and (b) donor iodine after gamma irradiation. It also contains an amount of iodide sufficient to maintain the minimum effective concentration of iodine available and (c) buffered saline.

In yet another embodiment, the invention is a sterile package composed of (a) a radiation safe material and (b) a sterile surgical disinfectant composition contained in the package, which is (i) available. Sufficient to provide initial non-toxic concentrations of povidone iodine above the minimum effective concentration of iodine and (ii) provide donor iodine after gamma irradiation to stabilize povidone iodine and maintain the minimum effective concentration of iodine available. Concerning a ready-to-use, finally sterile disinfectant delivery system comprising a surgical disinfectant composition comprising an amount of iodine and (iii) buffered physiological saline.

In yet another embodiment, the invention comprises a bottle configured for compact storage, comprising (a) a bottle containing a closed body defining an internal cavity for receiving the contents internally. Extends along the longitudinal axis, the bottle has the maximum width when measured laterally with respect to the longitudinal axis, the bottle is asymmetric with respect to its longitudinal axis and is complementary to the outer surface of the bottle. A longitudinal recess is formed on the outer surface of the first bottle adjacent to the protrusion extending to (b) thereby allowing the pair of bottles to have the respective protrusion of each bottle into the respective recess of the other bottle. When positioned in a positioned, nested juxtaposition relationship, a pair of bottles relates to a package having a combination width of less than twice the maximum width of one bottle.

FIG. 3 is a rear perspective view of an exemplary package of bottle properties according to an exemplary embodiment of the invention.

It is a front perspective view of the bottle of FIG.

It is a right side view of the bottle of FIG.

It is a front view of the bottle of FIG.

It is a left side view of the bottle of FIG.

It is a rear view of the bottle of FIG.

It is a top view of the bottle of FIG.

It is a bottom end view of the bottle of FIG.

FIG. 3 is a top view of a pair of bottles of FIG. 1 shown in a nested juxtaposition relationship.

9 is a perspective view of a pair of nested juxtaposed bottles of FIG.

The following paragraphs describe the invention in more detail by way of example. Throughout this description, the illustrated preferred embodiments and examples should be considered as illustrations, not as limitations to the present invention. As used herein, "present invention" refers to any one and any equivalent of the embodiments of the invention described herein. Further, references to the various configurations of the "invention" must include (s) configurations in which all claimed embodiments or methods are referred to throughout the specification. Doesn't mean.

Surprisingly, the diluted non-toxic concentration of povidone iodine dissolved in a phosphate buffered saline solution containing certain excipients is pharmaceutically stable even after sterilization by gamma irradiation. Found. These solutions still maintain their efficacy as antibacterial cleaning solutions over a long period of time.

As used herein, the non-toxic concentration of povidone iodine is localized to much higher skin with respect to the surgical application of antiseptic solutions to human and other mammalian tissues. Not related to the safe level of povidone iodine for application. Therefore, the non-toxic concentration of povidone iodine is lower than the topical application. In view of this disclosure, one of ordinary skill in the art will appreciate, for example, the tissue to be disinfected, the amount of disinfectant to be used, the patient's existing condition, the ability to remove excess disinfectant, the temperature of the solution, the pH, and others. Based on these considerations, the nontoxic concentration of povidone iodine can be determined. For example, in one embodiment the non-toxic concentration of povidone iodine is 3% or less, in another embodiment the non-toxic concentration of povidone iodine is 2% or less, and in another embodiment the non-toxic concentration of povidone iodine is It is 1% or less, and in yet another embodiment, the non-toxic concentration of povidone iodine is 0.5% or less.

As used herein, the minimum effective concentration of iodine means the concentration of iodine below which its efficacy is impaired. Again, in view of this disclosure, one of ordinary skill in the art will appreciate, for example, the tissue to be disinfected, the amount of disinfectant to be used, the patient's existing condition, the ability to remove excess disinfectant, the temperature of the solution, the pH. And other considerations can be used to determine the minimum effective concentration of iodine. For example, in one embodiment, the minimum effective concentration of iodine is 0.2% or more, in one embodiment, the minimum effective concentration of iodine is 0.3% or more, and in a more specific embodiment, iodine. The minimum effective concentration of iodine is 0.4% or more.

