Pharyngeal or buccal cavity rinse and process of use thereof

Abstract

A storage stable package is provided that includes a polymeric bottle having a volume filled with an aqueous saline composition acidified with an acid to a pH of 2 to 9 and having a hypertonic saline concentration relative to saliva and blood, or an aqueous hydrogen peroxide composition acidified with an acid to a pH of 2.7 to 5.3 and having a hydrogen peroxide concentration 0.5 to 3 total weight percent, either to achieve a storage stability at 20 degrees Celsius of the composition of at least 10 weeks. The aqueous composition is independent of a synthetic antimicrobial. A cap is provided that is complementary a package opening for selectively sealing the aqueous saline composition within the volume. A process for treating an infection of a pharyngeal or buccal cavity is provided that includes rinsing with one of the aqueous saline composition. The aqueous saline composition is then expectorated.

Claims

1. A storage stable package comprising: a polymeric bottle having a volume; an aqueous saline composition acidified with mineral acid to a pH of 3.0 to 7.0 and having a hypertonic saline concentration relative to saliva and blood to achieve a storage stability at 20 degrees Celsius of the composition of at least 10 weeks, said aqueous composition independent of a synthetic antimicrobial and free of phenols and ethanol; and a cap for selectively sealing said aqueous saline composition within the volume.

2. The package of claim 1 wherein said acid is hydrochloric acid.

3. The package of claim 1 wherein said acid is hydrobromic, phosphoric, sulfuric, nitric, or a combination thereof.

4. The package of claim 1 wherein said pH is 3.6 to 5.4.

5. The package of claim 1 further comprising a flavorant.

6. The package of claim 1 further comprising a desensitizer.

7. The package of claim 1 further comprising a fluoridation agent.

8. The package of claim 1 further comprising fucoidan.

9. The package of claim 8 wherein said fucoidan is present from 0.1 to 2.0 total weight percent of the said aqueous saline composition.

10. The package of claim 1 wherein the hypertonic saline concentration is between 1.7 and 5.0 total weight percent of the said aqueous saline composition.

11. A storage stable package comprising: a polymeric bottle having a volume; an aqueous hydrogen peroxide composition acidified with mineral acid to a pH of 2.7 to 5.3 and having a hydrogen peroxide concentration 0.5 to 2.5 total weight percent of said aqueous hydrogen peroxide composition to achieve a storage stability at 20 degrees Celsius of the composition of at least 10 weeks, said aqueous composition independent of a small molecule organic synthetic antimicrobial and free of phenols and ethanol; and a cap for selectively sealing said aqueous saline composition within the volume.

12. The package of claim 11 wherein said acid is hydrochloric acid.

13. The package of claim 11 wherein said acid is hydrobromic, phosphoric, sulfuric, nitric, or a combination thereof.

14. The package of claim 11 wherein said pH is 3.0 to 5.0.

15. The package of claim 11 wherein said pH is 3.6 to 4.4.

16. The package of claim 11 further comprising a desensitizer.

17. The package of claim 11 further comprising a fluoridation agent.

18. The package of claim 11 further comprising fucoidan.

19. The package of claim 18 wherein said fucoidan is present from 0.1 to 2.0 total weight percent of the said aqueous hydrogen peroxide composition.

20. A process for treating an infection of a pharyngeal or buccal cavity comprising: rinsing the pharyngeal or buccal cavity with said aqueous saline composition of claim 1 for an amount of time sufficient to treat the infection; and expectorating said aqueous saline composition.

21. The process of claim 20 wherein rinsing is gargling.

22. A process for treating an infection of a pharyngeal or buccal cavity comprising: rinsing the pharyngeal or buccal cavity with said hydrogen peroxide composition of claim 11 for an amount of time sufficient to treat the infection; and expectorating said hydrogen peroxide composition.

