Ready-to-use, sterilized packaging and instructions for use of surgical disinfectants.

Abstract

We provide a ready-to-use, gamma-sterilized package containing a gamma-sterilized povidone-iodine solution with an available iodine concentration exceeding the minimum effective concentration. [Solution] A ready-to-use gamma-ray sterilized surgical disinfectant composition comprising an initially non-toxic concentration of povidone-iodine exceeding the minimum effective concentration of available iodine, an amount of iodide sufficient to provide donor iodine after gamma irradiation to stabilize the povidone-iodine and maintain the minimum effective concentration of available iodine, and buffered saline.

Description

Technical Field

[0001] (Reference to Related Applications) This application claims the benefit of U.S. Provisional Application No. 62 / 702,863, filed Jul. 24, 2018, and U.S. Provisional Application No. 62 / 703,830, filed Jul. 26, 2018, the entire contents of each of which are hereby incorporated by reference herein.

[0002] The present invention generally relates to a ready-to-use sterilized surgical antiseptic and its packaging, and more specifically to facilitating its use in surgical procedures without further dilution in the operating room and within a sterile field without requiring initial preparation, and relates to a sterilized povidone-iodine solution having a non-toxic concentration of iodine in a terminally sterilized or sterilizable package.

Background Art

[0003] 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 iodine concentrations of 9% to 12%.

[0004] Povidone-iodine has traditionally been used for skin disinfection before and after surgery. It may be used for disinfecting both the patient's skin and the healthcare provider's hands. It may be used "as is" without a physician's prescription for localized or minor wounds, but for larger wounds, surgical applications, and applications to mammalian tissue in general, unprescribed concentrations are too high. In fact, povidone-iodine can be toxic at concentrations above 3% if applied directly to mammalian tissue. Therefore, surgeons typically reduce the concentration of povidone-iodine to below 3% in the operating room. This dilution requires opening the povidone-iodine packaging in the operating room and mixing it with saline solution at the time of use. This is typically done outside the sterile field because conventional packaging maintains the integrity of the povidone-iodine solution but is ultimately not sterilizable or can not be sterilized. Therefore, povidone-iodine solutions are typically prepared by opening the non-sterilized packaging just outside the sterile field and then passing a sterile solution through the sterile field.

[0005] While this technique is effective in disinfecting incisions and reducing the possibility of infection, the task of mixing povidone-iodine in the operating room to reduce its concentration tends to be a distraction and a waste of valuable time during surgery. What is needed is a ready-to-use povidone-iodine solution with a non-toxic concentration. Furthermore, what is needed is a ready-to-use package that is ultimately sterile (or sterilizable) while maintaining the integrity of the povidone-iodine solution, so that the package can be opened and used within the sterile field without the need to open the package and / or mix the solution outside the sterile field.

[0006] Providing low-concentration povidone-iodine solutions for surgical use is complicated by the requirement to use only sterile solutions. Sterile povidone-iodine is required because non-sterile forms of povidone-iodine are susceptible to endogenous contamination by B. cepacia and other opportunistic pathogens. However, sterilizing povidone-iodine, particularly with gamma rays, tends to degrade it, generally reducing the amount of available iodine. While this reduction in available iodine is acceptable for the relatively high concentrations of povidone-iodine found in over-the-counter (over-the-counter) products, if the concentration is reduced to less than 3%, or even less than 1%, as is the case for surgical use, the degradation of povidone-iodine is unacceptable because it results in available iodine falling below the minimum effective concentration. [Overview of the project] [Problems that the invention aims to solve]

[0007] 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, in particular, satisfies this need. [Means for solving the problem]

[0008] The following provides a general summary of the present invention to give a basic understanding of some aspects of the invention. This summary is not a comprehensive overview of the invention. It is not intended to identify key / important elements of the invention or to define its scope. Its sole purpose is to present some concepts of the invention in a simplified form as an introduction to the more detailed description that follows.

