Method and system for made-on-demand instantly formed hypochlorous acid GEL composition

Abstract

A method (100) to provide a Make-On-Demand hypochlorous acid gel composition based on an alkaline solution including a hypochlorite concentration of less than or equal to about 10,000 ppm and the alkaline solution having a pH range of about 12.0 to about 13.0, and an acidic solution, including a pH sensitive polymer thickener and a pH modifying agent, capable of forming an hypochlorous acid gel when the acidic solution is combined with the alkaline solution. The alkaline solution and the acidic solution are kept separate prior to use, and are combined immediately before or during use to form the hypochlorous acid gel composition when a pH of mixture is between about 5.0 to about 7.0. In composition, a system can be made up of two parts, three parts, four parts, or multi-part for on-site instantly forming the hypochlorous acid gels to achieve the Make-On-Demand function.

Description

METHOD AND SYSTEM FOR MADE-ON-DEMAND INSTANTLY FORMED HYPOCHLOROUS ACIDGEL COMPOSITIONFIELD OF THE DISCLOSURE

[0001] The present disclosure is directed generally to a make-on-demand instantly formed hypochlorous acid gel composition and related methods, systems, and kit for preparing such a composition.BACKGROUND

[0002] Periodontal health is an important component of oral health. It includes healthy gingivae and periodontal attachment in the natural dentition and the health of their equivalent structures around dental implants. In oral health care, the most common types of dental disease are tooth decay and gum diseases, including gingivitis and periodontitis. The underlying cause behind gingivitis, periodontitis, peri-implant mucositis, and peri-implantitis, is microbial plaque forming a biofilm, which is rich in pathogenic bacteria. The removal of the biofilm and effective elimination of the bacteria from teeth and gum is important for effective prevention of dental disease, treatment of gum diseases, and maintenance of oral health and hygiene.

[0003] For treatment and prevention of dental disease, a variety of oral health care products like mouthwashes and power toothbrushes have been developed. For periodontal disease prevention, daily brushing and flossing, using an antiseptic mouthwash and regular professional teeth cleaning are recommended. For periodontal disease treatment, use of disinfectant, antibiotics, or dental surgery is recommended. Normally, once a successful periodontal treatment has been completed, with or without surgery, an ongoing regimen of periodontal maintenance is required. In periodontal maintenance, using disinfectant and antiseptic containing mouthwash such as hydrogen peroxide, cetylpyridinium chloride, essential oils, or sodium hypochlorite is common practice.

[0004] Existing disinfectant products to treat or prevent periodontal and peri-implant diseases are typically produced in the form of solids, powder, liquid, cream, and sometimes in pre-formed gels. Due to the recalcitrant nature of biofilm against its removal and partly due to the stability issue of gel products that use strong oxidizing type disinfectants, there are several disadvantages to existing products, such as high concentrations of hydrogen peroxide (10 % to 30 %), long contact times required for sporicidal activity, a risk to develop drug or antibiotic resistance, high cost of the products, limited retention capability on the infected area, in particular for liquid type products, the use of large volumes of liquid inside the mouth or on the gum and / or tooth surface, and sometimes a recommendation to avoid eating or drinking anything for 30 minutes afterward. Those requirements bring discomfort and inconvenience to the user.

[0005] Other disadvantages of existing products may include the presence of a bad or unpleasant taste or smell. For example, one of the main causes of unpopularity of sodium hypochlorite mouthwashes is the bad taste. Furthermore, there may be undesired side effects during use, or accidental swallowing or overdosing of the product. Another disadvantage of existing products is the handling inconvenience when applying solid, powder, and liquid products to stay in a particular area.

[0006] In view of the foregoing, there is a persisting need to improve oral disinfecting technology.SUMMARY

[0007] Addressing a need for improvements in disinfecting technology, the present disclosure provides a make-on-demand instantly formed hypochlorous acid gel composition for oral healthcare and medical applications.

[0008] According to an example implementation of the inventive subject matter, a method of making a hypochlorous acid gel composition, may include the following steps: providing an alkaline solution including a hypochlorite concentration of less than or equal to about 10,000 ppm and the alkaline solution having a pH range of about 12.0 to about 13.0; providing an acidic solution, including a pH sensitive polymer thickener and a pH modifying agent,capable of forming an hypochlorous acid gel when the acidic solution is combined with the alkaline solution; keeping the alkaline solution and the acidic solution separate prior to use; and combining the alkaline solution and the acidic solution immediately before or during use to form the hypochlorous acid gel composition when a pH of the mixture is between about 5.0 to about 7.0.

[0009] In some embodiments, the hypochlorous acid gel composition is formed in less than about 10 seconds after combining the alkaline solution and the acidic solution. In some embodiments, the hypochlorous acid gel composition has a pH in the range of about 5.5 to about 6.0. In some embodiments, the alkaline solution includes a hypochlorite concentration of less than or equal to about 5000 ppm. In some embodiments, the pH sensitive polymer thickener includes a pH sensitive rheology modifying polymer of low viscosity that thickens at a pH of about 4.0 or above. In some embodiments, the pH sensitive polymer thickener is a hydrophobically modified alkali soluble polymer emulsion; in other embodiments, the pH sensitive polymer thickener is a highly crosslinked polyacrylic acid polymer. In some embodiments, the pH modifying agent is selected from citric acid, carbonic acid, acetic acid, phosphoric acid, or other compatible acid. In some embodiments, a mixing ratio of the alkaline solution to the acidic solution falls into a range of 1:1 to 10:1. In further embodiments, the alkaline solution further includes a functional agent that is compatible with hypochlorous acid for at least 0.5 hours at a temperature below or equal to 40 degrees Celsius.