23. The process of claim 22 wherein rinsing is gargling.

Description

DETAILED DESCRIPTION OF THE INVENTION

(1) The present invention has utility as a pharyngeal or buccal cavity rinse in the forms of a gargle or mouthwash to treat infections of such regions. Without intending to be bound to a particular theory, an inventive rinse is hypertonic relative to saliva and blood. This hypertonicity is believed to not only desiccate pathogens, but also reduce inflammation through drawing of excess fluid from inflamed tissue. Acidification of the rinse provides storage stability without resort to small organic molecule synthetic antimicrobials.

(2) It is to be understood that in instances where a range of values are provided that the range is intended to encompass not only the end point values of the range but also intermediate values of the range as explicitly being included within the range and varying by the last significant figure of the range. By way of example, a recited range of from 1 to 4 is intended to include 1-2, 1-3, 2-4, 3-4, and 1-4.

(3) As used herein a small organic molecule synthetic antimicrobial defines a molecule that has a molecular weight of less than 1000 atomic mass units that is present for this purpose. Specific small organic molecule synthetic antimicrobials excluded from inventive compositions include benzalkonium chloride, cetylpyridinium chloride, chlorhexidine gluconate, methylparaben, methyl salicylcate, and domiphen bromide.

(4) A storage stable package is provided includes a polymeric bottle with a cap for selectively enclosing a volume. An aqueous saline composition is provided that has been acidified with an acid to a pH of 2 to 9 and having a hypertonic saline concentration relative to saliva and blood. Alternatively, an aqueous hydrogen peroxide composition is provided that has been acidified with an acid to a pH of 2.7 to 5.3 and having a hydrogen peroxide concentration 0.5 to 3 total weight percent of the aqueous hydrogen peroxide. The saline or peroxide composition is placed in the bottle to achieve a storage stability at 20 degrees Celsius of the composition of at least 10 weeks. The saline or peroxide composition being independent of a synthetic antimicrobial.

(5) A plastic bottle of an inventive package is formed from a variety of polymers suitable for acid aqueous solution packaging. These polymers illustratively include polyethylene, polypropylene, polyvinyl chloride, polyterephthalates, and block co-polymers containing any of the aforementioned as blocks therein. A cap sized and shaped to engage a plastic bottle opening is likewise formed of any of the aforementioned polymers. It is appreciated that bottle and cap are each independently formed as transparent, translucent, or opaque articles. In certain inventive embodiments, both the bottle and the cap are opaque.

(6) An aqueous saline composition according to the present invention is formed by dissolution of sodium chloride in sterile water. In some inventive embodiments, the water has been deionized. The sodium chloride is present from 1.7 to 5.0 total weight percent of the solution. In certain inventive embodiments, the sodium chloride is present from 1.8 to 2.8 total weight percent. In some inventive embodiments, the saline composition pH is between 3.0 and 7.0. In still other, embodiments, the saline composition pH is between 3.6 and 5.4. Generally, an inventive composition is free of phenols and ethanol.

(7) A hydrogen peroxide composition is provided that includes hydrogen peroxide present in a concentration 0.5 to 3 total weight percent. Such a solution is readily formed through the dilution of more concentrated hydrogen peroxide. Owing to the role spurious metal ions play in catalytic degradation of hydrogen peroxide, the use of deionized water is preferred. In some inventive embodiments, the saline composition pH is between 3.0 and 5.0. In still other, embodiments, the saline composition pH is between 3.6 and 4.4.

(8) Acids suitable for pH reduction, or acidification, to form an inventive package of mouth wash or gargle include those that are compatible with human mucous membrane contact in diluted form and compatible with other composition and bottle components. Acids operative herein illustratively include hydrochloric, hydrobromic, lactic, citric, malic, acetic, benzoic, ascorbic, tartric, oxalic, tannic, butyric, caffeotannic, phosphoric, sulfuric, nitric, or a combination thereof.

(9) An inventive composition, regardless of whether saline or hydrogen peroxide based, includes various adjuvants. Adjuvants operative herein in terms of function illustratively include antimicrobial, flavorants, desensitizer, a fluoridation agent, or a combination thereof.