[0009] It was unexpectedly discovered that a diluted, non-toxic concentration of povidone-iodine in buffered saline, by including certain excipients, could be made pharmaceutically stable and retain its efficacy as an antimicrobial cleaning solution even after sterilization by gamma irradiation. Without being bound by any particular theory or limiting the scope of the claims in any way, the applicant speculates that this unexpected result may be a consequence of iodides providing donor iodine during gamma irradiation to stabilize povidone-iodine. More specifically, the povidone-iodine complex is initially formed by the reaction of elemental iodine (I2) with polyvinylpyrrolidone (also known as povidone or simply PVP), as follows:

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[0010] In its solid state, the povidone-iodine complex is very stable. However, when the povidone-iodine complex dissolves in water, an equilibrium reaction occurs in which some dissociation of the complex takes place, and iodide ions (I) are produced as effective decomposition products. ― This generates ). In simplified terms, the equilibrium between the povidone-iodine complex and the iodide ion can be described as follows:

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[0011] However, examination of the chemical equilibrium of equation (2) reveals that the addition of extra iodide ions (in the form of potassium iodide, sodium iodide, or ammonium iodide) to an aqueous solution containing the povidone-iodine complex suppresses the dissociation reaction and brings stability to the solution by better maintaining the copper content of the povidone-iodine complex. In other words, the addition of additional products to the solution favors the presence of the complex. This principle is achieved in our formulation, where we have found that the aqueous solution of the povidone-iodine complex maintains acceptable stability even at a concentration one-tenth that present in conventional formulations.

[0012] Furthermore, we showed that when the diluted formulation of our invention is sterilized by gamma radiation, the equilibrium position of equation (2) is further shifted so that the additional level of the povidone-iodine complex is favorable to the initial amount. This observation supports the equilibrium constant value (K) for reaction (2) during the irradiation process. eq This can only be explained by the increase in ). We found that by using the correct ratio of povidone-iodine to iodide ions in our initially prepared formulations, and subsequently sterilizing these solutions with gamma radiation, we obtained povidone-iodine solutions that were stable and effective even at complex concentrations about one-tenth the size of those in conventional formulations.

[0013] Accordingly, in one embodiment, the present invention relates to a ready-to-use gamma-sterilized surgical disinfectant composition comprising (a) an initially non-toxic concentration of povidone-iodine above the minimum effective concentration of available iodine, (b) a sufficient amount of iodide to provide donor iodine after gamma irradiation to stabilize the povidone-iodine and maintain the minimum effective concentration of available iodine, and (c) buffered saline.

[0014] In another embodiment, the present invention relates to a method of using the above-described composition, which includes non-local application of the composition to mammalian tissue without dilution.

[0015] In yet another embodiment, the present invention relates to a method for preparing the composition described in claim 1, comprising (a) placing the composition in a package, (b) sterilizing the package and the composition by exposing the package containing the composition to gamma radiation, and (c) during irradiation, the iodide donates iodine to stabilize the povidone-iodine and maintain a minimum effective concentration of available iodine.

[0016] In yet another embodiment, the present invention relates to a package comprising the above-described composition. In a specific embodiment, the package is a polypropylene spray bottle.

[0017] In yet another embodiment, the present invention relates to a package comprising a surgical disinfectant composition. In a specific embodiment, the package comprises (a) an initially non-toxic concentration of povidone-iodine above the minimum effective concentration of available iodine, (b) an amount of iodide sufficient to provide donor iodine after gamma irradiation to stabilize the povidone-iodine and maintain the minimum effective concentration of available iodine, and (c) buffered saline.

[0018] In yet another embodiment, the present invention relates to a ready-to-use, finally sterile disinfectant delivery system comprising (a) a sterile package made of radiation-safe material, and (b) a sterile surgical disinfectant composition contained in the package, the surgical disinfectant composition comprising (i) an initial non-toxic concentration of povidone-iodine above the minimum effective concentration of available iodine, (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 available iodine, and (iii) buffered saline.