[0010] According to another example implementation of the inventive subject matter, a Make-On-Demand hypochlorous acid gel composition includes an alkaline solution including a hypochlorite concentration of less than or equal to about 10,000 ppm and the alkaline solution having a pH range of about 12.0 to about 13.0; and an acidic solution, including a pH sensitive polymer thickener and a pH modifying agent, capable of forming an hypochlorous acid gel when the acidic solution is combined with the alkaline solution. Upon combining the alkaline solution and the acidic solution into a mixture immediately before or during use, the hypochlorous acid gel composition is formed when a pH of the mixture is between about 5.0 to about 7.0.

[0011] In some embodiments, the pH of the hypochlorous acid gel composition becomes centered around 5.8 within less than about 10 seconds after mixing the alkaline solution and the acidic solution.

[0012] According to another example implementation of the inventive subject matter, a system for making a hypochlorous acid gel composition, includes a dosing device including a first compartment containing an alkaline solution including a hypochlorite concentration of less than or equal to about 10,000 ppm and the alkaline solution having a pH of about 12.5, and a second compartment containing an acidic solution, including a thickener and a pH modifying agent, capable of forming the hypochlorous acid gel composition when the acidic solution is combined with the alkaline solution; and a mixing chamber to combine the alkaline solution and the acidic solution into a mixture wherein the hypochlorous acid gel composition is created when the pH of the mixture reaches a pH value between about 5.0 to about 7.0.

[0013] In some embodiments, the dosing device further comprises at least one additional compartment, and wherein a content of the at least one additional compartment is dispensed into the chamber.

[0014] According to another example implementation of the inventive subject matter, a kit for generating a Make-On-Demand hypochlorous acid gel composition, the kit includes a first composition including an alkaline solution including a hypochlorite concentration of less than or equal to about 10,000 ppm and the alkaline solution having a pH range of about 12.0 to about 13.0, and a second composition including an acidic solution, including a pH sensitive polymer thickener and a pH modifying agent, capable of forming an hypochlorous acid gel when the acidic solution is combined with the alkaline solution. The first composition and the second composition are kept separate prior to use. The first composition and the second composition are combined in a mixing chamber to form a mixture immediately before or during use, wherein the mixture generates the hypochlorous acid gel composition when the pH of the mixture is between about 5.0 to about 7.0. The mixing chamber is configured to dispense the hypochlorous acid gel composition to an area to be treated.

[0015] The disclosed subject matter is directed to a make-on-demand (MOD), instantly on-site produced hypochlorous acid based gel, which is safer, more effective, and more user-friendly than existing products for prevention and / or treatment of periodontal disease and periimplant diseases in oral health care. Furthermore, since hypochlorous acid is a broad-spectrum disinfectant and / or antiseptic, the disclosed subject matter can be expanded to hypochlorous- acid-based sanitization applications that require prolonged contact time to be effective, such as applications in household, industrial, institutional, and health care settings.

[0016] By using MOD, instantly gelling compositions, systems and methods disclosed herein, the inventive subject matter not only overcomes many disadvantages of the existing products, but also improves the freshness, speed, efficacy, efficiency, and process of producing powerful hypochlorous acid-based gels for the prevention or treatment of periodontal disease and peri-implant diseases, and for sanitization applications in other industries. The disclosed implementations can provide higherflexibility in product storage, shipping, and shelf-life control.

[0017] These and other aspects of the disclosure will be apparent from and elucidated with reference to the embodiment(s) described hereinafter.BRIEF DESCRIPTION OF THE DRAWINGS

[0018] In the drawings, like reference characters generally refer to the same parts throughout the different views. Also, the drawings are not necessarily to scale, emphasis instead generally being placed upon illustrating the principles of the inventive subject matter.

[0019] FIG. 1 is a schematic view of an example embodiment of a system for making a MOD, on-site hypochlorous acid gel composition with a dual-barrel dosing device.

[0020] FIG. 2 is a schematic representation of an exemplary system for forming and dispensing an on-site instant hypochlorous acid gel composition.

[0021] FIG. 3 is high-level flow chart of an exemplary method of making an hypochlorous acid gel composition using a two-part system.DETAILED DESCRIPTION OF EMBODIMENTS

[0022] The following disclosure provides different embodiments and examples for implementing different features of the provided subject matter. Specific examples ofcomponents and arrangements are described below to simplify the present disclosure. These are, of course, merely examples and are not intended to be limiting.

[0023] The present disclosure describes various implementations, embodiments, and examples of hypochlorous acid-based products that are formed as a make-on-demand (MOD), instantly formed hypochlorous acid gel composition right before or during use. The gel composition can be effectively used for prevention and treatment of gingivitis, periodontal diseases, and peri-implant diseases in oral health care, or for wound care and other medical applications.

