Methods of preparing non-alcohol bioactive essential oil mouth rinses
Abstract
The present invention relates, in general, to liquids such as mouthwashes for the prevention and elimination of bad breath, as well as for the reduction of oral microorganisms responsible for the development of dental plaque and tooth decay. Specifically, the present invention relates to a method for preparing mouthwashes without alcohol or with reduced alcohol content, effective in preventing the problems mentioned above.
Term
4.8 yearsleft in the term
Expires 30 June 2031.
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16 claims: 1 independent, 15 dependent
- 1REIVINDICAÇÕES 1. Método para preparar uma composição líquida, o qual compreende as etapas de:a. ) preparar uma primeira composição de pré-mistura, compreendendo: i. um primeiro óleo ou componente oleoso, ii. opcionalmente, um primeiro solvente à base de poliol, iii. opcionalmente, um flavorizante, b. ) preparar uma segunda composição de pré-mistura, compreendendo: i. um segundo óleo ou componente oleoso que tenha um grau de capacidade hidrofóbica menor que o grau de capacidade hidrofóbica do primeiro óleo ou componente oleoso, e ii. um segundo solvente à base de poliol, c. ) preparar uma terceira composição de pré-mistura, compreendendo: 1. pelo menos um tensoativo, e ii. uma fase aquosa compreendendo água, d. ) adicionar a primeira pré-mistura à terceira pré-mistura, e. ) misturar a composição da etapa d.) até que se obtenha uniformidade e homogeneidade, e f. ) adicionar a segunda pré-mistura à composição da etapa e.) e misturar até que se obtenha uniformidade e homogeneidade.
- 2Método, de acordo com a reivindicação 1, no quai a composição líquida é essencialmente isenta de álcool.
- 3Método, de acordo com a reivindicação 1, no qual um solvente à base de álcool de açúcar é adicionado à composição da etapa f.) e a composição é misturada até que se obtenha uniformidade e homogeneidade.
- 4Método, de acordo com a reivindicação 1, no quai o primeiro óleo ou o componente oleoso é um óleo essencial microbicida selecionado do grupo consistindo em mentol, eucaliptol, salicilato de metila, timol e mistu2/3 ras dos mesmos.
- 5Método, de acordo com a reivindicação 4, no qual os óleos essenciais mícrobicidas são uma mistura de mentol, eucaliptol, salicilato de metila e timol.
- 6Método, de acordo com a reivindicação 1, no qual o segundo óleo ou componente oleoso é um ácido orgânico selecionado do grupo consistindo em ácido ascórbico, ácido sórbico, ácido cítrico, ácido glicólico, ácido lático e ácido acético, ácido benzoico, ácido salicílico, ácido ftálico, ácido fenol sulfônico, ácido succínico, e misturas dos mesmos.
- 7Método, de acordo com a reivindicação 6, no qual o segundo óleo ou componente oleoso é um ácido orgânico selecionado a partir do grupo consistindo em ácido benzoico.
- 8Método, de acordo com a reivindicação 1, no qual o primeiro e o segundo solventes à base de poliol são selecionados do grupo consistindo em alcanos poli-hídricos, ésteres de alcano poli-hídrico, polialceno glicóis e misturas dos mesmos.
- 9Método, de acordo com a reivindicação 8, no qual o primeiro e o segundo solventes à base de poliol são alcano poli-hídrico.
- 10Método, de acordo com a reivindicação 9, no qual o alcano poli-hídrico é propileno glicol
- 11Método, de acordo com a reivindicação 3, no qual o solvente à base de álcool de açúcar é selecionado a partir do grupo consistindo em xilitol, sorbitol, manitol, maltitol, inositol, alitol, aitritol, dulcitol, galactitol, glucitol, hexitol, iditol, pentitol, ribitol, eritritol e misturas dos mesmos.
- 12Método, de acordo com a reivindicação 11, no qual o solvente à base de álcool de açúcar é sorbitol.
- 13Método, de acordo com a reivindicação 1, no qual a composição da etapa g.) tem uma turbidez menor que cerca de 12 unidades nefelométricas de turbidez.
- 14Método, de acordo com a reivindicação 13, no qual a composição da etapa g.) tem uma turbidez menor que cerca de 10 unidades nefelométricas de turbidez. 3/3
- 15Método, de acordo com a reivindicação 14, no qual a composição da etapa g.) tem uma turbidez menor que cerca de 8 unidades nefelométricas de turbidez.
- 16Composição líquida, produzida de acordo com o método 5 como definido na reivindicação 1. 1/1
Independent claims16
201 paragraphs in 4 sections, as filed
(54) Title: METHODS FOR THE PREPARATION OF ORAL RINSE WITHOUT ALCOHOL BASED ON BIOACTIVE ESSENTIAL OIL (30) Unionist Priority: 30/06/2010 us 12 / 827,970 (73) Holder (s): Mcneii-ppc, inc.
(72) Inventor (s): Carolyn J. Mordas, Daniel R. Queiroz, Patrick B. Tsai (57) Abstract: methods for preparing mouthwashes without alcohol based on essential bio-active oil. The present invention relates, in general, to liquids such as mouthwashes for the prevention and elimination of bad breath, as well as for the reduction of oral microorganisms responsible for the development of dental plaque and tooth decay. Specifically, the present invention relates to a method for preparing mouthwashes without alcohol or with reduced alcohol content, effective in preventing the problems mentioned above.
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Descriptive Report of the Invention Patent for METHODS FOR PREPARING Mouth Rinses WITHOUT ALCOHOL BASED ON BIOACTIVE ESSENTIAL OIL.
FIELD OF THE INVENTION
The present invention relates, in general, to liquids as mouthwashes for the prevention and elimination of bad breath, as well as for the reduction of oral microorganisms responsible for the development of dental plaque and tooth decay. Specifically, the present invention relates to methods for preparing mouthwashes without alcohol or with reduced alcohol content, effective in preventing the problems mentioned above.
BACKGROUND OF THE INVENTION
Mouthwash compositions have been used by people for many years to prevent bad breath and to eliminate bacteria and other oral microorganisms that are responsible not only for bad breath, but also for dental caries, plaque and diseases gums, such as gingivitis and periodontitis. For this purpose, antiseptic mouthwashes have been created in the past to clean the mouth cavity, provide fresh breath and kill these pathogenic microbes.
Antiseptic mouth rinses traditionally contained alcohol (ie, ethanol) in reasonably high levels, in the range of approximately 20% to about 30%, by volume, based on the total volume of mouthwash (from this point onwards in this document mentioned as% in v / v). Alcohol is used as a vehicle and as a solvent in which active ingredients and additives such as astringents, fluorides, color additives, flavoring oils and the like can be dissolved and then dispersed in solution. Alcohol also plays a preservative role in mouthwash during storage and use, and enhances the organoleptic characteristics of flavoring oil.
However, the use of high alcohol content can sometimes be seen as unacceptable by some mouthwash users. People
2/36 elderly women were also complaining of problems related to gargling with these mouthwashes, and it was found that chronic exposure results in a burning sensation in the gums, resulting from high concentrations of alcohol. There are also reports that alcoholic mouthwashes can result in an unpleasant feeling of dry mouth.
On the other hand, the reduction of alcohol content in these mouthwash compositions can have significant disadvantages. These disadvantages include a reduction in the solubility of the assets and / or other ingredients in the mouthwash.
It has been found, for example, that lowering the alcohol concentration (i.e., replacing alcohol with water) in commercially available mouthwash compositions can result in misty or cloudy compositions. Misty or cloudy compositions present a clear disadvantage from an aesthetic point of view, since clear mouthwash solutions are certainly more preferred by consumers than those with a cloudy, cloudy or otherwise heterogeneous appearance.
In addition, it was found that lower alcohol concentrations result in a noticeable decrease in the composition's ability to eliminate oral microorganisms responsible for bad breath, plaque and gum disease. This loss of microbicidal activity is not only due to the reduction of alcohol as a vehicle, but also to the reduced bioavailability of the solubilized assets.
Thymol, for example, is a well-known antiseptic compound, also known as an essential oil that, due to its microbicidal activity, is used in a variety of mouthwash preparations. In particular, thymol can be used in oral hygiene compositions, such as mouthwashes, in amounts sufficient to provide the desired beneficial therapeutic effects. Thymol mouthwashes are well known, and have been used by millions of people for over a hundred years. It has been proven that they are effective in the extermination of microbes present in the oral cavity, which are responsible for plaque, gingivitis and bad breath. Thymol, along with other oils
3/36 essentials such as methyl salicylate, menthol and eucalyptol, comprise the active component in some antiseptic mouthwashes. These oils have good efficacy, even when present in small amounts. Without adhering to any specific theory, it is now believed that the effectiveness and flavor of antiseptic mouthwashes may be due to the improved dispersion or dissolution of oils, and the bioavailability of these four active ingredients after such dispersion or dissolution.
