Method for measuring pH using NMR

Abstract

Provided is a method for measuring the pH of a gel, paste, colloid and aqueous solution such as a consumer product, food product, pet food, beverage product, pharmaceutical product and / or medical product. The method may include preparing a calibration curve of a chemical species comprising or having an acid dissociation constant. Preparing a calibration curve may include drawing the chemical shift of the chemical species relative to pH. The method may also include measuring the chemical shift of a gel, paste and colloid, aqueous solution such as a consumer product, food product, pet food, beverage product, pharmaceutical product and / or medical product comprising the chemical species. The method may also include determining the pH of a gel, paste, colloid and aqueous solution such as a consumer product, food product, pet food, beverage product, pharmaceutical product and / or medical product using the chemical shift and calibration curve of the product.

Description

Background Art

[0001] The accurate pH value of compositions including gels, pastes, colloids and aqueous solutions such as consumer products, food products, pet foods, beverage products, pharmaceutical products and / or medical products is a fundamental factor related to consumer health. It is also a key factor related to the stability and quality of one or more key ingredients in consumer products, food products, pet foods, beverage products, pharmaceutical products and / or medical products. For example, in oral care products, the stability of toothpaste is usually related to or closely related to the change of its pH. However, due to many factors, such as the heterogeneity of toothpaste and the relatively low water content, it is known that the existing methods of measuring the pH of toothpaste via pH meters or electrodes are inaccurate and unreliable. In addition, pH electrodes measure pH by measuring the total amount of hydrogen ions, and the determination of the total amount of hydrogen ions is difficult and inaccurate in pure or undiluted toothpaste containing less than or equal to about 80% by weight of water. In addition, attempts to increase the water content by preparing a slurry and then measuring the pH of the slurry have also been proven to be inaccurate because the added water may change or affect the corresponding structure and dynamics of one or more chemical species in the toothpaste, which may change the measured pH.

[0002] Therefore, there is a need for improved methods for measuring the pH of various compositions including, but not limited to, gels, pastes, colloids, and aqueous solutions, such as consumer products, food products, pet foods, beverage products, pharmaceutical products, and / or medical products. Summary of the invention

[0003] The present invention content is only intended to introduce a simplified overview of some aspects of one or more embodiments of the present disclosure. Other applicable areas of the present disclosure will become apparent from the detailed description provided below. The present invention content is not an exhaustive overview, nor is it intended to identify the key or important elements of the present teachings, nor is it intended to delimit the scope of the present disclosure. On the contrary, its purpose is only to present one or more concepts in a simplified form as a preface to the following specific embodiments.

[0004] The foregoing and / or other aspects and utilities embodied in the present disclosure can be achieved by providing a method for measuring the pH of a composition, including but not limited to a gel, a paste, a colloid and / or an aqueous solution, such as a consumer product (e.g., an oral care product), a food product, a pet food, a beverage product, a pharmaceutical product and / or a medical product. The method may include preparing a calibration curve of a chemical species comprising or having an acid dissociation constant. Preparing a calibration curve may include plotting the chemical shift of the chemical species relative to pH. The method may also include determining the chemical shift of a composition comprising the chemical species, including but not limited to a gel, a paste, a colloid and / or an aqueous solution. The method may also include determining the pH of a composition using the chemical shift and a calibration curve of the composition, including but not limited to a gel, a paste, a colloid and / or an aqueous solution.

[0005] In at least one embodiment, the chemical species may include a carbonyl group, optionally a carboxyl group. In another embodiment, the chemical species may include a bicarbonate ion or a carbonate ion. ... 13 C NMR) to measure chemical shifts in compositions including, but not limited to, gels, pastes, colloids, and / or aqueous solutions.

[0006] In at least one embodiment, the chemical species comprises a phosphate group. In at least one embodiment, the chemical species may include one or more of tetrasodium pyrophosphate, tetrapotassium pyrophosphate, phosphoric acid, sodium monofluorophosphate, calcium hydrogen phosphate dihydrate, sodium triphosphate, sodium hexametaphosphate, or a combination thereof. In at least one embodiment, the chemical species may include phosphoric acid. In at least one embodiment, the chemical species may include phosphoric acid via phosphorus-31 nuclear magnetic resonance spectroscopy ( 31 P NMR) was used to measure the chemical shifts of the compositions.

[0007] In at least one embodiment, the composition, including but not limited to gels, pastes, colloids and / or aqueous solutions, may contain water in an amount less than 80 wt %, optionally less than 70 wt %, less than 60 wt %, or less than 50 wt %, based on the total weight of the product.

[0008] In at least one embodiment, the composition, including but not limited to gels, pastes, colloids and / or aqueous solutions, can be a consumer product, a food product, a pet food, a beverage product, a pharmaceutical product and / or a medical product. The consumer product can include, for example, an oral care product, a home care product and / or a personal care product. In at least one embodiment, the oral care product can be a toothpaste.

[0009] In at least one embodiment, the chemical shift of a composition including, but not limited to, a gel, a paste, a colloid, and / or an aqueous solution can be determined without diluting the composition.

[0010] In at least one embodiment, chemical shifts of compositions including, but not limited to, gels, pastes, colloids, and / or aqueous solutions can be determined without pre-treating the composition.

[0011] In at least one embodiment, determining the chemical shift of the composition comprising the chemical species may include preparing a slurry of the composition, including but not limited to a gel, a paste, a colloid, and / or an aqueous solution.