[0024] Hypochlorous acid (HOCI) has been known as a wound care agent with powerful microbiocidal, antibiofilm, and wound healing potency. In clinical studies, HOCI is proven to be 80-100 times more effective and kills microorganisms faster than commonly used hypochlorite ions (CIO ). A reason for the effectiveness of hypochlorous acid is that in electrochemistry, HOCI is electrically neutral whereas CIO- is electrically negative. As a result, HOCI behaves differently than CIO’. For example, the cell wall of pathogenic microorganisms is negatively charged by nature. The negative charge of the hypochlorite ion will be repulsed by the negative charge of the pathogenic microorganism cell wall making it a weak disinfectant. Due to electrical neutrality, the neutral HOCI molecule can easily penetrate the cell wall of the pathogenic microorganism, thus making it a very effective disinfectant. Additionally, HOCI can also easily penetrate slime layers, cell walls, and protective layers of microorganisms and effectively kills pathogens as a result. Furthermore, HOCI is also a much more reactive and a stronger disinfectant than hypochlorite ions, as HOCI is split into hydrochloric acid (HCI) and an oxygen atom, which in itself is a powerful disinfectant.

[0025] In general, with an acidity pKa - 7.53, hypochlorous acid is a known weak acid that forms when chlorine dissolves in water, and itself partially dissociates, starting to form hypochlorite ions (CIO ) when the pH goes above approximately 5.5. HCIO cannot be isolated from solutions due to rapid equilibration with its precursor chlorine and its dissociated hypochlorite ions. There is a dynamic balance among Ch molecules, HOCI molecules, and CIO’ anions in aqueous hypochlorous acid solution within a pH range of about 4 to about 9. It is known that between pH 4 and 7, chlorine exists predominantly as HOCI. The amount of hypochlorousacid decreases dramatically into chlorine gas (CI2) when the pH is below 4. Above pH 9, CIO- predominates. When the pH of an aqueous solution is over 6.0, the proportion of HOCI declines from virtually 100 % down to almost 0 % at pH 9.0. When the pH of the solution is between 4.0 and 5.5, hypochlorous acid is at its maximum level. However, solutions with pH values lower than 5.0 will begin to generate and release potentially harmful levels of chlorine gas (Ch). Therefore, oral disinfection will ideally and safely take place when the pH is between 5.0 and 6.0, when an optimal level of hypochlorous acid, i.e., when the HCIO concentration is more than or equal to 95 %, is present and there is no risk for generation of harmful chlorine gas. For applications in this disclosure, an instantly formed hypochlorous acid gel with a pH in the range of about 5.5 to about 6.0 is desired, and preferably a pH centered around 5.8.

[0026] The term "about," as used herein, refers to variation in the numerical quantity that can occur, for example, through typical measuring and liquid handling procedures used for making concentrates or use solutions in the real world; through inadvertent error in these procedures; through differences in the manufacture, source, or purity of the ingredients used to make the compositions or carry out the methods; and the like. The term "about" also encompasses amounts that differ due to different equilibrium conditions for a composition resulting from a particular initial mixture.

[0027] As used herein, the term "Make on demand" in refers to the practice of preparing the hypochlorous acid gel composition as and when it is needed, rather than requiring storage and / or shipment of the hypochlorous acid gel in advance. Among other benefits, this ensures that the gel composition is as fresh and reactive as possible when needed.

[0028] As used herein, the term "immediately before use" refers to a period of time immediately before the gel composition is intended to be utilized, applied, or put into action, indicating that an action or preparation is to be carried out immediately before the intended use of the end product.

[0029] As used herein, the term "instantly formed" refers to a period of time need to transforms from a liquid or solid state into a gel-like structure when a specific trigger or condition is met. In embodiments described herein, the hypochlorous gel composition can be formed in less than about 10 seconds after combining the alkaline solution and the acidic solution and isready to be applied to a surface to be treated. In many embodiments, formation within 5 seconds after combining the alkaline solution and the acidic solution is preferred.

[0030] The disclosed subject matter can produce MOD, on-site, powerful hypochlorous acid gel instantly by mixing different parts of the composition before or during application and thereby overcomes the stability problem of pre-formed hypochlorous acid gel during long-term storage.

[0031] In general, to make an instantly formed gel product from a system with liquid components, a specific thickener is needed. As used herein, the term "thickening" refers to an increase in the viscosity of the composition. A pH sensitive thickener is capable of increasing the viscosity of a composition upon subjecting it to a pH change. In some embodiments, before the instant gel formation, the thickener exists as a stable, low viscosity ingredient in one component of the system. But when mixing the thickener with other one or more components of the system, some factors change or an ingredient in the final mixture will trigger the thickener to rapidly thicken in solution due to electrostatic repulsion within thickener molecules, hydrophobic parts building associations with one another and with other hydrophobes available in the formulation, and / or cross-linking reactions. In this disclosure, a pH change is used as the trigger factorto make the thickener immediately thicken the solution into the instantly formed gel. Instantly gelling around a pH of about 5.0 to about 6.0 of the hypochlorous acid-based gel is well suited for the intended applications.

