Disinfectant solution

Abstract

Various formulations of a high-level disinfectant and liquid chemical sterilant are provided. The formulations include a peracetic acid solution which has achieved equilibrium and is catalyzed by an amount of sulfuric acid in the solution. The inclusion of sulfuric acid greatly reduces the amount of time to achieve equilibrium, and despite the inclusion of a mineral acid the resulting solution has enhanced reuse stability and equivalent toxicity, improved sterilization properties, and material compatibility to non-catalyzed peracetic acid solutions.

Description

ASP-201DISINFECTANT SOLUTIONCLAIM OF PRIORITY

[0001] This application claims priority to Chinese patent application No. 2025108883966, filed on June 30, 2025 and also claims priority to United States Provisional Patent Application No. 63 / 708,493, filed on October 17, 2024, entitled DISINFECTANT SOLUTION, the contents of both of which are incorporated by reference in their entireties.BACKGROUND

[0002] In settings where patients receive healthcare, there is a need to create a sterile environment, which includes having sterile medical instruments and devices present within that environment. According to a study by the US Center for Disease Control and Prevention, nearly 1.7 million hospitalized patients acquire some sort of infection while receiving care. Of these patients, more than l-in-17 die from complications resulting from these types of infections, underscoring the need to easily and economically create sterile environments in areas where patients receive such care.

[0003] One of the challenges in consistently creating sterile environments is the availability of the materials used to sterilize such environments. While not an element that many commonly consider, many high-level disinfectants and liquid chemical sterilants take a considerable amount of time to manufacture, and for facilities that cannot accurately predict their disinfectant needs, this long lead-time can cause issues with the healthcare provider’s ability to sterilize their medical instruments and devices. Additionally, many such disinfectants have poor reuse stability, further compounding potential availability issues. Thus, being able to prepare effective and cost-efficient high-level disinfectants in a short amount of time, as well as having higher reuse stability is desirable both from a medical practitioner’s standpoint as well as from a manufacturing standpoint.

[0004] As such, there is a need for a disinfectant which is effective against pathogens while being able to be created in short-order and having a high reuse stability. The invention in accordance with the present disclosure meets and exceeds these needs.SUMMARY

[0005] The embodiments of the disinfectant solution in accordance with the present disclosure provide an effective high-level disinfectant solution and liquid chemical sterilant for reprocessing medical devices, reducing the risk of infections and cross-contamination, and ensuring patient safety. In these various embodiments, a high-level disinfectant being able to sterilize a provided medical device in a greatly reduced time from other peracetic acid based high-level disinfectants known in the art. The present disclosure provides for an embodiment of the disinfectant solution which comprises hydrogen peroxide, acetic acid, a stabilizer, mineral acid, and peracetic acid. In various embodiments, the stabilizer is etidronic acid, which is available commercially under the trade name Dequest® 2010LC. It should be noted that etidronic acid is known to act as a corrosion inhibitor as well as a stabilizer. In various embodiments, theASP-201 solution further comprises a solvent, and such solvent can be distilled water, hard water, and the like. Embodiments exists where the acetic acid present in the disinfectant solution is glacial acetic acid.

[0006] In various embodiments, the disinfectant solution in accordance with the present disclosure can have components thereof present in various concentrations. For example, embodiments exist where the hydrogen peroxide present in the disinfectant solution in accordance with the present disclosure has a concentration in the range of 4.0-5.0% w / w. For the purposes of this disclosure, % w / w being percentage weight by weight, which is used to express the concentration of a component as part of a solution. Embodiments also exist where the peracetic acid present in the disinfectant solution in accordance with the present disclosure has a concentration in the range of 0.3-0.4% w / w.

[0007] In an embodiment, the disinfectant solution in accordance with the present disclosure includes peracetic acid in a concentration of approximately 0.35% w / w, hydrogen peroxide in a concentration of approximately 4.66% w / w, acetic acid in a concentration of approximately 7% w / w, etidronic acid in a concentration of approximately 0.2% w / w, sulfuric acid in a concentration of approximately 0.25% w / w, and water in a concentration of approximately 87.54% w / w.