[0012] In at least one embodiment, preparing a calibration curve for a chemical species may include preparing a plurality of solutions containing the chemical species, wherein each of the plurality of solutions has or contains a different pH. Preparing a calibration curve for a chemical species may also include determining a chemical shift for each of the plurality of solutions having different pHs.

[0013] In at least one embodiment, preparing a calibration curve for chemical species may further include preparing a graph of chemical shift of each of the plurality of solutions versus pH of each of the plurality of solutions, and fitting a curve to the graph to prepare the calibration curve.

[0014] Other areas of applicability of the present disclosure will become apparent from the detailed description provided hereinafter.It should be understood that the detailed description and specific examples, while indicating some typical aspects of the present disclosure, are intended for illustrative purposes only and are not intended to limit the scope of the present disclosure. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] The present disclosure will be best understood from the following detailed description when read in conjunction with the accompanying drawings. It is emphasized that, in accordance with standard practice in the industry, various features are not drawn to scale. In fact, the size of the various features may be arbitrarily increased or reduced for clarity.

[0016] Figure 1 Illustrated are graphs of chemical shift versus pH for each of a plurality of solutions containing bicarbonate and carbonate according to one or more disclosed embodiments.

[0017] Figure 2 Illustrated are graphs of chemical shift versus pH for a number of solutions containing bicarbonate, carbonate, and varying amounts of sodium chloride (NaCl) according to one or more disclosed embodiments.

[0018] Figure 3 Illustrated are graphs of chemical shift versus pH for a number of solutions containing bicarbonate, carbonate, and varying amounts of arginine according to one or more disclosed embodiments.

[0019] Figure 4Schematically shows a graph of the chemical shift of each of a plurality of solutions containing phosphate groups relative to pH according to one or more of the disclosed embodiments.

[0020] Figure 5 Schematically shows a graph of the chemical shift of each of a plurality of solutions containing lactic acid relative to pH according to one or more of the disclosed embodiments. Detailed embodiments

[0021] The following description of various exemplary aspects is merely exemplary in nature and is in no way intended to limit the disclosure, its application, or uses.

[0022] The ranges used throughout this disclosure are used as shorthand for every value within the described range. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as a rigid limitation on the scope of any embodiment or implementation disclosed herein. Accordingly, the disclosed ranges should be interpreted as having specifically disclosed all possible sub-ranges and individual numerical values within that range. Thus, any value within the range can be selected as an endpoint of the range. For example, a description of a range such as 1 to 5 should be considered to have specifically disclosed sub-ranges such as 1.5 to 3, 1 to 4.5, 2 to 5, 3.1 to 5, etc., and individual numbers within that range, such as 1, 2, 3, 3.2, 4, 5, etc. This applies regardless of the width of the range.

[0023] Unless otherwise specified, all percentages and amounts expressed herein and elsewhere in this specification are to be understood to refer to weight percentages. The given amounts are based on the effective weight of the materials.

[0024] In addition, all numerical values are "about" or "approximately" the specified values, and experimental errors and variations contemplated by those of ordinary skill in the art are taken into account. It should be understood that all numerical values and ranges disclosed herein are approximate values and ranges, whether or not the term "about" is used in conjunction therewith. It should also be understood that, as used herein, the term "about" in connection with a number refers to a value that can be ±0.01% (including the endpoints), ±0.1% (including the endpoints), ±0.5% (including the endpoints), ±1% (including the endpoints) of that number, ±2% (including the endpoints) of that number, ±3% (including the endpoints) of that number, ±5% (including the endpoints) of that number, ±10% (including the endpoints) of that number, or ±15% (including the endpoints) of that number. It should also be understood that when a numerical range is disclosed herein, any numerical value belonging to the described range is also specifically disclosed.

[0025] As used herein, "free of" or "substantially free of" a material may refer to a composition, component, or phase in which the material is present in an amount of less than 10.0 wt%, less than 5.0 wt%, less than 3.0 wt%, less than 1.0 wt%, less than 0.1 wt%, less than 0.05 wt%, less than 0.01 wt%, less than 0.005 wt%, or less than 0.0001 wt%, based on the total weight of the composition, component, or phase.

[0026] All references cited herein are incorporated herein by reference in their entirety. In the event of a conflict in a definition in the present disclosure and that of a cited reference, the present disclosure controls.

[0027] The inventors have surprisingly and unexpectedly found that the pH of compositions including but not limited to gels, pastes, colloids and / or aqueous solutions, such as consumer products, food products, beverage products, pharmaceutical products and / or medical products, measured via the nuclear magnetic resonance (NMR) method disclosed herein is relatively more precise, accurate and / or reliable than the pH of the composition measured via a conventional pH meter based on a pH electrode. Specifically, the standard deviation of the pH measured via the NMR method is unexpectedly, significantly and surprisingly lower than the standard deviation of the pH measured via the conventional pH meter method. It was also surprisingly and unexpectedly found that the method of measuring the pH of a composition via an NMR spectrometer can be used to measure the pH of a composition containing phosphoric acid, sodium bicarbonate, sodium lactate, lactic acid and / or or will produce orthophosphate (PO 4 ) as a by-product of chemical species or molecular entities such as sodium monofluorophosphate (MFP), dibasic calcium phosphate dihydrate (Dical), tetrapotassium pyrophosphate (TKPP), sodium triphosphate (STPP) and tetrasodium pyrophosphate (TSPP).