[0032] In some embodiments, pH sensitive polymer thickeners such as hydrophobically modified alkali soluble polymer emulsion (HASE) thickeners can be used. Typically, HASE polymer thickeners have unusually high aqueous thickening and stabilizing efficiency only when the pH of final composition goes above 7.0. But there are some exceptions to that pH requirement. For example, a HASE-type polymer ACULYN™ 28thickensthe formulation from pH 5.5 to pH lO easily. At a pH around 5.8, it already reaches more than 95 % of its thickening capacity. Such thickening property is desirable for some implementations and embodiments described herein. ACULYN™ 28 is typically supplied as a low viscosity (<30 mPa.s) liquid emulsion with a pH around 3.0. But it will rapidly thicken solutions when their acid groups undergo ionization transitions from very acidic pH (pH< 5.0) to less acidic pH (pH 5.5 or above) or basic pH (7< pH <12). When the acidgroups lose their protons and are neutralized, they become anionic charged and water-soluble, thus swell due to dramatic charge-charge electrostatic repulsion. In addition, networking of numerous pendant hydrophobic groups of ACULYN™ 28 in their molecules with themselves and other hydrophobes available in the formulation also boost their thickening effect. The final composition immediately thickens exponentially to become a high viscous gel. When the pH of the final composition is above 5.5, it remains a high viscosity gel.0033] In other embodiments, pH sensitive polymer thickeners such as highly crosslinked polyacrylic acid polymer like Carbopol® polymers can be used. Carbopol® polymers, such as Carbopol® 940 NF, thicken the formulation in a pH range of about 4.0 to about 10. In that pH range, when carboxylic groups of Carbopol® polymers lose their protons and are neutralized, they become anionic charged and water-soluble, thus they swell due to dramatic charge-charge electrostatic repulsion. At a pH 5.8, Carbopol® 940 NF already reaches more than 95 % of its thickening capacity.

[0034] In some embodiments, the formation of the hypochlorous acid gel composition may occur as follows: when an alkaline solution of low hypochlorite concentration, drops below pH 7.0 after mixing with an acidic solution containing the right thickeners and a pH modifying agent, to a final pH of around 5.8, the final mixed composition thickens into a gel composition. The concentration of the alkaline solution of low hypochlorite concentration can be, for example, less than or equal to 10000 ppm (wt. / wt.), preferably less than or equal to 5000 ppm, with a pH of around 12.5. The pH drops preferably to around 5.0 to 6.0, with a pH of about 5.5 to about 6.0 being preferred for applications on humans. Examples of thickeners can include ACULYN™ 28 or Carbopol 940 NF. Examples of pH modifying agents include citric acid, carbonic acid, acetic acid, phosphoric acid, or other compatible acid.

[0035] According to the inventive subject matter, the on-site produced MOD hypochlorous acid gel can be prepared by combination of chemical and mechanical means. The chemical means include the selective formulation in composition. The mechanical means refer to specific MOD dosing systems and / or devices for different compositions.

[0036] In some implementations, systems for making hypochlorous acid gel compositions can consist of different components. Embodiments of systems for making hypochlorous acid gelcompositions including two parts, three parts, four parts, and multi-part components are discussed below.

[0037] Example embodiments of systems made of two parts

[0038] In some embodiments, part (a) includes an alkaline solution of hypochlorite having a concentration of less than or equal to 1 % (wt. / wt.), and / or other hypochlorite compatible functional agents, for example a desensitizer such as potassium nitrate, if needed.

[0039] In some embodiments, part (b) includes an acidic pH modifying agent, a HASE polymer, and flavor(s), solvent(s), surfactant(s), desensitizer, and / or other functional or inert chemical(s), depending on what other function(s) is provided for the product. The HASE polymer can be a HASE polymer that is compatible with hypochlorous acid having a concentration < 10000 ppm and a low pH, such as pH 2-4. Examples of suitable HASE polymers include ACULYN™ 28 and Carbopol® polymers such as Carbopol® 940 NF.

[0040] Example embodiments of systems made of three parts

[0041] In some embodiments, part (a) can includes an alkaline solution of hypochlorite component, and hypochlorite compatible functional agent(s) such as potassium nitrate, if needed.

[0042] In some embodiments, part (b) can include of a pH sensitive rheology modifying HASE polymer that is compatible with hypochlorous acid of a <10000 ppm concentration. Examples include ACULYN™ 28 or a Carbopol® polymer such as Carbopol® 940 NF, and other functional, inert agent(s) that are compatible with hypochlorous acid (< 10000 ppm), if needed.

[0043] In some embodiments, part (c) can include an acidic pH modifying agent(s) that is compatible with hypochlorous acid (<10000 ppm). In some embodiments, part (c) can include other functional ingredients / agents that are compatible with hypochlorous acid (<10000 ppm) and with a low pH (2-4). Examples of such other functional ingredients / agents include flavor(s), solvent(s), surfactant(s), desensitizer, and / or other chemical(s), depending on what function(s) is desired for the end product.

[0044] Example embodiments of systems made of four parts

[0045] In some embodiments, part (a) can include an alkaline solution of hypochlorite component, and / or hypochlorite (<1 % (wt. / wt.)) compatible functional agent(s), for example potassium nitrate, if needed.

[0046] In some embodiments, part (b) can include a "hypochlorous acid (<10000 ppm)" compatible pH sensitive rheology modifying HASE polymer such as ACULYN™ 28 or Carbopol® polymer such as Carbopol® 940 NF, and / or other "hypochlorous acid (<10000 ppm)" compatible functional / inert agent(s), if needed.

[0047] In some embodiments, part (c) can include a "hypochlorous acid (<10000 ppm)" compatible flavor(s), and / or other flavor(s) compatible functional or inert ingredient(s).

[0048] In some embodiments, part (d) can include a "hypochlorous acid (<10000 ppm)" compatible acidic pH modifying agent(s), and / or "hypochlorous acid (<10000 ppm) and low pH (pH 2-4) compatible" functional / inert chemical(s).

[0049] Example embodiments of systems made of multiple parts

[0050] In some embodiments, if the MOD, on-site instant gelling method uses an individual ingredient-feeding system similar to a soda fountain, then each one of the above ingredients may become one part of the multi-part system composition. However, not every available ingredient must be present in a single part of the multi-part composition. For example, a pH modifying agent and a desensitizer can be easily formulated as one part.

