PERACETIC ACID ANTIMICROBIAL COMPOSITION SYSTEM AND METHOD

Abstract

An antimicrobial composition includes peracetic acid and witch hazel extract. The peracetic acid can be formed by combining and reacting the acetic acid and hydrogen peroxide, for example at the point of use. Alternatively, the peracetic acid may be formed separately and mixed with the witch hazel extract prior to use. The resulting peracetic acid and hydrogen peroxide are, thus, combined with the witch hazel extract prior to use. The combination of peracetic acid, hydrogen peroxide and witch hazel extract may be applied as an antimicrobial. The antimicrobial composition may be applied topically to various organs (e.g., skin, nose, ears, mouth, throat, urethra, urinary bladder, gastrointestinal organs) or instilled through an indwelling urinary catheter or applied or inserted as a topical additive or coating to devices or other organ surfaces or other medical devices, or on the skin of the body or surfaces of inanimate objects.

Claims

1. A biological or inanimate surface cleansing, rinsing or coating antimicrobial composition, comprising: peracetic acid; and witch hazel extract.

2. The composition of claim 1, further comprising: hydrogen peroxide.

3. A reactive composition, comprising: acetic acid; and hydrogen peroxide; wherein the combination reacts to form peracetic acid, and oxygen gas allowed to escape.

4. The composition of claim 3, further comprising: witch hazel extract.

5. A method of preventing microbial proliferation, comprising: providing acetic acid; providing hydrogen peroxide; reacting the acetic acid and the hydrogen peroxide to obtain peracetic acid; providing witch hazel extract to the peracetic acid.

6. The composition of claim 4, further comprising: witch hazel extract.

7. A process for treating the surface of a medical device, comprising: exposing the medical device to a combination of peracetic acid and witch hazel extract.

8. A process for treating an organ, comprising: exposing the organ to a combination of peracetic acid and witch hazel extract.

9. A medical device manufactured by the method of claim 7.

10. An organ treated by the process of claim 8.

Description

DETAILED DESCRIPTION

[0019] Embodiments include peracetic acid compositions, as well as other formulations. As non-exclusive example, embodiments also can include organic extracts, such as Witch hazel extracts (WH), comprising hamamelitannin and/or gallic acid, combined with the peracetic acid, hydrogen peroxide and other constituents. The novel combination has been determined to be effective as an antimicrobial, for topical applications, including to surfaces of urinary catheters and devices, and as a internal rinse of the bladder lumenal mucosa, skin and other organs. Through benchtop experimentation, the peracetic acid+WH combination has been shown to be more effective as an antibacterial than the conventional Betadine solution. The formulations may take a variety of forms, such as the peracetic acid may be formed by reacting hydrogen peroxide with acetic acid at point of use, and may therefore include liquids, rinse, sprays, ointments, creams, colloids, and others.

Peracetic Acid

[0020] Peracetic acid (CH.sub.3CO.sub.3H) has been found to be a potent antimicrobial agent. Peracetic acid may be made by combining hydrogen peroxide (H.sub.2O.sub.2) and acetic acid (CH.sub.3CO.sub.2H). Acetic acid (3%) and water (97%) are commercialized as vinegar. Hydrogen peroxide (2%) in water is also commercialized as a cleansing agent. By mixing the two compounds, hydrogen peroxide and acetic acid, peracetic acid and water is obtained, generally as follows:

##STR00001##

Peracetic acid is, thus, an organic compound with component bonds as follow:

##STR00002##

It is a colorless liquid with a characteristic acrid odor and can be corrosive.

[0021] The U.S. Environmental Protection Agency has registered peracetic acid as an antimicrobial for indoor use on hard surfaces. Peracetic acid is also registered for use in dairy and cheese processing, on food processing equipment, and in pasteurizers in breweries, wineries and beverage plants. It has also been used for disinfection of medical supplies, to prevent biofilm formation in pulp industries, and as a water purifier and disinfectant. The acid has further been used as a cooling tower water disinfectant to prevent biofilm formation.

[0022] Although peracetic acid has been used in medical context, formulations for biocidal decontamination and bactericides used both internally and externally in the human body have become possible when combined in select antibacterial formulations in accordance with teachings herein.

Witch Hazel Extract

[0023] Combination of acidic aqueous combinations of peracetic acid with witch hazel concentrate has been found to be a very effective formulation for antimicrobial effects.