Obviously, then, there is a substantial need for the development of mouthwashes with reduced and / or zero alcohol content, and for methods of producing these or other liquids that are aesthetically pleasing to consumers and provide improved dispersion or dissolution of essential oils, while maintaining the bioavailability of said essential oils to prevent bad breath, exterminate oral microbes and reduce or eliminate plaque.
Accordingly, an aspect of the present invention relates to liquid compositions containing oil or oily components that have reduced turbidity or fog.
Another aspect of the present invention concerns obtaining mouthwash compositions that are aesthetically pleasing to consumers, and that provide improved dispersion or dissolution of essential oils but still maintain the bioavailability of essential oils to prevent bad breath, extermination of oral microbes and reduction or elimination of plaque.
SUMMARY OF THE INVENTION
In certain embodiments, the present invention relates to methods for preparing a liquid composition or a mouthwash comprising the steps of:
a.) preparing a first premix composition, comprising:
i. a first oil or oily component, ii. optionally, a first polyol-based solvent, and iii. optionally, a flavoring,
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B. ) prepare a second premix composition, comprising:
i. a second oil or oily component that has a degree of hydrophobic capacity less than the degree of hydrophobic capacity of the first oil or oil component, and ii. a second polyol-based solvent,
ç. ) prepare a third premix composition, comprising:
i. at least one surfactant, and ii. an aqueous phase comprising water,
d. ) add the first premix to the third premix,
and. ) mix the composition of step d.) until uniformity and homogeneity are obtained,
f. ) add the second premix to the composition of step e.) and mix until uniformity and homogeneity are obtained,
g. ) optionally, add a sugar alcohol based solvent, and
H. ) optionally, mix the composition of step g.) until uniformity and homogeneity are obtained.
In certain embodiments, the liquid composition or mouthwash is a composition with reduced alcohol content or without alcohol.
In additional modalities, a method is presented for preparing a microbicidal mouthwash composition with reduced alcohol content or without alcohol that exhibits a high level of microbicidal activity, as measured by an M factor greater than 0.5 (or about 0, 5), optionally 1.0 (or about 1.0), optionally 2.0 (or about 2.0) or, optionally, 3.0 (or about 3.0), the factor M being equal to the log RLU value of the biofilm treated with water used as a negative control minus the log RLU value of the biofilm treated with the mouthwash composition being tested. In addition, the mouthwash compositions of the present invention are clear products (to the naked eye) and aesthetically attractive.
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DETAILED DESCRIPTION
The liquid mouthwash or mouthwash compositions of the present invention may comprise, consist of, or consist essentially of essential elements and limitations of the invention described herein, as well as any additional or optional ingredients, components or limitations described herein. For use in the present invention, the term comprising (and its grammatical variations) is used in the inclusive sense of having or including and not in the exclusive sense of consisting only of.
For use in the present invention, the terms one, one, o and a are understood to encompass both the plural and the singular.
Except where otherwise indicated, all documents cited in the Detailed Description of the Invention are, for the most part, incorporated herein by reference, and the citation of any document should not be construed as admitting that it represents prior art with respect to present invention. In addition, all patent documents incorporated herein by reference, in their entirety, are only incorporated here to the extent that they are not inconsistent with this specification.
The mouthwash compositions with reduced alcohol content or without alcohol described here offer an effective amount of microbicide from one or more microbicidal essential oils directed to the oral microorganisms responsible for unpleasant odor in the oral cavity and the accumulation of plaque and calculus, with the resulting diseases of the teeth and gums that can be caused by them.
The phrase effective amount of microbicide means the concentration, amount or content of the compound of the present invention that can achieve a specific medical purpose of having toxic activity for oral microorganisms.
The phrase acceptable for oral use means that the vehicle is suitable for application to the surfaces of the oral cavity, or for ingestion by a living organism including, but not limited to, mammals and humans, without causing undue toxicity, incompatibility, instability,
6/36 allergic response and the like.
All percentages, parts and ratios are based on the total weight of the composition of the present invention, unless otherwise specified. All of these weights, with respect to the mentioned ingredients, are based on the content of the specific ingredient described and, therefore, do not include vehicles or by-products that may be included in commercially available materials, unless otherwise specified.
The phrase reduced alcohol or reduced alcohol content indicates that liquid compositions are essentially alcohol-free, which means that the liquid compositions or mouthwashes of the present invention contain up to 10% monohydric C2-C4 alcohol in v / v (or about 10% in v / v), optionally up to 5% in v / v (or about 5% in v / v), optionally up to 1.0% in v / v (or about 1 , 0% in v / v), optionally up to 0.1% in v / v (or about 0.1% in v / v) by volume of the total composition. Optionally, the compositions of the present invention are free of monohydric C2-C4 alcohols.
For use in the present invention, the term sterile water means sterile water USP for irrigation / injection. The USP designation means that sterile water for irrigation / injection is the subject of an official monograph in the current US Pharmacopeia (on the filing date of this order).
Unless otherwise specified, the phrase oil (s) or oily component (s) means any water immiscible hydrophobic compound, including, but not limited to, essential oils (such as menthol, thymol, eucalyptol and methyl salicylate) ), other flavoring oils, alcohols and / or long-chain unsaturated aliphatic aldehydes such as 1-decen-3-ol, cis2-nonen-1-ol, trans-2-decennial and mixtures thereof, other hydrophobic compounds such as organic acids, vitamin E, vitamin E acetate, apigenin, triclosan and mixtures thereof, as well as mixtures of any of the water immiscible hydrophobic compounds shown above.
The terms hydrophobic, hydrophobic capacity or degree of hydrophobic capacity of an oil or oily component of the present invention, or any mixture of these oils or oily components is shown by the Octanol-Water Separation Coefficient (K<sub>ow</sub>). K<sub>ow</sub> is the ratio between the concentration, by weight, of an oil or oily component in the octanol phase and the concentration, by weight, of the oil or oily component in the equilibrated aqueous phase and at a temperature specified for the two-phase octanol system and Water. The logarithm of K<sub>ow</sub> is called log
Q. The experimental values used to calculate K<sub>ow</sub> they are typically measured at a temperature between 20 ° C and 25 ° C.
Alternatively, log P values are conveniently calculated by the C log P program, also available from Daylight CIS. This program also presents a list of experimental P log values, when they are available in the Pomona92 database. The calculated P log (C log P) is determined by the Hansch and Leo fragment approach (cf., A. Leo, in Comprehensive Medicinal Chemistry, Volume 4, C. Hansch, PG Sammens, JB Taylor and CA Ramsden, Editors, page 295, Pergamon Press, 1990, hereby incorporated by reference). The fragment approach is based on the chemical structure of each oil or oily component, and takes into account the numbers and types of atoms, the connectivity of the atoms and the chemical bond. The C log P values, which are considered reliable and are a widely used estimate for this physicochemical property, can be used instead of the K method<sub>ow</sub> experimental method for measuring log P values.
The higher the P log of the oil or oily component, the more hydrophobic the oil or oily component (or the greater the degree of hydrophobic capacity of the oil).
For use in the present invention, the term turbidity means the haze or haze of a fluid, caused by individual particles (solids or liquids in suspension) that are generally invisible to the naked eye. Fluids can contain suspended solid or liquid matter, which consists of varying particle sizes. Although some suspended materials are large and heavy enough to settle quickly to the bottom of the container (or to separate into separate layers) if a liquid sample is left to stand, very small particles will settle (or separate) only very slowly, or they will not do so if the sample is regularly shaken or if the particles are colloidal. These small particles of solid or liquid make the liquid appear cloudy.
A property of these particles is that they will scatter a beam of light focused on them. This light scattering effect is considered a good measure of water turbidity. The turbidity measured in this way uses an instrument called a turbidimeter with the detector's configuration for the side of the light beam. The more particles floating in the water, the more light is spread towards the detector, and the greater the value of light detected. A lower value of detected light indicates a clearer or less cloudy solution. The turbidity units obtained from a calibrated Turbidimeter are called Nephelometric Turbidity Units (NTUs). A clear formulation is defined as a formulation with an NTU value less than 12 (or about 12).
First premix composition
The liquid or mouthwash compositions of the present invention comprise a first premix composition.
In certain embodiments, the first premix composition includes a first oil or oily component and a first polyol-based solvent.
First oil or oily component
The first premix composition of the present invention comprises a first oil or oily component, which consists of any oil or oily component, or mixture of those oils or oily components. In certain embodiments, the first oil or oily component has a log P of no less than or more than 2.1 (or about 2.1), optionally 2.2 (or about 2.2). In certain embodiments, such as certain mouthwash modalities, the first oil or oily component of the present invention comprises at least one microbicidal essential oil.
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Microbicidal essential oils
In certain embodiments, the enhanced microbicidal efficacy of alcohol-free mouthwash compositions, as described in the present invention, is attributed to the presence of small amounts of one or more microbicidal or bioactive essential oils (ie, thymol, eucalyptol, menthol and salicylate). methyl).