[0051] In the described embodiments, each functional agent or ingredient used in the composition should at least be compatible with hypochlorous acid for at least a short duration term (> 0.5 hours) at a temperature below or equal to 40 °C. The final pH of the mixture of all ingredients must be within a pH range of about 5.5 to about 6.0, and a final pH of around 5.8 of the mixture is desired for applications on humans. As used herein, a "functional agent or ingredient" can refer to any ingredient that improves stability or desired performance features of the end product. As such functional agents can include flavors, solvents, surfactants, desensitizers, and other suitable additives.

[0052] There are several methods in which MOD, on-site instantly formed hypochlorous acid gels can be formed, produced, dosed, and used. The following sections A to C are detailed descriptions of these exemplary methods.

[0053] A. Exemplary Method 1: On-site MOD, instantly formed hypochlorous acid gels by composition of two parts and dosing system

[0054] As described above, the inventive subject matter can provide a kit with two parts, part (a) and part (b). The compositions of part (a) and part (b) can be contained in separate reservoirs or cartridges of a single unit and can be adapted to produce a MOD, instantly formed on-site hypochlorous acid gel of by mixing part (a) and part (b). Upon combination of the two parts, the pH level is designed to trigger formation on-site of a MOD hypochlorous acid gel with a pH which maximizes the disinfection (pH 5.5-6) or sanitization (pH 5-7) efficiency. Detailed descriptions of ingredients, mixing ratio, and dosing devices used in Exemplary Method 1 are described below.

[0055] Hypochlorite(s) in part (a)

[0056] In some embodiments, the hypochlorite compound used can be sodium hypochlorite meeting the quality requirements set forth by Reagent Grade (RG), American Chemical Society (ACS) Grade, National Formulatory (NF) Grade, Food Chemical Codex (FCC) or US Pharmacopeia (USP) grade. Most stable commercial sodium hypochlorite products are at pH range of about 12.0 to about 13.0 with around 0.2-1.0 % excess caustic soda before dilution. The concentration of sodium hypochlorite in part (a) can be as high as 5 % (wt. %), but around 0.005- 1.0 % may be preferred in some embodiments. For hypochlorite stability purposes, a preferred pH can be within the pH range of 12.0 - 13.0 for part (a). In some embodiments, a recommended sodium hypochlorite concentration for part (a) can be within the range of 0.005 %-1.0 %, and 0.01 %-1.0 % strength, if refrigeration storage condition is not used. Since a potential dilution of high concentrations of commercial sodium hypochlorite raw material is included in preparation of 0.005 %-1.0 % strength of sodium hypochlorite, the excess of caustic soda in the diluted final solution of sodium hypochlorite can be controlled within the 0.04 %-0.2 % range. Thus, less acidic pH modifying agent would be needed in part (b) of the composition.

[0057] In some embodiments, to achieve accurate pH control of the final instantly formed hypochlorous acid gel, the excess sodium hydroxide (caustic soda) and total caustic content of sodium hypochlorite solution or other types of hypochlorite solution (as raw material) should be accurately determined and controlled using a test method such as ASTM D2022 or other suitable test methods. It will determine the amount of acidic part (b) that is needed to move the final gel pH to slightly acidic level within pH 5.5-6.0 to maximize the killing power of hypochlorous acidgel due to safety consideration and its highest Oxidation Reduction Potential (ORP) value at that pH range. In the alternative, other hypochlorites like calcium hypochlorite can be used and may be preferred when solutions of a soluble hypochlorite are employed.

[0058] Other hypochlorite(s) compatible functional ingredient(s) in part (a)

[0059] In some embodiments, other alkaline and hypochlorite compatible functional and / or inert ingredient(s) may be present in USP, ACS, Reagent, Food, or NF grade. Extra pH modifying agent may be added to control the solution pH to be within a pH range of 12.0-13.0, if needed. In some embodiments, the dosage of alkaline composition of part (a) may include 0.01- 0.1 molar commercial potassium hydroxide or caustic soda in aqueous solution. In some embodiments, potassium nitrate may also be present for desensitizing functions or the like.

[0060] pH sensitive rheology modifying polymer(s) in part (b)

[0061] In some embodiments, hypochlorite or hypochlorous acid (<1% (wt. / wt.)) compatible, non-hazardous, pH sensitive rheology modifying polymers in FCC, USP, ACS, Reagent or NF, Food, CG grade may be used. In some embodiments, the pH sensitive rheology modifying polymers should be at least compatible for more than 0.5 hour. Those polymers can thicken compositions substantially at an acidic pH of 5.5-7.0. Such polymers could be HASE-type polymer such as ACULYN™ 28 or Carbopol® polymer such as Carbopol® 940 NF. In some embodiments, a preferred dosage is between 0.1-3 % (solid %) level in the final finished gel.

[0062] pH modifying agent in part (b)

[0063] In some embodiments, in order to make the part (a) solution stable over long shelf life and also have the finished product attain the desired pH in the final composition gels, an acidic pH modifying agent(s) may be used in part (b). The acidic pH-modifying agent can be attained by using hydrochloric acid, citric acid, and other compatible inorganic or organic acids in USP, ACS, Reagent, Food, or NF grade. In some embodiments, it may be preferred that the dosage of the acidic composition of part (b) includes is 0.001-0.2 M commercial acid.