[0019] In yet another embodiment, the present invention is a package configured for compact storage, comprising a bottle including a closed body defining an internal cavity for receiving contents therein, the bottle extending along a longitudinal axis, the bottle having a maximum width when measured in a direction transverse to the longitudinal axis, the bottle being asymmetric about its longitudinal axis, and forming a longitudinally extending recess on the outer surface of the first bottle adjacent to a longitudinally extending protrusion that extends complementarily longitudinally on the outer surface of the bottle, (b) whereby, when a pair of bottles is positioned in a nested juxtaposed relationship where each respective protrusion of each bottle is positioned within a respective recess of the other bottle, the pair of bottles has a combined width less than twice the maximum width of one bottle.

Brief Description of the Drawings

[0020] [Figure 1] It is a rear perspective view of an exemplary package of the nature of a bottle according to an exemplary embodiment of the present invention.

[0021] [Figure 2] It is a front perspective view of the bottle of FIG. 1.

[0022] [Figure 3] It is a right side view of the bottle of FIG. 1.

[0023] [Figure 4] It is a front view of the bottle of FIG. 1.

[0024] [Figure 5] It is a left side view of the bottle of FIG. 1.

[0025] [Figure 6] It is a rear view of the bottle of FIG. 1.

[0026] [Figure 7] It is a top view of the bottle of FIG. 1.

[0027] [Figure 8]This is a bottom view of the bottle in Figure 1.

[0028] [Figure 9] This is a top view of the pair of bottles shown in Figure 1, arranged in a nested juxtaposition.

[0029] [Figure 10] Figure 9 is a perspective view of a pair of nested bottles placed side by side. [Modes for carrying out the invention]

[0030] The following paragraphs describe the present invention in detail by example. Throughout this description, preferred embodiments and examples shown should be considered illustrative rather than limiting to the invention. As used herein, “present invention” refers to any one of the embodiments of the invention described herein and any equivalent thereof. Furthermore, references to various (multiple) configurations of “present invention” do not mean that throughout this specification all claimed embodiments or methods must include the (multiple) configurations to which they are referenced.

[0031] Remarkably, diluted, non-toxic concentrations of povidone-iodine dissolved in phosphate-buffered saline containing specific excipients were found to be pharmaceutically stable even after sterilization by gamma irradiation. These solutions still maintain their efficacy as antimicrobial cleaning solutions over long periods of time.

[0032] When used herein, the non-toxic concentration of povidone-iodine refers to surgical applications where the disinfectant is applied to human and other mammalian tissues, and not to safe levels of povidone-iodine for topical applications to the skin, which are far more common. Therefore, the non-toxic concentration of povidone-iodine is lower than that for topical applications. In view of this disclosure, those skilled in the art can determine the non-toxic concentration of povidone-iodine based, for example, the tissue to be disinfected, the amount of disinfectant to be used, the patient's pre-existing condition, the ability to remove excess disinfectant, the temperature and pH of the solution, and other considerations. 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; in yet another embodiment, the non-toxic concentration of povidone-iodine is 1% or less; and in yet another embodiment, the non-toxic concentration of povidone-iodine is 0.5% or less.

[0033] 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, those skilled in the art can determine the minimum effective concentration of iodine based, for example, the tissue to be disinfected, the amount of disinfectant to be used, the patient's pre-existing condition, the ability to remove excess disinfectant, the temperature and pH of the solution, and other considerations. For example, in one embodiment, the minimum effective concentration of iodine is 0.2% or higher; in one embodiment, the minimum effective concentration of iodine is 0.3% or higher; and in a more specific embodiment, the minimum effective concentration of iodine is 0.4% or higher.