Thymol, [(CH<sub>3</sub>)<sub>2</sub>CHC6H3 (CH3) OH, also known as isopropyl-m-cresol], is only slightly soluble in water, but it is soluble in alcohol, and its presence is one of the reasons why alcohol was needed in well-established high-content mouthwashes. alcoholic, commercially available. Methyl salicylate [C6H<sub>4</sub>OHCOOCH3, also known as oil of wintergreen] additionally provides flavor to the composition, along with its microbicidal function. Eucalyptol (CioHisO, also known as cineol) is a terpene ether, and provides a refreshing spice flavor. In certain formulations eucalyptol can be used in place of thymol, in the same amount, if desired. Menthol (CH<sub>3</sub>Ç<sub>6</sub>H9 (C3H7) OH), also known as hexahydro thymol) is also only slightly soluble in alcohol, being reasonably volatile. Menthol, in addition to any antiseptic properties, provides a refreshing tingling sensation.
In certain embodiments, essential oils are used in effective amounts to provide microbicidal activity in the oral cavity. In specific embodiments, the total amount of essential oils present in the disclosed compositions can be from 0.001% (or about 0.001%) to 0.35% (or about 0.35%) in w / v or, optionally, from 0 , 16% (or about 0.16%) to 0.28% (or about 0.28%) w / v of the composition.
In some embodiments, the compositions of the present invention contain thymol and, in addition, eucalyptol, menthol or methyl salicylate, or mixtures thereof. Optionally, the composition contains all four of these essential oils.
In certain embodiments, thymol is used in amounts from 0.001% (or about 0.001%) to 0.25% (or about 0.25%) in w / v or,
10/36 optionally, from 0.04% (or about 0.04%) to 0.07% (or about 0.07%) in w / v of the composition. In certain embodiments, eucalyptol can be used in amounts from 0.001% (or about 0.001%) to 0.11% (or about 0.11%) in w / v or, optionally, 0.085% (or about 0.085%) to 0.10% (or about 0.10%) in w / v of the composition. In certain embodiments, menthol is used in amounts from 0.001% (or about 0.001%) to 0.25% (or about 0.25%) in w / v or, optionally, 0.035% (or about 0.035 %) to 0.05% (or about 0.05%) in w / v of the composition. In certain embodiments, methyl salicylate is used in amounts from 0.001% (or about 0.001%) to 0.08% (or about 0.08%) w / v or, optionally, 0.04% (or about 0.04%) to 0.07% (or about 0.07%) in w / v of the composition.
In some embodiments, the vehicle for essential oils (the active ingredients) is typically a mixture of water and alcohol, generally water and ethanol. In the past, some antiseptic mouthwash compositions needed ethanol contents of up to about 27% in v / v. These high levels were necessary to help the assets to provide the necessary microbicidal functionality, as well as to obtain a clear, aesthetically attractive liquid medium. The mere reduction in alcohol content, without the addition of other components of the formulation, results in a cloudy and less effective product.
Without sticking to the theory, it is believed that in these high alcohol content oral compositions, alcohol solubilizes microbicidal essential oils and, in doing so, acts in order to maintain the bioactivity of essential oils. Microbicidal essential oils are more readily dispersed throughout the solution, and remain free or unbound to attack pathogenic microbes throughout the oral cavity. It was believed that the reduction of alcohol levels would adversely affect this accentuation mechanism. In accordance with the present invention, however, it has surprisingly and unexpectedly been found that the alcohol content can be reduced or eliminated without sacrificing microbicidal efficacy or clarity, if the mouthwash composition contains a solvent and surfactant system as described in price 11 / 36 feels invented.
First polyol-based solvent
In certain embodiments, a first polyol-based solvent is added to the first premix composition. The first polyol-based solvent comprises a polyol or polyhydric alcohol selected from the group consisting of polyhydric alkanes (such as propylene glycol, glycerin, butylene glycol, hexylene glycol, 1,3-propanediol), polyhydric alkane ester (dipropylene glycol, ethoxy diglycol), polyalkylene glycols (such as polyethylene glycol, polypropylene glycol) and mixtures thereof. In certain embodiments, the polyol-based solvent can be present in an amount of 0% to 20.0% (or about 20.0%) in w / v, optionally 1.0% (or about 1, 0%) to 15.0% (or about 15.0%) in w / v or, optionally, from 2.5% (or about 2.5%) to 8.0% (or about 8, 0%) in w / v of the composition.
Flavors or flavors
In certain embodiments, the first premix composition further comprises flavors or flavors to modify or magnify the flavor of the liquid composition or mouthwash, or to reduce or mask the strong burning or burning of ingredients such as thymol. Suitable flavors that can be incorporated include, but are not limited to, anise oil, anethole, benzyl alcohol, mint oil, citrus oils, vanillin and the like. In these modalities, the amount of flavoring oil added to the composition can be from 0.001% (or about 0.001%) to 1.0% (or about 1.0%) in w / v or, optionally, 0.01% (or about 0.010%) to 0.30% (or about 0.30%) w / v of the total composition.
The specific flavors or flavorings and other flavor-optimizing ingredients employed will vary depending on the specific taste and sensation desired. Those skilled in the art can select and customize these types of ingredients to obtain the desired results. Second premix composition
The compositions of the present invention further comprise a second premix composition.
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In certain embodiments, the second premix composition comprises a water-insoluble component and a second solvent or solvent system comprising, consisting of, or consisting essentially of at least one polyol-based solvent.
Second oil or oily component
The second premix composition of the present invention comprises a second oil or oily component, which consists of any oil or oily component, or mixture of those oils or oily components, so that the hydrophobic capacity (or the degree of hydrophobic capacity) of the second oil or oily component is less than the hydrophobic capacity (or the degree of hydrophobic capacity) of the first oil or oily component. In certain embodiments, the second oil or oily component has a log P of no more than or less than 2.1 (or about 2.1), optionally 2.0 (or about 2.0). In certain embodiments, the second oil or oily component of the present invention consists of, or comprises, at least one organic acid. In certain embodiments, organic acid is used as a buffer or part of a buffering system.
Organic acid
Organic acids suitable for use in the compositions of the present invention include, but are not limited to, ascorbic acid, sorbic acid, citric acid, glycolic acid, lactic acid and acetic acid, benzoic acid, salicylic acid, phthalic acid, phenol sulfonic acid, succinic acid and mixtures thereof and, optionally, organic acid is selected from the group consisting of benzoic acid, sorbic acid, succinic acid, citric acid and mixtures thereof or, optionally, organic acid is benzoic acid. In certain embodiments, the organic acid buffer is present in amounts of 0.001% (or about 0.001% w / v) to 1.0% (or about 1.0% w / v) of the composition.
When used as buffers or as part of a buffering system, organic acids are incorporated in amounts that maintain the pH at levels of 3.0 (or about 3.0) to 8.0 (or about 8.0) , optionally from 3.5 (or about 3.5) to 6.5 (or about 6.5), optionally from 3.5 (or about 3.5) to 5.0 (or about of 5.0). Without adhering to theory, it is believed that these pH levels provide essential oils with an environment that also maximizes their microbicidal activity and promotes stability.
In certain embodiments, the total amount of any oils or oily components present in the compositions of the present invention presented here must not exceed 1.35%, in w / v (or about 1.35%, in w / v) of the total composition. Optionally, the total of all oils or oily components can be present in an amount of 0.04% (or about 0.04%) to 1.35% (or about 1.35%) in w / v or optionally from 0.10% (or about 0.10%) to 0.4% (or about 0.4%) in w / v of the total composition.
Second polyol-based solvent
A second polyol-based solvent is added to the second premix. In certain embodiments, the second polyol-based solvent may be the same as or different from the first polyol-based solvent, and comprises a polyol or polyhydric alcohol selected from the group consisting of polyhydric alkanes (such as propylene glycol, glycerin, butylene glycol, hexylene glycol, 1,3-propanediol), polyhydric alkane esters (dipropylene glycol, ethoxy diglycol), polyalkene glycols (such as polyethylene glycol, polypropylene glycol) and mixtures thereof. In certain embodiments, the polyol-based solvent can be present in an amount of 1% (or about 1%) to 15.0% (or about 15.0%) in w / v or, optionally, 2 , 5% (or about 2.5%) to 8.0% (or about 8.0%) w / v of the composition.
In certain embodiments, in which a first polyol-based solvent is not added to the first premix, the second polyol-based solvent may be present in an amount of 1.0% (or about
1.0%) to 30.0% (or about 30.0%) in w / v or, optionally, from 5.0% (or about 5.0%) to 15.0% (or about 15.0%) in w / v of the composition.
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Third premix composition
The compositions of the present invention further comprise a third premix composition. In certain embodiments, the third premix composition comprises a surfactant and an aqueous phase. Surfactant
Suitable examples of surfactants useful in the compositions of the present invention include anionic surfactants, non-ionic surfactants, amphoteric surfactants and mixtures thereof.