(10) An antimicrobial operative herein illustratively includes sodium benzoate, benzoic acid, methylparaben, ethylparaben, propylparaben, paraben derivatives, or a combination thereof. Typical quantities of an antimicrobial, if present, in the inventive composition range from 0.01-3 total weight percent.

(11) A flavorant operative herein illustratively includes an essential oil, a water soluble plant extract, an alcohol soluble plant extract, or a combination thereof. Exemplary flavorants include cloves, culeb oil, cedarwood oil, eucalyptus oil, lemon oil, menta arvensis extracts (e.g. menthol), mint, wintergreen oil, peppermint oil, mint tea concentrate, sucralose, sodium saccharin, other artificial and natural fruit flavors, and combinations thereof. Typical quantities of an anti-oxidant, if present, in the inventive composition range from 0.01-3 total weight percent.

(12) A desensitizer operative herein illustratively includes arginine, camphor, potassium nitrate, potassium chloride, potassium citrate, silver nitrate, zinc chloride, gluteraldehyde, strontium chloride hexahydrate, sodium fluoride, stannous fluoride, strontium chloride, potassium oxalate, calcium phosphate, nano-hydroxyapatite, or a combination thereof. Typical quantities of a desensitizer, if present, in the inventive composition range from 0.1-8 total weight percent.

(13) A fluoridation agent operative herein illustratively includes sodium fluoride, calcium fluoride, hexafluorosilicate, or a combination thereof. Typical quantities of a fluoridation agent, if present, in the inventive composition range from 0.01-0.2 total weight percent.

(14) In some inventive embodiments, fucoidan is present. Fucoidan is a sulfated polysaccharide. As used herein, fucoidan is intended to encompass both F-fucoidan, which is composed predominantly of sulfated esters of fucose, and U-fucoidan, which contains appreciable amounts of glucuronic acid (10-30 weight %). Typical quantities of fucoidan, if present, in the inventive composition range from 0.01-2.0 total weight percent.

(15) It has been discovered to improve the function of saline or hydrogen peroxide composition according to the present invention in terms of treating or preventing infections of the pharyngeal or buccal cavities.

(16) The present invention is further detailed with respect to the following nonlimiting examples. Unless otherwise specified, the percentages detailed herein are total weight percent of the inventive formulation.

EXAMPLE 1-6

(17) A series of inventive compositions are developed with a saline solution base as detailed in Tables 1-4:

(18) TABLE-US-00001 TABLE 1 Formulation of saline gargles with fucoidan. Example 1 Example 2 Saline Gargle with Fucoidan % (w/w) % (w/w) Water 97.49 97.3 NaCl 2.25 2.25 Fucoidan 0.1 0.2 HCl 10% 0.08495 0.08 Sodium Benzoate 0.05 0.05 Menthol 0.025 0.02 pH 4.01 3.75 Total osmolarity 0.78 0.78

(19) TABLE-US-00002 TABLE 2 Formulation of saline gargle without Fucoidan. Saline Gargle without Fucoidan Example 3 Water 97.59 NaCl 2.25 HCl 10% 0.08495 Sodium Benzoate 0.05 Menthol 0.025 pH 3.72 Total osmolarity 0.78

(20) TABLE-US-00003 TABLE 3 Formulation of saline mouthwash with fucoidan. Example 4 Example 5 Saline Mouth Wash with Fucoidan % (w/w) % (w/w) Water 97.185 97.085 NaCl 1.8 1.8 Sodium Benzoate 0.05 0.05 Fucoidan 0.1 0.2 Arginine 0.8 0.8 Sodium Fluoride 0.04 0.04 Menthol 0.025 0.025 pH 6.05 6.08 Total osmolarity 0.69 0.69