[0064] Flavors in part (b)

[0065] Flavoring agents are substances that trigger the sense of taste and / or smell. In some embodiments they can be used to improve the consumer perception and experience in application by either adding flavor to an otherwise flavorless product or to mask any undesirableflavors. In some embodiments, long or short-term compatible flavor agents in FCC, USP, ACS, Reagent, Food, or NF grade, such as menthol or peppermint oil may be preferred for dental applications.

[0066] Desensitizer, solvents, surfactants, and / or other chemicals in part (b)

[0067] In some embodiments, other "hypochlorous acid (<10000 ppm) and low pH (2-4)" compatible functional agents in FCC, USP, ACS, Reagent or NF grade may be added. The functional agents can be short-term or long-term compatible agents. Examples of suitable desensitizers include potassium nitrate and potassium chloride. An example of a suitable solvent includes propylene glycol. In some embodiments, surfactants such as sodium lauryl sulfate, Neodol ® 91- 8, and other suitable surfactants could also be added in part (b) to provide the desired functions.

[0068] Mixing Ratios

[0069] In some embodiments, it is preferred that a mixing ratio of part (a) to part (b) falls into the range of 1:1 - 10:1, with ratios around 1:1 to 4:1 being particularly preferred. The optimal mixing ratio will be dependent on the nature and quantities of the components present. The desired operative consideration being that the final mixed composition should have a pH within 5.5-6.0 for treatment or prevention of periodontal disease and peri-implant diseases, and a pH within the range of 5.0-7.0 for sanitization applications overall.

[0070] Dosing system

[0071] In some embodiments, for the two-part composition system, a dosing device can be a dual-barrel syringe, a dual-chamber bottle, or a dispensing device that can dispense two separate fluids to a specifically designed, detachable common mixing chamber or mixing tip. Such device can be formed with two compartments, for example in the form of detached containers, cartridges, or integrated chambers.

[0072] FIG. 1 shows an example embodiment of a dosing device 10 and an enlarged detail of a detachable, specific static mixing tip / chamber, hereinafter referred to as mixing chamber 12. Dosing device 10 includes a dual-barrel syringe 14 and mixing chamber 12. The two outlets of dual-barrel syringe 14 and the contents therein are sealed by a detachable cap (not shown) during storage or before application. During application, the detachable cap is removed, and mixing chamber 12 is arranged on dual-barrel syringe 14 and connected with the two outlets ofdual-barrel syringe 14. In design, mixing chamber 12 has two relatively long, separate passage tubes 16, 18 situated before the start of static mixing section 20 of mixing chamber 12.

[0073] In embodiments where the dosing device is carrying contents for more than one treatment, a purpose of mixing chamber 12 is to avoid cross contamination of the contents of the two liquid parts after dispensing and forming the first gel for initial application. In some embodiments, a simple replacement of such a detachable, and / or disposable, mixing chamber of the previous use by a new one from the gel dispensing device can be easily done for the second or next use. As a result, the remaining liquid contents of the dual-barrel, dual-chamber or dual cartridge will not be contaminated at the mixing section due to potential backflow and mixing, and the risk of cross contamination due to the mixing chamber is avoided.

[0074] In those embodiments where dosing device 10 is a dual-chamber dispensing device, dosing device 10 can further include a pump or vacuum means to simultaneously withdraw fluid from each compartment, via separate draw pipes, and discharge the fluid to a specific, detachable common static mixing chamber similar to mixing chamber 12 and after that, to the application areas to be treated. When needed, the alkaline and the acidic parts of materials are mixed and gelled at a joint static mixing point or chamber before starting the dental treatment or sanitization operation.

[0075] In some embodiments, due to the liquid properties of each part's composition in the dual-barrel syringe, dual-chamber bottle, or dispensing device with dual-cartridge, good sealing parts or valve design may be needed to safely hold the two liquid components in their respective syringe barrel, chamber, or cartridge during storage or before application.

[0076] An example formulation for an on-site instantly formed and produced hypochlorous acid-based gel, having a concentration of about 200 ppm, and including parts (a) and (b) is set forth in Table 1 below.

[0077] TABLE 1Part (a)Part (b)

[0078] In the example formulation, the mix ratio of part (a) and part (b) in Table 1 can be 1:1 (v / v) to create a finished gel with about 200 ppm hypochlorous acid strength and a final pH around 5.8.

[0079] In some embodiments, for prevention or treatment of periodontal disease and peri-implant diseases, the MOD, on-site instantly formed gels can also be transferred and dispensed onto the user's gum or infected area(s) by syringe, extruder, spray bottle, pipette, tray, brush, strips, or other suitable devices. In other embodiments, any tray, mouthpiece, or strip that is hypochlorous acid (< 10,000 ppm) compatible can be used to carry the final hypochlorous acid gels to the targeted part / area in dental prevention or treatment of periodontal disease and periimplant diseases.

[0080] B. Exemplary Method 2: On-site MOD, instantly formed hypochlorous acid gels by composition of three parts and the dosing system

[0081] In implementations using three parts, example embodiments may include a first composition and a second composition similar to the compositions described above in parts (a) and (b); and an additional functional ingredient can be formulated in part (c) depending on what other functions are desired for the end product. Furthermore, the ingredient concentration of each part may be higher than the ingredient concentration used in the above described two parts composition system. The mixing ratio of the three parts can be determined by the desired hypochlorite %, pH and % of other functional ingredients desired for the final product. In some embodiments, a ratio around 1:1:1 to 10:1:1 or 1:10:1 may be preferred if part (a), (b), and (c) are properly formulated to meet the targeted function of product.