[0024] Witch hazel (Hamamelis) is a genus of flowering plants in the family Hamamelidaceae. Four species are found in North America (H. ovalis, H. virginiana and H. vernalis), and one species each is found in Japan (H. japonica) and China (H. mollis). The leaves and bark of the North American witch hazel, Hamamelis virginiana, may be used to produce an astringent decoction. This witch hazel decoction can be an extract in liquid form. This concentrated extract liquid has been FDA approved, for example, for topical application to the nose, anus and skin.

[0025] Witch hazel liquid extract/concentrate can include such components as calcium oxalate, gallotannins, and safrole, and chemicals found in the essential oil (carvacrol, eugenol). Witch hazel for use as a topical can be a liquid, semisolid ointment, cream, gel or salve, as examples. Witch hazel extracts and concentrates are widely sold by pharmacies, grocery stores, and others, and they serve many uses to ease discomfort and provide soothing sensations.

[0026] A particular witch hazel extract (WH) in the embodiments, determined to provide beneficial attributes, is marketed over the counter as a product named whISOBAX™ available from Staph-Off Biotech, Inc. at staphoff.com, as example. The whISOBAX™ product comprises about 12.66 mg of gallic acid equivalent/ml. The planktonic minimum bactericidal concentration/minimum inhibitory concentration (MBC/MIC) for whISOBAX™ is about 0.31/0.15 mg/ml gallic acid equivalence method (GAE) and the minimum inhibitory concentration (MIC) for biofilm trapped bacteria is about 0.47 mg/ml GAE [~3X higher than the planktonic level].

[0027] Determined to be a particular anti-microbial component of the witch hazel extracts is the hamamelitannin molecule. The hamamelitannin molecule is substantially as follows:

##STR00003##

Various analogues of hamamelitannin are possible and all are contemplated as suitable for the combinations in embodiments. Hamamelitannin acts as a quorum signaling inhibitor (QSI) that suppresses microbial biofilm formation and toxin production of bacteria.

[0028] Other anti-microbial active components of witch hazel include gallic acid and other phenolic compounds. Gallic acid, for example, may prevent bacterial growth by binding/disrupting cell membranes. The various components of witch hazel extract are effective in multiple gram negative and positive bacteria that commonly colonize indwelling urinary catheters and the like. The primary function of witch hazel extract where deposited and in antimicrobial actions is to block microbial attachment to devices or biological surfaces, block biofilm formation, erode existing biofilm and block microbial toxins from being produced, and lower the MIC of other anti-microbial agents.

[0029] In certain embodiments, combinations of peracetic acid and witch hazel extract concentrate are found to be particularly effective antimicrobial compositions. The acidic aqueous solution is more efficacious than individual components in limiting microbial growth. Testing of the combination of aqueous ingredients reveals that no reactants, such as precipitates, flocculates, or color change (other than dilution), results.

[0030] In certain further embodiments, increasing the concentration and acidity of either or both peracetic acid and hydrogen peroxide, while simultaneously minimizing microbe protective biofilm formation with WH, furthers antimicrobial efficacy of the peracetic acid combinations. In the combination of aqueous peracetic acid and hydrogen peroxide with WH, the WH prevents and erodes microbe induced biofilm on cellular and prosthetic surfaces.

[0031] Exceptional bench-top testing results have been obtained in antimicrobial action from the peracetic acid and WH combination in the testing of multiple microbial species. As example, the following lab test results were obtained with three concentrations of combinations of peracetic acid and WH, with hydrogen peroxide, with exemplary results for three common microbes:

TABLE-US-00001 H2O2 .fwdarw. 6 mL H2O2 .fwdarw. 3 mL H2O2 .fwdarw. 6 mL whISOBAX .fwdarw. 1 mL whISOBAX .fwdarw. 1 mL whISOBAX .fwdarw. 1 mL Acetic acid .fwdarw. 1.5 mL Acetic acid .fwdarw. 1.5 mL Acetic acid .fwdarw. 5.0 mL pH .fwdarw. 3.5 pH .fwdarw. 3.5 pH .fwdarw. 2.5 *No reactivity observed upon initial agent mixture or three hours later **No reactivity observed at 24 hours at 37° C. incubation Staphylococcus aureus Formula 1 Formula 2 Formula 3 1:1 No Growth 1:1 No Growth 1:1 No Growth 1:100 No Growth 1:100 No Growth 1:100 No Growth 1:1000 No Growth 1:1000 No Growth 1:1000 No Growth Escherchia coli K-12 Formula 1 Formula 2 Formula 3 1:1 No Growth 1:1 No Growth 1:1 No Growth 1:100 No Growth 1:100 No Growth 1:100 No Growth 1:1000 No Growth 1:1000 No Growth 1:1000 No Growth Proteus vulgaris Formula 1 Formula 2 Formula 3 1:1 No Growth 1:1 No Growth 1:1 No Growth 1:100 No Growth 1:100 No Growth 1:100 No Growth 1:1000 No Growth 1:1000 No Growth 1:1000 No Growth