(21) TABLE-US-00004 TABLE 4 Formulation of saline mouthwash without fucoidan. Example 6 Saline Mouth Wash without Fucoidan % (w/w) Water 97.285 NaCl 1.8 Sodium Benzoate 0.05 Arginine 0.8 Sodium Fluoride 0.04 Menthol 0.025 pH 6.5 Total osmolarity 0.69

EXAMPLE 7-9

(22) A series of inventive compositions are developed with a hydrogen peroxide solution base as detailed in Tables 5 and 6:

(23) TABLE-US-00005 TABLE 5 Formulation of hydrogen peroxide gargle with fucoidan. Example 7 Example 8 H.sub.20.sub.2 Gargle with fucoidan % (w/w) % (w/w) Hydrogen Peroxide 3% 50 50 Fucoidan 0.1 0.2 HCl 10% 0.0849 0.0849 Sodium Benzoate 0.05 0.05 Menthol 0.025 0.025 Water 49.74 49.64 pH 3.87 4.29 Total osmolarity 0.45 0.45

(24) TABLE-US-00006 TABLE 6 Formulation of hydrogen peroxide gargle without fucoidan. Example 9 H.sub.20.sub.2 Gargle without fucoidan % (w/w) Hydrogen Peroxide 3% 50 Sodium Benzoate 0.05 HCl 10% 0.08495 Menthol 0.025 Water 49.84 pH 4.17 Total osmolarity 0.45

(25) The antimicrobial properties of the composition of Examples 1, 2, and 7-9 are evaluated using ASTM E1052 test method. In an ASTM E1052 test, a suspension of virus is exposed to a test product at a ratio of 1:10 (1 part virus suspension+9 parts prepared test product). A Control suspension is concurrently processed in the same manner, with cell culture medium employed in place of the test product. Following neutralization, the suspensions are enumerated using standard cell culture (e.g. TCID50) or plaque assay techniques. Log 10 and percent reduction values are calculated to determine the effectiveness of the test product suspension relative to the control suspension.

(26) According to this method MS2 Bacteriophage (MS2), ATCC 15597-B1 is the test virus. Bacterial cells are the hosts for bacteriophages, and E. coli 15597 serves this purpose for MS2 bacteriophage.

(27) In summary the method includes the steps of: Stock virus is thawed. Test and control substances are dispensed in 9-part equivalent volumes into sterile vessels. Test and control substances are each inoculated with 1-part equivalent volumes of the test virus. The test suspensions are held for the contact time(s), and then neutralized by ten-fold serial dilutions into the appropriate solution. Gel filtration is employed. The control suspension is neutralized in the same manner as the test suspensions. Viral suspensions are quantified to determine the levels of growth Infectious virus using standard cell culture (e.g. TCID50) or plaque assay techniques, samples are incubated for the period most suitable for the virus-host cell system (e.g. 7 days). After the incubation period, the assay is scored for the presence/absence of test virus and cytotoxic effects. The appropriate calculations are performed (e.g. Spearman-Karber) to determine viral titers and levels of test substance cytotoxicity, where applicable. Viral titers are computed for test suspensions relative to the control.

(28) The test results are summarized in Table 7.

(29) TABLE-US-00007 TABLE 7 bacteriophage inhibition of the Examples 1, 2, and 7-9. Percent Reduction Log1.sub.0 Reduction Compared to Compared to Test Contact Test Average Control at Time Control at Time Microorganism Time Substance Replicate PFU/ml PFU/ml Zero Zero MS2 Time Zero Control 1 8.65E+05 1.20E+06 N/A ATCC 15597- 2 7.70E+05 3 1.95E+06 30 Seconds Ex. 1 1 2.59E+05 2.09E+05 82.55% 0.76 2 1.86E+05 3 1.81E+05 Ex. 2 1 3.00E+05 2.51E+05 78.97% 0.68 2 2.22E+05 3 2.32E+05 Ex. 7 1 1.97E+05 1.90E+05 84.10% 0.80 2 2.18E+05 3 1.56E+05 Ex. 8 1 1.02E+05 9.55E+04 92.01% 1.10 2 8.80E+04 3 9.65E+04 Ex. 9 1 2.08E+05 2.07E+05 82.68% 0.76 2 2.06E+05 3 1.66E+05