[0082] In some embodiments, the dosing system can be a tri-barrel syringe, tri-chamber bottle, or a dispensing device that can dispense three separate fluids to a common static mixing tip or mixing chamber to form desired gels. In some embodiments, the dispensing device is formed with three compartments that provide triple reservoirs for the three parts of fluids. In some embodiments, the system can further comprise pump or vacuum means to simultaneously withdraw fluid from each compartment, via separate draw pipes, and discharge the fluid to a common static mixing tip or chamber. To avoid cross contamination after each gel dispensing, a specific, detachable and / or disposable static mixing tip or chamber is recommended.

[0083] C. Exemplary Methods 3 and 4: On-site MOD, instantly formed hypochlorous acid gels by composition of four parts or multiple parts and the dosing systems

[0084] In some embodiments, the ingredients in the composition of four parts and multiple parts systems are similar to the three-part system. The mixing ratio of each part can be determined by the desired functions of the end product and the formulation of each ingredient part. FIG. 2 illustrates ingredients in the respective compartments or parts. In the embodiment illustrated in FIG. 2, a hypochlorite solution, pH sensitive rheology modifier polymers, flavors, and other functional ingredients are housed in separate parts. The ingredients are blended or mixed into a blending / mixing chamber from where they are dispensed with a dispensing pump. As a result, an instantly formed gel is ready for use and can be applied to an area to be treated.

[0085] In some embodiments, an MOD dosing system for the four parts or multi-part composition can dispense functional ingredients similar to a soda fountain. For example, eachY1ingredient can be supplied in cartridge form to make it easier for dosing control, replacement, change, or instant multi-flavor or fragrance choice during application. In some embodiments, the MOD dosing / dispensing system can be easily designed into a touchscreen vending machine for dental or sanitization applications. In some embodiments, the MOD touchscreen options of hypochlorous acid-based gel vending machine could be designed as flavor or fragrance choices.

[0086] An exemplary method 100 of making an hypochlorous acid gel composition is illustrated in FIG. 3. At step 110, an alkaline solution is provided. The alkaline solution includes a hypochlorite concentration of less than or equal to about 10,000 ppm and the alkaline solution has a pH range of about 12.0 to about 13.0. At step 120 of method 100, an acidic solution is provided. The acidic solution includes a pH sensitive polymer thickener and a pH modifying agent, capable of forming a hypochlorous acid gel when the acidic solution is combined with the alkaline solution. At step 130, the alkaline solution and the acidic solution are kept separate prior to use. At step 140, the alkaline solution and the acidic solution are combined immediately before or during use to form the hypochlorous acid gel composition when a pH of the mixture is between about 5.0 to about 7.0.

[0087] This inventive subject matter can be used for commercial instant MOD, on-site hypochlorous acid based gel production for prevention or treatment of periodontal disease and peri-implant diseases in oral healthcare, or sanitization at the dental office, hospital, nursing house, sports venue, food-processing plant, and other facilities. It can be designed into MOD, vending machine-like device and placed at those facilities. It can easily be used for producing take-home or retail type, MOD hypochlorous acid-based gel products for dental application or sanitization. In some implementation, a MOD, dual-killing hand sanitizer, for example including an oxidizing agent and an alcohol, can be instantly produced by partly replacing the water in the composition with alcohol (e.g. ethanol or isopropanol) while keeping the hypochlorous acid concentration (<1000 ppm) in final gel safe enough for human contact.

[0088] All definitions, as defined and used herein, should be understood to control over dictionary definitions, definitions in documents incorporated by reference, and / or ordinary meanings of the defined terms.

[0089] The indefinite articles "a" and "an," as used herein in the specification and in the claims, unless clearly indicated to the contrary, should be understood to mean "at least one." In addition, singular references do not exclude a plurality. Thus, references to "a", "an", "first", "second" etc. do not preclude a plurality.

[0090] Reference signs in the claims are provided merely as a clarifying example shall not be construed as limiting the scope of the claims in any way.

[0091] The phrase "and / or," as used herein in the specification and in the claims, should be understood to mean "either or both" of the elements so conjoined, i.e., elements that are conjunctively present in some cases and disjunctively present in other cases. Multiple elements listed with "and / or" should be construed in the same fashion, i.e., "one or more" of the elements so conjoined. Other elements may optionally be present other than the elements specifically identified by the "and / or" clause, whether related or unrelated to those elements specifically identified.

[0092] As used herein in the specification and in the claims, "or" should be understood to have the same meaning as "and / or" as defined above. For example, when separating items in a list, "or" or "and / or" shall be interpreted as being inclusive, i.e., the inclusion of at least one, but also including more than one, of a number or list of elements, and, optionally, additional unlisted items. Only terms clearly indicated to the contrary, such as "only one of" or "exactly one of," or, when used in the claims, "consisting of," will refer to the inclusion of exactly one element of a number or list of elements. In general, the term "or" as used herein shall only be interpreted as indicating exclusive alternatives (i.e. "one or the other but not both") when preceded by terms of exclusivity, such as "either," "one of," "only one of," or "exactly one of."

[0093] It should also be understood that, unless clearly indicated to the contrary, in any methods claimed herein that include more than one step or act, the order of the steps or acts of the method is not necessarily limited to the order in which the steps or acts of the method are recited.

[0094] In the claims, as well as in the specification above, all transitional phrases such as "comprising," "including," "carrying," "having," "containing," "involving," "holding," "composedof," and the like are to be understood to be open-ended, i.e., to mean including but not limited to.