[0028] The present disclosure can provide a method for measuring the pH of a composition, the composition including but not limited to a gel, a paste, a colloid and / or an aqueous solution, such as a consumer product, a food product, a beverage product, a pharmaceutical product and / or a medical product. The method for measuring the pH of a composition may include preparing a calibration curve of one or more chemical species or molecular entities with an acid dissociation constant (pKa), determining the chemical shift of a product comprising the chemical species or molecular entity, and determining the pH of the product with the chemical shift and the calibration curve of the product. As further described herein, the calibration curve of a chemical species or molecular entity can be a graph of the chemical shift of a chemical species or molecular entity relative to pH.

[0029] The composition can be or can include but is not limited to any solution using water as a solvent. The aqueous solution can include water in an amount less than or equal to about 80% by weight based on the total weight of the solution. For example, the aqueous solution can include water less than or equal to 80% by weight, less than or equal to 75% by weight, less than or equal to 70% by weight, less than or equal to 65% by weight, less than or equal to 60% by weight, less than or equal to 55% by weight, less than or equal to 50% by weight, less than or equal to 45% by weight, less than or equal to 40% by weight, less than or equal to 35% by weight, less than or equal to 30% by weight, less than or equal to 25% by weight or less water based on the total weight of the composition or product. It should be understood that when the water content is less than or equal to about 80% by weight, the pH of the composition, consumer product, substance, component or material including but not limited to gel, paste, colloid and aqueous solution measured via a conventional pH meter will be inaccurate, showing relatively large changes or variability, and / or lack of precision. The composition measured can be natural or artificial.

[0030] Composition, including but not limited to gel, paste, colloid and / or aqueous solution, can be or can include consumer products, food products, pet food, beverage products, pharmaceutical products and / or medical products.Consumer products can be or can include but are not limited to home care products (for example, detergent, dish soap, detergent, etc.), personal care products (for example, deodorant, gel, hair care products, lotion, etc.), oral care products, etc. or any combination thereof.In an exemplary embodiment, consumer products include oral care products.Oral care products or their oral care compositions can form at least a portion of one or more oral care products or be used in one or more oral care products.Illustrative oral care products can be or can include but are not limited to toothpaste (dentifrices), preventive pastes, tooth powders, tooth polishes, tooth gels (for example, whitening gels), chewing gums, lozenges, mouthwashes, whitening strips, paint-on gels, varnishes, veneers, syringes or dental trays containing gels or pastes, gels or pastes applied on support such as floss or toothbrushes (for example, manual, electric, sonic, combinations thereof or ultrasonic toothbrushes), etc. In a preferred embodiment, the oral care composition may be or may form at least a part of a mouthwash.

[0031] Compositions, including but not limited to gels, pastes, colloids and / or aqueous solutions, may contain one or more chemical species, molecular species or entities, etc., or combinations thereof, having or containing an acid dissociation constant. As used herein, the term or expression "molecular entity" may refer to any compositionally or isotopically distinct atom, molecule, ion, ion pair, free radical, radical ion, complex, conformer, etc., that can be identified as individually distinguishable entities. As used herein, the term or expression "chemical species" may refer to any atom, molecule, molecular fragment, ion, etc. that can be subjected to a chemical process or measurement. For example, a chemical species may be a collection of chemically identical molecular entities that can explore the same set of molecular energy levels over the time scale of an experiment.

[0032] The one or more chemical species or molecular entities may each contain one or more functional groups, such as protonated functional groups. Illustrative functional groups may be or may include, but are not limited to, carboxyl groups, phosphate groups, carbonyl groups, hydroxyl groups, amine groups, ether groups, thiol groups, alkane groups, olefin groups, sulfoxide groups, alkyne groups, nitrile groups, ketone groups, aldehyde groups, alcohol groups, sulfonic acid groups, etc., or combinations thereof. In at least one embodiment, the chemical species or molecular entity comprises a carbonyl group, a carboxyl group, or a combination thereof. In another embodiment, the chemical species or molecular entity comprises a phosphate group. Illustrative chemical species or molecular entities may be or may include, but are not limited to, bicarbonate, carbonate, tetrasodium pyrophosphate (TSPP), tetrapotassium pyrophosphate (TKPP), sodium triphosphate (STPP), sodium hexametaphosphate (SHMP), phosphoric acid, sodium monofluorophosphate (MFP), dihydrated calcium phosphate (Dical), etc., or combinations thereof. In a preferred embodiment, the chemical species or molecular entity comprises one or more of bicarbonate, carbonate, phosphoric acid, or a combination thereof.

[0033] Calibration curve

[0034] As discussed above, the method may include preparing a calibration curve of one or more chemical species or molecular entities having an acid dissociation constant. Preparing a calibration curve may include preparing a plurality of standard or known solutions or samples comprising any one or more of the chemical species or molecular entities, wherein the plurality of solutions or samples have different pH. The pH of each of the plurality of solutions or samples may be acidic, neutral or alkaline. For example, the pH of each of the plurality of solutions or samples may be from about 1, about 2, about 3, about 4, about 5, about 6, or about 7 to about 8, about 9, about 10, about 11, about 12, about 13, or about 14. It should be understood that the pH of each of the plurality of solutions or samples may be adjusted to any desired pH by combining one or more bases, one or more acids, or a combination of one or more bases and one or more acids.