Anionic surfactants useful in the present invention include, but are not limited to, sarcosine or sarcosinate-type surfactants, taurates like sodium methyl cocoyl taurate, alkyl sulfates like sodium tridecet sulfate or sodium lauryl sulfate, sodium lauryl sulfate, lauroyl sodium isethionate, sodium lauret carboxylate, sodium dodecyl benzenesulfonate and mixtures thereof. Many suitable anionic surfactants are disclosed in US Patent 3,959,458 to Agrícola, et al., Incorporated herein by reference, in its entirety.
Nonionic surfactants that can be used in the compositions of the present invention include, but are not limited to, compounds produced by the condensation of alkylene oxide groups (of a hydrophilic nature) with an organic hydrophobic compound which can be of an aliphatic or alkyl-aromatic nature . Examples of suitable non-ionic surfactants include, but are not limited to, alkyl polyglycosides, block copolymers such as ethylene oxide and propylene oxide copolymers, for example poloxamers, commercially available ethoxylated hydrogenated castor oils, for example under trade name CRODURET (Croda Inc., Edison, NJ, USA), alkyl polyethylene oxide, for example, fatty alcohol polysorbates and / or ethoxylates, condensates of alkyl phenol polyethylene oxide, products derived from the condensation of ethylene oxide with the reaction product of propylene oxide and ethylenediamine, ethylene oxide condensates from aliphatic alcohols, long chain tertiary amine oxides, long chain tertiary phosphine oxides, dialkyl dialkyl sulfoxides long and mixtures thereof.
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Amphoteric surfactants useful in the present invention include, but are not limited to, derivatives of secondary and tertiary aliphatic amines, where the aliphatic radical can be a straight or branched chain, and where one of the aliphatic substituents contains from about 8 to about of 18 carbon atoms, and one contains an anionic group solubilizing for water, for example carboxylate, sulfonate, sulfate, phosphate or phosphonate. Examples of suitable amphoteric surfactants include, but are not limited to, alkylimino diproprionates, alkyl (mono or di) amphoglycinates, alkyl (mono or di) amphoproprionates, alkyl (mono or di) amphacetates, N-alkyl β- acids aminoproprionics, alkyl polyamino carboxylates, phosphorylated imidazolines, alkyl betaines, alkyl starch betaines, alkyl starch propyl betaines, alkyl sultaines, alkyl starch sultaines and mixtures thereof. In certain embodiments, the amphoteric surfactant is selected from the group consisting of alkyl starch propyl betaines, anphacetates such as sodium lauroamphoacetate and mixtures thereof. Mixtures of any of the above mentioned surfactants can also be used. A more detailed discussion of anionic, non-ionic and amphoteric surfactants can be found in US patents No. 7,087,650 to Lennon, 7,084,104 to Martin et al., 5,190,747 to Sekiguchi et al., And 4,051,234 to Gieske , et al., each of which is incorporated herein by reference, in its entirety.
In certain embodiments, liquid mouthwash or mouthwash compositions contain at least one alkyl sulfate-based surfactant, either alone or in addition to at least one of the other surfactants mentioned above. In certain embodiments, suitable alkyl sulfate surfactants include, but are not limited to, even-numbered alcohols with carbon chain lengths, from Cs to Ci<sub>8</sub> sulphates, optionally from C10 to C16 sulphates, neutralized with a suitable basic salt, such as sodium carbonate or sodium hydroxide and mixtures thereof, so that the alkyl sulphate-based surfactant has a chain length in even numbers of Csa C-is, optionally from C10 to C16- In certain embodiments, the alkyl sulfate is selected from the group consisting of sodium lauryl sulfate, sodium hexadecyl sulfate and mixtures thereof. In certain embodiments, commercially available mixtures of alkyl sulfates are used. A typical division into percentages of alkyl sulfates by length of the commercially available sodium lauryl sulfate (SLS) alkyl chain is as follows:
<td>Alkyl chain length</td><td>Percentage of component in SLS</td>
<td>C-I2</td><td> > 60%</td>
<td>C14</td><td> 20% - 35%</td>
<td>C-I6</td><td> < 10%</td>
<td>Cio</td><td> < 1%</td>
<td>Cl8</td><td> < 1%</td>
Suitable commercially available mixtures include Stepanol WA-100 NF USP, (Stepan, Northfield, IL, USA), Texapon K12 G PH, (Texapon, Cognis, Germany) and mixtures thereof.
In certain embodiments, the amount of the alkyl sulfate-based surfactant added to the composition may be 0.05% (or about 0.05%) to 2.0% (or about 2.0%) in w / v or, optionally, from 0.1% (or about 0.1%) to 0.5% (or about 0.5%) w / v of the composition.
The total surfactant concentration should not exceed or need to be less than 2% (or about 2%), optionally, the total surfactant concentration should not exceed or need to be less than 1.5% (or about 1.5%) ), optionally, the total surfactant concentration must not exceed or must be less than 1.0% (or about 1.0%), optionally, the total surfactant concentration must not exceed or must be less than 0.5% (or about 0.5%).
Water phase
The first premix and the second premix are added to an aqueous phase comprising water, to form oil-in-water or water-in-oil dispersions, microemulsions or emulsions.
In certain embodiments, the aqueous phase comprises from about 60% to about 95% or, optionally, from about 75% to about 93%, by weight of the composition.
17/36
Alternatively, the liquid or mouthwash compositions of the present invention can be formulated in the form of a dry powder, a chewing gum, a semi-solid, a solid or a liquid concentrate. In these embodiments, for example, water is added to qs, as needed in the case of concentrated liquid or powder formulations, or water can be removed using conventional evaporation procedures known in the art, to produce a composition in the form of a dry powder. Evaporated or freeze-dried forms are advantageous for storage and transportation.
Sugar alcohol based solvent
In certain embodiments, a sugar alcohol is also added to the liquid or mouthwash compositions of the present invention. The one or more solvents based on sugar alcohol can be selected from those multi-hydroxy-functional compounds that are conventionally used in oral and ingestible products. In certain embodiments, the one or more sugar alcohols must be non-metabolizable and non-fermentable sugar alcohols. In specific embodiments, sugar alcohols include, but are not limited to, sorbitol, xylitol, mannitol, maltitol, inositol, alitol, aitritol, dulcitol, galactitol, glucitol, hexitol, iditol, pentitol, ribitol, erythritol and mixtures thereof. Optionally, sugar alcohol is selected from the group consisting of sorbitol and xylitol, or mixtures thereof. Optionally, the sugar alcohol is sorbitol.
In certain embodiments, the total amount of one or more sugar alcohols, which are added to effectively assist in the dispersion or dissolution of the mouthwash or other ingredients, must not exceed 20% w / v (or about 20% w / w / v,, of the total composition Optionally, the total amount of sugar alcohol should not exceed 17% w / v (or about 17% w / v) of the total composition. Optionally, the total amount of sugar alcohol should not exceed 10% w / v (or about 10% w / v) of the total composition. Sugar alcohol can be present in an amount of 1.0% (or about 1.0%) to 20.0% (or about 20.0%) in w / v, optionally 2.5% ( or about 2.5%) to 17.0%
18/36 (or about 17.0%) in w / v or, optionally, from 5.0% (or about 5.0%) to 15.0% (or about 15.0%) in p / v, of the total composition.
In certain embodiments, the ratio of the sugar alcohol to the total polyol-based solvent component in the composition needs to be 10: 1 (or about 10:10) to 1:10 (or about 1: 10), optionally from 5: 1 (or about 5: 1) to 1: 5 (or about 1: 5), optionally 1: 1 (or about 1: 1), by weight.
In certain embodiments, the total amount of the solvent, including all polyol-based solvents and all sugar alcohol-based solvents, which is added to effectively assist in the dissolution or dispersion of the mouthwash or other ingredients, should not exceed 47% w / v (or about 47% w / v) of the total composition. Optionally, the total amount of the solvent system must not exceed 20% w / v (or about 20% w / v) of the total composition. The solvent system can be in an amount of 2% (or about 2%) to 47% (or about 47%) in w / v or, optionally, from 10% (or about 10%) to 20% ( or about 20%) in w / v of the total composition.
In certain embodiments, the ratio between the total solvent (ie, polyol-based solvent and sugar alcohol-based solvent) and the total surfactant in the composition needs to be 360: 1 (or about 360: 1) to 10: 1 (or about 10: 1), optionally from 100: 1 (or about 100: 1) to 20: 1 (or about 20: 1), by weight.
Manufacturing method
Each of the above premixes is mixed until uniformity and homogeneity are obtained. Once each pre-mix is mixed until uniformity and homogeneity are obtained, the first pre-mix is added to the third pre-mix and mixed until uniformity and homogeneity is obtained. Once the mixture of the first premix with the third premix is mixed until uniformity and homogeneity are obtained, the second premix is added to the mixture of the first premix with the third premix and mixed until obtaining uniformity and homogeneity.