[0034] A person skilled in the art, in view of this disclosure, can determine, without excessive experimentation, the amount of iodide sufficient to stabilize povidone-iodine in order to maintain the minimum effective concentration of available iodine. Generally, the concentrations of povidone-iodine and iodide in solution are similar, but the concentration of povidone-iodine is higher. Generally, as the concentration of povidone-iodine decreases and / or as the intensity of gamma irradiation increases, the relative concentration of iodide increases. Similarly, at higher initial concentrations of povidone-iodine and / or lower gamma irradiation doses, the relative concentration of iodide decreases. Again, a person skilled in the art, in view of this disclosure, can easily determine appropriate concentrations of povidone-iodine and iodide 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, and the relative concentration is 0.1x ≤ y ≤ 2x, in a more specific embodiment, 0.2x ≤ y ≤ lx, and in a more specific embodiment, 0.3x ≤ y ≤ 0.6x.

[0035] Measuring the amount of iodine in a composition is particularly important for evaluating the stability of the formulation, and spectrophotometric methods have been developed for this purpose. This method is based on the observation that when povidone-iodine complexes are dissolved in methanol, they exhibit a peak in their absorption spectrum at 360 nm. To perform the assay, first, 3 ml (V) initial Transfer the methanol (V) to the cuvette of the spectrophotometer using a pipette, and then measure the known microliters (V) added Transfer the ) amount of povidone-iodine composition to a cuvette using a pipette. After mixing, determine the absorbance of the resulting solution at 360 nm. The relationship between the absorbance (ABS) at 360 nm and the concentration of povidone-iodine in the analytical solution is measured, and the following relationship exists over the measured absorbance range from 0.05 ABS units to 0.75 ABS units.

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[0036] After converting all quantities to milliliters, the percentage ratio (in w / v units) of povidone-iodine initially present in the analyzed composition solution is determined using the following relationship.

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[0037] In addition to povidone-iodine and iodide ions, in some embodiments the composition may include surfactants, salts, and other additives to adjust the surface tension, buffering / pH, viscosity, or other properties of the fluid. Those skilled in the art will be able to determine and optimize the concentrations of these additives in view of this disclosure without excessive experimentation. For example, it is generally preferable that the solution be weakly acidic. Accordingly, the selection / concentration of these additives in the preferred embodiments described below is not limiting, and those skilled in the art should understand that the additives and their concentrations can vary considerably within the scope of the invention.

[0038] One advantage of the present invention is that its components are relatively inexpensive and commercially available. Those skilled in the art will be able to identify various commercial sources for the components of the claimed composition in 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. Sources of water-soluble iodide ions are also known to those skilled in the art and are commercially available. For example, the iodide ion may be any sodium iodide, potassium iodide, or ammonium iodide, to name a few. With respect to any additives, particularly surfactants, generally any surfactant may be used, but nonionic surfactants tend to be preferred.

[0039] In one embodiment, a pharmaceutically stable composition of povidone-iodine comprises 0.3% to 1.0% w / v povidone-iodine, 0.05% to 0.5% w / v water-soluble iodide 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 to between pH 5.1 and 5.7 before gamma radiation sterilization.

[0040] In a more specific embodiment, a pharmaceutically stable composition of povidone-iodine comprises 0.3% to 1.0% w / v povidone-iodine, 0.05% to 0.5% w / v potassium iodide, 0.01% to 0.02% w / v vitamin E TPGS, 0.9% sodium chloride, and 0.1M sodium phosphate. The pH of the composition is initially adjusted to between pH 5.1 and 5.7 before gamma radiation sterilization.

[0041] In a more specific embodiment, a pharmaceutically stable composition of povidone-iodine comprises 0.3% to 0.5% w / v povidone-iodine, 0.1% to 0.3% w / v potassium iodide, 0.01% to 0.015% w / v vitamin E TPGS, 0.9% sodium chloride, and 0.1M sodium phosphate. The pH of the composition is initially adjusted to between pH 5.2 and 5.7 before gamma-ray sterilization.