[0035] The preparation of the calibration curve may also include determining or measuring the chemical shift of each of the multiple solutions at each of the corresponding pH. The chemical shift of each of the multiple solutions may be determined or measured by nuclear magnetic resonance (NMR) spectroscopy. It should be understood that the type of NMR spectrum used to measure the chemical shift may be determined at least in part by the chemical species or molecular entities monitored or contained in the composition. For example, samples and / or solutions containing bicarbonate or carbonate as chemical species or molecular entities may use carbon-13NMR spectroscopy. For another example, samples and / or solutions containing chemical species or molecular entities with phosphate groups may use phosphorus-31 NMR spectroscopy. Although carbon-13NMR spectroscopy and phosphorus-31 NMR spectroscopy are shown, it should be understood that other types of NMR may be used, such as NMR measuring the chemical shift of any one or more of hydrogen nuclei, fluorine, boron, nitrogen, oxygen, tin, etc., or any combination thereof, each of which has a unique magnetic property.

[0036] Preparing the calibration curve may also include preparing a graph of the chemical shift of each of the plurality of samples and / or solutions relative to the pH of each of the plurality of samples and / or solutions. As discussed above, the chemical species or molecular entity may be or may include carbonate or bicarbonate. Since bicarbonate (HCO 3 - ) and carbonate (CO 3 2- ) will undergo rapid exchange on the NMR time scale, so the observed C-13 NMR chemical shift (δ) of the carboxyl group can be expressed as HCO according to equation (1): 3 - (δHCO 3 - ) and CO 3 2- (δCO 3 2- ) is expressed as the weighted average of the C-13 chemical shifts between:

[0037] δ C =xHCO 3 - δHCO 3 - +xCO 3 2 δCO 3 2- (1)

[0038] where xHCO 3 - and xCO 3 2are the molar ratios of bicarbonate and carbonate in the sample, respectively. The pH of bicarbonate can be expressed by the pKa of bicarbonate, as represented by equation (2):

[0039] pH = pKa + log[(δ C -δHCO 3 - ) / (δCO 3 2- -δ C )] (2).

[0040] Figure 1 Shown are graphs of chemical shift versus DH for each of a number of solutions containing bicarbonate and carbonate.

[0041] As discussed further above, the chemical species or molecular entity may be or may include a phosphate group, wherein the observed P-31 chemical shift may be expressed according to equation (3):

[0042] δ p =xH 2 PO 4 - δH 2 PO 4 - +xHPO 4 - δHPO 4 - (3)

[0043] where xH 2 PO 4 - and xHPO 4 - is the molar ratio of the two monophosphate species in the sample. The pH of the phosphate group can be expressed in terms of the pKa of the phosphate, as represented by equation (4):

[0044] pH = pKa + log[(δ P -δH 2 PO 4 - ) / (δHPO 4 2- -δ P )] (4)

[0045] Figure 3 Shown are graphs of chemical shift versus pH for each of a number of solutions containing phosphate groups.

[0046] In at least one embodiment, the chemical species or molecule or molecular entity may be or may include a carboxyl group, such as the carboxyl group of lactic acid, wherein the observed C-13 chemical shift may be expressed according to equation (5):

[0047] pH = pKa + log[(δ C -δCO 2 H) / (δCO 2 - -δ C )] (5)

[0048] Figure 2 Shown are graphs of chemical shift versus pH for each of a number of solutions containing carboxyl groups.

[0049] It will be appreciated that, based on equations (1)-(5), pH is determined by the molar ratio of chemical species in a sample and / or solution whose chemical shift is sensitive to pH. Unlike conventional methods of measuring pH via electrodes, the methods disclosed herein do not depend on the amount of hydrogen ions. Therefore, it will be appreciated that the methods disclosed herein can be used to accurately determine pH in samples and / or solutions having a low water content (e.g., less than 80% by weight).

[0050] Preparing the calibration curve may further include fitting a curve to a graph of chemical shift for each of the plurality of solutions versus pH for each of the plurality of solutions. Fitting the curve may include applying a nonlinear least squares analysis to the graph. Fitting the curve to the graph may allow one or more variables or values ​​of equations (2), (4), and / or (5) to be determined. For example, a nonlinear least squares fit may be applied to determine the pKa, δCO, and pH in equation (2). 3 2- and δHCO 3 - In addition, nonlinear least squares fitting can be applied to determine the pKa, 6H 2 PO 4 - and 6HPO 4 2- A nonlinear least squares fit can also be applied to determine the pKa, δCO of equation (5) 2 H and δCO 2 - The value of .

[0051] Determination of chemical shift

[0052] The method may include determining the chemical shift of a composition comprising the chemical species or molecular entity, the composition including but not limited to a gel, a paste, a colloid and / or an aqueous solution. The chemical shift of the composition may be determined by nuclear magnetic resonance (NMR). For example, a composition comprising bicarbonate or carbonate as a chemical species or molecular entity may use carbon-13 NMR spectroscopy. As another example, a composition comprising a chemical species or molecular entity having a phosphate group may use phosphorus-31 NMR spectroscopy. It should be understood that the type of NMR used may be at least partially determined by one or more chemical species or molecular entities contained in the gel, paste, colloid and aqueous solution and / or one or more chemical species or molecular entities used to prepare the calibration curve. It should also be understood that although carbon-13 NMR spectroscopy and phosphorus-31 NMR spectroscopy are shown below, it should be understood that other types of NMR may be used, such as NMR that measures the chemical shift of any one or more of hydrogen nuclei, fluorine, boron, nitrogen, oxygen, tin, etc., each of which has a unique magnetic property.