[0032] Furthermore, example lab test results of comparison of the peracetic acid+WH, in hydrogen peroxide, combination (identified in the table as Bug-Off™), to a Betadine solution as antimicrobial follow:

TABLE-US-00002 Organism Dilution Bug-Off™ Betadine Staphylococcus aureus 1:10 Susceptible Susceptible 1:20 Susceptible Susceptible 1:40 Susceptible Susceptible 1:100 Susceptible Susceptible 1:200 Susceptible Resistant 1:400 Susceptible Resistant 1:1000 Susceptible Resistant 1:1500 Susceptible Resistant Enterococcus faecalis 1:10 Susceptible Susceptible 1:20 Susceptible Susceptible 1:40 Susceptible Susceptible 1:100 Susceptible Intermediate 1:200 Resistant Resistant 1:400 Resistant Resistant 1:1000 Resistant Resistant 1:1500 Resistant Resistant Proteus mirabilis 1:10 Susceptible Resistant 1:20 Susceptible Resistant 1:40 Susceptible Resistant 1:100 Susceptible Resistant 1:200 Resistant Resistant 1:400 Resistant Resistant 1:1000 Resistant Resistant 1:1500 Resistant Resistant Klebsiella pneumoniae 1:10 Susceptible Susceptible 1:20 Susceptible Susceptible 1:40 Susceptible Resistant 1:100 Susceptible Resistant 1:200 Susceptible Resistant 1:400 Susceptible Resistant 1:1000 Susceptible Resistant 1:1500 Susceptible Resistant

It is noteworthy that all microbe strains, with the exception only of highest concentrations of Enterococcus faecalis and Proteus mirabilis, are more susceptible to prevention by the peracetic acid+WH+hydrogen peroxide combination (i.e., of Bug-Off™) than the conventional Betadine solution.

[0033] In use of the peracetic acid+WH+hydrogen peroxide combination, it has been the practice to obtain acetic acid and hydrogen peroxide, react the two compounds at time of use to obtain peracetic acid and remaining hydrogen peroxide, and to combine with WH. Thus, the three ingredients - hydrogen peroxide, acetic acid and WH - provide the peracetic acid+WH+hydrogen peroxide combination that has exceptional antimicrobial results. Means of mixing and dispensing are under study, such that the hydrogen peroxide and acetic acid react at point of use to yield the peracetic acid+hydrogen peroxide for combination with the WH at that point of use.

[0034] The combined peracetic acid+WH+hydrogen peroxide may be employed on surfaces of medical devices, such as for non-exclusive example Foley or other catheters, internally within organs, such as for non-exclusive example entry to the bladder, and otherwise, such as on surfaces, skin, implements and others, in the medical and microbe prevention contexts.

Other Additives

[0035] Silver, and other metals, and halogens may be additionally or alternately included in the various combinations. These additives may have enhanced antimicrobial effectiveness in the presence of a quorum-signaling inhibitor [e.g., witch hazel components] or the like. Of course, other components may be additionally or alternately included in various combinations, such as for desired pH, toxicity, emulsifiers, compounders, and other characteristics.

[0036] The foregoing components and combinations are employable as surface coatings, for example, on the skin, or on the surface of temporarily or permanently implanted devices, and/or as and as liquid aqueous additives to surface of temporary replaceable devices like urinary catheters, and as a cleansing or rinse agent on biological organs or biological or inanimate surfaces or the like. In particular, the combinations of peracetic acid with WH are particularly effective as antimicrobials on surfaces of urinary catheters and other devices, as well as skin and wounds. The various combinations appear to be more effective as antimicrobials than would be expected from results of each component acting alone or from other antimicrobials, such as Betadine or other.

[0037] Patients with indwelling catheters, for non-exclusive example, may receive at least one or twice daily [AM/PM] instillations of a peracetic acid and witch hazel combination, with or without additional hydrogen peroxide, as a rinse into the urinary bladder for at least two days and possibly for the duration of use of the indwelling catheter (or other device, as applicable). A combination of about 5 ml to about 6 ml of about 1% to about 3% peracetic acid plus about 1 ml to about 2 ml of witch hazel may be added to the bladder lumen. Following each instillation, bladder drainage will be capped/clamped to tolerance. Unclamping and drainage of bladder urine into collection bags will be initiated by the patient or caregiver when symptoms dictate a need for urine drainage. In other applications, the above agent delivery methodology could also be effective as a twice daily dental cleansing methodology.