[0042] In a very specific embodiment, the composition consists of an aqueous solution containing 0.4% w / v povidone / iodine, 0.3% w / v potassium iodide, 0.015% w / v vitamin E TPGS, 0.9% w / v sodium chloride, and 0.1 M sodium phosphate. The pH of the composition is initially adjusted to 5.5 before gamma radiation sterilization.

[0043] Figures 1 to 10 illustrate exemplary packages 10 according to the present invention. According to the present invention, exemplary packages 10 are formed from radiation-safe materials, particularly gamma radiation-safe materials. In this context, radiation-safe materials are materials that can be irradiated for sterilization purposes without causing structural damage to the package, so as to allow the contents of the package to be sterilized by radiation without causing an unacceptable loss of integrity of the disinfectant contained therein, while the package may continue to contain its contents. Unacceptable loss of integrity of disinfectant is a change in the properties of the disinfectant that makes it unsafe or unsuitable for use for its intended purpose as a disinfectant.

[0044] According to the present invention, package 10 is gamma-sterilizable, while also being ultimately sterilizable in that it contains a povidone-iodine solution with a concentration of available iodine exceeding the minimum effective concentration, in order to provide a ready-to-use, ultimately sterilized package containing a gamma-sterilized povidone-iodine solution with a concentration of available iodine exceeding the minimum effective concentration. Thus, the ultimately sterilized package can be introduced into a sterile field, handled within the sterile field, and opened, and can be used to measure and dispense its sterilized contents without compromising the integrity of the sterile field.

[0045] In this exemplary embodiment, the radiation-safe material is a polypropylene material, and more particularly, a gamma-ray radiation-safe polypropylene material.

[0046] The package 10 may have any suitable form, but in this exemplary embodiment, the package has the form of a bottle. Referring here to Figure 1, the package / bottle 10 has a closing body 12 that defines an internal cavity 14 for receiving contents therein. In the illustrated embodiment, the closing body 12 is continuous so as to completely enclose the internal cavity 14. In this embodiment, the closing body 12 may be perforated to provide an opening for measuring and dispensing the contents of the bottle 10. Furthermore, the illustrated exemplary bottle 10 is configured as a squirt bottle in that it is tapered to include a nozzle 14 and is made of a flexible material that can be easily squeezed by hand so that the contents of the bottle 10 can be measured and dispensed through the opening by squeezing the body 12 by hand.

[0047] The opening may be provided by puncturing the nozzle with its tip 16, which may have a recess 18 or other surface configuration that guides or facilitates puncturing the bottle at a preferred location, as shown in Figure 1. In other embodiments, the closure body is manufactured to be substantially closed except for the opening that forms the mouth of the bottle, and the package 10 includes a matable cap 60 that can interlock with the closure body to completely close the internal cavity, as best shown in Figure 2. For example, a mounting structure may be provided adjacent to the tip 16 to facilitate the attachment of the cap 20 to 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).

[0048] The package may contain a sterile surgical disinfectant composition within its cavity. The surgical disinfectant composition includes an initial non-toxic concentration of povidone-iodine exceeding the minimum effective concentration of available iodine, an amount of iodide sufficient to provide donor iodine after gamma irradiation to stabilize the povidone-iodine and maintain the minimum effective concentration of available iodine, and buffered saline. The flexible material may be a radiation-safe polypropylene material for the reasons described herein. Accordingly, the bottle may include a substantially closed body terminating at a nozzle defining an opening, such that squeezing the relatively soft material of the bottle body by hand results in the discharge of the solution from the bottle. Accordingly, the spray bottle may be used as an applicator device for the delivery of the surgical disinfectant. A ready-to-use, finally sterile disinfectant delivery system includes a sterile package made of radiation-safe material and a sterile surgical disinfectant composition contained in the package. Accordingly, the disinfectant delivery system may be sterilized, for example, by exposure to gamma rays or other radiation, in order to sterilize both the package and the disinfectant solution in a single irradiation process while the disinfectant solution is contained within the package.