19/36
Without adhering to the theory, it is believed that there is a competition between the first oil or oily component and the second oil or oily component for the surfactant and solvents in the aqueous phase of the present invention. When first mixing the first oil or oily component with a higher degree of hydrophobic capacity as a polyol-based solvent premix with an aqueous phase containing surfactant, before adding a solvent-based premix of polyol of the second oil or oily component with a lower degree of hydrophobic capacity to the aqueous phase containing surfactant, the first oil or oily component with a higher degree of hydrophobic capacity is mixed with the surfactant and / or solvent to obtain the dispersion and / or dissolution in the aqueous phase, necessary to produce compositions with turbidity less than 12 (or about 12 ) Nephelometric Turbidity Units (NTUs). The turbidity of the liquid composition or mouthwash is further reduced by the addition of any solvents based on sugar alcohol, after the first and second oils or oily components have been added to an aqueous phase.
In certain embodiments, the liquid or mouthwash compositions of the present invention have NTU values less than 10 (or about 10), optionally 8 (or about 8), optionally 6 (or about 6) or, optionally, 4 (or about 4).
Optional ingredients
Insoluble particulates
In certain embodiments, the oral treatment compositions of the present invention optionally comprise a safe and effective amount of a water-insoluble particulate. The water-insoluble particulate may consist of an abrasive particle (such as a dentinically acceptable abrasive) or a non-abrasive particle.
In certain moalities, dentinically acceptable abrasives include, but are not limited to, water insoluble calcium salts, such as calcium carbonate, as well as various calcium phosphates, alumina, silica, synthetic resins and mixtures thereof. Dentistically acceptable abrasives 20/36 suitable can generally be defined as those having an abrasion value for radioactive dentin (RDA) of about 30 to about 250, at the concentrations used in the compositions of the present invention. In certain embodiments, abrasives are abrasives based on hydrated non-crystalline silica, particularly in the form of commercially available precipitated or ground silica gels, for example, under the trade names ZEODENT (JM Huber Corporation, Edison, NJ, USA) and SYLODENT (WR Grace & Co., New York, NY, USA), respectively. In certain embodiments, the compositions according to the present invention comprise from about 1% to about 20% or, optionally, from about 5% to about 10%, by weight of the abrasive.
Alternatively, the insoluble particulate is a non-abrasive particulate that is visible to the naked eye and stable in the compositions of the present invention.
The non-abrasive particulate can be of any size, shape or color, according to the desired characteristic for the product. Non-abrasive particulates will typically have the shape of a small ball or round or substantially round bead, however configurations in the form of a tag or stick are also contemplated in the present invention. In general, a non-abrasive particulate has an average diameter of about 50 pm to about 5,000 pm, optionally from about 100 pm to about 3,000 pm or, optionally, from about 300 pm to about 1,000 pm. The terms stable and / or stability, mean that abrasive or non-abrasive particles do not undergo disintegration, agglomeration or separation under normal storage conditions. In certain embodiments, the terms stable and / or stability further mean that the compositions of the present invention do not contain any minimally visible visible signs (with the naked eye) of sedimentation of insoluble particles after 8 weeks, optionally 26 weeks and, optionally, 52 weeks at room temperature.
The non-abrasive particulates of the present invention are typically incorporated into the present compositions at levels of about
21/36
0.01% to about 25%, optionally from about 0.01% to about 5% or, optionally, from about 0.05% to about 3% by weight of the composition.
The non-abrasive particulate of the present invention will typically comprise a structural material and / or, optionally, a surrounding material.
The structural material provides a certain resistance to non-abrasive particles, so that they retain their distinctly detectable structure in the compositions of the present invention, under normal storage conditions. In one embodiment, the structural material can additionally be broken and disintegrated with very little shear on the teeth, tongue or buccal mucosa, during use.
Non-abrasive particles can be solid or liquid, filled or unfilled, as long as they are stable in the compositions of the present invention. The structural material used to produce the non-abrasive particles varies depending on the compatibility with other components, as well as the material to be surrounded by the non-abrasive particles, if any. Examples of materials for the production of the non-abrasive particulates of the present invention include: polysaccharide and saccharide derivatives such as crystalline cellulose, cellulose acetate, cellulose acetate butyrate, cellulose phthalate, cellulose nitrate, ethyl cellulose, propyl cellulose hydroxy, propyl methyl cellulose hydroxy, propyl methyl cellulose, methyl cellulose, methyl cellulose, carboxy methyl sodium cellulose, acacia gum (gum arabic, agar, agarose, maltodextrin, sodium alginate, calcium alginate, dextrin, starch, galactose, glucosamine, cyclodextrin, chitin, amylose, amylopectin, glycogen, laminaran, lichenan, curdlan, inulin, levan, pectin, mannan, xylan, alginic acid, arabic acid, glucomannan, agarose, agaropectin, profyran, carrageenan, fucoidan, glycosamino glycan, hyaluronic acid, chondroitin, lipidogol, peptidogol guar gum, starch and starch derivatives, oligosaccharides such as sucrose, lactose, maltose, uronic acid, muramic acid, cellobiose, isomaltose, planteose, melezitosis, gentian, maltotriosis, stachyose, glycoside and polyglycoside, monosaccharides like glucose, fructose and mannose, synthetic polymers like
22/36 acrylic polymers and copolymers, including polyacrylamide, poly (alkyl cyanoacrylate) and poly (ethylene-vinyl acetate), and vinyl carboxy polymer, polyamide, poly (methyl vinyl ether-eicomaleic anhydride, poly (adipyl-L- lysine), polycarbonate, polyetherphthalamide, polyvinyl acetate phthalate, poly (terephthaloyl-L-lysine), polyaryl sulfone, poly (methyl methacrylate), ally methacrylate, poly (ecprolactone), polyvinyl pyrrolidone, polydimethyl siloxane, polyester , polyglycolic acid, polylactic acid, polyglutamic acid, polylysine, polystyrene, poly (styrene-acrylonitrile), polyimide and poly (vinyl) alcohol, and other materials such as fat, fatty acid, fatty alcohol, milk solids, molasses, gelatin, gluten, albumin, shellac, caseinate, beeswax, carnauba wax, spermaceti wax, hydrogenated tallow, glycerol monopalmitate, glycerol dipalmitate, hydrogenated castor oil, glycerol monostearate, glycerol distearate, glycerol tristearate, stearyl 12-hydroxy alcohol, protein and protein derivatives, and mixtures thereof. The components of the present invention can be described in other sections as components useful for the present composition. In certain embodiments, the components as described in this section form the structure of the non-abrasive particles, so that they are not substantially dissolved or dispersed from the particles and into the compositions of the present invention under normal storage conditions.
In other embodiments, the structural material of the present invention comprises components selected from the group consisting of polysaccharides and their derivatives, saccharides and their derivatives, oligosaccharides, monosaccharides and mixtures thereof, or optionally comprises components with varying degrees of water solubility. In some embodiments, the structural material comprises lactose, cellulose and hydroxy propyl methyl cellulose.
Suitable non-abrasive particulates also include organogel particles as described in detail in US Patent No. 6,797,683. Non-abrasive particles that are organoge particles typically comprise a structural material selected from waxes (for example, beeswax, paraffin, water-insoluble wax,
23/36 carbon based, silicone wax, microcrystalline wax, etc.), trigiicerides, acid triglycerides, polymers, polymers and copolymers of fluoroalkyl (meth) acrylate, acrylate polymers, ethylene / acrylate copolymers, polyethylene, polymers and polypropylene copolymers, fatty acids, fatty alcohols, fatty acid esters, fatty acid ethers, fatty acid amides, alkylene pohydric alcohols, an alkanolamine fatty acid amide, glyceryl monostearate, sugars (substituted with aryl), dibenzyl sorbitol (or mannitol, rabitol, etc.), condensed and pre-condensed from lower monohydric alcohols, trihydric alcohols, lower polyglycols, polypropylene / ethylene condensates and the like. Optionally, the structural material for non-abrasive particles that are organogel particles include beeswax, carnauba wax, low molecular weight ethylene homopolymers (for example polyethylene materials such as Polywax 500, Polywax 1000 or Polywax 2000, available from Baker Petrolite Corp.), or paraffin wax.
The non-abrasive particles of the present invention can surround containing or being filled with a surrounding material. This surrounding material can be soluble in water or insoluble in water. Suitable encircled materials include beneficial agents as described in the present invention, such as: oral treatment actives, vitamins, pigments, dyes, microbicidal agents, chelating agents, optical brighteners, flavorings, perfumes, humectants, minerals and mixtures thereof. The surrounding materials of the present invention are substantially retained within the non-abrasive particles, and are not substantially dissolved from the particles and into the compositions of the present invention, under normal storage conditions.