[0038] A urine specimen will be collected each morning from the patient’s indwelling catheter. The indwelling and/or the continuous draining catheter may be clamped for 10-15 minutes prior to urine collection if needed. After the urine specimen is collected for urine culture testing, the indwelling catheter will be irrigated with 20+ml of sterile water or saline to remove any mucous, blood, blood clots or crystalline debris from the bladder lumen. This irrigant will be discarded. Promptly thereafter, an applicable combination additive will be instilled into the bladder lumen and the catheter will be clamped to tolerance to allow the additive to remain in the bladder lumen for multiple hours. This combination additive instilled into the bladder is to remain within the bladder until the patient has urge to urinate. The patient or caregiver will then unclamp/uncap drainage tube and allow the bladder to drain into a commode or collection bag. There is no need for additive placement into the bladder lumen except for the early morning and bed-time time periods at this time. Increase or decrease in the number and timing of daily bladder instillations may be variable according to implementation. Each of the collected urine specimens will have a label for patient ID #, date, time of specimen collection and earlier time that additive was added to the bladder lumen. Additional urine specimen(s) may or may not be collected for infection testing if symptoms prompt such concerns. The specimens will be refrigerated in a research refrigerator at the local institution and then transported to a certified lab for microbiology testing.

[0039] As further protocol detail, an initial screening visit will be held. Informed consent and demographic date will be obtained. All antibiotics will be stopped at least two days prior to urine collection for the pre-treatment urine culture and for duration of the protocol procedure.

[0040] A second screening visit will then be held at least two days after the initial screening visit. A urine culture will be performed at this second screening visit.

[0041] Thereafter, in days 1, 2, and 3, after beginning urine culture from the second screening, [0042] a. A urine dipstick test will be performed every morning. [0043] b. The urine collection bag will be emptied prior to each bladder instillation. [0044] c. The applicable combination shall be injected into and through the indwelling Foley catheter into the bladder in the morning and in the evening. Following instillation, the catheter will be capped, clamped or sealed in order to keep the additive within the bladder until the bladder is uncomfortably full. [0045] e. All patients will be encouraged to keep the catheter clamped to tolerance after instillation of above fluids. [0046] f. 10+ cc of urine will be collected directly from the indwelling bladder catheter each morning per day immediately before installation of the morning or evening combination agent. Early in day 1 collection will be made of urine specimen collection #1, followed by installation #1, and a second urine specimen collection #2 followed by installation #2 shall be made in the early AM of day 2. Third and fourth installations of the combination shall similarly be made on days 3 and 4 (mornings) Daily side effects will be logged and discussed with the patient. Single early AM bladder instillations are anticipated to eradicate the original microbial growth in the bladder urine. If single early AM instillations of the bladder additive do not sterilize bladder urine then twice daily instillations of the additive [i.e. early sunrise AM and late sunset PM] shall be offered.

[0047] Non-exclusive embodiments may take form of liquid, gel, or device coating or the like, for application to surfaces of devices or body organs or spaces or cavities for rinse or cleansing of the body or device. Additionally, the individual agents and/or combinations can be impregnated or disposed in or on tape, cloth, device, or other surfaces. The combination can be placed as a coating on devices, such as a catheter or other medical device made of polyethylene, silicone, composites, or other materials. Variations of viscosity and flow characteristics, as well as elution and retention properties, are possible in the embodiments. In certain non-exclusive alternatives, combinations of the embodiments are introduced by instillation into bodily cavities, such as bladder lumen, or other vessels or other body parts, or as coating or deposited ‘additive’ on body part, coating or deposition, as on a medical device, such as a urinary catheter or other device, or as topical application to the skin or bodily area, cavity or organ.

[0048] Of course, a wide variety of other variations are possible.

[0049] In the foregoing, therefore, the invention has been described with reference to specific embodiments. One of ordinary skill in the art will appreciate, however, that various modifications, substitutions, deletions, and additions can be made without departing from the scope of the invention. Accordingly, the specification and figures are to be regarded in an illustrative rather than a restrictive sense, and all such modifications substitutions, deletions, and additions are intended to be included within the scope of the invention. Any benefits, advantages, or solutions to problems that may have been described above with regard to specific embodiments, as well as device(s), connection(s), step(s) and element(s) that may cause any benefit, advantage, or solution to occur or become more pronounced, are not to be construed as a critical, required, or essential feature or element.