[0049] As can be seen from Figure 1, the closure body 12 is elongated so as to extend along the longitudinal axis indicated as AA'. In accordance with certain aspects of the present invention, the package is specifically configured for compact storage, for example, when two packages are packed in a box for shipping or storage purposes. An exemplary package 10 is configured in this manner, as shown in Figures 1 to 10. More specifically, as can be seen from Figures 1, 7, 8 and 9, the exemplary closure body / bottle 12 is asymmetrical with respect to its longitudinal axis AA (for example, in a cross section transverse to AA'). The bottle is asymmetrical so as to form a longitudinal recess 24 on the outer surface 26 of the bottle 10 adjacent to a complementary longitudinal projection 28 on the outer surface 26 of the bottle, as best shown in Figures 1, 7 and 8. The recess and bottle are hermaphroditic in that a single bottle forms complementary male and female parts that are arranged so that the bottles can interlock / nestable with each other.

[0050] Figures 9 and 10 are top and perspective views of the bottle pair of Figure 1. As can be seen from Figures 9 and 10, each bottle is asymmetrical with respect to its longitudinal axis, forming a longitudinally extending recess. The recess causes the bottle to have a smaller cross-sectional area than the corresponding cross-sectional area if the cross-section were symmetric without the recess. Furthermore, the shape of the recess is hermaphroditic, such that two bottles having the same (or at least nearly identical but complementary with respect to the recess) structure are placed in a nested juxtaposition, and the distance between their respective longitudinal axes is shorter than the corresponding distance if the bottles were symmetrical with respect to their axes (having corresponding diameters or other dimensions), as can be seen from Figure 9.

[0051] As a further example, the bottle / body 12 has a maximum width MW measured laterally with respect to the longitudinal axis, as best shown in Figures 1, 7, and 9. Thus, a pair of bottles has a combined maximum width (MCW) equal to 2MW. However, the bottles described herein, as can be understood from Figure 9, have a minimum combined width of less than twice the maximum width of one bottle when a pair of bottles is positioned in a nested juxtaposition relationship, with each projection 28 of one bottle located in each recess 24 of the other bottle. As a result, two of the bottles 10 can be arranged in a nested relationship (e.g., co-packaged) in a relatively more compact arrangement than when the bottles lack such recesses.

[0052] In some embodiments, a ready-to-use, ultimately sterilized disinfectant delivery system may include two sterile packages made of radiation-safe material. In certain embodiments, the first sterile package may contain a sterile surgical disinfectant composition, and the second sterile package may contain a sterile cleaning solution, such as sterile saline. The two sterile packages may be packaged together while they are nested side-by-side to provide a compact packaged configuration for the sterile package.

[0053] Another aspect of the present invention relates to a method for using the composition described above. In one embodiment, the method includes opening a package containing the composition and applying the composition non-locally to mammalian tissue without diluting it. In one embodiment, the package is opened in a sterile field in an operating room.

[0054] In yet another embodiment, the present invention relates to a package comprising the above-described composition. In a particular embodiment, the package is a polypropylene spray bottle.

[0055] In yet another embodiment, the present invention relates to a method for preparing a ready-to-use, finally sterilized package for a disinfectant, comprising: (a) placing the above-described composition in a package made of a radiation-safe material, such as polypropylene; and (b) sterilizing the package and the composition contained therein by exposing the package containing the composition to gamma radiation during irradiation such that the iodide of the composition donates iodine to stabilize the povidone-iodine and maintain the lowest possible concentration of available iodine.

[0056] These and other advantages may be realized according to the specific embodiments and other variations described. It should be understood that the above description is intended to be illustrative and not limiting. Many other embodiments and modifications within the spirit and scope of the claims will become apparent to those skilled in the art after considering the above description. Accordingly, the scope of the invention should be determined by reference to such claims, along with the full scope of the equivalents for which rights are granted by the appended claims.