Those skilled in the art can determine in view of the present disclosure an amount of iodide sufficient to stabilize povidone iodine to maintain the minimum effective concentration of iodine available, without undue experimentation. In general, the concentrations of povidone iodine and iodide in solution are similar, but the concentration of povidone iodine is higher. In general, as the concentration of povidone iodine decreases and / or the intensity of gamma irradiation increases, the relative concentration of iodide increases. Similarly, at higher initial concentrations of povidone iodine and / or at lower gamma radiation doses, the relative concentration of iodide decreases. Again, one of ordinary skill in the art can readily determine appropriate concentrations of povidone iodine and iodide in view of the present disclosure to provide sufficient donor iodine to maintain the minimum effective concentration of available iodine. In one embodiment, x is the concentration of povidone iodine, y is the concentration of iodide, the relative concentration is 0.1x ≦ y ≦ 2x, and in more specific embodiments 0.2x ≦. y ≦ lx, and in a more specific embodiment, 0.3x ≦ y ≦ 0.6x.

Measuring the amount of iodine in the composition is particularly important for assessing the stability of the pharmaceutical product, and spectrophotometric methods have been developed for this purpose. This method is based on the observation that the povidone iodine complex shows a peak in its absorption spectrum at 360 nm when dissolved in methanol. To perform the assay, firstly, pipetted into the cuvette of methanol spectrophotometer 3 ml _{(V initial),} after which the known microliters _{(V an added)} amount of povidone-iodine composition pipetted into the cuvette Transfer. After mixing, the absorbance of the resulting solution at 360 nm is determined. The relationship between the absorbance at 360 nm (ABS) and the concentration of povidone iodine in the analytical solution was measured and the following relationships exist over the measured absorbance range from 0.05 ABS units to 0.75 ABS units.

After converting all quantities to milliliters, the percentage ratio (w / v units) of povidone iodine initially present in the composition solution analyzed using the following relationship is determined.

In addition to povidone iodine and iodide ions, in some embodiments, the composition is added with a surfactant, salt, and other additives to adjust the surface tension, buffer / pH, viscosity, or other properties of the fluid. It may contain an agent. Those skilled in the art may identify and optimize the concentrations of these additives in view of the present disclosure without undue experimentation. For example, it is generally preferred that the solution is weakly acidic. Therefore, the selection / concentration of these additives in the preferred embodiments described below is not limited and one of ordinary skill in the art should understand that the additives and their concentrations can vary considerably within the scope of the invention. Is.

One advantage of the present invention is that the components are relatively inexpensive and commercially available. Those skilled in the art may identify various commercial sources of the components of the claimed composition in the light of this disclosure. For example, in one embodiment, the povidone iodine component of the composition is supplied as a powdered product consisting of a complex of polyvinylpyrrolidone (povidone or PVP) and iodine. For example, a povidone iodine product identified by BASF Corporation as containing povidone K30 / 06 in the composition may be used. Water-soluble iodide ion sources are also known to those of skill in the art and are commercially available. For example, the iodide ion may be any sodium iodide, potassium iodide, or ammonium iodide, to name just a few. With respect to any additive, especially the surfactant, generally any surfactant may be used, but nonionic surfactants tend to be preferred.

In one embodiment, the pharmaceutically stable composition of povidone iodine is 0.3% to 1.0% w / v povidone-iodine, 0.05% to 0.5% w / v water soluble iodide. It contains an ion source, 0.01% to 0.02% w / v surfactant, 0.9% w / v sodium chloride, and 0.1 M sodium phosphate. The pH of the composition is initially adjusted between pH 5.1-5.7 prior to gamma radiation sterilization.

In a more specific embodiment, the pharmaceutically stable composition of povidone iodine is 0.3% to 1.0% w / v povidone-iodine, 0.05% to 0.5% w / v iodine. It contains potassium iodide, 0.01% to 0.02% w / v Vitamin E TPGS, 0.9% sodium chloride, and 0.1 M sodium phosphate. The pH of the composition is initially adjusted between pH 5.1-5.7 prior to gamma radiation sterilization.