[0053] In at least one embodiment, when analyzing compositions including but not limited to gels, pastes, colloids and / or aqueous solutions, the chemical shift determination of the composition can be performed without any prior treatment of the composition. For example, the chemical shift of the composition can be measured without diluting, filtering, buffering or otherwise changing the composition. For another example, the chemical shift of the composition can be measured as is or as a pure composition such as a pure oral care product. For example, the oral care product can be a toothpaste or tooth gel, and the chemical shift can be measured by directly measuring the toothpaste or tooth gel in an NMR spectrometer.

[0054] In another embodiment, the composition can be pre-treated before measuring the chemical shift. For example, if the composition is an oral care product, the oral care product can be diluted with water or combined to prepare a slurry, and the chemical shift of the slurry can be measured. For example, before measuring its chemical shift, the composition can be aged for at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 10 days, at least 30 days, at least 60 days or more. The composition can be aged at any temperature. For example, the composition can be aged at room temperature (RT). For example, the composition can be aged at a temperature below 0°C, about 0°C, above 0°C, above 10°C, above 30°C, above 50°C or higher.

[0055] The measured chemical shift of the composition can then be used to determine the pH of the composition. For example, the measured chemical shift of the composition can then be used together with a calibration curve to determine the pH of the composition.

[0056] All ingredients used in the compositions and methods described herein should be orally acceptable. As used herein, "orally acceptable" can refer to any ingredient present in a composition as described in an amount and form that does not render the composition unsafe for use in the oral cavity.

[0057] Example

[0058] The examples and other embodiments described herein are exemplary and are not intended to be limiting in describing the full scope of the compositions and methods of the present disclosure. Equivalent changes, modifications and variations of specific embodiments, materials, compositions and methods may be made within the scope of the present disclosure with substantially similar results.

[0059] Example 1

[0060] By using standardized NaHCO in water maintained at different pH 3 The samples were used to prepare a calibration curve for measuring bicarbonate by NMR. The solution contained about 0.5 wt% sodium bicarbonate, and the pH was changed using hydrochloric acid (HCl) and sodium hydroxide (NaOH). The samples were subjected to NMR to obtain C-13 chemical shift values. A pH electrode was used to measure the pH of each standardized sample, and a calibration curve was prepared by correlating the measured C-13 chemical shift with the pH value measured by the pH electrode, as shown in Figure 2. Figure 1 Therefore, the observed carbonyl group 13 C chemical shift (δ C )HCO 3 - (δHCO 3 - ) and CO 3 2- (δCO 3 2- )between 13 The pH of bicarbonate is described by the pKa of bicarbonate, as expressed by Equation 2.

[0061] pH = pKa + log[(δ C -δHCO 3 - ) / (δCO 3 2- -δ C )] (2)

[0062] Application of nonlinear least squares fitting to determine pKa, δCO 3 2- and δHCO 3 - The values ​​of each are summarized in Table 1. Figure 1The bicarbonate 13 Fitting curve of the change of C chemical shift with pH. Figure 1 The curve graph and the corresponding R 2 It shows that sodium bicarbonate is 13 C NMR is a reliable candidate for measuring pH.

[0063] Table 1

[0064] The parameter variables in Equation 1

[0065] parameter value pKa 10.36 <![CDATA[δCO 3 2- ]]> 160.25 <![CDATA[δHCO 3 - ]]> 168.24 <![CDATA[R 2 ]]> 0.98

[0066] In order to evaluate any interference or interaction between sodium bicarbonate and the other major components of toothpaste compositions (1)-(10), NaHCO was measured in the presence of different amounts of sodium chloride (NaCl). 3 of 13 C NMR chemical shift. In particular, Figure 2 NaHCO containing up to about 20 wt % sodium chloride is evaluated and illustrated in 3 of 13 C NMR chemical shift. Figure 2 As surprisingly and unexpectedly shown in the present invention, sodium chloride in an amount of about 5 wt %, about 10 wt % and about 20 wt % is not present in the bicarbonate. 13 This further supports the hypothesis that bicarbonate is produced by 13 C NMR is a reliable candidate for measuring pH.

[0067] In addition to the above, NaHCO was measured at different pH in the presence of 1.5% and 8% arginine. 3 of 13 C NMR chemical shift. Figure 3 The bicarbonate containing different amounts of arginine is shown in FIG. 13 C NMR chemical shift changes with pH. Figure 3 As surprisingly and unexpectedly shown in the literature, the presence of arginine at 1.5% and 8% does not appear in the presence of bicarbonate. 13 This further supports the hypothesis that bicarbonate is produced by 13 C NMR is a reliable candidate for measuring pH.

[0068] Example 2

[0069] Ten oral care compositions (1)-(10) were prepared or obtained to evaluate pH. In particular, ten toothpaste compositions (1)-(10) were prepared or obtained for testing. Each toothpaste composition (1)-(10) contained sodium bicarbonate in an amount greater than 0.5 wt % and water in an amount from about 14 wt % to about 18 wt %. The key ingredients contained in each toothpaste composition (1)-(10) are summarized in Table 1.

[0070] Table 1

[0071] Key ingredients in toothpaste compositions (1)-(10)

[0072]

[0073] Example 3

[0074] The pH of each toothpaste composition (1)-(10) as a pure paste (without dilution) and as a slurry was measured via a conventional pH meter. The pH meter or electrode used was a benchtop pH meter (Mettler Toledo, F20, Switzerland) with a glass pH electrode (ORION, Thermo Fisher). It should be understood that before measuring the pH, the pH meter was calibrated using a standard buffer solution, and each measurement was independently repeated three times at room temperature to obtain an average pH value. It should also be understood that between each measurement, the tip of the pH electrode was thoroughly washed with distilled water and acetone, and then dried.