(30) To further evaluate antimicrobial properties of the inventive compositions, Minimum Inhibitory Concentration Method (MIC) is performed. This is a general microbiological test method that is used to measure the lowest level of an antimicrobial agent that can inhibit microbial proliferation in liquid. The procedure is summarized as follows: Test microorganisms are prepared in liquid culture medium for bacteria or on agar for fungi. The test substance is prepared by conducting several serial 1:1 dilutions in a 96-well microtiter r in small test tubes, through Mueller-Hinton broth or other appropriate medium. All wells or tubes containing diluted test substances are inoculated with test microorganisms, individually, resulting in one additional and final dilution of the product in all test vessels. The microtiter plate or test tubes are incubated for 18-24 hours. After the incubation period, observations are made.

(31) The results for various organisms are detailed in Tables 8-13.

(32) TABLE-US-00008 TABLE 8 24 hour results for Examples 1-3. Test Microorganism Test Substance 24 Hour Result E. coli Solution Ex. 3 ATCC 8739 Solution Ex. 1 + Solution Ex. 2 H. influenzae Solution Ex. 3 ATCC 8149 Solution Ex. 1 Solution Ex. 2 K. pneumoniae Solution Ex. 3 ATCC 29019 Solution Ex. 1 + Solution Ex. 2 L. acidophilus Solution Ex. 3 + ATCC 4356 Solution Ex. 1 + Solution Ex. 2 + M. catarrhalis Solution Ex. 3 ATCC 25238 Solution Ex. 1 Solution Ex. 2 P. aeruginosa Solution Ex. 3 + ATCC 15442 Solution Ex. 1 + Solution Ex. 2 P. mirabilis Solution Ex. 3 + ATCC 7002 Solution Ex. 1 + Solution Ex. 2 S. pneumoniae Solution Ex. 3 ATCC 49619 Solution Ex. 1 + Solution Ex. 2 + S. pyogenes Solution Ex. 3 + ATCC 19615 Solution Ex. 1 + Solution Ex. 2 + S. aureus Solution Ex. 3 + ATCC 33592 Solution Ex. 1 + Solution Ex. 2

(33) TABLE-US-00009 TABLE 9 24 hour results for Examples 4-6. Test Microorganism Test Substance 24 Hour Result L. acidophilus Solution EX. 6 + ATCC 4356 Solution Ex. 4 + Solution Ex. 5 + S. sobrinus Solution Ex. 6 + ATCC 33478 Solution Ex. 4 + Solution Ex. 5 + S. sobrinus Solution EX. 6 + ATCC 33478 Solution Ex. 4 + Solution Ex. 5 + ATCC 25175 Solution EX. 6 Solution Ex. 4 Solution Ex. 5

(34) TABLE-US-00010 TABLE 10 24 hour results for Examples 7-9. Test Microorganism Test Substance 24 Hour Result H. influenzae Solution Ex. 9 ATCC 8149 Solution Ex. 7 + Solution Ex. 8 S. pneumoniae Solution Ex. 9 ATCC 49619 Solution Ex. 7 Solution Ex. 8 S. pyogenes Solution Ex. 9 ATCC 19615 Solution Ex. 7 Solution Ex. 8