In an even more specific embodiment, the pharmaceutically stable composition of povidone iodine is 0.3% to 0.5% w / v of povidone-iodine, 0.1% to 0.3% w / v. It contains potassium iodide, 0.01% to 0.015% w / v Vitamin E TPGS, 0.9% sodium chloride, and 0.1 M sodium phosphate. The pH of the composition is initially adjusted between pH 5.2-5.7 prior to gamma radiation sterilization.

In a very specific embodiment, the composition is 0.4% w / v povidone / iodine, 0.3% w / v potassium iodide, 0.015% w / v vitamin E TPGS, 0.9. It consists of an aqueous solution containing% w / v sodium chloride and 0.1 M sodium phosphate. The pH of the composition is initially adjusted to 5.5 prior to gamma radiation sterilization.

1 to 10 are diagrams of an exemplary package 10 according to the present invention. According to the present invention, the exemplary package 10 is formed from a radiation safety material, in particular a gamma radiation safety material. In this context, a radiation safety material is one in which the contents of the package may continue to contain the contents of the package without causing an unacceptable loss of completeness of the disinfectant contained therein. A material that can be irradiated for sterilization purposes without structural damage to the package so that it can be sterilized by radiation. An unacceptable loss of disinfectant integrity is a change in the properties of the disinfectant that makes the disinfectant unsafe or unsuitable for its intended use as a disinfectant.

According to the present invention, the package 10 is gamma-rayed in order to provide a ready-to-use, finally sterilized package containing a gamma-ray sterilized povidone iodine solution having a concentration of iodine available above the minimum effective concentration. While sterilizable, it is ultimately sterilizable in that it contains a povidone iodine solution with a concentration of available iodine above the minimum effective concentration. Therefore, the finally sterile package can be introduced into the sterile field, handled and opened in the sterile field, and the sterile contents are weighed and distributed (dispensed) without compromising the integrity of the sterile field. ) Can be used to.

In this exemplary embodiment, the radiation safety material is a polypropylene material, in particular a gamma ray radiation safety polypropylene material.

The package 10 may have any suitable form, but in this exemplary embodiment, the package has the form of a bottle. Referring now to FIG. 1, the package / bottle 10 has a closed body 12 in which an internal cavity 14 for receiving the contents is defined. In the illustrated embodiment, the closed body 12 is continuous so as to completely surround the internal cavity 14. In this embodiment, the closing body 12 may be punctured to provide an opening for weighing and distributing the contents of the bottle 10. Further, the illustrated exemplary bottle 10 is tapered to include the nozzle 14 and is manually squeezed so that the contents of the bottle 10 can be weighed and distributed through the openings. It is constructed as a squirt bottle in that it is made of a flexible material that can be easily squeezed.

The opening may be provided by puncturing the nozzle with its tip 16 which, as shown in FIG. 1, comprises a recess 18 or other surface configuration that guides or facilitates the puncture of the bottle in a preferred location. good. In another embodiment, the closed body is manufactured to be substantially closed, except for the opening that forms the mouth of the bottle, and the package 10 is completely filled with the internal cavity, as best shown in FIG. Includes a matable cap 60 that can be meshed with the closing body to close. For example, a mounting structure may be provided adjacent to the tip 16 to facilitate mounting and mounting of the cap 20 on the bottle after the tip has been punctured. In the illustrated embodiment, the mounting structure includes an external thread 20 and the cap 60 includes a complementary internal thread (not shown).

The package may contain a sterile surgical disinfectant composition within its cavity. The surgical disinfectant composition provides donor iodine after gamma irradiation to stabilize the initial non-toxic concentration of povidone iodine above the minimum effective concentration of available iodine, to stabilize povidone iodine and to maintain the minimum effective concentration of available iodine. Sufficient amount of iodide, and buffered saline solution. The flexible material may be a radiation safe polypropylene material for the reasons described herein. Thus, the bottle may include a substantially closed body that terminates in a nozzle defining an opening so that manual squeezing of the relatively soft material of the body of the bottle results in the drainage of the solution from within the bottle. .. Therefore, the jet bottle may be used as an applicator device for the delivery of surgical disinfectants. The ready-to-use, finally sterilized disinfectant delivery system includes a sterilized package constructed of radiation safety material and a sterilized surgical disinfectant composition contained in the package. Thus, the disinfectant delivery system is, for example, gamma rays or other to sterilize both the package and the disinfectant solution in a single irradiation process, especially while the disinfectant solution is contained within the package. It may be sterilized by exposure to radiation.