The commercially available and particularly useful non-abrasive particles of the present invention are those with the trade names Unisphere and Unicerin, available from Induchem AG (Switzerland), and Confetti Dermal Essentials available from United-Guardian Inc. (NY, USA). Unisphere and Unicerin particles are made of microcrystalline cellulose, hydroxy propyl cellulose, lactose, vitamins, pigments and proteins. Du24 / 36 Before use, Unisphere and Unicerin particles can be disintegrated with very little shear and with virtually no resistance, readily dispersing in the compositions of the present invention.
Non-abrasive particles suitable for incorporation into the present compositions are described in detail in US Patent No. 6,797,683 (organogel particles), US Patent No. 6,045,813 (breakable beads), US 2004/0047822 A1 (visible capsules), and US patent No. 6,106,815 (encapsulated or particulate oily substances), each of these patent documents being incorporated by reference in its entirety by reference.
In certain embodiments, the abrasive and / or non-abrasive particles have a different density or, optionally, substantially different from that of the carrier in which these particles are formulated. Fluoride-releasing compounds
In certain embodiments, fluoride-providing compounds may be present in the mouthwash compositions of the present invention. These compounds can be slightly soluble in water or can be completely soluble in water, and are characterized by their ability to release fluoride ions or fluoride-containing ions into water. Typical fluoride-providing compounds are inorganic fluoride salts such as soluble salts of alkali metal, alkaline earth metal and heavy metal, for example sodium fluoride, potassium fluoride, ammonium fluoride, cupric fluoride, zinc fluoride, stanic fluoride, stannous fluoride , barium fluoride, sodium hexafluorosilicate, ammonium hexafluorosilicate, sodium fluorozirconate, sodium monofluorophosphate, monium and aiumium difluorophosphate and fluorinated sodium and calcium pyrophosphate. Amine fluorides, such as N'-octadecyl trimethylene diamine-Ν, Ν, Ν'- tris (2-ethanoyl) and 9-octadecenylamine fluoride, can also be used.
In certain embodiments, the fluoride-providing compound is generally present in an amount sufficient to release up to 0.15% (or about 0.15%), optionally from 0.001% (or about 0.001%) to 0.1 % (or about 0.1%), optionally 0.001% (or about 0.001%)
25/36 to 0.05% (or about 0.05%) fluoride, by weight of the composition.
Zinc salts
In certain embodiments, zinc salts such as zinc chloride, zinc acetate or zinc citrate can be added as an astringent for an antiseptic cleansing sensation, as a breath protection enhancer, or as an anti-calculating agent in an amount of 0.0025% w / v (or about 0.0025% w / v) to 0.1% w / v (or about 0.1% w / v) of the composition.
Sensitivity reducing agents
In certain embodiments, sensitivity reducing agents, specifically potassium nitrate and oxalate salts in an amount of 0.1% (or about 0.1%) to 5.0% (or about 5.0%) in w / v of the composition can be incorporated into the present invention. Other potassium-releasing compounds can also be used (for example, KCI). High concentrations of calcium phosphates can also provide some additional relief from sensitivity. These agents are believed to work either by forming an occlusive mineral deposit on the dental surface or by supplying potassium to the nerves inside the teeth, in order to depolarize said nerves. A more detailed discussion of suitable sensitivity-reducing compounds can be found in US 20060013778, by Hodosh, and in US patent 6,416,745, by Markowitz et al., Both of which are incorporated herein by reference in their entirety. Anti-calculation agents
In certain embodiments, compounds with anticalculation benefits (for example, polyphosphates, phosphonates, various carboxylates, polyaspartic acid, inositol phosphate, etc.) can be incorporated into the present invention. Anionic polymeric polycarboxylates are also useful as an anti-calculating agent. Such materials are well known in the art, being used in the form of their free acids, or alkali metal salts (eg, potassium and, preferably, sodium) or water-soluble ammonium, partially or, preferably, totally neutralized . Copolymers of 1: 4 to 4: 1, by weight, of anhydride or maleic acid with a
26/36 another ethylenically unsaturated polymerizable monomer, preferably methyl vinyl ether (ethylene methoxy) having a molecular weight (MW) of about 30,000 to about 1,000,000. These copolymers are available, for example, as Gantrez AN 139 (PM 500,000), AN 119 (PM 250,000) and, preferably, pharmaceutical grade S-97 (PM 70,000), from GAF Chemicals Corporation.
Additional ingredients
Although the liquid or mouthwash compositions of the present invention can be formulated so as to be substantially clear and / or colorless to the naked eye, acceptably approved food dyes are preferably used to impart a pleasing color to the compositions of the invention. These can be selected from, but not limited to, a long list of acceptable food colors. Dyes suitable for this purpose include yellow FD&C n ° 5, yellow FD&C ri 10, blue FD&C ri 1 and green FD&C n ° 3. These are added in conventional amounts, typically in individual amounts of 0.00001% w / v ( or about 0.00001% w / v) to 0.0008% w / v (or about 0.0008% w / v), optionally 0.00035% w / v (or about 0 , 00035% w / v) to 0.0005% w / v (or about 0.0005% w / v) of the composition.
Other conventional ingredients can be used in the liquid or mouthwash compositions of the present invention, including those known and used in the art. Examples of such ingredients include thickeners, suspending agents and softeners. Thickeners and suspending agents useful in the compositions of the present invention can be found in US Patent No. 5,328,682, to Pullen et al, incorporated herein by reference, in its entirety. In certain embodiments, these are incorporated in amounts from 0.1% w / v (about 0.1% w / v) to 0.6% w / v (or about 0.6% w / v) v), optionally 0.5% w / v (or about 0.5% w / v) of the composition.
A more detailed description of the useful and / or inactive ingredients for oral treatment useful, and other examples of them, can
27/36 can be found in US Patent No. 6,682,722 to Majeti et al. and 6,121,315 by Nair et al., each of which is incorporated herein, by reference, in its entirety.
In certain embodiments, the compositions of the present invention are free of, or essentially free of, compounds that affect bioavailability. For use in the present invention, the term compound that affects bioavailability refers to compounds that negatively affect the bioavailability of any essential oils incorporated, such as by binding essential oils or otherwise inactivating essential oils. The term essentially exempt, as used in relation to compounds that affect bioavailability, is defined as formulations having less than 5% (or about 5%), optionally 3% (or about 3%), optionally 1% (or about 1%), optionally 0.1 or, optionally, 0.01% (or about 0.01%), by weight (w / v) of the total composition, of a compound that affects bioavailability. In certain embodiments, the compound that affects bioavailability may include, but is not limited to, polyethylene oxide / polypropylene block copolymers, such as poloxamers, cyclodextrins, polysorbates such as Tweens and mixtures thereof.
Methods for practicing the present invention
The invention shown here can be practiced in the absence of any component, ingredient or step that is not specifically presented in this document.
In certain embodiments, the compositions of the present invention are applied to teeth and / or soft surfaces of the oral cavity for at least two consecutive applications, optionally at least (or more than) 3 (or about 3) or, optionally, at least (or more than) 5 (or about 5) consecutive applications.
When applied to teeth and / or soft surfaces of the oral cavity, in certain embodiments, the composition is allowed to remain in contact with the teeth and / or the soft surfaces of the oral cavity for at least (or more than) 10 (or about 10) seconds, optionally 28/36 t and 20 (or about 20) seconds, optionally 30 (or about 30) seconds, optionally 50 (or about 50) seconds or, optionally, 60 (or about 60) seconds.
Various embodiments of the invention have been presented above. Each embodiment is provided in order to explain the invention, and not to limit the invention. Indeed, it will be apparent to those skilled in the art that various modifications and variations can be made to the present invention without departing from the scope or spirit of the invention. For example, features illustrated or described as part of one embodiment can be used in another embodiment to produce an additional embodiment. Therefore, it is intended that the present invention will cover such modifications and variations by including them within the scope of the appended claims and their equivalents. Examples
The following examples are illustrative only, and should not be construed as limiting the invention in any way. Those skilled in the art will understand that variations are possible that are within the spirit and scope of the appended claims.
Example 1: effect of various methods of forming the formulations, and increasing levels of surfactant
Nine propylene glycol mouthwash formulations have been prepared by a variety of methods, using various surfactants that are approved for use in oral care products. The formulations were tested for turbidity and microbicidal activity. Turbidity was tested using a model 2100N laboratory turbidimeter, available from Hach Company (Loveland, CO, USA). The formulations were also tested using an in-vitro biofilm model with a single species of S. mutans. A biofilm of S. mutans with 22 hours was cultured (N = 96) and exposed to the formulations, as well as to positive and negative controls, for 30 seconds. Sterile water was used as a negative control. After treatment, the biofilm was neutralized and rinsed. The biofilm was collected by sonication using a Misonix XL-2000 Ultrasonic processor (Qsonica, LLC, Newtown, CT, USA). A Celsis Ra29 / 36 pid Detection RapiScreen kit (Celsis International PLC, Chicago, USA) was used. The bacteria were lysed with Celsis Luminex, and the ATP from them was measured using the Celsis LuminATE bioluminescence marker. A decrease in log RLUs (relative light units) indicates fewer live bacteria after treatment. The nine formulations are shown in Table 1. The final formulations were adjusted to pH 4.2 with 0.1 M NaOH or 0.1 M HCI, if necessary.