(35) TABLE-US-00011 TABLE 11 MIC and MBC results for Examples 1-3. Test CFU/ml Test Positive Negative Microorganism Results Substance MIC MBC Control Control E. coli 2.05E+05 Solution EX. 3 No Growth No MBC + ATCC 8739 Observed Observed Solution Ex. 1 Growth No MBC + Observed Observed Solution Ex. 2 No Growth No MBC + Observed Observed H. influenzae 3.15E+06 Solution Ex. 3 No Growth No MBC + ATCC 8149 Observed Observed Solution Ex. 1 No Growth No MBC + Observed Observed Solution Ex. 2 No Growth No MBC + Observed Observed K. pneumoniae 3.00E+04 Solution Ex. 3 No Growth No MBC + ATCC 29019 Observed Observed Solution Ex. 1 Growth No MBC + Observed Observed Solution Ex. 2 No Growth No MBC + Observed Observed L. acidophilus 3.15E+06 Solution Ex. 3 Growth No MBC + ATCC 4356 Observed Observed Solution Ex. 1 Growth No MBC + Observed Observed Solution Ex. 2 Growth No MBC + Observed Observed M. catarrhalis 4.35E+06 Solution Ex. 3 No Growth No MBC + ATCC 25238 Observed Observed Solution Ex. 1 No Growth No MBC + Observed Observed Solution Ex. 2 No Growth No MBC + Observed Observed P. aeruginosa 2.05E+04 Solution Ex. 3 Growth No MBC + ATCC 15442 Observed Observed Solution Ex. 1 Growth No MBC + Observed Observed Solution Ex. 2 No Growth No MBC + Observed Observed P. mirabilis 7.65E+05 Solution Ex. 3 Growth No MBC + ATCC 7002 Observed Observed Solution Ex. 1 Growth No MBC + Observed Observed Solution Ex. 2 No Growth No MBC + Observed Observed S. pneumoniae 1.75E+04 Solution Ex. 3 No Growth MBC + ATCC 49619 Observed Solution Ex. 1 Growth No MBC + Observed Observed Solution Ex. 2 Growth No MBC + Observed Observed S. pyogenes 1.15E+06 Solution Ex. 3 Growth No MBC + ATCC 19615 Observed Observed Solution Ex. 1 Growth No MBC + Observed Observed Solution Ex. 2 Growth No MBC + Observed Observed S. aureus 2.40E+05 Solution Ex. 3 Growth No MBC + ATCC 33592 Observed Observed Solution Ex. 1 Growth No MBC + Observed Observed Solution Ex. 2 No Growth No MBC + Observed Observed

(36) TABLE-US-00012 TABLE 12 MIC and MBC results for Examples 4-6. Test Positive Negative Microorganism CFU/ml Results Test Substance MIC MBC Control Control L. acidophils 3.00E+05 Solution Ex. 5 Growth No MBC + ATCC 4356 Observed Observed Solution Ex. 4 Growth No MBC + Observed Observed Solution Ex. 6 Growth No MBC + Observed Observed S. sobrinus 5.40E+04 Solution Ex. 4 Growth No MBC + ATCC 33478 Observed Observed Solution Ex. 5 Growth No MBC + Observed Observed S. mutans 8.00E+05 Solution Ex. 6 Growth No MBC + ATCC 25175 Observed Observed Solution Ex. 4 No Growth MBC + Observed Observed Solution Ex. 5 No Growth MBC + Observed Observed

(37) TABLE-US-00013 TABLE 13 MIC and MBC results for Examples 7-9. Test CFU/ml Positive Negative Microorganism Results Test Substance MIC MBC Control Control S. influenenzae 3.15E+06 Solution Ex. 9 No Growth No MBC + ATCC 8149 Observed Observed Solution Ex. 7 No Growth No MBC + Observed Observed Solution Ex. 8 No Growth MBC + Observed Observed S. pneumoniae 1.75E+04 Solution Ex. 9 No Growth MBC + ATCC 49619 Observed Solution Ex. 7 No Growth MBC + Observed Solution Ex. 8 No Growth MBC + Observed S. pyogenes 1.15E+06 Solution Ex. 9 No Growth MBC + ATCC 19615 Observed Solution Ex. 7 No Growth MBC + Observed Solution Ex. 9 No Growth MBC + Observed

(38) Any patents or publications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication was specifically and individually indicated to be incorporated by reference.

(39) The foregoing description is illustrative of particular embodiments of the invention, but is not meant to be a limitation upon the practice thereof.