[0008] Embodiments of the disinfectant in accordance with the present can include hydrogen peroxide with a concentration in the range of 4.20% -5.00% w / w, acetic acid or glacial acetic acid with a concentration in the range of 5.30%-9.20% w / w, 60% etidronic acid with a concentration in the range of 0.15%-0.25% w / w, 95%-98% sulfuric acid with a concentration in the range of 0.15%-0.40% w / w, peracetic acid with a concentration in the range of 0.25% -0.45% w / w, and deionized water with a concentration in the range of 84.70%-89.95% w / w. Other embodiments of the disinfectant in accordance with the present disclosure can include hydrogen peroxide with a concentration in the range of 4.30%- 4.90% w / w, acetic acid or glacial acetic acid with a concentration in the range of 5.80%-8.20% w / w, stabilizer with a concentration in the range of 0.16%-0.23% w / w mineral acid with a concentration in the range of 0.20%-0.30% w / w, peracetic acid with a concentration in the range of 0.28%-0.43% w / w, and deionized water with a concentration in the range of 85.00%-88.00% w / w.

[0009] Embodiments of the disinfectant in accordance with the present disclosure also exist where the disinfectant includes hydrogen peroxide in a concentration of 4.66% w / w, glacial acetic acid or acetic acid in a concentration of 7.00% w / w, 60% etidronic acid in a concentration of 0.20% w / w, 95%-98% sulfuric acid in a concentration of 0.25% w / w, peracetic acid in concentration of 0.35% w / w, and deionized water in a concentration of 87.54% w / w.

[0010] The present disclosure also provides for a method of preparing a ready-to-use soludon. In various embodiments, this method begins by first providing an amount of hydrogen peroxide, an amount of acetic acid, an amount of a stabilizer, an amount of mineral acid, and a solvent. These methods then proceed to the step of placing the hydrogen peroxide, the acetic acid, the stabilizer, the mineral acid, and the solvent into a container and then stirring the contents of the container placed therein in the previous step for approximately one hour at ambient temperature and ambient humidity such that an amount of peracetic acid is generated in situ. In some embodiments ambient temperature is approximately 20 degrees Celsius and ambient humidity is approximately 60%. Once completely mixed, the method proceeds to anASP-201 evaluation of a concentration of the hydrogen peroxide to determine said concentration is within a first specification, and upon confirmation that this first specification has been met, the total acid concentration of the solution is tested to determine whether the total acid concentration is within a second specification. Upon reaching the desired total acid concentration, the mixture is transferred to an area substantially devoid of light where it is allowed to rest for a period of approximately 6 days until equilibrium within the solution is achieved.DETAILED DESCRIPTION

[0011] The present disclosure provides for multiple embodiments of a ready-to-use low concentration peracetic acid solution for use as a liquid chemical sterilant and a high-level disinfectant for use in medical devices. In these various embodiments, this disinfectant operates as a liquid chemical sterilant and high-level disinfectant by systemically oxidizing any microbes in the presence of said disinfectant. In some embodiments, the peracetic acid is present in the solution in concentrations ranging from 0.07% w / w to 0.8% w / w. Embodiments exist where the peracetic acid is present in a concentration of 0.35% w / w.

[0012] Peracetic acid can be produced by the reaction of hydrogen peroxide and acetic acid in the presence of a suitable stabilizer, such as etidronic acid. This solution, after some time, will achieve equilibrium such that the resulting solution contains peracetic acid, hydrogen peroxide, acetic acid, and the suitable stabilizer. Under normal circumstances this solution will take approximately 35 days to achieve equilibrium with a peracetic acid concentration of approximately 0.35% w / w. In an attempt to help reduce the above reaction time, the inventors of the embodiments in accordance with the present disclosure, after much experimentation, have determined that a catalytic amount of a mineral acid will reduce the reaction time-to-equilibrium down to a period of roughly 6 days. Various types of mineral acids are contemplated by the present disclosure, and include sulfuric acid, hydrochloric acid, phosphoric acid, nitric acid, perchloric acid, hydrofluoric acid, and hydrobromic acid. For example, when utilizing sulfuric acid to catalyze this reaction, the time-to-equilibrium decreases by approximately 83%, which will provide for a much lower risk of the disinfectant in accordance with the present disclosure being out of stock as opposed to a non-catalyzed version. The use of a mineral acid in the context of a disinfectant to be used in medical devices for humans is quite uncommon due to concerns surrounding patient safety as well as with material compatibility.