[0095] While several inventive embodiments have been described and illustrated herein, those of ordinary skill in the art will readily envision a variety of other means and / or structures for performing the function and / or obtaining the results and / or one or more of the advantages described herein, and each of such variations and / or modifications is deemed to be within the scope of the inventive embodiments described herein. More generally, those skilled in the art will readily appreciate that all parameters, dimensions, materials, and configurations described herein are meant to be exemplary and that the actual parameters, dimensions, materials, and / or configurations will depend upon the specific application or applications for which the inventive teachings is / are used. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific inventive embodiments described herein. It is, therefore, to be understood that the foregoing embodiments are presented by way of example only and that, within the scope of the appended claims and equivalents thereto, inventive embodiments may be practiced otherwise than as specifically described and claimed. Inventive embodiments of the present disclosure are directed to each individual feature, system, article, material, kit, and / or method described herein. In addition, any combination of two or more such features, systems, articles, materials, kits, and / or methods, if such features, systems, articles, materials, kits, and / or methods are not mutually inconsistent, is included within the inventive scope of the present disclosure.

Claims

CLAIMSWhat is claimed is:

1. A method (100) of making a hypochlorous acid gel composition, the method comprising: providing (110) an alkaline solution including a hypochlorite concentration of less than or equal to about 10,000 ppm and the alkaline solution having a pH range of about 12.0 to about 13.0; providing (120) an acidic solution, including a pH sensitive polymer thickener and a pH modifying agent, capable of forming an hypochlorous acid gel when the acidic solution is combined with the alkaline solution; keeping (130) the alkaline solution and the acidic solution separate prior to use; and combining (140) the alkaline solution and the acidic solution immediately before or during use to form the hypochlorous acid gel composition when a pH of the mixture is between about 5.0 to about 7.0.

2. The method of claim 1, wherein the hypochlorous acid gel composition is formed in less than about 10 seconds after combining the alkaline solution and the acidic solution.

3. The method of claim 1, wherein the hypochlorous acid gel composition has a pH in the range of about 5.5 to about 6.0.

4. The method of claim 1, wherein the alkaline solution includes a hypochlorite concentration of less than or equal to about 5000 ppm.

5. The method of claim 1, wherein the pH sensitive polymerthickener includes a pH sensitive rheology modifying polymer of low viscosity that thickens at a pH of about 4.0 or above.

6. The method of claim 1, wherein the pH sensitive polymer thickener is a hydrophobically modified alkali soluble polymer emulsion.

7. The method of claim 1, wherein the pH sensitive polymer thickener is a highly crosslinked polyacrylic acid polymer.

8. The method of claim 1, wherein the pH modifying agent is selected from citric acid, carbonic acid, acetic acid, phosphoric acid, or other compatible acid.

9. The method of claim 1, wherein a mixing ratio of the alkaline solution to the acidic solution falls into a range of 1:1 to 10:1.

10. The method of claim 1, wherein the alkaline solution further includes a functional agent that is compatible with hypochlorous acid for at least about 0.5 hours at a temperature below or equal to 40 degrees Celsius.

11. A Make-On-Demand hypochlorous acid gel composition comprising: an alkaline solution including a hypochlorite concentration of less than or equal to about 10,000 ppm and the alkaline solution having a pH range of about 12.0 to about 13.0; an acidic solution, including a pH sensitive polymer thickener and a pH modifying agent, capable of forming an hypochlorous acid gel when the acidic solution is combined with the alkaline solution; wherein upon combining the alkaline solution and the acidic solution into a mixture immediately before or during use, the hypochlorous acid gel composition is formed when a pH of the mixture is between about 5.0 to about 7.0.

12. The composition of claim 11, wherein the pH of the hypochlorous acid gel composition becomes centered around 5.8 within less than about 10 seconds after mixing the alkaline solution and the acidic solution.

13. A system for making a hypochlorous acid gel composition, comprising:a dosing device (10) comprising a first compartment (16) containing an alkaline solution including a hypochlorite concentration of less than or equal to about 10,000 ppm and the alkaline solution having a pH of about 12.5, and a second compartment (18) containing an acidic solution, including a thickener and a pH modifying agent, capable of forming the hypochlorous acid gel composition when the acidic solution is combined with the alkaline solution; and a mixing chamber (12) to combine the alkaline solution and the acidic solution into a mixture wherein the hypochlorous acid gel composition is created when the pH of the mixture reaches a pH value between about 5.0 to about 7.0.

14. The system of claim 13, wherein the dosing device further comprises at least one additional compartment, and wherein a content of the at least one additional compartment is dispensed into the chamber.

15. A kit for generating a Make-On-Demand hypochlorous acid gel composition, the kit comprising: a first composition comprising an alkaline solution including a hypochlorite concentration of less than or equal to about 10,000 ppm and the alkaline solution having a pH range of about 12.0 to about 13.0; a second composition comprising an acidic solution, including a pH sensitive polymer thickener and a pH modifying agent, capable of forming an hypochlorous acid gel when the acidic solution is combined with the alkaline solution; wherein the first composition and the second composition are kept separate prior to use; wherein the first composition and the second composition are combined in a mixing chamber (12) to form a mixture immediately before or during use, wherein the mixture generates the hypochlorous acid gel composition when the pH of the mixture is between about 5.0 to about 7.0; andwherein the mixing chamber (12) is configured to dispense the hypochlorous acid gel composition to an area to be treated.

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