As can be seen from FIG. 1, the closed body 12 is elongated so as to extend along the longitudinal axis indicated as AA'. Consistent with certain aspects of the invention, packages are specifically configured for compact storage, for example, when two packages are packaged in a box for shipping or storage purposes. The exemplary package 10 is configured as such, as shown in FIGS. 1-10. More specifically, as can be seen from FIGS. 1, 7, 8 and 9, the exemplary closed body / bottle 12 has its length (eg, in a cross section lateral to AA'). It is asymmetric about axis AA. The bottle has a longitudinal recess 24 extending into the outer surface 26 of the bottle 10 adjacent to a complementary longitudinal projection 28 of the outer surface 26 of the bottle, as best shown in FIGS. 1, 7 and 8. Is asymmetric to form. Recesses and bottles are hermaphroditic in that a single bottle forms complementary male and female parts that are arranged so that the bottle can mesh / nestable with itself. (hermaphroditic).

9 and 10 are top and perspective views of the pair of bottles of FIG. As can be seen from FIGS. 9 and 10, each bottle is asymmetric about its longitudinal axis so as to form a longitudinal recess. The indentation causes the bottle to have a smaller cross-sectional area than the corresponding cross-sectional area if the cross-section is symmetrical without the indentation. In addition, the shape of the indentation is hermaphroditic so that two bottles with the same (or at least almost identical but complementary in respect to the indentation) structure are arranged in a nested juxtaposition relationship. Thus, the distance between their respective longitudinal axes is greater than the corresponding distance, as can be seen from FIG. 9, if the bottle is symmetric about those axes (having a corresponding diameter or other dimension). Is also short.

As a further illustration, the bottle / body 12 has a maximum width MW measured laterally with respect to the longitudinal axis, as best shown in FIGS. 1, 7 and 9. Thus, a pair of bottles has a combined maximum width (MCW) equal to 2 MW. However, the bottles described herein have a pair of bottles in a nested juxtaposition, with each protrusion 28 of each bottle located within each recess 24 of the other bottle, as will be appreciated from FIG. When positioned in a relationship, it has a minimum combination width of less than twice the maximum width of one bottle. As a result, two of the bottles 10 are arranged in a nested relationship (eg, co-packaged) in a relatively more compact arrangement than if the bottle lacked such a recess. )be able to.

In some embodiments, the ready-to-use, finally sterile disinfectant delivery system may include two sterile packages composed of radiation safety materials. In certain embodiments, the first sterile package may contain a sterile surgical disinfectant composition and the second sterile package may contain a sterile wash solution, such as sterile saline. The two sterile packages may be included while they are in a nested juxtaposition relationship to provide a compact packaged configuration of the sterile package.

Another aspect of the invention relates to a method of using the above composition. In one embodiment, the method comprises opening the package containing the composition and applying the composition non-locally to mammalian tissue without diluting the composition. In one embodiment, the package is opened in a sterile field in the operating room.

In yet another embodiment, the invention relates to a package containing the above composition. In certain embodiments, the package is a polypropylene injection bottle.

In yet another embodiment, the invention comprises (a) placing the composition described above in a package made of a radiation safe material, eg, polypropylene, and (b) while being irradiated. The package containing the composition is exposed to gamma radiation so that the iodide donates iodine to stabilize the povidone iodine and maintain the lowest concentration of iodine available, the package and the composition contained therein. Concerning how to prepare a ready-to-use, finally sterilized package of disinfectant, including sterilizing objects.

These and other advantages may be realized according to the particular embodiments and other modifications described. It should be understood that the above description is intended to be exemplary and not limiting. The spirit of the claims and many other embodiments and modifications within the scope will be apparent to those skilled in the art after reviewing the above description. Therefore, the scope of the invention must be determined with reference to the scope of such claims, as well as the complete scope of the equivalents entitled by the appended claims.