[0013] Despite the fact that persons having ordinary skill in the art would expect that liquid chemical sterilants and high-level disinfectants that contain a mineral acid such as sulfuric acid would have high toxicity and poor material compatibility, toxicological testing and material compatibility testing show that the mineral acid catalyzed peracetic acid disinfectant in accordance with the present disclosure performs similarly to peracetic acid disinfectant solutions that are not catalyzed with sulfuric acid. Such testing was performed in accordance with “Technical Standard for Disinfection” (2002, Ministry of Public Health, People’s Republic of China). When similar tests were performed against other low-concentration peracetic acid disinfectant solutions known in the prior art, similar performance was observed suggestingASP-201 the unexpected result of the presence of sulfuric acid not affecting any toxicology or material compatibility properties.

[0014] Additionally, the mineral acid catalyzed peracetic acid solutions have the additional benefit of having dramatically improved reuse stability, which is the ability for a liquid chemical sterilant and / or high-level disinfectant to maintain efficiency of sterilization after daily use for a period of time. Known peracetic acid solutions exhibit roughly 7 days of reuse stability, while the mineral acid catalyzed peracetic acid solution in accordance with the present disclosure exhibits roughly 28 days of reuse stability, yet another dramatic improvement over the soludons known in the art. The improved reuse stability exhibited by the mineral acid catalyzed peracetic acid solution in accordance with the present disclosure is a result of the catalytic amounts of sulfuric acid increasing the solution’s equilibrium rate. That is, the peracetic acid present in this solution is regenerated more quickly as part of a catalyzed solution as opposed to a non-catalyzed counterpart when the peracetic acid is consumed via either sterilization or degradation in solution.

[0015] Embodiments exist where the method of creating the mineral acid catalyzed peracetic acid solution in accordance with the present disclosure proceeds as follows. These embodiments of the method begin by adding 35% hydrogen peroxide (H2O2), acetic acid such as glacial acetic acid, a stabilizer such as Dequest® 2010LC, 97% sulfuric acid, and deionized water are added to a container equipped with a stirring device. Embodiments exist where this stirring device is a magnetic stir bar and corresponding magnetic drive system, an overhead mixer, a propeller, and similar laboratory-grade mixing devices. In some embodiments, the hydrogen peroxide is added in an amount of 13.2% w / w, the acetic acid is added in an amount of 7% w / w, the stabilizer is added in an amount of 0.2% w / w, and sulfuric acid is added in an amount of 0.10-0.70% w / w. It should be noted that the amount of sulfuric acid or other mineral acid which is used can be modified depending on the ultimate use case desired by the healthcare provider.

[0016] Once these components are added to the container, the resulting solution is allowed to mix for 1 hour at an ambient laboratory temperature and humidity, such as ~20°C and 60% relative humidity. After this approximately 1 hour of mixing, the hydrogen peroxide concentration is determined via an iodometric titration method. Additionally, the method also includes a step of testing for the total acid content, which can be measured via an acid / base titration method. After determining that both the hydrogen peroxide and total acid concentrations are within a desired predetermined specification, the container is transferred to a dark location where the solution is allowed to mature. Embodiments exist where this maturation period is approximately 6 days, however in other embodiments this period of time may be altered such that the proper concentration of both peracetic acid and hydrogen peroxide in the solution is achieved. After the maturation period, the solution is then tested for both peracetic acid and hydrogen peroxide to determine if the desired concentrations have been achieved. This testing can be performed via back-to-back redox titration methods.

[0017] Experimentation to assess the time-to-equilibrium for both uncatalyzed peracetic acid solutions and mineral acid catalyzed peracetic acid solution in accordance with the present disclosure were performed. During this experimentation, both catalyzed and uncatalyzed solutions were prepared and thenASP-201 incubated at room temperature within a chemical cabinet. Further experiments where the starting hydrogen peroxide and acetic acid from different suppliers were also performed. Across all soludons tested, catalyzed solutions reached equilibrium after 10 days of room temperature incubation as shown in Table 1, below. The uncatalyzed solutions reached equilibrium after 28 days of room temperature incubation as shown in Table 2, below. For the solutions tested under manufacturing settings, the catalyzed solutions reached equilibrium after 6 days, as shown in Table 3 and the uncatalyzed solutions reached equilibrium after 21 days, as shown in Table 4.

[0020] Table 3

[0021] Table 4ASP-201

[0022] Additionally, experiments to assess the reuse stability of the mineral acid catalyzed peracetic acid solution in accordance with the present disclosure were also performed. As noted above, for the purposes of this disclosure reuse stability or continuous use stability refer to the stability of a disinfectant and the ability of said disinfectant to achieve sterilization after multiple days of use. These experiments to assess the reuse stability were performed in accordance with the Chinese standard GB 27949, entitled “General requirements for disinfectant of medical instruments” and “Disinfection Technical Specification” (2002). The results of these tests are shown below in Table 5. As can be seen below, the catalyzed solution exhibits unexpectedly improved reuse stability when compared with the uncatalyzed solution.