[0075] To determine the pH of each toothpaste composition (1)-(10) as a pure paste (without dilution), the pH electrode of the pH meter was directly inserted into the corresponding tube of each toothpaste composition (1)-(10) so that the pH electrode was in full contact with the paste for at least 5 minutes to allow the measured pH value to stabilize. To prepare a slurry of each toothpaste composition (1)-(10), 9 grams (g) of distilled water and 1 g of the corresponding toothpaste composition (1)-(10) were combined with each other in a glass vial and stirred at 25° C. for about 10 minutes. To determine the pH of each toothpaste composition (1)-(10) as a slurry, the pH electrode was placed in the slurry under stirring. The results of the pH measured by the pH meter are summarized in Table 2.

[0076] Example 4

[0077] via 13 The pH of each toothpaste composition (1)-(10) was measured by C NMR as a neat paste (without dilution) and as a slurry. The NMR measurements were performed on an AVANCE The NMR spectrometer was run at 25 °C with a 5 mm CryoProbe.1 H, running at 500.13MHz, for 13 C, operating at 125.8 MHz. During acquisition, a zgig pulse sequence with proton decoupling was used to obtain the 13 C NMR spectroscopy was performed to avoid signal accumulation due to the NOE effect. During the measurement, the following parameters of the NMR spectrometer were maintained: pulse length = 5 μs; cycle delay = 20 sec; scan number = 64. It should be understood that each 13 C NMR spectra were collected for approximately 15 to 20 min to ensure adequate signal-to-noise ratio to record bicarbonate (HCO 3 2- )of 13 C NMR chemical shift values. 13 C chemical shifts were referenced to 1% tetramethylsilane (zero).

[0078] To determine the pH of each toothpaste composition (1)-(10) as a pure paste (without dilution), 1 g of each toothpaste composition (1)-(10) was placed into a corresponding 5 mm NMR tube using a syringe and gently centrifuged (about 1,000 rpm) for about 1 minute (min) to ensure that the paste settled to the bottom of the NMR tube without any phase separation. To prepare a slurry of each toothpaste composition (1)-(10), each toothpaste composition (1)-(10) was combined with water at a weight ratio of 1:9 (toothpaste: water) without centrifugation. The results of the pH measured via a pH meter are summarized in Table 2.

[0079] Table 2

[0080] The pH meter and 13 pH of toothpaste compositions (1)-(10) measured by C NMR

[0081]

[0082] As shown in Table 2, the standard deviation (SD) of pH measured via the NMR method is unexpectedly, significantly, and surprisingly lower than the SD of pH measured via the pH meter method. In some cases, the SD of pH measured via the NMR method is at least one order of magnitude lower than the SD of pH measured via the pH meter method. It should be understood that the SD indicates the precision, accuracy, reliability, and / or reproducibility of measuring pH via the NMR method relative to the pH meter method.

[0083] Example 5

[0084] By using sodium dihydrogen phosphate (NaH 2 PO 4 ) and disodium hydrogen phosphate (Na2 HPO 4 ) in water to prepare a calibration curve for the measurement of phosphate groups by NMR. 2 PO 4 and Na 2 HPO 4 Phosphate buffer solutions having a 100 mM phosphate concentration adjusted at various pHs (ie, pH from about 5 to about 8.5) were used for P-31 NMR pH titration experiments. 2 PO 4 and Na 2 HPO 4 exchange occurs relatively quickly on the NMR time scale. 31 P chemical shift (δ P ) 2 PO 4 - (δH 2 PO 4 - ) and HPO 4 2- (δHPO 4 2- ) 31 The pH of the phosphate group can be described by the pKa of the phosphate, as expressed by equation (4).

[0085] pH = pKa + log[(δ P -δH 2 PO 4 - ) / (δHPO 4 2- -δ P )] (4)

[0086] Apply nonlinear least squares fitting to determine pKa, δH 2 PO 4 - and δHPO 4 2- The values ​​of each are summarized in Table 3. Figure 3 The phosphate 31 Fitting curve of the chemical shift versus pH. Figure 3 The curve graph and the corresponding R 2 It shows that phosphate is 31 P NMR is a reliable candidate for measuring pH.

[0087] Table 3

[0088] The parameter variables in Equation 2

[0089] parameter value pKa 6.82 <![CDATA[δH 2 AFTER 4 - ]]> -0.0479 <![CDATA[δHPO 4 2-- ]]> 2.437 <![CDATA[R 2 ]]> 0.99

[0090] Example 6

[0091] Eight oral care compositions (11)-(18) were prepared or obtained to evaluate pH. In particular, eight toothpaste compositions (11)-(18) were prepared or obtained for testing. Each toothpaste composition (11)-(18) contained water in an amount of about 14 wt % to about 20 wt %. The key ingredients contained in the toothpaste compositions (11)-(18) included arginine (Arg), tetrasodium pyrophosphate (TSPP), phosphoric acid (H 3 PO 4 ), sodium monofluorophosphate (MFP) and calcium hydrogen phosphate dihydrate (Dical), the contents of the ingredients contained in each toothpaste composition (11)-(18) are summarized in Table 3.

[0092] Table 3

[0093] Key ingredients in toothpaste compositions (11)-(18)

[0094]

[0095]

[0096] It should be understood that toothpaste compositions (12), (14) and (17) comprise the same composition as (11), (13) and (16), but toothpaste compositions (12), (14) and (17) are aged. Specifically, toothpaste compositions (12) and (14) are aged at about 49° C. for 6 weeks, while toothpaste composition (17) is aged at room temperature (RT) for one year.