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Table 1
<td rowspan="10">Formulations</td><td>Control negative</td><td> 1 1</td><td> 1 1</td><td>s 1</td><td> 1 1</td><td> 1 1 1</td><td>j</td><td> 1 1 1</td><td> 1 1 1</td><td> 1 1</td><td> 1 1</td><td>i</td><td>1 t t</td><td> 1 1</td><td> 1 1</td>
<td>11 (% w / w)</td><td>O r-</td><td> 0,0413</td><td> 0,0620</td><td> 0,0641</td><td> 96800</td><td>O O O O</td><td>O O O d T ~</td><td> 0,3150</td><td> 1 1</td><td> 1 1</td><td> 9090‘0</td><td> 0,0100</td><td> 0,0859</td><td> 0,0773</td>
<td>AND (D</td><td>O</td><td> 0,0413</td><td> 0,0620</td><td> 0,0641</td><td> 0,0895</td><td> 0001/0</td><td> 10,000</td><td> 0,3150</td><td> 1 1</td><td> !</td><td> 0,0606</td><td>O O δ O</td><td> 0,0859</td><td> 0,0773</td>
<td>AND <D £</td><td>O r--</td><td> 0,0413</td><td> 0,0620</td><td> 0,0641</td><td> 0,0895</td><td> 0,1000</td><td> 10,000</td><td> 0,3150</td><td> 1 1 1</td><td>1 1 I</td><td> 0,0606</td><td> 0,0100</td><td> 0,0859</td><td> 0,0773</td>
<td>AND <D</td><td>O</td><td> 0,0413</td><td> 0,0620</td><td> 0,0641</td><td> 0,0895</td><td>O O O O</td><td> 10,000</td><td> 0,3150</td><td> 1 1 1</td><td>1 1 I</td><td> 0,0606</td><td> 0,0100</td><td> 0,0859</td><td> 0,0773</td>
<td>1 AND (% w / w)</td><td>O r <</td><td> 0,0413</td><td> 0,0620</td><td> 0,0641</td><td> 0,0895</td><td> 0,1000</td><td> 10,000</td><td> ! 1</td><td> 1 1 1</td><td> 2,0000</td><td> 9090‘0</td><td> 0,0100</td><td> 0,0859</td><td> 0,0773</td>
<td>1D (% w / w)</td><td>O</td><td> 0,0413</td><td> 0,0620</td><td> 0,0641</td><td> 0,0895</td><td> 0,1000</td><td> 10,000</td><td>1 r</td><td> 2,0000</td><td></td><td> 0,0606</td><td> 0,0100</td><td> 6980‘0</td><td> 0,0773</td>
<td>1C (% w / w)</td><td>O</td><td> 0,0413</td><td> 0,0620</td><td> 0,0641</td><td> 0,0895</td><td> 0,1000</td><td> 10,000</td><td> 0,3150</td><td> 1 1 1</td><td> |</td><td> 0,0606</td><td> 0,0100</td><td> 0,0859</td><td> 0,0773</td>
<td>1B (% w / w)</td><td>O r <</td><td> 0,0413</td><td> 0,0620</td><td> 0,0641</td><td> 0,0895</td><td> 0,1000</td><td> 10,000</td><td> 0,3150</td><td> 1 1 1</td><td> 1 1 1</td><td> 0,0606</td><td> 0,0100</td><td> 0,0859</td><td> 0,0773</td>
<td>1A (% w / w)</td><td>O</td><td> 0,0413</td><td> 0,0620</td><td> 0,0641</td><td> 0,0895</td><td>O O O O</td><td> 10,000</td><td> 0,3150</td><td> 1 1</td><td> 1 1 1</td><td> 0,0606</td><td>O O δ θ '</td><td> 0,0859</td><td> 0,0773</td>
<td colspan="2">Ingredients</td><td>Propylene glycol USP</td><td>L-menthol USP</td><td>Timol NF</td><td>NF methyl salicylate</td><td>Eucalyptol USP</td><td>Flavor</td><td>Sorbitol (70% solution) USP</td><td>Sodium Lauryl Sulfate USP</td><td>Poloxamer 407 NC</td><td>Tween 20</td><td>Sodium saccharin USP</td><td>sucralose NF</td><td>Benzoic acid USP</td><td>Sodium benzoate</td>
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<td rowspan="10">Formulations</td><td>Control negative</td><td></td><td> 1 1 1</td><td> 1 1</td><td> 1 1</td><td></td><td>r- CO H-</td><td>O</td><td></td>
<td>AND Φ sX> O. 7 Ga</td><td></td><td>CM O O O O O</td><td>ώ cr</td><td>O θ ' O x—</td><td></td><td>to io IO ~</td><td>CM cm</td><td>CM</td>
<td>AND Φ</td><td></td><td>O O O O O ~ CM</td><td><n cr</td><td>O O O</td><td></td><td>CM IO ιθ</td><td>IO cm</td><td>CD io</td>
<td>AND Φ</td><td></td><td>O O O O the CM</td><td>üi O</td><td>O O O</td><td></td><td>CM (O IO ~</td><td>LO O cm</td><td>CO <d co</td>
<td>1F (% w / w)</td><td></td><td>CM O O O O O'</td><td>ώ O</td><td>O O O T "</td><td></td><td>CD m- io</td><td>co cm</td><td>co</td>
<td>AND φ</td><td></td><td>O O O O d CM</td><td>w cr</td><td>O O' O</td><td></td><td>co co Γ—</td><td>O O 1</td><td>CM CM cm</td>
<td>AND φ</td><td></td><td>O O O O θ “CM</td><td>w cr</td><td>O O O T—</td><td></td><td>τΤ CO r- ~</td><td>CO O O</td><td>B- the ~</td>
<td></td><td></td><td>CM O O O O O</td><td>ώ O</td><td>O θ ' O</td><td></td><td>IO M to</td><td>CM CM cm</td><td>00 cm</td>
<td>AND φ “El</td><td></td><td>O O O O the CM</td><td>ώ σ</td><td>O O O</td><td></td><td>co M Ιθ</td><td>CM cm</td><td>co co</td>
<td>AND φ 2l o.</td><td></td><td>CM O O O O O'</td><td>ώ O</td><td>O O O</td><td></td><td>O co</td><td>CO co_ v—</td><td></td>
<td colspan="2">Ingredients</td><td>Ll H</td><td>Green FD&C No. 3</td><td>USP purified water</td><td>£ O l · -</td><td></td><td>Z) _J Q £ CD _O</td><td>L_ O , · - » 45</td><td>Turbidity (NTU)</td>
32/36
The procedure for mixing the formulations was as follows:
Formulation 1A: the water was placed in an appropriately sized tank (or container) and then all the remaining ingredients were added to the water and mixed until dispersed. No separate premix was formed.
Formulation 1B: In step 1, the polyol-based solvent (ie, propylene glycol) was placed in a suitably sized tank (or container). The active oils and flavor were added to the polyol-based solvent in the tank, and mixed until homogeneity and uniformity were obtained, to form a premix. In step 2, instead of being added as the final component in the final step of the formulation process, sugar alcohol was added to the premix and mixed until the formulation was homogeneous and uniform, before adding the surfactant, the water, organic acid buffer, preservative, sweeteners and dyes. In step 3, the surfactant was added to the pre-mixture and mixed until the formulation was homogeneous and uniform. In step 4, the water was added to the premix and mixed until the formulation was homogeneous and uniform. In step 5, the organic acid buffer, preservative and sweeteners were added to the premix and mixed until homogeneity and uniformity were obtained. In step 6, the dye was added to the premix and mixed until the formulation was homogeneous and uniform.
Formulations 1C, 1D and 1E: in step 1, the polyol-based solvent (ie, propylene glycol) was placed in an appropriately sized tank (or container). The organic acid buffer was added to the polyol-based solvent to form a first premix, and mixed until homogeneity and uniformity were obtained. In step 2, instead of forming a second premix of active oil with a second solvent based on polyol, and adding the second premix to a third premix comprising water, surfactant, preservative and sweetener, the active oils and flavor were added directly to the first premix and mixed until homogeneity and uniformity were obtained. In step 3, the co-solvent based
33/36 of sugar alcohol was added to the first premix and mixed until the formulation was homogeneous and uniform. In step 4, the surfactant was added to the first premix and mixed until the formulation was homogeneous and uniform. In step 5, water, sweeteners and preservative were added to the first premix, and mixed until homogeneity and uniformity were obtained. In step 6, the dye was added to the first premix and mixed until the formulation was homogeneous and uniform. In Formulations 1D and 1E, higher levels of surfactant were added, compared to Formulation 1C.