[0023] Table 5

[0024] Material compatibility of the uncatalyzed peracetic acid solution as well as the mineral acid catalyzed peracetic acid solution were also assessed. This assessment was also performed in accordance with Chinese standard GB 27949 “General requirements for disinfectant of medicalASP-201 instruments” and “Disinfection Technical Specification”. The results of these tests are provided below inTable 6.

[0025] Table 6

[0026] The results shown in Table 6 illustrate that the catalyzed solutions exhibit similar corrosion rates to the uncatalyzed solution despite the presence of sulfuric acid, a known corroding agent. This property of the mineral acid catalyzed peracetic acid solution in accordance with the present disclosure shows yet another unexpected result offered by said solution.

[0027] Further corrosion tests were also performed on embodiments of the disinfectant solution in accordance with the present disclosure on stainless steel, carbon steel, copper, and aluminum. The results of these tests are shown below in Table 7, and the classification of the amount of corrosion is consistent with the 2002 edition of the Technical Standard for Disinfection published by the National Health Commission of the People’s Republic of China.

[0028] Table 7

[0029] The comparative toxicity of the catalyzed peracetic acid solution against the externally sourced PAA solution was also tested. This testing too was performed in conformance with the 2002 Chinese standard GB 27949 “General requirements for disinfectant of medical instruments” and “Disinfection Technical Specification”.

[0030] Skin irritation was also checked as part of the toxicity analysis. Any mutagenicity caused by the catalyzed solution was also assessed. Results of these various toxicity tests are presented below in Table 8.ASP-201

[0031] Table 8

[0032] Further toxicity tests were performed to assess the genotoxicity of an embodiment of the disinfectant solution in accordance with the present disclosure against a negative control and a positive control, assessing polychromatic erythrocytes (“PCE”) and normochromatic erythrocytes (“NCE”). As can be seen from the data of these tests, shown in Table 9, below, there is no significant difference between the tested embodiment in each lot and the negative control, suggesting that the tested embodiments are not genotoxic pursuant to the 2002 edition of “Technical Standard for Disinfection” published by the National Health Commission of the People’s Republic of China.

[0033] Table 9ASP-201

[0034] Moreover, acute oral toxicity of embodiments of the disinfectant solution in accordance with the present disclosure was also tested via animal testing. The results of these tests are shown below inTable 10, and these results illustrate that the tested embodiments do not exhibit acute oral toxicity.

[0035] Table 10

[0036] In addition to the above toxicity analysis, skin irritation was also more comprehensively assessed in further tests where the presence of any skin irritation was measured at certain intervals of exposure. Such tests were performed in accordance with the 2002 edition of “Technical Standard for Disinfection” published by the National Health Commission of the People’s Republic of China. Results of two lots of said testing are provided below in Table 11. As can be seen below, the highest level of skin irritation which was observed is 0.0. Thus, these results qualify for a classification as “non-irritating” in accordance with said Technical Standard for Disinfection.

[0037] Table 11ASP-201

[0038] Embodiments exist where the stabilizer used as part of the mineral acid catalyzed peracetic acid formulation in accordance with the present disclosure is selected from the group consisting of pyridinedicarboxylic acid, l-hydroxyethylidene-l,l-diphosphonic acid, and 2,6-pyridinedicarboxylic acid. In various embodiments, the mineral acid catalyzed peracetic acid formulation in accordance with the present disclosure can be used as a liquid chemical sterilant in an Automatic Endoscope Reprocessor, where the solution is mixed in a 1 : 1 ratio with an appropriate buffer solution.

[0039] Tests on the comparative sterilization efficacy of embodiments of the disinfectant soludon in accordance with the present disclosure were also tested against other non-mineral acid-catalyzed peracetic acid solutions. Some of the results from these tests are provided below in Table 12, where the concentration of peracetic acid within each solution is listed, as well as the contact time required to achieve sterilization consistent with both the WS / T 10009-2023 and EN 17126 testing standards.

[0040] Table 12

[0041] Embodiments of preparing a disinfectant solution in accordance with the present disclosure can include the steps of mixing an amount of hydrogen peroxide, an amount of acetic acid, an amount of a stabilizer, an amount of mineral acid, and a solvent into the disinfectant solution, then evaluating a concentration of the hydrogen peroxide to be within a first specification or a total acid concentration to be within a second specification, and finally facilitating the disinfectant solution to achieve equilibrium.