Claims (22)

A ready-to-use gamma-ray sterilized surgical disinfectant composition
Initially non-toxic concentrations of povidone iodine above the minimum effective concentration of iodine available,
With an amount of iodide sufficient to provide donor iodine after gamma irradiation to stabilize the povidone iodine and maintain the minimum effective concentration of the available iodine.
Including buffered saline,
Composition. The composition according to claim 1, wherein the non-toxic concentration of the povidone iodine is 3% w / v or less. The composition according to claim 1, wherein the minimum effective concentration of iodine is 0.2% w / v or more. The composition according to claim 1, wherein x is the w / v concentration of the povidone iodine, y is the w / v concentration of the iodide, and 0.1x ≦ y ≦ 2x. The fourth aspect of the present invention, wherein the concentration of the povidone iodine is 0.3% to 1.0% w / v, and the concentration of the iodide is 0.05% to 0.5% w / v. Composition. The composition according to claim 1, wherein the buffered saline solution contains sodium phosphate. The composition according to claim 1, wherein the composition is weakly acidic. The composition of claim 7, wherein the composition has a pH between about 5 and about 6. A method using the composition according to claim 1.
Containing non-local application of the composition to mammalian tissue without diluting the composition.
Method. The method of claim 9, wherein the composition is applied during surgical transplantation of a prosthesis. 9. The application without dilution comprises opening the package containing the composition in a sterile field in an operating room and applying the composition directly from the package to the tissue. The method described in. 11. The method of claim 11, wherein the package is an injection bottle. A package containing a surgical disinfectant composition
Initially non-toxic concentrations of povidone iodine above the minimum effective concentration of iodine available,
With an amount of iodide sufficient to provide donor iodine after gamma irradiation to stabilize the povidone iodine and maintain the minimum effective concentration of the available iodine.
Including buffered saline,
package. 13. The package of claim 13, wherein the package comprises polypropylene. a) A sterilized package made of radiation safety material and
b) A sterile surgical disinfectant composition contained in the package.
i) The initial non-toxic concentration of povidone iodine above the minimum effective concentration of iodine available, and
ii) A sufficient amount of iodide to provide donor iodine after gamma irradiation to stabilize the povidone iodine and maintain the minimum effective concentration of the available iodine.
iii) Containing buffered saline,
Containing with surgical disinfectant composition,
Ready-to-use, finally sterile disinfectant delivery system. The ready-to-use, finally sterile disinfectant delivery system of claim 15, wherein the package comprises polypropylene. The ready-to-use, finally sterile disinfectant delivery system of claim 15, wherein both the sterile package and the sterile surgical disinfectant composition are sterile by exposure to radiation. The ready-to-use, finally sterile disinfectant delivery system of claim 15, wherein the package is asymmetric about its longitudinal axis to form a longitudinal recess. The ready-to-use, finally sterilized disinfectant delivery system of claim 18, wherein the recess is male-female. Claimed, further comprising a second injection bottle having the same main body and each recess as the injection bottle, allowing the arrangement of the injection bottle and the second injection bottle in a nested juxtaposition relationship. 18. The ready-to-use, finally sterilized disinfectant delivery system according to 18. The method for preparing the composition according to claim 1.
Placing the composition in a package and
Including exposing the package containing the composition to gamma-ray radiation to sterilize the package and the composition.
During irradiation, the iodide donates iodine to stabilize the povidone iodine and maintain the minimum effective concentration of the available iodine.
Method. A package designed for compact storage
Includes a bottle containing a closed body that defines an internal cavity for receiving the contents internally, the bottle extends along a longitudinal axis and the bottle is measured laterally with respect to the longitudinal axis. Having a maximum width, the bottle is asymmetric about its longitudinal axis and forms a longitudinal recess on the outer surface of the first bottle adjacent to a complementary longitudinal protrusion on the outer surface of the bottle.
Thereby, when the pair of bottles is positioned in a nested juxtaposition relationship in which the respective protrusions of each bottle are positioned within the respective recesses of the other bottles, the pair of bottles is one bottle. Has a combination width of less than twice the maximum width of
package.

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