Formulation 1F: In step 1, in a properly sized first tank (or container), a first premix was formed by adding 5% of the first polyol-based solvent (ie propylene glycol) to the active oils and the flavor, and mixed until they are homogeneous and uniform. In step 2, in a second tank (or container) properly sized, a second premix was formed by adding 2.0% of the second polyol-based solvent, which was the same as the first solvent based on polyol, to an organic acid buffer, being mixed in the second tank until homogeneity and uniformity are obtained. In step 3, instead of being added as the final component in the final step of the formulation process, the sugar alcohol based solvent was added and mixed directly in the first premix, until homogeneity and uniformity was obtained, before adding a surfactant, water, preservative, sweeteners and dyes. In step 4, the surfactant was added and mixed with the first pre-mixture, until the formulation was homogeneous and uniform. In step 5, the water was added and mixed with the first pre-mixture, until the formulation was homogeneous and uniform. In step 6, the second premix was added to the first premix and mixed until the formulation was homogeneous and uniform. In step 7, the preservative and sweeteners were added and mixed until homogeneity and uniformity were obtained. In step 8, the dye was added and mixed until the formulation was homogeneous and uniform.
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Formulation 1G (using the process of the invention): in step 1, in a suitably sized first tank (or container), a premix was formed by adding 5.0% of the first polyol-based solvent (ie, propylene glycol), active oils and flavor, and mixed until homogeneity and uniformity are obtained. In step 2, in a second tank (or container) properly sized, a second premix was formed by adding 2.0% of the second polyol-based solvent, which was the same as the first polyol-based solvent, to an organic acid buffer, being mixed until homogeneity and uniformity are obtained. In step 3, in a third tank (or container) suitably sized ), a third premix was formed by adding surfactant, preservative and sweeteners to the water, and mixed until homogeneity and uniformity were obtained. In step 4, the first premix was added to the third premix, and mixed until the formulation was homogeneous and uniform. In step 5, the second premix was added to the mixture of the first with the third premixes, and mixed until homogeneity and uniformity were obtained. In step 6, the dye was added to the mixture of the three premixes, and mixed until homogeneity and uniformity were obtained. In step 7, sugar alcohol was added as the final component to the mixture of the three premixes, and mixed until the final mixture was homogeneous and uniform.
Formulation 1H: in step 1, in a properly sized first tank (or container), instead of forming separate premixes (a premix containing the active oils and another premix containing the organic acid buffer), a The first pre-mixture was formed by adding both the organic acid buffer and the active oils to a polyol-based solvent (ie, propylene glycol) and flavor, being mixed until homogeneity and uniformity were obtained. In step 2, in a second tank (or container) suitably sized, instead of being added as the final component in the final step of the formulation process, the sugar alcohol based solvent was added to the surfactant, preservative, sweeteners and water, and mixed until homogeneity35 / 36 and uniformity are obtained to form a second premix. In step 3, the first pre-mix was added to the second pre-mix, and mixed until the formulation was homogeneous and uniform. In step 4, the dye was added to the mixture of the two premixes, and mixed until homogeneity and uniformity were obtained.
Formulation 11: In step 1, in a properly sized first tank (or container), a first premix was formed by adding 5.0% of the first polyol-based solvent (ie, propylene glycol) to the active oils and flavored, and mixed until it was homogeneous and uniform. In step 2, in a second tank (or container) properly sized, a second premix was formed by adding 2.0% of the second polyol-based solvent, which was the same as the first solvent based on polyol, to an organic acid buffer, being mixed until homogeneity and uniformity are obtained. In step 3, in a third tank (or container) properly sized, a third premix was formed by adding a surfactant, sorbitol, preservative and sweeteners to the water, and mixed until homogeneity and uniformity were obtained. In step 4, instead of adding the first premix to the third premix, the second premix was added to the third premix and mixed until homogeneity and uniformity were obtained. In step 5, the first premix was added to the mixture of the second premix with the third premix, and mixed until homogeneity and uniformity were obtained. In step 6, the dye was added and mixed until uniformity was obtained.
In addition to the list of formulation ingredients, Table 1 shows the results of the turbidity test, in Nephelometric Turbidity Units (NTU), and S. mutans biofilm elimination tests, in log units RLU and factor M. A typical M-factor value for a commercially available essential oil-based mouthwash containing alcohol is about 1.87 (log RLU of 5.8) in this model.
Table 1 also shows that all formulations containing sodium lauryl sulfate (Formulations 1A, 1B, 1C and 1F to 11) showed high
36/36 biocidal activity (M factor between 1.66 and 2.22). However, the turbidity of all three formulations containing sodium lauryl sulfate (1A, 1B and 1C) was high (NTU greater than about 10.5). When the total surfactant concentration was raised to 2.0% (Formulations 1D and 1E), turbidity improved, but at such high levels of surfactant concentration, biocidal activity, as measured by factor M, decreased substantially (factor M = 0.03 and -0.01, respectively). Only the formulation formed by the inventive processes of the present invention (Formulation 1G) offered both good efficiency (factor M = 2.05) and the lowest turbidity (NTU less than 4.0).
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Contents4
31 members in 12 offices
Priority claims2
| Document | Office | Kind | Date |
|---|---|---|---|
| 12827970 | United States of America | – | |
| 82797010 | United States of America | A |
Members31
| Document | Office | Kind | |
|---|---|---|---|
| CA2744676A1 | Canada | A1 | |
| MX2011007096A | Mexico | A | |
| EP2401999A2 | European Patent Office (EPO) | A2 | |
| US2012003162A1 | United States of America | A1 | |
| CN102309424A | China | A | |
| AU2011202511A1 | Australia | A1 | |
| JP2012012393A | Japan | A | |
| AR082052A1 | Argentina | A1 | |
| BRPI1102829A2This record | Brazil | A2 | |
| CO6590202A1 | Colombia | A1 | |
| RU2011126881A | Russian Federation | A | |
| AU2011202511B2 | Australia | B2 | |
| US2014322146A1 | United States of America | A1 | |
| CN102309424B | China | B | |
| EP2401999A3 | European Patent Office (EPO) | A3 | |
| RU2582222C2 | Russian Federation | C2 | |
| JP5944117B2 | Japan | B2 | |
| MX342354B | Mexico | B | |
| EP2401999B1 | European Patent Office (EPO) | B1 | |
| US9693944B2 | United States of America | B2 | |
| US2017216173A1 | United States of America | A1 | |
| US9763863B2 | United States of America | B2 | |
| ES2637836T3 | Spain | T3 | |
| US2017326047A1 | United States of America | A1 | |
| BRPI1102829B1 | Brazil | B1 | |
| CA2744676C | Canada | C | |
| US10434050B2 | United States of America | B2 | |
| US2019365618A1 | United States of America | A1 | |
| US2021085578A9 | United States of America | A9 | |
| US10993894B2 | United States of America | B2 | |
| BRPI1102829B8 | Brazil | B8 |
13 legal events, as the office reported them to INPADOC
Over the term
Point at a mark for the eventEvents
| Event | Code | |
|---|---|---|
| Requested change of name of applicant approvedB25D | B25D | |
| Requested change of headquarter approvedB25G | B25G | |
| Requested change of name of applicant approvedB25D | B25D | |
| Requested transfer of rights approvedB25A | B25A | |
| Requested change of name of applicant approvedB25D | B25D | |
| Requested transfer of rights approvedB25A | B25A | |
| Requested transfer of rights approvedB25A | B25A | |
| Requested transfer of rights approvedB25A | B25A | |
| Requested change of name of applicant approvedB25D | B25D | |
| Patent or certificate of addition of invention granted [chapter 16.1 patent gazette]GrantedB16A | B16A | |
| Decision: intention to grant [chapter 9.1 patent gazette]B09A | B09A | |
| Application suspended after technical examination (opinion) [chapter 7.1 patent gazette]B07A | B07A | |
| Publication of a patent application or of a certificate of addition of invention [chapter 3.1 patent gazette]B03A | B03A |
Numbers
- Publication
- PI1102829
- Application
- 11028297
Titles2
- Portuguese
- MÉTODOS PARA PREPARO DE ENXAGUATÓRIOS BUCAIS SEM ÁLCOOL À BASE DE ÓLEO ESSENCIAL BIOATIVO
- English
- METHODS FOR THE PREPARATION OF MOUTHAL RINSE WITHOUT ALCOHOL BASED ON BIOACTIVE ESSENTIAL OIL
Classification
- CPC, 17
- A61K8/345
- A61K8/34
- A61K8/347
- A61K8/368
- A61K8/39
- A61K8/463
- A61K8/90
- A61Q11/00
- A61K8/37
- A61P1/02
- A61K8/4973
- A61K8/498
- A61K8/86
- A61K8/922
- A61K2800/30
- A61K2800/74
- A61K2800/92
- IPC, 2
- A61K8 97
- A61Q11 00