[0097] As shown in Table 3, toothpaste compositions (11)-(15) contain phosphoric acid and tetrasodium pyrophosphate (TSPP), toothpaste compositions (16)-(18) contain at least TSPP and Dical, and toothpaste compositions (16)(17) contain TSPP, Dical, and MFP. It should be understood that toothpaste composition (18) contains only TSPP, which is partially degraded to orthophosphate as a byproduct. In addition, MFP is also partially degraded to orthophosphate as a byproduct.

[0098] Example 7

[0099] The pH of each toothpaste composition (11)-(18) as a pure paste (without dilution) and as a slurry was measured via a conventional pH meter. It should be understood that before measuring the pH, the pH meter was calibrated using a standard buffer solution, and each measurement was repeated three times independently to obtain an average pH value. It should also be understood that between each measurement, the tip of the pH electrode was thoroughly washed with distilled water and acetone, and then dried.

[0100] To measure the pH of each toothpaste composition (11)-(18) as a pure paste (without dilution), the pH electrode of the pH meter was directly inserted into the corresponding tube of each toothpaste composition (11)-(18) so that the pH electrode was in full contact with the paste for at least 5 minutes to allow the measured pH value to stabilize. To prepare a slurry of each toothpaste composition (11)-(18), 9 grams (g) of distilled water and 1 g of the corresponding toothpaste composition (11)-(18) were combined with each other in a glass vial and stirred at 25° C. for about 10 minutes. To measure the pH of each toothpaste composition (11)-(18) as a slurry, the pH electrode was placed in the slurry under stirring. The results of the pH measured by the pH meter are summarized in Table 4.

[0101] Example 8

[0102] via 31 The pH of each toothpaste composition (11)-(18) was measured by P NMR as a neat paste (without dilution) and as a slurry. The NMR measurements were performed on a 10 μM silica gel column (Billerica, MA, USA) obtained from Bruker Biospin Corp. The NMR spectrometer was run at 25 °C with a 5 mm CryoProbe. 1 H, running at 500.13MHz, for 31 P, operating at 202.46 MHz. The zg pulse sequence was used to obtain the 31 During the measurement, the following parameters of the NMR spectrometer were maintained: pulse length = 5 μs; cycle delay = 30 sec; scan number = 8. It should be understood that each 31 The P NMR spectra were collected for approximately 2 min to ensure sufficient signal-to-noise ratio to record the phosphate 31 PNMR chemical shift values. 31 The chemical shift of P is 85% of H 3 PO 4 (zero) as a reference.

[0103] To determine the pH of each toothpaste composition (11)-(18) as a pure paste (without dilution), 1 g of each toothpaste composition (11)-(18) was placed into the corresponding 5 mm NMR tube using a syringe and gently centrifuged (about 1,000 rpm) for about 1 minute (min) to ensure that the paste settled to the bottom of the NMR tube without any phase separation. To prepare a slurry of each toothpaste composition (11)-(18), each toothpaste composition (11)-(18) was combined with water at a weight ratio of 1:9 (toothpaste:water) without centrifugation. The results of pH measured via a pH meter are summarized in Table 4.

[0104] Table 4

[0105] The pH meter and 13 pH of toothpaste compositions (11)-(18) measured by C NMR

[0106]

[0107] It should be understood that the estimated pH of toothpaste compositions (11) and (13) are about 7.0 and 6.5, respectively. As shown in Table 4, although both the NMR method and the pH meter method show the same pH trend indicating that the acidity of toothpaste composition (13) is relatively higher than that of toothpaste composition (11), the pH measured by the NMR method is closer to the estimated pH or more accurate. In addition, the standard deviation (SD) of the pH measured via the NMR method is unexpectedly, significantly and surprisingly lower than the SD of the pH measured via the pH meter method.

[0108] As further shown in Table 4, upon aging, the pH of each of toothpaste compositions (12) and (14) decreased to about 6.5. Without being bound by theory, it is believed that the flavor compound (i.e., wintergreen oil) partially decomposes upon aging to produce salicylic acid, which results in the decrease in pH.

[0109] As discussed above, some toothpaste compositions (16)-(18) do not contain phosphoric acid. Therefore, it was surprisingly and unexpectedly discovered that the method of measuring the pH of toothpaste compositions (16)-(18) can be extended to other phosphate species, namely orthophosphate (PO4) formed as a by-product in toothpastes containing MFP, Dical and TSPP. 4 ).

[0110] Example 9

[0111] A calibration curve for measuring lactic acid by NMR was prepared by using standardized buffer solutions of sodium lactate and lactic acid at different molar ratios in water at different pH. The solutions contained about 1% by weight of the total concentration of sodium lactate and lactic acid, and the pH varied between pH about 2 and about 5.5. NMR was performed on the samples to obtain C-13 chemical shift values. A pH electrode was used to measure the pH of each standardized sample, and a calibration curve was prepared by correlating the measured C-13 chemical shift with the pH value measured by the pH electrode, as shown in FIG. Figure 4 Therefore, the observed carbonyl group 13 C chemical shift (δ C )CO 2 H(δCO 2 H) and CO 2 - (δCO 2 - )between 13 The pH of a carboxyl group is described by the pKa of the carboxyl group, as expressed by Equation 5.