Claims

1. A gamma-ray sterilized surgical disinfectant composition that is ready for immediate use, Initially non-toxic concentrations of povidone-iodine exceeding the minimum effective concentration of available iodine, 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, Buffered saline and A surfactant containing vitamin E TPGS, and Surgical disinfectant composition.

2. The surgical disinfectant composition according to claim 1, wherein the non-toxic concentration of povidone-iodine is 0.3% w / v or less.

3. The surgical disinfectant composition according to claim 1 or 2, wherein the minimum effective concentration of the iodide is 0.2% w / v or more.

4. The surgical disinfectant composition according to any one of claims 1 to 3, wherein x is the w / v concentration of povidone-iodine, y is the w / v concentration of the iodide, and 0.1x < y < 2x.

5. The surgical disinfectant composition according to claim 4, wherein the concentration of povidone-iodine is 0.3% to 1.0% w / v, and the concentration of iodide is 0.05% to 0.5% w / v.

6. The surgical disinfectant composition according to any one of claims 1 to 5, wherein the buffered saline solution contains sodium phosphate.

7. The surgical disinfectant composition is weakly acidic, as described in any one of claims 1 to 6.

8. The surgical disinfectant composition according to claim 7, wherein the surgical disinfectant composition has a pH between about 5 and about 6.

9. A method for using the surgical disinfectant composition described in any one of claims 1 to 8, This includes applying the surgical disinfectant composition non-locally to maintain the tissue without diluting the surgical disinfectant composition, method.

10. The method according to claim 9, wherein the surgical disinfectant composition is applied during the surgical implantation of a prosthesis.

11. The method according to claim 9 or 10, wherein the application without dilution includes opening a package containing the surgical disinfectant composition in a sterile field of an operating room and applying the surgical disinfectant composition directly from the package to the tissue.

12. The method according to claim 11, wherein the package is a spray bottle.

13. A package containing a surgical disinfectant composition, The surgical disinfectant composition, Initially non-toxic concentrations of povidone-iodine exceeding the minimum effective concentration of available iodine, 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, Buffered saline and A surfactant containing vitamin E TPGS, and package.

14. The package according to claim 13, wherein the package comprises polypropylene.

15. a) A sterilized package made of radiation-safe materials, b) A sterile surgical disinfectant composition contained in the package, i) An initial non-toxic concentration of povidone-iodine that exceeds the minimum effective concentration of available iodine, ii) an amount of iodide sufficient to provide donor iodine after gamma irradiation to stabilize the povidone-iodine and maintain the minimum effective concentration of available iodine, iii) Buffered saline solution, iv) A surfactant containing vitamin E TPGS, and A surgical disinfectant composition comprising, A ready-to-use, ultimately sterilized disinfectant delivery system.

16. The package comprises polypropylene, as described in claim 15, for a ready-to-use, finally sterilized disinfectant delivery system.

17. The ready-to-use, finally sterilized disinfectant delivery system according to claim 15 or 16, wherein both the sterilized package and the sterilized surgical disinfectant composition are sterilized by exposure to radiation.

18. The ready-to-use, finally sterilized disinfectant delivery system according to any one of claims 15 to 17, wherein the package is asymmetrical with respect to its longitudinal axis so as to form a longitudinally extending recess.

19. The shape of the recess is hermaphroditic, according to claim 18, a ready-to-use, finally sterilized disinfectant delivery system.

20. A ready-to-use, finally sterilized disinfectant delivery system according to claim 18 or 19, further comprising a second spray bottle having the same body and recess as the spray bottle, and allowing the spray bottle and the second spray bottle to be arranged in a nested juxtaposition relationship.

21. A method for preparing the surgical disinfectant composition according to any one of claims 1 to 8, The surgical disinfectant composition is placed inside the package, The process includes sterilizing the package containing the surgical disinfectant composition by exposing the package to gamma radiation, During irradiation, the iodide provides iodine to stabilize the povidone-iodine and maintain the minimum effective concentration of available iodine. method.

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