[0042] Although the invention herein has been described with reference to particular embodiments, it is to be understood that these embodiments are merely illustrative of the principles and applications of the present invention. It is therefore to be understood that numerous modifications may be made to the illustrative embodiments and that other arrangements may be devised without departing from the spirit and scope of the present invention as defined by the appended claims.

Claims

ASP-201CLAIMS1. A disinfectant solution, comprising: hydrogen peroxide having a concentration in the range of 4.0-5.0% w / w; acetic acid; a stabilizer; a mineral acid; and peracetic acid.

2. The solution of claim 1, wherein the stabilizer is etidronic acid.

3. The solution of claim 1, wherein the solution has reuse stability as a disinfectant of at least 14 days.

4. The solution of claim 1, wherein the peracetic acid is present in a concentration of 0.25%-0.45% w / w, the hydrogen peroxide is present in a concentration of 4.20%-5.00% w / w, the acetic acid is present in a concentration of 5.30%-9.20% w / w, the stabilizer is present in a concentration of 0.15%-0.25% w / w, the mineral acid is present in a concentration of 0.15%-0.40% w / w, or the water is present in a concentration of 84.70%-89.95% w / w.

5. The solution of claim 4, wherein the peracetic acid is present in a concentration of 0.28%-0.43% w / w, the hydrogen peroxide is present in a concentration of 4.30% w / w and 4.90% w / w, the acetic acid is present in a concentration of 5.80%-8.20% w / w, the stabilizer is present in a concentration of 0.16%-0.23% w / w, the mineral acid is present in a concentration of 0.20%- 0.30% w / w, or the water is present in a concentration of 85.00%-88.00% w / w.

6. The solution of claim 5, wherein the peracetic acid is present in a concentration of 0.30%-0.43% w / w, the hydrogen peroxide is present in a concentration of 4.40%-4.80% w / w, the acetic acid is present in a concentration of 6.80%-7.20% w / w, the stabilizer is present in a concentration of 0.18%-0.22% w / w, the mineral acid is present in a concentration of 0.24%-0.26% w / w, or the water is present in a concentration of 86.86%-87.54% w / w.

7. The solution of claim 6, wherein the peracetic acid is present in a concentration of 0.35% w / w, the hydrogen peroxide is present in a concentration of 4.66% w / w, the acetic acid is present in a concentration of 7% w / w, the stabilizer is present in a concentration of 0.2% w / w, the mineral acid is present in a concentration of 0.25% w / w, or the water is present in a concentration of 87.54% w / w.

8. A method for preparing or using a disinfectant, comprising the steps of: a. providing an amount of hydrogen peroxide, an amount of acetic acid, an amount of a stabilizer, an amount of mineral acid, and a solvent; b. placing the hydrogen peroxide, the acetic acid, the stabilizer, the sulfuric acid, and the solvent into a container; c. stirring the contents of the container placed therein in the previous step such that an amount of peracetic acid is generated in situ;ASP-201 d. evaluating a concentration of the hydrogen peroxide to determine said concentration is within a first specification; e. testing a total acid concentration of the solution to determine the total acid concentration is within a second specification; f. transferring the container to an area substantially devoid of light; g. allowing the solution to rest for a period of time until equilibrium is achieved thereby creating the ready-to-use disinfectant solution.

9. The method of claim 8, wherein the period of time is less than 10 days.

10. The method of claim 8, further comprising the step of exposing at least one medical instrument to the ready-to-use disinfectant solution for 5 minutes or less resulting in the disinfection or sterilization of the at least one medical instrument.

11. The method of claim 8, wherein the ready-to-use disinfectant solution exhibits reuse stability of at least 14 days.

12. The method of claim 10, wherein the disinfection of the least one medical instrument is in accordance with a regulatory standard, where the regulatory standard WS / T 10009-2023.

13. The method of claim 8, wherein step c is performed for one hour at ambient temperature and ambient humidity.

14. A disinfectant solution, comprising: peracetic acid, wherein the disinfectant solution is configured to disinfect or sterilize a medical instrument within five minutes or less in conformity with regulatory standard WS / T 10009-2023.

15. The disinfectant solution of claim 11, further comprising a mineral acid.

16. The disinfectant solution of claim 12, further comprising hydrogen peroxide having a concentration in the range of 4.0-5.0% w / w, acetic acid, and a stabilizer.

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