[0112] pH = pKa + log[(δ C -δCO 2 H) / (δCO 2 - -δ C )] (5)

[0113] Application of nonlinear least squares fitting to determine pKa, δCO 2 - , and δCO 2 The values ​​of H are summarized in Table 5. Figure 4 The carboxyl group is shown in 13 Fitting curve of the change of C chemical shift with pH. Figure 4 The curve graph and the corresponding R 2 It shows that the carboxyl group of lactic acid is 13 C NMR is a reliable candidate for measuring pH.

[0114] Table 5

[0115] The parameter variables in Equation 1

[0116] parameter value pKa 3.73 <![CDATA[δCO 2 - ]]> 178.62 <![CDATA[δCO 2 H]]> 182.67 <![CDATA[R 2 ]]> 0.99

[0117] Example 10

[0118] Four personal care compositions (19)-(22) were prepared or obtained to evaluate pH. Each personal care composition (19)-(22) comprises lactic acid in an amount greater than 0.8 wt % and water in an amount from about 68.5 wt % to about 74.5 wt %. The key ingredients contained in each personal care composition (19)-(22) are summarized in Table 6.

[0119] Table 6

[0120] Key ingredients in personal care compositions (19)-(22)

[0121]

[0122] The pH of each personal care composition (19)-(22) as neat gel (undiluted) was measured via a pH meter according to the above procedure. 13 C NMR measured the pH of each personal care composition (19)-(22) in the form of neat gel. The NMR measurement was performed according to the above procedure. The results of pH measured via the pH meter are summarized in Table 2.

[0123] Table 7

[0124] The pH meter and 13 pH of personal care compositions (19)-(22) measured by C NMR

[0125]

[0126] The present disclosure has been described with reference to exemplary embodiments. Although a limited number of embodiments have been shown and described, it will be appreciated by those skilled in the art that changes may be made in these embodiments without departing from the principles and spirit of the previous specific embodiments. The present disclosure is intended to be interpreted as including all such modifications and changes as long as they are within the scope of the appended claims or their equivalents.

Claims

1. A method for determining the pH of a composition, the method comprising: include: preparing a calibration curve for a chemical species comprising an acid dissociation constant, wherein preparing the calibration curve comprises plotting a chemical shift of the chemical species relative to pH; determining a chemical shift of a composition comprising the chemical species; as well as determining the pH of the composition using the chemical shift of the composition and the calibration curve; wherein the composition is selected from the group consisting of consumer products, food products, pet foods, beverage products, pharmaceutical products, medical products, and combinations thereof, wherein the chemical species comprises a carbonyl group, a carboxyl group, a bicarbonate ion, a carbonate ion, or a phosphate group; and wherein the chemical shift of the composition is determined by carbon-13 nuclear magnetic resonance spectroscopy ( 13 C NMR) or phosphorus-31 nuclear magnetic resonance spectroscopy ( 31 P NMR) determination.

2. The method of claim 1, wherein the chemical species comprises a carbonyl group, optionally a carboxyl group.

3. The method of claim 1 or 2, wherein the chemical species comprises bicarbonate ions or carbonate ions.

4. The method according to claim 1 or 2, wherein the chemical shift of the composition is determined by carbon-13 nuclear magnetic resonance spectroscopy ( 13 C NMR). The method of claim 1 , wherein the chemical species comprises a phosphate group.

6. The method of claim 1 or claim 5, wherein the chemical species comprises one or more of tetrasodium pyrophosphate, tetrapotassium pyrophosphate, phosphoric acid, sodium monofluorophosphate, calcium hydrogen phosphate dihydrate, sodium triphosphate, sodium hexametaphosphate, or a combination thereof. The method of claim 6 , wherein the chemical species comprises phosphoric acid.

8. The method of claim 1 or 7, wherein the chemical shift of the composition is determined by phosphorus-31 nuclear magnetic resonance spectroscopy ( 31 P NMR) determination.

9. The method of any one of claims 1, 2 and 5, wherein the composition comprises water in an amount less than 80 wt% based on the total weight of the composition.

10. The method of any one of claims 1, 2, and 5, wherein the composition comprises water in an amount less than 70 wt. %, based on the total weight of the composition.

11. The method of any one of claims 1, 2 and 5, wherein the composition comprises water in an amount less than 60 wt% based on the total weight of the composition.

12. The method of any one of claims 1, 2, and 5, wherein the composition comprises water in an amount less than 50 wt. %, based on the total weight of the composition.

13. The method of claim 1, wherein the composition is a consumer product.

14. The method of claim 13, wherein the chemical shift of the consumer product is determined without diluting the consumer product.

15. The method of claim 13, wherein the chemical shift of the consumer product is determined without pre-treating the consumer product.

16. The method of any one of claims 1, 2 and 5, wherein the chemical shift of the composition is determined without pre-treating the composition.

17. The method of claim 13, wherein determining the chemical shift of a consumer product comprising the chemical species comprises preparing a slurry of the consumer product.

18. The method according to any one of claims 1, 2 and 5, wherein the calibration curve for preparing the chemical species is further include: preparing a plurality of solutions comprising the chemical species, wherein each of the plurality of solutions comprises a different pH; as well as A chemical shift is determined for each of the plurality of solutions comprising the different pHs.

19. The method of claim 18, wherein preparing the calibration curve of the chemical species further comprises: include: preparing a graph of the chemical shift for each of the plurality of solutions versus pH for each of the plurality of solutions; as well as A curve is fitted to the graph to prepare the calibration curve.

20. The method of claim 1, wherein the composition is selected from the group consisting of a gel, a paste, a colloid, an aqueous solution, and mixtures thereof.

Images